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IVIg improves strength in patients with untreated CIDP by day 10 with continued benefit through day 42; more than one third improve by at least a functional grade on a disability scale. This study provides data supporting IVIg as the initial treatment for CIDP.

Previous studies demonstrated age- and height-related slowing of nerve conduction velocity (NCV) and reduction in nerve response amplitude. Unfortunately, many studies examined discontinuous populations, preventing regression analysis. The correlation coefficients of available studies vary widely, preventing clear conclusions. We retrospectively examined 3969 clinically normal subjects ranging in age from 20 to 95 years from a total of 22,420 electrodiagnostic studies done between 1986 and 1998. The correlation of NCV with height was stronger than with age. Regression equations using both factors account for 12--27% of the variance. Responses were seen in the majority of patients aged 70 years and older, but the percentage of normals who had no response increased with advancing age. Age was strongly inversely correlated with the amplitudes of both sensory and motor responses, accounting for 7--16% of the variance. Regression equations using both height and age improved this correlation, accounting for 7--22% of the variance. Therefore, both height and age must be taken into consideration when normal values are developed.

ContributorsGIW wrote and revised the manuscript in response to co-author comments. He finalized all the figures and tables, performed the literature search, and assisted with data interpretation. HJK critically reviewed the manuscript and made important suggestions to improve it. He assisted with data interpretation. IBA performed the data analysis, constructed the figures and tables, and made important suggestions to improve the manuscript. H-CK assisted with the data analysis and also reviewed the manuscript. GRC critically reviewed the manuscript and made important suggestions to improve it. He assisted with data interpretation. All other authors were given the opportunity to review the manuscript and make suggestions which GIW received, either revising the paper or providing explanations. All who are not deceased were involved with approval of the manuscript.

Of 50 normal subjects, 23 (46%) had at least one false positive electrodiagnostic test for carpal tunnel syndrome (CTS). There were 30% of the subjects who exhibited an abnormal median to ulnar sensory amplitude ratio of less than 1.1. In 7 subjects 8 extremities (14%) revealed prolonged residual latencies, and 4 extremities in 4 subjects (8%) had a difference of 0.4 msec between the median and ulnar palmar sensory latencies. The results of this study indicate that certain reported criteria for CTS are abnormal in a high percentage of normal subjects, thereby making them of limited value in the diagnosis of CTS. Of all the criteria studied, it appears that the comparison of the median to ulnar sensory latency across the carpal tunnel is of greatest potential value. However, even here a more conservative difference of 0.5 msec between median and ulnar nerves must be used to avoid false positive tests for CTS.

IMPORTANCE Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor nervous system. Clinical studies have demonstrated cortical and spinal motor neuron hyperexcitability using transcranial magnetic stimulation and threshold tracking nerve conduction studies, respectively, although metrics of excitability have not been used as pharmacodynamic biomarkers in multi-site clinical trials. OBJECTIVE To ascertain whether ezogabine decreases cortical and spinal motor neuron excitability in ALS. DESIGN, SETTING, AND PARTICIPANTSThis double-blind, placebo-controlled phase 2 randomized clinical trial sought consent from eligible participants from November 3, 2015, to November 9, 2017, and was conducted at 12 US sites within the Northeast ALS Consortium. Participants were randomized in equal numbers to a higher or lower dose of ezogabine or to an identical matched placebo, and they completed in-person visits at screening, baseline, week 6, and week 8 for clinical assessment and neurophysiological measurements. INTERVENTIONS Participants were randomized to receive 600 mg/d or 900 mg/d of ezogabine or a matched placebo for 10 weeks. MAIN OUTCOMES AND MEASURESThe primary outcome was change in short-interval intracortical inhibition (SICI; SICI −1 was used in analysis to reflect stronger inhibition from an increase in amplitude) from pretreatment mean at screening and baseline to the full-dose treatment mean at weeks 6 and 8. The secondary outcomes included levels of cortical motor neuron excitability (including resting motor threshold) measured by transcranial magnetic stimulation and spinal motor neuron excitability (including strength-duration time constant) measured by threshold tracking nerve conduction studies.RESULTS A total of 65 participants were randomized to placebo (23), 600 mg/d of ezogabine (23), and 900 mg/d of ezogabine (19 participants); 45 were men (69.2%) and the mean (SD) age was 58.3 (8.8) years. The SICI −1 increased by 53% (mean ratio, 1.53; 95% CI, 1.12-2.09; P = .009) in the 900-mg/d ezogabine group vs placebo group. The SICI −1 did not change in the 600-mg/d ezogabine group vs placebo group (mean ratio, 1.15; 95% CI, 0.87-1.52; P = .31). The resting motor threshold increased in the 600-mg/d ezogabine group vs placebo group (mean ratio, 4.61; 95% CI, 0.21-9.01; P = .04) but not in the 900-mg/d ezogabine group vs placebo group (mean ratio, 1.95; 95% CI, −2.64 to 6.54; P = .40). Ezogabine caused a dose-dependent decrease in excitability by several other metrics, including strength-duration time constant in the 900-mg/d ezogabine group vs placebo group (mean ratio, 0.73; 95% CI, 0.60 to 0.87; P < .001).CONCLUSIONS AND RELEVANCE Ezogabine decreased cortical and spinal motor neuron excitability in participants with ALS, suggesting that such neurophysiological metrics may be used as pharmacodynamic biomarkers in multisite clinical trials.

