Increased severity over generations of Charcot-Marie-Tooth disease type 1A.

BACKGROUND: Charcot-Marie-Tooth type 1A (CMT1A) is an autosomal dominant polyneuropathy due to a 1.5 Mb tandem duplication in chromosome 17p11.2, containing the PMP22 gene. This mutation is not modified during inheritance. OBJECTIVES: We set forth to test the hypothesis that in a subgroup of CMT1A patients there is clinical anticipation, namely an increase in disease severity over generations. METHODS: Thirty-nine CMT1A mutation-positive patients in 16 families and 23 parent-offspring pairs were evaluated. This included 14 families with 2 generations and 2 families with 3 generations. Age of presentation was assessed by interviewing the patients and clinical severity was measured using the CMT neuropathy score (CMTNS). RESULTS: In 21/23 parent-child pairs and 14/16 families, there was an earlier age of presentation in children of genetically affected parents. The mean age of onset in the progeny was 12.61 years compared to 41.22 years in the parent generation, (p < 0.001). Mean severity in the younger generation was slightly higher than that of the parent generation. When corrected for the age difference, the trend for a worse phenotype in the younger generation became statistically significant (p < 0.02,Wilcoxon signed rank test). CONCLUSIONS: Our findings suggest that in a subgroup of CMT1A patients there is an increase in clinical severity over generations. The mechanism responsible for this observation remains unknown. Our findings should be validated on a larger cohort of CMT1A families.

The palmomental reflex predicts earlier corticobulbar involvement in ALS.

OBJECTIVE: The palmomental reflex (PMR) is a primitive reflex, which may appear when cortical inhibitory pathways are disrupted by disease. In this study, we examined whether the PMR is associated with corticobulbar involvement in people with ALS (PALS). METHODS: PMR was routinely tested for each patient attending the ALS clinic. Three hundred and eighteen consecutive PALS were included, of whom 271 were PMR positive (PMR+). Clinical evaluation defined the presence of upper motor neuron (UMN) and lower motor neuron (LMN) signs in the bulbar, cervical and lumbosacral segments. RESULTS: The PMR + group had a higher rate of both UMN and LMN bulbar involvement (BI) as well as more UMN upper-limb involvement and UMN involvement of any type, the strongest association being between PMR + and UMN BI. In patients without BI at presentation, UMN BI developed roughly 15 months early in the PMR + group compared to the PMR- group. CONCLUSION: We found that the PMR is strongly associated with UMN signs within the bulbar region and to a lesser extent with upper-limb UMN involvement. We propose the PMR be considered a harbinger of corticobulbar involvement in PALS.

Effect of neck flexion on somatosensory and motor evoked potentials in Hirayama disease.

UNLABELLED: Hirayama disease (HD) is a rare motor disorder mainly affecting young men, characterized by atrophy and weakness of forearm and hand muscles corresponding to a C7-T1 myotome distribution. The weakness is usually unilateral or asymmetric and progression usually stops within several years. The etiology of HD is not well understood. One hypothesis, mainly based on MRI findings, is that the weakness is a consequence of cervical flexion myelopathy. The aim of this study was to explore the function of corticospinal and ascending somatosensory pathways during neck flexion using evoked responses. MATERIALS AND METHODS: 15 men with HD and 7 age-matched control male subjects underwent somatosensory evoked potentials (SSEP) and motor evoked potentials (MEP) studies with the neck in neutral position and fully flexed. SSEP studies included electrical stimulation of median and ulnar nerves at the wrist, and tibial nerve at the ankle with recording over the ipsilateral Erb's point, cervical spine, and contralateral sensory cortex. MEP recordings were obtained by magnetic stimulation of the motor cortex and the cervical lower spinal roots; the evoked responses were recorded from the contralateral thenar and abductor hallucis muscles. RESULTS: MEP recordings demonstrated significant lower amplitudes, and slightly prolonged latencies in HD patients on cervical stimulation, compared to control subjects. During neck flexion, MEP studies also demonstrated a statistically significant drop in mean upper limb amplitude on cervical stimulation in HD patients, as well as in control subjects, although to a lesser degree. In contrast, no significant differences were found in SSEP studies in HD patients compared to control subjects, or between neutral and flexed position in these groups. CONCLUSION: The study shows a negative effect of cervical flexion on MEP amplitudes in HD patients as well as in control subjects, requiring more studies to investigate its significance. Neck flexion did not have an influence on any SSEP parameters in patients or controls.