Case Presentation: Neurology/Neurosurgery Grand Rounds February 28, 2006 Gabriel Zada, MD Christopher Aho, MD Neurosurgery Blue LAC-USC Medical Center

Patient G.P. History of Present Illness: 44-year-old Latino man Complains of progressive headache x 2-3 months Headache worse throughout course of day Developed nausea/vomiting 1-2 weeks prior to admission Intermittent double vision, dizziness Hit head while working 6 months ago, but symptoms developed much later No sensory or motor complaints Denies fevers, chills Denies seizures

History of Present Illness:

44-year-old Latino man

Complains of progressive headache x 2-3 months

Headache worse throughout course of day

Developed nausea/vomiting 1-2 weeks prior to admission

Intermittent double vision, dizziness

Hit head while working 6 months ago, but symptoms developed much later

No sensory or motor complaints

Denies fevers, chills

Denies seizures

History (continued) Past Medical History: None Past Surgical History: None Medications: Tylenol, Ibuprofen for Has Allergies : None known Social History: Works for pool chemical company Smokes ~ 5 cigarettes/day Denies alcohol or other drugs

Past Medical History: None

Past Surgical History: None

Medications: Tylenol, Ibuprofen for Has

Allergies : None known

Social History:

Works for pool chemical company

Smokes ~ 5 cigarettes/day

Denies alcohol or other drugs

Physical Examination Mental Status: Awake, alert, oriented to person, place, time, and situation. Speech fluent. Cranial Nerves: Right partial 3rd nerve palsy (x 1 day) Pupil 7  5mm, sluggish. Partial ptosis. No oculomotor deficit. Left pupil 5  3mm, brisk. Face symmetric Cranial nerves otherwise intact.

Mental Status:

Awake, alert, oriented to person, place, time, and situation. Speech fluent.

Cranial Nerves:

Right partial 3rd nerve palsy (x 1 day)

Pupil 7  5mm, sluggish.

Partial ptosis.

No oculomotor deficit.

Left pupil 5  3mm, brisk.

Face symmetric

Cranial nerves otherwise intact.

Physical Examination Motor: Tone Normal No pronator drift Power 5/5 in all extremities Reflexes: 2+, symmetric throughout No Hoffman’s sign Toes downgoing bilaterally Sensory: Sensation intact in all extremities. Cerebellar/Gait: Finger-nose-finger normal. Gait exam deferred.

Motor:

Tone Normal

No pronator drift

Power 5/5 in all extremities

Reflexes:

2+, symmetric throughout

No Hoffman’s sign

Toes downgoing bilaterally

Sensory:

Sensation intact in all extremities.

Cerebellar/Gait:

Finger-nose-finger normal. Gait exam deferred.

Head CT

Initial Hospital Course Developing concern that patient had increased intracranial pressures and brainstem herniation Mannitol trial  Right 3 rd nerve palsy improved Emergent neurosurgery consult requested Initial concern per neurosurgery for subarachnoid hemorrhage and ruptured P-Comm aneurysm Nimodipine + increased intravenous fluids started empirically Emergent cerebral angiogram  no aneurysm, AVM Hospital day 3: Right 3 rd palsy recurred, now with altered mental status and lethargy

Developing concern that patient had increased intracranial pressures and brainstem herniation

Mannitol trial  Right 3 rd nerve palsy improved

Emergent neurosurgery consult requested

Initial concern per neurosurgery for subarachnoid hemorrhage and ruptured P-Comm aneurysm

Nimodipine + increased intravenous fluids started empirically

Emergent cerebral angiogram  no aneurysm, AVM

Hospital day 3: Right 3 rd palsy recurred, now with altered mental status and lethargy

CT Scan: Final Report High density material within confines of Circle of Willis, concerning for possible SAH. Left frontal subdural collection (subacute or chronic SDH) Rule out empyema, meningitis, SAH.

High density material within confines of Circle of Willis, concerning for possible SAH.

Left frontal subdural collection (subacute or chronic SDH)

Rule out empyema, meningitis, SAH.

Brain MRI

MRI: Final Report Bilateral SDH Evidence of SAH Diffuse meningeal enhancement Decreased caliber of right ICA and MCA, may be suggestive of vasospasm.

Bilateral SDH

Evidence of SAH

Diffuse meningeal enhancement

Decreased caliber of right ICA and MCA, may be suggestive of vasospasm.

