Neurology and Neurosurgery

Neurology andNeurosurgery

INNOVATIONS | 2008 EDIT ION

J O H N S H O P K I N S M E D I C I N E 1

Table of Contents

NEUROLGY AND NEUROSURGERY

Department Overview 4

Demonstrating Clinical Innovation and New Discoveries 11

Patient Safety and Quality Measures 40

The Patient Experience 48

Our Faculty 55

How to Refer a Patient 58

Locations 58

Referral Assistance 59

Johns Hopkins Medicine Overview 61

MissionThe mission of Johns Hopkins

Medicine is to improve the healthof the community and the world

by setting the standard ofexcellence in medical education,

research and clinical care. Diverseand inclusive, Johns HopkinsMedicine educates medical

students, scientists, health careprofessionals and the public;

conducts biomedical research; andprovides patient-centered medicine

to prevent, diagnose and treathuman illness.

VisionJohns Hopkins Medicine provides adiverse and inclusive environmentthat fosters intellectual discovery,creates and transmits innovative

knowledge, improves humanhealth, and provides medical

leadership to the world.

Core ValuesExcellence & Discovery Leadership & Integrity Diversity & InclusionRespect & Collegiality

E very aspect of our professional life at JohnsHopkins is devoted to patient care. Both our clinical work and our research are designed to

clarify conditions and diseases to develop enhancedtreatments for our patients.

We are pleased to share with you a glimpse into ourongoing efforts, innovations and discoveries on the jour-ney to superior patient care. Inside, you’ll find some ofour latest research that is helping to translate into betterpatient outcomes, innovations that bring treatments to anew level and steps we’re taking every day to improvequality, outcomes and patient safety.

Each patient we care for remains our first priority.When you refer to us, you’ve placed tremendous confi-dence and trust in us, and we’ll work with you to ensure the best possible results.

Finally, we are committed to excellence in everything we do. This book ispart of an ongoing initiative to relay information about activities in our depart-ments, report on innovations and discoveries in the field of neurology and neu-rosurgery, and enhance patients’ access and experience. We are looking forwardto continuing this important initiative.

Warm regards,

Justin McArthur, M.B.B.S., M.P.H.Director (interim)Department of NeurologyProfessor of Neurology, Pathology and Epidemiology


2 NEUROLOGY AND NEUROSURGERY

Dear Colleague:

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You may refer a patient to any member of our faculty by calling 410-955-9441 (Neurology) or410-955-2248 (Neurosurgery) or e-mail us at [email protected].

For urgent referrals or consultation, call the Hopkins Access Line (HAL) at 1-800-765-5447.

For more information about Johns Hopkins Neurology and Neurosurgery, visit our Web site atwww.hopkinsneuro.org.

HENRY BREM, M.D.

JUSTIN MCARTHUR,M.B.B.S., M.P.H.

Henry Brem, M.D.Director Department of NeurosurgeryHarvey Cushing Professor of NeurosurgeryOncology and Ophthalmology

2008 Highlights

In this booklet, we’ve showcasedsome of our recent clinical innova-tions, discoveries, and safety andquality measures. We’ve also in-cluded sections that illustrate thepatient experience at Johns Hop-kins. Published research is listedthroughout. Here are some of theclinical and research highlights for 2008:

n Centers of excellence for encephalitis (page 47), adult hydrocephalus (page 25)and pituitary tumors (page 17).

n New cancer treatment deliverymethods for brain and spinaltumors (page 27).

n Novel techniques in cere-brovascular neurosurgery (page 12).

n The role of stem cells in brain tumors (page 34).

n Repairing injured peripheralnerves (page 48).

n Genetic targets for tumor therapy (page 30).

n Measuring the onset ofAlzheimer’s disease (page 36).



Opened in 1889, The Johns Hop-kins Hospital is not a particularlyold institution, but it has whatmight be called a very long history.It was here in the early 1900s thatHarvey Cushing, “the father of neurosurgery,” performed the firstsuccessful operations for brain tu-mors; here, in 1937, that WalterDandy performed the firstaneurysm clipping.

Our team quickly emerged asleaders with research on how thebrain reacts to injury and with in-novations like the use of X-rays toguide brain surgery. The field ofneurocritical care was brought tolife at The Johns Hopkins Hospi-tal. Here, our neurologists, anes-thesiologists and neurosurgeonspioneered one of the first dedicat-ed neurological critical care unitsin the nation.

Since that time, we are pleasedthat our program is consistentlyrecognized by peers around thecountry and ranked among thebest for both pediatric and adultneurology and neurosurgery byU.S.News & World Report.

Safety and Quality Measures

Protocols for briefing and debrief-ing in each OR case, for reducingsurgical site infections and for as-suring optimal stroke outcomes—these are examples of the initiativeswe’ve undertaken. Our electronicmedical record and provider orderentry enhance patient safety. Ournursing staff is specially trainedand specialty certified to ensure thebest management and patient out-comes. Some of the safety andquality initiatives we highlight inthis booklet are:

n Reducing infection rates in pediatric hydrocephalus(page 40).

n Diagnosing encephalitis(page 47).

One of our goals is to developthe next generation of leaders inneurology and neurosurgery. Ourclinical training programs—uniquein their depth in areas like neu-roimmunology, acute-care neurolo-gy, spine, vascular, tumors and cog-nitive neuroscience—guide ourresidents and fellows as they buildan academic career.

Our faculty, strengthened byour tradition of sharing ideasacross disciplines and melding lab-oratory-based and clinical re-search, can offer patients new andexceptional diagnostic capabilitiesand therapies.

For brain tumor patients, for ex-ample, they can choose from notonly standard treatments, but alsonovel ways to deliver radiation,chemotherapy, vaccines and genetherapy. All patients are assessed byexpert teams that cross multi-spe-cialties. Our patients have access tothe best current therapies as well asto clinical trials that bring thenewest experimental treatments tothose who need them most.

D E PA RT M E N T OV E RV I E W

Overview of Neurology and Neurosurgery at Johns Hopkins


Research

In the past decade, we have seenour funding from the National In-stitutes of Health as well as fromother private sources double. Our


Experience and Outcomes

Neurology and Neurosurgerywork together to diagnose andtreat the full range of adult andpediatric neurological diseases.Each year we provide more than30,000 outpatient consultations,admit approximately 5,000 inpa-tients, and perform over 4,000brain tumor, vascular, spine andpediatric neurosurgery operations.

Our NCCU remains one ofthe most comprehensive inthe country; our two certifiedstroke units have some of thelowest stroke mortality ratesin the nation, while our pa-tients often have an extremelycomplex mix of medical prob-lems underlying their neuro-logical diseases.


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Total Inpatient Discharges(includes The Johns Hopkins Hospital and

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Our mortality rates are be-tween .77 and 2.47 percent low-er than expected mortality rate

for neurology and neurosurgerypatients treated at comparableacademic medical centers.




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In 2007, The Johns Hopkins Hospital recorded a 1.97 percent mortality rate forall neurology inpatient discharges, which is .77 percentage points lower thanthe expected mortality rate for neurology inpatients treated at an academicmedical center. *Significant difference from expected at .05 level of significance.

In 2007, The Johns Hopkins Hospital recorded a 2.57 percent mortality rate forall neurosurgery inpatient discharges, which is 2.47 percentage points lower thanthe expected mortality rate for neurosurgery inpatients treated at an academicmedical center. *Significant difference from expected at .01 level of significance.

Patient Origin

While many of our patients arefrom our local community, otherscomes from all over the world fortreatment. Last year, about half of

our neurology and neurosurgeryadult inpatients were from out-side of the Baltimore region andMaryland.

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Demonstrating ClinicalInnovation

n Aneurysm Expertisen A Surgical Approach to

the Odontoidn Managing Pituitary

Tumors: It Takes a Teamn Reversing the Blindness of

Central Retinal ArteryOcclusion

n Skin Punch Biopsy to Assess Neuropathy and Nerve Regneration

n Dietary Therapy for Seizures

n Attacking AdultHydrocephalus

Moving Discovery Forward

n A Promising Treatment for Brain and Spinal Tumors

n Probing Genetic Changes for New Brain Tumor Treatments

n The Role of Stem Cells in Brain Tumors

n Who Will Develop Alzheimer’s Disease? What Drugs Will Help?

n Stem Cells that Undo Nerve Damage

n Nanofibers with Protein Regenerate Damaged Nerves

CLINICAL INNOVATION & NEW DISCOVERIES

Neurosurgery-OutpatientNeurosurgery-Inpatient

Neurology-OutpatientNeurology-Inpatient

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July 2007 – May 2008

Demonstrating Clinical Innovation and Moving Discovery Forward

Learn on the following pages how we are breaking new ground in patient care.

Neurosurgery-OutpatientNeurosurgery-Inpatient

Neurology-OutpatientNeurology-Inpatient

Overall Quality of Care

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Patient Satisfaction

In our efforts to provide our patientswith the best treatment and care, wecontinually solicit patient feedback anduse this infomation to help improvethe patient experience. Results from

our most recent patient satisfaction sur-veys, July 2007 to May 2008, indicatethat the majority of patients would rec-ommend the practice and feel the quali-ty of care is good or very good.



Aneurysm Expertise

Johns Hopkins cerebrovascular sur-geons approach brain surgery muchlike a chess team approaches a tour-nament: with a strategy to win. “Weincorporate innovative solutions totreating aneurysms and other condi-tions and end up with excellent out-comes,” says Rafael Tamargo.

Tamargo, head of cerebrovascularneurosurgery, has built one of thelargest centers for aneurysm treat-ment in the United States. His teamtreats about 170 aneurysms a year,both surgically and endovascularly.Volumes like those are exceptionalfor a state like Maryland. “There isonly one hospital in the entire stateof New York that treats more than100 aneurysm cases a year, and NewYork has a far greater populationthan Maryland,” Tamargo says.

