Focal EEG slowing and chorea: electroclinical clues to the diagnosis of anti-NMDAR encephalitis.

Variations in clinical presentation can lead to delays in the diagnosis and initiation of treatment of anti-N-methyl-D-aspartate receptor encephalitis. Most patients have an EEG study performed early in the course of their illness. Although not specific, there may be clues in the electroclinical features that should alert clinicians and electroencephalographers to the possibility of this diagnosis. This case is a reminder that anti- anti-N-methyl-D-aspartate receptor encephalitis may present initially with a movement disorder as the sole symptom, without features of an encephalopathy. In addition, it adds to the growing body of evidence that recognition of certain electroclinical clues may shorten the time to diagnosis. [Published with video sequence].

Focal reading epilepsy--a rare variant of reading epilepsy: a case report.

Reading epilepsy is a distinct form of epilepsy in which all or almost all seizures are precipitated by reading. Seizures typically show orofacial or jaw myoclonus. Nevertheless, reading epilepsy is not homogenous and its classification is unclear. We report a patient with reading-induced prolonged left temporal seizures, presenting clinically as dyslexia.

Haplotype and linkage disequilibrium analysis to characterise a region in the calcium channel gene CACNA1A associated with idiopathic generalised epilepsy.

Idiopathic generalised epilepsy (IGE) is a common form of epilepsy, including several defined and overlapping syndromes, and likely to be due to the combined actions of mutations in several genes. In a recent study we investigated the calcium channel gene CACNA1A for involvement in IGE, unselected for syndrome, by means of association studies using several polymorphisms within the gene. We reported a highly significant case/control association with a silent single nucleotide polymorphism (SNP) in exon 8 that we confirmed by within-family analyses. In this present study we screened the gene for novel SNPs within 25 kb of exon 8, which have enabled us to define the critical region of CACNA1A in predisposing to IGE. Several intronic SNPs were identified and three, within 1.5 kb of exon 8 and in strong linkage disequilibrium with each other and with the original SNP, were significantly associated with IGE (P=0.00029, P=0.0015 and P=0.010). The associations were not limited to an IGE syndrome or other subgroup. Another SNP, 25 kb away, in intron 6 was also significantly associated with IGE (P=0.0057) but is not in linkage disequilibrium with the SNPs around exon 8. Haplotype predictions revealed even more significant associations (3-marker haplotype: P<10(-6)). Logistic regression showed that all the data can be explained by two of the SNPs, which is consistent with two functionally significant variants being responsible for all five associations, although a single variant cannot be excluded. The functionally significant variant(s) are unlikely to be exonic and suggests an effect on expression or alternative splicing.

Optimising the detection of upper motor neuron function dysfunction in amyotrophic lateral sclerosis--a transcranial magnetic stimulation study.

Evidence of upper motor neuron (UMN) dysfunction is essential in making the diagnosis of amyotrophic lateral sclerosis (ALS). Central motor conduction (CMC) abnormalities detected using transcranial magnetic stimulation (TMS) are presumed to reflect UMN dysfunction. CMC is, however, often normal in patients with classical sporadic ALS. The aim of the study was to determine whether the utility of the CMC measure in ALS could be enhanced. We measured CMC to four pairs of muscles (abductor digiti minimi (ADM), biceps, vastus medialis (VM) and abductor hallucis (AH) in 20 controls and 25 ALS patients. The commonest abnormality detected in the ALS patients was an absent MEP, found in 11 patients (44 %) and in 25 of 200 muscles examined. Studying a minimum of three muscles increased the probability of detecting UMN dysfunction. Weakness in the muscle as well as selecting a distal rather than a proximal muscle was significantly associated with an abnormal CMC. Interside differences in CMC were significantly more pronounced in the patient group. In 30% of patients a significant interside difference in AH CMC time was the sole abnormality, suggesting mild UMN dysfunction on the side with the longer CMC.

A novel central motor conduction abnormality in D90A-homozygous patients with amyotrophic lateral sclerosis.

Patients with amyotrophic lateral sclerosis (ALS) who are homozygous for the D90A SOD1 mutation have been noted to have central motor abnormalities distinct from those of patients with idiopathic ALS. We stimulated the motor cortex of ten patients homozygous for the D90A SOD1 mutation, using transcranial magnetic stimulation (TMS), and recorded the response evoked in the right first dorsal interosseous muscle when the muscle was at rest and when voluntarily active. A subgroup of patients had two distinct evoked responses when the cortex was stimulated at high intensity with the muscle at rest. When the muscle was modestly contracted, the first of these responses disappeared, whereas the second response was facilitated. Both fast and slow components of the corticospinal tract were usually intact and excited by TMS in these patients. We propose that there is an abnormality of intracortical or intraspinal inhibition in a subgroup of D90A SOD1 ALS patients, which suppresses fast-conducted activity when the muscle is active. Apart from further defining the phenotype of familial ALS, these findings may have importance in understanding the pathogenesis of central motor abnormalities in these patients.