📅 Nov 16, 2017

Re: 2017 IFP Gotham Awards

From: Steven Pfeiffer

To: jeffrey E.

Hello Jeffrey — I hope all is well with you. As per Peggy Siegal's office, I have included here the invitation to the IFP Gotham Awards ceremony, which will be held on Monday, November 27 at Cipriani Wall Street in New York City. This year's ceremony is going to be another successful event. We couldn't be more thrilled with this year's impressive group of Tributees. The Actress Tribute will go to Nicole Kidman and the Actor Tribute to Dustin Hoffman. The Director Tribute will be given to Sofia

Hello Jeffrey —

I hope all is well with you. As per Peggy Siegal's office, I have included here the invitation to the IFP Gotham Awards ceremony, which will be held on Monday, November 27 at Cipriani Wall Street in New York City.

This year's ceremony is going to be another successful event. We couldn't be more thrilled with this year's impressive group of Tributees. The Actress Tribute will go to Nicole Kidman and the Actor Tribute to Dustin Hoffman. The Director Tribute will be given to Sofia Coppola, with the Cinematographer Tribute going to Ed Lachman. With the Industry Tribute, we will be honoring Jason Blum, founder of Blumhouse Productions. And we simply couldn't be more pleased to honor Vice President Al Gore with this year's special Humanitarian Tribute. With nominees this year ranging from Willem Dafoe, Adam Sandler and Robert Pattison to Margot Robbie, Lois Smith and Mary J. Blige, this year's ceremony looks to be the most star studded ever.

Please let me know if you have any questions.

Best regards,
Steven

Steven Pfeiffer
Associate Director, Development
Independent Filmmaker Project

Made in NY Media Center by IFP

Brooklyn, NY 11201
P:

EFTA00955986

www.ifp.org

📅 Nov 16, 2017

Re: 2017 IFP Gotham Awards

From: jeffrey E.

To: Steven Pfeiffer, Peggy Siegal, Richard Kahn

happy to buy your 10k of chairs and will need me plus 3 seats.

happy to buy your 10k of chairs and will need me plus 3 seats.

📅 Nov 16, 2017

Re: 2017 IFP Gotham Awards

From: Steven Pfeiffer

To: jeevacation@gmail.com, Peggy Siegal

Hi Jeffrey — Sounds good. Thanks so much for confirming. If you or someone in your office could provide the information below, I can send along an invoice and contribution letter for your $10K donation toward the chairs. COMPANY NAME (if applicable): CONTACT NAME: ADDRESS LINE 1: ADDRESS LINE 2: EFTA00955985 Many thanks. Best, Steven Steven Pfeiffer Associate Director, Development Independent Filmmaker Project Made in NY Media Center by IFP Brooklyn NY 11201 p: ‘wrw.ifp.org

Hi Jeffrey —

Sounds good. Thanks so much for confirming. If you or someone in your office could provide the information below, I can send along an invoice and contribution letter for your $10K donation toward the chairs.

COMPANY NAME (if applicable):
CONTACT NAME:
ADDRESS LINE 1:
ADDRESS LINE 2:

EFTA00955985

Many thanks.

Best,
Steven

Steven Pfeiffer
Associate Director, Development
Independent Filmmaker Project

Made in NY Media Center by IFP

Brooklyn NY 11201
p:
‘wrw.ifp.org

📅 Nov 16, 2017

Re: 2017 IFP Gotham Awards

From: jeffrey E.

To: Steven Pfeiffer, Peggy Siegal

just send to peggy. you her co . its better for her

just send to peggy. you her co . its better for her

📅 Nov 16, 2017

Re: 2017 IFP Gotham Awards

From: Steven Pfeiffer

To: jeevacation@gmail.com, Peggy Siegal

Sounds good, works for me. So, Peggy, if you could just let me know what info to include on the donation letter and invoice, I’ll send that along your way. COMPANY NAME (if applicable): <empty> CONTACT NAME: <empty> ADDRESS LINE 1: <empty> ADDRESS LINE 2: <empty> Thanks, Steven Steven Pfeiffer Associate Director, Development Independent Filmmaker Project Made in NY Media Center by IFP Brooklyn, NY 11201 p: www.ifp.org

Sounds good, works for me.

So, Peggy, if you could just let me know what info to include on the donation letter and invoice, I’ll send that along your way.

COMPANY NAME (if applicable): <empty>
CONTACT NAME: <empty>
ADDRESS LINE 1: <empty>
ADDRESS LINE 2: <empty>

Thanks,
Steven

Steven Pfeiffer
Associate Director, Development
Independent Filmmaker Project

Made in NY Media Center by IFP
Brooklyn, NY 11201
p:
www.ifp.org

📅 Mar 8, 2013 FROM EPSTEIN REDACTED

Re: post TED

From: jeevacation@gmail.com

fund myself, racnh island vegas new york „ your call. On Fri, Mar 8, 2013 at 6:54 PM, wrote: Outstanding!! Location preference? or should we ask Tom Pritzker to make some suggestions? Do you want to fund all of this or charge something to attendees (or first year free for all, see how it goes?)? Any date windows you prefer? Any topics that would be especially fun for you? FUN++ is the best email for me. ΧΟΧΟ On Mar 8, 2013, at 2:50 PM, Jeffrey Epstein wrote: im in On Fri, Mar 8, 2013

fund myself, racnh island vegas new york „ your call.

On Fri, Mar 8, 2013 at 6:54 PM, wrote:

Outstanding!!

Location preference? or should we ask Tom Pritzker to make some suggestions?

Do you want to fund all of this or charge something to attendees (or first year free for all, see how it goes?)? Any date windows you prefer?

Any topics that would be especially fun for you?

FUN++

is the best email for me.

ΧΟΧΟ

On Mar 8, 2013, at 2:50 PM, Jeffrey Epstein wrote:

im in

On Fri, Mar 8, 2013 at 6:41 PM, [Redacted] < [Redacted] > wrote:
Great to see you!!

Chris is really moving in the direction of "do good," so the program is very different...

I always like Juan Enriquez. Have you met him? he's a friend, lives in Boston. I can easily set that up.

Amanda Palmer's talk is up on TED.com -- I'm not sure if you'll be interested. She's a first rate original. Musician. The Art of Asking. She stopped working with a record company and now just relies on fans to donate and makes much more money.

Beardyman is a cool beatbox dude.

Liu Bolin (art -- he makes himself invisible in these photos of China --- art is amazing and he was fascinating)

Mary Lou Jepsen - you'll love her. Tech to read thoughts. I know her. She is brilliant and really out there. She just took a job with Google and they don't really want her talking about this stuff. Based in the bay area.

Larry Lessig on government corruption - it's worth watching this talk and learning about the movement he's working to create. He will be successful. The force is with him. Harvard guy.

EFTA00955988

MIT Media Lab open house spring event is 4/22-23. I'll be there. Joi Ito (one of the most interesting people at TED!) - whom you met - is in charge.

I enjoyed TED, but I'm pretty sure you'd be bored out of your mind.

Oh - another person, friend of mine, for you to meet in NY or bay area, if I can snag him - James Joaquin. Very interesting, smart guy.

On another note --

If you're serious about doing a "conference" that would be FUN+++ Let me know.

Preliminary thoughts --

Since the conference takes on the personality of the curator(s),

I would get 6-9 curators (depending on how long we wanted to go)

Ask each to identify 3-4 speakers (people they are blown away by)

Curators: Danny Hillis, Dan Ariely, Dave Gallo (rhythms), Dean Kamen (?), Boris, Juan Enriquez, George Dyson, and you? and me?, Bartunde

The lack of women (except for me!) is not intentional. I need to think more about this...

We could come up with the guest list or could ask each of the folks above to name 10-12 of the folks they think would be most interesting to have as attendees....

What do you think?

хохо

On Mar 8, 2013, at 2:23 PM, Jeffrey Epstein wrote:

interesting names?

The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein

Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jeevacation@gmail.com, and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved

EFTA00955989

****************

*****************

***********

The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein

Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jea@gmail.com and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved

The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein

Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jeevacation@gmail.com, and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved

********

EFTA00955990

📅 Mar 8, 2013 FROM EPSTEIN

Re:

From: jeevacation@gmail.com

To: President

am On Fri, Mar 8, 2013 at 6:56 PM, President < > wrote: Sure Sunday am or evening Sent from my iPhone On Mar 8, 2013, at 4:45 PM, Jeffrey Epstein <jeevacation@gmail.com> wrote: can we have a call this weekend. ****** The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein Unauthorized use, disclosure or copying of this comm

am

On Fri, Mar 8, 2013 at 6:56 PM, President < > wrote:
Sure Sunday am or evening

Sent from my iPhone

On Mar 8, 2013, at 4:45 PM, Jeffrey Epstein <jeevacation@gmail.com> wrote:

can we have a call this weekend.

******

The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein

Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jeevacation®gmail.com, and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved

********

The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jeevacation®gmail.com, and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved

📅 Mar 8, 2013

The J.P. Morgan View : Equity market rally relies on value not growth

From: US GIO

To: Undisclosed recipients

J.P. Morgan Logo Global Asset Allocation The J.P. Morgan View: Equity market rally relies on value not growth Click here for the full Note and disclaimers. • Asset allocation — Equities are the only major risk market rallying, and then not in all countries. The high equity risk premium relative to other risk markets, and the way US corporates are reacting to it by buying back shares financed with cash and debt are, in our view, a major factor as to why US stocks are doing so well, despite an

J.P. Morgan Logo

Global Asset Allocation

The J.P. Morgan View: Equity market rally relies on value not growth

Click here for the full Note and disclaimers.

• Asset allocation — Equities are the only major risk market rallying, and then not in all countries. The high equity risk premium relative to other risk markets, and the way US corporates are reacting to it by buying back shares financed with cash and debt are, in our view, a major factor as to why US stocks are doing so well, despite an uncertain economic outlook.

• Economics — Good US payrolls appear to confirm that US companies are not retrenching in response to fiscal tightening. We await Feb/Mar consumption data to gauge how the US consumer is reacting.

• Fixed Income — Focus on cross-market allocations: long EM vs DM, US vs UK, and Spain vs Italy.

• Equities — Open an OW in US Small Caps and Value stocks.

• Credit — ISDA is proposing to overhaul the standards governing credit default swaps.

• Currencies — Buy CAD/JPY to reflect stronger domestic data in Canada and the yen's persistent vulnerability to higher global rates.

• Commodities — Be long base metals and natural gas and underweight gasoline, zinc and lead.

• If you like the video, click on the picture in the upper right in the pdf.

• Equity markets are on a tear, with the Dow and US small caps reaching new historic highs this week. But the rally has been quite narrow so far this year, with Europe and EM, as well as other risk markets such as credit, commodities, and EM FX barely participating (chart on right). And the rally has come without any upgrading ofglobal growth and earnings expectations, aside from early signs that the forecast rebound in growth from Q4 is actually taking place. The narrowness of the rally is seen by many as a warning that US stocks in particular have gone out on a limb and are set up for a bad correction. We are more sanguine and see a good reason for equities doing better: This is where the real value is, in our opinion.

• Policy and position divergences across regions and asset classes help explain some of these performance gaps, but to us, the most important single explanation of why certain risk markets are doing better is Value, and the way investors are reacting to it. We have argued frequently that the foundation ofour ovenveight in risk assets is not any economic

EFTA00955992

bullishness, but a belief that risk premia over rock-bottom safe yields are high relative to delivered volatility and fading uncertainty and tail risks. This is a general statement that hides the fact that not all risk premia are equally high or attractive. We reviewed different asset class risk premia relative to their own history in GMOS this week, and found that it is the equity risk premium over both cash and safe government debt that stands out as most elevated relative to its own long-term history.

• The table on p. 2 lists ow perception of different risk premia, volatilities and expected returns to risk relative to historic means. Virtually each market has below average volatility currently, in line with record low macro volatility & the downside protection of global QE. But it is only equities that have record high risk premia against depressed yields on cash and safe government debt.

• The big flow by investors from safe assets into the broad credit and EM bond world has brought credit spreads to historic averages, even as they remain higher than at comparable points in past US economic cycles. Credit spreads and yields remain high relative to depressed volatility in fixed income, although this low volatility is unlikely to survive a market correction. Term premia on bonds and roll premia in commodities are just below average. Carry in currencies, both in EM and DM, are in turn well below historic means.

• The degree to which equity risk premia stand out relative to other asset classes in a world where there is no economic growth momentum is to us a major reason why equities have been beating other risk asset YTD. Obviously, positions, which are especially heavy in credit, matter also, but they are also the reason why some of the extra value in credit has been exhausted. Equity risk premia stand out because they have been the asset class that has been shunned by most investors so far this cycle.

• It has been argued by many that equities are not really cheap as their multiples are near historic means. That would appear correct, but to us not of great relevance as investors can only buy assets that are on their plate today and can't buy assets at yesterday's prices. The relative IRR between equities and all other assets and, in particular, safe cash and debt define the premium that investors can capture today by switching into stocks.

• In previous years we have made more use of momentum than value as a signal for tactical positioning, as the former provides better timing. Value can offer good timing, however, when and where it is supported by flow evidence. That is, one should buy cheap assets when one sees other economic agents starting to do the same. And it is here that were are seeing not only end investors in DM starting to prefer stocks over credit, but, more importantly, corporates who are reacting to the massive funding cost difference between debt & equities by issuing corporate debt to buy back shares, both their own and somebody else's though M&A. The last few weeks have seen the biggest pace of US buyback announcements over the past 3 years. As a result, while still holding on to credit spread positions in our model portfolios, we have a significantly larger ovenveight in equities, as this appears to offer more value.

Fixed Income

• Bond yields backed up hard, without hitting the headlines like the new highs in equities. Treasuries underperformed, and the 10-year is now near the top of its range. We don't think today's upside payroll surprise is yet enough to change the Fed's stance, and go long Treasuries. In Europe, we stay bullish on German Bunds, but keep a bearish tilt on UK gilts, with uncertainty around the Bank of England's remit still brewing.

• We expect a new remit to be enshrined before new BoE Governor Carney arrives in July, explicitly giving the central bank more leeway in bringing inflation back to target. We also expect a Carney-led Bank of England to follow the trend in introducing policy rate guidance, although the experience of those central banks which have published policy rates forecasts for many years suggests that central banks are only marginally more successful than the market in predicting short rates more than a few quarters ahead (see Monday's Rule-based fixed income monthly for a discussion).

• We continue to focus most ofour risk on cross-market trades: OW EM vs DM, on strong EM inflows and the broader theme of spread compression; short UK vs US, on BoE remit change; short Italy vs Spain, given continued uncertainty over the formation of a new Italian government, and as a countenveight to a positive medium-term view on Euro area peripherals; and money market flatteners in New Zealand vs steepeners in Canada, positioning for convergence in central bank tightening expectations.

