Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

User menu

  • Subscribe
  • My Alerts
  • Log in

Search

  • Advanced search
Neurology
Home
The most widely read and highly cited peer-reviewed neurology journal
  • Subscribe
  • My Alerts
  • Log in
Site Logo
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

Share

November 01, 2022; 99 (18) Research ArticleOpen Access

Headache, Opiate Use, and Prescribing Trends in Women With Idiopathic Intracranial Hypertension

A Population-Based Matched Cohort Study

View ORCID ProfileNicola Jaime Adderley, Anuradhaa Subramanian, Mary Perrins, Krishnarajah Nirantharakumar, View ORCID ProfileSusan P. Mollan, View ORCID ProfileAlexandra Jean Sinclair
First published August 19, 2022, DOI: https://doi.org/10.1212/WNL.0000000000201064
Nicola Jaime Adderley
From the Institute of Applied Health Research (N.J.A., A.S., M.P., K.N.), University of Birmingham; Centre for Endocrinology, Diabetes, and Metabolism (K.N.), Birmingham Health Partners; Health Data Research UK (K.N.), Birmingham; Birmingham Neuro-Ophthalmology (S.P.M.), Queen Elizabeth Hospital; Metabolic Neurology (A.J.S.), Institute of Metabolism and Systems Research, University of Birmingham; and Department of Neurology (A.J.S.), University Hospitals Birmingham, Queen Elizabeth Hospital, United Kingdom.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Nicola Jaime Adderley
Anuradhaa Subramanian
From the Institute of Applied Health Research (N.J.A., A.S., M.P., K.N.), University of Birmingham; Centre for Endocrinology, Diabetes, and Metabolism (K.N.), Birmingham Health Partners; Health Data Research UK (K.N.), Birmingham; Birmingham Neuro-Ophthalmology (S.P.M.), Queen Elizabeth Hospital; Metabolic Neurology (A.J.S.), Institute of Metabolism and Systems Research, University of Birmingham; and Department of Neurology (A.J.S.), University Hospitals Birmingham, Queen Elizabeth Hospital, United Kingdom.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mary Perrins
From the Institute of Applied Health Research (N.J.A., A.S., M.P., K.N.), University of Birmingham; Centre for Endocrinology, Diabetes, and Metabolism (K.N.), Birmingham Health Partners; Health Data Research UK (K.N.), Birmingham; Birmingham Neuro-Ophthalmology (S.P.M.), Queen Elizabeth Hospital; Metabolic Neurology (A.J.S.), Institute of Metabolism and Systems Research, University of Birmingham; and Department of Neurology (A.J.S.), University Hospitals Birmingham, Queen Elizabeth Hospital, United Kingdom.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Krishnarajah Nirantharakumar
From the Institute of Applied Health Research (N.J.A., A.S., M.P., K.N.), University of Birmingham; Centre for Endocrinology, Diabetes, and Metabolism (K.N.), Birmingham Health Partners; Health Data Research UK (K.N.), Birmingham; Birmingham Neuro-Ophthalmology (S.P.M.), Queen Elizabeth Hospital; Metabolic Neurology (A.J.S.), Institute of Metabolism and Systems Research, University of Birmingham; and Department of Neurology (A.J.S.), University Hospitals Birmingham, Queen Elizabeth Hospital, United Kingdom.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susan P. Mollan
From the Institute of Applied Health Research (N.J.A., A.S., M.P., K.N.), University of Birmingham; Centre for Endocrinology, Diabetes, and Metabolism (K.N.), Birmingham Health Partners; Health Data Research UK (K.N.), Birmingham; Birmingham Neuro-Ophthalmology (S.P.M.), Queen Elizabeth Hospital; Metabolic Neurology (A.J.S.), Institute of Metabolism and Systems Research, University of Birmingham; and Department of Neurology (A.J.S.), University Hospitals Birmingham, Queen Elizabeth Hospital, United Kingdom.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Susan P. Mollan
Alexandra Jean Sinclair
From the Institute of Applied Health Research (N.J.A., A.S., M.P., K.N.), University of Birmingham; Centre for Endocrinology, Diabetes, and Metabolism (K.N.), Birmingham Health Partners; Health Data Research UK (K.N.), Birmingham; Birmingham Neuro-Ophthalmology (S.P.M.), Queen Elizabeth Hospital; Metabolic Neurology (A.J.S.), Institute of Metabolism and Systems Research, University of Birmingham; and Department of Neurology (A.J.S.), University Hospitals Birmingham, Queen Elizabeth Hospital, United Kingdom.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alexandra Jean Sinclair
Full PDF
Short Form
Citation
Headache, Opiate Use, and Prescribing Trends in Women With Idiopathic Intracranial Hypertension
A Population-Based Matched Cohort Study
Nicola Jaime Adderley, Anuradhaa Subramanian, Mary Perrins, Krishnarajah Nirantharakumar, Susan P. Mollan, Alexandra Jean Sinclair
Neurology Nov 2022, 99 (18) e1968-e1978; DOI: 10.1212/WNL.0000000000201064

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
420

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

Abstract

Background and Objectives Physician prescribing habits for opiates and headache therapies have not been previously evaluated in a large, matched cohort study in idiopathic intracranial hypertension (IIH). Our objective was to evaluate opiate and headache medication prescribing habits in women with IIH compared with matched women with migraine and population controls. We also investigated the occurrence of new onset headache in IIH compared with population controls.

