Guillain-Barré syndrome is classified into acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) by electrodiagnostic and pathological criteria. In AMAN, the immune attack appears directed against the axolemma and nodes of Ranvier. Threshold tracking was used to measure indices of axonal excitability (refractoriness, supernormality, and threshold electrotonus) for median nerve axons at the wrist of patients with AMAN (n = 10) and AIDP (n = 8). Refractoriness (the increase in threshold current during the relative refractory period) was greatly increased in AMAN patients, but the abruptness of the threshold increases at short interstimulus intervals indicated conduction failure distal to the stimulation (ie, an increased refractory period of transmission). During the 4 week period from onset, the high refractoriness returned toward normal, and the amplitude of the compound muscle action potential increased, consistent with improvement in the safety margin for impulse transmission in the distal nerve. In contrast, refractoriness was normal in AIDP, even though there was marked prolongation of distal latencies. Supernormality and threshold electrotonus were normal in both groups of patients, suggesting that, at the wrist, membrane potential was normal and pathology was relatively minor. These results support the view that the predominantly distal targets of immune attack are different for AMAN and AIDP. Possible mechanisms for the reduced safety factor in AMAN are discussed.

Machado-Joseph disease is one of the most common hereditary spinocerebellar degenerative disorders with a wide range of clinical manifestations. Pathology studies have shown mild to moderate loss of anterior horn cells and, in terms of spinal pathology, Machado-Joseph disease is regarded as a type of lower motoneuron disease. Muscle cramps are often associated with lower motoneuron disorders, but features of cramps in Machado-Joseph disease patients have never been studied. We investigated the incidence and nature of muscle cramps in Machado-Joseph disease patients, the excitability properties of motor axons [strength-duration time constant (tau(SD)), threshold electrotonus, refractoriness and supernormality] using threshold tracking and the effects of mexiletine hydrochloride on those cramps. Of 20 consecutive patients, 16 (80%) had frequent, severe muscle cramps in the legs, trunk or arms that disturbed their daily activities. The frequency of pathological muscle cramps was similar to that for patients with amyotrophic lateral sclerosis (68%) and higher than those for patients with spinal muscular atrophy (33%) or peripheral axonal neuropathy (24%). Threshold-tracking studies showed that tau(SD), which in part reflects Na(+) conductance at the resting membrane potential, was significantly greater in the Machado-Joseph disease patients than in normal subjects; severe muscle cramps were associated with a longer tau(SD). Threshold electrotonus, refractoriness and supernormality were not significantly different between Machado-Joseph disease patients and normal subjects. Eight Machado-Joseph disease patients with severe cramps, who received mexiletine treatment, experienced nearly complete relief with a partial normalization of tau(SD) (P = 0.08). Muscle cramps are a very frequent and disabling factor in Machado-Joseph disease. Pathological muscle cramps responded well to mexiletine treatment, and this is consistent with the hypothesis that they are caused by an increase in persistent Na(+) conductance, possibly associated with axonal regeneration or collateral sprouting.

Polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome is a rare cause of demyelinating and axonal neuropathy. POEMS syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP) cause peripheral nerve demyelination, and the electrodiagnostic findings may therefore be similar, but the two disorders are distinct. To elucidate the electrodiagnostic features of POEMS syndrome, we reviewed nerve conduction studies of 8 patients, and compared their results with those in 42 patients with CIDP. The patients with POEMS syndrome showed (1) slowing of nerve conduction that was more predominant in the intermediate than distal nerve segments, (2) rare conduction block (6% of the tested nerves), and (3) more severe attenuation of compound muscle action potentials in the lower than upper limbs. Findings in the CIDP patients were characterized by multifocal conduction slowing that was occasionally dominant distally, frequent conduction block (44% of tested nerves), and less discrepancy between upper and lower limb nerves. The pattern of nerve conduction abnormalities differs between these disorders. Recognition of these typical patterns may be helpful for early diagnosis of POEMS syndrome.

To evaluate the development of diabetic neuropathy, the current study examined changes in peripheral axonal function. Nerve excitability techniques were undertaken in 108 type 2 diabetic patients with nerve conduction studies (NCS), HbA1c levels, and total neuropathy score (TNS). Patients were categorized into two cohorts: patients with diabetes without neuropathy (DWN group [n = 56]) and patients with diabetes with neuropathy (DN group [n = 52]) and further into severity grade 0 (TNS 0–1 [n = 35]), grade 1 (TNS 2–8 [n = 42]), and grade 2/3 (TNS 9–24 [n = 31]). Results revealed that the DWN group had a significantly increased threshold, prolonged latency, and changes in excitability parameters compared with age-matched control subjects. Patients with neuropathy demonstrated significant alteration in recovery cycle parameters and depolarizing threshold electrotonus. Within the DWN cohort, there were significant correlations between HbA1c level and latency and subexcitability, whereas the estimated glomerular filtration rate correlated with superexcitability in patients with neuropathy. Furthermore, excitability parameters became progressively more abnormal with increasing clinical severity. These results suggest a spectrum of excitability abnormalities in patients with diabetes and that early axonal dysfunction may be detected prior to the development of neuropathy. As progressive changes in excitability parameters correlated to neuropathy severity, excitability testing may provide a biomarker of the early development and severity of diabetic neuropathy, providing insights into the pathophysiological mechanisms producing axonal dysfunction.