Nobuo Kohara

F-wave latency serves as the most reproducible measure in nerve conduction studies of diabetic polyneuropathy: multicentre analysis in healthy subjects and patients with diabetic polyneuropathy

Aims/hypothesis. For use in future drug development for diabetic polyneuropathy, we conducted multicentre trials to assess the reproducibility of nerve conduction studies.¶Methods. All measurements were repeated twice at a time interval of 1–4 weeks in 132 healthy subjects (63 men) and 172 patients (99 men) with diabetic polyneuropathy. Using a standardised method, 32 centres participated in the study of control subjects and 65, in patients with diabetic polyneuropathy. Motor nerve conduction studies consisted of stimulating the left median and tibial nerves and recording the compound action potential from abductor policis and adductor hallucis for measuring amplitude, terminal latency and minimal F-wave latency. For sensory conduction studies, sensory nerve action potentials were recorded antidromically from the second digit and the posterior aspect of the lateral malleous after distal stimulation of the left median and sural nerves. We also calculated motor conduction velocity, F-wave conduction velocity and sensory conduction velocity. The relative intertrial variation and intraclass correlation coefficient were used as an index of reproducibility.¶Results. Of all the measurements, F-wave latency yielded the highest intraclass correlation coefficient with the smallest relative intertrial variation for both median and tibial nerves in both groups.¶Conclusion/interpretation. Median and tibial F-wave latency provide the most reproducible measures for a nerve conduction study, serving as one of the best measures in multicentre drug trials for diabetic polyneuropathies. [Diabetologia (2000) 43: 915–921]

Comparison of Therapeutic Efficacies of Type A and F Botulinum Toxins for Blepharospasm A double-blind, controlled study

Article abstract-Type F botulinum toxin can be used for treating patients with dystonia who become refractory to type A toxin injection due to antibody development. We compared the therapeutic efficacy of type F botulinum toxin to that of type A toxin in a self-controlled, double-blind clinical trial. In nine patients with blepharospasm, we injected type A toxin on one side and the same units of type F toxin on the other side. Although the onset of clinical effect, maximal benefit, and adverse reactions were similar between type A and F toxins, the duration of the clinical effect was significantly shorter on the side injected with type F toxin. Although type F toxin proved its promise as an alternative to type A toxin, its usefulness is limited by the shorter duration of action. NEUROLOGY 1995;45: 506-508

Pre-movement gating of short-latency somatosensory evoked potentials.

Somatosensory evoked potentials (SEPs) are reduced in amplitude during movement (gating). The mechanism involves central gating of afferent input and competition from other afferents activated by the movement. We distinguished these two by giving 11 normal subjects a warning sound followed 1 s later by an electric stimulus to the right median nerve at the wrist. The latter served both as a cue to start a finger movement and as stimulation to evoke SEPs. Gating effects were widespread in frontal (N30) and central (N60) areas, but were also seen, albeit to a lesser extent, in the recordings at P3 (P30). Since finger movement began after the stimulus, such gating must have been purely central in origin, presumably reflecting motor preparation.

Effect of maturation on nerve excitability in an experimental model of threshold electrotonus.

Threshold electrotonus (TE) is a new tool for investigating axonal function noninvasively in vivo. To increase its potential clinical value, we developed a rat model of TE, and examined the effects of maturation and pharmacological intervention. We recorded TE in 92 male rats (body weight 90–650 g) by stimulating the motor nerve in the tail, and applying 100‐ms conditioning currents. Motor conduction velocities increased up to a body weight of 330 g, and remained constant thereafter. TE in mature rats was similar to that in humans, and two parameters were analyzed: TEd10–20 or the mean threshold reduction 10–20 ms after the onset of the depolarizing conditioning current at 40% of threshold intensity; and TEh10–20 or the corresponding threshold decrease on hyperpolarization. Like latency, the absolute value of TEh10–20 decreased up to 330 g, and then stabilized thereafter, probably reflecting the progressive increase in the axonal diameter and relative reduction in internodal impedance. In contrast, TEd10–20 gradually decreased up to 330 g, and then jumped to a higher level, which was maintained for animals of >400 g. 4‐Aminopyridine, a blocker of fast potassium channels, selectively increased TEd10–20 only in the immature or young (<330 g) rats. This suggests that, in the mature animals, fast potassium channels become sequestrated from the nodal membrane and not activated in response to nodal depolarization. These findings indicate that mature rats (>400 g) may provide a useful experimental model for interpreting abnormal TE responses in humans, and provide evidence for nonlinear maturation of potassium channel function in myelinated axons.

Intravenous Autologous Bone Marrow Mononuclear Cell Transplantation for Stroke: Phase1/2a Clinical Trial in a Homogeneous Group of Stroke Patients

The goal of this clinical trial was to assess the feasibility and safety of transplanting autologous bone marrow mononuclear cells into patients suffering severe embolic stroke. Major inclusion criteria included patients with cerebral embolism, age 20–75 years, National Institute of Health Stroke Scale (NIHSS) score displaying improvement of ≤5 points during the first 7 days after stroke, and NIHSS score of ≥10 on day 7 after stroke. Bone marrow aspiration (25 or 50 mL; N = 6 patients in each case) was performed 7–10 days poststroke, and bone marrow mononuclear cells were administrated intravenously. Mean total transplanted cell numbers were 2.5 × 108 and 3.4 × 108 cells in the lower and higher dose groups, respectively. No apparent adverse effects of administering bone marrow cells were observed. Compared with the lower dose, patients receiving the higher dose of bone marrow cells displayed a trend toward improved neurologic outcomes. Compared with 1 month after treatment, patients receiving cell therapy displayed a trend toward improved cerebral blood flow and metabolic rate of oxygen consumption 6 months after treatment. In comparison with historical controls, patients receiving cell therapy had significantly better neurologic outcomes. Our results indicated that intravenous transplantation of autologous bone marrow mononuclear cells is safe and feasible. Positive results and trends favoring neurologic recovery and improvement in cerebral blood flow and metabolism by cell therapy underscore the relevance of larger scale randomized controlled trials using this approach.