Methods We performed a population-based matched, retrospective cohort study to explore headache outcomes. Cross-sectional analyses were used to describe medication prescribing patterns. We used data from IQVIA Medical Research Data, an anonymized, nationally representative primary care electronic medical record database in the United Kingdom, from January 1, 1995, to September 25, 2019. Women aged 16 years and older were eligible for inclusion. Women with IIH (exposure) were matched by age and body mass index with up to 10 control women without IIH but with migraine (migraine controls), and without IIH or migraine (population controls).

Results A total of 3,411 women with IIH, 13,966 migraine controls, and 33,495 population controls were included. The adjusted hazard ratio for new onset headache in IIH compared with population controls was 3.09 (95% CI 2.78–3.43). In the first year after diagnosis, 58% of women with IIH were prescribed acetazolamide and 20% topiramate. In total, 20% of women with IIH were prescribed opiates within the first year of their diagnosis, reducing to 17% after 6 years, compared with 8% and 11% among those with migraine, respectively. Twice as many women with IIH were prescribed opiates compared with migraine controls, and 3 times as many women with IIH were prescribed opiates compared with population controls. Women with IIH were also prescribed more headache preventative medications compared with migraine controls.

Discussion Women with IIH were more likely to be prescribed opiate and simple analgesics compared with both migraine and population controls. Women with IIH trialed more preventative medications over their disease course suggesting that headaches in IIH may be more refractory to treatment.

Glossary

BMI=
body mass index;
CGRP=
calcitonin gene-related peptide;
IIH=
idiopathic intracranial hypertension;
IMRD=
IQVIA Medical Research Data;
THIN=
The Health Improvement Network

Idiopathic intracranial hypertension (IIH)1 is a relatively uncommon condition characterized by raised intracranial pressure and papilloedema with no direct identifiable cause.2,3 It has clear diagnostic criteria which include normal neuroimaging and venography (which may have stigmata of raised intracranial pressure only) and a lumbar puncture opening pressure >25 cm CSF.4 This secondary headache condition has an established association with obesity, and recent weight gain is a key risk factor for developing the disease.5,-,7 There is an increasing incidence and prevalence of IIH.8,-,11 Most of those with IIH have headaches at diagnosis, with up to 86% reporting daily headaches.12,-,16 It is of interest that a relatively high portion of those with IIH headache will have a preexisting headache history, up to 44% in one study17 and up to 68% in another.16 After resolution of the raised intracranial pressure, 63% of the patients with IIH go on to have a persistent post-IIH headache at 12 months after initial diagnosis.18

Disability in patients with IIH is predominantly driven by headache19,20; however, vision and conditions such as depression and anxiety are known to be contributing factors in IIH.21 There are no licensed therapies for IIH, and there remains a lack of dedicated abortive or preventative headache therapy in IIH.4,12,22,23 There have been no specific studies evaluating the use of acute pain relief in IIH headache, although a number of studies have documented a regular use of analgesic medications in up to half of the patients with IIH.14,17,24 Headache in IIH is most frequently migraine-like,12,-,15 and therefore, migraine therapeutics are often used.16,22,24 However, the choice of drugs used for IIH headaches is limited because of the need to avoid drugs that may cause weight gain or those that cause exacerbation of depression or fatigue.4,24 The use of calcitonin gene-related peptide (CGRP) monoclonal antibodies as a headache preventative strategy has recently been demonstrated to be of benefit in those with chronic IIH headaches.14 It is hypothesized that medicine prescribing habits in IIH are likely to be different compared with age-matched and sex-matched individuals with migraine.

Medication overuse headache is defined by the International Headache Society as headache occurring on 15 or more days per month as a consequence of regular overuse of acute or symptomatic headache medication (on 10 or more or 15 or more days per month, depending on the medication) for more than 3 months.25 In primary headache disorders such as migraine, medication overuse is commonly reported as between 25% and 50%, where it is known to significantly exacerbate the underlying headache morbidity.26 In episodic migraine, there is clear documentation of medication overuse, where 11% routinely used opiates and 6% used compounds with barbiturates, which increased to over a third in those with chronic migraine.27 Opiate use not only is a driver for medication overuse headache but also leads to numerous other negative sequalae, including insomnia, constipation, cardiac problems, and suicide.

Medication overuse has been documented in IIH, occurring in up to 23% at diagnosis17 and up to 35% of those with established disease.16 Up to 37% have been noted to use analgesics daily because their disease becomes more chronic.17 When the intracranial pressure has settled, evidenced by resolution of papilloedema, up to 48% have medication overuse documented.14 The use of opiates in patients with IIH has not been previously evaluated.

The aims of this study were to evaluate the prescribing of opiates, headache therapies, and IIH medications in primary care before and after a diagnosis of IIH compared with control women both with and without migraine and to investigate the hazard of new onset headache in women with IIH compared with women with neither IIH nor migraine.

Methods

Study Design

We performed an age-matched and body mass index (BMI)–matched retrospective cohort study using data from 1st January 1995 to 25th September 2019.

Data Source

Data for this study were extracted from IQVIA Medical Research Data (IMRD-UK), which incorporates data from The Health Improvement Network (THIN), a national database of electronic primary care records, which is generalizable to the UK population.28 The database contains anonymized medical records of more than 15 million patients from 808 practices in the United Kingdom. It comprises coded information on patient demographics, symptoms and diagnoses, drug prescriptions, consultations, and diagnostic tests and their results. An IIH diagnosis necessitates a hospital encounter for diagnostic investigations in the United Kingdom, and the diagnosis is then reported to general practice or primary care physicians; this process increases the likelihood that a record of IIH diagnosis in the primary care electronic record is accurate. Studies using IMRD data for IIH analysis have previously been published.10 Data were extracted using Data Extraction for Epidemiological Research (DEXTER).29

Population

To ensure high data quality, general practices were eligible for inclusion in the study from the latest of 12 months after the date from which they reported acceptable mortality recording rates30 and 12 months after the practice began using electronic medical records. Women registered with any of the eligible general practices for at least 365 days formed the source study population. Adult women aged 16 years and older were included.

