T.J. Steiner

Lamotrigine versus Placebo in the Prophylaxis of Migraine with and without Aura

Lamotrigine blocks voltage-sensitive sodium channels, leading to inhibition of neuronal release of glutamate. Release of glutamate may be essential in the propagation of spreading cortical depression, which some believe is central to the genesis of migraine attacks. This study compared safety and efficacy of lamotrigine and placebo in migraine prophylaxis in a double-blind randomized parallel-groups trial. A total of 110 patients entered; after a 1-month placebo run-in period, placebo-responders and non-compliers were excluded, leaving 77 to be treated with lamotrigine (n=37) or placebo (n=40) for up to 3 months. Initially lamotrigine therapy was commenced at the full dose of 200 mg/day, but, following a high incidence of skin rashes, a slow dose-escalation was introduced: 25 mg/day for 2 weeks, 50 mg/day for 2 weeks, then 200 mg/day. Attack rates were reduced from baseline means of 3.6 per month on lamotrigine and 4.4 on placebo to 3.2 and 3.0 respectively during the last month of treatment. Improvements were greater on placebo and these changes, not statistically significant, indicate that lamotrigine is ineffective for migraine prophylaxis. There were more adverse events on lamotrigine than on placebo, most commonly rash. With slow dose-escalation their frequency was reduced and the rate of withdrawal for adverse events was similar in both treatment groups.

Noncompliance May Render Migraine Prophylaxis Useless, But Once-Daily Regimens Are Better

Medicines work better if taken, which must be true of migraine prophylaxis. There is evidence that compliance with regular medication can be badly deficient. To assess how serious the problem might be in routine migraine management, we undertook a covert observational 2-month survey in a specialist headache clinic using objective measures of compliance. Subjects were 38 patients needing prophylaxis with medication prescribed once (od), twice (bd), or three times daily (tds). Medication was dispensed, unknown to them, in Medication Event Monitoring Systems (MEMS) to record openings in real time. Number, timing, and pattern of actual openings were compared with what was expected. Compliance rates averaged 66%, although returned pill counts indicated 91%. A substantial and significant difference was shown between od and bd or tds regimens. Measures of dosing interval—used-on-schedule rate and therapeutic coverage—averaged between 44% and 71%. Once-daily treatment was associated with a used-on-schedule rate more than double those of multiple daily dosing, but still only 66%. We conclude that routine use of drug prophylaxis in migraine may be so seriously undermined by poor compliance that it has little chance of efficacy. Returned-pill counting is inadequate for compliance assessment.

Double-Blind Randomized Placebo-Controlled Study of Homoeopathic Prophylaxis of Migraine

Homoeopathic remedies for migrane are widely available over the counter, statutorily offered by the national health service in the UK, and apparently popular with patients. Do they work? Sixty-three outpatients with migraine with or without aura b IHS criteria entered a 4-month randomized placebo-controlled, double-blind, parallel-groups trial of individualized homoeopathic prophylaxis, the first month being baseline with all patients on placebo. Three patients (4.8%) dropped out, leaving 30 in each treatment group. There were chance differences in attack frequency and severity between the groups at baseline (attacks were more frequent but less severe in the placebo group). Both groups improved on therapy but neither to a great extent on the primary outcome measure of attack frequency (verum: —19%; placebo: -16%). Reduction was mostly in mild attacks on placebo, more in moderate and severe attacks on homoeopathy. Few adverse events were reported. Overall, there was no significant benefit over placebo of homoeopathic treatment. The course of change differed between groups, and suggested that improvement reversed in the last month of treatment on placebo. On this evidence we cannot recommend homoeopathy for migraine prophylaxis, but cannot conclude that it is without effect.

A comparison of the distributions of eight peptides in spinal cord from normal controls and cases of motor neurone disease with special reference to Onuf's nucleus

The distributions of 8 peptides were studied in the 4 major segmental levels (cervical, thoracic, lumbar, sacral) of the spinal cord in 52 neurologically normal cases. Similar regions from 36 cases of motor neurone disease (MND) were compared using the same procedures to determine possible changes in the distribution of peptides in areas associated with sensory, motor and autonomic function. In normal spinal cords, calcitonin gene-related peptide (CGRP)-, the C-flanking peptide of neuropeptide Y (CPON)-, enkephalin-, galanin-, neurokinin-like-, somatostatin- and vasoactive intestinal polypeptide (VIP)-immunoreactive fibres were abundant in the dorsal horn. Numerous somatostatin-immunoreactive cell bodies were also present. In the ventral horn, immunoreactive fibres were less abundant. Most motoneurones were closely apposed by fibres immunoreactive for enkephalin, neurokinin, somatostatin and thyrotrophin-releasing hormone (TRH). A subpopulation of motoneurones, most notable in lumbar segments, displayed CGRP immunoreactivity. In common with autonomic nuclei, Onufs nucleus, which is thought to innervate perineal striated muscle and external urethral and anal sphincters, was densely innervated with CPON-, enkephalin-, and in particular somatostatin-immunoreactive fibres, thus suggesting Onufs nucleus may have an autonomic component. In the diseased cords, there was a reduction in the area of the ventral horn and numbers of motoneurones as revealed by conventional histological staining and immunostaining of neurofilament triplet proteins. No changes in the distribution of peptides was noted in the dorsal horn or autonomic nuclei. By contrast, in the ventral horn, neurokinin-, enkephalin-, somatostatin- and TRH-immunoreactive fibres, which are normally found associated with motoneurones, were absent. Therefore, not only are motoneurones lost in MND, but also the fibres which innervate them. CGRP-immunoreactive motoneurones were not observed, a finding consistent with the proposed role of this peptide as a muscle-trophic factor. In contrast to the large motoneurone groups in the ventral horn, the neuronal integrity of Onufs nucleus and the peptides associated with it were spared. These data further imply that Onufs nucleus is not a typical motor nucleus and it is not purely somatic. The coincident loss of peptide immunoreactivity and motoneurones from the large motor nuclei and sparing of Onufs nucleus and its peptide-containing constituents in the diseased state suggests that peptides contribute to maintenance of neural integrity.

