1. S PONTANEOUS I NTRACRANIAL H YPOTENSION : V ERTICAL P AN -M ODALITY I NTEGRATIVE U NDERSTANDING S PONTANEOUS I NTRACRANIAL H YPOTENSION : V ERTICAL P AN -M ODALITY I NTEGRATIVE U NDERSTANDING E E D E-74 Sepand Salehian, Marco Pinho, Justin Tran, Lon Hoang, William Moore, Edward Stehel

2. The authors have no financial disclosures.

3. Epidemiology  Prevalence 1/50,000  Incidence 5/100,000  More likely to be underdiagnosed  Difficult to clinically characterize  Spontaneous intracranial hypotension affects women more frequently than men  Female-male ratio of 2:1  Onset is in the 4 th or 5 th decade of life; peak incidence at age 40  Of note, large scale epidemiological studies are not entirely available and such estimates are based on small studies Wouter I. Schievink, MD. Spontaneous Spinal Cerebrospinal Fluid Leaks and Intracranial Hypotension JAMA. 2006;295(19):2286-2296.

4. Genesis  SIH is caused by a spontaneous CSF leak  Authors believe that the vast majority are caused by a spinal leak  CSF leak, by itself, does not cause focal symptoms  The CSF leak, over the course of time, remains undetected, contributing to the chronicity of SIH  CSF leak does not pose risk of meningitis  CSF evolving from spinal leakage is absorbed by the epidural venous plexus or paraspinal soft tissues; and is not exposed to the external environment

5. Genesis Spontaneous intracranial hypotension is thought to be due to a CSF leak. In this pictorial, a dural rupture arising from a perineural cyst is depicted.

6. Genesis  Underlying structural weakness of the dura in the spine is thought to be the cause of CSF leakage into epidural space  History of mild and trivial traumatic event is often retrieved from patient  i.e., sneeze, mild car accident, moving boxes Pictorial demonstrates underlying structural weakness of the dura in the spine with resultant CSF leakage in the epidural space.

7. Genesis  Wide array of dural defects:  Simple dural holes  Complex fragile meningeal diverticula  Complete absence of dura  Generalized connective tissue disorders may contribute to the development of CSF leaks  Marfan syndrome  Ehlers-Danlos syndrome  Autosomal dominant polycystic kidney disease  Isolated skeletal features of Marfan syndrome  Isolated joint hypermobility  Joint hypermobility with fascial thinning  Spontaneous retinal detachment

8. Genesis  Other causes of SIH  Osseous spinal pathology Congenital osseous spur Degenerative disk disease Theoretically, may have capacity to pierce the dura  Loss of CSF volume does occur in CSF rhinorrhea or otorrhea, however, the typical imaging features of SIH are rarely seen in those conditions  This has ramifications germane to the pathogenesis of spontaneous intracranial hypotension  The cause may not simply be linked to CSF hypovolemia, but perhaps may be due to the idea that the altered distribution of craniospinal elasticity due to spinal loss of CSF results in a spontaneous emergence of a positional headache seen in association with imaging abnormalities

9. Clinical presentation  Positional Headache  Orthostatic headache  headache occurs when standing up  Headache is relieved when laying down  Headache may be diffuse or localized  Occipital (common)  Frontal  Temporal  Throbbing or non-throbbing

10. Clinical presentation  Unique patient descriptors  “ice cube in an empty glass”  “pulling sensation from my head down to my neck”  Headache can resolve within 72 hours after epidural blood patch

11. Clinical presentation  Headache is a direct result of downward displacement of the brain due to loss of CSF buoyancy  Stretching of the dura activates pain receptors  Because of wide variety of headache patterns, MRI is typically reserved for patient with unexplained headaches to evaluate for SIH