Inclusion Criteria for Women With IIH (Exposed Group)

IIH diagnosis was ascertained by the presence of an IIH clinical (Read) code in the patient's medical records (eTable 1A, links.lww.com/WNL/C262). Read codes are a hierarchical system of coding symptoms and diagnoses used in UK primary care since 1985.31 Any IIH patients with a simultaneous clinical code for hydrocephalus or cerebral venous sinus thrombosis (eTables 1B and 1C) were excluded, in case they had been miscoded. For drug prescriptions, only women with incident IIH (newly diagnosed during the study period) and their corresponding matched controls were included in the analysis to capture drugs prescribed from the time of diagnosis. To assess rates of new onset headache and migraine (Read code lists in eTables 1D and 1E), women with prevalent and incident IIH and their corresponding population controls were included; in a sensitivity analysis, only women with incident IIH (and their corresponding controls) were included.

Inclusion Criteria for Migraine Controls (Unexposed)

For each incident patient with IIH, up to 10 controls with a migraine diagnosis,32 but no IIH, and matched using propensity scores based on index date, age, BMI category, Townsend deprivation quintile, ethnicity, and smoking status were randomly selected. Propensity score matching was used to maximize the number of migraine controls.

Inclusion Criteria for Population Controls (Unexposed)

For each patient with IIH, up to 10 population controls—women without a record of IIH and without a record of migraine—matched on the index date for age (±1 year) and BMI (±2 kg/m2), were randomly selected. Controls with a diagnosis of hydrocephalus or cerebral venous sinus thrombosis were excluded.

Follow-up Period

For incident/newly diagnosed patients with IIH, index date was the date of diagnosis. For prevalent exposed/IIH patients with a preexisting diagnosis, the index date was 1 year after registration or 1 year after the date the practice became eligible to take part in the study, whichever was the latest, to ensure sufficient time for documentation of important baseline comorbidities. Population controls were assigned the same index date as their corresponding patient with IIH to mitigate immortal time bias.33 For migraine controls, index date was date of migraine diagnosis; index year was included among the propensity score matching variables.

All patients were followed-up from index date until the date of the earliest of the following endpoints: outcome, death, patient left the practice, practice ceased contributing to the database, or study end (September 25, 2019).

Outcomes

Drug Prescriptions

Prescription of the following drugs in women with incident IIH and both control groups was explored: analgesics, migraine prevention therapies, and carbonic anhydrase inhibitors (eTable 2, links.lww.com/WNL/C262). In the United Kingdom, prescribing of migraine preventative medications is guided by the National Institute of Health and Clinical Excellence and other national body recommendations. There are also disease-specific recommendations for prescribing in IIH headache4,22; however, they were introduced at the end of our study period. The choice of medications to include in the analysis was based on UK guidance, and therefore, medications such as gepants, lisinopril, and memantine, which are either unavailable or not recommended in the United Kingdom, were not included. Prescriptions for botulinum toxin and CGRP monoclonal antibodies for migraine have been recent additions to the National Health Service prescribing formulary, CGRP therapy was not initiated until after the study period in the United Kingdom, and botulinum toxin therapy has been used for refractory migraine but not IIH headaches. Furthermore, these are prescribed within hospital care and are not recorded in IMRD/primary care data and, therefore, could not be explored in this analysis. Ditans have recently been approved by the Food and Drug Administration and were not included.

Headache and Migraine Outcomes

Outcomes were new onset headache and migraine. Outcomes were defined by a first record of a relevant clinical (Read) code which specified the headache or migraine diagnosis (eTables 1D and 1E, links.lww.com/WNL/C262). Patients with a record of the outcome at baseline were excluded. New onset headache and migraine were compared only with population controls because all women diagnosed with migraine would have a record of headache or migraine at index date.

Analysis

Drug Prescriptions

A series of annual cross-sectional analyses were performed to calculate total counts and proportions of patients within each exposure group with a prescription record for each of the drug categories during the year before index date and during each year up to 6 years after index. Drugs were categorized into the following groups: analgesics: all acute analgesics, opiates, simple analgesics, and triptans; migraine preventative therapies: all, epilepsy drugs, tricyclics, beta blockers, candesartan, and pizotifen and methysergide; and medicines used to treat IIH (acetazolamide, diuretics, and topiramate). The proportion of women prescribed therapies in each of the drug categories was plotted over time, as a proportion of participants still being followed up at the given time point. Finally, the number of headache preventative medicine classes each participant had been trialed on at baseline and at 3 years was counted.

Headache and Migraine

Incidence rates for new onset headache and migraine per 1,000 person-years were calculated in women with a record of IIH (prevalent or incident) and in the population control group. Cox proportional hazards regression was used to calculate crude and adjusted hazard ratios (aHRs) and their corresponding 95% CIs for rates in women with IIH compared with population controls for both outcomes. Regression models were adjusted for age category, BMI category (categorized as underweight [<18.5 kg/m2], normal weight [18.5–25 kg/m2], overweight [25–30 kg/m2], and obese [>30 kg/m2]), Townsend deprivation quintile, smoking status (categorized as nonsmoker, current smoker, and ex-smoker), eating disorder, severe mental illness, back pain, osteoarthritis, rheumatoid arthritis, fibromyalgia, epilepsy, obstructive sleep apnea, and polycystic ovary syndrome, based on biological plausibility and report ed associations in the literature.10,34,-,38 Mental health conditions were considered as a potential confounder because drugs for mental health can also be prescribed for headache prophylaxis. The proportional hazards assumption was checked using the Schoenfeld residuals test.