Equities

• Equities are up 2% on the week, more than reversing the small correction seen in the week post Italian elections. The rally this year brought the cumulative rise in the MSCI AC World Index to 23% since last June. The MSCI AC World index has

EFTA00955993

reached a new post Lehman high in dollar terms, marginally surpassing its previous May 2011 peak. Today's strong payroll report also helped although most of the rise in equities took place before the US payroll report.

• As explained in the front section, we are long equities in our model portfolio on valuation grounds. Within our equity model portfolio, which focuses on regional and sectoral trades we are overweight EM equities vs. Euro equities. As we explained last week, given rising appetite for US assets and rising risks to Euro area growth following the Italian election, we prefer to express the EM equity overweight vs. Euro area rather than US equities. This week's ratings downgrades of Italian government debt would seem to add justification to this call.

• Unfortunately, neither our EM equity overweight nor our Cyclical overweight managed to add beta to our equity portfolio. Not only YTD, but also since the equity rally started last June, EM equities have underperformed their DM counterparts and Cyclical sectors have underperformed defensive sectors globally.

• In fact given a decline in the global manufacturing PMI in February, we cut ow Cyclical sectoral exposures. We instead open an OW in small vs. large caps in the US, i.e. long in Russell 2000 vs. S&P500 to add beta to our equity portfolio. The Russell 2000 index underperformed in 2011 but was flat last year. It is outperforming again this year (see top chart). Beyond beta, we view additional arguments to favor small vs. large caps as improving retail investor sentiment and valuations. The Russell 2000 is trading at a NB ratio of 1.8 vs. 2.3 for the S&P500.

• We also open an overweight in Value stocks to capture increasing investor focus on value. Value stocks outperformed significantly since last June, raising the chance that a 5-year old previous underperformance might be coming to an end. The chart at the bottom shows the performance of Value stocks globally and within the US. Value stocks have followed similar patterns in both the US and globally. But the rebound ofUS Value stocks has been more pronounced more recently.

Credit

• In line with the rally in equities, spreads tightened significantly this week and high-yield sectors outperformed. The flow picture into US high-yield mutual funds also improved after several weeks of outflows. Our credit portfolio performed well after a slow February (see this week's GMOS), helped by the outperformance of European credit and the compression of financials to non-financials in US HG this week. In fact, European high-yield CDS (-47bp) outperformed US high-yield CDS (-2lbp) by the widest margin since October last year and US HG Financial spreads are now just II bp wider than non-financials, down from I 00bp one year ago. Momentum suggests that financials could trade at lower spreads than non-financials within weeks, which has not occurred since October 2007.

• ISDA is planning to overhaul the standards governing credit-default swaps in the most significant update of the CDS documentation 2009. Current proposals aim to make CDS contracts more robust to sovereign defaults and corporate mergers as well as standardize reference obligations (see Proposed CDS Revamp by Saul Doctor and Danny White for more details).

Foreign Exchange

• Today's payrolls report is sustaining several of 2013's clearest trends: stronger US equities, rising US Treasury yields, a stronger trade-weighted dollar and mixed commodity currencies. The last link in this chain — year-to-date declines in AUD, NZD, CAD, RUB, COP and PEN — is the most surprising element given that so much else seems to be going right for commodity currencies. Asian economies (and for once, Japan) are accelerating, central bank balance sheets (ex ECB) are expanding and tail risks are showing more bark than bite (US budget sequester, Italian elections). Still, of the world's commodity currencies only BRL and CLP are up this year (4.8% and 1.5%, respectively), while all others are down 1%-4%. The easy answer for relative FX performance is the rate story — Brazil and Chile are on the verge of tightening while Australia, Canada and Russia am easing or turning dovish. That rate story likely has a bit further to run, but given that other supports for commodity FX are lining up in the background, this edition ofFXMW puts a few catalysts on the radar. Buy CAD, since domestic factors are firming.

• Given the dominance oflocal rather than systemic factors, the portfolio strategy this year has had no dominant funding or investment currency. Instead, we have held a mix of USD longs versus currencies where central bank easing has been most imminent (GBP, JPY); commodity currency shorts where valuations have been most stretched (NZD); GBP shorts broadly (vs USD, EUR, SEK) given a unique combination of fiscal and monetary risks (possible rate cut/QE, budget slippage); and JPY shorts broadly (vs USD and EUR) for similar reasons. Normally, a US payrolls report like today's, which could heighten suspicions of a shift in Fed tone and/or policy at the March 20 FOMC meeting, would argue for broadening the basket of USD longs and JPY shorts globally. The caveat is that Canadian payrolls were outstanding too and China data are firming, so some currencies like CAD, Latam and Southeast might resist the dollar's pull. Thus the main portfolio shift is to

buy CAD/JPY to reflect an important Canadian catalyst (stronger domestic data) falling into place, as well as the yen's persistent vulnerability to higher global rates (note that 10-yr Germany is selling off too as JOBs rally ahead of the Bars duration extension on April 4). In EM FX, we also stay focused on idiosyncratic stories. BRL and IDR, where central banks are constrained by inflation pressures, should continue to deliver. Add to short JPY/KRW.

Commodities

• Commodities are slightly up this week but down on the year in line with worries about the impact ofChinese real estate tightening that has also damaged stocks in the area. As an asset class, commodities have broken up with equities, likely in our mind as the equity rally is driven by value and not by any growth optimism in the world. As a result, we are modestly underweight commodities versus equities and credit in a long only portfolio as the latter offer better value, in our view. Within commodities, we position tactically on relative demand and supply conditions, by being long base metals and natural gas and underweight gasoline, zinc and lead. See this week's Global Markets Outlook and Strategy for details.

The image contains a list of names, presumably analysts from J.P. Morgan, followed by black bars. These black bars are likely redacted information, possibly representing email addresses or other contact details.

Key Entities:
* Jan Loeys
* John Normand
* Nikolaos Panigirtzoglou
* Seamus Mac Gorain
* Matthew Lehmann
* Leo Evans
* J.P. Morgan

Analyst certification: I certify that: (1) all of the views expressed in this research accurately reflect my personal views about any and all of the subject securities or issuers; and (2) no part ofmy compensation was, is, or will be directly or indirectly related to the specific recommendations or views expressed herein. Important disclosures, including price charts, are available for compendium reports and all J.P. Morgan-covered companies by visitingIturs://mmjpmorgan.comidisclosureskompany, calling 1-800-477-0406, or e-mailing research.disclosure.inquiriekajpmorgan.com with your request. J.P. Morgan's Strategy, Technical, and Quantitative Research teams may screen companies not covered by J.P. Morgan. For important disclosures for these companies, please call 1-800-477-0406 or e-mail research.disclosureinquiriesOjpinorgan.com.

J.P. Morgan does and seeks to do business with companies covered in its research reports. As a result, investors should be aware that the firm may have a conflict ofinterest that could affect the objectivity of this report. Investors should consider this report as only a single factor in making their investment decision.

Confidentiality and Security Notice: This transmission may contain information that is privileged, confidential, legally privileged, and/or exempt from disclosure under applicable law. If you are not the intended recipient, you are hereby notified that any disclosure, copying, distribution, or use of the information contained herein (including any reliance thereon) is STRICTLY PROHIBITED. Although this transmission and any attachments are believed to be free ofany virus or other defect that might affect any computer system into which it is received and opened, it is the responsibility ofthe recipient to ensure that it is virus free and no responsibility is accepted by JPMorgan Chase & Co., its subsidiaries and affiliates, as applicable, for any loss or damage arising in any way from its use. If you received this transmission in error, please immediately contact the sender and destroy the material in its entirety, whether in electronic or hard copy format.

EFTA00955995

This email is confidential and subject to important disclaimers and conditions including on offers for the purchase or sale of securities, accuracy and completeness of information, viruses, confidentiality, legal privilege, and legal entity disclaimers, available at http://wwwjpmorgan.corn/pages/disclosures/email.

EFTA00955996

📅 Mar 8, 2013 FROM EPSTEIN

(no subject)

From: jeevacation@gmail.com

To: Lang, Caroline

may i have eitiene contact? looking forward to our dinner and then concert ******* ******** The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, plea

may i have eitiene contact? looking forward to our dinner and then concert

*******

********

The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein

Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jeevacation@gmail.com, and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved

📅 Mar 8, 2013 FROM EPSTEIN

Re:

From: jeevacation@gmail.com

To: roger schank

ok On Fri, Mar 8, 2013 at 7:03 PM, roger schank < wrote: in the am please On Mar 8, 2013, at 5:56 PM, President wrote: Sure Sunday am or evening Sent from my iPhone On Mar 8, 2013, at 4:45 PM, Jeffrey Epstein <jeevacation@gmail.com> wrote: can we have a call this weekend. ***** The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffr

ok

On Fri, Mar 8, 2013 at 7:03 PM, roger schank < wrote: in the am please

On Mar 8, 2013, at 5:56 PM, President wrote:

Sure Sunday am or evening

Sent from my iPhone

On Mar 8, 2013, at 4:45 PM, Jeffrey Epstein <jeevacation@gmail.com> wrote:

can we have a call this weekend.

*****

The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein

Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jeevacation®gmail.com, and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved

roger schank

john evans professor emeritus, northwestern university

******************

************

The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for

EFTA00955998

the use of the addressee. It is the property of Jeffrey Epstein Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jeevacation@gmail.com, and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved

EFTA00955999

📅 Mar 8, 2013 FROM EPSTEIN

<empty>

From: jeevacation@gmail.com

To:

is the r. o gone, what other equiptment is still left ? ******** ********** The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us imme

is the r. o gone, what other equiptment is still left ?

********

**********

The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jeevacation®gmail.com, and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved

📅 Mar 8, 2013 FROM EPSTEIN REDACTED

Re:

From: jeevacation@gmail.com

what question did you have? On Fri, Mar 8, 2013 at 7:33 PM, [REDACTED] < [REDACTED] > wrote: Jeffrey! Let's meet up then 20th or 21st! Sent from my iPhone On Mar 8, 2013, at 5:03 PM, Jeffrey Epstein <jeevacation@gmail.com> wrote: will be back in ny 20th and 21 then to paris -- ***************** The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the pr

what question did you have?

On Fri, Mar 8, 2013 at 7:33 PM, [REDACTED] < [REDACTED] > wrote:
Jeffrey! Let's meet up then 20th or 21st!

Sent from my iPhone

On Mar 8, 2013, at 5:03 PM, Jeffrey Epstein <jeevacation@gmail.com> wrote:

will be back in ny 20th and 21 then to paris

--

*****************
The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein
Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jeevacation@gmail.com, and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved

********

The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jeevacation®gmail.com, and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved

📅 Mar 8, 2013 FROM EPSTEIN REDACTED

(no subject)

From: Jeffrey Epstein <jeevacation@gmail.com>

dean, if you need to ask me a question im availble ********** The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by retu

dean, if you need to ask me a question im availble

**********

The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jeevacation®gmail.com, and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved

📅 Mar 8, 2013 FROM EPSTEIN

Fwd: melanie has sent you an UpToDate topic

From: jeevacation@gmail.com

To: roger schank

Forwarded message From: melanie Date: Fri, Mar 8, 2013 at 6:43 PM Subject: melanie has sent you an UpToDate topic To: jeevacation@gmail.com JEE - read through this article. It is the most comprehensive that I could find related to low CSF pressure headaches. Perhaps there is something in here that will resonate, or at least it will tell us that this ISN'T what she's got. ©2013 UpToDate® Official Topic from UpToDate®, the clinical information service on the web and mobile devices. To subscri

Forwarded message

From: melanie Date: Fri, Mar 8, 2013 at 6:43 PM Subject: melanie has sent you an UpToDate topic To: jeevacation@gmail.com

JEE - read through this article. It is the most comprehensive that I could find related to low CSF pressure headaches.

Perhaps there is something in here that will resonate, or at least it will tell us that this ISN'T what she's got.

©2013 UpToDate®

Official Topic from UpToDate®, the clinical information service on the web and mobile devices. To subscribe to UpToDate®, visit us online at http://www.uptodate.com/store.

Pathophysiology, clinical features, and diagnosis of spontaneous low cerebrospinal fluid pressure headache Authors Christina Sun-Edelstein, MD Christine L Lay, MD, FRCPC Section Editor Jerry W Swanson, MD Deputy Editor John F Dashe, MD, PhD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Feb 2013. &#124 This topic last updated: Jan 17, 2013.

INTRODUCTION AND TERMINOLOGY — The production, absorption, and flow of cerebrospinal fluid (CSF) play key roles in the dynamics of intracranial pressure. Alterations in CSF pressure can lead to neurologic symptoms, the most common being headache. Most often, the headaches associated with low CSF pressure are orthostatic and occur after lumbar puncture, but similar headaches occur with spontaneous low CSF pressure due to spinal CSF leaks and with CSF shunt overdrainage. In addition, trauma, surgery, and other medical conditions have also been associated with low CSF pressure headache [I].

Spontaneous low CSF pressure headache is being recognized with increasing frequency. Orthostatic headache, low CSF pressure, and diffuse meningeal enhancement on brain magnetic resonance imaging (MRI) are the major features of the classic syndrome. However, some cases have nonorthostatic headache, normal CSF pressure, or no evidence of diffuse meningeal enhancement [2].

Our understanding of this syndrome is still evolving, and historically a number of terms have been used to describe it:

EFTA00956003

• Spontaneous (or idiopathic) low CSF pressure headache

• Spontaneous (or primary) intracranial hypotension

• Low CSF volume headache

• Hypoliquorrhoeic headache

- Aliquorrhea

• CSF leak headache

• CSF hypovolemia

• CSF volume depletion

This topic will discuss the pathophysiology, epidemiology, clinical features, and diagnosis of spontaneous low CSF pressure headache. Treatment is discussed separately. (See "Treatment and prognosis of spontaneous low cerebrospinal fluid pressure headache".)

Post-lumbar puncture headache is also discussed separately. (See "Post-lumbar puncture headache".)

PATHOPHYSIOLOGY - In the intact craniospinal vault, the brain is supported by the cerebrospinal fluid (CSF), such that a brain weight of 1500 gin air is only 48 gin CSF [a]. As the CSF pressure decreases, there is a reduction in the buoyancy of the brain's supportive cushion. As a result, the brain "sags" in the cranial cavity, causing traction on the anchoring and supporting structures of the brain [47).

Cause of headache — Traction on pain-sensitive intracranial and meningeal structures, particularly sensory nerves and bridging veins, is thought to cause headache and some of the associated symptoms In the upright position this traction is exaggerated, hence the postural component of the headache. Secondary vasodilation of the cerebral vessels to compensate for the low CSF pressure may contribute to the vascular component of the headache by increasing brain volume [5]. Because jugular venous compression increases headache severity, it seems likely that venodilation is a contributing factor to the headache.