An electrophysiological study of the corticospinal projections in amyotrophic lateral sclerosis.

OBJECTIVE To elucidate the pattern of corticospinal tract involvement in patients with amyotrophic lateral sclerosis (ALS), we analyzed motor evoked potential (MEP) waveforms and their relationship to the behaviour of single motor units using the peristimulus time histogram (PSTH) technique. METHODS Abnormality of the corticospinal pathways was studied in 35 ALS patients using MEPs. PSTHs were also constructed to assess the effect of magnetic cortical stimulation on the discharge pattern of a voluntarily activated motor unit. RESULTS MEPs showed a complex waveform in 10 out of 18 (56%) ALS patients with upper motor neuron signs (UMN). PSTHs revealed double primary peaks (PPs), PP1 and PP2, in 6 out of 16 motor units (38%) in ALS with UMN, as compared to only 2 out of 16 (13%) motor units in multiple sclerosis or cerebrovascular disease with UMN. None of the patients with lower motor neuron diseases or ALS without UMN had these abnormalities. The late component of complex MEPs showed a good correlation to PP2 (P < 0.0001), both probably being mediated by relatively preserved slower conducting corticospinal volleys. CONCLUSIONS These findings suggest preferential involvement of the fast conducting direct corticospinal tracts, sparing the slower or polysynaptic projections in ALS.

High-frequency SEP components generated in the somatosensory cortex of the monkey.

To investigate the origin of high-frequency somatosensory evoked potential (SEP) components, we recorded median nerve SEPs from the scalp and the depth in six monkeys. Laminar field potentials were analyzed in area 3b (N10; corresponding to human N20) and area 1 (P12; corresponding to human P25). After digital filtering (300–900 Hz), 4–6 components were identified, and the 1st to 4th peaks in area 3b (7–11 ms in latency) and the 3rd to 5th in area 1 (9–13 ms) showed clear polarity reversals between the surface and the depth of the cortex. These results provide direct evidence for intracortical origin of early high-frequency components in area 3b and of late ones in area 1.

Chronic motor axonal neuropathy associated with antibodies monospecific for n‐acetylgalactosaminyl GD1a

We report on three patients with chronic motor neuropathy who had elevated titers of immunoglobulin (Ig)G antibodies against N‐acetylgalactosaminyl GD1a (GalNAc‐GD1a) and normal titers of antibodies against other gangliosides. Presenting with progressive muscular atrophy, fasciculations, and no sensory deficits, the patients had been diagnosed to have motor neuron disease. Electrodiagnostic features were predominantly axonal. Two patients clinically improved after intravenous Ig infusion and cyclophosphamide therapy. Increased titers of IgM antibodies to GalNAc‐GD1a were also found in two of 15 patients with multifocal motor neuropathy with conduction block but were associated with concomitant rise of anti‐GM1 antibodies. These three cases represent a chronic motor axonal neuropathy in which antibody testing for a minor ganglioside was helpful for instituting therapy.

Effect of ultrahigh-dose methylcobalamin on compound muscle action potentials in amyotrophic lateral sclerosis : A double-blind controlled study

To develop a symptomatic treatment for amyotrophic lateral sclerosis, we compared the effects of ultrahigh‐dose and low‐dose (25 and 0.5 mg/day, intramuscularly, for 14 days) methylcobalamin on averaged compound muscle action potential amplitudes (CMAPs) in a double‐blind trial. No significant changes in CMAP amplitude were found in 12 patients who had the low‐dose treatment at either 2 or 4 weeks after start of treatment. By contrast, 12 patients assigned to the ultrahigh‐dose group demonstrated a significant increase at 4 weeks. This method may provide a clinically useful measure to improve or retard muscle wasting, if a larger extended trial fulfills its promise.

Movement-related cortical potentials before jaw excursions in oromandibular dystonia.

Oromandibular dystonia is a neurological disorder characterized by involuntary contraction of masticatory and/or tongue muscles. Cortical negative shifts preceding voluntary movements called “movement‐related cortical potentials” (MRCPs) reflect a central motor control process. Reduced amplitude of MRCPs has been reported in other types of dystonia. To elucidate whether the abnormality is observed also in oromandibular dystonia, we compared MRCPs associated with mandibular movements in 6 patients with this condition and in 8 normal subjects. Electroencephalograms (EEGs) were recorded from 11 electrodes, and electromyograms (EMGs) were recorded from the masseter muscle and the suprahyoid muscles. The subjects were asked to repeat mouth opening, closing, and left and right lateral mandibular excursions. MRCPs were obtained by averaging the EEG using the EMG onset as the trigger signal. In the patient group, MRCP amplitudes over central and parietal areas for mouth opening and lateral movements were significantly reduced compared to normal subjects. In normal controls, the MRCPs at mouth opening and closing were symmetrically distributed, whereas those at lateral movements showed predominance over the hemisphere ipsilateral to the direction of the movement. This laterality was lost in the patient group. These results suggest impaired cortical preparatory process for jaw movements in oromandibular dystonia.