Inclusion of individuals with a prevalent (preexisting) IIH diagnosis increases sample size but may result in survival bias because anyone with prevalent IIH who had also developed the outcome before study entry would be excluded from the analysis. A sensitivity analysis was therefore performed limiting the analysis to patients with incident IIH (newly diagnosed during the study period and followed up from the time of diagnosis) and their corresponding population controls to explore any effect of survival bias.

All analyses were performed in Stata IC version 16. Two-sided p values were obtained; p values <0.05 were considered statistically significant.

Missing Data

Missing data for BMI, Townsend deprivation quintile, ethnicity, and smoking status were treated as a separate missing category in propensity score matching and the regression models, where relevant. Exposed patients with missing BMI were matched to population controls with missing BMI. The absence of a clinical code for a disease or of a prescription code for a given medication was taken to indicate the absence of the corresponding disease or prescription, respectively.

Standard Protocol Approvals, Registrations, and Patient Consents

The use of IMRD-UK is approved by the UK Research Ethics Committee (Ref. No. 18/LO/0441); in accordance with this approval, the study protocol was reviewed and approved by an independent Scientific Review Committee (Ref. No. 18THIN070). IMRD-UK incorporates data from THIN, A Cegedim Database. Reference made to THIN is intended to be descriptive of the data asset licensed by IQVIA. This work used deidentified data provided by patients as a part of their routine primary care.

Results

Baseline Characteristics

A total of 3,411 women with IIH, 13,966 migraine controls, and 33,495 controls were included in the analysis. Baseline characteristics are presented in Table 1. The mean age in prevalent and incident IIH and population controls was 34 years; in incident only IIH and corresponding matched controls, the mean age was 32 years in all exposure groups. The mean (SD) BMI was 35.7 (8.1), 29.4 (6.5), and 35.1 (7.7) in the incident IIH, migraine control, and population control groups, respectively. Approximately a quarter of the participants were smokers. The proportion of participants with back pain, polycystic ovary syndrome, osteoarthritis, epilepsy, fibromyalgia, sleep apnea, and severe mental illness was higher in women with IIH compared with both control groups (Table 1).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table 1

Baseline Characteristics of Exposed Participants With IIH, Matched Controls With Migraine, and Matched Population Controls

Drug Prescriptions

IIH Treatments

As expected, acetazolamide was the most common drug prescribed in women with IIH within their first year of diagnosis (58%), followed by topiramate (20%) (eFigure 1, eTable 3, links.lww.com/WNL/C262). Both acetazolamide and topiramate continued to be prescribed, but in decreasing numbers, up to 6 years. Diuretics (furosemide and spironolactone) were rarely prescribed (eFigure 1).

Acute Analgesics

Overall, prescribing of acute analgesics was similar in women with IIH and migraine controls, and lowest in population controls (Figure 1, eTable 4, links.lww.com/WNL/C262). A greater proportion of women with IIH were prescribed opiates compared with both migraine controls (approximately twice the proportion) and population controls (approximately 3-fold higher overall). The proportion of women with IIH prescribed analgesics remained relatively constant over time from the point of diagnosis (Figure 1).

Figure 1
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1 Analgesic Prescriptions in Women With IIH and Matched Migraine and Population Controls

IIH = idiopathic intracranial hypertension.

Migraine Prevention Drugs

Overall, prescribing of prevention drugs was substantially higher in women with IIH compared with either migraine controls (around 50% higher on average) or population controls (approximately 3-fold higher) (Figure 2, eTable 5, links.lww.com/WNL/C262). In particular, prescribing of epilepsy class drugs, tricyclic antidepressants, and candesartan was higher in women with IIH. Prescribing of pizotifen/methysergide was highest in migraine controls; prescribing of beta-blockers was similar in women with IIH and migraine controls, with around a 2- to 3-fold higher proportion prescribed beta-blockers compared with population controls. In women with IIH, for most of the preventative drugs, the overall trend was for prescribing to peak in the year of IIH diagnosis and then decline slightly thereafter (Figure 2). The number of preventative medications that had been prescribed was counted at index and 3 years. Those with IIH tried more preventative medications compared with the migraine and population controls (Figure 3). By 3 years, patients with IIH were more likely to have tried 2, 3, or more than 3 preventatives than the migraine controls.

Figure 2
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2 Preventative Prescriptions in Women With IIH and Matched Migraine and Population Controls

IIH = idiopathic intracranial hypertension; TCA = tricyclic antidepressants.

Figure 3
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 3 Number of Preventative Medications Initiated at Baseline and Within 3 Years in Women With IIH and Matched Migraine and Population Controls

IIH = idiopathic intracranial hypertension.

