Spontaneous Intracranial Hypotension Headache Master School 2015 Spontaneous Intracranial Hypotension Jong-Ling Fuh Neurology, Taipei Veterans General Hospital Schools of Medicine, National Yang-Ming University Beijing, Oct 18, 2015

Spontaneous intracranial hypotension (SIH) estimated prevalence: 1 per 50,000 Incidence: 5 per 100,000 per year cardinal symptom: orthostatic headache other associated symptoms nausea/vomiting Photophobia hearing loss tinnitus Spontaneous intracranial hypotension (SIH) is a rare cause of secondary headache, with an estimated prevalence of 1 per 50,000 and an incidence of 5 per 100,000 per year in community-based and emergency department-based settings, respectively1 1. Schievink WI, et al. J Neurosurg 1998; 88: 243–246. 2. Rahman M, et al. Neurosurgery 2011; 69: 4–14.

7.2.3 Headache attributed to spontaneous (or idiopathic) low CSF pressure ICHD-2 Diffuse and/or dull headache that worsens within 15 minutes after sitting or standing, with at least one of the following and fulfilling criteria C and D: 1. neck stiffness, 2. tinnitus, 3. hypacusia 4. photophobia, 5. nausea At least one of the following: 1. evidence of low CSF pressure on MRI (eg. pachymeningeal enhancement) 2. evidence of CSF leakage on conventional myelography, CT myelography, or cisternography 3. CSF opening pressure < 60 mmH2O in sitting position C. No history of dural puncture or other cause of CSF fistula D. Headache resolves within 72 hours after epidural blood patching Cephalalgia 2004; 24 (Supl 1): 1-160.

7.2.3 Headache attributed to spontaneous intracranial hypotension ICHD-3β Cephalalgia 2013; 33: 629-808.

Brain descent → traction of pain-sensitive structures CSF leakage Asymptomatic in supine position

CSF Hypovolemia SIH is caused by occult CSF leak→ CSF hypovolemia → brain sag, downward traction on leptomeninges and neural structures, compensatory venous engorgement, and enlargement of subdural/subarachnoid space1 The core pathophysiologic factor is a decreased volume of CSF rather than its pressure2 1. Schievink WI, et al. J Neurosurg 2005; 103: 608–613. 2. Mokri B, et al. Neurol Clin 2014; 32: 397–422.

Etiology A history of trivial trauma in a substantial minority of patients Weakness of the dural sac (meningeal diverticula)? Stigmata of disorders of connective tissue matrix (Marfanoid habitus, joint hypermobility, skin hyperextensibility)? Mokri B, et al. Neurology 2002;58:814-6 Schievink W, et al, Neurosurgery 2004;54:65-71

Meningeal diverticula Neurosurgery 2004;54:65-71.

JAMA. 2006; 295: 2286-2296.

Connective tissue laxity Ehlers-Danlos syndrome Type II hypermobility  Neurosurgery 2004; 54: 65-71.

Connective tissue laxity in SIH Disproportionately long limbs: span/height>1.05 or upper/lower body<0.89 Liu FC et al. Cephalalgia 2011; 31: 691-5.

Etiology Stigmata of connective tissue disorders, especially dolichostenomelia, are common among SIH patients Most SIH patients do not harbor mutations in FBN1 gene (classic Marfan syndrome), encoding fibrillin 1, or TGFBR2 gene (Marfan syndrome type 2, aka Loeys–Dietz syndrome type 2B), encoding TGF-β receptor 2. 約有1/5的病患有joint hypermobility，有約1/3的病患有dolichostenomelia Trivial trauma resulting in rupture in pre-existing dural weaknesses. 韓國的研究找不出fibrillin 1 mutation. Schievink2008年的文章也找不出TGFBR2的mutation. Schrijver I, et al. J Neurosurg 2002;96:483-9. Chung SJ, et al. Headache 2007;47:111-5. Schievink WI, et al. J Headache Pain 2008;9:99-102. Liu FC et al. Cephalalgia 2011; 31: 691-5.

