Surgical Procedures for CSF Problems: The Neurosurgical Perspective

M. Sean Grady, MD Department of Neurosurgery University of Pennsylvania

CSF Hydrodynamics
Obstructive hydrocephalus Communicating hydrocephalus Normal pressure hydrocephalus Idiopathic intracranial hypertension benign intracranial hypertension, pseudotumor cerebri

CSF Hydrodynamics

NPH Surgery

Marmarou et al, Supplement to Neurosurgery, 57, S2-1-S2-52, 2005.

Potential supplemental tests for shunt responsiveness

Radionuclide cisternography Aqueductal CSF flow velocity ICP monitoring High volume LP External lumbar drain CSF Ro

Radionuclide cisternography & Aqueductal CSF flow velocity

No evidence to support improvement of diagnostic accuracy at this time through either measure

Vanneste et al, 1992. Bradley et al, 1996; Dixon et al, 2002.

ICP monitoring
Often used in conjunction with ELD Elevated ICP suggests another source Use of frequency of A and B waves controversial

McGirt et al, 2005; Raftopoulos et al, 1992.

High volume LP
High positive predictive value Low specificity Positive test suggests shunt responsiveness but negative test is not helpful.

Haan & Thomeer, 1988; Kahlon et al, 2002; Malm et al, 1995; Walchenbach et al, 2002; Wikkelso et al, 1986.

External lumbar drain

High positive predictive value (like LP) Improved specificity from LP Requires hospital admission Higher morbidity

Haan & Thomeer, 1988; Marmarou,Young et al, 2005; Walchenbach et al, 2002; Williams et al, 1998.

CSF Ro
Outflow resistance measurement Multiple methods used to determine with different threshold values May improve identification in patients with negative tap test

Boon et al, 1997; Borgeson et al, 1979; Kahlon et al, 2002; Malm et al, 1995; Meier & Bartels, 2001; Takeuchi et al, 2000.

Recommended Algorithm

Supplemental Test Improvement

Trial of tests should include:
Probable and possible NPH patients Multiple supplemental tests Randomize CSF volume removal Shunt everybody with acceptable surgical risk Use good endpoints with high inter-observer reliability

Surgical Treatment
Medical clearance Choice of device and configuration Complications
Hematoma (intracerebral and subdural) Subdural hygroma Shunt infection Shunt malfunction Seizure

Devices
Differential pressure valves Flow-limiting valves Programmable valves Antisiphon devices

Post-operative cognitive deficits

Patients may worsen initially after surgery even if they eventually will respond to shunting.

Markov Decision Analysis: Shunting

Simulate the course of 1000 patients with suspected NPH Outcomes measured in quality adjusted life years Base case -- 65 year old with suspected NPH and moderate dementia (CERAD)
Significant response is improvement to mild dementia
Stein et al, in press.

Results
Shunt insertion added an average of 1.7 QALYs Empirically shunting all potential patients is better than the natural history for all published rates of shunt response and complications

Markov Decision Analysis: Supplemental Tests

Modification of previous model to include a test arm Used a pessimistic 25% shunt response rate and 30% complication rate Cost based on Medicare reimbursement for testing, treatments, and custodial care Cost-effectiveness threshold at $60,000 per QALY (high standard)
Burnett et al, in press.

Results - Test Effectiveness

To achieve better outcomes than empiric shunting require:
Minimal sensitivity of 0.95 (with 80% specificity)
Sensitivity requirement increases with decreased specificity

Based on recent published data, only ELD is close to threshold sensitivity but still not sufficient

Results - Cost Effectiveness

A perfect test (100% sensitivity and specificity) could cost up to $6000 to be cost-effective Decreasing parameters decreases the cost limit

Penn NPH Study

Multidisciplinary problem Involves neurologists, neuropsychologists, neurosurgeons, neuropathologists

Initial evaluation
Neuropsychological standardized dementia workup performed at the Memory Disorders Clinic (MDC) of the Alzheimers Disease Center at the University of Pennsylvania
Includes taped gait assessment and review of urinary symptomatology Patients reviewed and discussed by cognitive neurologists