“At Hopkins, a team of neuro-surgeons, neurologists and neurora-diologists evaluates every case to de-termine the best way to treatpatients,” Tamargo says. This is oneof a handful of centers in which gi-ant and complex aneurysms are re-paired under hypothermic car-diopulmonary bypass. Cardiac

D E M O N S T R AT I N G C L I N I C A L I N N OVAT I O N

Tuffiash E, Tamargo R, Hillis A.Craniotomy for treatment ofunruptured aneurysms is notassociated with long-term cognitivedysfunction. Stroke 2003;34:2195.

Komotar R, Olivi A, Rigamonti D,Tamargo R. Microsurgical fenestrationof the lamina terminalis reduces theincidence of shunt-dependenthydrocephalus after aneurysmalsubarachnoid hemorrhage.Neurosurgery 2002;51:1403.

Chiang V, Gailloud P, Murphy K,Rigamonti D, Tamargo R. Routineintraoperative angiography duringaneurysm surgery. Journal ofNeurosurgery 2002;96:988.

Oshiro E, Rini D, Tamargo R.Contralateral approaches to bilateralcerebral aneurysms: a microsurgicalanatomical study. Journal ofNeurosurgery 1997;87:163.

Miller N, Monsein L, Debrun G,Tamargo R, Nauta H. Treatment ofcarotid-cavernous sinus fistulas using asuperior ophthalmic vein approach.Journal of Neurosurgery 1995;83:838.

tients with aneurysmal subarach-noid hemorrhage.

In a recent discovery, publishedin December 2007, our neurosur-geons found that some people maybe genetically predisposed to devel-oping vasospasm, or the narrowingof vessels after hemorrhage. Withthese insights, Tamargo says, doc-tors will be better equipped toavoid vasospasm in those at risk.

Finally, Hopkins is one of a fewcenters nationwide to treat cere-brovascular insufficiency from in-tracranial disease, which can leadto stroke. To increase blood supplyto the brain, our neurosurgeonsconnect an artery that typicallysupplies blood to the scalp to anartery in the brain.

RESEARCH PUBLISHED:

Chaichana K, Levy A, Miller-LotanR, Shakur S, Tamargo R.Haptoglobin 2-2 genotype determineschronic vasospasm after experimentalsubarachnoid hemorrhage. Stroke.2007 Dec;38(12):3266-71.

Huang J, McGirt M, Gailloud P,Tamargo R. Intracranial aneurysms inthe pediatric population: case seriesand literature review. SurgicalNeurology 2005;63:424.

surgeons lower the body tempera-ture, stop the heart and halt theflow of blood to the brain for up to45 minutes. With the blood flowreduced, the aneurysm softens,buying time for neurosurgeons timeto map out a plan for clipping theaneurysm.

Twenty percent of aneurysm pa-tients have multiple aneurysms, of-ten on opposite sides of the brain.Traditionally, surgeons perform twoseparate operations, one for eachside of the brain. Tamargo is amonga handful of surgeons worldwide touse a one-surgery, contralateral ap-proach. He first clips the aneurysmon one side. Then, through thesame opening, he dissects a safepathway to the other side of thebrain and reaches the otheraneurysm sites.

Another innovation helps avoidhydrocephalus, a major complica-tion of aneurysm surgery. Thisbuild-up of fluid usually requires im-planting a shunt—and a second sur-gery. Hopkins neurosurgeons haveshown that making an opening inthe lamina terminalis reduces the in-cidence of hydrocephalus from 15percent to less than 2 percent in pa-

Demonstrating Clinical Innovation




A Surgical Approach to the Odontoid

A minimally invasive surgical ap-proach developed by a JohnsHopkins neurosurgeon has beenshown to safely allow access forresection of the odontoid anddecompression of the brain stemand spinal cord in patients witha rare condition known as basilarinvagination. Compared to tra-ditional approaches, it may alsoreduce the risks of complicationand infection.

Basilar invagination occurswhen the odontoid, the secondvertebra of the neck, migratesupward through the opening inthe skull where the spinal cordjoins the brain stem, puttingpressure on the spinal cord orthe brain stem. The conditioncan cause difficulty swallowingor speaking, headache, muscleweakness, numbness in the neckor hands, and in extreme cases,sudden death. It may be congen-ital or develop in those withbone diseases such as rheumatoid

arthritis. It can also be caused byinjuries from vehicular accidentsor falls.

The standard operation tocorrect basilar invagination iscomplex because gaining accessto the site is so difficult. Tradi-tional methods require traversingthe oral cavity. This approach,though, offers a limited opera-tive view and requires an inti-mate understanding of oral andpharyngeal anatomy. Othermethods may increase morbidityrates during the operation, aswell as postoperative complica-tions, infections and scarring.

Jean-Paul Wolinsky, assistantprofessor of neurosurgery, hasdeveloped an endoscopic tran-scervical odontoidectomy, an al-ternative to traditional tech-niques that use a transoral or atransmandibular/transoral ap-proach.

Image courtesy of the Journal of Neurosurgery.

Figure 1: Artist’s rendition showing the tubular retractor placed against the anteriorcervical spine acting as a working channel for instruments and endoscope. The insetshows the orientation of the patient in the operating room. (a = artery)


“The image-guided endoscop-ic transcervical odontoidectomyhas many advantages over theconventional techniques. Mostimportantly it allows surgeons toavoid traversing the oral cavity,”says Wolinsky. It also gives sur-geons a better angle of view. Forpatients, it reduces the need forprolonged intubation and tubefeeding, causes less postoperativepain and produces better cosmet-ic results. In addition, there’s adecreased risk for infections andother complications because re-covery time is shorter.

Wolinsky and his teamworked out the approach basedon their experience with theplacement of odontoid screwsand with other skull-base proce-dures and endoscopic neuro-surgery. They created a table-mounted tubular retractor systemthat is inserted while the patientis supine with the neck gently ex-tended (see Figure 1). After per-forming several feasibility studies

on foam models and then on ca-davers, the team used the methodin patients. Ten patients (includ-ing four children) have had theprocedure so far; all experiencedcomplete decompression with noserious complications.

Says Wolinsky, “The techniqueis safe and effective and opens upa new surgical route for this com-plex surgery.”

RESEARCH PUBLISHED:

Wolinsky JP, Sciubba DM, Suk I,Gokaslan ZL. Endoscopic image-guided odontoidectomy fordecompression of basilarinvagination via a standard anteriorcervical approach. Technical note.Journal of Neurosurgery: Spine2007;6:184.


Managing Pituitary Tumors:It Takes a Team

It may be no bigger than a pea, butthe tiny pituitary has a tall order tofill. From its lofty position deepwithin the skull, this master glandoversees most of the body’s otherendocrine glands, regulating andcontrolling the secretion of hor-mones they produce.

Pituitary tumors, though usual-ly benign, can wreak real havoc.They can bring on conditions likegigantism or acromegaly, hypothy-roidism and Cushing syndrome.Even tumors that don’t producehormones, or nonfunctioning tu-mors, can cause headaches, nauseaand vision problems as they growand interfere with neighboringstructures in the brain. Not sur-prisingly, making the differentialdiagnosis is difficult.

“Because these tumors affect so many different areas, we devel-oped the Johns Hopkins PituitaryTumor Center. Now patients have in one place all the resourcesthey need for successful treat-ment,” says neurosurgeon HenryBrem, who works closely withRoberto Salvatori, center director.


Henry Brem (seated) confers withendocrinologist Roberto Salvatori.


Reversing the Blindness ofCentral Retinal ArteryOcclusion

It is sudden, painless and pro-found. And loss of vision in oneeye—essentially a “stroke” of theeye or central retinal artery occlu-sion—is of special interest tostroke specialist Eric Aldrich.

The neurologist and his teamare perfecting a technique to im-prove visual acuity followingCRAO. Building on research byphysicians in Europe, Aldrich andneuro-ophthalmologist NeilMiller, reviewing a series of Hop-kins cases from 2000 to 2007,found that 42 patients who had in-tra-arterial thrombolysis usingsmall amounts of the clot-bustingtPA had better results than stan-dard therapy.

The European trial used contin-uous infusion—a microcatheterwas placed in the neck for up to anhour to deliver the tPA. The Hop-kins technique involves using themicrocatheter to deliver a slow in-jection by hand over two minutes,removing the catheter for five to10 minutes, and then repeating theslow injection. Aldrich attributesmuch of the technique’s success tointerventional neuroradiologists

D E M O N S T R AT I N G C L I N I C A L I N N OVAT I O N18 NEUROLOGY AND NEUROSURGERY

The Pituitary Tumor Center ismanaged by a team of neurosur-geons, endocrinologists, neuro-ophthalmologists, neuroradiolo-gists, radiation therapists andspecialized nurses. Treatments, tailored to tumor type and size aswell as the patient’s age and overallhealth, include medical manage-ment, radiotherapy and surgery.Whatever the approach, the goal isto normalize hormonal secretionand halt the progression of neuro-logical defects and other symptoms.

For many patients, hormone re-placement therapy may control tu-mor growth. For those who needsurgery, the center offers a combi-nation of microsurgery and endo-scopic surgery. Brem and his col-leagues have refined thetranssphenoidal approach with in-traoperative MRI and computernavigation, techniques that make itpossible to monitor progressthroughout the intricate operation.A direct endonasal approach, ver-sus the conventional sublabial ap-proach, allows the mass to be re-moved via an incision in the liningof the nose.

Multiple radiation options areavailable, including Gamma Knife.Treatments are individually tailoredto each patient.

The Pituitary Tumor Centerteam also collaborates with Hop-kins researchers who are studyingways to control excessive hormonesecretion and shrink tumors. Col-laborative efforts like these, saysBrem, are already improving pa-tient outcomes. Normal retina orange-red in appearance

(full of blood); with CRAO, pale white(absence of blood)

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Skin Punch Biopsy to AssessNeuropathy and NerveRegeneration

In 1995, a skin punch biopsy de-veloped by Hopkins neurologistsbecame clinically available to as-sess the early onset of neu-ropathies. Since then, our neurol-ogists have evaluated more than17,000 biopsy specimens fromaround the country. To meet thedemand, they created the JohnsHopkins Cutaneous Nerve Laband trained physicians at five oth-er facilities around the country toalso evaluate these biopsies.

