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To describe clinical features, disease course, treatment response, and sural nerve biopsy findings in a patient with chronic sensory ataxic neuropathy, Binet stage A chronic lymphocytic leukemia, and monoclonal IgMλ paraprotein against ganglioside GD1b. During 9 months of hospitalization at two neurologic centers, the patient underwent serial neurologic examinations, neurophysiologic studies, imaging investigations, extensive laboratory work-up, bone marrow, and sural nerve biopsies. The patient had a severe progressive sensory neuropathy accompanied by motor involvement, dysautonomia, and marked bulbar weakness with preserved ocular movements. Conduction studies were characterized by prolonged F-wave minimal latencies, prolonged distal latencies, reduction of compound motor action potentials, and absence of sensory nerve action potentials. Sural nerve biopsy showed endoneurial edema, axonal degeneration, and regeneration, in the absence of cellular inflammation, macrophagic activation, and B-lymphocyte infiltration; no IgM or complement deposition was detected. Myelinated fibers showed redundant/abnormally thickened myelin, myelin vacuolation, and frank intramyelinic edema with condensed axoplasm. Ultrastructural features included axo-glial detachment, disruption of membrane integrity, and myelin uncompaction. This study shows that monospecific anti-GD1b IgM paraprotein is associated with non-inflammatory nerve damage. We suggest that the loss of myelin and axonal integrity reflects antibody-induced disruption of membrane lipid rafts.

Spasticity leads to functional and structural changes in nerves and muscles, which alter skeletal muscle function. To evaluate whether short-term electrical nerve stimulation (NS) improves the effect of botulinum toxin in spastic skeletal muscle, we studied changes in the amplitude of the compound muscle action potential (CMAP) recorded from the extensor digitorum brevis (EDB) muscle in response to peroneal nerve stimulation at the ankle after injection of botulinum toxin type A (BTXA) alone or combined with short-term NS. In paraparetic patients, both EDB muscles were injected with BTXA; and NS was applied to one EDB muscle alone. All patients received a 30-minute session of electrical NS once a day for 5 consecutive days after BTXA injection. We used two different stimulation frequencies (low-frequency, 4 Hz; and high-frequency, 25 Hz). EDB-CMAP amplitudes were evaluated before BTXA injection (day 0) and changes in CMAP amplitude, expressed as a percentage (CMAP%), were measured at various time points over a 30-day period after BTXA injection. We compared changes in the CMAP% amplitude on the stimulated and contralateral nonstimulated sides. We also studied the electromyographic activity recorded from EDB muscles over a 30-day period. CMAP% amplitudes measured at all time points after BTXA injections were significantly reduced in both EDB muscles. On days 4, 10, and 15, the CMAP% amplitude reduction was significantly greater for the low-frequency stimulated EDB than for the contralateral nonstimulated EDB. No significant differences in CMAP% were observed for the high-frequency stimulated and nonstimulated EDB. After BTXA injection, spontaneous activity appeared in both EDB muscles; but it appeared earlier and involved larger areas in the stimulated than in the nonstimulated EDB. In conclusion, short-term NS accelerates the effectiveness of intramuscular BTXA injections on the neuromuscular blockade in patients with spastic paraparesis and could induce a rapid and persistent improvement in spasticity. Its action probably arises mainly from low-frequency NS.

Despite the fact that somatosensory processing is inherently dependent on inhibitory functions, only excitatory aspects of the somatosensory feedback have so far been assessed in dystonic patients. We studied the recovery functions of spinal N13, brainstem P14, parietal N20, P27, and frontal N30 somatosensory evoked potentials (SEPs) after paired median nerve stimulation in 10 patients with dystonia and in 10 normal subjects. The recovery functions were assessed (conditioning stimulus: S1; test stimulus: S2) at interstimuls intervals (ISIs) of 5, 20, and 40 ms. SEPs evoked by S2 were calculated by subtracting the SEPs of the S1 only response from the SEPs of the response to the paired stimuli (S1 + S2), and their amplitudes were compared with those of the control response (S1) at each ISI considered. This ratio, (S2/S1)*100, investigates changes in the excitability of the somatosensory system. No significant difference was found in SEP amplitudes for single stimulus (S1) between dystonic patients and normal subjects. The (S2/S1)*100 ratio at the ISI of 5 ms did not significantly differ between dystonic patients and normal subjects, but at ISIs of 20 and 40 ms, this ratio was significantly higher in patients than in normals for spinal N13 and cortical N20, P27, N30 SEPs. These findings suggest that in dystonia there is an impaired inhibition at spinal and cortical levels of the somatosensory system which would lead to an abnormal sensory assistance to the ongoing motor programs, ultimately resulting in the motor abnormalities present in this disease.