Todd D. Rozen

Female cluster headache in the United States of America: What are the gender differences?: Results from the United States Cluster Headache Survey

OBJECTIVE To present results from the United States Cluster Headache Survey regarding gender differences in cluster headache demographics, clinical characteristics, diagnostic delay, triggers, treatment response and personal burden. BACKGROUND Very few studies have looked at the gender differences in cluster headache presentation. The United States Cluster Headache Survey is the largest study of cluster headache sufferers ever completed in the United States and it is also the largest study of female cluster headache patients ever presented. METHODS The total survey consisted of 187 multiple choice questions which dealt with various issues related to cluster headache including: demographics, clinical characteristics, concomitant medical conditions, family history, triggers, smoking history, diagnosis, treatment response and personal burden. A group of questions were specifically targeted to female cluster headache patients. The survey was placed on a website from October to December 2008. For all survey responders the diagnosis of cluster headache needed to be made by a neurologist but there was no validation of the headache diagnosis by the authors. RESULTS 1134 individuals completed the survey (816 male, 318 female). Key Points that define the differences between female and male cluster headache include: a. Age of onset: women develop cluster headache at an earlier age than men and are more likely to develop a second peak of cluster headache onset after 50 years of age. b. Family history: woman cluster headache sufferers are more likely to have a family history of both cluster headache and migraine and have an increased familial risk of Parkinsons disease. c. Comorbid conditions: female cluster headaches sufferers are significantly more likely to experience depression and have asthma than males. d. Aura issues: aura with cluster headache is equally common in both sexes, but aura duration is shorter in women. Women are much more likely to experience sensory, language and brainstem auras. e. Pain location: cluster headache pain is typically retro-orbital in location in both sexes but women are significantly more likely to experience cluster headache pain in the jaw, cheek and ear than men. f. Associated symptoms: women with cluster headache develop more “migrainous” associated symptoms than men, especially nausea and they are also more likely to have self-injurious behavior than men. g. Triggers: women with cluster headache are much less likely to have alcohol trigger a headache, but are significantly more likely to have “migrainous” triggers for their cluster headaches than men. h. Smoking issues: women are much less likely to have a smoking history than male cluster headache sufferers, more likely to have never smoked prior to cluster headache onset. i. Cycle issues: spring and fall are the most common time to start a cluster headache cycle in both sexes. Women are statistically significantly less likely to start a cluster headache cycle in the months of October–December than men. Women have more attacks per day and higher pain intensity nighttime attacks than men. j. TREATMENT in regard to acute treatment women statistically were less response to sumatriptan injectable and nasal spray than men, but statistically more likely to respond to inhaled lidocaine. There was equal efficacy in the sexes to inhaled oxygen but slower response in women. For preventive treatment no significant gender differences were noted, but overall women were less responsive to almost all preventives than men. k. Diagnostic delay: there remains a significant diagnostic delay for cluster headache patients in both sexes but women were more likely to be diagnosed after 10 years of symptom onset than males and significantly fewer women were diagnosed correctly at an initial physician visit than men. l. Female specific issues: cluster headache does not appear to be influenced by menses or menopause but 50% of the survey responders stated their headaches improved with pregnancy. Cluster headache does not appear to alter fertility rates in female cluster headache sufferers. m. Personal burden: cluster headache causes significantly more personal burden in women than men with more loss of employment and/or need of disability, as well as more homebound days. CONCLUSION Overall women and men with cluster headache have a similar presentation but there are some distinct differences that have been suggested in smaller studies of female cluster headache that we have now verified, while some of our study conclusions have not been shown previously. One major limitation to the study is a lack of validation of diagnosis. A substantial false positive cluster headache diagnosis rate, especially in females, cannot be excluded by the study methods utilized.

A history of cigarette smoking is associated with the development of cranial autonomic symptoms with migraine headaches.

(Headache 2011;51:85‐91)

Brief Sharp Stabs of Head Pain and Giant Cell Arteritis

Giant cell arteritis (GCA) should be considered in the differential diagnosis of any new onset headache occurring in individuals over the age of 50 years. Headache is the most common complaint in GCA patients but the clinical characteristics of the headache itself does not help in making a diagnosis as the headache can occur anywhere on the head, not just the temples, be mild to severe in intensity and be dull to throbbing in quality. As other things can cause new onset headache in older individuals, additional clinical symptoms or signs that may suggest GCA as a diagnosis would be useful to clinicians. Two cases are presented that suggests that new onset stabbing headache associated with a new daily persistent headache is a possible diagnostic sign for a diagnosis of GCA. Nothing in the literature to date has mentioned new onset stabbing headache as part of the presenting symptom complex for GCA.

Non–hypothalamic cluster headache: the role of the greater occipital nerve in cluster headache pathogenesis

Cluster headache is marked by its circadian rhythmicity and the hypothalamus appears to have a significant influence over cluster pathogenesis. However, as not all cluster patients present in the same manner and not all respond to the same combination of medications, there is likely a nonhypothalamic form of cluster headache. A patient is presented who began to develop cluster headaches after receiving bilateral greater occipital nerve (GON) blockade. His headaches fit the IHS criteria for cluster headache but had some irregularities including frequent side shifting of pain, irregular duration and time of onset and the ability of the patient to sit completely still during a headache without any sense of agitation. This article will suggest that some forms of cluster headache are not primarily hypothalamic influenced and that the GON may play a significant role in cluster pathogenesis in some individuals.