CSF hypovolemia, rather than CSF hypotension per se, has been proposed as the underlying cause of the headache syndrome [2], as patients with normal CSF pressure have been described who have clinical and radiographic features that are otherwise typical of orthostatic headache [2,8-10]. In this paradigm, the CSF pressures, clinical manifestations, and imaging abnormalities of the syndrome are thought to be variables dependent on CSF volume [n]. Some authors [12] have therefore advocated the name "CSF hypovolemia syndrome" for the constellation of symptoms associated with CSF leakage.

An alternative hypothesis is that spinal loss of CSF results in an increased compliance at the caudal end of the spinal CSF space, and the abnormal distribution of craniospinal elasticity causes the headache syndrome Ent This explanation is compatible with the observation that spinal sites of CSF leakage commonly produce orthostatic headache, whereas cranial sites of CSF leakage (eg, seen with spontaneous CSF rhinorrhea or CSF otorrhea) are less likely to do so.

Cause of low CSF pressure — In 1891 Quincke introduced the lumbar puncture (LP) [L]i, and in 1898 Bier suffered and was the first to report post-LP headache [15]. He proposed that ongoing leakage of cerebrospinal fluid (CSF) through the dural puncture site was the cause of the headache. This belief is still held today. It is thought that leakage of CSF through the dural rent made by the LP needle exceeds the rate of CSF production, resulting in low CSF volume and pressure [ lfi]. (See "Post-lumbar puncture headache".)

The clinical syndrome of spontaneous low CSF pressure has been recognized for many years. The syndrome was first proposed in 1938 by Schaltenbrand [11,11], who termed it aliquorrhea, and described a headache syndrome virtually identical to that following LP. He proposed three possible mechanisms (decreased CSF production by the choroid plexus, increased CSF absorption, and CSF leakage through small tears) to explain the symptoms.

CSF leak — Today, the prevailing etiology is that of CSF leakage, which may occur in the context of rupture of an arachnoid membrane [19]. An underlying connective tissue disorder may result in dural weakness and play a role in the development of spontaneous low CSF pressure, as suggested by studies reporting abnormal connective tissue abnormalities in patients with spontaneous CSF leaks mai and/or deficient fibrillin, elastin,

EFTA00956004

or both in dermal fibroblast cultures from such patients [22]. Meningeal diverticula, often seen in patients with CSF leaks, may be related to this connective tissue problem W], and meningeal diverticula have been described in patients with Marfan's syndrome [n].

A potential contributing factor to the development of spontaneous low CSF pressure is that of minor trauma or an inciting event, including a fall, a sudden twist or stretch, sexual intercourse or orgasm, a sudden sneeze, sports activity, or "trivial trauma" [24]. These relatively minor events may cause rupture of spinal epidural cysts (formed during fetal development) or perineural (Tarlov) cysts, or may cause a tear in a dural nerve sheath [12] with resultant cryptic CSF leakage.

Finally, degenerative disc disease and osseous spurs may rarely cause spontaneous low CSF pressure headache, presumably by causing dural tears [25-28].

Low venous pressure — An alternative hypothesis postulates that spontaneous intracranial hypotension results primarily from the lowering of venous pressure within the inferior vena cava system, amplified by the displacement of blood toward the heart that occurs due to the activation of leg muscles during standing and walking [29]. The lower pressure in the inferior vena cava leads to epidural venous hypotension and outflow of CSF along the spinal cavity, and in some cases precipitates actual CSF leaks from existing radicular arachnid diverticula or cysts. In this paradigm, dural tears are not the cause of the condition but instead are a result of the low epidural pressure. Blood patching at the epidural lumbar space used to treat the condition does not work by sealing CSF leaks, but instead is effective because it disconnects the low-pressure epidural lumbar venous network that drains to the inferior vena cava and diverts venous return to the epidural thoracic and cervical venous network that drains to the superior vena cava.

This hypothesis has been challenged by experts who dispute a number of its assumptions regarding the anatomic and pathophysiologic characteristics of the spinal epidural veins [11]. In addition, the skeptics point out radiologic evidence that epidural veins are distended and the epidural sac is collapsed in patients with spontaneous intracranial hypotension prior to treatment, and that the epidural veins and dural sac return to normal proportions after treatment with blood patch [31]. These pre-treatment observations are best explained by CSF hypotension with dural sac collapse and expansion of the extradural space [311].

EPIDEMIOLOGY — There are few data regarding the incidence of low cerebrospinal fluid (CSF) pressure headache. In a systematic review published in 2006, the following observations were made [32]:

■ The estimated annual incidence is 5 per 100,000

■ The peak incidence is around age 40, but children and elderly are also affected

■ Women are affected more frequently than men, with a female to male ratio of 2:1

The author concluded that spontaneous intracranial hypotension should be considered an important cause of new daily persistent headaches, particularly among young and middle-aged patients [32]. (See "New daily persistent headache".)

CLINICAL FEATURES — Postural headache is usually but not always the major manifestation of spontaneous low cerebrospinal fluid (CSF) pressure. Occasional patients report no headache, typically when other symptoms of low CSF pressure are predominant [32].(See 'Associated symptoms and complications' below.)

Headache — The headache caused by low CSF pressure may be of sudden or gradual onset. Rarely, it starts as a thunderclap headache [23]. (See "Thunderclap headache".)

Headache pain with this syndrome is often described as an intense, throbbing, or dull pain that may be generalized or focal. However, headache severity is widely variable and ranges from mild to incapacitating [32]. Frontal pain is reported by patients as often as occipital and diffuse pain [24].

Headache relief is typically obtained with recumbency, usually within minutes. In rare cases associated with an asymmetric cervical CSF leak, headache relief occurs only with lying on one side of the body [33]. The headache

EFTA00956005

is seldom relieved with analgesics. Exacerbating factors include erect posture, head movement, coughing, straining, sneezing, jugular venous compression, and high altitude [34].

During the course of the illness, the orthostatic features may disappear, and a chronic daily headache may develop []. On occasion, the postural component may not be present at all. Furthermore, paradoxical headache, worse with recumbency and better with the upright position, has been reported in rare patients with spontaneous low CSF pressure [35,36]. In other cases, the headache can mimic a primary headache syndrome, such as primary cough headache [E] or primary exertional headache [M]. These primary headache syndromes are discussed separately. (See "Primary cough headache".)

Most CSF leaks occur at the thoracic or cervicothoracic junction. Leakage of CSF into the petrous or ethmoidal regions or through the cribriform plate can also occur, and although overt CSF otorrhea and CSF rhinorrhea may result, it is not uncommon for the patient to swallow the fluid and be unaware of the leak.

Low CSF pressure headache may spontaneously resolve within two weeks [39]. In some cases, it lasts months or rarely years.

Associated symptoms and complications - In 1825, Magendie described vertigo and unsteadiness in a patient following the removal of CSF [40]. Today, the list of reported associated symptoms is varied and extensive. The most common associated symptoms with spontaneous low CSF pressure headache, reported in about half of patients, are [32]:

■ Neck pain or stiffness

■ Nausea

■ Vomiting

Other associated symptoms include the following [32]:

• Change in hearing (eg, hyperacusis, echoing, or tinnitus) [2,14,24]

• Anorexia

• Vertigo

• Dizziness

• Diaphoresis

• Blurred vision

- Diplopia

• Transient visual obscurations [3]

- Photophobia

■ Unsteadiness or staggering gait [16]

" Hiccups

- Dysgeusia [24]

Other rare symptoms associated with the syndrome are probably due to distortion or compression of brain and/or spinal cord structures. These rare manifestations (and associated central nervous system structures) are as follows [41]:

■ Galactorrhea and hyperprolactinemia (pituitary stalk)

■ Ataxia (posterior fossa)

- Quadriparesis (brainstem and upper cervical spinal cord) [36]

■Cerebellar hemorrhage (cerebellar bridging veins) [36]

■ Parkinsonism [42] and chorea [43] (deep midline structures)

■ Hypoactive, hypoalert behavior (pons and midbrain) [44]

■ Stupor and coma (diencephalon) [45,46]

Except for hemorrhage, these manifestations are typically reversible with successful treatment of the CSF leak.

EFTA00956006

Subtle cognitive deficits may be associated with the syndrome and are typically reversible with successful treatment of the CSF leak [32]. Frank dementia is rare, but a case of reversible frontotemporal dementia attributed to low CSF pressure has been reported [An Another report described eight patients with "frontotemporal brain sagging syndrome" (FBSS) who presented with progressive behavioral symptoms and cognitive dysfunction suggestive of behavioral variant frontotemporal dementia [M. Atypical clinical features included headache and daytime somnolence. MRI in all cases revealed sagging of the frontal and temporal lobes with downward displacement of the cerebellar tonsils, swelling of the midbrain, flattening of the ventral pons and effacement of the basal cisterns. Two patients had pachymeningeal enhancement. Treatments directed at intracranial hypotension led to unsustained improvement in a few patients. Frontotemporal dementia is discussed separately. (See "Frontotemporal dementia: Clinical features and diagnosis".)

Examination — The neurologic examination is typically normal [19]. Unilateral or bilateral abducens palsies have been reported, as have visual field defects [1]. A slow pulse, or vagus pulse, has also been described [5].

Cerebrospinal fluid analysis — The opening pressure with lumbar puncture (LP) in patients with spontaneous intracranial hypotension usually ranges from 0 to 70 mmH20 [4], whereas normal opening pressure is generally considered to be 60 to 200 mmH2O in adults and children; opening pressures up to 250 mmH2O may be normal in obese people. (See "Cerebrospinal fluid: Physiology and utility of an examination in disease states", section on 'Physiology of CSF formation and flow'.)

The opening pressure is in the normal range in some cases of proven spontaneous intracranial hypotension, especially if the measurement is made after a period of recumbency, or if the CSF leak is intermittent. Even within the same patient, the CSF pressure may vary from LP to LP.

In patients with spontaneous intracranial hypotension, LPs are often difficult. Repeated attempts may be needed to obtain CSF, and traumatic blood-tinged fluid may result. In addition, so-called "thy taps" may be encountered, requiring cistemal taps to collect the fluid. In rare instances, the CSF pressure is negative (below that of atmospheric pressure), and a sucking noise may be heard when the stylet is removed from the LP needle.

The CSF is typically clear and colorless. Common CSF abnormalities include a moderate lymphocytic pleocytosis (up to 50 cells/mm3), the presence of red blood cells, and elevated protein (commonly up to 100 mg/dL) [R]. The CSF pleocytosis likely reflects a reactive phenomenon secondary to hydrostatic pressure changes [39]. The elevated protein may be related to lowered CSF pressure leading to disruption of normal hydrostatic and oncotic pressure across the venous sinus and arachnoid villi, resulting in the passage of serum protein into the CSF Lan

CSF cytology and microbiology is always normal and CSF glucose is never low [zn].

Brain MRI — The advent of MRI has greatly improved the diagnosis of low CSF headaches. While brain and/or spine MRI is abnormal in most patients with spontaneous intracranial hypotension, a systematic review estimated that brain MRI remains normal in up to 20 percent of patients [32].

Prominent abnormal features on brain MRI include the following:

■ Diffuse meningeal enhancement (DME) (image 1) [50]

■ Subdural hematomas or hygromas, presumably from rupture of the bridging veins as the CSF volume decreases [40,51]

■"Sagging" of the brain, with cerebellar tonsillar herniation and descent of the brainstem mimicking a Chiari I malformation (image 2) [52]

" Engorgement of cerebral venous sinuses [53]

" Pituitary enlargement [54,55], flattening of the optic chiasm, and increased anteroposterior diameter of the brainstem

• Decrease in the size of cisterns and ventricles

EFTA00956007

The acronym SEEPS (for Subdural fluid collections, Enhancement of the pachymeninges, Engorgement of the venous structures, Pituitary enlargement, and Sagging of the brain) recalls the major features of spontaneous intracranial hypotension on brain MRI [32].

Meningeal enhancement involves the pachymeninges and spares the leptomeninges, without abnormal enhancement in the depth of the cortical sulci or around the brainstem (image I) [R,a56-58].It is also contiguous (without skip areas), non-nodular, and involves both supratentorial and infratentorial compartments. The enhancement is often thick and obvious, but sometimes can be quite thin. Diffuse meningeal enhancement may improve or resolve with resolution of the headache.

Diffuse meningeal enhancement is believed to be secondary to vascular dilatation. According to the Monro-Kellie doctrine [9], any decrease in CSF volume must be compensated given the noncompressible nature of the skull. As a result, loss of CSF volume results in an increase in intracranial blood volume, and venous engorgement results in a greater concentration of gadolinium in the dural vasculature and interstitial fluid of the dun.

A minority ofpatients with spontaneous intracranial hypotension may present with swelling of the upper brainstem and diencephalon, but limited to absent DME and subdural fluid collections on MRI [60]. The upper brainstem swelling is hypothesized to be a manifestation of venous stagnation caused by downward stretching of the vein of Galen, which results in a functional stenosis where the vein of Galen joins the straight sinus.

Head CT — Head computed tomography (CT) in patients with CSF leaks is usually normal. However, subdural fluid collections or increased tentorial enhancement may be noted [E]. In addition, slit-shaped ventricles have been reported, with associated tight basal cisterns and scant CSF over the cortex [U. These changes resolve after resolution of the headache and are believed to be secondary to brain edema, perhaps itself secondary to venous dilatation.

DIAGNOSIS — The diagnosis of low cerebrospinal fluid (CSF) pressure headache should be considered in patients who present with positional orthostatic headache, with or without associated symptoms, perhaps in the setting ofminor trauma, and in the absence ofa history of dural puncture or other cause of CSF fistula. Low CSF pressure headache following a lumbar puncture (LP) rarely creates a clinical dilemma.

Confirmation of the diagnosis requires evidence of low CSF pressure by MRI (eg, pachymeningeal enhancement) or LP, and/or evidence of a CSF leak on neuroimaging studies, mainly computed tomographic (CT) myelography or, less often, radioisotope cisternography.

For patients with suspected CSF pressure headache, we recommend brain MRI with gadolinium to assess for the typical features. (See 'Brain MRI' above and Neuroimaging' below.)

Diagnostic criteria — Diagnostic criteria for "headache attributed to spontaneous (or idiopathic) low cerebrospinal fluid (CSF) pressure," as delineated in the second edition of the International Classification of Headache Disorders, are as follows MI

• A. Diffuse and/or dull headache that worsens within 15 minutes after sitting or standing, with at least one of the following (and fulfilling criterion D):

⚫ Neck stiffness

• Tinnitus

• Hypacusia

• Photophobia

• Nausea

• B. At least one of the following:

• Evidence of low CSF pressure on MRI (eg, pachymeningeal enhancement)

EFTA00956008

• Evidence of CSF leakage on conventional myelography, CT myelography, or cistemography

• CSF opening pressure <60 mmH2O in sitting position

■ C. No history of dural puncture or other cause of CSF fistula

■ D. Headache resolves within 72 hours after epidural blood patching

A separate set of criteria exists for post-dural (post-lumbar) puncture headache.

