Amyotrophic lateral sclerosis is a severe neurodegenerative disease whose exact cause is still unclear. Currently, research attention is turning to the mitochondrion as a critical organelle of energy metabolism. Current knowledge is sufficient to confirm the involvement of the mitochondria in the pathophysiology of the disease, since the mitochondria are involved in many processes in the cell; however, the exact mechanism of involvement is still unclear. We used peripheral blood mononuclear cells isolated from whole fresh blood from patients with amyotrophic lateral sclerosis for measurement and matched an age- and sex-matched set of healthy subjects. The group of patients consisted of patients examined and diagnosed at the neurological clinic of the University Hospital Martin. The set of controls consisted of healthy individuals who were actively searched, and controls were selected on the basis of age and sex. The group consisted of 26 patients with sporadic forms of ALS (13 women, 13 men), diagnosed based on the definitive criteria of El Escorial. The average age of patients was 54 years, and the average age of healthy controls was 56 years. We used a high-resolution O2K respirometry method, Oxygraph-2k, to measure mitochondrial respiration. Basal respiration was lower in patients by 29.48%, pyruvate-stimulated respiration (respiratory chain complex I) was lower by 29.26%, and maximal respiratory capacity was lower by 28.15%. The decrease in succinate-stimulated respiration (respiratory chain complex II) was 26.91%. Our data confirm changes in mitochondrial respiration in ALS patients, manifested by the reduced function of complex I and complex II of the respiratory chain. These defects are severe enough to confirm this disease’s hypothesized mitochondrial damage. Therefore, research interest in the future should be directed towards a deeper understanding of the involvement of mitochondria and respiratory complexes in the pathophysiology of the disease. This understanding could develop new biomarkers in diagnostics and subsequent therapeutic interventions.

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease type of motor neuron disorder characterized by degeneration of the upper and lower motor neurons resulting in dysfunction of the somatic muscles of the body. The ALS condition is manifested in progressive skeletal muscle atrophy and spasticity. It leads to death, mostly due to respiratory failure. Within the pathophysiology of the disease, muscle energy metabolism seems to be an important part. In our study, we used blood plasma from 25 patients with ALS diagnosed by definitive El Escorial criteria according to ALSFR-R (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale) criteria and 25 age and sex-matched subjects. Aside from standard clinical biochemical parameters, we used the NMR (nuclear magnetic resonance) metabolomics approach to determine relative plasma levels of metabolites. We observed a decrease in total protein level in blood; however, despite accelerated skeletal muscle catabolism characteristic for ALS patients, we did not detect changes in plasma levels of essential amino acids. When focused on alterations in energy metabolism within muscle, compromised creatine uptake was accompanied by decreased plasma creatinine. We did not observe changes in plasma levels of BCAAs (branched chain amino acids; leucine, isoleucine, valine); however, the observed decrease in plasma levels of all three BCKAs (branched chain alpha-keto acids derived from BCAAs) suggests enhanced utilization of BCKAs as energy substrate. Glutamine, found to be increased in blood plasma in ALS patients, besides serving for ammonia detoxification, could also be considered a potential TCA (tricarboxylic acid) cycle contributor in times of decreased pyruvate utilization. When analyzing the data by using a cross-validated Random Forest algorithm, it finished with an AUC of 0.92, oob error of 8%, and an MCC (Matthew’s correlation coefficient) of 0.84 when relative plasma levels of metabolites were used as input variables. Although the discriminatory power of the system used was promising, additional features are needed to create a robust discriminatory model.

Background: Antibodies to glutamic acid decarboxylase (anti-GAD) can give rise to stiff person syndrome (SPS), an infrequent autoimmune condition of the central nervous system marked by fluctuating muscular rigidity and stimulus-evoked spasms. Disturbances in eye-movement control are rarely identified yet may provide insight into underlying neural involvement. Methods: Two individuals with anti-GAD-related SPS showing distinctive ocular-motor abnormalities were examined with quantitative videonystagmography, supplemented by representative video documentation. Results: Recordings demonstrated varied patterns of ocular-motor disturbance, including reduced smooth-pursuit accuracy, delayed saccadic initiation, dysmetria, intrusive saccades, and several nystagmus types. Partial improvement occurred after immunomodulatory therapy. Conclusions: These findings extend current understanding of the anti-GAD SPS phenotype and indicate that quantitative analysis of eye movements may offer a sensitive, non-invasive marker of disease activity. Larger, prospective studies are needed to clarify prevalence and responsiveness to treatment.

The autoimmune nodopathies are a distinct subgroup of immune-mediated polyneuropathies with characteristic clinical, pathophysiological, and electrophysiological features. IgG4 is the most frequently identified subclass and is typically associated with poor responsiveness to conventional therapies such as intravenous immunoglobulin and corticosteroids. However, emerging evidence highlights the relevance of non-IgG4 subclasses (e.g., IgG1), which may confer differential treatment responsiveness and prognostic implications. We report a 15-year-old boy with subacute, progressive distal sensorimotor polyneuropathy who initially fulfilled the clinical and electrophysiological criteria for the distal variant of chronic inflammatory demyelinating polyneuropathy. Despite multiple courses of IVIG, the patient’s symptoms worsened, prompting further investigation for nodal/paranodal antibodies. Serum testing revealed high-titre anti-NF155 antibodies of the IgG1 subclass, the IgG4 subclass was not detected. Due to the negative results of IgG4 we have decided not to start treatment with rituximab but with high-dose pulsed oral dexamethasone which resulted in marked clinical and electrophysiological improvement over a 36-month period, with excellent tolerance and no adverse effects. Pediatric patients presenting with demyelinating polyneuropathies unresponsive to intravenous immunoglobulins should be evaluated for autoimmune nodo-paranodopathies, including subclass-specific antibody profiling. In IgG1-NF155 associated autoimmune nodopathy, pulsed oral corticosteroids may represent an effective therapeutic option, whereas the response to intravenous immunoglobulin can be suboptimal.