Markedly reduced axonal potassium channel expression in human sporadic amyotrophic lateral sclerosis: an immunohistochemical study.

Fasciculations are characteristic features of amyotrophic lateral sclerosis (ALS), suggesting abnormally increased excitability of motor axons. Previous nerve excitability studies have shown reduced axonal potassium currents in ALS patients that may contribute to the hyperexcitability and thereby generation of fasciculations. To clarify changes in axonal ion channel expression in motor axons of ALS, we performed immunohistochemistry of potassium and sodium channels in the C7 and L5 ventral/dorsal roots obtained from five autopsy cases of sporadic ALS.

Changes in Na(+) channel expression and nodal persistent Na(+) currents associated with peripheral nerve regeneration in mice.

Patients with peripheral neuropathy frequently suffer from positive sensory (pain and paresthesias) and motor (muscle cramping) symptoms even in the recovery phase of the disease. To investigate the pathophysiology of increased axonal excitability in peripheral nerve regeneration, we assessed the temporal and spatial expression of voltage-gated Na(+) channels as well as nodal persistent Na(+) currents in a mouse model of Wallerian degeneration. Crushed sciatic nerves of 8-week-old C57/BL6J male mice underwent complete Wallerian degeneration at 1 week.

Changes in excitability properties associated with axonal regeneration in human neuropathy and mouse Wallerian degeneration.

Objective: The aim of this study was to investigate changes in excitability properties associated with axonal regeneration in human neuropathy and a mouse Wallerian degeneration model.

Methods: Threshold tracking was used to measure axonal excitability indices such as strength-duration time constant (SDTC), threshold electrotonus, supernormality in median motor axons at the wrist of 13 patients with vasculitic neuropathy in their recovery phase, and in tibial motor axons at the ankle of mice with sciatic nerve crush. In the mouse model, excitability testing was performed 4, 8, 12, and 20weeks after the nerve crush.

Genetically confirmed Huntington's disease masquerading as motor neuron disease.

We describe a patient with Huntington's disease (HD) who showed asymmetrical upper limb amyotrophy as a main manifestation. Chorea and psychiatric symptoms were not prominent. Electromyography revealed generalized active and chronic denervation and fasciculations.

Anti-GQ1b antibody does not affect neuromuscular transmission in human limb muscle.

Anti-ganglioside GQ1b antibody induces neuromuscular blocking on mouse phrenic nerve-diaphragm preparations. Several reports suggest that patients with this antibody show abnormal neuromuscular transmission in the facial or limb muscles, but limb muscle weakness is unusual in Miller Fisher syndrome that is often associated with anti-GQ1b antibody. To determine whether anti-GQ1b sera affect neuromuscular transmission in human limb muscles, axonal-stimulating single fiber electromyography was performed in the forearm muscle of seven patients with anti-GQ1b antibody.

Is excitation-contraction coupling impaired in myasthenia gravis?

Objective: To investigate whether excitation-contraction (E-C) coupling of muscle is impaired in patients with myasthenia gravis (MG).

Methods: In 51 patients with generalized MG and 35 normal subjects, compound muscle action potentials (CMAPs) of the abductor pollicis brevis, and movement-related potentials using an accelerometer placed at the thumb tip were simultaneously recorded after median nerve stimulation at the wrist. The E-C coupling time (ECCT) was estimated by a latency difference between CMAP and movement-related potential.

Time course of axonal regeneration in acute motor axonal neuropathy.

Patients with acute motor axonal neuropathy (AMAN) generally recover well. We reviewed clinical and electrophysiologic recovery in 13 patients for up to 5 years. Twelve patients showed rapid recovery over 12 months, whereas in the remaining one the recovery was slow and incomplete at 5 years.

The effects of physiological fluctuation of serum potassium levels on excitability properties in healthy human motor axons.

Objective: Previous axonal excitability studies suggest hyperkalemia or hypokalemia can significantly alter membrane potential and thereby, excitability properties. We studied whether physiological fluctuation of serum potassium levels affects axonal excitability in normal human axons.

Methods: Threshold tracking was used to measure strength-duration properties, refractory periods, supernormality, and threshold electrotonus in median motor axons of 12 normal volunteers.

Increased nodal persistent Na+ currents in human neuropathy and motor neuron disease estimated by latent addition.

Objective: To investigate the changes in nodal persistent Na(+) currents in human neuropathy and motor neuron disease. In human motor axons, approximately 1.0% of total Na(+) channels are active at rest, termed "persistent" Na(+) channels, and the conductance can be non-invasively estimated by the technique of latent addition in vivo.

Distal excitability changes in motor axons in amyotrophic lateral sclerosis.

Objective: Previous axonal excitability studies in amyotrophic lateral sclerosis (ALS) have suggested that impaired potassium channel function could be responsible for the generation of fasciculations, but the ectopic activity arises predominantly from the motor nerve terminals. This study tested the hypothesis that dysfunction of potassium channels is more pronounced in the more distal parts of axons.

