Functional Characteristics of the Nav1.1 p.Arg1596Cys Mutation Associated with Varying Severity of Epilepsy Phenotypes.

Mutations of the SCN1A gene, which encodes the voltage-dependent Na+ channel's α subunit, are associated with diverse epileptic syndromes ranging in severity, even intra-family, from febrile seizures to epileptic encephalopathy. The underlying cause of this variability is unknown, suggesting the involvement of additional factors. The aim of our study was to describe the properties of mutated channels and investigate genetic causes for clinical syndromes' variability in the family of five SCN1A gene p.Arg1596Cys mutation carriers. The analysis of additional genetic factors influencing SCN1A-associated phenotypes was conducted through exome sequencing (WES). To assess the impact of mutations, we used patch clamp analysis of mutated channels expressed in HEK cells and in vivo neural excitability studies (NESs). In cells expressing the mutant channel, sodium currents were reduced. NESs indicated increased excitability of peripheral motor neurons in mutation carriers. WES showed the absence of non-SCA1 pathogenic variants that could be causative of disease in the family. Variants of uncertain significance in three genes, as potential modifiers of the most severe phenotype, were identified. The p.Arg1596Cys substitution inhibits channel function, affecting steady-state inactivation kinetics. Its clinical manifestations involve not only epileptic symptoms but also increased excitability of peripheral motor fibers. The role of Nav1.1 in excitatory neurons cannot be ruled out as a significant factor of the clinical phenotype.

Accessory deep peroneal nerve - a clinically significant anomaly?

BACKGROUND AND PURPOSE: The accessory deep peroneal nerve (ADPN), a variant of the peroneal nerve, may give motor branches to the extensor digitorum brevis muscle (EDB) in 19-28% of the general population and in up to 78% of subjects in familial cases. The aim of our study was to evaluate its significance in the examination of the peroneal nerve. MATERIAL AND METHODS: Three groups of patients were analyzed. Group I consisted of 310 patients whose neurography recordings were analyzed retrospectively. Group II consisted of 24 healthy controls and group III consisted of 8 relatives of a healthy control having the ADPN detected. All patients underwent routine neurography of the peroneal nerve with muscular response recorded from the EDB. Groups II and III had additional stimulation behind the lateral malleolus. RESULTS: On routine neurography, ADPN was found in 7.7% of patients in group I and 12.5% in group II. Stimulation behind the lateral malleolus detected it in 25% of group II and in 50% of group III. The highest CMAP amplitude obtained by stimulation of the ADPN equalled 3.71 mV and was over half of the total EDB response. The presence of the ADPN significantly influences routine neurography of the peroneal nerve in 7.7-12.5% of patients. Stimulation behind the lateral malleolus detected it in 25% of group II and in 50% of the maternal line of the family in group III. In the familial case ADPN was present in 50% of maternally related subjects, reflecting autosomal dominant transmission. CONCLUSIONS: ADPN may innervate the greater part of the EDB and in cases of peroneal neuropathy may be important for preserving function of the muscle.

[F-wave amplitude in peripheral nervous system lesions]. / Amplituda fali F w uszkodzeniach obwodowego ukladu nerwowego.

BACKGROUND AND PURPOSE: F-wave is a late response recorded from muscle elicited by electric impulse conveyed antidromically to alpha-motor neurons of the spinal cord. F-wave latency and frequency are assessed in routine electroneurography providing information of conduction in the proximal segment of the nerves. F-wave amplitude is rarely analyzed, while it could add valuable information on excitability of motor neurons in different disease states. This study was conducted to determine whether F-wave amplitude is indicative of the level of the peripheral nervous system lesion. MATERIAL AND METHODS: EMG recordings of 204 consecutive patients suspected of peripheral nerves system lesion were retrospectively analyzed. Based on the clinical diagnosis three groups were defined: neuropathy (N=100), myopathy (N=33), ALS (N=18), reference (musculoskeletal pain syndromes: N=53). F-wave amplitude and F/CMAP-ratio (CMAP-compound motor action potential) and their relation to parameters of impulse conduction in motor nerve fibers was analyzed. RESULTS: Mean F/CMAP ratio was 11.1% in ALS, 5% in myopathy (p=0.008), 7.1% in neuropathies and 5.6% in the reference group. Giant F-wave (more than 10% of CMAP) was observed in 30% of nerves in ALS, 15% in neuropathy and 10% in myopathy (p=0.036). F-wave amplitude correlated significantly with CMAP amplitude in all groups, while F/CMAP ratio was inversely related to CMAP amplitude in ALS (r=-0.43, p<0.01) and neuropathy (r=-0.37, p<0.0001). F-wave frequency was similar in all groups and correlated with CMAP amplitude. CONCLUSIONS: F-wave amplitude is not indicative of the level of peripheral nervous system lesions. Giant F-wave is observed in neurogenic processes. It reflects an increase of motor unit size in the reinnervation process, but possibly also a change of excitability of motor neuron and its axon.