Survey on Nutrition in Neurological Intensive Care Units (SONNIC)-A Cross-Sectional Survey among German-Speaking Neurointensivists on Medical Nutritional Therapy.

Medical nutritional therapy (MNT) in neurointensive care units (NICUs) is both particularly relevant and challenging due to prolonged analgosedation, immobilization, disorders of consciousness, and the high prevalence of dysphagia. Moreover, current guideline recommendations predominantly address the general intensive care unit (ICU) population, overlooking specific characteristics of neurological patients. We, therefore, conducted a web-based, cross-sectional survey for German-speaking neurointensivists mapping the clinical practices of MNT on NICUs to identify research gaps and common grounds for future clinical trials. A total of 25.9% (56/216) NICU representatives responded to our questionnaire. A total of 78.2% (43/55) were neurologist and 63% (34/54) held a leadership role. Overall, 80.4% (41/51) had established a standard operating procedure (SOP), largely based on the DGEM-Guideline (53.7%; 22/41), followed by the ESPEN-Guideline (14.6%; 6/41). Upon admission, 36% (18/50) conducted a risk stratification, with 83.3% primarily relying on past medical history (15/18) and clinical gestalt (15/18). Energy expenditure (EE) was measured or calculated by 75% (36/48), with 72.2% (26/36) using pragmatic weight-based equations. Indirect calorimetry was used by 19.4% (7/36). A total of 83.3% (30/36) used the patient's serum glucose level as the primary biomarker to monitor metabolic tolerance. SOPs regarding ICU-Acquired Weakness (ICUAW) were found in 8.9% (4/45) of respondents. Overall, guideline adherence was 47%. In summary, this is, to the best of our knowledge, the first study systematically describing the currently applied concepts of MNT on NICUs. The data reveal great variations in the implementation of guideline recommendations, indicating the need for further research and tailored approaches to optimize nutritional therapy in neurointensive care settings.

The new missense G376V-TDP-43 variant induces late-onset distal myopathy but not amyotrophic lateral sclerosis.

TDP-43-positive inclusions in neurons are a hallmark of several neurodegenerative diseases including familial amyotrophic lateral sclerosis (fALS) caused by pathogenic TARDBP variants as well as more common non-Mendelian sporadic ALS (sALS). Here we report a G376V-TDP-43 missense variant in the C-terminal prion-like domain of the protein in two French families affected by an autosomal dominant myopathy but not fulfilling diagnostic criteria for ALS. Patients from both families presented with progressive weakness and atrophy of distal muscles, starting in their 5th-7th decade. Muscle biopsies revealed a degenerative myopathy characterized by accumulation of rimmed (autophagic) vacuoles, disruption of sarcomere integrity and severe myofibrillar disorganization. The G376 V variant altered a highly conserved amino acid residue and was absent in databases on human genome variation. Variant pathogenicity was supported by in silico analyses and functional studies. The G376 V mutant increased the formation of cytoplasmic TDP-43 condensates in cell culture models, promoted assembly into high molecular weight oligomers and aggregates in vitro, and altered morphology of TDP-43 condensates arising from phase separation. Moreover, the variant led to the formation of cytoplasmic TDP-43 condensates in patient-derived myoblasts and induced abnormal mRNA splicing in patient muscle tissue. The identification of individuals with TDP-43-related myopathy but not ALS implies that TARDBP missense variants may have more pleiotropic effects than previously anticipated and support a primary role for TDP-43 in skeletal muscle pathophysiology. We propose to include TARDBP screening in the genetic work-up of patients with late-onset distal myopathy. Further research is warranted to examine the precise pathogenic mechanisms of TARDBP variants causing either a neurodegenerative or myopathic phenotype.

Intrahospital Transport of Critically Ill Patients with Subarachnoid Hemorrhage-Frequency, Timing, Complications, and Clinical Consequences.