New Daily Persistent Headache: An Update

New daily persistent headache is a primary headache disorder marked by a unique temporal profile which is daily from onset. For many sufferers this is their first ever headache. Very little is known about the pathogenesis of this condition. It might be a disorder of abnormal glial activation with persistent central nervous system inflammation and it may be a syndrome that occurs in individuals who have a history of cervical hypermobility. At present there is no known specific treatment and many patients go for years to decades without any improvement in their condition despite aggressive therapy. This article will present an up-to-date overview of new daily persistent headache on the topics of clinical presentation, treatment, diagnostic criteria, and presumed pathogenesis. It will also provide some of the authors own treatment suggestions based on recognized triggering events and some suggestions for future clinical trials.

Images From Headache: White Matter Lesions of Migraine Are Not Static

Migraine sufferers have an increased risk of developing white matter (WM) lesions on MRI. There is a suggestion that these lesions are ischemic but the true etiology is unknown. The natural history and clinical consequence of these lesions is also not understood. If these are brain infarctions then what does that mean for the neurologic health for the multitude of individuals who suffer from migraine? Several recent reports have suggested these lesions may reverse which would call into question an ischemic etiology. Brain MRIs (Figs. 1 and 2) of a chronic migraine patient (normotensive with mild hyperlipidemia) taken 5 months apart are presented showing resolution of 2 right-sided WM lesions on fluid-attenuated inversion recovery imaging. During this time period the patient was on no specific migraine acute or preventive treatment and on no antiplatelet therapy. She had a normal CT angiogram of the intraand extracranial blood vessels and negative testing for a coagulopthy. This imaging finding further suggests that the WM lesions of migraine in some patients are not static and may resolve. This could be a comforting fact to the millions of individuals who have migraine and who are worried that they will at some point develop strokes. Post-mortem pathology samples, however, are needed to define the etiology of these lesions but the fact that they may reverse would suggest a more benign condition than brain ischemia.

How Effective Is Melatonin as a Preventive Treatment for Hemicrania Continua? A Clinic-Based Study

To assess the efficacy of melatonin as a preventive therapy for hemicrania continua in a larger population of patients than has previously been studied.

Pachymeningeal Enhancement on MRI: A Venous Phenomena Not Always Related to Intracranial Hypotension (Resolving Pachymeningeal Enhancement and Cerebral Vein Thrombosis)

Bilateral diffuse pachymeningeal enhancement on magnetic resonance imaging (MRI) in a patient with daily headache is basically synonymous with intracranial hypotension. Based on the Monroe– Kellie doctrine, a loss of cerebrospinal fluid (CSF) volume is compensated by an increase in intracranial blood volume that occurs through the cerebral venous system. It is this secondary venous dilation with meningeal venous hyperemia that leads to pachymeningeal enhancement on MRI. A patient is presented who developed a daily holocranial headache out of the blue, nonthunderclap, with questionable orthostatic features (improvement after taking a nap but pain not dramatically different lying or standing). Five days after headache onset, the patient developed a probable seizure. On imaging, he was found to have a large cerebral vein thrombosis (CVT) involving the right superior sagittal sinus, transverse sinus, sigmoid sinus, and proximal jugular vein (Fig. 1). Also noted, however, was bilateral pachymeningeal enhancement that was more predominant on the right side (Fig. 2A,B). There is recent recognition that CVT can be a secondary consequence of intracranial hypotension, and as this patient had negative clotting studies, repeat imaging was completed 5 days later to see if the enhancement was still present, thus requiring further evaluation for an underlying CSF leak. The repeat imaging showed almost complete resolution of the pachymeningeal enhancement (Fig. 3). As the patient had resolving enhancement with no direct treatment of a CSF leak, it was presumed that the pachymeningeal enhancement was caused by meningeal venous hyperemia from venous collateral dilation post thrombus formation. The resolution of enhancement occurred after

Triggering Events and New Daily Persistent Headache: Age and Gender Differences and Insights on Pathogenesis–A Clinic-Based Study

To define what are the age and gender differences for new daily persistent headache (NDPH) triggering events and how this may relate to the pathogenesis of NDPH. To describe several new triggering events for NDPH.

Complete alleviation of treatment refractory primary SUNCT syndrome with clomiphene citrate (a medicinal deep brain hypothalamic modulator).

Objective To report the first ever case of primary short-lasting unilateral neuralgiform headache attacks (SUNCT) syndrome completely responsive to clomiphene citrate. Methods Case report. Results SUNCT is a primary headache disorder marked by frequent attacks of one-sided headache with cranial autonomic associated symptoms. When SUNCT is deemed medicinally treatment refractory, it can cause tremendous patient-related disability. Surgical treatment options are available including hypothalamic deep brain stimulation, occipital nerve stimulator placement or arterial decompression surgery, but these procedures carry significant morbidity. A patient presented with a 10 month complaint of multiple, daily short-lasting, right-sided headaches each lasting from 60 to 120 seconds in duration and occurring from 100 to 200 times per day. The head pain was associated with ipsilateral eyelid ptosis and conjunctival injection. The patient was diagnosed with SUNCT but was unresponsive to multiple recognized medicinal treatments. He had complete alleviation of his attacks with clomiphene citrate, a synthetic, non-steroidal, ovulatory stimulant that directly binds to hypothalamic estrogen receptors. The clomiphene was tolerated without any adverse events. A putative mechanism of action for clomiphene in the prevention of SUNCT will be presented. Conclusion Clomiphene citrate is a unique treatment for SUNCT and appears to be very safe and effective.