Skin punch biopsy allowsphysicians to measure the loss ofthe small sensory nerve fibers thatsupply the skin’s surface and con-duct information about pain andtemperature. “It helps us quantifythe severity of a neuropathy,” saysJustin McArthur, co-director ofthe cutaneous nerve lab and co-developer of the minimally inva-sive technique. The biopsy is use-ful in making the differentialdiagnosis.

Previous methods of evaluatingneuropathies tested damage onlyto the large-fiber nerves. They

could be invasive, requiring exci-sion of larger nerves in the leg. Skinpunch biopsy is minimally invasive,sensitive to minor nerve changes,and can be easily repeated.

McArthur and colleagueMichael Polydefkis, co-director ofthe nerve lab, are also using thebiopsies to follow changes in nervefiber densities in clinical trials test-ing promising neuroregenerativeand neuroprotective agents. Theyare involved in several trials focus-ing on diabetic neuropathy, HIV

Phillipe Gailloud was able to in-sert a 1 millimeter catheter into a 1millimeter artery during a cerebralangiogram and guide it to within ahalf-inch of the clot.

Minimizing the time thecatheter sits in place reduces therisk of stroke, Aldrich says. “We’veimproved the technique and repli-cated the European results.” Thoseresults showed that 76.4 percent ofpatients who received tPA treat-ment improved in visual acuityversus 33 percent who receivedstandard therapy alone.

Standard therapy involves para-centesis, or inserting a needle inthe eye to withdraw fluid and de-crease pressure so that the clotmoves away from the retina. Pa-tients also inhale carbogen, a mix-ture of oxygen and carbon dioxide,to dilate the arteries and force theclot to shift. “Those treatments arerarely curative,” Adrich says, “andnothing new has been exploreduntil now.”

At follow-up, one-third of the

patients in the Hopkins study whoreceived the tPA treatment im-proved by three lines or more onthe Snellen chart versus only 4.8percent in the control group. “Sta-tistically, you are 13 times morelikely to have a three-line improve-ment in visual acuity—a substan-tial jump in vision—if you receivethis treatment,” says Aldrich.

FDA guidelines state that thesooner tPA is administered, thebetter the results. During a stroke,the window of opportunity is threehours. For artery occlusion,Aldrich has found, it is 15 hours.

A phase II trial is planned.

IN PRESS:

Aldrich E, Lee A, Chen C,Gottesman R, Bahouth M, GailloudP, Murphy K, Wityk R, Miller N.Local intra-arterial fibrinolysisadministered in aliquots for thetreatment of central retinal arteryocclusion: The Johns HopkinsHospital Experience. Stroke 2008;June 39 (6):1746-50. Epub 2008Apr.17

Double-stained confocal images of thepanaxonal marker protein gene product 9.5 with the schwann cell marker p75 incutaneous nerves in human controls. PGP9.5-stained epidermal nerve fibers (arrows)(red) extend into the epidermis butschwann cells (broken arrow) stop at thejunction between epidermis and dermis.


22 NEUROLOGY AND NEUROSURGERY D E M O N S T R AT I N G C L I N I C A L I N N OVAT I O N

Dietary Therapy for Seizures

Over the past 40 years, the John M.Freeman Pediatric Epilepsy Centerhas helped develop and promotethe ketogenic diet, the high-fat,low-carbohydrate, adequate-proteinregimen that controls seizures in atleast half of the patients who faildrug treatments. The Johns Hop-kins protocol for initiating andmaintaining the diet is in use atcenters around the world.

Now, Hopkins researchers havefound that the ketogenic diet maybe just as effective as medicationsin treating new-onset epilepsy—specifically, a rare form of epilepsyknown as infantile spasms. “To ourknowledge, this is the first de-scribed use of the ketogenic dietfor the initial treatment of a specif-ic childhood epilepsy syndrome,”says Eric Kossoff, medical directorof the Johns Hopkins KetogenicDiet Program.

In a retrospective, case-cohortstudy, Kosoff and his group demon-strated that the diet was generally aseffective as the standard medication,adrenocorticotrophic hormone(ACTH), with fewer side effects andseizure recurrences and a much low-er cost. They are now designingprospective studies on the diet fornew-onset infantile spasms as well asother causes of seizures.

With all its advantages, the keto-genic diet does have its drawbacks.It is restrictive and requires a majorchange in lifestyle that most adultsare unwilling to accept. Moreover,scientists are still not sure exactlywhy the ketogenic diet works, saysAdam Hartman, an assistant pro-fessor of neurology and pediatrics.They do know, however, that itmimics the effects of fasting andproduces ketones, which may inhib-it seizures and have other neuropro-tective properties.

Hartman is researching themechanisms of the diet and its po-tential benefits in other neurologicalillnesses. “By isolating the relevantmechanisms of its effects, we hopeto optimize the diet as it is currentlyadministered and identify otherneurological indications that dietary

neuropathy (an NIH-funded trial)and chemotherapy neuropathy.

In addition, Polydefkis is re-searching nerve regeneration usinga method he and his team devel-oped in which they slightly dam-age nerve fibers in normal skin towatch how fast they grow back.They found that the chemical cap-saicin—which causes a mild burn-ing sensation and is safe and well-tolerated in humans—doesn’tdestroy nerve fibers but merelytrims them away from the skin.The team can then measure therate at which they regenerate.

This model is more accuratethan others at determining the rateof nerve growth. “We’re able to de-tect even miniscule improvementin nerve regeneration,” says Poly-defkis. The model also allows theteam to compare nerve regrowth inhealthy subjects with that in peo-ple with diabetes and prediabetes,and to determine whether a drugaccelerates regrowth. Even diabet-ics who had no other signs orsymptoms of neuropathy, had re-duced rates of regeneration. Thissuggests that neuropathy-free sub-jects with diabetes could be includ-ed in trials of regenerative agents.

The skin punch biopsy model isan objective tool, Polydefkis says.Physicians read the biopsy bycounting nerve fibers on a piece oftissue without knowing the statusof the patient. He hopes the re-search will soon identify a drug tocure neuropathy. “We’re continu-ing to refine the process, and as wemove forward, skin punch biopsywill be a big part of our strategy.”

RESEARCH PUBLISHED:

Gibbons CH, Griffin JW, PolydefkisM, Bonyhay I, Brown A, Hauer PE,McArthur JC. The utility of skinbiopsy for prediction of progression insuspected small fiber neuropathy.Neurology 2006;66:256.

Lauria G, Cornblath DR, JohanssonO, McArthur JC, Mellgren SI,Nolano M, Rosenberg N, Sommer C.EFNS guidelines on the use of skinbiopsy in the diagnosis of peripheralneuropathy. European Journal ofNeurology 2005;12:747.

Polydefkis M, Hauer P, Sheth S,Sirdofsky M, Griffin JW, McArthurJC. The time course of epidermalnerve fibre regeneration: studies innormal controls and in people withdiabetes, with and withoutneuropathy. Brain 2004;127:1606.




Attacking AdultHydrocephalus

Weeks after Selvin Madow bangedhis head in an automobile acci-dent, he thought he’d completelyrecovered. But every morning heawoke with a strange feeling offullness in his head.

Madow was eventually diag-nosed with adult hydrocephalus,or normal pressure hydrocephalus(NPH), the condition in whichcerebrospinal fluid accumulates in the ventricles of the brain.

Hopkins neurosurgeon DanieleRigamonti wanted to place a shuntto drain the fluid, but Madow resis-ted, believing he would improvewith time. Finally, his wife im-plored him to do something abouthis peculiar gait, one of the chiefsymptoms of his disorder, andMadow had the shunt placed. To-day, the retired Baltimore shoemanufacturer is back to normal.

At the Johns Hopkins Hydro-cephalus Center many specialistswork together to help patients like

therapy may improve,” he says. “Wealso hope to find a way to achievesimilar effects more conveniently, insuch a way that would not requirethe major lifestyle change that typi-cally accompanies dietary therapy ofany sort.”

A pill form would be ideal, Kos-soff and Hartman say. The modifiedAtkins diet, which was developed asa treatment for epilepsy in 2002 byKossoff and other neurologists atJohns Hopkins, has recently beendemonstrated to be therapeutic forboth children and adults. This dietdoes not restrict calories, fluid orprotein and can be started without afast or first admitting the patient tothe hospital.

Both Kossoff and Hartman agree:As further studies of this alternativediet for adults continue, the potentialfor the ketogenic diet is wide open.

RESEARCH PUBLISHED:

Kossoff EH, Hedderick EF, Turner Z,Freeman JM. A case-controlevaluation of the ketogenic diet versusACTH for new-onset infantile spasms.Epilepsia, Epub 10 April 2008; doi:10.1111/j.1528-1167.2008.01606.x.

Kossoff E, Rowley H, Sinha S, ViningE. A prospective study of the modifiedAtkins diet for intractable epilepsy inadults. Epilepsia 2008;49:316.

Hartman AL, Gasior M, Vining EPG,Rogawski MA. The neuropharmacologyof the ketogenic diet. PediatricNeurology 2007;36:281.

Kossoff E, Turner Z, Bluml R, Pyzik P,Vining E. A randomized, crossovercomparison of daily carbohydrate limitsusing the modified Atkins diet. Epilepsy& Behavior 2007;10:432.

Freeman J, Kossoff E, Hartman AL.The ketogenic diet: one decade later.Pediatrics 2007;119;535.

Amari A, Dahlquist L, Kossoff E,Vining E, Trescher W, Slifer K.Children with seizures exhibitpreferences for foods compatible withthe ketogenic diet. Epilepsy & Behavior2007;11:98.