Headache and Migraine Outcomes (IIH and Population Controls Only)

A total of 1,455 women with IIH and 26,403 population controls (with neither IIH nor migraine) were included in the analysis for new onset headache. The crude incidence of new onset headache was 71.6 and 23.9 per 1,000 person-years in the IIH and population control groups, respectively (Table 2). Compared with control women, the aHR for new onset headache in women with IIH was 3.09 (95% CI 2.78–3.43). In a sensitivity analysis restricted to only women with incident IIH and their corresponding controls, aHR was 4.92 (95% CI 4.21–5.74) (eTable 6, links.lww.com/WNL/C262).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table 2

Incidence Rates and Hazard Ratios of New Onset Headache and Migraine in Women With IIH Compared With Matched Population Controls (With Neither IIH nor Migraine)

A total of 2,685 women with IIH and 33,495 population controls were included in the analysis for a diagnosis of new onset migraine. The crude incidence of migraine was 18.0 and 7.5 per 1,000 person-years in the IIH and population control groups, respectively (Table 2). Compared with population controls, the aHR for new onset migraine in women with IIH was 2.32 (95% CI 2.01–2.67). In a sensitivity analysis restricted to only women with incident IIH and their corresponding controls, aHR was 3.25 (95% CI 2.69–3.91) (eTable 6, links.lww.com/WNL/C262).

Discussion

In this large population-based, age-matched, and BMI-matched cohort study, we found that women with IIH had a 3-fold increased hazard of new onset headache and more than twice the hazard of a diagnosis of new onset migraine compared with women without IIH (population controls). Prescribing data suggest that headache in IIH is challenging to treat, as evidenced by the increased opiate, simple analgesics, and preventative medications prescribed in IIH compared with the migraine and population control groups.

Although IIH has high headache morbidity,1,14,17,20 there has only been 1 open label study specifically evaluating headache treatment in IIH.14 When a priority setting partnership was concluded, understanding headache and new treatments was highly prioritized for the disease.39 This burden of headache is reflected in the prescribing patterns recorded here. The proportion of women with IIH prescribed simple analgesics remained at a relatively constant level over the study period from 1 year before diagnosis up to year 6 and was higher (ranging between 29% and 39%) than both control groups. A greater proportion of the IIH group were prescribed opiates compared with both migraine controls (approximately double) or population controls (approximately triple). This implies that headache in IIH remains uncontrolled and that the IIH population is at significant risk of medication overuse headaches. In other headache disorders, overuse of analgesic medications is believed to contribute to the frequency and severity of headache and may have a role in progression from episodic to chronic headaches.40 It is also notable that obesity and female sex are important risk factors for medication overuse, both of which are common characteristics of IIH.41

This study has demonstrated that existing migraine preventative drugs are commonly prescribed in IIH. These are currently used off-label without evidence of efficacy in this population. A number of the classes of headache prevention drugs can cause weight gain as an unwanted side effect. This limits treatment choices in IIH where weight loss is central to management and for remission of the disease.4,7,22,42 In this study, we have provided evidence of the prescribing of headache preventatives that could induce weight gain, and physicians should consider alternative options. Currently, as there are no licensed treatment options, the IIH population remains at significant risk of medication overuse.

A recent open label study using erenumab in 55 IIH women, with a mean disease duration of 10 years, recorded on average 3.7 preventative treatment failures,14 indicating headache in IIH is resistant to medical therapy used in migraine. The burden of headache seen in this small prospective study is replicated here. For escalation to second-line treatment of either botulinum toxin or CGRP monoclonal antibodies, the person has to fulfil a diagnosis of chronic migraine and importantly have trialed and failed at least 3 preventative drug treatments. To understand the proportion of people with migraine and those with IIH that fulfil the criteria for chronic migraine headaches who may be eligible for this escalation of treatment, the number of preventative medications that had been prescribed was measured both at diagnosis and 3 years. Those with IIH had trialed more classes of preventative medications, compared with both the migraine and population control groups. By 3 years, patients with IIH were more likely to have trialed 2, 3, or more than 3 preventative medicine classes than the migraine controls. These data further suggest that a persistent IIH headache is refractory to conventional migraine preventative treatment.12

Our research has several strengths. A large sample size has been used to explore a rare condition (IIH) and to understand its association with headache and migraine outcomes, and prescribing habits. Patients included in IMRD-UK are generalizable to the UK population. In the United Kingdom, diagnosis of IIH is made in the hospital setting in line with diagnostic criteria; however, the diagnostic criteria for IIH have evolved over time.4,22,23 The diagnosis is then communicated to the general practice. However, there is a known risk of diagnostic error causing misclassification bias43 and a possibility of data entry error in the hospital or general practice. To mitigate this, we excluded those with a record of hydrocephalus or cerebral venous sinus thrombosis. It is possible that there may be underrecording of IIH due to either undiagnosed cases or cases being diagnosed in secondary care and not being documented/recorded in the patient's primary care record. Overdiagnosis is possible but unlikely due to diagnosis being made by specialists in secondary care. Diagnosis of migraine in primary care has been found to be 98% accurate in accordance with the International Headache Society classification of migraine44; however, it is not possible to ascertain from the data whether some of those with new onset headache may have a migraine phenotype, and there is ongoing debate as to whether people with IIH have a chronic headache that is physiologically different from chronic migraine. Drug prescriptions are accurately recorded in primary care data; however, the use of paracetamol, aspirin, and nonsteroidal anti-inflammatory drugs obtained personally/over-the-counter by the patient could not be captured here; furthermore, any drugs prescribed in secondary care would not be captured in the data set. It is possible that the lower prescription rates of migraine preventatives observed in women with migraine compared with those with IIH may be partially due to undertreatment of migraine. We were not able to perform a sensitivity analysis in acute vs chronic IIH because information regarding papilloedema status is not recorded within the IMRD database. This may have clear influence on prescribing habits; however, overall, we note from the data that prescribing of analgesics continues long term (with the proportion remaining similarly high at least up to 5 years after diagnosis) in those diagnosed with IIH. The results detailing opiate prescribing would be representative of other international populations where opiate prescribing is permitted for pain and headache, but not necessarily reflect prescribing habits where opiate prescribing has been restricted by public policy or laws. As this study included women only, the findings are not directly generalizable to men with IIH.