Neuroimaging — The advent of brain MRI has greatly improved the diagnosis of low CSF headaches. Spine MRI, radioisotope cistemography, and CT myelography can be useful in evaluating patients with spontaneous low pressure headache, particularly when brain MRI is nondiagnostic. These imaging studies are generally not done in patients with post-lumbar puncture headache, where the diagnosis is more obvious.

The utility of head CT for confirming the diagnosis is limited, as head CT is often normal in patients with spontaneous low CSF pressure headache. However, head CT may suggest the diagnosis by demonstrating subdural fluid collections, slit-shaped ventricles, tight basal cisterns, scant CSF over the cortex, or increased tentorial enhancement [32]. (See 'Head CT' above.)

MRI of brain and spine — For patients with suspected low CSF pressure headache, we recommend obtaining brain MRI with gadolinium to assess for the typical features of the syndrome, which are diffuse pachymeningeal enhancement (image 1), "sagging" of the brain, tonsillar descent, and posterior fossa crowding (image 2). (See 'Brain MRI' above.)

While brain and/or spine MRI is abnormal in most patients with spontaneous intracranial hypotension, a systematic review published in 2006 estimated that brain MRI remains normal in up to 20 percent of patients [32]. A subsequent report evaluated 18 patients with spontaneous intracranial hypotension and found that the sensitivities of brain and spine MRI were 83 and 94 percent, respectively [31].

Spinal MRI may be helpful for confirming the diagnosis and for identifying the exact location of the CSF leakage. Such studies may reveal [zR]:

■ Extra-arachnoid fluid collections

■ Collapse of the dural sac and engorgement of the epidural venous plexus

■ Meningeal diverticula

■ Extradural extravasation of fluid

In a series of 10 women who had characteristic orthostatic headache without a previous history of dural tear, spinal MRI revealed dilated cervical epidural veins [12]. The authors concluded that this finding is an indicator of CSF hypovolemia and can be used to differentiate spontaneous low CSF pressure from the other causes of diffuse meningeal enhancement.

Subtraction MRI employs rapid postprocessing image analysis of standard T2 and T1 MRI sequences in order to delineate the dural sac of the spinal cord and distinguish between fluid and fat. In a report of 17 patients with spontaneous intracranial hypotension, subtraction MRI of the spinal cord identified the epidural CSF fluid collection in all patients, although the site of the CSF leak was not detected [64]. Additional studies are needed to determine the sensitivity and specificity of this method.

Radioisotope cistemography — Radioisotope cistemography is particularly useful for identifying CSF leaks. It is usually obtained as the next step if a CSF leak is suspected and MRI is normal or nondiagnostic.

Since a lumbar puncture is required as part of the procedure, opening CSF pressure is measured, and CSF is sent for analysis at the same time. Placement of numbered cotton pledgets in the nose for subsequent detection of radioactivity aids in detection and localization of CSF leakage through the paranasal sinuses.

Normal CSF flow involves cephalad migration from the site of injection to the cerebral convexities and the sylvian fissures [5], and, therefore, the most common cisternographic abnormality in CSF leaks is the absence or

EFTA00956009

paucity of activity over the cerebral convexities [65-67]. It is advisable to look for early accumulation within the bladder and kidneys, or leakage of isotope outside of the normal confines of the subarachnoid space. Early soft tissue uptake of radioisotope may also be suggestive of CSF leak, perhaps reflecting unusually rapid uptake of the radioisotope into the bloodstream through the epidural venous plexus [M.

In a small retrospective study of patients with spontaneous CSF leaks, the diagnosis of intracranial hypotension was supported in all 10 patients who had radionucleotide cistemography, which showed early bladder accumulation of the nucleotide and reduced activity over the cerebral hemispheres, consistent with rapid uptake of the tracer in the bloodstream [0]. In addition, the location of the leaks was identified in 7 of the 10 patients with this method.

Iatrogenic CSF leak from the lumbar puncture is a potential complication of radioisotope cistemography [69].

CT myelography — Computed tomographic (CT) myelography is the best test to identify the site of the leak. CT myelography is most commonly used in order to localize the level of the spinal leak when treatment beyond epidural blood patch (such as surgery or fibrin glue injection) is contemplated.

Both early and delayed cuts should be obtained at each spinal level, since CSF leaks may be rapid or slow. In cases where radiocistemography or spinal MRI has identified the approximate level of the leak, focused CT cuts can be used to locate the source more precisely.

MR myelography — Preliminary evidence suggests that magnetic resonance (MR) myelography using heavily T2-weighted sequences may be an alternative to CT myelography for detecting the level of CSF leaks.

• In a report of 19 patients with spontaneous intracranial hypotension, the accuracy of MR myelography for demonstrating and localizing CSF leaks was similar to CT myelography [242].

• In a study involving 17 patients with spontaneous intracranial hypotension, characteristic imaging features of spontaneous intracranial hypotension were seen on initial brain MRI in 13 patients (76 percent), and abnormal CSF collections were seen on MR myelography in the four patients (24 percent) whose initial head MRI was negative [n]. The authors suggested that the combination of brain MRI and MR myelography may improve the early diagnostic rate for spontaneous intracranial hypotension.

Lumbar puncture —A lumbar puncture (LP) can document low CSF pressure in suspected cases of spontaneous low CSF pressure headache, and may be diagnostically useful when MRI is not available or is not tolerated. However, LP is generally not necessary in cases where MRI is consistent with low CSF pressure headache. There is also concern that dural puncture from the procedure could potentially worsen the low CSF pressure and exacerbate the syndrome. In addition, the opening pressure is normal in some patients with proven spontaneous intracranial hypotension. (See 'Cerebrospinal fluid analysis' above.)

Although current diagnostic criteria define low CSF pressure based upon measurements taken in the sitting position [63], we recommend using the lateral decubitus position for greater accuracy. To ascertain correct placement of the spinal needle, CSF flow should be observed either spontaneously, with gentle aspiration, or with Valsalva maneuver [14]. (See "Lumbar puncture: Technique; indications; contraindications; and complications in adults".)

Differential diagnosis — Patients who have CSF shunts placed for various neurosurgical indications may develop a syndrome identical to that of spontaneous intracranial hypotension, probably secondary to overdrainage (overshunting) of CSF [a].

Orthostatic headache in the absence of CSF leak may also be a manifestation of the postural tachycardia syndrome or orthostatic intolerance [M]. (See "Postural tachycardia syndrome".)

One case report described spontaneous orthostatic headache and a "dry tap" at lumbar puncture that was attributed to an intradural myxopapillary ependymoma [73].

EFTA00956010

Misdiagnosis — The syndrome of spontaneous low CSF pressure headache has been under-recognized, in part because headache in general is a common ailment, and because patients with low CSF pressure headache typically present with a normal neurologic examination. The diagnosis was often missed prior to the advancement of MRI imaging and the specific MRI findings associated with low CSF pressure headache. Even in the modern era of MRI availability, misdiagnosis is common [L4].

Inappropriate and unnecessary clinical investigations may result if the diagnosis of spontaneous low CSF pressure headache is not considered. As an example, before diffuse meningeal enhancement on brain MRI was a recognized feature of spontaneous intracranial hypotension, patients with this finding were often subjected to extensive testing to rule out other causes such as meningeal carcinomatosis, meningitis, subarachnoid hemorrhage, neuroborreliosis, and neurosarcoidosis. (See 'Brain MRI' above.)

SUMMARY AND RECOMMENDATIONS

• The major features of the classic spontaneous low cerebrospinal fluid (CSF) pressure headache syndrome are orthostatic headache, low CSF pressure, and diffuse meningeal enhancement on brain MRI. (See 'Introduction and terminology' above and 'Clinical features' above.)

• The prevailing etiology is CSF leakage, which may occur in the context of rupture of an arachnoid membrane. An alternative hypothesis is that low CSF pressure is caused by epidural venous hypotension from the lowering of venous pressure within the inferior vena cava system. Most CSF leaks occur at the thoracic or cervicothoracic junction. An underlying connective tissue disorder may play a role in the development of CSF leaks. Other potential contributing factors are minor trauma, degenerative disc disease, and osseous spurs. (See 'Pathophysiology' above.)

• The estimated annual incidence of spontaneous low CSF pressure headache is 5 per 100,000, with a peak incidence around age 40 and a female to male ratio of 2:1. (See 'Epidemiology' above.)

• The headache caused by low CSF pressure may be sudden or gradual in onset, and severity is widely variable. The headache is typically relieved with recumbency and exacerbated with upright posture. Other headache patterns have also been reported with this syndrome. Commonly associated symptoms are neck pain or stiffness, nausea and vomiting, change in hearing, and photophobia. There is a varied and extensive list of additional associated symptoms. (See 'Clinical features' above and 'Headache' above and 'Associated symptoms and complications' above.)

• Traction on pain-sensitive intracranial and meningeal structures, particularly sensory nerves and bridging veins, is thought to cause headache and some of the associated symptoms. (See 'Pathophysiology' above.)

• Some rare but serious symptoms (eg, altered level of consciousness, parkinsonism) associated with the syndrome are probably caused by distortion or compression of brain and/or spinal cord structures. (See 'Associated symptoms and complications' above.)

• For patients with suspected low CSF pressure headache, we recommend brain MRI with gadolinium to assess for the typical features, which include diffuse meningeal enhancement (image 1), subdural hematomas or hygromas, sagging of the brain (image 2), engorgement of cerebral venous sinuses, and pituitary enlargement. Brain MRI remains normal in up to 20 percent of patients with low CSF pressure headache. (See 'Brain MRI' above.)

• The diagnosis of low CSF pressure headache should be considered in patients who present with positional orthostatic headache, with or without associated symptoms, perhaps in the setting of minor trauma, and in the absence of a history of dural puncture or other cause of CSF fistula. Confirmation of the diagnosis requires evidence of low CSF pressure by MRI or lumbar puncture and/or evidence of a CSF leak on CT myelography or radioisotope cisternography. Low CSF pressure headache following a lumbar puncture rarely creates a clinical dilemma. (See 'Diagnosis' above.)

• Diagnostic criteria for headache attributed to spontaneous low CSF pressure are discussed above. (See 'Diagnostic criteria' above.)

• Patients who have CSF shunts in place may develop a syndrome identical to that of spontaneous intracranial hypotension, probably secondary to overdrainage (overshunting) of CSF. (See 'Differential diagnosis' above.)

• Initial therapy for most patients with a confirmed diagnosis of spontaneous low CSF pressure headache consists of conservative measures and/or epidural blood path therapy. For patients who fail these

EFTA00956011

treatments, additional options include continuous epidural saline infusion, epidural fibrin glue, or surgical repair of the defect. Treatment of spontaneous low CSF pressure headache is discussed separately. (See "Treatment and prognosis of spontaneous low cerebrospinal fluid pressure headache".)

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

| 1 Schievink WI Reimer R, Folger WN. Surgical treatment of spontaneous intracranial hypotension associated<br />with a spinal arachnoid diverticulum. Case report. J Neurosurg 1994. 80:736. |
|-|
| 2 Mokri B. Spontaneous cerebrospinal fluid leaks: from intracranial hypotension to cerebrospinal fluid<br />hypovolemia--evolution of a concept. Mayo Clin Proc 1999; 74:1113. |
| 3 Horton JC, Fishman RA. Neurovisual findings in the syndrome of spontaneous intracranial hypotension from<br />dural cerebrospinal fluid leak. Ophthalmology 1994. 101:244. |
| 4 Lipman with traction IJ. Primary headache. intracranial Dis Nery hypotension: Syst 1977; 38:212. the syndrome of spontaneous low cerebospinal fluid pressure |
| 5 Marcelis J, Silberstein SD. Spontaneous low cerebrospinal fluid pressure headache. Headache 1990. 30:192. |
| 6 Swanson Practice, Bradley JW, Dodick WG, DW, Daroff Capobianco RB, Fenichel DJ. Headache GM, Marsden and other CD. (Eds), craniofacial Butterworth, pain. In: Boston Neurology 2000. in p.1832. Clinical |
| 7 Capobianco DI Kuczler FJ Jr. Case report: primary intracranial hypotension. Mil Med 1990; 155:64. |
| 8 Mokri gadolinium B Piepgras enhancement. DG, Miller Mayo GM. Clin Syndrome Proc 1997. of 72:400. orthostatic headaches and diffuse pachymeningeal |
| 9 Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 2-1998. A<br />50-year-old woman with increasing headache and a left abducent-nerve palsy. N Engl J Med 1998. 338:180. |
| 10 Mokri B Hunter SF, Atkinson JL, Piepgras DG. Orthostatic headaches caused by CSF leak but with normal<br />CSF pressures. Neurology 1998. 51:786. |
| 11 Chung and outcome. Si Kim Neurology JS, Lee MC. 2000; Syndrome 55:1321. of cerebral spinal fluid hypovolemia: clinical and imaging features |
| 12 Miyazawa K, Shiga Y, Hasegawa T, et al. CSF hypovolemia vs intracranial hypotension in "spontaneous<br />intracranial hypotension syndrome". Neurology 2003; 60:941. |
| 13 Levine DN, Rapalino O. The pathophysiology of lumbar puncture headache. J Neurol Sci 2001; 192:1. |
| 14 Silberstein 32:84. SD Marcelis J. Headache associated with changes in intracranial pressure. Headache 1992; |
| 15 Raskin NH. Lumbar puncture headache: a review. Headache 1990; 30:197. |
| 16 Fernandez E. Headaches associated with low spinal fluid pressure. Headache 1990; 30:122. |
| 17 Schaltenbrand 1938; 3:290. G. Neuere Anschauungen zur Pathophysiologie der Liquorzirkulation. Zentralbl Neurochir |
| 18 SCHALTENBRAND 1953; 1:805. G. Normal and pathological physiology of the cerebrospinal fluid circulation. Lancet |
| 19 Lasater GM. Primary intracranial hypotension. The low spinal fluid pressure syndrome. Headache 1970;<br />10:63. |
| 20 Mokri B Maher CO, Sencakova D. Spontaneous CSF leaks: underlying disorder of connective tissue.<br />Neurology 2002; 58:814. |
| 21 Ferrante E, Citterio A, Savino A Santalucia P. Postural headache in a patient with Marfan's syndrome.<br />Cephalalgia 2003; 23:552. |
| 22 Schrijver I, Schievink WI, Godfrey M et al. Spontaneous spinal cerebrospinal fluid leaks and minor skeletal<br />features of Marfan syndrome: a microfibrillopathy. J Neurosurg 2002. 96:483. |
| 23 Grimaldi D, Mea E Chiapparini L et al. Spontaneous low cerebrospinal pressure: a mini review. Neurol Sci<br />2004. 25 Suppl 3:S135. |

