Among the CIDP spectrum, typical CIDP and MADSAM are the major subtypes, and their pathophysiology appears to be distinct. In typical CIDP, the distal nerve terminals and possibly the nerve roots, where the blood-nerve barrier is anatomically deficient, are preferentially affected, raising the possibility of antibody-mediated demyelination, whereas cellular immunity with breakdown of the barrier may be important in MADSAM neuropathy.

Objectives:To study the utility of muscle ultrasound (US) for detection of fasciculations and its contribution to diagnosis in amyotrophic lateral sclerosis (ALS). Fasciculations are characteristic features of ALS, and US can detect them easily and reliably. New diagnostic criteria for ALS, the Awaji algorithm, reintroduced fasciculations as evidence of acute denervation equivalent to that of fibrillations and positive sharp waves. Methods:In 81 consecutive patients with sporadic ALS, we prospectively performed needle EMG and US in 6 muscles (tongue, biceps brachii, first dorsalis interosseous, paraspinalis, vastus lateralis, and tibialis anterior), and diagnostic category were determined by revised El Escorial criteria and Awaji criteria. Results:Fasciculations were much more frequently detected by US than by EMG in the tongue (60% vs 0%), biceps brachii (88% vs 60%), and tibialis anterior muscles (83% vs 45%). The proportion of the patients with definite or probable ALS was 48% by revised El Escorial criteria and 79% by Awaji criteria using US. Conclusions:Muscle US is a practical and efficient tool to detect fasciculations, particularly in the tongue. A combination of US and EMG substantially increases the diagnostic sensitivity of ALS.

To assess the significance of distal compound muscle action potential (CMAP) duration for diagnosis of demyelinating neuropathies, electrophysiologic data were reviewed from 471 subjects, including 145 normal controls, 60 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 205 with other neuropathy, and 61 with amyotrophic lateral sclerosis (ALS). The duration of distally evoked CMAP was measured in the median, ulnar, tibial, and peroneal nerves. Optimal cut-off values were calculated with receiver-operating characteristic (ROC) curves. In comparison of normal controls and CIDP patients, ROC analyses showed the sufficient area under the curves (82-93%). When the cut-off values in the detection of demyelination were determined as the point with 98% specificity vs. normal on the ROC curves (median, 6.6 ms; ulnar, 6.7 ms; peroneal, 7.6 ms; tibial, 8.8 ms), the sensitivity was 77% for CIDP, with a specificity of 90% vs. ALS and 95% vs. diabetic neuropathy. The distal CMAP duration is a useful index for the detection of distal demyelination. We suggest the above cut-off values for each nerve as one of the electrodiagnostic criteria for demyelinating neuropathies, preferentially affecting the distal nerve terminals, such as CIDP.

TAR DNA binding protein of 43 kDa (TDP-43) is likely to be the major pathogenetic protein in amyotrophic lateral sclerosis (ALS). A previous study has shown that levels of TDP-43 in CSF measured by an ELISA are significantly higher for ALS patients than for controls. The aim of this study was to investigate whether elevated CSF TDP-43 levels are specific to ALS, and are associated with clinical profiles in ALS patients. We measured CSF TDP-43 levels by the same ELISA in 27 ALS patients and 50 neurodegenerative or inflammatory disease controls such as Parkinson's disease, multiple sclerosis, and Guillain-Barré syndrome. Results showed that the CSF TDP-43 levels were increased only in ALS patients. Receiver operating characteristic (ROC) analyses showed a sensitivity of 59.3% and a specificity of 96.0%. We also found that lower CSF TDP-43 levels may be associated with shorter survival time. In conclusion, the CSF TDP-43 is a potential biomarker that supports a diagnosis of ALS. Moreover, among ALS patients, lower levels of CSF TDP-43 may reflect the accumulation of TDP-43 in the cortical and spinal motor neurons and thereby shorter survival time, although this should be confirmed in larger prospective studies.

Axonal persistent sodium currents, estimated by SDTC and latent addition, are strong and independent predictors for shorter survival in patients with ALS. Membrane hyperexcitability is possibly associated with motor neuronal death, and modulation of excessive sodium currents could be a novel therapeutic option for ALS.