Abstract
Background
In 2013, one of the authors described a 36-year-old female with orthostatic headache without documented intracranial hypotension or evidence of cerebrospinal fluid leak, despite extensive workup. Headache was unresponsive to conservative treatment since 2010, showed only transient benefit after repeated epidural blood patches while vitamin A supplementation resulted in progressive improvement.
Case
Since 2013, the patient followed a relapsing and remitting course yet relapse control became difficult after a drug induced liver injury required vitamin A discontinuation in 2017, when her headache became chronic. Greater occipital nerve blocks provided pain relief as alternative but were stopped due to the pandemic and her latest severe relapse, in late 2020, required not only restarting anaesthetic blocks and aggressive medication management, but also reassessing and treating comorbidities (obstructive sleep apnoea and major depressive disorder) with modest benefit.
Conclusion
Orthostatic headache without intracranial hypotension is rare, with only 28 cases reported so far, all treated empirically and all treatment options revealing to be mostly ineffective. Vitamin A anecdotally appeared to be useful in our case but had to be stopped for severe side effects, so unfavourable long-term prognosis, in ours and 2/3 of the reported cases, seems to be the rule in this intriguing entity.
In 2010 a 36-year-old female developed orthostatic headache after a generalized tonic-clonic seizure. Several spinal taps showed normal opening pressures and no stigma of intracranial hypotension or evidence of cerebrospinal fluid (CSF) leak was found after extensive workup. Headache was unresponsive to conservative treatment and had transient benefit after repeated epidural blood patches. She was started on vitamin A with progressive improvement and the case was reported in 2013(1). In the following years she had three short-lived relapses requiring additional blood patches and treatment escalation, that improved within three weeks whenever vitamin A was reintroduced or the dose increased, but allowing gradual taper of all medication between relapses.
In 2017, triggered by a mastitis, her headache worsened and became chronic. Theophylline and valproic acid were tried without benefit so high dose vitamin A (7500 IU/day) was reintroduced until she developed a drug induced liver injury (confirmed by biopsy). Worsening of headache ensued, most days were spent lying so she lost her job, further increased weight (BMI 33 kg/m2) and was diagnosed with major depressive disorder. Amantadine, duloxetine, fentanyl, gabapentin, lamotrigine, lithium, prednisolone and sulpride were tried, with either insufficient response or intolerable side effects. Amitriptyline provided mild relief and sertraline resulted in mood improvement. Repeat blood patches provided transient relief but after the 10th and 11th patches she developed intense bilateral radicular leg pain and benefit was scarce, hence they were stopped. Botulinum toxin (195 units, 5 cycles) and sphenopalatine ganglion block (twice) provided no sustained relief. IV caffeine, IV methylprednisolone and oxygen were ineffective as rescue medication. Bilateral greater occipital nerve blocks with lidocaine were started in late 2019, resulting in pain intensity improvement, and were repeated every 4 to 6 weeks, allowing her to resume an active professional life despite her chronic daily orthostatic headaches.
In late 2020 her headaches worsened; nerve blocks had been stopped due to the COVID pandemic. She required multiple non-steroidal anti-inflammatory drugs (NSAIDs) and still could not tolerate more than 2h of orthostatism, and complained of marked daytime somnolence. A sleep study confirmed obstructive sleep apnoea and her headache intensity improved after continuous positive airway pressure (CPAP) therapy, reinstatement of the occipital nerve blocks, physical therapy and psychotherapy, allowing her to resume work. She is currently on sertraline, amitriptyline and monthly greater occipital nerve blocks with lidocaine, still very symptomatic, yet able to function.
Orthostatic headache without intracranial hypotension is a poorly understood disorder that remains very challenging to treat. This condition may be caused by lumbar thecal hypercompliance, lowering intracranial pressure with orthostatism without lowering supine CSF lumbar pressure or requiring a CSF leak. The anecdotal response to vitamin A reported seemed consistent yet had to be stopped due to hepatic toxicity. The mechanism behind this response, although speculative, could relate an increment in the conversion of excess retinol to all-transretinoic acid (ATRA) in the choroid plexus, leading to increased resistance to CSF absorption (2). Three retrospective case series have been published (3–5) adding up to 28 cases (Table 1). Only a third of patients report a trigger and most follow a prolonged or chronic course, often showing transient response to blood patches. Most have depression as comorbidity, but antidepressants seem no more effective than any other medication, with high failure rate. Only a third of the patients fully recover implying a bad long-term prognosis, in line with our case-report.
Summary of previously reported cases of orthostatic headache without intracranial hypotension
NI: no information; NP: not performed.
Clinical Implications
Orthostatic headache without intracranial hypotension remains poorly understood and challenging to treat. Vitamin A anecdotally seems effective, but has a serious risk of liver injury that limits its use. Depressive disorders were reported as frequent comorbidities, the treatment of which may help. No optimal treatment has emerged and this condition remains debilitating and with a chronic course in most patients.
Footnotes
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