EFTA00956012

<table><tr><th>24</th><th>Lay CL, Campbell JK, Mokri B. Low cerebrospinal fluid pressure headache. In: Headache, Goadsby PJ,
Silberstein SD (Eds), Butterworth-Heinemann, Boston 1997. p.355.</th></tr><tr><td></td><td>Vishteh AG, Schievink WI, Baskin JJ, Sonntag VK. Cervical bone spur presenting with spontaneous</td></tr><tr><td>25</td><td>intracranial hypotension. Case report. J Neurosurg 1998; 89:483.</td></tr><tr><td></td><td>Eross EJ, Dodick DW, Nelson KD, et al. Orthostatic headache syndrome with CSF leak secondary to bony</td></tr><tr><td>26</td><td>pathology of the cervical spine. Cephalalgia 2002; 22:439.</td></tr><tr><td></td><td>Winter SC, Maartens NF, Anslow P, Teddy PJ. Spontaneous intracranial hypotension due to thoracic disc</td></tr><tr><td>27 22</td><td>herniation. Case report. J Neurosurg 2002; 96:343.</td></tr><tr><td></td><td>Rapport RL, Hillier D, Scearce T, Ferguson C. Spontaneous intracranial hypotension from intradural thoracic</td></tr><tr><td>28</td><td>disc herniation. Case report. J Neurosurg 2003; 98:282.</td></tr><tr><td></td><td>Franzini A, Messina G, Nazzi V, et al. Spontaneous intracranial hypotension syndrome: a novel speculative</td></tr><tr><td>29</td><td>physiopathological hypothesis and a novel patch method in a series of 28 consecutive patients. J Neurosurg
2010; 112:300.</td></tr><tr><td>30</td><td>Groen RJ, Hoogland PV. Spontaneous intracranial hypotension. J Neurosurg 2010; 113:685.</td></tr><tr><td></td><td>Watanabe A, Horikoshi T, Uchida M, et al. Diagnostic value of spinal MR imaging in spontaneous</td></tr><tr><td>31</td><td>intracranial hypotension syndrome. AJNR Am J Neuroradiol 2009; 30:147.</td></tr><tr><td>32</td><td>Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA 2006;</td></tr><tr><td>32

33</td><td>295:2286.
Schievink WI. Headache relief from lateralizing head and neck positions in spontaneous intracranial
hypotension. Neurology 2011; 77:799.
Batsis JA, Phy MP. Intracranial hypotension: aggravation of headache at high altitude. Headache 2005;</td></tr><tr><td>34 +4</td><td>45:380.</td></tr><tr><td></td><td>Mokri B, Aksamit AJ, Atkinson JL. Paradoxical postural headaches in cerebrospinal fluid leaks. Cephalalgia</td></tr><tr><td>35 55</td><td>2004; 24:883.</td></tr><tr><td></td><td>Schievink WI, Maya MM. Quadriplegia and cerebellar hemorrhage in spontaneous intracranial hypotension.</td></tr><tr><td>36</td><td>Neurology 2006; 66:1777.</td></tr><tr><td>37</td><td>Evans RW, Boes CJ. Spontaneous low cerebrospinal fluid pressure syndrome can mimic primary cough</td></tr><tr><td></td><td>headache. Headache 2005; 45:374.</td></tr><tr><td>38</td><td>Mokri B. Spontaneous CSF leaks mimicking benign exertional headaches. Cephalalgia 2002; 22:780.</td></tr><tr><td>39</td><td>Rando TA, Fishman RA. Spontaneous intracranial hypotension: report of two cases and review of the</td></tr><tr><td></td><td>literature. Neurology 1992; 42:481.</td></tr><tr><td>40</td><td>PAGE F. Intracranial hypotension. Lancet 1953; 1:1.</td></tr><tr><td>41</td><td>Mokri B. Spontaneous intracranial hypotension. Curr Pain Headache Rep 2001; 5:284.</td></tr><tr><td></td><td>Pakiam AS, Lee C, Lang AE. Intracranial hypotension with parkinsonism, ataxia, and bulbar weakness. Arch</td></tr><tr><td>42</td><td>Neurol 1999; 56:869.</td></tr><tr><td></td><td>Mokri B, Ahlskog JE, Luetmer PH. Chorea as a manifestation of spontaneous CSF leak. Neurology 2006;</td></tr><tr><td>43</td><td>67:1490.</td></tr><tr><td>44</td><td>Vetrugno R, Mascalchi M, Chierichetti F, et al. Hypoactive-hypoalert behavior ("psychic akinesia") in</td></tr><tr><td></td><td>intracranial hypotension syndrome. Neurology 2008; 71:1452.
Pleasure SJ, Abosch A, Friedman J, et al. Spontaneous intracranial hypotension resulting in stupor caused by</td></tr><tr><td>45</td><td>diencephalic compression. Neurology 1998; 50:1854.</td></tr><tr><td></td><td>Kashmere JL, Jacka MJ, Emery D, Gross DW. Reversible coma: a rare presentation of spontaneous</td></tr><tr><td>46</td><td>intracranial hypotension. Can J Neurol Sci 2004; 31:565.</td></tr><tr><td>47</td><td>Hong M, Shah GV, Adams KM, et al. Spontaneous intracranial hypotension causing reversible</td></tr><tr><td></td><td>frontotemporal dementia. Neurology 2002; 58:1285.
Wicklund MR, Mokri B, Drubach DA, et al. Frontotemporal brain sagging syndrome: an SIH-like</td></tr><tr><td>48</td><td>presentation mimicking FTD. Neurology 2011; 76:1377.</td></tr><tr><td>49</td><td>Mokri B. Low cerebrospinal fluid pressure syndromes. Neurol Clin 2004; 22:55.</td></tr></table>

EFTA00956013

<table><tr><th></th><th>Mokri, B, Krueger, BR, Miller, GM, Piepgras, DG. Meningeal gadolinium enhancement in low-pressure</th></tr><tr><td>50</td><td>headaches. J Neuroimaging 1993; 3:11.</td></tr><tr><td>51</td><td>Chung SJ, Lee JH, Kim SJ, et al. Subdural hematoma in spontaneous CSF hypovolemia. Neurology 2006;
67:1088.</td></tr><tr><td>52</td><td>Atkinson JL, Weinshenker BG, Miller GM, et al. Acquired Chiari I malformation secondary to spontaneous
spinal cerebrospinal fluid leakage and chronic intracranial hypotension syndrome in seven cases. J
Neurosurg 1998; 88:237.</td></tr><tr><td>53</td><td>Bakshi R, Mechtler LL, Kamran S, et al. MRI findings in lumbar puncture headache syndrome: abnormal
dural-meningeal and dural venous sinus enhancement. Clin Imaging 1999; 23:73.</td></tr><tr><td>54</td><td>Mokri B, Atkinson JL. False pituitary tumor in CSF leaks. Neurology 2000; 55:573.</td></tr><tr><td>55 SSSS</td><td>Alvarez-Linera J, Escribano J, Benito-León J, et al. Pituitary enlargement in patients with intracranial
hypotension syndrome. Neurology 2000; 55:1895.</td></tr><tr><td>56</td><td>Pannullo SC, Reich JB, Krol G, et al. MRI changes in intracranial hypotension. Neurology 1993; 43:919.</td></tr><tr><td>552</td><td>Spelle L, Boulin A, Tainturier C, et al. Neuroimaging features of spontaneous intracranial hypotension.</td></tr><tr><td>57</td><td>Neuroradiology 2001; 43:622.</td></tr><tr><td>58</td><td>Lin WC, Ling JF, Fuh JL, et al. MR findings of spontaneous intracranial hypotension. Acta Radiol 2002;
43:249.</td></tr><tr><td>59</td><td>Mokri B. The Monro-Kellie hypothesis: applications in CSF volume depletion. Neurology 2001; 56:1746.</td></tr><tr><td>60</td><td>Savoiardo M, Minati L, Farina L, et al. Spontaneous intracranial hypotension with deep brain swelling. Brain
2007; 130:1884.</td></tr><tr><td>61</td><td>Mokri B. Headaches associated with abnormalities in intracranial structure and function: low cerebrospinal
fluid pressure headaches. In: Wolff's headache and other head pain, Silberstein SD, Lipton RB, Dalessio DJ.
(Eds), Oxford University Press, New York 2001. p.417.</td></tr><tr><td>62</td><td>Murros K, Fogelholm R. Spontaneous intracranial hypotension with slit ventricles. J Neurol Neurosurg
Psychiatry 1983; 46:1149.</td></tr><tr><td>63</td><td>Headache Classification Subcommittee of the International Headache Society. The International
Classification of Headache Disorders: 2nd edition. Cephalalgia 2004; 24 Suppl 1:9.</td></tr><tr><td>64</td><td>Bonetto N, Manara R, Citton V, Cagnin A. Spinal subtraction MRI for diagnosis of epidural leakage in SIH.
Neurology 2011; 77:1873.</td></tr><tr><td>65 65</td><td>Molins A, Alvárez J, Sumalla J, et al. Cisternographic pattern of spontaneous liquoral hypotension.
Cephalalgia 1990; 10:59.</td></tr><tr><td>66 66</td><td>Bai J, Yokoyama K, Kinuya S, et al. Radionuclide cisternography in intracranial hypotension syndrome. Ann
Nucl Med 2002; 16:75.</td></tr><tr><td>67</td><td>Sakurai K, Nishio M, Yamada K, et al. Comparison of the radioisotope cisternography findings of
spontaneous intracranial hypotension and iatrogenic cerebrospinal fluid leakage focusing on chronological
changes. Cephalalgia 2012; 32:1131.</td></tr><tr><td>68 88</td><td>Schievink WI, Meyer FB, Atkinson JL, Mokri B. Spontaneous spinal cerebrospinal fluid leaks and
intracranial hypotension. J Neurosurg 1996; 84:598.</td></tr><tr><td>69 69</td><td>Sakurai K, Nishio M, Sasaki S, et al. Postpuncture CSF leakage: a potential pitfall of radionuclide
cisternography. Neurology 2010; 75:1730.</td></tr><tr><td>70 70</td><td>Wang YF, Lirng JF, Fuh JL, et al. Heavily T2-weighted MR myelography vs CT myelography in
spontaneous intracranial hypotension. Neurology 2009; 73:1892.</td></tr><tr><td>71</td><td>Tsai PH, Fuh JL, Lirng JF, Wang SJ. Heavily T2-weighted MR myelography in patients with spontaneous
intracranial hypotension: a case-control study. Cephalalgia 2007; 27:929.</td></tr><tr><td>72</td><td>Mokri B, Low PA. Orthostatic headaches without CSF leak in postural tachycardia syndrome. Neurology
2003; 61:980.</td></tr><tr><td>73</td><td>Schievink WI, Akopov SE. Filum ependymoma mimicking spontaneous intracranial hypotension. Headache
2005; 45:607.</td></tr><tr><td>74</td><td>Schievink WI. Misdiagnosis of spontaneous intracranial hypotension. Arch Neurol 2003; 60:1713.</td></tr></table>

EFTA00956014

Topic 3359 Version 10.0
All rights reserved.
2013 UpToDate, Inc. customerservice@mptodate.com
glQpToDate 
www.uptodate.com

This e-mail message may contain confidential and/or privileged information. If you are not an addressee or otherwise authorized to receive this message, you should not use, copy, disclose or take any action based on this e-mail or any information contained in the message. If you have received this material in error, please advise the sender immediately by reply e-mail and delete this message.

Thank you.

*********

The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jeevacation@gmail.com, and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved

EFTA00956015

📅 Mar 8, 2013 FROM EPSTEIN

Re: melanie has sent you an UpToDate topic

From: jeevacation@gmail.com

To: melanie

great On Fri, Mar 8, 2013 at 6:43 PM, melanie < wrote: JEE - read through this article. It is the most comprehensive that I could find related to low CSF pressure headaches. Perhaps there is something in here that will resonate, or at least it will tell us that this ISN'T what she's got. ©2013 UpToDate® Official Topic from UpToDate®, the clinical information service on the web and mobile devices. To subscribe to UpToDate®, visit us online at Pathophysiology, clinical features, and diagnosi

great

On Fri, Mar 8, 2013 at 6:43 PM, melanie < wrote:

JEE - read through this article. It is the most comprehensive that I could find related to low CSF pressure headaches.

Perhaps there is something in here that will resonate, or at least it will tell us that this ISN'T what she's got.

©2013 UpToDate®

Official Topic from UpToDate®, the clinical information service on the web and mobile devices. To subscribe to UpToDate®, visit us online at

Pathophysiology, clinical features, and diagnosis of spontaneous low cerebrospinal fluid pressure headache

Authors

Christina Sun-Edelstein, MD

Christine L Lay, MD, FRCPC

Section Editor

Jerry W Swanson, MD

Deputy Editor

John F Dashe, MD, PhD

All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Feb 2013. &#124 This topic last updated: Jan 17, 2013.

INTRODUCTION AND TERMINOLOGY — The production, absorption, and flow of cerebrospinal fluid (CSF) play key roles in the dynamics of intracranial pressure. Alterations in CSF pressure can lead to neurologic symptoms, the most common being headache. Most often, the headaches associated with low CSF pressure are orthostatic and occur after lumbar puncture, but similar headaches occur with spontaneous low CSF pressure due to spinal CSF leaks and with CSF shunt overdrainage. In addition, trauma, surgery, and other medical conditions have also been associated with low CSF pressure headache [I].

Spontaneous low CSF pressure headache is being recognized with increasing frequency. Orthostatic headache, low CSF pressure, and diffuse meningeal enhancement on brain magnetic resonance imaging (MRI) are the major features of the classic syndrome. However, some cases have nonorthostatic headache, normal CSF pressure, or no evidence of diffuse meningeal enhancement [2].

Our understanding of this syndrome is still evolving, and historically a number of terms have been used to describe it:

■ Spontaneous (or idiopathic) low CSF pressure headache

■ Spontaneous (or primary) intracranial hypotension

■ Low CSF volume headache

■  Hypoliquorrhoeic headache

	- Aliquorrhea

■CSF leak headache

EFTA00956016

■ CSF hypovolemia

■ CSF volume depletion

This topic will discuss the pathophysiology, epidemiology, clinical features, and diagnosis of spontaneous low CSF pressure headache. Treatment is discussed separately. (See "Treatment and prognosis of spontaneous low cerebrospinal fluid pressure headache".)

Post-lumbar puncture headache is also discussed separately. (See "Post-lumbar puncture headache".)

PATHOPHYSIOLOGY — In the intact craniospinal vault, the brain is supported by the cerebrospinal fluid (CSF), such that a brain weight of 1500 g in air is only 48 g in CSF [I]. As the CSF pressure decreases, there is a reduction in the buoyancy of the brain's supportive cushion. As a result, the brain "sags" in the cranial cavity, causing traction on the anchoring and supporting structures of the brain [4-7].