12. Clinical presentation: International Classification of Headache Disorders  International Classification of Headache Disorders [2 nd Edition]  The ICHD has proposed a set of diagnostic criteria specifically for headache due to spontaneous spinal CSF leak and intracranial hypotension: A.Diffuse/dull headache that worsens within 15 minutes after sitting or standing, fulfilling criterion D and with greater than 1 of the following: 1.Neck stiffness 2.Tinnitus 3.Hypacusia 4.Photophobia 5.Nausea B.At least 1 of the following: 1.Evidence of low CSF pressure on MRI (pachymeningeal enhancement) 2.Evidence of CSF leakage on conventional myelography, CT myelography, or cisternography 3.CSF opening pressure less than 6 cm H2O C.No history of dural puncture or other cause of CSF fistula D.Headache resolves within 72 hours after epidural blood patching Headache Classification Subcommittee of the International Headache Society. The international Classification of Headache Disorders, 2 nd ed. Cephalgia. 2004; 24 (suppl 1): 1-160

13. Clinical presentation Trigeminal nerve Facial numbness Facial nerve Facial weakness Chorda tympani or glossopharyngeal nerve Dysgeusia Distortion of pituitary stalk Hyperprolactinemia and galactorhea Diencephalic herniation Decreased level of consciousness Downward displacement of brain may cause stretching of the cranial nerves, which may explain the neuronal variations and disruptions noted in SIH: Vestibulocochlear nerve Altered hearing “Echoing” “Being underwater” Tinnitus Optic nerve/chiasm Visual blurring Abducens nerve Diplopia

14. Imaging Findings  A wide array of imaging findings on various modalities present an opportunity to determine the cause and the location of the CSF leak  Each modality presents a different vantage point in its ability to convey information regarding the origin of the CSF leak  CT and MR imaging of the head reveal the sequelae of a spinal CSF leak  MR spine and heavily T2 weighted MR myelography imaging may reveal the origin of a CSF leak  Localization of a high flow CSF leak (for instance, caused by a large dural tear), may require dynamic CT myelography which permits immediate CT acquisition of the spine following myelographic contrast administration.

15. Imaging Findings: CT head  CT head  Widely available, and likely to be the initial imaging modality for evaluation of acute intracranial pathology, especially for patients presenting to the emergency department  Signs of SIH may be difficult to detect on axial images alone  Sagittal reformatted images may demonstrate sagging appearance of the midbrain/tonsils

16. Imaging Findings: CT head  CT may demonstrate overt findings of SIH  Subdural fluid collections  Obliteration of cisterns + ventricular collapse  Paucity of CSF  Sagging brainstem

17. Sagittal CT head without contrast, with demonstration of low-lying cerebellar tonsils, and “sagging” appearance of the midbrain with flattening of the pons.

18. Imaging Findings: MRI Brain  MRI of the brain with contrast has been reported to demonstrate abnormalities in up to 83% of patients with clinical presentation of SIH:  Diffuse pachymeningeal enhancement is the most common finding (83%)  Descent of cerebellar tonsils (72%)  Brainstem sagging (72%)  Enlargement of pituitary (67%)  Subdural fluid collection (72%)  Interestingly, treatment of underlying cause may treat subdural hematoma, and avert need for craniotomy Watanabe A., et al. Diagnostic Value of Spinal MR Imaging in Spontaneous Intracranial Hypotension Syndrome. AJNR. Jan 2009. 30:147-151.

19. Imaging Findings: MRI Brain  Improvement of MRI abnormalities can be expected to resolve within days to weeks of treatment of CSF leak  Clinical improvements precedes normalization of imaging changes

20. Axial T1 weighted image with contrast showing diffuse dural thickening and enhancement.

21. Sagittal T1 weighted MR images without and with contrast, demonstrating typical findings of SIH including descent of cerebellar tonsils at the foramen magnum, “sagging” midbrain, flattened pons, and enlargement of the pituitary gland. Note the increased engorgement of the dural sinus and increased convexity of the torcula.

22. Axial T1 and T2 FLAIR images of the brain demonstrating bilateral complex, multiloculated subdural fluid collections with mixed signal intensity in this patient with confirmed intracranial hypotension and no history of trauma.