Head Movement Correlates of Juncture and Stress at Sentence Level

Body movement during speech has been recognized as closely relating to suprasegmental features, but little evidence has been offered to support this thesis, probably for lack of adequate techniques. The present study investigated this issue by continuously recording, with a polarized-light goniometer, movement of the head in four subjects engaged in conversation. Rapid movements were found to indicate stress, while juncture involved contrasting ordinary movements with stillness. This was believed to indicate that the dissipative structure coordinating speech resorts to body movement in regulating high energies, and that prosodic features may accentuate inner continuity by varying smoothly towards terminal juncture.

Kinematics of head movements accompanying speech during conversation

Abstract Head movement during conversation is closely related to the suprasegmental features of concurrent speech. Study of this relationship builds heavily on speed-related parameters of movement, the kinematic description of which is made here. In 4 subjects, movement of the head monitored by polarised-light goniometer was continuously recorded, together with the associated speech and a signal proportional to the peak loudness of speech. Results revealed a division of head movements into five kinematic classes: recognition of these may be helpful in understanding the role of head movements during speech.

Neurological morbidity of arch and carotid arteriography in cerebrovascular disease. The influence of contrast medium and radiologist.

A prospective study of 230 arch and carotid arteriograms in 229 patients with symptomatic cerebrovascular disease revealed that neurological morbidity was not significantly affected by patient age, nature of neurological symptoms, duration of procedure, volume of contrast medium or degree of arterial stenosis. The total neurological morbidity of 132 examinations carried out with non-ionic contrast medium (iohexol) was slightly lower than that of 98 examinations carried out with ionic contrast medium (meglumine and sodium iothalamate) but the difference was not statistically significant. However, the morbidity of 185 examinations performed by an experienced vascular radiologist was significantly lower (p less than 0.025) than the morbidity of 45 examinations performed by a series of radiologists in training and the mean time required for the procedure was 18 min longer in the latter group (p less than 0.001). These findings suggest that the neurological morbidity of arch and carotid arteriography in patients with cerebrovascular disease depends largely upon catheter technique and will not be significantly reduced by the use of non-ionic contrast medium.

Chocolate is a Migraine-Provoking Agent

Patients with migraine who believed that chocolate could provoke their attacks were challenged with either chocolate or a closely matching placebo. In a double-blind parallel group study, chocolate ingestion was followed by a typical migraine episode in 5 out of 12 patients, while none of the 8 patients challenged with placebo had an attack (p = 0.051). The median time to the onset of the attack was 22 h. This brief study provides some objective evidence that chocolate is able to provoke a migraine attack in certain patients who believe themselves sensitive to it.

Contribution of Diaschisis to the Clinical Deficit in Human Cerebral Infarction

BACKGROUND AND PURPOSE Regions of decreased cerebral blood flow are often seen on single-photon emission computed tomography (SPECT) after stroke and have been widely reported to add to the clinical deficit. However, such reports have not distinguished between correlation and causation. We analyzed 124 serial SPECT scans performed in 50 patients to assess the role of diaschisis in the clinical deficit after stroke. METHODS SPECT with the use of 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) was performed in a prospective, unselected series of 50 patients with cerebral infarcts studied at a median of 1.1, 6.8, and 95 days after ictus. Patients were also assessed with the use of the Canadian Neurological Scale, the Barthel Index, a neuropsychological evaluation, and infarct volume measurement. RESULTS One hundred twenty-four serial SPECT scans were done in 50 patients. Diaschisis was identified at 168 sites. There was insufficient correlation between diaschisis and the clinical measurements to support the suggestion that diaschisis independently causes clinical deficits beyond those due to the infarct itself. Unlike the clinical status, diaschisis showed little tendency to resolve during the 3-month follow-up period of the study. Several of the instances of correlation were shown to be of a noncausal kind, with both the diaschisis and the clinical deficit being due to the lesion directly; there was no known mechanism for the diaschisis to cause the clinical deficit. CONCLUSIONS Diaschisis does not independently add to the clinical deficit after stroke. It is more likely that it simply represents part of the damage done by the stroke.

Metoprolol in the Prophylaxis of Migraine: Parallel‐Groups Comparison withPlacebo and Dose‐Ranging Follow‐Up

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