Hospital Course (continued) Lumbar Puncture felt to be contraindicated Right ventriculostomy placed on HD#5 ICPs range: -6 to 4 CSF studies: RBCs 485, WBCs 0, Glucose 59, Protein 8 PMNs 84, Lymphocytes 10 No improvement in neuro status. Patient became progressively more obtunded and developed additional left 3 rd nerve palsy,.

Lumbar Puncture felt to be contraindicated

Right ventriculostomy placed on HD#5

ICPs range: -6 to 4

CSF studies:

RBCs 485, WBCs 0, Glucose 59, Protein 8

PMNs 84, Lymphocytes 10

No improvement in neuro status.

Patient became progressively more obtunded and developed additional left 3 rd nerve palsy,.

MRI: Final Report Interval placement of R frontal ventriculostomy Left greater than right SDH

Interval placement of R frontal ventriculostomy

Left greater than right SDH

Hospital Course (continued) Discussion over intracranial hypertension versus hypotension began. Patient started on trial of IV caffeine, supine position. ICP Monitor (Bolt) placed to recheck ICPs ICP range: -7 to 5 That night, patient developed rapid progression of bradycardia to the 40s + apneic episodes Emergent CT myelogram ordered

Discussion over intracranial hypertension versus hypotension began.

Patient started on trial of IV caffeine, supine position.

ICP Monitor (Bolt) placed to recheck ICPs

ICP range: -7 to 5

That night, patient developed rapid progression of bradycardia to the 40s + apneic episodes

Emergent CT myelogram ordered

Diagnosis Spontaneous Intracranial Hypotension (SIH) secondary to Cervical and Thoracic CSF leak CSF Leak at C1-C3 Left epidural space Additional leak from T6-T10 ventrally Patient started on IV caffeine drip Placed in Trendelenburg position with increase in ICPs to 10-18 range and improvement in mental status

Spontaneous Intracranial Hypotension (SIH) secondary to Cervical and Thoracic CSF leak

CSF Leak at C1-C3 Left epidural space

Additional leak from T6-T10 ventrally

Patient started on IV caffeine drip

Placed in Trendelenburg position with increase in ICPs to 10-18 range and improvement in mental status

Treatment Anesthesia contacted for emergent epidural blood patch Case done in IR suite under fluoroscopic guidance C2 region received 8 cc autologous blood patch T6-7 region received 21 cc blood patch Immediate relief of headaches and increased ICPs to 15-19 (flat)

Anesthesia contacted for emergent epidural blood patch

Case done in IR suite under fluoroscopic guidance

C2 region received 8 cc autologous blood patch

T6-7 region received 21 cc blood patch

Immediate relief of headaches and increased ICPs to 15-19 (flat)

Post-treatment Course Post-patch day 1: Patient awake, alert x 2. Complete resolution of 3 rd nerve palsies Bolt removed Sat up post-patch day 2 Patient home day 7 following procedure, completely intact

Post-patch day 1: Patient awake, alert x 2. Complete resolution of 3 rd nerve palsies

Bolt removed

Sat up post-patch day 2

Patient home day 7 following procedure, completely intact

Spontaneous Intracranial Hypotension (SIH) Patient Demographics: Often occurs in middle-aged patients Mean age ~40 years Female preponderance Higher incidences in patients with Marfan’s disease, other connective tissue diseases, and weightlifters

Patient Demographics:

Often occurs in middle-aged patients

Mean age ~40 years

Female preponderance

Higher incidences in patients with Marfan’s disease, other connective tissue diseases, and weightlifters

Spontaneous Intracranial Hypotension (SIH) Clinical findings: Orthostatic headache similar to post-lumbar puncture spinal HA Exacerbated by laughing, coughing, Valsalva, physical exertion Often refractory to analgesic agents Nausea/vomiting, anorexia, neck pain/rigidity, dizziness, diplopia are common Cranial nerve palsies (often VI) Diverse presentation: Hearing changes, galactorrhea, facial numbness, radicular symptoms, parkinsonism, seizures, coma, death have been reported

Clinical findings:

Orthostatic headache

similar to post-lumbar puncture spinal HA

Exacerbated by laughing, coughing, Valsalva, physical exertion

Often refractory to analgesic agents

Nausea/vomiting, anorexia, neck pain/rigidity, dizziness, diplopia are common

Cranial nerve palsies (often VI)

Diverse presentation: Hearing changes, galactorrhea, facial numbness, radicular symptoms, parkinsonism, seizures, coma, death have been reported