Brain MRI with contrast Subdural fluid collection Enhancement of the pachymeninges Engorgement of venous structures Pituitary hyperemia Sagging of the brain => SEEPS Schievink WI. JAMA 2006;295:2286-96.

Pituitary hyperemia Sagging of the brain Subdural hematoma Enhancement of the pachymeninges Engorgement of venous structures (venous distension sign) After treatment Pituitary hyperemia Sagging of the brain

Brain descent Incisural line: from anterior tuberculum sellae to confluence of great cerebral vein, straight sinus, and inferior sagittal sinus Foramen magnum line: from inferior tip of clivus to inferior tip of bony base of foramen magnum Iter >=1.8mm below insisural line tonsil >=4.3 mm below foramen magnum line Ann Neurol 1993;33:159-70 Acta Radiologica 2002;43:249-55

Brain descent Before Tx After Tx 31F

Detection of spinal CSF leakage Radionuclide cisternography (ICHD-2) Conventional myelography (ICHD-2) CT myelography (ICHD-2) Gd-enhanced MR cisternography/myelography HeavilyT2-weighted MR myelography (HT2W MRM) Mokri B. Neurol Clin 2004;22:55-74. Schievink WI. JAMA 2006;295:2286-96. Schievink WI. Cephalalgia 2008;28:1347-56. Tsai PH et al. Cephalalgia 2007;27:929-34 Wang YF et al. Neuorology 2009;73:1892-8 17

Radionuclide cisternography Indium-111, at intervals of 24 to 48 hrs. meningeal div may assume a similar appearance as CSF leaks. Exact level could not be localized. Clin Neurol Neurosurg 2008: 110: 657-661.

CSF leaks on CTM Multiple thoracic CSF leaks associated with meningeal diverticula CSF collection anterolateral to the thoracic spinal cord Bilateral CSF leaks at the cervicothoracic junction extending into the paraspinal soft tissues JAMA. 2006; 295: 2286-2296.

CSF leaks on CTM Bilateral cervicothoracic CSF leaks without an associated meningeal diverticulum Left thoracic meningeal diverticulum with an associated CSF leak Right thoracic meningeal diverticulum without an associated CSF leak Cephalalgia. 2008, 28, 1347–1356.

CSF leaks on CTM J Neurosurg 1998; 88:243–246.

Conventional spinal MRI 高長蘇承珊醫師 Limited diagnostic value! Eur Neurol 2009; 61: 301-7.

Conventional T2WI vs HT2W MRM

Conventional T2WI vs HT2W MRM

HT2W MRM vs CTM for SIH Kappa=0.71, p<0.001 Agreement=95% Wang YF, et al. Neurology 2009; 73: 1892-1898. 25

Before and after EBP HT2W MRM Before tx Axial CTM HT2W MRM s/p EBP Conventional T2WI s/p EBP 26

Gd-enhanced MR cisternography/myelography Albayram S, et al. Am J Neuroradiol 2008; 29: 116-21.

Gd-enhanced MR myelography/cisternography ►1.5T or 3T. T1WI with FS after intrathecal Gd inj. ►27 patients (18F/9M), mean age 45 (18-73) ►CSF leakage identified in 6/8 CSF rhinorrhea, 3/5 recur. bac. meningitis, and 9/14 SIH Belgean study. Gd-enhanced MRM is gaining popularity, but the results should be interpreted with caution. Esp for lower T and LS leaks, which could result from LP. The evidence supporting such a view point will be mentioned in a minute. Caveats: Gd-containing contrast not approved for intrathecal use Some “leaks” could result from LP Vanopdenbosch LJ, et al. J Neurol Neurosurg Psychiatry 2011; 82: 456-8. 28

Complications: subdural fluid collection SDH in 20%, non-hemorrhagic fluid collection in 23% SDH was almost male gender, recurrence of severe headache, and neurologic deficits May cause herniation and deterioration of neurological status T1WI T2WI Lai TS, et al. Cephalalgia 2007; 27: 133-138. de Noronha RJ, et al. JNNP 2003; 74: 752-755.