Cause of headache — Traction on pain-sensitive intracranial and meningeal structures, particularly sensory nerves and bridging veins, is thought to cause headache and some of the associated symptoms [4]. In the upright position this traction is exaggerated, hence the postural component of the headache. Secondary vasodilation of the cerebral vessels to compensate for the low CSF pressure may contribute to the vascular component of the headache by increasing brain volume [5]. Because jugular venous compression increases headache severity, it seems likely that venodilation is a contributing factor to the headache.

CSF hypovolemia, rather than CSF hypotension per se, has been proposed as the underlying cause of the headache syndrome [2], as patients with normal CSF pressure have been described who have clinical and radiographic features that are otherwise typical of orthostatic headache [2,8-10]. In this paradigm, the CSF pressures, clinical manifestations, and imaging abnormalities of the syndrome are thought to be variables dependent on CSF volume [11]. Some authors [fl] have therefore advocated the name "CSF hypovolemia syndrome" for the constellation of symptoms associated with CSF leakage.

An alternative hypothesis is that spinal loss of CSF results in an increased compliance at the caudal end of the spinal CSF space, and the abnormal distribution of craniospinal elasticity causes the headache syndrome [12]. This explanation is compatible with the observation that spinal sites of CSF leakage commonly produce orthostatic headache, whereas cranial sites of CSF leakage (eg, seen with spontaneous CSF rhinorrhea or CSF otorrhea) are less likely to do so.

Cause of low CSF pressure — In 1891 Quincke introduced the lumbar puncture (LP) [14], and in 1898 Bier suffered and was the first to report post-LP headache [15]. He proposed that ongoing leakage of cerebrospinal fluid (CSF) through the dural puncture site was the cause of the headache. This belief is still held today. It is thought that leakage of CSF through the dural rent made by the LP needle exceeds the rate of CSF production, resulting in low CSF volume and pressure um. (See "Post-lumbar puncture headache".)

The clinical syndrome of spontaneous low CSF pressure has been recognized for many years. The syndrome was first proposed in 1938 by Schaltenbrand [L7,1a], who termed it aliquorrhea, and described a headache syndrome virtually identical to that following LP. He proposed three possible mechanisms (decreased CSF production by the choroid plexus, increased CSF absorption, and CSF leakage through small tears) to explain the symptoms.

CSF leak — Today, the prevailing etiology is that of CSF leakage, which may occur in the context of rupture of an arachnoid membrane [n]. An underlying connective tissue disorder may result in dural weakness and play a role in the development of spontaneous low CSF pressure, as suggested by studies reporting abnormal connective tissue abnormalities in patients with spontaneous CSF leaks [20,21] and/or deficient fibrillin, elastin, or both in dermal fibroblast cultures from such patients [22]. Meningeal diverticula, often seen in patients with CSF leaks, may be related to this connective tissue problem [23], and meningeal diverticula have been described in patients with Marfan's syndrome [21].

EFTA00956017

A potential contributing factor to the development of spontaneous low CSF pressure is that of minor trauma or an inciting event, including a fall, a sudden twist or stretch, sexual intercourse or orgasm, a sudden sneeze, sports activity, or "trivial trauma" [24]. These relatively minor events may cause rupture of spinal epidural cysts (formed during fetal development) or perineural (Tarlov) cysts, or may cause a tear in a dural nerve sheath [12] with resultant cryptic CSF leakage.

Finally, degenerative disc disease and osseous spurs may rarely cause spontaneous low CSF pressure headache, presumably by causing dural tears [25-28].

Low venous pressure — An alternative hypothesis postulates that spontaneous intracranial hypotension results primarily from the lowering of venous pressure within the inferior vena cava system, amplified by the displacement of blood toward the heart that occurs due to the activation of leg muscles during standing and walking [22]. The lower pressure in the inferior vena cava leads to epidural venous hypotension and outflow of CSF along the spinal cavity, and in some cases precipitates actual CSF leaks from existing radicular arachnid diverticula or cysts. In this paradigm, dural tears are not the cause of the condition but instead are a result of the low epidural pressure. Blood patching at the epidural lumbar space used to treat the condition does not work by sealing CSF leaks, but instead is effective because it disconnects the low-pressure epidural lumbar venous network that drains to the inferior vena cava and diverts venous return to the epidural thoracic and cervical venous network that drains to the superior vena cava.

This hypothesis has been challenged by experts who dispute a number of its assumptions regarding the anatomic and pathophysiologic characteristics of the spinal epidural veins [30]. In addition, the skeptics point out radiologic evidence that epidural veins are distended and the epidural sac is collapsed in patients with spontaneous intracranial hypotension prior to treatment, and that the epidural veins and dural sac return to normal proportions after treatment with blood patch [11]. These pre-treatment observations are best explained by CSF hypotension with dural sac collapse and expansion of the extradural space [30].

EPIDEMIOLOGY — There are few data regarding the incidence of low cerebrospinal fluid (CSF) pressure headache. In a systematic review published in 2006, the following observations were made [32]:

• The estimated annual incidence is 5 per 100,000

• The peak incidence is around age 40, but children and elderly are also affected

• Women are affected more frequently than men, with a female to male ratio of 2:1

The author concluded that spontaneous intracranial hypotension should be considered an important cause of new daily persistent headaches, particularly among young and middle-aged patients [R]. (See "New daily persistent headache".)

CLINICAL FEATURES — Postural headache is usually but not always the major manifestation of spontaneous low cerebrospinal fluid (CSF) pressure. Occasional patients report no headache, typically when other symptoms of low CSF pressure are predominant [M. (See 'Associated symptoms and complications' below.)

Headache — The headache caused by low CSF pressure may be of sudden or gradual onset. Rarely, it starts as a thunderclap headache [21]. (See "Thunderclap headache".)

Headache pain with this syndrome is often described as an intense, throbbing, or dull pain that may be generalized or focal. However, headache severity is widely variable and ranges from mild to incapacitating [R]. Frontal pain is reported by patients as often as occipital and diffuse pain [24].

Headache relief is typically obtained with recumbency, usually within minutes. In rare cases associated with an asymmetric cervical CSF leak, headache relief occurs only with lying on one side of the body [M]. The headache is seldom relieved with analgesics. Exacerbating factors include erect posture, head movement, coughing, straining, sneezing, jugular venous compression, and high altitude [34].

EFTA00956018

During the course of the illness, the orthostatic features may disappear, and a chronic daily headache may develop [a]. On occasion, the postural component may not be present at all. Furthermore, paradoxical headache, worse with recumbency and better with the upright position, has been reported in rare patients with spontaneous low CSF pressure [M,36]. In other cases, the headache can mimic a primary headache syndrome, such as primary cough headache [37] or primary exertional headache [M]. These primary headache syndromes are discussed separately. (See "Primary cough headache".)

Most CSF leaks occur at the thoracic or cervicothoracic junction. Leakage of CSF into the petrous or ethmoidal regions or through the cribriform plate can also occur, and although overt CSF otorrhea and CSF rhinorrhea may result, it is not uncommon for the patient to swallow the fluid and be unaware of the leak.

Low CSF pressure headache may spontaneously resolve within two weeks [39]. In some cases, it lasts months or rarely years.

Associated symptoms and complications - In 1825, Magendie described vertigo and unsteadiness in a patient following the removal of CSF [in]. Today, the list of reported associated symptoms is varied and extensive. The most common associated symptoms with spontaneous low CSF pressure headache, reported in about half of patients, are [32]:

■ Neck pain or stiffness

■ Nausea

	- Vomiting

Other associated symptoms include the following [32]:

■ Change in hearing (eg, hyperacusis, echoing, or tinnitus) [2,14,24]

• Anorexia

	- Vertigo

■ Dizziness

■ Diaphoresis

■Blurred vision

	- Diplopia

■ Transient visual obscurations [3]

■  Photophobia

■ Unsteadiness or staggering gait [M]

■  Hiccups

- Dysgeusia [24]

Other rare symptoms associated with the syndrome are probably due to distortion or compression of brain and/or spinal cord structures. These rare manifestations (and associated central nervous system structures) are as follows [41]:

■ Galactorrhea and hyperprolactinemia (pituitary stalk)

■ Ataxia (posterior fossa)

■ Quadriparesis (brainstem and upper cervical spinal cord) [36]

■ Cerebellar hemorrhage (cerebellar bridging veins) [36]

■ Parkinsonism [42] and chorea [43] (deep midline structures)

■ Hypoactive, hypoalert behavior (pons and midbrain) [44]

■Stupor and coma (diencephalon) [45,46]

Except for hemorrhage, these manifestations are typically reversible with successful treatment of the CSF leak.

Subtle cognitive deficits may be associated with the syndrome and are typically reversible with successful treatment of the CSF leak [32]. Frank dementia is rare, but a case of reversible frontotemporal dementia attributed to low CSF pressure has been reported [An Mother report described eight patients with

EFTA00956019

"frontotemporal brain sagging syndrome" (FBSS) who presented with progressive behavioral symptoms and cognitive dysfunction suggestive of behavioral variant frontotemporal dementia [4a]. Atypical clinical features included headache and daytime somnolence. MRI in all cases revealed sagging of the frontal and temporal lobes with downward displacement of the cerebellar tonsils, swelling of the midbrain, flattening of the ventral pons and effacement of the basal cisterns. Two patients had pachymeningeal enhancement. Treatments directed at intracranial hypotension led to unsustained improvement in a few patients. Frontotemporal dementia is discussed separately. (See "Frontotemporal dementia: Clinical features and diagnosis".)

Examination — The neurologic examination is typically normal [R]. Unilateral or bilateral abducens palsies have been reported, as have visual field defects [1]. A slow pulse, or vagus pulse, has also been described [5].

Cerebrospinal fluid analysis — The opening pressure with lumbar puncture (LP) in patients with spontaneous intracranial hypotension usually ranges from 0 to 70 mmH20 [4], whereas normal opening pressure is generally considered to be 60 to 200 mmH2O in adults and children; opening pressures up to 250 mmH2O may be normal in obese people. (See "Cerebrospinal fluid: Physiology and utility of an examination in disease states", section on 'Physiology of CSF formation and flow'.)

The opening pressure is in the normal range in some cases of proven spontaneous intracranial hypotension, especially if the measurement is made after a period of recumbency, or if the CSF leak is intermittent. Even within the same patient, the CSF pressure may vary from LP to LP.

In patients with spontaneous intracranial hypotension, LPs are often difficult. Repeated attempts may be needed to obtain CSF, and traumatic blood-tinged fluid may result. In addition, so-called "dry taps" may be encountered, requiring cistemal taps to collect the fluid. In rare instances, the CSF pressure is negative (below that of atmospheric pressure), and a sucking noise may be heard when the stylet is removed from the LP needle.

The CSF is typically clear and colorless. Common CSF abnormalities include a moderate lymphocytic pleocytosis (up to 50 cells/mm3), the presence of red blood cells, and elevated protein (commonly up to 100 mg/dL) [al The CSF pleocytosis likely reflects a reactive phenomenon secondary to hydrostatic pressure changes [39]. The elevated protein may be related to lowered CSF pressure leading to disruption of normal hydrostatic and oncotic pressure across the venous sinus and arachnoid villi, resulting in the passage of serum protein into the CSF [39].

CSF cytology and microbiology is always normal and CSF glucose is never low [49].

Brain MRI — The advent of MRI has greatly improved the diagnosis of low CSF headaches. While brain and/or spine MRI is abnormal in most patients with spontaneous intracranial hypotension, a systematic review estimated that brain MRI remains normal in up to 20 percent of patients [a].

Prominent abnormal features on brain MRI include the following:

• Diffuse meningeal enhancement (DME) (image 1) [50]

• Subdural hematomas or hygromas, presumably from rupture of the bridging veins as the CSF volume decreases [O,51]

• "Sagging" of the brain, with cerebellar tonsillar herniation and descent of the brainstem mimicking a Chiari I malformation (image 2) [52]

• Engorgement of cerebral venous sinuses [a]

• Pituitary enlargement [M,55], flattening of the optic chiasm, and increased anteroposterior diameter of the brainstem

• Decrease in the size of cisterns and ventricles

The acronym SEEPS (for Subdural fluid collections, Enhancement of the pachymeninges, Engorgement of the venous structures, Pituitary enlargement, and Sagging of the brain) recalls the major features of spontaneous intracranial hypotension on brain MRI [32].

EFTA00956020

Meningeal enhancement involves the pachymeninges and spares the leptomeninges, without abnormal enhancement in the depth of the cortical sulci or around the brainstem (image 1) [ ,50,56-58]. It is also contiguous (without skip areas), non-nodular, and involves both supratentorial and infratentorial compartments. The enhancement is often thick and obvious, but sometimes can be quite thin. Diffuse meningeal enhancement may improve or resolve with resolution of the headache.

Diffuse meningeal enhancement is believed to be secondary to vascular dilatation. According to the Monro-Kellie doctrine [52], any decrease in CSF volume must be compensated given the noncompressible nature of the skull. As a result, loss of CSF volume results in an increase in intracranial blood volume, and venous engorgement results in a greater concentration of gadolinium in the dural vasculature and interstitial fluid of the dura.

A minority of patients with spontaneous intracranial hypotension may present with swelling of the upper brainstem and diencephalon, but limited to absent DME and subdural fluid collections on MRI [60]. The upper brainstem swelling is hypothesized to be a manifestation of venous stagnation caused by downward stretching of the vein of Galen, which results in a functional stenosis where the vein of Galen joins the straight sinus.

Head CT — Head computed tomography (CT) in patients with CSF leaks is usually normal. However, subdural fluid collections or increased tentorial enhancement may be noted [fil]. In addition, slit-shaped ventricles have been reported, with associated tight basal cisterns and scant CSF over the cortex [62]. These changes resolve after resolution of the headache and are believed to be secondary to brain edema, perhaps itself secondary to venous dilatation.

DIAGNOSIS — The diagnosis of low cerebrospinal fluid (CSF) pressure headache should be considered in patients who present with positional orthostatic headache, with or without associated symptoms, perhaps in the setting of minor trauma, and in the absence of a history of dural puncture or other cause of CSF fistula. Low CSF pressure headache following a lumbar puncture (LP) rarely creates a clinical dilemma.

Confirmation of the diagnosis requires evidence of low CSF pressure by MRI (eg, pachymeningeal enhancement) or LP, and/or evidence of a CSF leak on neuroimaging studies, mainly computed tomographic (CT) myelography or, less often, radioisotope cistemography.

For patients with suspected CSF pressure headache, we recommend brain MRI with gadolinium to assess for the typical features. (See 'Brain MRI' above and 'Neuroimaging' below.)

