Treatment of orthostatic headache without intracranial hypotension: A case report

Abstract

Introduction:

Orthostatic headache is very suggestive of intracranial hypotension. It has a good prognosis as it usually responds to conservative treatment or epidural blood patches.

Case report:

A 36-year-old female presented with severe and prolonged orthostatic headache starting after a seizure. No stigma of intracranial hypotension was detected on brain MRI, and intracranial pressure was within normal range. No imaging evidence of a fistula was found. She was refractory to symptomatic treatment including five epidural blood patches. Progressive improvement occurred simultaneously to the introduction of vitamin A supplementation.

Discussion:

A series of six similar patients is discussed, in which five patients remained severely symptomatic and workdisabled at an average follow-up of four years. It is proposed that the pathophysiological mechanism producing orthostatic headache might not be dependent on intracranial hypotension and could respond to vitamin A.

Introduction

Orthostatic headache with or without associated symptoms is indicative of intracranial hypotension that occurs after active cerebrospinal fluid (CSF) removal (e.g. after a lumbar puncture) or spontaneously (spontaneous intracranial hypotension, SIH) as a result of a meningeal CSF leak (1,2). Spontaneous CSF leaks are attributed to underlying fragility of the spinal meninges (often associated with connective-tissue disorders) that easily tear when exposed to a mechanical factor, such as a minor trauma (1). Diagnosis is based on clinical presentation and typical brain magnetic resonance imaging (MRI) aspects that, when present, avoid the need for measurement of the CSF opening pressure (2–4). The first-line treatment of this disorder is conservative, including bed rest, oral hydration, analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs) and caffeine intake (1,5). Spinal MRI, computed tomography (CT) or MRI myelography and radionuclide cisternography should be used to identify the site of the CSF leak (1,3,5,6) if conservative treatment fails. A minority of resistant cases can be treated with epidural injection of autologous venous blood; injection of fibrin glue or surgical repair of the dural tear is reserved for refractory cases (1,3,5).

Case report

A 36-year-old female patient suffered a generalized tonic-clonic seizure on June 30, 2010. Immediately upon recovery, she complained of generalized headache and nausea that was partially relieved by bed rest and analgesics. In the following 48 hours she developed pure orthostatic pressure-like non-throbbing headache bilaterally in the frontal, occipital and neck areas. The pain subsided with recumbence and occurred a few minutes after sitting or standing. It was accompanied by pallor, sensation of ear fullness, dizziness, nausea and vomiting. Neurological observation was normal. Brain MRI with arterial and venous MRI angiography was normal.

Her past medical history was positive for chronic fatigue syndrome since 2004 (following an infectious mononucleosis) and an increased body mass index (28 kg/m²). She was being treated with bupropion 150 mg qd, amitriptyline 35 mg qd and amantadine 100 mg bid.

She was admitted on July 23, 2010, because of a disabling orthostatic headache that had failed to resolve with conservative treatment (bed rest, hydration, NSAIDs, analgesics and caffeine). Neurological examination was normal except for facial pallor and vomiting occurring after one minute of sitting. Three-Tesla brain and spinal MRI with gadolinium were repeated, again without stigmata of intracranial hypotension nor evidence of CSF leaks. Arterial and venous MRI angiographies and CSF dynamic study were normal. The spinal tap revealed a recumbent CSF opening pressure of 110 mmH₂O, a value later confirmed on a second tap. CSF analysis and routine blood screen were normal. She maintained disabling orthostatic headache and vomiting despite intravenous treatment with NSAIDs, steroids, opioids, metoclopramide and ondansetron. A first epidural blood patch was performed on September 8, resulting in a 48-hour pain-free period. Headache recurred on the third day although she could then tolerate sitting or standing for periods as long as 90 minutes. From September 2010 to March 2011 she was kept on symptomatic treatments including bed rest, hydration, NSAIDs, analgesics, caffeine, bupropion, amitriptyline, quetiapine, sodium valproate, topiramate, betahistine, cinarizine and theophylline without benefit. Three additional epidural blood patches were repeated (October, November and February), the last in the Trendelenburg position, after pre-medication with a single dose of acetazolamide (500 mg) with the aim of reducing CSF production to favor the collapse of a possible slow-draining leak (7); that resulted in brief or no improvement. Radioisotope cisternography with 99 mTc-diethylentriamene pentaacetate (DTPA), spinal MRI with heavily T2-weighted MR myelography and dynamic CT myelography (8) showed no evidence of CSF leak. Owing to accompanying orthostatic dizziness, a tilt test was performed that was positive for mild orthostatic hypotension, but fludrocortisone yielded no response.

