By Louise M. Klebanoff, MD
Associate Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Klebanoff reports no financial relationships relevant to this field of study.
Synopsis: In a prospective study of 35 patients with newly diagnosed idiopathic intracranial hypertension confirmed by diagnostic lumbar puncture and treated with standard medication regimens, 43% of patients had excellent headache outcome at 12 months, with the major improvement seen within the first month of diagnosis. Chronic headache was seen in another 43% of patients despite identical treatment, normalization of intracranial pressure, and resolution of papilledema.
Source: Yri HM, et al. The course of headache in idiopathic intracranial hypertension: A 12-month prospective follow-up study. Eur J Neurol 2014;21:1458-1464.
Idiopathic intracranial hypertension (IIH), a condition defined by elevated intracranial pressure (ICP) of unknown etiology, primarily affects young women. More than 90% of patients present with severe headache. Patients are at risk for developing chronic headache and permanent visual loss due to papilledema and secondary optic nerve atrophy. In many patients, chronic headache persists even after papilledema and other signs of intracranial hypertension have resolved. Data on the long-term outcome of IIH headache are sparse. This prospective study aimed to describe the course of headache and papilledema during the first year after the IIH diagnosis and to define possible predictors of headache outcome.
The study included patients with newly diagnosed IIH referred within 7 days of diagnostic lumbar puncture. All patients underwent detailed neurological examinations, brain imaging studies (including magnetic resonance or computed tomography with venous sequences) and comprehensive neuro-ophthalmological examination (Snellen visual acuity, Humphrey automated visual fields, Ishihara color-plates, motility, slit-lamp, and fundus examination) to confirm the diagnosis. Papilledema was quantified by optical coherence tomography measures of peripapillary retinal nerve fiber layer thickness. Standardized lumbar puncture ICP manometry was performed at diagnosis and after 3 months. Headache history and follow-up were obtained by a standardized structured interview that included details of headache onset, frequency, duration, intensity, character of pain, location, accompanying symptoms, pre-existing headache, and detailed medication history (including over-the-counter analgesics). Following diagnostic lumbar puncture, treatment with acetazolamide and/or topiramate was initiated. Weight loss was encouraged and dietician consultations were offered. Simple analgesics were allowed up to 14 days per month; other than topiramate, no medications for headache prophylaxis were allowed.
Forty-four patients with newly diagnosed IIH were included in the study. The median age was 27.5 years; all but one patient was female. Eighty-nine percent had papilledema. Pre-existing headaches were noted in 45% of the patients. Sixty-eight percent of the headaches reported fulfilled diagnostic criteria for migraine, and 82% if headache attacks < 4 hours were included. Headaches were frequently exacerbated by cough or strain (70%), bending forward (52%), or physical activity (64%). Acetazolamide (750-2225 mg/day) was the sole medication in 36 patients, two patients were treated solely with topiramate, and three were treated with a combination of the two medications. Three patients underwent ventriculoperitoneal shunting during the study period, two due to progressive visual deterioration and one due to intractable headache and medication intolerance. Thirty-five patients (80%) completed the 12-month follow-up.
The most dramatic improvement in headache was seen within the first month following diagnosis. At the 1-month follow-up, headache index had reduced by > 75% in two-thirds of patients and almost one-third of patients reported that the headache had completely resolved. The prevalence of constant headache improved from 64% to only 13%. Proportions of patients reporting daily occurring headache reduced from 86% to 41%. The median intensity of daily occurring headache reduced from 7.5 to 5.0 on the 0-10 visual analogue scale. There was only a minor reduction in headache characteristics between the 1-month and 12-month follow-up.
Forty-three percent of patients reported persisting headache at the 12-month follow-up. Half of these patients had a history of pre-existing headache. Young age at onset and high opening pressure were both associated with better odds of being headache-free or having infrequent (< 1 day/month) headache after 12 months.
The extent of papilledema at diagnosis was linearly associated with the diagnostic ICP and inversely correlated with age at onset. Papilledema improved significantly within the first 3 months of treatment. At 12 months, there was no difference in retinal nerve fiber layer thickness between patients and controls. Visual outcome was excellent in most cases. At 3- and 12-month follow-up, visual fields and acuity were normal in the majority of eyes. Severe deterioration of vision of organic origin was found in only one patient with fulminant IIH.
In 43% of patients, there was significant improvement or complete resolution of headache, with most of the improvement occurring within the first month of diagnosis and treatment. Despite identical treatment, an equal number of patients had persistent chronic headache. Young age at onset and high opening pressure at the time of diagnosis were associated with better headache outcome. Short duration of headache prior to diagnosis and subsequent weight loss did not improve the chance of headache resolution. Normalization of ICP at the 3-month follow-up was also not related to headache resolution, supporting the concept that elevated ICP alone is not responsible for the headache in IIH. Although half of the patients with persistent headache reported a pre-existing headache syndrome, half of the patients had no prior headache syndrome, suggesting the development of a de novo chronic headache syndrome induced by IIH despite the normalization of ICP. The mechanism of chronification of headache in IIH is unknown. One possible mechanism is the sensitization of central pain pathways, although the lack of correlation of symptom duration and headache outcome in this group of patients argues against this mechanism. Headache in IIH is likely attributed more complex mechanisms than ICP elevation alone.