Eur Neurol. 2002;47(2):99‐107 The 5‐HT(1B/1D/1F) agonist eletriptan, at an oral dose of 80 mg, has been shown to be more efficacious than sumatriptan 100 mg and placebo in the treatment of migraine attacks with or without aura. Another commonly prescribed oral treatment for migraine attacks is Cafergot (1 mg ergotamine tartrate with 100 mg caffeine per tablet). The efficacy, tolerability and safety of 40‐ and 80‐mg doses of eletriptan and 2 tablets of Cafergot were compared in a double‐blind, randomised, placebo‐controlled, parallel‐group trial involving 733 migraine patients. Patients recorded symptoms at baseline (before treatment) and 1, 2, 4 and 24 h after dosing. Headache intensity was assessed on a 4‐point scale (3  =  severe pain, 2  =  moderate pain, 1  =  mild pain, 0  =  no pain). Significantly more eletriptan‐treated patients (80 mg, 68%; 40 mg, 54%) than Cafergot‐treated patients (33%; p  <  0.001) reported headache response (improvement from moderate‐to‐severe to mild or no pain) at 2 h. Substantially more eletriptan recipients reported no pain (80 mg, 38%; 40 mg, 28%; Cafergot, 10%; placebo, 5%; p  <  0.001). Eletriptan headache response rates at 1 h were significantly higher (80 mg, 39%; 40 mg, 29%; Cafergot, 13%; placebo, 13%; p  <  0.002 for each comparison). Both doses of eletriptan were significantly more effective than Cafergot in reducing nausea (p  <  0.0001), photophobia (80 mg, p  <  0.0001; 40 mg, p  <  0.002), phonophobia (80 mg, p  <  0.0001; 40 mg, p  <  0.003) and functional impairment (p  <  or  =  0.001) at 2 h. Adverse events were generally mild or moderate and transient. This randomised trial shows that oral eletriptan is more efficacious in the acute treatment of migraine than oral Cafergot and is well tolerated. Comment: As with all comparative trials with eletriptan, this comparative trial raises the important issue of blinding. Was the Cafergot encapsulated (hence potentially hindering the early phase of absorbtion)? This approach has been a major issue with previous eletriptan studies and may potentially make the results from this trial difficult to interpret. DSM One key issue in ensuring methodologically rigorous comparative trials is symmetry of comparative groups. I have come to believe that the controversy over encapsulation for blinding is neither about the pharmacokinetics of encapsulation, nor about the effectiveness of eletriptan, but rather about the methodology of comparison, which requires as much symmetry as possible. As Gawel and Wiebe wrote in a superb article explaining how to critically evaluate a comparison trial, “When faced with a potential confounder … readers need to estimate in which direction the results would be biased” in any comparative trial (Gawel M, Wiebe S. Evidence‐based analysis of a migraine treatment drug comparison trial. Cephalalgia. 2000;20[suppl 2]:33‐38). SJT

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Background: Choreoacanthocytosis (CHAC) is a slowly progressive multisystem disorder with involuntary movements, cognitive decline, behavioral changes, seizures, and polyneuropathy caused by mutations in the VPS13A gene. Objective: To describe the early clinical features and possible genotype-phenotype correlation in CHAC. Design and Setting: Case series in a tertiary care center. Patients and Main Outcome Methods: Choreoacanthocytosis was diagnosed in 3 patients of Jewish origin from 3 unrelated families. We reviewed their medical histories and performed molecular analysis by screening all 73 exons of VPS13A. Results: Trichotillomania, hypertrophic cardiomyopathy, and idiopathic hyperCKemia, in 1 patient each, preceded the development of the full clinical spectrum of CHAC by 2 to 20 years. At diagnosis, 2 patients manifested signs of overt neuromuscular involvement and were homozygous for the 6059delC mutation, whereas 1 patient had only hyporeflexia and was homozygous for the EX23del mutation. Because only 1 of the 2 patients with 6059delC had cardiomyopathy, its relevance to CHAC is unclear. Conclusions: These findings extend the knowledge of significant early clinical heterogeneity in CHAC and suggest a possible genotype-phenotype correlation. Awareness of the early manifestations may prevent misdiagnosis and enable appropriate genetic counseling.

Summary: Rhesus and vervet monkeys respond differently to treatment with I -methyl-4-phenyl-I ,2,3,6-tetrahydropyridine hydrochloride neurotoxin (MPTP). Both species develop akinesia. rigidity, and severe postural instability. However, rhesus monkeys only develop infrequent. short episodes of highfrequency tremor. whereas vervet monkeys have many prolonged episodes of low-frequency tremor. After MPTP treatment. the spiking activity of many pallidal neurons became oscillatory and highly correlated. Oscillatory autocorrelation functions were dominated by lower frequencies, crosscorrelograms by higher frequencies. The phase shift distribution of the oscillatory cross-correlograms of pallidal cells in MPTP-treated vcrvet monkey were clustered around 0 phase shift. unlike the oscillatory correlograms in the MPTP-treated rhesus monkey, which were widely distributed between 0" and Low-frequency resting tremor is frequently reported as the initial symptom of idiopathic Parkinson's disease (PD). Most patients (70-100%) manifest rest tremor during the course of the disease.' The typical frequency is 4-5 Hz; however, in several patients with early-onset parkinsonism, higher frequencies have been observed.' Posturalhction tremor of smaller amplitude and higher (6-12 Hz) frequency may be seen in most parkinsonian patients.3,4Understanding of the basic mechanisms of PD was enhanced by the discovery of I -methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride neurotoxin (MPTP). ',6 In people, MPTP can produce all major parkinsonian symptoms, including typical parkinsonian rest tremor.'.' The experimental study of tremor in parkinsonism was further advanced by the introduction of the MPTP- treated primate as a reliable animal model for PD."-" However, most primates develop akinesiahradykinesia, flexed posture, and rigidity but usually fail to develop low-frequency Short episodes of highfrequency (10-16 Hz) tremor have been described in MPTP-treated rhesus monkeys, possibly corresponding to postural/action tremor of human parkinsonian patients. In contrast, vervet (African green) monkeys develop prolonged episodes of low-frequency (4-6 Hz) tremor. 13. '4 This article summarizes the authors' electrophysiologic studies on the globus pallidus of MPTP-treated rhesus and vervet monkeys. These studies indicate that transient synchronization of neural activity is the hallmark of the spiking activity of neurons in the pallidum of MPTP-treated monkeys. If the tremor phenomenon is caused by these neural events, transient episodes of tremor coherency between different muscle groups or body segments should be observed. Testing for such episodes of synchronization of tremor was performed between different extremities of MPTP-treated monkeys and human parkinsonian patients.

Summary. Recent evidence points to involvement of central nervous system oscillators in Parkinson's disease (PD) rest tremor. It remains unknown whether one or multiple oscillators cause tremor in multiple limbs. Based on the prediction that multiple oscillators would cause low coherence even with similar average frequency, we studied 22 PD patients using accelerometers on multiple limbs. Records were digitized and spectral analysis was performed. Peak frequencies in the arms, legs, and chin were similar, indicating that biomechanical factors did not determine the frequency. Coherence between different axes of individual accelerometers and between different segments of the same limb was high. However, coherence between tremor in different limbs was low. There was no consistent pattern across patients of ipsi-vs. contralateral predominance of coherence. These data suggest that tremor in PD is generated by multiple oscillatory circuits, which operate on similar frequencies.