Oral supplementation with vitamin A was started in March, in progressively higher doses up to 7500 IU daily, when a benefit was identified. Supplement dose was always kept under 10,000 IU to avoid toxicity and serious side effects. The patient was advised not to start any concomitant treatments with tetracyclin or isotretinoin and to avoid pregnancy. Blood levels of vitamin A and hepatic function were monitored during the treatment.

Her orthostatic tolerance progressively improved; although she maintained continuous headaches, she was able to sit and stand for six hours, which enabled her to return to work on a part-time basis. In September 2011 she suddenly worsened and could not tolerate more than one hour without lying down. No precipitants or changes in current treatment were identified. A fifth blood patch was performed in November 2011 that resulted in progressive improvement; at that time vitamin A dosage was increased to 10,000 IU qd. She kept working despite daily headaches since December 2001. By the end of February she started having some headache-free days that progressively increased in frequency. Since April 2012 her headaches subsided yet she had, in the following seven months, five self-limited episodes of orthostatic headaches lasting three to 12 days, always related to periods of more intense physical effort. She maintains daily treatment with vitamin A 7500 IU qd, bupropion 150 mg qd, amitriptyline 20 mg qd and omeprazol 20 mg qd. Hepatic function tests and vitamin A blood level remain within the normal range. The spinal tap was not repeated after clinical improvement because of the risk of post-dural puncture headache.

Discussion

Although it is generally a straightforward diagnosis when the orthostatic aspect of the headache is depicted, SIH syndrome can be atypical—up to 20% of patients have typical headache, low CSF opening pressure and normal MRI (1) (“MRI-negative SIH”). Some reports describe typical headache, typical MRI findings with normal CSF opening pressure (“normal-pressure SIH”); others identify typical MRI aspects with low CSF opening pressure in asymptomatic patients (“asymptomatic SIH”), and atypical headaches and neurological symptoms (“atypical SIC”) can present with typical MRI findings and low CSF pressure (3,6).

Our patient suffers from typical orthostatic headache and associated symptoms, starting after a clear precipitating event (1,3,5,6,9) yet no stigmata of intracranial hypotension was documented and no CSF leak was identified, despite extensive and adequate investigation—she has a orthostatic headache without intracranial hypotension.

A small series of six similar patients has been published (10), and the most likely explanation for these cases is the existence of an intermittent or very slow-flow leak that would evade identification by existing imagining techniques. Alternative etiological hypotheses are of increased compliance of the lower spinal CSF space shifting the hydrostatic indifferent point downward in the orthostatic position (inducing compensatory dilation of pain-sensitive intracranial venous structures without changing CSF pressure at the lumbar level (10)) or of orthostatic CSF leakage to the epidural venous network (11).

Whatever of the etiology, the absence of MRI aspects of intracranial venous engorgement (gadolinium enhancement of the pachymeninges, engorgement of cerebral venous sinuses, engorgement and enlargement of pituitary gland or prominence of spinal epidural venous plexus) despite long-lasting (average 45 months) continuous incapacitating orthostatic headaches (10) is consistent with normal pressure measurements in these patients but fails to explain their symptoms.

The previous reported series also has a consistent outcome—most patients were extremely refractory to treatment (10). Apart from relief with recumbence, all patients showed minimal or no response to several options of conservative treatment, to symptomatic headache treatment and to repeated epidural blood patches (10). Prognosis was very bad in the presented series; only one patient had a spontaneous recovery after one year while the rest maintained continuous symptoms and were severely work-disabled (10). Our patient started to recover after nine months of severe disability despite adequate standard treatment. Her improvement was progressive and simultaneous to oral vitamin A supplementation. Vitamin A supplementation treatment was initiated empirically with the aim of increasing intracranial pressure (12) despite a complete absence of previous evidence supporting this treatment in SIH. Despite the initial improvement, she had a severe unexplained recurrence six months into treatment, requiring a fifth blood patch. A progressive and steady recovery was achieved during the last year, although some self-limited episodes of recurrences occurred that related to increased physical effort. A beneficial effect of vitamin A supplementation can be speculated from this report, although a spontaneous recovery is also possible.

Clinical implications

A young woman with a severe and refractory orthostatic headache without intracranial hypotension improved progressively after starting vitamin A supplementation.

This case suggests that the pathophysiological mechanism producing orthostatic headache might not be dependent on intracranial hypotension nor hypovolemia.

Vitamin A supplementation may be a useful adjuvant to treatment of orthostatic headaches.