Spontaneous Intracranial Hypotension: an imaging review Dr D. J. Warren Neuroradiology Fellow Sheffield NHS Teaching Hospitals Trust. UK.

Objectives Symptoms and clinical presentation Imaging armamentarium & characteristic findings How to manage?

Background The 'Monroe - Kelly Doctrine' ‘incompressible structures within the cranial vault are in a state of volume equilibrium, such that any increase of the volumes of one component (i.e. blood, CSF, or brain tissue) must be compensated by a decrease in the volume of another’ Monroe A. Observations on the structure and function of the nervous system, Edinburgh: Creech & Johnson; 1783.  Kelly G. An account of the appearances observed in the dissection of two of three individuals presumed to have perished in the storm of the 3rd, and whose bodies were discovered in the vicinity of the Leith on the morning of the 4th of November 1821, with some reflections on the pathology of the brain, Trans Med Chir Sci Edinb 1824;1:84-169. Hence, a reduction in CSF volume must be, therefore, compensated by an increase in extracellular fluid and or blood volume. According to this hypothesis, increased intracranial blood volume compensates for acute loss of CSF. Most of the compensation, as we will see, occurs through dilatation of the venous side of the circulation, given its greater compliance and capacitance. Thus some characteristic signs such as venous sinus engorgement, abnormal pachymeningeal enhancement, subdural effusions, and enlargement of the pituitary gland occurring in this condition may represent compensatory changes to maintain intracranial volume in the face of CSF loss.

Presentation Spontaneous intracranial hypotension is an increasingly recognised cause of a new daily persistent headache, particularly amongst young and middle aged patients – with a greater propensity to female patients; however, initial misdiagnosis remains common. This Clinical syndrome was first described by Scaltenbrand in 1938 The syndrome of ICH is a single pathophysiological entity of diverse origin. Usually, it is characterized by an orthostatic headache, that is, one that occurs or worsens with upright posture, although patients with chronic headaches or even no headache have been described.[31] The nature and location of the headache vary greatly from patient to patient; but consistently the pain is exacerbated by laughing, coughing, jugular venous compression, and Valsalva manoeuvre, and is resistant to treatment with analgesic agents.[24,42] Other presenting symptoms have included cranial nerve palsies such as unilateral or bilateral sixth nerve palsies, transient visual obscuration, field defects (6), photophobia, auditory symptoms, unilateral facial numbness and weakness Intracranial hypotension generally is considered to be a benign condition, and most cases resolve with conservative management. With advances in diagnosis, however, atypically disabling presentations are increasingly recognized including parkinsonism, frontotemporal dementia, syringomyelia, hypopituitarism, seizures, coma, and death.

Misdiagnosis In 2003 Schievink published an article in archives of Neurology detailing his review of the clinical course of 18 consecutive patients with spontaneous intracranial hypotension. All patients presented with a classical positional headache and all but 2 of the patients could remember the time date and circumstances at the onset of headache. Only one patient was diagnosed as having SIH at the first physician encounter – 17 initially received an incorrect diagnosis as detailed in this table. These 17 patients subsequently sought attention from 1 to 6 physicians before the correct diagnosis was made and the diagnostic delay ranged from 4 days to 13 years (median 5 weeks mean 13 months). Such diagnostic delay results in delay in initiation of effective treatments and may expose patients to the risks associated with treatment for disorders that mimic intracranial hypotension. An increase in awareness of this entity is therefore required to reduce the high rate of misdiagnosis. Schievink WI. Misdiagnosis of spontaneous intracranial hypotension. Arch Neurol 2003;60:1713-1718

Diagnosis Classical clinical presentation – orthostatic headache Onset of symptoms at time of:- Sexual intercourse, coughing, bending, falling on buttocks, chiropractic manipulation, gardening (digging). Low CSF opening pressure < 60mm H2O. Characteristic Neuro-imaging findings The spectrum of clinical as well as radiographic manifestations of spontaneous intracranial hypotension is usually broad. If the syndrome is unrecognised, evaluation of the patient’s headache may include lumbar puncture. The opening pressure is characteristically low -less than 60mm water. – commonly with either a leucocytosis or elevated protein Onset of symptoms at time of:- Sexual intercourse, coughing, bending down, falling on buttocks, chiropractic manipulation, gardening (digging) There may be trauma to the nerve root sleeve at the lumbosacral level or disruption of a Tarlov cyst. Similarly, repetitive strenuous upper extremity sports such as fishing, or racket sports may precipitate symptoms due to nerve root sheath tears at the brachial plexus level Schievink et al published a revised criterion for its diagnosis in AJNR may 2008 to encompass its varied clinical and radiographic manifestations.

