Nocturnal vestibular stimulation using a rocking bed improves a severe sleep disorder in a patient with mitochondrial disease.

Mitochondrial diseases are rare genetic disorders often accompanied by severe sleep disorders. We present the case of a 12-year-old boy diagnosed with a severe primary mitochondrial disease, exhibiting ataxia, spasticity, progressive external ophthalmoplegia, cardiomyopathy and severely disrupted sleep, but no cognitive impairment. Interestingly, his parents reported improved sleep during night train rides. Based on this observation, we installed a rocking bed in the patient's bedroom and performed different interventions, including immersive multimodal vestibular, kinesthetic and auditory stimuli, reminiscent of the sensory experiences encountered during train rides. Over a 5-month period, we conducted four 2-week nocturnal interventions, separated by 1-week washout phases, to determine the subjectively best-perceived stimulation parameters, followed by a final 4-week intervention using the optimal parameters. We assessed sleep duration and quality using the Mini Sleep Questionnaire, monitored pulse rate changes and used videography to document nocturnal interactions between the patient and caregivers. Patient-reported outcome measures, clinical examinations and personal outcomes of specific interests were used to document daytime sleepiness, restlessness, anxiety, fatigue, cognitive performance and physical posture. In the final 4-week intervention, sleep duration increased by 25%, required caregiver interactions reduced by 75%, and caregiving time decreased by 40%. Subjective fatigue, assessed by the Checklist Individual Strength, decreased by 40%, falling below the threshold of severe fatigue. Our study suggests that rocking beds could provide a promising treatment regime for selected patients with persistent severe sleep disorders. Further research is required to validate these findings in larger patient populations with sleep disorders and other conditions.

Do cardiopulmonary exercise tests predict summit success and acute mountain sickness? A prospective observational field study at extreme altitude.

OBJECTIVE: During a high-altitude expedition, the association of cardiopulmonary exercise testing (CPET) parameters with the risk of developing acute mountain sickness (AMS) and the chance of reaching the summit were investigated. METHODS: Thirty-nine subjects underwent maximal CPET at lowlands and during ascent to Mount Himlung Himal (7126 m) at 4844 m, before and after 12 days of acclimatisation, and at 6022 m. Daily records of Lake-Louise-Score (LLS) determined AMS. Participants were categorised as AMS+ if moderate to severe AMS occurred. RESULTS: Maximal oxygen uptake (V̇O2max) decreased by 40.5%±13.7% at 6022 m and improved after acclimatisation (all p<0.001). Ventilation at maximal exercise (VEmax) was reduced at 6022 m, but higher VEmax was related to summit success (p=0.031). In the 23 AMS+ subjects (mean LLS 7.4±2.4), a pronounced exercise-induced oxygen desaturation (ΔSpO2exercise) was found after arrival at 4844 m (p=0.005). ΔSpO2exercise >-14.0% identified 74% of participants correctly with a sensitivity of 70% and specificity of 81% for predicting moderate to severe AMS. All 15 summiteers showed higher V̇O2max (p<0.001), and a higher risk of AMS in non-summiteers was suggested but did not reach statistical significance (OR: 3.64 (95% CI: 0.78 to 17.58), p=0.057). V̇O2max ≥49.0 mL/min/kg at lowlands and ≥35.0 mL/min/kg at 4844 m predicted summit success with a sensitivity of 46.7% and 53.3%, and specificity of 83.3% and 91.3%, respectively. CONCLUSION: Summiteers were able to sustain higher VEmax throughout the expedition. Baseline V̇O2max below 49.0 mL/min/kg was associated with a high chance of 83.3% for summit failure, when climbing without supplemental oxygen. A pronounced drop of SpO2exercise at 4844 m may identify climbers at higher risk of AMS.

Triheptanoin - Novel therapeutic approach for the ultra-rare disease mitochondrial malate dehydrogenase deficiency.

Mitochondrial malate dehydrogenase (MDH2) deficiency (MDH2D) is an ultra-rare disease with only three patients described in literature to date. MDH2D leads to an interruption of the tricarboxylic acid (TCA) cycle and malate-aspartate shuttle (MAS) and results in severe early onset encephalopathy. Affected infants suffer from psychomotor delay, muscular hypotonia and frequent seizures. Laboratory findings are unspecific, including elevated lactate in blood and cerebrospinal fluid. Brain magnetic resonance imaging reveals delayed myelination and brain atrophy. Currently there is no curative therapy to treat this devastating disease. Here, we present a female patient diagnosed with MDH2D after a stroke-like episode at 18 months. Trio-whole exome sequencing revealed compound heterozygous missense variants in the MDH2 gene: c.398C>T, p.(Pro133Leu) and c.445delinsACA, p.(Pro149Hisfs*22). MDH2 activity assay and oxygraphic analysis in patient's fibroblasts confirmed the variants were pathogenic. At the age of 36 months, a drug trial with triheptanoin was initiated and well tolerated. The patient's neurologic and biochemical phenotype improved and she had no further metabolic decompensations during the treatment period suggesting a beneficial effect of triheptanoin on MDH2D. Further preclinical and clinical studies are required to evaluate triheptanoin treatment for MDH2D and other TCA cycle and MAS defects.