Nicola J. Giffin

Premonitory symptoms in migraine An electronic diary study

Background: Migraine is frequently associated with nonheadache symptoms before, during, and after the headache. Premonitory symptoms occurring before the attack have not been rigorously studied. Should these symptoms accurately predict headache, there are considerable implications for the pathophysiology and management of migraine. Methods: Electronic diaries were used in a 3-month multicenter study to record nonheadache symptoms before, during, and after migraine. The authors recruited subjects who reported nonheadache symptoms in at least two of three attacks that they believed predicted headache. Symptoms were entered in the diaries by patient initiation and through prompted entries at random times daily. Entries could not be altered retrospectively. Data recorded included nonheadache symptoms occurring during all three phases of the migraine, prediction of the attack from premonitory symptoms, general state of health, and action taken to prevent the headache. Results: One hundred twenty patients were recruited: 97 provided usable data. Patients correctly predicted migraine headaches from 72% of diary entries with premonitory symptoms. A range of cognitive and physical symptoms was reported at a similar rate through all three phases of the migraine. The most common premonitory symptoms were feeling tired and weary (72% of attacks with warning features), having difficulty concentrating (51%), and a stiff neck (50%). Subjects who functioned poorly in the premonitory phase were the most likely to correctly predict headache. Conclusions: Using an electronic diary system, the authors show that migraineurs who report premonitory symptoms can accurately predict the full-blown headache.

A randomized controlled trial of intranasal ketamine in migraine with prolonged aura

Objective: The aim of our study was to test the hypothesis that ketamine would affect aura in a randomized controlled double-blind trial, and thus to provide direct evidence for the role of glutamatergic transmission in human aura. Methods: We performed a double-blinded, randomized parallel-group controlled study investigating the effect of 25 mg intranasal ketamine on migraine with prolonged aura in 30 migraineurs using 2 mg intranasal midazolam as an active control. Each subject recorded data from 3 episodes of migraine. Results: Eighteen subjects completed the study. Ketamine reduced the severity (p = 0.032) but not duration of aura in this group, whereas midazolam had no effect. Conclusions: These data provide translational evidence for the potential importance of glutamatergic mechanisms in migraine aura and offer a pharmacologic parallel between animal experimental work on cortical spreading depression and the clinical problem. Classification of evidence: This study provides Class III evidence that intranasal ketamine is effective in reducing aura severity in patients with migraine with prolonged aura.

The electrophysiology of migraine.

&NA; Migraine is currently regarded as a neurovascular disorder of trigeminal sensory processing, generated centrally, probably at the level of the brainstem. In the past, electrophysiological techniques have drawn no definite conclusions on either interictal or ictal changes in migraineurs compared with controls, largely because of methodological differences. Recently, two findings have been shown consistently: an interictal increasing lack of habituation of evoked potentials with a normalization at the start of the attack and strong intensity dependence of auditory evoked potentials. These findings substantiate migraine sufferers as having an abnormal trait interictally, with the attack characterized by a change in the state of central processing. Exploitation of these differences may be a useful tool to study the mechanism of action of drugs used for the treatment of migraine. Curr Opin Neurol 15:303‐309.

Imaging patients with suspected brain tumour: guidance for primary care.

The number of referrals by primary care practitioners to secondary care neurology services, particularly for headache, may be difficult to justify. Access to imaging by primary care practitioners could avoid referral without compromising patient outcomes, but the decision to refer is based on a number of complex factors. Due to the paucity of rigorous evidence in this area, available data are combined with expert opinion to offer support for GPs. The study suggests management for three levels of risk of tumour: red flags>1%; orange flags 0.1-1%; and yellow flags<0.1% but above the background population rate of 0.01%. Clinical presentations are stratified into these three groups. Important secondary causes of headache where imaging is normal should not be overlooked, and normal investigation does not eliminate the need for follow-up or appropriate management of headache.

The migraine postdrome: An electronic diary study.

Objective: To report migraine postdrome symptoms in patients who report nonheadache symptoms as part of their attacks. Methods: A prospective daily electronic diary study was conducted over 3 months in 120 patients with migraine. Nonheadache symptoms before, during, and after headache were collected on a daily basis. Visual analogue scales were used to capture the overall level of functioning and the severity of the headache. The postdrome was defined as the time from resolution of troublesome headache to return to normal. Results: Of 120 evaluable patients, 97 (81%) reported at least one nonheadache symptom in the postdrome. Postdrome symptoms, in order of frequency, included feeling tired/weary and having difficulty concentrating and stiff neck. Many patients also reported a mild residual head discomfort. In most attacks (93%), there was return to normal within 24 hours after spontaneous pain resolved. There was no relationship between medication taken for the headache and the duration of the postdrome. The severity of the migraine was not associated with the duration of the postdrome. Overall state of health scores remained low during the postdrome. Conclusion: Nonheadache symptoms in the postdrome were common and may contribute to the distress and disability in the patients studied. Postdrome symptoms merit larger observational studies and careful recording in clinical trials of acute and preventive migraine treatments.

The dynamic regulation of cortical excitability is altered in episodic ataxia type 2.