Diagnosis The demonstration of a spinal CSF leak on spinal imaging. Imaging modalities may include CT myelography, MR imaging, MR myelography, or radionuclide cisternography and must demonstrate the presence of extrathecal CSF. Indirect evidence for a spinal CSF leak such as early appearance of contrast in the kidney on CT myelography or early uptake of isotope in the bladder and kidneys on radionuclide cisternography is not sufficient to make the diagnosis. Criterion B, if criterion A not met. Cranial MR imaging changes of spontaneous intracranial hypotension and at least one of the following: low opening pressure, 2) spinal meningeal diverticulum, or 3) improvement of symptoms after epidural blood patch. A positive MR imaging result is defined as the presence of at least one of the 3 major MR imaging findings of spontaneous intracranial hypotension (ie, subdural fluid collections, enhancement of the pachymeninges, and sagging of the brain). Low opening pressure is defined as less than or equal to 60 mm of water with the patient in the lateral decubitus Position. Criterion C, if criteria A and B not met. The presence of all of the following or at least 2 of the following if typical orthostatic headaches are present: 2) spinal meningeal diverticulum, and 3) improvement of symptoms after epidural blood patch. Schievink WI, et al. Diagnostic criteria for spontaneous spinal CSF leaks and intracranial hypotension.AJNR Am J Neuroradiol. 2008 May;29(5):853-6.

Imaging Armamentarium Magnetic Resonance Imaging (cranial & spinal) Radioisotope Cisternography CT Myelography MR imaging has revolutionized the diagnosis of intracranial hypotension and is the initial imaging modality of choice for assessment of this condition although other, more invasive techniques, such as radioisotope cisternography and CT myelography do have a role.

SIH: Imaging Features Subdural effusions Enhancing Pachymeninges Engorged venous structures Pituitary enlargement Sagging of brain Of these findings only subdural fluid collections, enhancement of the pachymeninges and sagging of the brain are reliably demonstrated on the initial MR imaging examination; Whereas Engorgement of the venous structures and pituitary hyperaemia are often not apparent until compared with a post treatment MR. Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA 2006; 295:2284-96.

SEEPS: Subdural effusions on the application of the Monro–Kellie hypothesis, which states that the sum of the volumes of intracranial blood, CSF, and brain tissue must remain constant in an intact cranium. According to this hypothesis, increased intracranial blood volume compensates for acute loss of CSF. Most of this compensation occurs through dilation of the venous side of the circulation, given its greater compliance and capacitance Subdural effusions are seen overlying the cerebral hemispheres and characteristically beneath the tentorium cerebelli . Typically thin, crescentic, and located either below or between enhancing membranes. They may be bilateral and are usually without mass effect. The dura mater does not contribute to the blood–brain barrier and therefore lacks tight junctions. Consequently, the pressure gradient established by increased volume in the dural vasculature causes extravasation of fluid into this innermost dural border-cell layer. Effusions occur when the aforementioned extravasation continues to the point of fluid accumulation in the subdural space. Such collections correlate with the most significant meningeal thickening 10

SEEPS: Subdural effusions 11

SEEPS: Subdural effusions 12

SEEPS: Enhancing pachymeninges Enhancement of the pachymeninges and engorgement of the venous structures. Meningeal enhancement in ICH is thick, linear, without nodularity, and involves the pachymeninges of both the infra- and supratentorial compartments without evidence of involvement of the leptomeninges The dura mater does not contribute to the blood–brain barrier and therefore lacks tight junctions. Consequently, the pressure gradient established by increased volume in the dural vasculature causes extravasation of fluid into this innermost dural border-cell layer.[35] V Venous engorgement thus results in a greater concentration of contrast not only in the dural vasculature, but also in the interstitium. Note the partial effacement of the peri mesencepahlic cistern.

