A. Polo

A somatic and germline mosaic mutation in MPZ/P0 mimics recessive inheritance of CMT1B

Objective: To identify the molecular basis of a demyelinating Charcot–Marie–Tooth disease type 1 (CMT1) with presumed autosomal recessive inheritance. Background: CMT1, an inherited motor and sensory neuropathy with low nerve conduction velocities, is caused by dominantly inherited mutations in the genes of the peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ/P0), and early growth response 2 transcription factor (EGR2/Krox-20). Patients and methods: Two young sisters born of clinically and electrophysiologically healthy parents had a severe CMT1 neuropathy of presumed autosomal recessive inheritance. The older sister underwent a nerve biopsy. The authors analyzed PMP22, MPZ/P0, and EGR2/Krox-20 by automated direct nucleotide sequencing. For rapid mutation detection, they determined the restriction-fragment-length polymorphisms for TaqI in the fluorescein-labeled target DNA sequence amplified by PCR. Results: Nerve biopsy disclosed a demyelinating and remyelinating neuropathy with onion bulb formations. Both sisters had a novel heterozygous G308→A transition of MPZ/P0 without any mutation of PMP22 or EGR2/Krox-20. The G308→A transition was a nonconservative mutation that changed a glycine into a glutamate at the amino acid residue 74 in the extracellular domain of the mature MPZ/P0. None of 50 healthy controls had the mutation. The healthy mother had a low amount of the mutation in blood (≅ 20%) as well as in skin, buccal epithelium, and hairs (30%). Because the healthy mother carried clones of somatic mutant cells and had transmitted the G308→A transition to the affected daughters, she also harbored germline mutant cells. Conclusion: In hereditary demyelinating neuropathies, somatic and germline mosaicism of dominant mutations in the myelin protein genes may mimic autosomal recessive inheritance.

Polyneuritis cranialis: clinical and electrophysiological findings.

A 13 year old boy, developed bilateral facial weakness, dysphonia and dysphagia acutely after a febrile illness. Neurological examination and MRI of the brain were normal. The CSF protein level increased. Blink reflex monitoring during clinical recovery was consistent with demyelination of the lower cranial nerves innervating the branchial arch musculature, a rare variant of Guillain-Barré syndrome.

LOWER-LIMB LENGTHENING IN SHORT STATURE: AN ELECTROPHYSIOLOGICAL AND CLINICAL ASSESSMENT OF PERIPHERAL NERVE FUNCTION

We assessed peripheral nerve function during and after lower-limb lengthening by callotasis in 14 patients with short stature, using motor conduction studies. Four patients with short stature of varying aetiology showed unilateral and one showed bilateral weakness of foot dorsiflexion. Both clinical and electrophysiological abnormalities consistent with involvement of the peroneal nerve were observed early after starting tibial callotasis. There was some progressive electrophysiological improvement despite continued bone distraction, but two patients with Turners syndrome had incomplete recovery. A greater percentage increase in tibial length did not correspond to a higher rate of peroneal nerve palsy. The function of the posterior leg muscles and the conduction velocity of the posterior tibial nerve were normal throughout the monitoring period. The F-wave response showed a longer latency at the end of the bone distraction than in basal conditions; this is probably related to the slowing of conduction throughout the entire length of the nerve.

Peripheral and segmental spinal abnormalities of median and ulnar somatosensory evoked potentials in Hirayama’s disease

Objectives: To investigate the origin of juvenile muscle atrophy of the upper limbs (Hirayama’s disease, a type of cervical myelopathy of unknown origin). Subjects: Eight male patients were studied; data from 10 normal men were used as control. Methods: Median and ulnar nerve somatosensory evoked potentials (SEP) were recorded. Brachial plexus potentials at Erb’s point (EP), dorsal horn responses (N13), and subcortical (P14) and cortical potentials (N20) were evaluated. Tibial nerve SEP and motor evoked potentials (MEP) were also recorded from scalp and spinal sites to assess posterior column and pyramidal tract conduction, respectively. Results: The most important SEP findings were: a very substantial attenuation of both the EP potentials and the N13 spinal responses; normal amplitude of the scalp N20; and normal latency of the individual peaks (EP-N9-N13-P14-N20). Although both nerves were involved, abnormalities in response to median nerve stimulation were more significant than those in response to ulnar nerve stimulation. There was little correlation between the degree of alterations observed and the clinical state. Latencies of both spinal and cortical potentials were normal following tibial nerve stimulation. The mean latency of cervical MEP and the central conduction time from the thenar eminence were slightly but significantly longer in patients than in controls. Conclusions: The findings support the hypothesis that this disease, which is clinically defined as a focal spinal muscle atrophy of the upper limb, may also involve the sensory system; if traumatic injury caused by stretching plays a role in the pathogenesis, the damage cannot be confined to the anterior horn of the spinal cord.

Neural generators of tibial nerve P30 somatosensory evoked potential studied in patients with a focal lesion of the cervicomedullary junction

The tibial nerve P30 potential was studied in 6 patients with focal lesions located in the vicinity of the cervicomedullary junction. P30 potential was unaffected while cortical P39 was abnormal in the patients with a supramedullary lesion affecting the somatosensory pathway just above its decussation. Conversely, P30 was abnormal in the presence of a lesion situated caudally to the cervicomedullary junction affecting the lower limb sensory fibers just below their decussation. Median nerve P14 behaved similarly to the P30 potential in these cases. These clinical observations suggest that P30 potential, as P14 of median nerve somatosensory evoked potentials, is generated in the lower brain stern probably before the decussation of the sensory fibers; nucleus gracilis and medial lemniscus fibers in the lower brain stem are probably the anatomical structures generating P30 potential. This suggests that P30 potential may be used to study intraspinal and intracranial conduction times separately in the afferent somatosensory pathways.

Retinal oscillatory potential abnormalities in patients with chronic renal failure, before and after dialytic treatment

Nineteen patients with chronic renal failure were studied, oscillatory potentials (OPs) being recorded shortly before and after dialytic treatment. Mean values of either onset latency (O1 latency) and duration of the complex (O1-N4 inter-peak latency) were found to be significantly longer in patients than in controls (p < 0.001). Most of the patients (12) showed a pathological prolongation of latency (>2.5 SD). Amplitude changes also affected OPs, but earlier components were reduced to a lesser degree than the later ones, as shown by statistical analysis. Moreover, seven patients showed an almost complete loss of O3 and O4 peaks. Latency changes may be transiently reversed by dialysis, suggesting a functional impairment of the retinal response; the loss of later components is a more persistent abnormality probably related with a structural damage.