23. Imaging Findings: MRI Spine  Numerous spinal manifestations have been reported  Dilated epidural veins  Dilated intradural veins  Dural enhancement  Meningeal diverticula  Extrathecal CSF collections  Syringomyelia  Retrospinal C1-2 collections

24. Sagittal T2WI (left) and sagittal T1WI(right) without contrast demonstrating thin circumferential epidural fluid collection throughout the lumbar spinal canal, with signal characteristics of fluid equal to CSF on both sequences.

25. Axial T2WI in the same patient, showing an epidural fluid collection as well as serpiginous flow voids in the epidural space related to enlargement of venous plexus.

26. Axial T2WI at the cervical spine with a ruptured nerve root sleeve diverticulum within the right neural foramen, with accompanying CSF in the epidural space.

27. Heavily T2-weighted MRI Myelography MRI myelogram demonstrates a prominent right T6-7 perineural diverticulum. In lieu of utilizing gadolinium enhanced MR Myelography or CT myelography, heavily T2 weighted MR myelography serves as a powerful, non-invasive surrogate for the detection of CSF collections and leaks.

28. Imaging Findings: CT Myelography  CT myelography provides precise anatomic data  Accurately delineates the site of CSF leak  Can quantify size of CSF leak

29. Imaging Findings: CT Myelography  CT myelography  Requires lumbar puncture for injection of intrathecal contrast, but may be useful for accurate characterization of CSF leak location and extent  Leak may vary from small amount of contrast tracking along a single nerve root, to a large collection of contrast in the paraspinal soft tissues

30. Imaging Findings: CT Myelography  CT myelography (cont’d)  The majority of CSF leaks are found at the cervicothoracic junction or thoracic spine  Delayed imaging should be considered to increase sensitivity for detection of slow or intermittent CSF leaks  Additionally, preservative-free normal saline can be injected with the iodine contrast to provide additional volume to the thecal sac, theoretically increasing sensitivity for detection of leak

31. Axial CT images of the thoracic and lumbar spine obtained immediately after intrathecal injection of 15 mL Isovue- M 200, diluted with an additional 15 mL of sterile preservative-free normal saline. Abnormal contrast accumulation is seen both ventral and dorsal to the thecal sac in the epidural space, with additional small amount of contrast tracking along the bilateral nerve root sleeves at multiple levels confirming CSF leak.

32. Imaging Findings: Radionuclide Cisternography  Radionuclide cisternography requires lumbar puncture for intrathecal injection of ~500 µCi In-111 DTPA  May detect CSF leak with greater sensitivity, though exact site of leak may not be determined in many cases

33. Imaging Findings: Radionuclide Cisternography  Extensively used in evaluation of SIH  Limited utility  Imaging findings:  Early accumulation of tracer in kidneys and urinary bladder  Slow ascent along the spinal axis  Paucity of activity over the cerebral convexities  Extradural tracer accumulation adjacent to the spinal canal

34. Diagnosis: Radionuclide Cisternography – Example A At 24 hours: Radionuclide scintigraphy demonstrates delayed transit of radiotracer to the convexities at 24 hours, with pooling at the basal cisterns. At 72 hours: There is appropriate distribution of radiotracer about the convexities. No evidence of intraventricular activity. Findings are nonspecific but can be seen in the setting of intracranial hypotension

35. Diagnosis: Radionuclide Cisternography – Example B At 24 hours: Radionuclide scintigraphy demonstrates activity in the interhemispheric fissure, and minimal activity along the anterior and lateral convexities. There is no intraventricular activity. There is very faint renal activity. At 48 hours: There is minimal redistribution radiotracer about the cerebral convexities, with pooling of radiotracer in the skull base, and no ventricular activity. Findings may be seen in the setting of intracranial hypotension