SEEPS: Engorged Venous Structures Prominent cortical veins & venous sinuses First sign to improve with treatment Due to reduced CSF volume and need to maintain intracranial volume (Monro-Kellie principle) Meningeal engorgement 14

SEEPS: Pituitary enlargement The pituitary gland is a densely vascularized organ surrounded by the cavernous sinus.[17] Its size appears larger on MR images during the symptomatic phase of intracranial hypotension compared with after recovery. Like venous engorgement, increased meningeal enhancement, and subdural fluid collections, this increase in volume presumably reflects compensatory venous hyperemia. This scan also demonstrates brain SAG. 15

SEEPS: Sagging of the brain Imaging evidence of descent of the brain includes the following: descent of cerebellar tonsils which may be mistaken for an Arnold–Chiari malformation Type I; reduction in size or effacement of the prepontine cistern; inferior displacement of the optic chiasm; effacement or obliteration of perichiasmatic cisterns; reduction of subarachnoid cisterns; and descent of the iter (opening of the sylvian aqueduct on MR imaging) judged relative to the incisural line (connecting the anterior tuberculum sellae to the point of confluence of straight and inferior sinuses and the great cerebral vein). In normal adults the iter lies 0.2mm caudal to the incisural (or Reich’s) line. Flattening of the contour of the midbrain and pons (flattened against the clivus) may also be observed. The buoyant action of CSF reduces the effective weight of the brain to less than 50 g.[33] Loss of this buoyant force allows the brain to sag, which is seen as evidence of descent of the brain on MR imaging. The supine position of the patient during MR imaging may lead investigators to underestimate imaging evidence of descent.

Cranial MR findings in SIH E PD – Subtle ‘ pencilled in’ subdural effusion Coronal T2 – thin effusion and engorged venous structures SEEPS SEEPS

Cranial MR findings in SIH E PS SEEPS SEEPS

Effusions: can be large

SIH: Spinal imaging findings Extradural / subdural fluid collections / ‘hygroma’ Enlarged epidural veins Perineural (tarlov) cysts Contrast leakage into the epidural space The cardinal MR imaging findings include extraarachnoid fluid collections, spinal meningeal enhancement, and dilation of the anterior internal vertebral (epidural) venous plexus.

Spinal Hygroma It is uncertain whether the hygromas are in the epidural or subdural space although it is thought that they lie in the subdural space. They may be either anterior or posterior to the dural sac. The presence of raised CSF protein in the collection raises the possibility that it is caused by a transudate caused by spinal meningeal hyperaemia Clumping of the cauda equina may also be seen.

Spinal Hygroma: Fat sat T2 Fat sat imaging enhances visualisation

Epidural venous engorgement

Spinal assessment Indium Radioisotope Cisternography CT Myelography Imaging confirms a left sided T11/ T12 meningeal diverticulum / arachnoid cyst Indium Radioisotope Cisternography CT Myelography

Spinal assessment

Spinal assessment Sag T2 and axial imaging demonstrate the prominent extra arachnoid fluid collections. Heavily weighted T2 myelography demonstrates a perineural cyst. MR myelography has a sensitivity of around 80% for detection of leakage site.

Treatment Bed rest Hydration IV / oral caffeine and theophylline Steroid therapy Targeted / blind epidural blood patch Surgery – repair dural tear The headache of ICH typically resolves with conservative management and bed rest. It is believed that the supine position reduces CSF pressure at the site of leakage and therefore allows healing of the underlying meningeal defects.[38] Intravenous or oral caffeine and theophylline have been reported to be dramatically effective in 75% of cases of ICH caused by LP.[48] It has been proposed that methylxanthines produce arterial constriction through the blockade of adenosine receptors.[26] Consequently, intracranial blood flow and, presumably, venous engorgement are decreased. Other treatments aim at increasing CSF volume either by fluid restoration or by eliminating the leak. Strategies used in an effort to restore CSF volume include intravenous or oral hydration, increased salt intake, carbon dioxide inhalation, and steroid therapy. Few investigators have evaluated the efficacy of these empirical strategies, and therefore their role in the management of ICH remains unclear. Although some patients' clinical improvement has been coincident with glucocorticoid or mineralocorticoid treatment, other study results have shown such measures to be of questionable value.[26,35] Furthermore, although these drugs cause systemic fluid retention, there is no convincing evidence indicating that steroid agents have any effect on CSF production or absorption.[41] When these measures fail, epidural blood patches are generally considered to be a safe and effective treatment.

Conclusion Characteristic imaging findings : SEEPS Subdural effusions Enhancing Pachymeninges Engorged venous structures Pituitary enlargement Sagging of brain MR imaging modality of choice Consider the diagnosis. The patient presenting with headache is often a diagnostic dilemma, and the indiscriminate screening of these patients by performing MR imaging is not a good use of an expensive resource. Correlation of the headache with the patient position, a recent history of LP, or an accompanying cranial nerve deficit should trigger a suspicion of ICH and prompt the appropriate use of Gd-enhanced MR imaging of the brain. The headache of ICH usually resolves with conservative management, but if it does not, epidural blood patching is highly effective. Nb complications – subdural haematoma – rupture of bridging veins as CSF vol decreases and the brain sags, pulling away the dura.