SIH: Diagnosis Often misdiagnosed (94% in one series) 14% misdiagnosed as SAH and underwent cerebral angiography Diagnostic delay: 4 days to 13 years (mean 20 days) CT Scan often misleading Lumbar Puncture: Opening pressures usually < 60 mm H20 in SIH (normal 150-400 mm H20) “ Sucking noise” reported with LP on occasion, indicating subatmospheric pressure CSF studies: increased protein, lymphocytic pleocytosis,xanthochromia

Often misdiagnosed (94% in one series)

14% misdiagnosed as SAH and underwent cerebral angiography

Diagnostic delay: 4 days to 13 years (mean 20 days)

CT Scan often misleading

Lumbar Puncture:

Opening pressures usually < 60 mm H20 in SIH

(normal 150-400 mm H20)

“ Sucking noise” reported with LP on occasion, indicating subatmospheric pressure

CSF studies:

increased protein, lymphocytic pleocytosis,xanthochromia

SIH: Radiographic Findings CT Scan: Effacement of basal cisterns Subdural hygromas/hematomas Pseudo-SAH: (10%) Hyperdensity in basal cisterns (? obliteration of cisterns with arterial + venous engorgement) MR Imaging: Diffuse meningeal enhancement (pachymeninges, not leptomeninges) Venous sinus engorgement Pituitary gland enlargement/hyperemia Downward displacement of brain/ tonsillar ectopia Subdural fluid collections and hematomas, often without mass effect (50%)

CT Scan:

Effacement of basal cisterns

Subdural hygromas/hematomas

Pseudo-SAH: (10%)

Hyperdensity in basal cisterns (? obliteration of cisterns with arterial + venous engorgement)

MR Imaging:

Diffuse meningeal enhancement (pachymeninges, not leptomeninges)

Venous sinus engorgement

Pituitary gland enlargement/hyperemia

Downward displacement of brain/ tonsillar ectopia

Subdural fluid collections and hematomas, often without mass effect (50%)

SIH: Radiographic Findings CT Myelography Study of choice for localizing leaks Lower cervical and thoracic region most common Often reveals CSF leaks and meningeal diverticula Better localization than spinal MR imaging Sensitivity: 67% in one study Radionuclide Cisternography Radioactive tracer injected into lumbar subarachnoid space Normally, CSF travels upwards and is absorbed into sinuses Can detect CSF leaks Sensitivity: 60% for actual CSF leak, 90% for “abnormal study” Doppler Flow Imaging Superior ophthalmic vein engorgement on TCDs Sensitive/specific in 26 of 26 patients (100%) Compared to healthy volunteers Improved with treatment

CT Myelography

Study of choice for localizing leaks

Lower cervical and thoracic region most common

Often reveals CSF leaks and meningeal diverticula

Better localization than spinal MR imaging

Sensitivity: 67% in one study

Radionuclide Cisternography

Radioactive tracer injected into lumbar subarachnoid space

Normally, CSF travels upwards and is absorbed into sinuses

Can detect CSF leaks

Sensitivity: 60% for actual CSF leak, 90% for “abnormal study”

Doppler Flow Imaging

Superior ophthalmic vein engorgement on TCDs

Sensitive/specific in 26 of 26 patients (100%)

Compared to healthy volunteers

Improved with treatment

SIH: Pathophysiology Brain weighs approximately 1500g Intracranial weight is ~ 48g because of suspension in CSF Brain otherwise supported by meninges, veins, cranial nerves (esp. CNs V, IX, X) Depletion of CSF in SIH causes downward pressure on these structures with traction on cranial nerves Monro-Kellie Hypothesis: Decreased CSF leads to venous engorgement and cerebral edema/hyperemia.

Brain weighs approximately 1500g

Intracranial weight is ~ 48g because of suspension in CSF

Brain otherwise supported by meninges, veins, cranial nerves (esp. CNs V, IX, X)

Depletion of CSF in SIH causes downward pressure on these structures with traction on cranial nerves

Monro-Kellie Hypothesis: Decreased CSF leads to venous engorgement and cerebral edema/hyperemia.