Gasior M, Rogawski MA, HartmanAL. Neuroprotective and disease-modifying effects of the ketogenic diet.Behavioural Pharmacology 2006;17:431.

Freeman JM, Kossoff EH, Kelly MT,Freeman JB. The Ketogenic Diet: ATreatment for Epilepsy in Children andOthers, fourth ed. New York: Demos2006.

Daniele Rigamonti checks the shunt Selvin Madow received after developinghydrocephalus resulting from a head injury.

Madow. People suspected of havingNPH are evaluated in a single outpa-tient visit. Diagnosis is a challengebecause two of NPH’s three chiefsymptoms—gait problems and de-mentia (the third is urinary inconti-nence)—are also signs of diseases likeParkinson’s and Alzheimer’s disease.

Gait and vestibular specialistDavid Solomon and AbhayMoghekar, who specializes in cogni-tive disorders, have joined Rigamontiin the center. Together they offer thegold standard for a definitive evalua-tion for shunt surgery. Candidates areadmitted to the hospital for a rigor-ous evaluation during which morethan 300 milliliters of CSF is drainedover a period of three days. The teamapplies quantitative assessments be-fore, during and after the lumbardrainage to discover if shunt surgerywould be beneficial.

“We’re continuously working to-gether to modify our protocol,”Solomon says. “We review the accu-mulated experience from Johns Hop-kins, and we incorporate best practicesfrom published guidelines. We seemore than 100 new patients a year, sowe’re able to truly test new hypothesesfor treatment and diagnosis.”

The three specialists see patientsfrom all over the world and have

added a program coordinator tohelp guide and educate patientsabout NPH. Patients who needcomplex and long-term manage-ment of nonfunctioning shunts areoften referred to the center,Moghekar says.

“By refining diagnosis and treat-ment, we’re selecting appropriatepatients for surgery and helping alarge number of elderly people whowould otherwise go into a nursinghome at a large cost to society,”says Rigamonti.

RESEARCH PUBLISHED

Gallia G, Rigamonti D, Williams M.The diagnosis and treatment ofidiopathic normal pressurehydrocephalus. Nature ClinicalPractice Neurology 2006;Jul:2(7)375

Rigamonti D et al. Normal PressureHydrocephalus: Very long termoutcome after shunt surgery. Journalof Neurology, Neurosurgery andPsychiatry 2008;Mar 20 [Epub aheadof print]

Williams MA, Sharkey P, van DorenD, Thomas G, Rigamonti D.Influence of shunt surgery onhealthcare expenditures of elderly fee-for-service Medicare beneficiaries withhydrocephalus. Journal of Neurosurgery2007 Jul;107(1):21-8.



N E W D I S C O V E R I E S

A Promising Treatment forBrain and Spinal Tumors

A new therapy for treating brainand spinal tumors is being takenfrom the laboratory to the bedside.A drug delivery treatment system

that has been shown to be safe andeffective for brain tumors now alsolooks promising for metastatic spinaldisease, which has not had many ef-fective chemotherapy options todate, Hopkins physicians say.

Moving Discovery Forward

Artist’s rendering of the landmarks for the L-6 vertebral body in rodent model. Inset: The drilling and sealing procedure: the concavity is created using the burr (A);the initial PMMA plug is inserted (B); the reinforcing PMMA barrier is applied (C);and as the tumor grows, it causes spinal cord compression (D). A = artery.

Image courtesy of the Journal of Neurosurgery: Spine




in their legs. The researchers thentested surgery, radiation therapyand local chemotherapy usingOncoGel. Animals treated with ra-diation had significant delay intheir time to paralysis. Those treat-ed with OncoGel implantationachieved similar outcomes. A com-bination of the two treatments fur-ther prolonged time to paralysisand in some animals completelyeradicated the tumor.

“Our researchers plan to use asimilar strategy in patients withbreast metastases to the spinal col-umn,” Gokaslan says. “They areapplying for internal review boardapproval and hope to start humantrials soon.”

Gokaslan and his team have al-ready introduced fundamentallynew successful surgical treatmentsfor spine cancers that have previous-ly been thought of as inoperable.

PUBLISHED IN:

Bagley CA, Bookland MJ, PindrikJA, Ozmen T, Gokaslan ZL, Witham TF Local delivery of oncogel delays paresisin rat metastatic spinal tumor model. Journal of Neurosurgery: Spine 20077;194.

Tyler B, Renard V, Kaiser K, Fowers K, BremH. 20Gy Radiotherapy with Locally DeliveredOncoGel (6.0-mg/ml Paclitaxel) SignificantlyProlongs Survival in an Experimental RodentGlioma Model. AANS/CNS Section onTumors Seventh Biennial Satellite Symposium,Washington, D.C., April 13–14, 2007.

Pennant W, Caplan J, Reidler J, Hdeib A,Pradilla G, Tyler B, Jallo G. 20Gyradiotherapy prolongs paresis-free survivalalone and in combination with locallydelivered paclitaxel (OncoGel in anexperimental rat intramedullary spinal cordtumor model. American Association ofNeurological Surgeons, San Francisco, April22–27, 2006.

Hdeib AM, Caplan J, Pradilla G, Tyler B,Legnani FG, Brem H, Jallo GI. Locallydelivered OncoGel against an established 9Lintramedullary spinal cord gliosarcoma delaysthe onset of paresis in an experimental rodentmodel. Congress of Neurological Surgeons,Boston, October 8–13, 2005.

Mantha A, Legnani FG, Bagley CA, GalliaGL, Garonzik I, Pradilla G, Amundson E,Tyler BM, Brem H, Gokaslan ZL: A novel ratmodel for the study of intraosseous metastaticspine cancer. Journal of Neurosurgery: Spine.2005 2;303.

The OncoGel delivery systemallows for the slow release of anti-cancer drugs over several weekswhen it is injected directly into thetumor or into the tumor resectioncavity. Biodegradable and ther-mosensitive, OncoGel is liquidwhen cool but forms a gel whenbody temperature warms it. Thesystem can be tailored to delivervarious agents at different rates, re-leasing drugs 3 to 5 centimetersfrom the initial injection spot.Since gliomas recur at or near theprimary tumor site, placement ofOncoGel into the tumor resectioncavity may prevent or prolong timeto tumor recurrence.

Henry Brem, director of neu-rosurgery, explains that new FDA-approved drugs for treating braincancer and tumors are rare becauseit is so difficult to get drugs pastthe blood-brain barrier. In fact, thefirst FDA-approved drug in 20years, the Gliadel wafer, was devel-oped in Brem’s lab. It deliverschemotherapy directly to thebrain. It was approved by the FDAin 1994 and is now the standardtherapy for malignant brain tu-mors all over the world.

Two years ago, Brem’s lab start-

ed working with OncoGel. “WithOncoGel, we can get through theblood-brain barrier to target thebrain directly to enhance exposureto medication while minimizingside effects,” he says. The data gen-erated in the Brem lab has been re-viewed by the FDA and is the sci-entific basis for an ongoing,multicenter phase I clinical trial.Several patients have been enrolledto date.

Hopkins researcher Betty Tylersays the investigators hope tomimic results found in rats thatshowed OncoGel combined withradiation therapy was more effec-tive than either OncoGel or radia-tion therapy alone.

Ziya Gokaslan, director of theHopkins Spine Division, is look-ing at OncoGel for treatingmetastatic spinal tumors and can-cer, which affect thousands of peo-ple a year. Treatment options areminimal, and the outlook forthose patients is not positive.

Gokaslan’s team developed ananimal model for metastatic spinaltumors. As with human spinalmetastases, the tumors extendedinto the spinal canals, and the ani-mals gradually developed weakness

changes a normal cell into acancer cell. Those are our tar-gets for therapy.”

Researchers seek small mole-cules (biologically active sub-stances or drug candidates) thatcan block the genes’ actions totest as possible therapies. Newdrug candidates, Riggins says,have been identified and areunder development.

Neurosurgeon Gary Gallia,along with other full time braintumor neurosurgeons, is work-ing closely with Riggins tomake these new therapies avail-able to patients.




Probing Genetic Changes for New Brain TumorTreatments

Approximately 44,000 new casesof primary brain and central nerv-ous system tumors are reportedeach year in the United States;more than 13,000 people die ofthese cancers each year. In theBrain Cancer Biology and TherapyResearch Laboratory, directed byGregory Riggins, researchers areworking to locate the genetic andgenomic changes that occur inbrain cancers. “Understandingthese mutations and other molecu-lar events can help us develop bet-ter treatments,” Riggins says. “Forexample, we’re looking at mutatingproteins and changes in geneticDNA to discover what process

SAGE Brain AnatomicViewer ResultsThe SAGE Genie anatomicviewer tool developed byRiggins’ lab and the NationalCancer Institute is a cancerresearch tool available on theWeb used to determine whatgenes are expressed in cancer.

Normal

Cancer

Cortex

Cerebellum

Spinal Cord

Thalamus

Substantia Nigra

Oligodendroglioma

Glioblastoma

Medulloblastoma

Grade IIIAstrocytoma

Grade IIAstrocytoma

Grade IAstrocytomaEpendymoblastoma

Ependymoma

Tags per200,000

<2

2 to 3

4 to 7

8 to 15

16 to 31

32 to 53

64 to 127

128 to 255

256 to 512

>512

RESEARCH PUBLISHED:

Trembath D, Lal A, Kroll D, OberliesN, Riggins G. A novel small moleculethat selectively inhibits glioblastomacells expressing EGFRvIII. MolecularCancer 2007;6:30.

Gallia G, Rand V, Siu I, Eberhart C,James C, Marie S, Oba-Shinjo S,Carlotti C, Caballero O, Simpson A,Brock M, Massion P, Carson B,Riggins G. PIK3CA gene mutations inpediatric and adult glioblastomamultiforme. Molecular Cancer Research2006;4:709.