BACKGROUND: Patients with subarachnoid hemorrhage (SAH) often necessitate intra-hospital transport (IHT) during intensive care treatment. These transfers to facilities outside of the neurointensive care unit (NICU) pose challenges due to the inherent instability of the hemodynamic, respiratory, and neurological parameters that are typical in these patients. METHODS: In this retrospective, single-center cohort study, a total of 108 IHTs were analyzed for demographics, transport rationale, clinical outcomes, and pre/post-IHT monitoring parameters. After establishing clinical thresholds, the frequency of complications was calculated, and predictors of thresholds violations were determined. RESULTS: The mean age was 55.7 (+/-15.3) years, with 68.0% showing severe SAH (World Federation of Neurosurgical Societies Scale 5). IHTs with an emergency indication made up 30.8% of all transports. Direct therapeutic consequences from IHT were observed in 38.5%. On average, the first IHT occurred 1.5 (+/-2.0) days post-admission and patients were transported 4.3 (+/-1.8) times during their stay in the NICU. Significant parameter changes from pre- to post-IHT included mean arterial pressure, systolic blood pressure, oxygen saturation, blood glucose levels, temperature, dosages of propofol and ketamine, tidal volume, inspired oxygen concentration, Horovitz index, glucose, pH, intracranial pressure, and cerebral perfusion pressure. Relevant hemodynamic thresholds were violated in 31.5% of cases, while respiratory complications occurred in 63.9%, and neurological complications in 20.4%. For hemodynamic complications, a low heart rate with a threshold of 61/min (OR 0.96, 95% CI 0.93-0.99, p = 0.0165) and low doses of midazolam with a threshold of 17.5 mg/h (OR 0.97, 95% CI 0.95-1.00, p = 0.0232) significantly predicted adverse events. However, the model did not identify significant predictors for respiratory and neurological outcomes. CONCLUSIONS: Conclusively, IHTs in SAH patients are associated with relevant changes in hemodynamic, respiratory, and neurological monitoring parameters, with direct therapeutic consequences in 4/10 IHTs. These findings underscore the importance of further studies on the clinical impact of IHTs.

Vitamin B12 in Leber hereditary optic neuropathy mutation carriers: a prospective cohort study.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder, frequently resulting in acute or subacute severe bilateral central vision loss. Vitamin B12 deficiency is also a known cause of optic neuropathy through mitochondrial dysfunction. Here we evaluated the prevalence and clinical significance of vitamin B12 deficiency in a large cohort of LHON patients and asymptomatic mutation carriers from a tertiary referral center. METHODS: From the Munich LHON prospective cohort study, participants included all LHON patients and asymptomatic LHON mutation carriers, who were recruited between February 2014 and March 2020 and consented to participate. Neurological, general, and ophthalmological examinations were regularly performed, as were laboratory tests. Vitamin B12 deficiency was diagnosed if serum vitamin B12 was below 201 pg/mL, or if 201-339 pg/mL plus low serum holotranscobalamin or elevated serum methylmalonic acid or elevated total plasma homocysteine. RESULTS: We analyzed 244 subjects, including 147 symptomatic LHON patients (74% males) and 97 asymptomatic mutation carriers (31% males). Median age at study baseline was 34 years (range 5-82 years). The prevalence of vitamin B12 deficiency was higher for LHON mutation carriers than for the general population in all age categories. This was statistically significant for the LHON mutation carriers under 65 years (21% vs. 5-7%, p = 0.002). While vitamin B12 deficiency prevalence was not statistically different between LHON patients and asymptomatic mutation carriers, its clinical correlates, e.g., macrocytosis and polyneuropathy, were more frequent in the subgroup of LHON patients. Excessive alcohol consumption was a significant predictor of vitamin B12 deficiency (p < 0.05). CONCLUSIONS: The high prevalence of vitamin B12 deficiency in LHON mutation carriers, both asymptomatic mutation carriers and LHON patients, highlights the need for regular vitamin B12 screening in this population, in order to ensure early treatment, aiming for better outcomes. Our study is not conclusive regarding vitamin B12 deficiency as determinant for disease conversion in LHON, and further research is warranted to disentangle the role of vitamin B12 in the pathophysiology and prognosis of LHON.