SIH: Treatment Options Symptomatic relief (Conservative Management) Often successful as first-line therapy Supine position Caffeine or theophylline (IV or PO) effective in ~75% of cases (vasoconstriction resulting in decreased CBF) Fluid restoration: Increased IV/oral hydration, salt intake, CO2 inhalation No proven efficacy for these therapies

Symptomatic relief (Conservative Management)

Often successful as first-line therapy

Supine position

Caffeine or theophylline (IV or PO) effective in ~75% of cases (vasoconstriction resulting in decreased CBF)

Fluid restoration: Increased IV/oral hydration, salt intake, CO2 inhalation

No proven efficacy for these therapies

SIH: Treatment Options Epidural Blood Patch Technique developed by Gromley 85-90% efficacy for first trial Up to 98% efficacy with repeat patches Most effective if placed within 1 level of the leak If leak site undetectable, may place patch in lumbar spine and place in trendelenburg position (up to 9 level efficacy in models) Immediate relief often observed (90%) Initial relief: gelatinous seal over hole Long-term: Collagen deposition, fibroblast activity, scar formation

Epidural Blood Patch

Technique developed by Gromley

85-90% efficacy for first trial

Up to 98% efficacy with repeat patches

Most effective if placed within 1 level of the leak

If leak site undetectable, may place patch in lumbar spine and place in trendelenburg position (up to 9 level efficacy in models)

Immediate relief often observed (90%)

Initial relief: gelatinous seal over hole

Long-term: Collagen deposition, fibroblast activity, scar formation

SIH: Treatment Options Surgical repair of CSF leak: For refractory cases Especially for meningeal divertcula Treatment with ligation of diverticula Meningeal tears show less success with surgical repair Fibrin Glue reported with success

Surgical repair of CSF leak:

For refractory cases

Especially for meningeal divertcula

Treatment with ligation of diverticula

Meningeal tears show less success with surgical repair

Fibrin Glue reported with success

SIH: Long term Outcomes Berroir S, Neurology, 2004: 30 patients receiving early epidural blood patch Follow-up time 1-4 years 77% of patients cured with epidural blood patch 57% after 1 patch 20% after 2 nd patch Kong DS et al, Neurosurgery, 2005: 13 patients treated with nonsurgical measures Mean follow-up 51 months One recurrence (8%) Six patients with persistent HAs (4 mild, 2 moderate)

Berroir S, Neurology, 2004:

30 patients receiving early epidural blood patch

Follow-up time 1-4 years

77% of patients cured with epidural blood patch

57% after 1 patch

20% after 2 nd patch

Kong DS et al, Neurosurgery, 2005:

13 patients treated with nonsurgical measures

Mean follow-up 51 months

One recurrence (8%)

Six patients with persistent HAs (4 mild, 2 moderate)

References 1. Paldino M et al. Intracranial hypotension Syndrome: a comprehensive review. Neurosurgical Focus 15 (6). 2003, 1-8. 1. 2. Schievink WI et al. Pseudo-subarachnoid hemorrhage: A CT finding in SIH. Neurology 2005;65: 135-137 3. Schievink WI et al. Misdiagnosis of spontaneous intracranial hypotension. Arch Neurol. 60 (12). 2003. 1713-18. 4. Inenaga C. Diagnostic and surgical strategies for intractable SIH. J Neurosurg. 94(4). 2001. 914-916. 5. Schievink WI et al. SIH mimicking aneurysmal SAH. Neurosurgery. 48(3). 2001. 516-517. 6. Rai A et al. Epidural Blood Patch at C2: Diagnosis and Treatment of SIH. AJNR. 26. 2005. 2663-2666. 7. Berroir S et al. Early epidural blood patch in SIH. Neurology 63; 1950-1951, 2004. 8. Kong, DS et al. Clinical features and long-term results of SIH. Neurosurgery. 57(1). 2005. 91-96.

1. Paldino M et al. Intracranial hypotension Syndrome: a comprehensive review. Neurosurgical Focus 15 (6). 2003, 1-8. 1.

2. Schievink WI et al. Pseudo-subarachnoid hemorrhage: A CT finding in SIH. Neurology 2005;65: 135-137

3. Schievink WI et al. Misdiagnosis of spontaneous intracranial hypotension. Arch Neurol. 60 (12). 2003. 1713-18.

4. Inenaga C. Diagnostic and surgical strategies for intractable SIH. J Neurosurg. 94(4). 2001. 914-916.

5. Schievink WI et al. SIH mimicking aneurysmal SAH. Neurosurgery. 48(3). 2001. 516-517.

6. Rai A et al. Epidural Blood Patch at C2: Diagnosis and Treatment of SIH. AJNR. 26. 2005. 2663-2666.

7. Berroir S et al. Early epidural blood patch in SIH. Neurology 63; 1950-1951, 2004.

8. Kong, DS et al. Clinical features and long-term results of SIH. Neurosurgery. 57(1). 2005. 91-96.

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