Beaty R, Edwards J, Boon K, Siu I,Conway J, Riggins G. PLXDC1(TEM7) is identified in a genome-wideexpression screen of glioblastomaendothelium. Journal of Neuro-oncology2007;81:241.

Rand V, Huang J, Stockwell T, FerrieraS, Buzko O, Levy S, Busam D, Li K,Edwards J, Eberhart C, Murphy K,Tsiamouri A, Beeson K, Simpson A,Venter J, Riggins G, Strausberg R.Sequence survey of receptor tyrosinekinases reveals mutations inglioblastomas. Proceedings of the NationalAcademy of Sciences; 2005;102:14344.

Brem SS, Bierman PJ, Black P, Brem H,Chamberlain MC, Chiocca EA,Deangelis LM, Fenstermaker RA,Friedman A, Gilbert MR, Glass J,Grossman SA, Heimberger AB, Junck L,Linette GP, Loeffler JJ, Maor MH,Moots P, Mrugala M, Nabors LB,Newton HB, Olivi A, Portnow J, PradosM, Raizer JJ, Shrieve DC, Sills AK Jr.Central nervous system cancers : Journalof the National Comprehensive CancerNetwork. 2008 May;6(5):456-504.

N E W D I S C O V E R I E S32 NEUROLOGY AND NEUROSURGERY

0 100 200 300 400 500 600 700 800 900 1000

Surgery

Radiosurgery

Acoustic

Pituitary Tumor

Metastases

Low grade Gliomas

Malignant Gliomas (grade 3/4)

Meningiomas

JHH Brain Tumor Cases1996 – 2006

Cases

Image courtesy of theJournal of Neurosurgery


and brain tumor stem cell migration. “These discoveries and our in-

creasing understanding of the hu-man brain could help pave the wayfor a number of therapeutic treat-ments for brain cancer, neurodegen-erative diseases and brain damage,”says Quiñones.

Alessandro Olivi, Director of theJohns Hopkins Neurosurgical BrainTumor Program and colleagues haverecently discovered that bone mor-phogenetic proteins (BMP) can in-hibit the growth of brain tumor stemcells and thus may prove extremelyimportant in the development ofnew treatments to brain cancer.

RESEARCH PUBLISHED:

Chaichana K, Capilla-Gonzalez V, Gonzalez-PerezO, Pradilla G, Han J, Olivi A, Brem H, Garcia-Verdugo JM, Quiñones-Hinojosa A. Preservationof glial cytoarchitecture from ex vivo human tumorand non-tumor cerebral cortical explants: A humanmodel to study neurological diseases. Journal ofNeuroscience Methods 2007;164:261.

Stem Cells in Neurosurgery Topic Editors: AQuiñones-Hinojosa & Nader Sanai.Neurosurgical Clinics of North America, Volume18:1, January 2007

Piccirillo SG, Reynolds BA, Zanetti N, LamorteG, Binda E, Broggi G, Brem H, Olivi A, DimecoF, Vescovi AL. Bone morphogenetic proteinsinhibit the tumorigenic potential of human braintumour-initiating cells. Nature 2006 Dec 7:444(7120): 687-8.

N E W D I S C O V E R I E S34 NEUROLOGY AND NEUROSURGERY

The Role of Stem Cells inBrain Tumors

Using their knowledge of the proper-ties of stem cells, investigators aresearching for answers to some ele-mental mysteries about the humanbrain. How do cells migrate? What isthe cell-of-origin for brain tumors?This work, says neurosurgeon Alfre-do Quiñones-Hinojosa, aims to gaina new understanding of the brain’spotential and its ability to regenerateor produce abnormal pathologies.

Research indicates that brain tumorstem cells may be derived from neuralstem cells and that both of these cellpopulations may originate in an area of

the brain known as the subventricularzone, or SVZ. The SVZ contains astro-cytes, cells known to produce growthfactors critical to the regeneration ofdamaged neural tissue. Astrocytes po-tentially serve as brain stem cells.Quiñones is now developing the firstcomprehensive map of the SVZ in theadult human brain.

Because human and animal SVZsare very different, Quiñones says, thechallenge was to create a viable model.Thanks to a method his lab developed,human tumor and healthy brain tissuediscarded from the operating room af-ter surgery can be kept alive for up totwo weeks, time enough to study neural

Figure A: Mouse SVZ contains type B astrocytes (B) that form the glial tubes in which type A neuroblasts (A) migrate through.

Figure B:Human SVZ withfour layers that are absent in mice(I-ependymal layer,II-hypocellular gap,III-astrocytic ribbon,IV-transitional zone). These cellsare separated from the lateralventricles (LV) by a monolayer ofependymal cells (E).

Human and rodent subventricular zone (SVZ)

Images courtesy ofExperimental Neurology


E

Killiany RJ, Hyman BT, Gomez-IslaT, Moss MB, Kikinis R, Jolesz F,Tanzi R, Jones K, Albert MS. MRImeasures of entorhinal cortex vshippocampus in preclinical AD.Neurology 2002;58:1188.

Killiany RJ, Gomez-Isla T, Moss M,Kikinis R, Sandor T, Jolesz F, TanziR, Jones K, Hyman BT, Albert MS.Use of structural magnetic resonanceimaging to predict who will getAlzheimer's disease. Annals ofNeurology 2000;47:430.


Marilyn Albert reviews MRI scans.


Who Will DevelopAlzheimer’s Disease? What Drugs Will Help?

Marilyn Albert, director of theDivision of Cognitive Neuro-science, is researching measure-ments that could predict who isgoing to develop Alzheimer’s dis-ease. She’s exploring whether thesemeasures can be used in clinicaltrials to assess the effectiveness ofnew medications.

“We know there are changes inthe brain that precede the full-blown symptoms of the disease byat least as long as a decade,” Albertsays. “Using MRI scans of thebrain, we’ve been following peoplewho have mild symptoms to seewhat measures or biological mark-ers are going to predict who willprogress to dementia. Once wefind such measures, we look to seeif they might be useful in evaluat-ing new medications.”

A measurable biomarker wouldprovide a more accurate way to tellwhether a drug treatment is work-ing. Collaborating with researchersin biomedical engineering and radi-ology, Albert developed an auto-mated labeling system for analyzingMRI data images. The system com-bines different measurements toform a more accurate picture ofwhat changes are occurring in thebrain over time.

RESEARCH PUBLISHED:

Desikan RS, Segonne F, Fischl B,Quinn BT, Dickerson BC, Blacker D,Buckner RL, Dale AM, Maguire RP,Hyman BT, Albert MS, Killiany RJ.An automated labeling system forsubdividing the human cerebral cortexon MRI scans into gyral based regionsof interest. Neuroimage 2006; 31:968.Epub March 10, 2006.

Dickerson B, Fenstermacher E, SalatD, Wolk D, Maguire R, Desikan R,Pacheco J, Quinn B, Van der KouweA, Blacker D, Albert M, Killiany R,Fischi B. Detection of corticalthickness correlates of cognitiveperformance: Reliability across scansessions, scanners and field strengths.Neuroimage 2008; Jan 1;31(1):10-8.Epub September 5, 2007.


Stem Cells That Undo Nerve Damage

Using mouse embryonic stem cells,a team of Johns Hopkins scientistshas engineered new, complete, ful-ly working motor neuron circuitsstretching from spinal cord to tar-get muscles in paralyzed adult rats.Now they’re using human embry-onic stem cells in larger mammalsto see how well the technique ap-plies to human nerve recovery. Theresearch could lead to an approachto repair damage from ALS (LouGehrig’s disease), multiple sclero-sis, transverse myelitis and trau-matic spinal cord injury, the inves-tigators say.

This team has found that stemcells can be made to retrace com-plex pathways of nerve develop-ment long shut off in adult mam-mals. By injecting embryonic stemcells at the right time and place,physicians might restore the bio-logical memory for growing neu-rons.

There will be several years oftesting and thorough data evalua-tion before human clinical trialscould begin, says Douglas Kerr,the neurologist who is leading theresearch, but “this is proof that wecan recapture what happens in ear-

ly stages of motor neuron develop-ment and use that to repair dam-aged nervous systems.”

RESEARCH PUBLISHED:

Kim Y, Martinez T, Deshpande D,Drummond J, Provost-Javier K,Williams A, McGurk J, Maragakis N,Song H, Ming G, Kerr D. Correctionof humoral derangements frommutant superoxide dismutase 1 spinalcord. Annals of Neurology2006;60:716.

Deshpande D, Kim Y, Martinez T,Carmen J, Dike S, Shats I, Rubin L,Drummond J, Krishnan C, Höke A,Maragakis N, Shefner J, Rothstein J,Kerr D. Recovery from paralysis inadult rats using embryonic stem cells.Annals of Neurology 2006;60:32.


Nanofibers with ProteinRegenerate Damaged Nerves

Nerves damaged in accidents orother trauma cannot repair them-selves. Currently, surgeons trans-plant the patient’s own nerves(usually taken from the leg) toguide regrowth, but the techniqueis not very effective. Research intospeeding the repair of injured pe-ripheral nerves could one day ben-efit 100,000 people with this prob-lem each year.

Led by Ahmet Höke, JohnsHopkins neuroscientists foundthat nanofiber nerve guides, lacedwith human glial cell-derived neu-rotrophic factor (GDNF) and oth-er proteins, improve tissue regener-ation in rats. Biomedical engineerKam Leong, Höke’s longtime col-laborator, created artificial nerveguides from biodegradable polymer.The guides bridge the damagednerves. Höke and Leong manufac-tured the circular tubes of poly-mer—much thinner than a humanhair—with nanofibers (or nano-spaghetti, see photo) infused withGDNF and other proteins to speed

the process of regeneration.“The polymer allows nutrients from

the blood to pass through and pick upthe GDNF to encourage regrowth ofnerves,” Höke says. The next step, headds, is research with primates. If that issuccessful, human testing could follow.