Surgical evaluation & treatment

Patient referral for surgery if probable or possible NPH Surgery to include sampling of CSF and frontal cortex, optional LP for CSF CSF and frontal cortex to be analyzed at the Penn Center for Neurodegenerative Disease Research

Follow-up
Regular neurosurgical follow-up including monthly CT scans and possible valve adjustments for 3 months Patients will have repeat evaluation at the MDC 3, 6, and 12 months post-operatively to objectively test for changes
Will include repeat neuropsychological battery and taped gait assessment for blinded review

Analysis
Correlate clinical response with:
Pre-operative clinical data
History Exam, neuropsychological, laboratory, and imaging findings

Histopathological data
CSF
Routine chemistry, tau, abeta, isoprostanes

Cortex
Plaques and tangles Neurodegenerative disease proteins Biochemical analysis Electron microscopy

Valve Adjustments* Subject ID NPH-02 NPH-03 NPH-04 NPH-05 NPH-06 NPH-07 NPH-08 NPH-09 NPH-10 NPH-11 NPH-12 NPH-13 NPH-14 1-Month 2-Month 3-Month Follow-up Follow-up Follow-up 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.5 1.5 1.0 1.0 1.0 1.0 1.5 1.0 0.5 1.0 1.0 8/11/06 8/11/06 1.0 1.0 1.0 8/25/06 9/15/06 9/15/06 9/15/06 1.0 8/11/06 1.0 1.5 8/11/06 1.5 8/25/06 2.0 8/25/06 8/11/06 4+ Month Follow-up

Symptom Improvement# Gait + + + + + + + + + + + + + + + + + + Cognition + + + + + Bladder Control +

* Initial Valve setting was 1.5 for all subjects # Symptom improvement is patient reported, not clinically measured

Shunt Adverse Events

Complication Abdominal shunt tip in extraperitoneal, not intraperitoneal cavity Ventricular catheter inserted into interhemispheric fissure instead of the ventricles Overdrainage => Bilateral Subdural Hematoma Abdominal Pain Number of Patients in Study Group (n=13) 1* Number of Patients in Excluded Group (n=2) Subject ID

NPH-02

1*

NPH-04

2 2# 1#

NPH-04 NPH-06 NPH-11 NPH-13

* Required second operation # Found not to be due to shunt placement

Shunt Adverse Events

Complication Number of Patients in Study Group (n=13) 3 1 1 2 1 1 1 Number of Patients in Excluded Group (n=2) Subject ID NPH-04 NPH-05 NPH-13 NPH-09 NPH-06 NPH-05 NPH-12 NPH-10 NPH-13

Dizziness Chest Pain Seizure Heightened emotions Swelling at scalp incision site Headache

Acknowledgements
Roy Hamilton, MD Sunil Patel, MD Joanna Lopinto, RN Anuj Basil, MD Joel Bauman, MD Eric Jackson, MD

Endoscopic 3rd ventricuolostomy

Endoscopic 3rd ventricuolostomy

Hailong, et al J Neurosurg: 109, 2008

Idiopathic Intracranial Hypertension

Sagittal sinus thrombosis Vitamin A, cyclines Dural AV fistula Slit ventricle syndrome Idiopathic F>M 7:1 obesity

Idiopathic Intracranial Hypertension

Small ventricles on CT HA Visual deficits High pressure on LP

LP vs VP shunt
Complications LP: iatrogenic Chiari, overdrainage VP: ICH Revision rate Shunt evaluation

LP Shunt Revision Rate

Average: 2.5/patient (1-10)

Burgett: Neurology, Volume 49(3).September 1997.734-739

VP shunt revision rate

Average: 1.5/patient (1-2)

Bynke: Neurology, Volume 63(7).October 12, 2004.1314-1316

Alternative Treatments
Subtemporal decompression Sagittal sinus shunt Optic nerve sheath fenestration

IIH Conclusions
CSF diversion surgery effective but technically challenging VP shunt with stereotactic guidance may have best outcome, but trial needed Shunt does not always relieve visual problems