Rinshō shinkeigaku = Clinical neurology
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Using clinical information, it was investigated whether lesions in sporadic amyotrophic lateral sclerosis (sALS) spread contiguously from an onset site to the another regions in domino-like manner as hypothesized by prion-like propagation of pathogenic proteins. First, the data from medical records of 53 sALS patients with bulbar or lower limb onset showed that the symptom has noncontiguously spread from the bulbar region to the lower limbs or vice versa, skipping the upper limbs, in 18.9% of the patients. ⋯ The two parameters should be positively correlated, if the lesion propagates contiguously from an initially affected motoneuron to the neighbouring ones within the same motoneuron pool (local progression) and then propagates to the another motoneuron pools (regional spread). However, the statistically significant correlation was not found, suggesting that there may be the different mechanisms between local progression and regional spread of ALS lesions.
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While triptans, the 5-HT1B/1D agonists, are effective and generally well-tolerated in many patients up to one-third of migraine patients either may not respond well to triptans, may not tolerate their side effects, or may have contraindications that preclude their use. Recurrence, triptan-related side effects, and cardiovascular constriction effects are demerits for acute migraine treatment. CGRP receptor antagonists, the so-called gepants, were clearely designed and expected to be better than triptans. ⋯ A small number of patients taking olcegepant showed marked elevation in liver transaminase levels. It was decided to discontinue development of olcegepant. New CGRP receptor antagonists would be expected for acute migraine treatment.
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Cortical spreading depression (CSD) is a slowly propagated wave of depolarization of neurons and glial cells, followed by a subsequent sustained suppression of spontaneous neuronal activity. Functional imaging studies of migraine patients have shown dramatic changes in blood flow and brain activity whose characteristics are similar to those of CSD, implicated in migraine visual aura. Although the trigeminal nerve innervates the meninges and participates in the genesis of migraine headaches, triggering mechanisms remain controversial and poorly understood. ⋯ Additional molecular insight into the pathophysiology of migraine may come from other monogenic syndromes such as CADASIL, RVCL. Several genetic associations with candidate migraine genes like ESR1, MTHFR, and INSR, have been convincingly replicated. The genome-wide association studies may be a successful strategy toward identification of migraine susceptibility genes.