RESEARCH PUBLISHED:

Chew SY, Mi R, Höke A, Leong K.Aligned protein–polymer composite fibersenhance nerve regeneration: a potentialtissue-engineering platform. AdvancedFunctional Materials 2007;17:1288.


Embryonic stem (ES) cell-derived motoraxons reach skeletal muscle targets atthree months after transplantation.Arrowheads denote transplant-derivedmotor neurons. Dashed line denotes thegray/white matter junction.

“Nano-spaghetti": Nanofibers aligned along thelength of the tube, fill up artificial nerve guideslike spaghetti in a box and provide a substrate forperipheral nerves to regenerate more efficiently.

For more information about our published research, visit PubMed at www.pubmed.gov. Articles and abstracts are indexed by author, topic or journal.


PAT I E N T SA F E T Y A N D QUA L I T Y ME A S U R E S40 NEUROLOGY AND NEUROSURGERY

Infection Rates Plummet inPediatric Hydrocephalus

Shunt infection rates for pediatrichydrocephalus patients at JohnsHopkins have fallen from 12 per-cent to 2 percent thanks to a newprotocol for draining the cere-brospinal fluid (CSF) from thebrain through an antibiotic-impreg-nated shunt.

Treatment for hydrocephalus,the condition that occurs when anexcessive amount of CSF builds upin the ventricles of the brain, oftenincludes implanting a shunt systemto divert the flow of CSF to anotherarea of the body where it can be ab-sorbed.

About one in 10 implantedCSF shunts becomes infected, andthat can be a severe, life-threaten-ing complication, says pediatricneurosurgeon George Jallo. Mostshunt infections occur within sixmonths of placement.

To combat that risk, antibiotic-impregnated shunt systems weredeveloped; the technology is anoutgrowth of the Hopkins tech-niques for using brain polymers todeliver chemotherapy. The newantibiotic-loaded shunts were

Patient Safety and Quality Measures

Kaplan–Meier analyses comparingshunt revision rates as a function ofprogrammable vs set-pressure valvesystems. By 24 months after shuntplacement, 26 (35 percent)programmable valve shunt cathetershad failed compared to 109 (54percent) set-pressure valve catheters.Patients receiving programmablevalve shunt catheters were 1.5-foldless likely to require shunt revisionfor the first 25 months after shuntinsertion (p<0.05).

Kaplan–Meier analyses comparing etiology of shunt failure as a function of programmable vsset-pressure valve systems. a Proximal obstruction By 24 months after shunt placement,proximal obstruction had occurred in only 9 (12 percent) programmable valve shuntcatheters compared to 58 (29 percent) set-pressure valve catheters. Patients receivingprogrammable valve shunt catheters were 2.5-fold less likely to experience proximal shuntobstruction (p<0.01). b Distal obstruction There was no risk reduction for the occurrence ofdistal obstruction in patients receiving programmable vs set-pressure valve shunt catheters[relative risk (95 percent CI); 0.69 (0.22–2.28); p=0.56]. c Shunt infection There was no riskreduction for the occurrence of shunt infection in patients receiving programmable vs set-pressure valve shunt catheters [relative risk (95 percent CI); 1.31 (0.47–3.79); p=0.585]. dValve change There was a trend toward decreased valve changes [relative risk (95 percentCI); 0.34 (0.15–1.27), p=0.121) in patients receiving programmable vs set-pressure valveshunt catheters.

found to significantly reduce in-cidence of shunt infection inchildren. “These catheters deliv-er a slow-release, low-dose an-tibiotic that almost completelyerases the risk of infection,” Jallosays. “As a result, we’re usingthem with excellent outcomes.”



RESEARCH PUBLISHED:

Sciubba DM, McGirt MJ,Woodward GF, Carson B, Jallo GI.Prolonged exposure to antibiotic-impregnated shunt catheters does notincrease incidence of late shuntinfections. Child's Nervous System2007;23:867.

Sciubba DM, Stuart RM, McGirtMJ, Woodward GF, Samdani A,Carson B, Jallo GI. Antibiotic-impregnated shunt catheters decreasethe incidence of shunt infection in thetreatment of hydrocephalus. Journal ofNeurosurgery: Pediatrics 2005;103:131.

Illustrations of the AIS catheters and the traditionalshunt system.

Upper: The surgeon’spreference forplacement of a VP shunt.

Lower left: Traditionalcatheter with valveassembly.

Lower right: The AIScatheters attached tothe valve assembly.

D.M. Sciubba, et al.

Illustration depicting the Medtronic Shata© valve system.Adjustment of valve pressure from 1.0 to 1.5 allows anoninvasive increase in the opening valve pressure.

Image courtesy ofChild’s Nervous System Image courtesy of the Journal

of Neurosurgery: Pediatrics



with clinical observation and pro-gressed with further study in thelaboratory by Mirski and others,now is in use in the NCCU andhas significantly reversed brainswelling, reduced brain pressureand improved survival.

These examples illustrate theimportance of taking a problemfrom the bedside to the bench andback again. Says Geocadin, “It’sthe only way to advance the field.”

RESEARCH PUBLISHED:

Stevens RD, Mirski MA,Ulatowski JA, and Geocadin RG.Specialized intensive care andclinical outcomes in patients withacute neurologic injury. Asystematic review. Critical CareClinic 2007. In press.

Thakor N, Shin HC, Tong S,Geocadin R. Quantitative EEGassessment. IEEE Engineering inMedicine and Biology 2006;25:20.

Research in the Neuro ICU

In the Johns Hopkins neuro-sciences critical care unit, physicianand nurse specialists work togetherto improve patient outcomesthrough extensive collaboration,constant monitoring and integra-tion of research.

“The NCCU manages the entirepatient medical profile. Once a pa-tient is admitted to the unit, allcare and decisions are transferred tothe NCCU team,” says MarekMirski, director of the neuro-sciences critical care division.

Johns Hopkins has two neuro-ICUs. One, at Hopkins Hospital, isdirected by Mirski; the other, atJohns Hopkins Bayview MedicalCenter, is directed by RomergrykoGeocadin. Both are managed bythe same faculty on a rotating basis.The y work closely with faculty inneurosurgery, neurology and highlyspecialized nursing colleagues. Together, they admit more than1,700 patients a year.

The units champion expert clini-cal bedside management as well asthe integration of research and pa-tient care. “Every day, our teambrings a scientific eye to improving

care,” Geocadin says. “When weencounter a clinical question, wetake it to the lab, create an animalmodel to study, get the answersand bring them to the bedside.”

Geocadin, for example, has a$2.8 million NIH grant to studya novel application of the EEG.Using the EEG, he is trying tounderstand how the brain regainsconsciousness after a comatosestate such as cardiac arrest. Geo-cadin studied animal models andtested his findings on 30 patients.Now, he and his team are partici-pating in a multicenter studywith 100 patients.

“We’re getting EEGs as closeto cardiac arrest as possible tohelp determine the neurologicalstatus of the patient,” says Geo-cadin. “Our eventual goal is tohelp clinicians make therapeuticdecisions that will improve pa-tient outcomes.”

The NCCU team also studiedthe management of massive brainswelling associated with severebrain injuries. To reduce swellingand pressure, they raised the levelof salt concentration in the brain.The approach, which originated


Even after extensive evaluations,many patients do not have firm di-agnoses right away, and some getsicker. So the focus is on making adiagnosis within three days to twoweeks, says Romergryko Geo-cadin, director of the neuro-sciences critical care unit at JohnsHopkins Bayview Medical Center.“We’re reviewing all the literatureand organizing a list of protocolswith the appropriate testing in theright order. We want to maximizethe window of time in which to di-agnose and treat this condition.”

The neurocritical care units atBayview and Hopkins Hospitalcollaborate with the encephalitiscenter to provide care. The centerhas all the resources to perform fulldiagnostic evaluations. “Althoughstill young,” says Jana Goins, exec-utive director of the encephalitiscenter, “our center has the ground-work in place.”


Toward Better Encephalitis Diagnosis

Hopkins neurologists and neuro-surgeons in the newly createdJohns Hopkins Encephalitis Cen-ter are defining protocols to moreaccurately diagnose acute en-cephalitis.

There are about 20,000 cases ofacute encephalitis a year in theUnited States. Up to 70 percent ofcases have no identified cause. Inthe past eight years, there has beenan increase in viral encephalitis, es-pecially the type associated withthe West Nile virus.

“Determining the cause of en-cephalitis is the real challenge,”says center director BenjaminGreenberg. “Treatment varieswidely, and it is imperative to diag-nose the cause correctly in order tosave patients.”

Mirski M, Chang CWJ, Cowan R.Impact of a neuroscience intensivecare unit on neurosurgical patientoutcomes and cost of care: evidence-based support for an intensivist-directed specialty ICU model of care.Journal of Neurosurgical Anesthesiology2001;13:83.

Mirski MA, Denchev ID, SchnitzerSM, Hanley FD. Comparisonbetween hypertonic saline andmannitol in the reduction of elevatedintracranial pressure in a rodentmodel of acute cerebral injury.Journal of Neurosurgery: Anesthesiology2000;12:334.

Qureshi AI, Geocadin RG, Suarez JI,Ulatowski JA. Long-term outcomeafter medical reversal of transtentorialherniation in patients withsupratentorial mass lesions. CriticalCare Medicine 2000;28:1556.

Koenig MA, Bryan M, Lewin III JL,Mirski MA, Geocadin RG, StevensRD. Reversal of transtentorialherniation from supratentorial lesionswith 23.4 percent saline. Neurology2008; Marc 25;709(13):1023-9, EpubFebruary 13, 2007.

Jia XF, Koenig MA, Shin H, Zhen G,Pardo-Villamizar C, Hanley DF,Thakor NV, Geocadin RG.Improving neurologic outcomes post-cardiac arrest in a rodent model:immediate hypothermia andquantitative EEG monitoring.Resuscitation 2008; Mar 7 6(3):431-42Epub 2007 Oct 23.


been pulled from the spinal cord.They redirected one nerve headedfor the scapula to a shoulder muscle,another nerve headed for the tricepsto a second shoulder muscle, and athird nerve headed for the hand tothe biceps muscle.