Episodic ataxia type 2 and familial hemiplegic migraine are two rare hereditary disorders that are linked to dysfunctional ion channels and are characterized clinically by paroxysmal neurological symptoms. Impaired regulation of cerebral excitability is thought to play a role in the occurrence of these paroxysms, but the underlying mechanisms are poorly understood. Normal ion channels are crucial for coordinating neuronal firing in response to facilitatory input. Thus, we hypothesized that channel dysfunction in episodic ataxia type 2 and familial hemiplegic migraine may impair the ability to adjust cerebral excitability after facilitatory events. We tested this hypothesis in patients with episodic ataxia type 2 (n = 6), patients with familial hemiplegic migraine (n = 7) and healthy controls (n = 13). All subjects received a high-frequency burst (10 pulses at 20 Hz) of transcranial magnetic stimulation to transiently increase the excitability of the motor cortex. Acute burst-induced excitability changes were probed at 50, 250, 500 and 1000 ms after the end of the burst. This was done using single-pulse transcranial magnetic stimulation to assess corticospinal excitability, and paired-pulse transcranial magnetic stimulation at an interstimulus interval of 2 and 10 ms to assess intracortical inhibition and facilitation, respectively. The time course of burst-induced excitability changes differed between groups. Healthy controls showed a short-lived increase in excitability that was only present 50 ms after the burst. In contrast, patients with episodic ataxia type 2 showed an abnormally prolonged increase in corticospinal excitability that was still present 250 ms after the transcranial magnetic stimulation burst. Furthermore, while controls showed a decrease in intracortical facilitation during the 1 s period following the transcranial magnetic stimulation burst, patients with episodic ataxia type 2 had increased intracortical facilitation 1000 ms after the burst. Intracortical inhibition was unaltered between groups. Patients with familial hemiplegic migraine were not significantly different from either controls or patients with episodic ataxia type 2. Together, these findings indicate that patients with episodic ataxia type 2 have an excessive increase in motor cortex excitability following a strong facilitatory input. We argue that this deficient control of cortical excitability may set the stage for the emergence of paroxysmal neural dysfunction in this disorder.

Mesothelioma and anti-Ma paraneoplastic syndrome; heterogeneity in immunogenic tumours increases

We present a patient with opsoclonus and diffuse cerebellar signs who had an anti-Ma2 antibody-associated paraneoplastic syndrome secondary to a sarcomatoid mesothelioma. This case highlights the importance of early tumour detection, instigation of therapeutic measures, and the heterogeneity of underlying malignancies in neurological paraneoplastic syndromes.

Post market pilot programme with single pulse transcranial magnetic stimulation (sTMS) for acute treatment of migraine: SpringTMS™ use in migraine

Some patients suffer disabling, frequent migraine without effective treatment as current pharmacological options are either contra-indicated, poorly tolerated or overused. A post market pilot programme with the sTMS device was initiated for patients with migraine.

Surfing for headache.

Web sites for headache vary tremendously in their usefulness to physician and patient. There are those set up by national and international organisations aimed at the clinician and concerned with the structure and organisation of the relevant organisation and management issues. These include the site for the British Association for the Study of Headache (BASH) (http://www.bash.org.uk/), the most useful section of which is probably the British migraine management guidelines. The US equivalent, the site of the American Headache Society (http://www.ahsnet.org/), is more comprehensive with links to useful topics on migraine management. The International Headache Society site (http://www.i-h-s.org/) is aimed particularly at those in clinical headache research with guidelines for drug trials and notice of meetings, but does have some sections of practical …

Handbook of Headache, Second Edition

A good textbook on headache is noticeable by its absence in most neurologists bookcases. It would be a rare neurologist who did not occasionally confess to being stumped by a patient with unusual or intractable headaches.A user-friendly handbook of headache on the shelf may make the pursuit of treatment options for these suffering patients a more attractive proposition. This book gives a wonderful, upto-date and accurate account of headaches and their management. All sections from chronic daily headache to headache and pregnancy are given appropriate space and consideration. The section on cluster headache gives a succinct resumé of research into hypothalamic dysfunction and the treatment of cluster with topiramate. The pathophysiology of migraine is described as best as it could be in such a small book. But unfortunately despite excellent intentions this Handbook of Headache may not quite fill the bill for the user-friendly one that neurologists should have at their fingertips. The authors have attempted to squash a textbook into a small paperback: the result is a textbook, a very informative one at that, in very small print. For a ‘handbook’ the text is too wordy and over-referenced. A structure with more bullet points and subheadings would be more readable and encourage a baffled clinician to quickly dip in and out e. g. the features of carotid artery dissection, including useful figures such as 50 % of patients having a Horner’s syndrome and 45 % of patients having a bruit, would be far mare easy to digest in bullet point form. Similarly, there are some excellent tables of data, e. g. comparison of migraine prophylactics, but there could be more. In the post-lumber puncture headache section, I learnt that it takes 43 seconds to read the CSF pressure through a 20 g needle but 225 seconds with a 22 g needle, but this and other useful comparison data between needle types would be better presented as a table rather than in prose. I particularly enjoyed playing ‘what’s my headache’ in the section on case studies (a great resource for those of us involved in headache teaching). In the section on ‘patient resources and educational material’ I learnt that Ben and Jerry’s No Fat Coffee Fudge Frozen Yogurt contains almost three times as much caffeine as Haagen-Dazs Coffee Fudge Ice Creem and that a brewed cup of coffee contains more than three times as much caffeine as a 12oz coca-cola: I was left unsure as to the relevance of these gems. The book is best suited to American readers with American drug names and a medicolegal section, which perhaps should be heeded to even on this side of the Atlantic. This section gave me a fascinating, if alarming, insight into American practice: for example if a neurologist recommends a scan but the patient is unable to pay for one, it advises neurologists to document ‘informed refusal’ as the patient may later go to an attorney telling them you did not arrange a scan, even though they could not pay for one. This is an excellent little book, certainly the best that I have seen on the market, containing a comprehensive and accurate account of current headache pathophysiology, diagnosis and management.