This article discusses the neurophysiology of myofascial pain syndrome. The local twitch response is a characteristic finding of this condition; it is activated by snapping palpation, pressure, or needle insertion at the trigger point. It is manifested by a burst of activity in the muscle band that contains the activated trigger point. No activity is seen at other muscles bands. Data from experiments with the rabbit indicate that this is a spinal reflex, as it is abolished by transection of the motor nerve innervating the trigger point and infusion of lidocaine. Transection of the spinal cord above the level of the trigger point fails to permanently alter the trigger point response. Needle examination recordings from trigger points show low-voltage spontaneous activity and activity resembling end-plate spikes. This activity is reduced with infusion of phentolamine and local intramuscular infusions of phenoxybenzamine. There are four hypotheses to explain the findings seen at the trigger point. The first is that trigger points are found at the muscle spindle. While this theory may explain the effects of alpha-adrenergic antagonists at the trigger point, it does not fully explain the electromyographic (EMG) findings recorded at the trigger point. The second theory is that trigger points represent hyperactive end-plate regions, as the EMG activity recorded at trigger points resembles that described at the end-plate region. Other theories that either deny the existence of myofascial pain syndrome or believe it represents a focal dystonia are also discussed.

In autoimmune myasthenia gravis (MG), the identification of antibodies and characterization of serological subgroups is of great importance for diagnosis and management of the disease. Our aims were to study the frequency of antibodies against lipoprotein-related protein 4 (LRP4), agrin, and titin using the most recent techniques, and to characterize corresponding clinical features and autoimmune diseases (AID) in 100 MG-patients. The antibody frequencies in the 55 AChR-antibody positive patients were 7% LRP4, 5% agrin, 53% titin, and in the 45 AChR-antibody negative patients 2% MuSK, 2% LRP4, 2% agrin, and 27% titin. LRP4-MG presented late-onset age, mild symptoms, good therapeutic response, and no thymic changes. Agrin-MG showed early onset age, mild-to-severe symptoms, and moderate treatment response. The phenotype of titin-MG depended on AChR-antibodies: AChR-antibody negative patients presented with mostly mild limb muscle weakness, whereas AChR-antibody positive patients showed more frequently severe symptoms, including myasthenic crisis, bulbar predominance, and thymoma. Additional AID were detected in 32% of MG-patients, most frequently Hashimoto's thyroiditis (21%). Based on our data, we recommend the detection of LRP4-antibodies for at least AChR-antibody negative MG-patients and titin-antibodies for all MG-patients. We propose taking an accurate medical history for typical symptoms of Hashimoto's thyroiditis in MG-patients.