For a time, Belzberg explains, thetransplanted nerves “remember” theirold functions. At first, McCreery hadto think “make a fist” to bend her el-bow. But with time, the nerves adaptand movements come automatically.

E48 NEUROLOGY AND NEUROSURGERY T H E PAT I E N T E X P E R I E N C E

McCreery put in many hours ofhard work and physical therapy tohelp those movements along. Herdetermination has paid off. Now,though she’ll be on medicine fornerve pain for a few more years,people don’t even know she was inan accident.

“I’ve had the best physicians andfamily support,” McCreery says,unpacking boxes in her new place.“I’m finally getting my life back.”

Denise McCreery with physical therapist Kristin Ameraron, MSPT, OCS.

Life After Brachial Plexus Injury

Today, Denise McCreery, 34, en-joys rock climbing, swimming andplaying with her 4-year-old niece.She also just moved back into ahome of her very own. But it hastaken time to get to this point.Two and a half years ago, an acci-dent forced McCreery to quit a jobshe loved and move back homewith her parents, who helped herthrough months of rehabilitationto regain movement in her para-lyzed arm.

In March 2005, the Leesburg,Va. resident, a director and in-structor at a local college, wasdriving north on I-95 heading toNew Jersey. She remembers a con-tinuous flow of traffic—and thenwaking up in the driver’s seat ofher car, covered in glass from abroken windshield. She’d been in-jured by a brake drum that hadbroken off a truck ahead. Bounc-ing off the asphalt, it hurtledthrough the window and penetrat-ed her left shoulder, slicingthrough the intricate brachialplexus area of her upper torso.

It cracked three vertebrae andbroke her collarbone, two ribs andsix other vertebrae, paralyzing herleft shoulder and arm down to thewrist. “My arm just hung there,useless,” she recalls. After weeks ofphysical therapy, a specialist nearher home told her, “I’m afraidthere’s no way you’re going to getyour arm back.”

Such predictions are all toocommon, says neurosurgeon AllanBelzberg. What happens then isthat patients don't seek out properhelp quickly. “Don’t wait,”Belzberg says. “The earlier we getthe patients, the better our results.”

Belzberg did not see McCreeryuntil about three months after theaccident. When the surgical teamopened McCreery’s brachial plexusstructure, they had to navigatearound already formidable stretch-es of inflexible scar tissue that hadrendered some portions of nervematerial unusable. Still, theyfound working nerve portionsthey could repair.

During the 11-hour operation,the team rewired and designed analternate nerve pattern for the partof the brachial plexus that had

The Patient Experience


Managing a Complex Brain Tumor

Ten years ago, when Tom Robertsand Patti Mallin married, they en-visioned a future full of adventure,travel and eventually, children.Never did the path they picturedinclude a brain tumor. NowRoberts, 39, can’t imagine goingthrough tumor treatment, rehabili-tation and recovery without hiswife. “She’s my strength,” he says.“We’re doing this together.”

In May 1999, Roberts, an Inter-net and Web specialist at the Na-tional Academy of Sciences, wastraining for the Marine Corpsmarathon. He chalked up his un-steady gait and difficulty runningto the challenging training. Thenhe had a grand mal seizure.

“We were stunned. I was young,healthy and had no history ofseizures,” says the Takoma Park,Md., resident. Testing revealed alarge tumor mass in his brain


called an oligodendroglioma. He immediately had surgery at alarge regional hospital in the D.C.area and then opted to have hisongoing treatment managed atJohns Hopkins.

At Hopkins, specialists in neu-rology, neurosurgery, neuro-oncol-ogy. neuro-radiation therapy, neu-ro-radiology, neuro-pathologynursing and physical and occupa-tional therapy review complex cas-es weekly and weigh in on eachtreatment decision. “We provide athoughtful approach to balance at-tacking the cancer with aggressivetherapies while maximizing qualityof life,” says Jaishri Blakeley,Roberts’ neuro-oncologist. “Wedon’t give up, and as a result, we’veseen good long-term outcomes.”

Roberts continued to work untilApril 2006, when MRI scans indi-cated new tumor growth, prompt-ing a second round of radiation,more chemotherapy and a secondcraniotomy in January 2007. Re-cently though, he received goodnews: The tumor mass had de-creased. Now the team is treating

the damage to the brain resultingfrom radiation and chemotherapy.

“Currently, we’re jugglingmedication to maximize my levelof activity and minimize fatiguefrom the brain tumor treatmentover the years,” Roberts says. Hecontinues occupational therapyexercises and attends physicaltherapy sessions, and he’s workingto surpass plateaus and to recog-nize when he’s reached his limit.“There are lots of things I can’tdo, but more that I can.”

All in all, he counts himselflucky. “I wouldn’t do anythingdifferently in my current treat-ment,” he says. “I have terrificsupport and resources both athome and at Hopkins.”

Throughout the “adventure,”as he calls it, Roberts and his wifehave educated themselves on allaspects of his diagnosis and triedto live as normally as they could.Camden, their daughter, wasborn in the midst of treatment.She is now 6.

T H E PAT I E N T E X P E R I E N C E

Patti Mallin and Tom Roberts


This new treatment could bene-fit thousands, Kerr says. To date, 11patients have received the treatmentat Hopkins, with excellent results,and doctors plan to treat more pa-tients in the near future. “Most pa-tients have shown substantial im-provement, and many have acomplete elimination of signs ofthe disease even after two years,”says Kerr. He is recruiting for amulticenter, phase II clinical trial.

CLINICAL TRIAL:

MS Clinical Trial: High-Dose Cyclophosphamidein Multiple Sclerosis. Investigating the use of high-dose cyclophosphamide (HiCy) in the treatment ofmultiple sclerosis. HiCy uses an ultra-high intensity,short-course of an intravenous formulation ofcyclophosphamide to “reboot” a patient's immunesystem, thereby eliminating autoimmunity.

PI: Douglas Kerr, MD/PhDContact information: Edward HammondEmail: [email protected] Tel: 410-502-8626

T H E PAT I E N T E X P E R I E N C E52 NEUROLOGY AND NEUROSURGERY

An Experimental Drug for MS

Kathy Gewain knows somethingabout longevity: last year, theRockville, Md. insurance represen-tative helped her parents celebratetheir 50th wedding anniversary,and she herself has been marriedfor 28 years. Unfortunately, her ill-ness knows something aboutlongevity as well.

Her symptoms started in 1988when she awoke one morning andcouldn’t feel her feet. Gewain dealtwith slowly progressing symptoms,until finally in 2000, an MRI clear-ly showed multiple sclerosis, thedisease that occurs when the im-mune system attacks the centralnervous system.

Gewain came to Hopkins, whereover the next four years she triedtreatment after treatment with disap-pointing results. That is not surpris-ing, because of the 400,000 peoplein the United States who have MS,40 percent to 50 percent simply donot improve with conventional ther-apy, says neurologist Douglas Kerr.“Current MS therapies are onlymodestly effective, with significantside effects and risks, and many pa-tients continue to accrue disabilityeven with treatment.”

Kerr is leading clinical trials forRevimmune, an experimental high-dose treatment for MS made by Ac-centia Biopharmaceuticals. “Revim-mune is an aggressive, chemo-basedtherapy that we’re testing in patientswho are failing standard therapy,”Kerr says. It uses a one-time, ultra-high intensity course of an approveddrug, cyclophosphamide, deliveredintravenously for four hours a dayover four days.

Gewain met the rigid criteria as acandidate and had the treatment inJune 2004. Although the aggressive-ness of the treatment made hernervous, she never got sick. Shestayed in Baltimore during and fortwo weeks after the therapy so doc-tors could monitor her progress. Shereturned for neurological testingevery three months.

Six months later, she was able towalk up the stairs to watch her songraduate from college. More than36 months post-Revimmune andon no other medications, Gewainsays she still feels occasional numb-ness in her feet and the heat stillbothers her, but otherwise she hasn’thad any recurrence of MS symp-toms. She’s back to walking themall, grocery shopping and climb-ing ladders to paint her walls. Kathy Gewain


Henry Brem is the Harvey Cush-ing Professor of Neurosurgery, aprofessor of oncology and ophthal-mology, and director of the Depart-ment of Neurosurgery at the JohnsHopkins University School ofMedicine.

Dr. Brem graduated from Har-vard Medical School with honorsand trained in neurosurgery at Co-lumbia University’s Neurological In-stitute. He completed a fellowship inneurosurgery and ophthalmology atJohns Hopkins and then joined thefaculty in 1984. Dr. Brem rose to therank of full professor and helpedbuild one of the leading brain tumorcenters in the United States. He alsodirects the Hunterian Research Lab-oratory, which has introduced newtherapies for brain tumors. In 1998,Brem was elected to the NationalAcademy of Sciences’ Institute ofMedicine. He is one of the few neu-rosurgeons in the country to benamed to this national organization.In 2000, Dr. Brem was appointedthe Harvey Cushing Professor, neu-rosurgeon-in-chief and chairman ofthe Department of Neurosurgery at Hopkins.

Dr. Brem focuses his clinical prac-tice on the surgical treatment of pitu-itary tumors, meningiomas, gliomas,acoustic neuromas, skull-base tumorsand other solid brain tumors. He hasdeveloped new clinical treatments forbrain tumors, including the delivery ofchemotherapy directly to the brainthrough the Gliadel wafer, anti-angio-genesis therapies, computer navigationsystems used during surgery and braintumor vaccines. Dr. Brem is board-cer-tified in neurological surgery.

Our Faculty


A Stroke Treatment ThatSpeaks for Itself

Author and political science professorRobert (Dan) Tschirgi was not yet 60when he had an ischemic stroke thatrobbed him of his speech and vocab-ulary—in all three languages hespeaks fluently. But Tschirgi, a resi-dent of Cairo and Cozumel, recov-ered his ability to speak English,Turkish and Spanish after undergoingan investigational treatment forstroke at Johns Hopkins.

