ObjectiveDistinguishing normal, neuropathic and myopathic electromyography (EMG) traces can be challenging. We aimed to create an automated time series classification algorithm.MethodsEMGs of... Show moreObjectiveDistinguishing normal, neuropathic and myopathic electromyography (EMG) traces can be challenging. We aimed to create an automated time series classification algorithm.MethodsEMGs of healthy controls (HC, n = 25), patients with amyotrophic lateral sclerosis (ALS, n = 20) and inclusion body myositis (IBM, n = 20), were retrospectively selected based on longitudinal clinical follow-up data (ALS and HC) or muscle biopsy (IBM). A machine learning pipeline was applied based on 5-second EMG fragments of each muscle. Diagnostic yield expressed as area under the curve (AUC) of a receiver-operator characteristics curve, accuracy, sensitivity, and specificity were determined per muscle (muscle-level) and per patient (patient-level).ResultsDiagnostic yield of the classification ALS vs. HC was: AUC 0.834 ± 0.014 at muscle-level and 0.856 ± 0.009 at patient-level. For the classification HC vs. IBM, AUC was 0.744 ± 0.043 at muscle-level and 0.735 ± 0.029 at patient-level. For the classification ALS vs. IBM, AUC was 0.569 ± 0.024 at muscle-level and 0.689 ± 0.035 at patient-level.ConclusionsAn automated time series classification algorithm can distinguish EMGs from healthy individuals from those of patients with ALS with a high diagnostic yield. Using longer EMG fragments with different levels of muscle activation may improve performance. Show less
Imaging studies showed that the structure of the corpus callosum (CC) is affected in amyotrophic lateral sclerosis (ALS). Some clinical studies also suggest that interhemispheric connectivity is... Show moreImaging studies showed that the structure of the corpus callosum (CC) is affected in amyotrophic lateral sclerosis (ALS). Some clinical studies also suggest that interhemispheric connectivity is altered, since mirror movements seem to occur in ALS. Finally, reduced interhemispheric inhibition (IHI), studied by transcranial magnetic stimulation (TMS), has been reported. It is not known whether there is any association between these findings. Here, we studied the integrity of the CC in ALS on the morphological, the functional, the electrophysiological, and the clinical level. Twenty-seven right-handed ALS patients and 21 healthy right-handed controls were included. Mirror activity (MA) was quantified using surface EMG. Diffusion tensor imaging tractography was used to segment the CC and quantify fractional anisotropy (FA). We studied the diffusivity of the intra-axonal markers N-acetylaspartate+N-acetyl aspartyl glutamate D(tNAA) within the CC. IHI was studied as a marker of CC function using a double-pulse TMS protocol. ALS patients showed significantly decreased FA in the motor segment of the CC (p < 0.01), and IHI was significantly reduced compared to controls (p = 0.01). However, no differences were observed regarding D(tNAA) and MA. The morphological as well as the functional integrity of the CC are altered in ALS. IHI was reduced in ALS, associated with decreased FA in the motor CC. Patients did not exhibit increased MA. Also, no differences within the CC were observed using diffusion-weighted spectroscopy. IHI might serve as a marker of transcallosal pathway disruption in ALS, even before clinical deficits become apparent. Show less
Meyer, M.; Kruse, M.S.; Garay, L.; Lima, A.; Roig, P.; Hunt, H.; ... ; Nicola, A.F. de 2020
The Wobbler mouse spinal cord shows vacuolated motoneurons, glial reaction, inflammation and abnormal glutamatergic parameters. Wobblers also show deficits of motor performance. These conditions... Show moreThe Wobbler mouse spinal cord shows vacuolated motoneurons, glial reaction, inflammation and abnormal glutamatergic parameters. Wobblers also show deficits of motor performance. These conditions resemble amyotrophic lateral sclerosis (ALS). Wobbler mice also show high levels of corticosterone in blood, adrenals and brain plus adrenal hypertrophy, suggesting that chronically elevated glucocorticoids prime spinal cord neuroinflammation. Therefore, we analyzed if treatment of Wobbler mice with the glucocorticoid receptor (GR) antagonist CORT113176 mitigated the mentioned abnormalities. 30 mg/kg CORT113176 given daily for 3 weeks reduced motoneuron vacuolation, decreased astro and microgliosis, lowered the inflammatory mediators high mobility group box 1 protein (HMGB1), toll-like receptor 4, myeloid differentiation primary response 88 (MyD88), p50 subunit of nuclear factor kappa B (NF kappa B), tumor necrosis factor (TNF) receptor, and interleukin 18 (IL18) compared to untreated Wobblers. CORT113176 increased the survival signal pAKT (serine-threonine kinase) and decreased the death signal phosphorylated Junk-N-terminal kinase (pJNK), symptomatic of antiapoptosis. There was a moderate positive effect on glutamine synthase and astrocyte glutamate transporters, suggesting decreased glutamate excitotoxicity. In this pre-clinical study, Wobblers receiving CORT113176 showed enhanced resistance to fatigue in the rota rod test and lower forelimb atrophy at weeks 2-3. Therefore, long-term treatment with CORT113176 attenuated degeneration and inflammation, increased motor performance and decreased paw deformity. Antagonism of the GR may be of potential therapeutic value for neurodegenerative diseases. Show less
Lee, S.J. van der; Conway, O.J.; Jansen, I.; Carrasquillo, M.M.; Kleineidam, L.; Akker, E. van den; ... ; GIFT Genetic Invest 2019