This was the largest national study providing epidemiologic data evaluating prescribing habits for those with IIH and comparing them with matched migraine controls and population controls. The finding that opiate use in IIH was 3 times higher than in the population controls and double that observed in migraine controls is a major concern. There are likely to be multiple contributing factors, including the major burden of headache these patients experience. However, the consequences of such dominant opiate use in IIH are likely be extensive and contribute to the poor quality of life that has previously been noted. We also observed increased prescribing of simple analgesics and preventative drugs in IIH compared with migraine controls. These data may point toward a refractory nature of IIH headache. Headache management in IIH remains an unmet clinical need, and the development of targeted therapies may help reduce the multiple prescriptions of preventative migraine medications and curb the opiate prescribing trends.

Study Funding

This study was funded by The Midland Neurosciences and Teaching Research Fund (MNTRF, Registered Charity No. 313446; Project Ref. No. 38). AJS was funded by a National Institute for Health Research (NIHR) clinician scientist fellowship (NIHR-CS-011-028) and the Medical Research Council, United Kingdom (MR/K015184/1), for the duration of the study. A.J. Sinclair was funded by a Sir Jules Thorn Award for Biomedical Science. The view expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health and Social Care. MNTRF, the NIHR, and the MRC had no role in the design or conduct of the study; no role in collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and no role in the decision to submit the manuscript for publication in the design, execution, or write up of this trial.

Disclosure

S.P. Mollan reports other funding from Invex Therapeutics and Heidelberg engineering during the conduct of the study and other funding from Chugai-Roche Ltd., Janssen, Allergan, Santen, Roche, and Neurodiem outside the submitted work. A.J. Sinclair reports personal fees from Invex therapeutics during the conduct of the study. All other authors declare no competing interests. Go to Neurology.org/N for full disclosures.

Appendix Authors

Table

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • The Article Processing Charge was funded by MRC and NIHR.

  • Submitted and externally peer reviewed. The handling editor was Rebecca Burch, MD.

  • Received February 24, 2022.
  • Accepted in final form June 21, 2022.
  • Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