Non-hemorrhagic subdural fluid collection

Acute SDH with midline shift

Bleeding into non-hemorrhagic fluid collections SDE only 10 days later…

Neuroimaging Findings In SIH patients, SDH displayed on initial and/or series of neuroimaging studies could be: - acute, subacute or chronic hematoma, unilateral or bilateral - recurrent SDH (acute expansion of a preexistent hematoma) - bleeding into a non-hemorrhagic fluid collection

Cause of SDH in SIH Patients The persistence of negative pressure within the subdural space elicits subdural hygroma in patients with SIH In addition, tearing of bridging veins or bleeding from engorged veins in the subdural space produces SDH Schievink WI, et al. J Neurosurg 2005; 103: 608–613.

A Cause of Nongeriatric SDH A recent study suggests that spinal CSF leaks may be a frequent cause of nongeriatric chronic SDH Spinal CSF leakage was proven in 7 (26%) of 27 consecutive patients 60 years of age or younger who underwent operations for chronic SDH Hematomas were unilateral in 20 patients (74%) and bilateral in 7 patients (26%) Beck J et al. J Neurosurg 2014; 121: 1380–1387.

Complications: cerebral venous thrombosis 2.1% (3/141) in SIH. 85% involve venous sinus 3 + 17 (literature): 11M/9F, age 39.5 years 40% (8/20) had a change in headache pattern 40% (8/20) had complications of CVT: ►Seizure in 5 ►Venous infarctions in 3 ►ICH in 3 ►Dural AVF in 2. Schievink WI, et al. Headache 2008; 48: 1511-1519. Wang YF, et al. Cephalalgia 2007; 27: 1413-1417.

To drain or not to drain, that is the question. SIH is not as benign as previously thought. Paradoxical herniation is a real concern. Timing of drainage controversial. Lai TS, et al. Cephalalgia 2007; 27: 133-138. de Noronha RJ, et al. JNNP 2003; 74: 752-755. Vogel TW, et al J Neurosurg 2010; 113: 955-60.

Timing for Surgical Intervention Uncal herniation => poor prognosis. Early surgical intervention should be considered for those with SDH ≥ 10mm and decreased GCS (and CSF leakage adequately treated). Chen YC, et al. Cephalalgia 2015 (in press)

Complications: cerebral venous thrombosis 2.1% (3/141) in SIH. 85% involve venous sinus 3 + 17 (literature): 11M/9F, age 39.5 years 40% (8/20) had a change in headache pattern 40% (8/20) had complications of CVT: ►Seizure in 5 ►Venous infarctions in 3 ►ICH in 3 ►Dural AVF in 2. Schievink WI, et al. Headache 2008; 48: 1511-1519. Wang YF, et al. Cephalalgia 2007; 27: 1413-1417.

Treatment Bed rest, hydration, caffeine, steroid, aminophylline, and abdominal binder Epidural blood patching (EBP) ►Treatment of choice ►Early EBPs helpful in the majority of patients ►Immediate and lasting effect ►Directed (targeted) vs non-directed (untargeted) Transcutaneous fibrin sealant injection Surgical repair Schievink WI. JAMA 2006;295:2286-96. Wang YF, et al. Neurology 2009; 73: 1892-1898. Cho KI et al. Neurology 2011; 76: 1139-44.

Targeted EBPs vs blind EBPs for SIH Korean study. EBP under fluoroscopy. Targeted EBPs are more effective than blind EBPs (87.1% vs 52%, p<0.05). Cho KI et al. Neurology 2011; 76: 1139-44. 41

Surgical treatment for CSF leaks J Neurosurg 1998; 88:243–246.

Surgical treatment for CSF leaks Neurosurgery. 2006 Apr;58(4 Suppl 2):ONS-238-45.

Take home message Cranial imaging: S-E-E-P-S Detection of CSF leakage: HT2W MRM (non-invasive, sensitive) Targeted EBPs better than non- targeted EBPs; periradicular leaks as a reasonable target. SDH ≥ 10mm + decreased GCS => early surgical intervention Jong-LingFuh,M.D. jlfuh@vghtpe.gov.tw Taipei Veterans General Hospital