Tschirgi, who is also proficient inseveral other languages, awoke one dayin August 2005 with impaired visionand problems with his coordination.By that night, he was in a Cozumelclinic, where he was diagnosed as hav-ing had a stroke. His wife madearrangements to transport him toJohns Hopkins.

By the time he arrived, Tschirgi hadsuffered occlusions in both carotid ar-teries, triggering a small stroke in hisleft hemisphere, says Argye Hillis,Hopkins professor of neurology andmedicine and co-director of the cere-brovascular division. But the real prob-lem was the low blood flow in the big-ger region of his left hemisphere,causing severe aphasia, a commonneurological symptom when thestroke is in that region.

But Tschirgi was in the right place:Hillis had just completed a randomizedtrial that showed treating appropriatestroke candidates with medically in-duced hypertension resulted in betteroutcomes for neurologic functionswhen compared to conventional care.

“Animal studies had shown that in-creasing blood flow to ischemic tissuethat was not yet dead resulted in im-proved outcomes,” she says. “So weaugment the blood pressure for a shorttime to boost blood flow to that areauntil we see improvement.”

Research shows that this methodcan even be helpful more than 24hours after stroke onset, Hillis says.“Dan had been having symptoms forwell over 24 hours, and he was get-ting worse. But he started improvingas soon as we started the blood pres-sure augmentation.”

Dan Tschirgi

Henry Brem, M.D.

O U R FA C U LT Y


O U R FA C U LT Y56 NEUROLOGY AND NEUROSURGERY

Brain Injury Outcome StudiesDaniel Hanley, M.D.

Cerebrovascular – NeurosurgeryRafael J. Tamargo, M.D., F.A.C.S.

Cerebrovascular – NeurologyArgye Hillis, M.D., M.A.Robert Wityk, M.D.

Cognitive NeuroscienceMarilyn Albert, Ph.D.

Epilepsy – AdultGregory Bergey, M.D.

Epilepsy – PediatricEileen P.G. Vining, M.D.

Functional NeurosurgeryFrederick Lenz, M.D., Ph.D.

Johns Hopkins Bayview Medical Center NeurologyRichard O’Brien, M.D.

Johns Hopkins Bayview Medical Center NeurosurgeryAlessandro Olivi, M.D.

Institute for Cell Engineering – Neuroregeneration ProgramTed Dawson, M.D., Ph.D.

Movement DisordersTed Dawson, M.D., Ph.D.

Neuroimmunology and Neurological InfectionsPeter Calabresi, M.D.Avindra Nath, M.D.

Neurological Critical CareRomergryko Geocadin, M.D.

(Johns Hopkins Bayview Medical Center)Marek Mirski, M.D., Ph.D.

(Johns Hopkins Hospital)

Neuromuscular Ahmet Höke, M.D., Ph.D.

Neuro-oncologyJohn Laterra, M.D., Ph.D.

Neurosurgical OncologyAlessandro Olivi, M.D.

Pediatric NeurologyHarvey Singer, M.D.

Pediatric NeurosurgeryBenjamin Carson, M.D.George Jallo, M.D.

Peripheral NerveAllan Belzberg, M.D.

RadiosurgeryDaniele Rigamonti, M.D.

SpineZiya Gokaslan, M.D.

Vestibular DisordersDavid Zee, M.D.

Justin McArthur is a professor ofneurology, pathology and epidemiol-ogy and interim director of the De-partment of Neurology at the JohnsHopkins University School of Medi-cine. He is also the director of theJohns Hopkins/National Institute ofMental Health Research Center forNovel Therapeutics of HIV-associat-ed Cognitive Disorders.

Dr. McArthur received his med-ical degree from Guys Hospital Med-ical School in London, England. Hecompleted an internship and residen-cy in internal medicine at The JohnsHopkins Hospital. Dr. McArthurcontinued his education at Hopkinsby completing a residency in neurol-ogy and earning his master’s degreein public health.

Now the interim director of theDepartment of Neurology, Dr.McArthur is nationally and interna-tionally recognized for his work instudying the natural history, develop-ment and treatment of HIV infec-tion, multiple sclerosis and otherneurological infections and immune-mediated neurological disorders. Dr.McArthur has also developed a tech-nique to use cutaneous nerves tostudy sensory neuropathies, includ-ing those associated with chemother-apy, HIV and diabetes.

As director of the Johns Hopkins/National Institute of Mental HealthResearch Center for Novel Therapeu-tics of HIV-associated Cognitive Disorders, Dr. McArthur leads his interdisciplinary research team intranslating discoveries of the patho-physiological mechanisms into noveltherapeutics for HIV-associated de-mentia (HIV-D). Dr. McArthur is board-certified in neurology and internal medicine.

Johns Hopkins Neurology and Neurosurgery Divisions and Division Directors

Justin McArthur, M.B.B.S., M.P.H.


E58 NEUROLOGY AND NEUROSURGERY R E F E R R A L A S S I S TA N C E

Referral Assistance

Hopkins USA

Hopkins USA provides one pointof contact for our out-of-town pa-tients. Our staff can help patientsidentify appropriate physicians orspecialists, coordinate multiplemedical appointments, arrange sec-ond opinions, and obtain generalinformation on Johns Hopkins’numerous services. In addition,Johns Hopkins USA staff can pro-vide information regarding trans-portation, lodging and other travelneeds. Call 410-735-HUSA(4872)to talk with Hopkins USA. Forfamily accommodations on the patient floor, see information re-garding the Marburg Pavilion onpage 60.

Johns Hopkins MedicineInternational

The professional staff of Interna-tional Services coordinates all as-pects of international patients’medical care, paying special atten-tion to personal, cultural, and trav-el-related needs. The staff willarrange consultations, secondopinions or treatments and coordi-

nate appointments in a timelymanner. The staff also providesmedical records reviews before thepatient travels to the United States,language interpreters, cost esti-mates and assistance with travelarrangements. For more informa-tion, call 410-955-8032. Fromoutside the country, call +01-410-955-8032 or visit the website,www.jhintl.net.

Accommodations Assistance

Accommodations OfficeThe Johns Hopkins Hospital hasarranged special rates (and shuttleservice in some instances) at localhotels for patients and their fami-lies. A full-service travel agency isavailable to help patients and theirfamilies with air, hotel or groundaccommodations. It is open Mon-day through Friday, 8:30 a.m. to 5p.m. Please call 1-800-225-2201or 410-614-1911 for assistance.

For urgent physician-to-physicianreferrals or consultation, please call the Hopkins Access Line(HAL) at 1-800-765-5447.

You may also refer patients to Neurology faculty by calling 410-955-9441 or [email protected]. To referpatients to Neurosurgery facultycall 410-955-2248.

For more information aboutJohns Hopkins Neurology andNeurosurgery, visit our Web site at www.hopkinsneuro.org.

How to Refer a Patient

Johns Hopkins Neurology andNeurosurgery offers patient con-sultations in offices throughout the Baltimore metropolitan area,including the Outpatient Center at The Johns Hopkins Hospital,Johns Hopkins Bayview MedicalCenter, and ambulatory outpatientcenters at Green Spring Stationand Cedar Lane in Howard County. For directions and maps, please visit our Web site at www.hopkinshospital.org/directions.

Locations


J O H N S H O P K I N S M E D I C I N E OV E RV I E W

Johns Hopkins Medicine Overview

Johns Hopkins Medicine, estab-lished in 1995 to unite Hopkinsbiomedical research, clinical teach-ing and business enterprises,brings together the Johns HopkinsUniversity School of Medicine andits faculty with the facilities andprograms of The Johns HopkinsHealth System. The Health Sys-tem, which has its origins in thefounding of the world famousJohns Hopkins Hospital, nowcomprises three hospitals, as well

as other elements of an integratedsystem, from a community physi-cians group to home care. Thecomponents of Johns HopkinsMedicine consistently are named atthe top of national rankings forbest hospital and best school ofmedicine, and its faculty consis-tently win the largest share of NIHresearch funds. Results of this re-search continue to advance effortsto diagnose, treat and preventmany diseases.


Marburg PavilionLocated in the historic MarburgBuilding, the Marburg Pavilion of-fers deluxe accommodations foradult patients. A limited numberof private rooms and two-roomsuites are available for an addition-al charge and feature fine woodfurniture, private baths, entertain-ment centers and an array of serv-ices such as expanded diningmenus and overnight sleeping ac-commodations for family mem-bers. For more information call410-614-4777.

Patient RelationsPatient Representatives are avail-able to help resolve any concernsabout patient care, interpret thepolicies and procedures of the hos-pital, and arrange for services pa-tients may need. At The JohnsHopkins Hospital, call 410-955-CARE (2273) to speak with a pa-tient representative. Hours are8:30 a.m. to 5 p.m. and the officeis located in the hospital atCarnegie 100.

At Johns Hopkins Bayview Med-ical Center, call 410-550-0626 tospeak with a patient representativeabout any patient care concerns.Hours are 8:30 a.m. to 5 p.m. Theoffice is located in the Bayview Med-ical Office on the main level.

Sign LanguageDeaf and hearing-impaired patientscan arrange for interpreters or usethe TTY in the patient relations of-fices at both The Johns HopkinsHospital and Johns HopkinsBayview Medical Center. They canalso arrange for interpreters, sign lan-guage interpreters for deaf and hear-ing impaired patients.

For more information, call 410-955-2273at Hopkins Hospital or 410-550-0626at Bayview, or visit the JHH website atwww.hopkinsmedicine.org or Bayview’swebsite at www.hopkinsbayview.org.

For patient information and visitors guide to The Johns Hopkins Hospital, visitwww.hopkinshospital.org/patients/index.html.

Visit our Web site at www.hopkinsneuro.org

Department of Neurology 410-955-9441

Department of Neurosurgery410-955-2248

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