Diagnostic criteria — Diagnostic criteria for "headache attributed to spontaneous (or idiopathic) low cerebrospinal fluid (CSF) pressure," as delineated in the second edition of the International Classification of Headache Disorders, are as follows [bI]:

• A. Diffuse and/or dull headache that worsens within 15 minutes after sitting or standing, with at least one of the following (and fulfilling criterion D):

	⚫ Neck stiffness

	⚫ Tinnitus

	⚫ Hypacusia

	• Photophobia

	• Nausea

• B. At least one of the following:

	• Evidence of low CSF pressure on MRI (eg, pachymeningeal enhancement)

	• Evidence of CSF leakage on conventional myelography, CT myelography, or cistemography

	• CSF opening pressure <60 mmH2O in sitting position

• C. No history of dural puncture or other cause of CSF fistula

EFTA00956021

■ D. Headache resolves within 72 hours after epidural blood patching

A separate set of criteria exists for post-dural (post-lumbar) puncture headache.

Neuroimaging — The advent of brain MRI has greatly improved the diagnosis of low CSF headaches. Spine MRI, radioisotope cistemography, and CT myelography can be useful in evaluating patients with spontaneous low pressure headache, particularly when brain MRI is nondiagnostic. These imaging studies are generally not done in patients with post-lumbar puncture headache, where the diagnosis is more obvious.

The utility of head CT for confirming the diagnosis is limited, as head CT is often normal in patients with spontaneous low CSF pressure headache. However, head CT may suggest the diagnosis by demonstrating subdural fluid collections, slit-shaped ventricles, tight basal cisterns, scant CSF over the cortex, or increased tentorial enhancement [R]. (See 'Head CT' above.)

MRI of brain and spine — For patients with suspected low CSF pressure headache, we recommend obtaining brain MRI with gadolinium to assess for the typical features of the syndrome, which are diffuse pachymeningeal enhancement (image 1), "sagging" of the brain, tonsillar descent, and posterior fossa crowding (image 2). (See 'Brain MRI' above.)

While brain and/or spine MRI is abnormal in most patients with spontaneous intracranial hypotension, a systematic review published in 2006 estimated that brain MRI remains normal in up to 20 percent of patients [32]. A subsequent report evaluated 18 patients with spontaneous intracranial hypotension and found that the sensitivities of brain and spine MRI were 83 and 94 percent, respectively [11J.

Spinal MRI may be helpful for confirming the diagnosis and for identifying the exact location of the CSF leakage. Such studies may reveal [49]:

■  Extra-arachnid fluid collections

■ Collapse of the dural sac and engorgement of the epidural venous plexus

■  Meningeal diverticula

■ Extradural extravasation of fluid

In a series of 10 women who had characteristic orthostatic headache without a previous history of dural tear, spinal MRI revealed dilated cervical epidural veins [U]. The authors concluded that this finding is an indicator of CSF hypovolemia and can be used to differentiate spontaneous low CSF pressure from the other causes of diffuse meningeal enhancement.

Subtraction MRI employs rapid postprocessing image analysis of standard T2 and T1 MRI sequences in order to delineate the dural sac of the spinal cord and distinguish between fluid and fat. In a report of 17 patients with spontaneous intracranial hypotension, subtraction MRI of the spinal cord identified the epidural CSF fluid collection in all patients, although the site of the CSF leak was not detected [64]. Additional studies are needed to determine the sensitivity and specificity of this method.

Radioisotope cistemography — Radioisotope cistemography is particularly useful for identifying CSF leaks. It is usually obtained as the next step if a CSF leak is suspected and MRI is normal or nondiagnostic.

Since a lumbar puncture is required as part of the procedure, opening CSF pressure is measured, and CSF is sent for analysis at the same time. Placement of numbered cotton pledgets in the nose for subsequent detection of radioactivity aids in detection and localization of CSF leakage through the paranasal sinuses.

Normal CSF flow involves cephalad migration from the site of injection to the cerebral convexities and the sylvian fissures [5], and, therefore, the most common cisternographic abnormality in CSF leaks is the absence or paucity of activity over the cerebral convexities [65-67]. It is advisable to look for early accumulation within the bladder and kidneys, or leakage of isotope outside of the normal confines of the subarachnoid space.

EFTA00956022

Early soft tissue uptake of radioisotope may also be suggestive of CSF leak, perhaps reflecting unusually rapid uptake of the radioisotope into the bloodstream through the epidural venous plexus [Ill

In a small retrospective study of patients with spontaneous CSF leaks, the diagnosis of intracranial hypotension was supported in all 10 patients who had radionucleotide cisternography, which showed early bladder accumulation of the nucleotide and reduced activity over the cerebral hemispheres, consistent with rapid uptake of the tracer in the bloodstream [68]. In addition, the location of the leaks was identified in 7 of the 10 patients with this method.

Iatrogenic CSF leak from the lumbar puncture is a potential complication of radioisotope cistemography [E)].

CT myelography — Computed tomographic (CT) myelography is the best test to identify the site of the leak. CT myelography is most commonly used in order to localize the level of the spinal leak when treatment beyond epidural blood patch (such as surgery or fibrin glue injection) is contemplated.

Both early and delayed cuts should be obtained at each spinal level, since CSF leaks may be rapid or slow. In cases where radiocistemography or spinal MRI has identified the approximate level of the leak, focused CT cuts can be used to locate the source more precisely.

MR myelography — Preliminary evidence suggests that magnetic resonance (MR) myelography using heavily T2-weighted sequences may be an alternative to CT myelography for detecting the level of CSF leaks.

• In a report of 19 patients with spontaneous intracranial hypotension, the accuracy of MR myelography for demonstrating and localizing CSF leaks was similar to CT myelography [n].

• In a study involving 17 patients with spontaneous intracranial hypotension, characteristic imaging features of spontaneous intracranial hypotension were seen on initial brain MRI in 13 patients (76 percent), and abnormal CSF collections were seen on MR myelography in the four patients (24 percent) whose initial head MRI was negative [71]. The authors suggested that the combination of brain MRI and MR myelography may improve the early diagnostic rate for spontaneous intracranial hypotension.

Lumbar puncture — A lumbar puncture (LP) can document low CSF pressure in suspected cases of spontaneous low CSF pressure headache, and may be diagnostically useful when MRI is not available or is not tolerated. However, LP is generally not necessary in cases where MRI is consistent with low CSF pressure headache. There is also concern that dural puncture from the procedure could potentially worsen the low CSF pressure and exacerbate the syndrome. In addition, the opening pressure is normal in some patients with proven spontaneous intracranial hypotension. (See 'Cerebrospinal fluid analysis' above.)

Although current diagnostic criteria define low CSF pressure based upon measurements taken in the sitting position we recommend using the lateral decubitus position for greater accuracy. To ascertain correct placement of the spinal needle, CSF flow should be observed either spontaneously, with gentle aspiration, or with Valsalva maneuver [14]. (See "Lumbar puncture: Technique; indications; contraindications; and complications in adults".)

Differential diagnosis — Patients who have CSF shunts placed for various neurosurgical indications may develop a syndrome identical to that of spontaneous intracranial hypotension, probably secondary to overdrainage (overshunting) of CSF [1].

Orthostatic headache in the absence of CSF leak may also be a manifestation of the postural tachycardia syndrome or orthostatic intolerance [M. (See "Postural tachycardia syndrome".)

One case report described spontaneous orthostatic headache and a "dry tap" at lumbar puncture that was attributed to an intradural myxopapillary ependymoma [11].

Misdiagnosis — The syndrome of spontaneous low CSF pressure headache has been under-recognized, in part because headache in general is a common ailment, and because patients with low CSF pressure headache

EFTA00956023

typically present with a normal neurologic examination. The diagnosis was often missed prior to the advancement of MRI imaging and the specific MRI findings associated with low CSF pressure headache. Even in the modern era of MRI availability, misdiagnosis is common [14].

Inappropriate and unnecessary clinical investigations may result if the diagnosis of spontaneous low CSF pressure headache is not considered. As an example, before diffuse meningeal enhancement on brain MRI was a recognized feature of spontaneous intracranial hypotension, patients with this finding were often subjected to extensive testing to rule out other causes such as meningeal carcinomatosis, meningitis, subarachnoid hemorrhage, neuroborreliosis, and neurosarcoidosis. (See 'Brain MRI' above.)

SUMMARY AND RECOMMENDATIONS

■ The major features of the classic spontaneous low cerebrospinal fluid (CSF) pressure headache syndrome are orthostatic headache, low CSF pressure, and diffuse meningeal enhancement on brain MRI. (See 'Introduction and terminology' above and 'Clinical features' above.)

■ The prevailing etiology is CSF leakage, which may occur in the context of rupture of an arachnid membrane. An alternative hypothesis is that low CSF pressure is caused by epidural venous hypotension from the lowering of venous pressure within the inferior vena cava system. Most CSF leaks occur at the thoracic or cervicothoracic junction. An underlying connective tissue disorder may play a role in the development of CSF leaks. Other potential contributing factors are minor trauma, degenerative disc disease, and osseous spurs. (See 'Pathophysiology' above.)

■ The estimated annual incidence of spontaneous low CSF pressure headache is 5 per 100,000, with a peak incidence around age 40 and a female to male ratio of 2:1. (See 'Epidemiology' above.)

■ The headache caused by low CSF pressure may be sudden or gradual in onset, and severity is widely variable. The headache is typically relieved with recumbency and exacerbated with upright posture. Other headache patterns have also been reported with this syndrome. Commonly associated symptoms are neck pain or stiffness, nausea and vomiting, change in hearing, and photophobia. There is a varied and extensive list of additional associated symptoms. (See 'Clinical features' above and 'Headache' above and 'Associated symptoms and complications' above.)

■ Traction on pain-sensitive intracranial and meningeal structures, particularly sensory nerves and bridging veins, is thought to cause headache and some of the associated symptoms. (See 'Pathophysiology' above.)

■ Some rare but serious symptoms (eg, altered level of consciousness, parkinsonism) associated with the syndrome are probably caused by distortion or compression of brain and/or spinal cord structures. (See 'Associated symptoms and complications' above.)

■ For patients with suspected low CSF pressure headache, we recommend brain MRI with gadolinium to assess for the typical features, which include diffuse meningeal enhancement (image 1), subdural hematomas or hygromas, sagging of the brain (image 2), engorgement of cerebral venous sinuses, and pituitary enlargement. Brain MRI remains normal in up to 20 percent of patients with low CSF pressure headache. (See 'Brain MRI' above.)

■ The diagnosis of low CSF pressure headache should be considered in patients who present with positional orthostatic headache, with or without associated symptoms, perhaps in the setting of minor trauma, and in the absence of a history of dural puncture or other cause of CSF fistula. Confirmation of the diagnosis requires evidence of low CSF pressure by MRI or lumbar puncture and/or evidence of a CSF leak on CT myelography or radioisotope cisternography. Low CSF pressure headache following a lumbar puncture rarely creates a clinical dilemma. (See 'Diagnosis' above.)

■ Diagnostic criteria for headache attributed to spontaneous low CSF pressure are discussed above. (See 'Diagnostic criteria' above.)

■ Patients who have CSF shunts in place may develop a syndrome identical to that of spontaneous intracranial hypotension, probably secondary to overdrainage (overshunting) of CSF. (See 'Differential diagnosis' above.)

■ Initial therapy for most patients with a confirmed diagnosis of spontaneous low CSF pressure headache consists of conservative measures and/or epidural blood path therapy. For patients who fail these treatments, additional options include continuous epidural saline infusion, epidural fibrin glue, or

EFTA00956024

surgical repair of the defect. Treatment of spontaneous low CSF pressure headache is discussed separately. (See "Treatment and prognosis of spontaneous low cerebrospinal fluid pressure headache".) Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

<table><tr><th>1</th><th>Schievink WI, Reimer R Folger WN. Surgical treatment of spontaneous intracranial hypotension
associated with a spinal arachnoid diverticulum. Case report. J Neurosurg 1994. 80:736.</th></tr><tr><td>2</td><td>Mokri B. Spontaneous cerebrospinal fluid leaks: from intracranial hypotension to cerebrospinal fluid
hypovolemia--evolution of a concept. Mayo Clin Proc 1999; 74:1113. </td></tr><tr><td>3</td><td>Horton JC, Fishman RA. Neurovisual findings in the syndrome of spontaneous intracranial hypotension
from ducal cerebrospinal fluid leak. Ophthalmology 1994; 101:244. </td></tr><tr><td>4</td><td>Lipman II. Primary intracranial hypotension: the syndrome of spontaneous low cerebospinal fluid pressure
with traction headache. Dis Nery Syst 1977. 38:212. </td></tr><tr><td>5</td><td>Marcelis J, Silberstein SD. Spontaneous low cerebrospinal fluid pressure headache. Headache 1990;
30:192. </td></tr><tr><td>6</td><td>Swanson JW, Dodick DW, Capobianco DJ. Headache and other craniofacial pain. In: Neurology in
Clinical Practice, Bradley WG, Daroff RB, Fenichel GM, Marsden CD. (Eds), Butterworth, Boston 2000.
p.1832. </td></tr><tr><td>7</td><td>Capobianco DJ, Kuczler FJ Jr. Case report: primary intracranial hypotension. Mil Med 1990; 155:64. </td></tr><tr><td>8</td><td>Mokri B Piepgras DG, Miller GM. Syndrome of orthostatic headaches and diffuse pachymeningeal
gadolinium enhancement. Mayo Clin Proc 1997. 72:400. </td></tr><tr><td></td><td>Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 2-1998. A</td></tr><tr><td>9</td><td>50-year-old woman with increasing headache and a left abducent-nerve palsy. N Engl J Med 1998;
338:180. </td></tr><tr><td>10</td><td>Mokri B, Hunter SF, Atkinson JL, Piepgras DG. Orthostatic headaches caused by CSF leak but with
normal CSF pressures. Neurology 1998; 51:786.</td></tr><tr><td>11</td><td>Chung SJ Kim JS, Lee MC. Syndrome of cerebral spinal fluid hypovolemia: clinical and imaging features
and outcome. Neurology 2000; 55:1321.</td></tr><tr><td>12</td><td>Miyazawa K, Shiga Y, Hasegawa T, et al. CSF hypovolemia vs intracranial hypotension in "spontaneous
intracranial hypotension syndrome". Neurology 2003; 60:941.</td></tr><tr><td>13
14</td><td>Levine DN, Rapalino O. The pathophysiology of lumbar puncture headache. J Neurol Sci 2001; 192:1.
Silberstein SD Marcelis J. Headache associated with changes in intracranial pressure. Headache 1992-
32:84. </td></tr><tr><td>15</td><td>Raskin NH. Lumbar puncture headache: a review. Headache 1990; 30:197. </td></tr><tr><td>16</td><td>Fernandez E. Headaches associated with low spinal fluid pressure. Headache 1990; 30:122. </td></tr><tr><td>17</td><td>Schaltenbrand G. Neuere Anschauungen zur Pathophysiologie der Liquorzirkulation. Zentralbl Neurochir
1938; 3:290.</td></tr><tr><td>18</td><td>SCHALTENBRAND G. Normal and pathological physiology of the cerebrospinal fluid circulation. Lancet
1953; 1:805.</td></tr><tr><td>19</td><td>Lasater GM. Primary intracranial hypotension. The low spinal fluid pressure syndrome. Headache 1970-
10:63. </td></tr><tr><td>20</td><td>Mokri B, Maher CO, Sencakova D. Spontaneous CSF leaks: underlying disorder of connective tissue.
Neurology 2002. 58:814.</td></tr><tr><td>21</td><td>Ferrante E, Citterio A Savino A, Santalucia P. Postural headache in a patient with Marfan's syndrome.
Cephalalgia 2003. 23:552. </td></tr><tr><td>22</td><td>Schrijver I Schievink WI, Godfrey M et al. Spontaneous spinal cerebrospinal fluid leaks and minor
skeletal features of Marfan syndrome: a microfibrillopathy. J Neurosurg 2002. 96:483.</td></tr></table>