Methods: Threshold electrotonus was used to compare accommodation at the motor point of abductor pollicis brevis, and at the wrist portion of the median nerve, between 22 patients with ALS and 19 normal subjects.

Aseptic meningoencephalitis presenting with bilateral vestibular ataxia: a case report.

Bilateral vestibular dysfunction is a rare condition, of which peripheral disorders are most common, whereas central disorders are extremely rare. A 35-year-old woman developed fever, headache, dizziness, convulsion, and disturbance of consciousness at the same time. MRI findings were normal.

Latent addition in human motor and sensory axons: different site-dependent changes across the carpal tunnel related to persistent Na+ currents.

Objective: To compare site-dependent changes across the carpal tunnel in axonal persistent Na+ conductances in motor and sensory axons. Positive sensory symptoms are prominent features in carpal tunnel syndrome, and a persistent Na+ current is a major determinant of axonal excitability.

Methods: The technique of latent addition was used to estimate persistent Na+ currents in median motor and sensory axons at the wrist and palm of 10 normal subjects.

Nodal persistent Na+ currents in human diabetic nerves estimated by the technique of latent addition.

Objective: To investigate the effects of hyperglycemia on persistent Na+ currents in human diabetic nerves, eliminating the factors of passive membrane properties as a factor. Previous studies show that strength-duration time constant of a nerve is shortened under hyperglycemia, suggesting reduced axonal persistent Na+ currents. However, the time constant is also affected by changes in passive membrane properties.

Altered axonal excitability properties in amyotrophic lateral sclerosis: impaired potassium channel function related to disease stage.

Fasciculations are a characteristic feature of amyotrophic lateral sclerosis (ALS), and can arise proximally or distally in the motor neuron, indicating a widespread disturbance in membrane excitability. Previous studies of axonal excitability properties (i.e.

[A patient with coccidioidal meningoencephalitis].

A 37-year-old man presented with coccidioidal meningoencephalitis (CM) 1 month after a preceding case of pneumonia. Initially, he could not be definitely diagnosed with CM because of nonspecific features of the clinical, laboratory, and radiological findings. However, we began to suspect CM because the patient had lived in endemic area of coccidioidomycosis, and our subsequent analysis provided evidence of complement-fixing antibodies for Coccidioides immitis in serum and CSF, leading us to a final diagnosis.

Superficial radial sensory nerve potentials in immune-mediated and diabetic neuropathies.

Objective: The pattern of abnormal median-normal sural sensory nerve action potential (SNAP) is frequently found in acute/chronic inflammatory demyelinating polyneuropathy (AIDP/CIDP), whereas sural/radial SNAP amplitude ratio is sensitive to detect dying-back degeneration. To investigate whether radial SNAP and its amplitude ratio to median or sural SNAP provide additional particular patterns of sensory nerve involvement.

Methods: Superficial radial, median, and sural SNAPs were recorded in 63 normal subjects and in 132 patients with AIDP/CIDP (n = 22), diabetic neuropathy (n = 83), or other axonal polyneuropathy (n = 27).

Axonal potassium conductance and glycemic control in human diabetic nerves.

Objective: To investigate the effects of hyperglycemia on axonal excitability and potassium conductance in human diabetic nerves.

Methods: Threshold tracking was used to measure excitability indices, which depend on potassium channels (supernormality, late subnormality, threshold electrotonus, and a current/threshold relationship) in median motor axons of 96 diabetic patients. The effects of hyperglycemia on these indices were analyzed.

The effects of mexiletine on excitability properties of human median motor axons.

Objective: To investigate the effects of mexiletine, an analog of lidocaine, on excitability of human axons in vivo.

Methods: Threshold tracking was used to measure multiple excitability indices (strength-duration time constant, rheobase, refractoriness, supernormality, and threshold electrotonus) in median motor axons of 20 patients with neuropathic pain or muscle cramping, before and 3 months after treatment with oral 300 mg mexiletine per day.

Results: After treatment, there was a reduction in pain/muscle cramps, associated with decreased strength-duration time constants (P=0.

Hyperreflexia in axonal Guillain-Barré syndrome subsequent to Campylobacter jejuni enteritis.

We describe a patient with the acute motor axonal neuropathy (AMAN) form of Guillain-Barré syndrome (GBS), who showed generalized hyperreflexia. A 24-year-old man developed acute paralysis following Campylobacter jejuni enteritis. He showed exaggerated tendon reflexes with abnormal reflex spread to other segments, and was initially diagnosed as having post-infectious myelitis.

Regulation of transformed state by calpastatin via PKCepsilon in NIH3T3 mouse fibroblasts.

Ca(2+)-activated neutral protease calpain is ubiquitously expressed and may have pleiotropic biological functions. We have previously reported that repeated treatment of NIH3T3 mouse fibroblasts with the calpain inhibitor N-acetyl-Leu-Leu-norleucinal (ALLN) resulted in the induction of transformed foci [T. Hiwasa, T.