Idiopathic intracranial hypertension (IIH), by definition of unknown etiology, may be in need of a new name. The article by Warner et al in this issue of the Journal of Neuro-Ophthalmology (1) offers evidence that abnormal retinol (vitamin A) transport and metabolism is involved in the pathogenesis of the disease. There is a significant elevation of the retinol to retinol-binding protein (RBP) ratio with less RBP and more unbound retinol in the cerebrospinal fluid (CSF) of patients with IIH than of control subjects. To grossly simplify and to extrapolate, the findings suggest that IIH results from vitamin A toxicity localized to the CSF.

Vitamin A toxicity has long been acknowledged as a cause of the severe headaches and papilledema associated with intracranial hypertension. The classic tale is of the Eskimo (Inuit) who for centuries have hunted polar bears for fur and meat but do not eat the liver for fear of the headaches and blurred vision that result from ingestion. Polar bears, as carnivores at the top of the Arctic food chain, have very high hepatic vitamin A levels. Human consumption of their livers would induce acute vitamin A toxicity. Although polar bear liver is not part of our modern day diet, chronic excessive consumption of foods rich in vitamin A has been linked to intracranial hypertension. Case reports of a ‘‘carrot craver’’(2) and several ‘‘liver lovers’’(3)(of cow—not polar bear—liver) describe elevated intracranial pressure with complete resolution after removal of the offending foods from the diet. Intracranial hypertension and/or papilledema associated with hypervitaminosis A has also been reported in a number of ‘‘vitamin junkies’’(added to the lexicon in the spirit of carrot cravers and liver lovers) and in children and teenagers given vitamin A for treatment of acne and other ailments in decades past. The doses leading to elevated intracranial pressure have ranged from 25,000 to 200,000 IU of vitamin A per day and were taken for months to years before diagnosis (4, 5).(The recommended daily allowance of vitamin A is 2,300–3,000 IU). Intracranial hypertension is also a well-documented side effect of therapeutic doses of the synthetic vitamin A derivative 13-cis-retinoic acid (generic name isotretinoin; brand name Accutane)(6) used for treatment of acne and of the vitamin A metabolite all-transretinoic acid used in the treatment of acute promyelocytic leukemia (7, 8). In an analysis of adverse ocular events after 13-cis-retinoic acid treatment that were reported to the Food and Drug Administration, the World Health Organization Spontaneous Reporting System, and the National Registry of Drug-Induced Ocular Side Effects at the Casey Eye Institute, Fraunfelder et al (9) identified 179 cases of intracranial hypertension associated with 13-cis-retinoic acid, with 6 of the cases having a positive rechallenge, a mean time of 2.3 months between initial exposure and diagnosis, and documented resolution of 86 cases within weeks to a few months after cessation of the drug.