EFTA00956025

<table><tr><th></th><th>Grimaldi D, Mea E, Chiapparini L, et al. Spontaneous low cerebrospinal pressure: a mini review. Neurol</th></tr><tr><td>23</td><td>Sci 2004; 25 Suppl 3:S135.</td></tr><tr><td>24 24</td><td>Lay CL, Campbell JK, Mokri B. Low cerebrospinal fluid pressure headache. In: Headache, Goadsby PJ,
Silberstein SD (Eds), Butterworth-Heinemann, Boston 1997. p.355.</td></tr><tr><td></td><td>Vishteh AG, Schievink WI, Baskin JJ, Sonntag VK. Cervical bone spur presenting with spontaneous</td></tr><tr><td>25 25</td><td>intracranial hypotension. Case report. J Neurosurg 1998; 89:483.</td></tr><tr><td></td><td>Eross EJ, Dodick DW, Nelson KD, et al. Orthostatic headache syndrome with CSF leak secondary to bony</td></tr><tr><td>26</td><td>pathology of the cervical spine. Cephalalgia 2002; 22:439.</td></tr><tr><td></td><td>Winter SC, Maartens NF, Anslow P, Teddy PJ. Spontaneous intracranial hypotension due to thoracic disc</td></tr><tr><td>22 27</td><td>herniation. Case report. J Neurosurg 2002; 96:343.</td></tr><tr><td></td><td>Rapport RL, Hillier D, Scearce T, Ferguson C. Spontaneous intracranial hypotension from intradural</td></tr><tr><td>28</td><td>thoracic disc herniation. Case report. J Neurosurg 2003; 98:282.</td></tr><tr><td></td><td>Franzini A, Messina G, Nazzi V, et al. Spontaneous intracranial hypotension syndrome: a novel speculative</td></tr><tr><td>29</td><td>physiopathological hypothesis and a novel patch method in a series of 28 consecutive patients. J
Neurosurg 2010; 112:300.</td></tr><tr><td>30</td><td>Groen RJ, Hoogland PV. Spontaneous intracranial hypotension. J Neurosurg 2010; 113:685.</td></tr><tr><td>33</td><td>Watanabe A, Horikoshi T, Uchida M, et al. Diagnostic value of spinal MR imaging in spontaneous</td></tr><tr><td>31</td><td>intracranial hypotension syndrome. AJNR Am J Neuroradiol 2009; 30:147.</td></tr><tr><td></td><td>Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA 2006;</td></tr><tr><td>32</td><td>295:2286.</td></tr><tr><td></td><td>Schievink WI. Headache relief from lateralizing head and neck positions in spontaneous intracranial</td></tr><tr><td>33</td><td>hypotension. Neurology 2011; 77:799.</td></tr><tr><td></td><td>Batsis JA, Phy MP. Intracranial hypotension: aggravation of headache at high altitude. Headache 2005;</td></tr><tr><td>ब्ल 34</td><td>45:380.</td></tr><tr><td></td><td>Mokri B, Aksamit AJ, Atkinson JL. Paradoxical postural headaches in cerebrospinal fluid leaks.</td></tr><tr><td>35</td><td>Cephalalgia 2004; 24:883.</td></tr><tr><td></td><td>Schievink WI, Maya MM. Quadriplegia and cerebellar hemorrhage in spontaneous intracranial</td></tr><tr><td>36</td><td>hypotension. Neurology 2006; 66:1777.</td></tr><tr><td>37</td><td>Evans RW, Boes CJ. Spontaneous low cerebrospinal fluid pressure syndrome can mimic primary cough</td></tr><tr><td>37</td><td>headache. Headache 2005; 45:374.</td></tr><tr><td>38</td><td>Mokri B. Spontaneous CSF leaks mimicking benign exertional headaches. Cephalalgia 2002; 22:780.</td></tr><tr><td></td><td>Rando TA, Fishman RA. Spontaneous intracranial hypotension: report of two cases and review of the</td></tr><tr><td>39</td><td>literature. Neurology 1992; 42:481.</td></tr><tr><td>40</td><td>PAGE F. Intracranial hypotension. Lancet 1953; 1:1.</td></tr><tr><td>41</td><td>Mokri B. Spontaneous intracranial hypotension. Curr Pain Headache Rep 2001; 5:284.</td></tr><tr><td></td><td>Pakiam AS, Lee C, Lang AE. Intracranial hypotension with parkinsonism, ataxia, and bulbar weakness.</td></tr><tr><td>42</td><td>Arch Neurol 1999; 56:869.</td></tr><tr><td></td><td>Mokri B, Ahlskog JE, Luetmer PH. Chorea as a manifestation of spontaneous CSF leak. Neurology 2006;</td></tr><tr><td>43</td><td>67:1490.</td></tr><tr><td></td><td>Vetrugno R, Mascalchi M, Chierichetti F, et al. Hypoactive-hypoalert behavior ("psychic akinesia") in</td></tr><tr><td>44</td><td>intracranial hypotension syndrome. Neurology 2008; 71:1452.</td></tr><tr><td></td><td>Pleasure SJ, Abosch A, Friedman J, et al. Spontaneous intracranial hypotension resulting in stupor caused</td></tr><tr><td>45</td><td>by diencephalic compression. Neurology 1998; 50:1854.
Kashmere JL, Jacka MJ, Emery D, Gross DW. Reversible coma: a rare presentation of spontaneous</td></tr><tr><td>46</td><td>intracranial hypotension. Can J Neurol Sci 2004; 31:565.</td></tr><tr><td>47</td><td>Hong M, Shah GV, Adams KM, et al. Spontaneous intracranial hypotension causing reversible
frontotemporal dementia. Neurology 2002; 58:1285.</td></tr></table>

EFTA00956026

| 48 Wicklund presentation MR, mimicking Mokri B, FTD. Drubach Neurology DA, et 2011; al. Frontotemporal brain sagging syndrome: an SIH-like                                                                                                                                       |
|-|
| 49 Mokri B. Low cerebrospinal fluid pressure syndromes. Neurol Clin 2004; 22:55.                                                                                                                                                                                                          |
| 50 Mokri, headaches. B. Krueger, J Neuroimaging BR, Miller, 1993; GM, 3:11. Piepgras, DG. Meningeal gadolinium enhancement in low-pressure                                                                                                                                                |
| 51 51 Chung SJ, Lee JH, Kim SJ, et al. Subdural hematoma in spontaneous CSF hypovolemia. Neurology 2006;<br />67:1088.                                                                                                                                                                    |
| Atkinson JL, Weinshenker BG, Miller GM, et al. Acquired Chiari I malformation secondary to                                                                                                                                                                                                |
| 52 spontaneous spinal cerebrospinal fluid leakage and chronic intracranial hypotension syndrome in seven<br />cases. J Neurosurg 1998; 88:237.                                                                                                                                            |
| 53 Bakshi dural-meningeal R, Mechtler and LL, dural Kamran venous S, sinus et al. enhancement. MRI findings Clin in lumbar Imaging puncture 1999; headache 23:73. syndrome: abnormal<br />55                                                                                              |
| 54 Mokri B, Atkinson JL. False pituitary tumor in CSF leaks. Neurology 2000; 55:573.                                                                                                                                                                                                      |
| 55 Alvarez-Linera hypotension syndrome. J, Escribano Neurology J, Benito-León 2000; 55:1895. J, et al. Pituitary enlargement in patients with intracranial                                                                                                                                |
| 56 Pannullo SC, Reich JB, Krol G, et al. MRI changes in intracranial hypotension. Neurology 1993; 43:919.<br />57 Spelle L, Boulin A, Tainturier C, et al. Neuroimaging features of spontaneous intracranial hypotension.<br />Neuroradiology 2001; 43:622.                               |
| 58 43:249. Lin WC, Lirng JF, Fuh JL, et al. MR findings of spontaneous intracranial hypotension. Acta Radiol 2002;<br />59                                                                                                                                                                |
| 59 Mokri B. The Monro-Kellie hypothesis: applications in CSF volume depletion. Neurology 2001; 56:1746.                                                                                                                                                                                   |
| 60 Savoiardo M, Minati L, Farina L, et al. Spontaneous intracranial hypotension with deep brain swelling.<br />Brain 2007; 130:1884.                                                                                                                                                      |
| Mokri B. Headaches associated with abnormalities in intracranial structure and function: low cerebrospinal<br />61 fluid pressure headaches. In: Wolff's headache and other head pain, Silberstein SD, Lipton RB, Dalessio<br />DJ. (Eds), Oxford University Press, New York 2001. p.417. |
| 62 Psychiatry Murros K, Fogelholm 1983; 46:1149. R. Spontaneous intracranial hypotension with slit ventricles. J Neurol Neurosurg                                                                                                                                                         |
| 63 Classification Headache Classification of Headache Subcommittee Disorders: 2nd of the edition. International Cephalalgia Headache 2004; 24 Society. Suppl The 1:9. International                                                                                                       |
| 64 Bonetto SIH. Neurology N, Manara 2011; R, 77:1873. Citton V, Cagnin A. Spinal subtraction MRI for diagnosis of epidural leakage in                                                                                                                                                     |
| 65 Molins Cephalalgia A, Alvárez 1990; J, 10:59. Sumalla J, et al. Cisternographic pattern of spontaneous liquoral hypotension.                                                                                                                                                           |
| 66 Bai Ann J, Nucl Yokoyama Med 2002; K, Kinuya 16:75. S, et al. Radionuclide cisternography in intracranial hypotension syndrome.                                                                                                                                                        |
| Sakurai K, Nishio M, Yamada K, et al. Comparison of the radioisotope cisternography findings of<br />67 spontaneous intracranial hypotension and iatrogenic cerebrospinal fluid leakage focusing on chronological<br />changes. Cephalalgia 2012; 32:1131.                                |
| 68 88 Schievink intracranial WI, hypotension. Meyer FB, J Atkinson Neurosurg JL, 1996; Mokri 84:598. B. Spontaneous spinal cerebrospinal fluid leaks and                                                                                                                                  |
| 69 Sakurai cisternography. K, Nishio Neurology M, Sasaki 2010; S, et 75:1730. al. Postpuncture CSF leakage: a potential pitfall of radionuclide                                                                                                                                           |
| 70 70 Wang spontaneous YF, Lirng intracranial JF, Fuh JL, hypotension. et al. Heavily Neurology T2-weighted 2009; MR 73:1892. myelography vs CT myelography in                                                                                                                            |
| 71 Tsai intracranial PH, Fuh hypotension: JL, Lirng JF, a Wang case-control SJ. Heavily study. T2-weighted Cephalalgia MR 2007; myelography 27:929. in patients with spontaneous                                                                                                          |
| 72 Mokri 2003; 61:980. B, Low PA. Orthostatic headaches without CSF leak in postural tachycardia syndrome. Neurology                                                                                                                                                                      |

EFTA00956027

Schievink WI, Akopov SE. Filum ependymoma mimicking spontaneous intracranial hypotension. 73 Headache 2005; 45:607. 74 Schievink WI. Misdiagnosis of spontaneous intracranial hypotension. Arch Neurol 2003. 60:1713. Topic 3359 Version 10.0 All rights reserved. O 2013 UpToDate, Inc. customerservice@uptodate.com 2,UpToDate www.uptodate.com

This e-mail message may contain confidential and/or privileged information. If you are not an addressee or otherwise authorized to receive this message, you should not use, copy, disclose or take any action based on this e-mail or any information contained in the message. If you have received this material in error, please advise the sender immediately by reply e-mail and delete this message.

Thank you.

***********

The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein

Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jeevacation@gmail.com, and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved

EFTA00956028

📅 Mar 8, 2013 FROM EPSTEIN

(no subject)

From: Jeffrey Epstein <jeevacation@gmail.com>

To: Ian Osborne

did you get your 2012 distribution, of the 3 million? , darren woudl like you to post the facebook stock as collateral, as well as an accountant statment re , cash flow , is that a problem? he said the lease has not been sent? is that true? ***** The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein Unauthorized use, disclosu

did you get your 2012 distribution, of the 3 million? , darren woudl like you to post the facebook stock as collateral, as well as an accountant statment re , cash flow , is that a problem? he said the lease has not been sent? is that true?

*****

The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein

Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jeevacation@gmail.com, and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved

*********

📅 Mar 8, 2013 FROM EPSTEIN

(no subject)

From: jeevacation@gmail.com

To: Bobby Slayton

will you be out in la april 29 30

will you be out in la april 29 30

📅 Mar 8, 2013 FROM EPSTEIN REDACTED

Re:

From: jeevacation@gmail.com

great On Fri, Mar 8, 2013 at 6:20 PM, < > wrote: YES!! Get home 28th leave the 1st!! Sent from my Verizon Wireless BlackBerry

great

On Fri, Mar 8, 2013 at 6:20 PM, < > wrote:
YES!! Get home 28th leave the 1st!!
Sent from my Verizon Wireless BlackBerry

📅 Mar 8, 2013 FROM EPSTEIN REDACTED

Re:

From: jeevacation@gmail.com

pizza On Fri, Mar 8, 2013 at 5:29 PM, < > wrote: Obviously my turn to buy dinner. Will start saving now. Sent from my Verizon Wireless BlackBerry

pizza

On Fri, Mar 8, 2013 at 5:29 PM, < > wrote:
Obviously my turn to buy dinner. Will start saving now.
Sent from my Verizon Wireless BlackBerry

📅 Mar 8, 2013 FROM EPSTEIN

(no subject)

From: Jeffrey Epstein <jeevacation@gmail.com>

To: Roy Hodges

tell the boys that you are buying them all lunch they get to order ********* The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us imme

tell the boys that you are buying them all lunch they get to order

*********

The information contained in this communication is confidential, may be attorney-client privileged, may constitute inside information, and is intended only for the use of the addressee. It is the property of Jeffrey Epstein Unauthorized use, disclosure or copying of this communication or any part thereof is strictly prohibited and may be unlawful. If you have received this communication in error, please notify us immediately by return e-mail or by e-mail to jeevacation®gmail.com, and destroy this communication and all copies thereof, including all attachments. copyright -all rights reserved