36. Diagnosis: Lumbar puncture  CSF opening pressure < 6 cm H2O  Can be unmeasurable or even negative  Some patients may have normal CSF pressures  CSF may be abnormal  Primary lymphocytic pleocytosis (200 cell/mm 3 )  Elevated protein content (1000 mg/dL)  Xanthochromia that is probably due to increased permeability of dilated meningeal blood vessels and decreased CSF flow in the lumbar subarachnoid space

37. Treatment  SIH is often reported to resolve spontaneously without specific therapy  Purely conservative  Bed rest  Oral hydration  Generous caffeine intake  Abdominal binder  Steroids, IV caffeine, theophylline

38. Treatment  Primary treatment: Epidural Blood Patch  Injection of autologous blood (20-30 mL) into the epidural space  Relief of symptoms can be instantaneous Blood occupies the epidural space, creating a shift in the way CSF is distributed within the spinal canal  Mechanism is presumably by the formation of a dural tamponade

39. Treatment  Epidural blood patch (cont’d)  Proposed mechanism of action: tamponade effect seals the leak, and/or concurrent restriction of CSF absorption  For the first treatment, 20-30 mL of blood can be injected  Minimum of 5 days between blood patches is advised  If first treatment is unsuccessful in relieving symptoms, subsequent treatments can be performed with a larger volume of blood injected (in rare instances, high volume epidural blood patch can be up to 100 mL)  Injected blood volume is typically limited by local back pain or development of radiculopathy

40. Treatment  Epidural blood patch (cont’d)  After injection of blood patch, patient should be placed in Trendelenburg position for 30-60 minutes to allow blood to travel over multiple segments of the spine toward level of leak; allowing epidural blood to migrate to more cephalad components of the spinal column Contrast is injected confirming location of needle tip within epidural space. Subsequently, 20-30 cc of autologous blood is administered into the epidural space.

41. Treatment  If non-targeted lumbar epidural blood patch is unsuccessful, and other imaging modalities are able to localize the CSF leak, a directed approach may be considered  Directed epidural blood patch or percutaneous placement of fibrin sealant  Requires exact site of CSF leak to be known

42. Treatment  Surgical treatment  Surgical options for CSF leak and SIH are reserved for patients in whom nonsurgical measures have failed, and structural abnormality or focal CSF leak has been detected on imaging Focal CSF leak can be ligated with suture, metal aneurysm clip Dural rents can be repaired with suture, muscle pledgets, gelfoam, fibrin sealant

43. Bibliography Wouter I. Schievink, MD. Spontaneous Spinal Cerebrospinal Fluid Leaks and Intracranial Hypotension JAMA. 2006;295(19):2286-2296. Watanabe A., et al. Diagnostic Value of Spinal MR Imaging in Spontaneous Intracranial Hypotension Syndrome. AJNR. Jan 2009. 30:147-151. Berrior S., et al. Early epidural blood patch in spontaneous intracranial hypotension. Neurology. Nov 2004. Vol 63, no. 10, 1950-1951. Sencakova D., et al. The efficacy of epidural blood patch in spontaneous CSF leaks. Neurology. Nov 2001, Vol. 57, no. 10, 1921-1923. Mario Savoiardo, Ludovico Minati, Laura Farina, et al. Spontaneous intracranial hypotension with deep brain swelling. Brain: A Journal of Neurology. 2007; 130: 1884-1893 Paldino M, Mogilner AY, Tenner MS. Intracranial hypotension syndrome: a comprehensive review. Neurosurg Focus. 2003 Dec 15;15(6) M. Todd Burtisa, John L. Ulmera, Glenn A. Millerb, et al. Intradural Spinal Vein Enlargement in Craniospinal Hypotension. AJNR Am J Neuroradiol. 2005 26: 34-38 Wang YF, Lirng JF, Fuh JL, Hseu SS, Wang SJ. Heavily T2-weighted MR myelography vs CT myelography in spontaneous intracranial hypotension. Neurology. 2009 Dec 1;73(22):1892-8.