References

  1. 1.↵
    1. Mollan SP,
    2. Hoffmann J,
    3. Sinclair AJ
    . Advances in the understanding of headache in idiopathic intracranial hypertension. Curr Opin Neurol. 2019;32(1):92-98.
    OpenUrlCrossRef
  2. 2.↵
    1. Virdee J,
    2. Larcombe S,
    3. Vijay V,
    4. Sinclair AJ,
    5. Dayan M,
    6. Mollan SP
    . Reviewing the recent developments in idiopathic intracranial hypertension. Ophthalmol Ther. 2020;9(4):767-781.
    OpenUrl
  3. 3.↵
    1. Hornby C,
    2. Mollan SP,
    3. Botfield H,
    4. OʼReilly MW,
    5. Sinclair AJ
    . Metabolic concepts in idiopathic intracranial hypertension and their potential for therapeutic intervention. J Neuroophthalmol. 2018;38(4):522-530.
    OpenUrlPubMed
  4. 4.↵
    1. Mollan SP,
    2. Davies B,
    3. Silver NC, et al
    . Idiopathic intracranial hypertension: consensus guidelines on management. J Neurol Neurosurg Psychiatry. 2018;89(10):1088-1100.
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    1. Daniels AB,
    2. Liu GT,
    3. Volpe NJ, et al
    . Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol. 2007;143(4):635-641.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Andrews LE,
    2. Liu GT,
    3. Ko MW
    . Idiopathic intracranial hypertension and obesity. Horm Res Paediatr. 2014;81(4):217-225.
    OpenUrlPubMed
  7. 7.↵
    1. Mollan SP,
    2. Tahrani AA,
    3. Sinclair AJ
    . Body weight the potential modifiable risk factor in idiopathic intracranial hypertension. Neurol Clin Pract. 2021;11(4):e504-e507.
    OpenUrlAbstract/FREE Full Text
  8. 8.↵
    1. McCluskey G,
    2. Doherty-Allan R,
    3. McCarron P, et al
    . Meta-analysis and systematic review of population-based epidemiological studies in idiopathic intracranial hypertension. Eur J Neurol. 2018;25(10):1218-1227.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Mollan SP,
    2. Aguiar M,
    3. Evison F,
    4. Frew E,
    5. Sinclair AJ
    . The expanding burden of idiopathic intracranial hypertension. Eye (Lond). 2019;33(3):478-485.
    OpenUrl
  10. 10.↵
    1. Adderley NJ,
    2. Subramanian A,
    3. Nirantharakumar K, et al
    . Association between idiopathic intracranial hypertension and risk of cardiovascular diseases in women in the United Kingdom. JAMA Neurol. 2019;76(9):1088-1098.
    OpenUrl
  11. 11.↵
    1. Mollan SP,
    2. Mytton J,
    3. Tsermoulas G,
    4. Sinclair AJ
    . Idiopathic intracranial hypertension: evaluation of admissions and emergency readmissions through the hospital episode statistic dataset between 2002-2020. Life (Basel). 2021;11(5):417.
    OpenUrl
  12. 12.↵
    1. Mollan SP,
    2. Grech O,
    3. Sinclair AJ
    . Headache attributed to idiopathic intracranial hypertension and persistent post-idiopathic intracranial hypertension headache: a narrative review. Headache. 2021;61(6):808-816. doi:10.1111/head.14125.
    OpenUrlCrossRef
  13. 13.↵
    1. Raggi A,
    2. Marzoli SB,
    3. Chiapparini L, et al
    . Headache frequency and symptoms of depression as predictors of disability in patients with idiopathic intracranial hypertension. Neurol Sci. 2018;39(suppl 1):139-140.
    OpenUrlPubMed
  14. 14.↵
    1. Yiangou A,
    2. Mitchell JL,
    3. Fisher C, et al
    . Erenumab for headaches in idiopathic intracranial hypertension: a prospective open-label evaluation. Headache. 2021;61 (1):157-169.
    OpenUrl
  15. 15.↵
    1. Yri HM,
    2. Jensen RH
    . Idiopathic intracranial hypertension: clinical nosography and field-testing of the ICHD diagnostic criteria. A case-control study. Cephalalgia. 2015;35(7):553-562.
    OpenUrlCrossRefPubMed
  16. 16.↵
    1. Mollan SP,
    2. Wakerley BR,
    3. Alimajstorovic Z, et al
    . Intracranial pressure directly predicts headache morbidity in idiopathic intracranial hypertension. J Headache Pain. 2021;22(1):118.
    OpenUrlCrossRef
  17. 17.↵
    1. Friedman DI,
    2. Quiros PA,
    3. Subramanian PS, et al
    . Headache in idiopathic intracranial hypertension: findings from the idiopathic intracranial hypertension treatment trial. Headache. 2017;57(8):1195-1205.
    OpenUrlPubMed
  18. 18.↵
    1. D Amico D,
    2. Curone M,
    3. Ciasca P, et al
    . Headache prevalence and clinical features in patients with idiopathic intracranial hypertension (IIH). Neurol Sci. 2013;34(suppl 1):S147-S149.
    OpenUrlCrossRefPubMed
  19. 19.↵
    1. Kleinschmidt JJ,
    2. Digre KB,
    3. Hanover R
    . Idiopathic intracranial hypertension: relationship to depression, anxiety, and quality of life. Neurology. 2000;54(2):319-324.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    1. Mulla Y,
    2. Markey KA,
    3. Woolley RL,
    4. Patel S,
    5. Mollan SP,
    6. Sinclair AJ
    . Headache determines quality of life in idiopathic intracranial hypertension. J Headache Pain. 2015;16:521.
    OpenUrlPubMed
  21. 21.↵
    1. de Oliveira MF,
    2. Yamashita RHG,
    3. Boa Sorte AA Jr., et al
    . Psychiatric symptoms are frequent in idiopathic intracranial hypertension patients. Neurosurg Rev. 2021;44(2):1183-1189. doi:10.1007/s10143-020-01321-3.
    OpenUrlCrossRef
  22. 22.↵
    1. Hoffmann J,
    2. Mollan SP,
    3. Paemeleire K,
    4. Lampl C,
    5. Jensen RH,
    6. Sinclair AJ
    . European headache federation guideline on idiopathic intracranial hypertension. J Headache Pain. 2018;19(1):93.
    OpenUrl
  23. 23.↵
    1. Mollan SP,
    2. Hornby C,
    3. Mitchell J,
    4. Sinclair AJ
    . Evaluation and management of adult idiopathic intracranial hypertension. Pract Neurol. 2018;18(6):485-488.
    OpenUrlAbstract/FREE Full Text
  24. 24.↵
    1. Mollan SP,
    2. Grech O,
    3. Sinclair AJ
    . Headache attributed to idiopathic intracranial hypertension and persistent post-idiopathic intracranial hypertension headache: a narrative review. Headache. 2021;61(6):808-816.
    OpenUrlCrossRef
  25. 25.↵
    Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629-808. doi:10.1177/0333102413485658.
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Diener HC,
    2. Dodick D,
    3. Evers S, et al
    . Pathophysiology, prevention, and treatment of medication overuse headache. Lancet Neurol. 2019;18(9):891-902.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Bigal ME,
    2. Borucho S,
    3. Serrano D,
    4. Lipton RB
    . The acute treatment of episodic and chronic migraine in the USA. Cephalalgia. 2009;29(8):891-897.
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Blak BT,
    2. Thompson M,
    3. Dattani H,
    4. Bourke A
    . Generalisability of The Health Improvement Network (THIN) database: demographics, chronic disease prevalence and mortality rates. Inform Prim Care. 2011;19(4):251-255.
    OpenUrlCrossRefPubMed
  29. 29.↵
    1. Gokhale KM,
    2. Chandan JS,
    3. Toulis K,
    4. Gkoutos G,
    5. Tino P,
    6. Nirantharakumar K
    . Data extraction for epidemiological research (DExtER): a novel tool for automated clinical epidemiology studies. Eur J Epidemiol. 2021. 36(2):165-178. doi:10.1007/s10654-020-00677-6.
    OpenUrlCrossRefPubMed
  30. 30.↵
    1. Maguire A,
    2. Blak BT,
    3. Thompson M
    . The importance of defining periods of complete mortality reporting for research using automated data from primary care. Pharmacoepidemiol Drug Saf. 2009;18(1):76-83.
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Booth N
    . What are the read codes? Health Libr Rev. 1994;11(3):177-182.
    OpenUrlCrossRefPubMed
  32. 32.↵
    1. Hennessy S,
    2. Bilker WB,
    3. Berlin JA,
    4. Strom BL
    . Factors influencing the optimal control-to-case ratio in matched case-control studies. Am J Epidemiol. 1999;149(2):195-197.
    OpenUrlCrossRefPubMed
  33. 33.↵
    1. Lévesque LE,
    2. Hanley JA,
    3. Kezouh A,
    4. Suissa S
    . Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes. BMJ. 2010;340:b5087.
    OpenUrlFREE Full Text
  34. 34.↵
    1. O'Reilly MW,
    2. Westgate CSJ,
    3. Hornby C, et al
    . A unique androgen excess signature in idiopathic intracranial hypertension is linked to cerebrospinal fluid dynamics. JCI Insight. 2019;4(6):e125348. doi:10.1172/jci.insight.125348.
    OpenUrlCrossRef
  35. 35.↵
    1. Hulens M,
    2. Rasschaert R,
    3. Vansant G,
    4. Stalmans I,
    5. Bruyninckx F,
    6. Dankaerts W
    . The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology. J Pain Res. 2018;11:3129-3140.
    OpenUrl
  36. 36.↵
    1. Marcus DM,
    2. Lynn J,
    3. Miller JJ,
    4. Chaudhary O,
    5. Thomas D,
    6. Chaudhary B
    . Sleep disorders: a risk factor for pseudotumor cerebri? J Neuroophthalmol. 2001;21(2):121-123. doi:10.1097/00041327-200106000-00014.
    OpenUrlCrossRefPubMed
  37. 37.↵
    1. Cheema S,
    2. Cooper S
    . 253 Idiopathic intracranial hypertension causing back pain and visual loss without headache. J Neurol Neurosurg Psychiatry. 2019;90:e61.
    OpenUrlAbstract/FREE Full Text
  38. 38.↵
    1. Puustinen T,
    2. Tervonen J,
    3. Avellan C, et al
    . Psychiatric disorders are a common prognostic marker for worse outcome in patients with idiopathic intracranial hypertension. Clin Neurol Neurosurg. 2019;186:105527.
    OpenUrl
  39. 39.↵
    1. Mollan S,
    2. Hemmings K,
    3. Herd CP,
    4. Denton A,
    5. Williamson S,
    6. Sinclair AJ
    . What are the research priorities for idiopathic intracranial hypertension? A priority setting partnership between patients and healthcare professionals. BMJ Open. 2019;9(3):e026573.
    OpenUrlAbstract/FREE Full Text
  40. 40.↵
    1. Bigal ME,
    2. Rapoport AM,
    3. Sheftell FD,
    4. Tepper SJ,
    5. Lipton RB
    . Transformed migraine and medication overuse in a tertiary headache centre—clinical characteristics and treatment outcomes. Cephalalgia. 2004;24(6):483-490.
    OpenUrlCrossRefPubMed
  41. 41.↵
    1. Diener HC,
    2. Holle D,
    3. Solbach K,
    4. Gaul C
    . Medication-overuse headache: risk factors, pathophysiology and management. Nat Rev Neurol. 2016;12(10):575-583.
    OpenUrlCrossRefPubMed
  42. 42.↵
    1. Mollan SP,
    2. Mitchell JL,
    3. Ottridge RS, et al
    . Effectiveness of bariatric surgery vs community weight management intervention for the treatment of idiopathic intracranial hypertension: a randomized clinical trial. JAMA Neurol. 2021:78(6):678-686.
    OpenUrl
  43. 43.↵
    1. Fisayo A,
    2. Bruce BB,
    3. Newman NJ,
    4. Biousse V
    . Overdiagnosis of idiopathic intracranial hypertension. Neurology. 2016;86(4):341-350.
    OpenUrlCrossRefPubMed
  44. 44.↵
    1. Tepper SJ,
    2. Dahlöf CGH,
    3. Dowson A, et al
    . Prevalence and diagnosis of migraine in patients consulting their physician with a complaint of headache: data from the landmark study. Headache. 2004;44(9):856-864. doi:10.1111/j.1526-4610.2004.04167.x.
    OpenUrlCrossRefPubMed

Letters: Rapid online correspondence

  • Author Response: Headache, Opiate Use, and Prescribing Trends in Women With Idiopathic Intracranial Hypertension: A Population-Based Matched Cohort Study
    • Susan P Mollan, Consultant neuro-ophthalmologist, University Hospitals Birmingham NHS Trust
    • Alex J Sinclair, Clinician Scientist, a.b.sinclair@bham.ac.uk
    Submitted September 26, 2022
  • Reader Response: Headache, Opiate Use, and Prescribing Trends in Women With Idiopathic Intracranial Hypertension: A Population-Based Matched Cohort Study
    • Vinod K Gupta, Physician-Medical Director, GUPTA MEDICAL CENTRE, MIGRAINE-HEADACHE INSTITUTE, S-407, Greater Kailash-Part Two, New Delhi, INDIA-110048
    Submitted September 12, 2022
Comment

REQUIREMENTS

If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Abstract
    • Glossary
    • Methods
    • Results
    • Discussion
    • Study Funding
    • Disclosure
    • Appendix Authors
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures
Advertisement

Hemiplegic Migraine Associated With PRRT2 Variations A Clinical and Genetic Study

Dr. Robert Shapiro and Dr. Amynah Pradhan

► Watch

Related Articles

  • No related articles found.

Topics Discussed

  • Migraine
  • Cohort studies
  • Idiopathic intracranial hypertension
  • Medical care

Alert Me

  • Alert me when eletters are published
Neurology: 100 (4)

Articles

  • Ahead of Print
  • Current Issue
  • Past Issues
  • Popular Articles
  • Translations

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Activate a Subscription
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology | Print ISSN:0028-3878
Online ISSN:1526-632X

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise