Time-Restricted Ketogenic Diet in Huntington's Disease: A Case Study.

Huntington's disease (HD) is a progressive, fatal neurodegenerative disorder with limited treatment options. Substantial evidence implicates mitochondria dysfunction in brain and skeletal muscle in the pathogenesis of HD. Metabolic strategies, such as fasting and ketogenic diets, theoretically enhance brain and muscle metabolism and mitochondria function, which may improve the clinical symptoms of HD. We report the case of a 41-year-old man with progressive, deteriorating HD who pursued a time-restricted ketogenic diet (TRKD) for 48 weeks. Improvements were measured in his motor symptoms (52% improvement from baseline), activities of daily living (28% improvement), composite Unified HD Rating Scale (cUHDRS) score (20% improvement), HD-related behavior problems (apathy, disorientation, anger, and irritability improved by 50-100%), and mood-related quality of life (25% improvement). Cognition did not improve. Weight remained stable and there were no significant adverse effects. This case study is unique in that a patient with progressive, deteriorating HD was managed with a TRKD, with subsequent improvements in his motor symptoms, activities of daily living, cUHDRS score, most major HD-related behavior problems, and quality of life. Our patient remains dedicated to his TRKD, which continues to provide benefit for him and his family.

Extended Interval Dosing Natalizumab and impact on neuropsychological deficits in Relapsing-Remitting Multiple Sclerosis.

Background: Cognitive impairment and neuropsychiatric symptoms are frequently reported in Relapsing-Remitting Multiple Sclerosis (RRMS). Natalizumab (NTZ) is usually administered on a 4-weekly Standard Interval Dosing (SID) schedule. However, Extended Interval Dosing (EID) at 6-8 weekly intervals has been proven non-inferior regarding relapse risk, with a lower risk of Progressive Multifocal Leukoencephalopathy (PML). The impact of EID NTZ on neuropsychological deficits in RRMS has not been studied. Objective: To determine if EID NTZ demonstrates an improvement in neuropsychological parameters in RRMS patients. Method: We performed a retrospective, observational analysis of 34 RRMS patients treated between August 2015-2017. Patients underwent baseline neuropsychological testing before commencing EID NTZ. A second evaluation was performed, on average 28 months after commencing treatment. Results: Z scores at the initial assessment showed baseline cognitive impairment in multiple domains. 14/20 Z-scores showed an improvement post-NTZ and 5/14 reached statistical significance; namely Trails A (visual attention/processing speed), Line-orientation (visual-spatial), Picture-naming (word finding), Digital-Span (attention, executive function and memory) and Story-recall (memory). The Hospital Anxiety and Depression Scale (HADS) data remained unchanged. Correlation matrix showed no association between HADS scores, the time between assessments and the changes in Z scores. Conclusion: This data suggests the efficacy of EID NTZ in improving cognitive impairment in RRMS. A prospective observational study is warranted.

Metabolics risk factors in a New Zealand glioblastoma cohort.

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive form of glioma. There is growing recognition that mitochondrial metabolism plays a role in cancer development. Metabolic syndrome is a risk factor for several cancers; however, the prevalence in GBM patients in New Zealand (NZ) is unknown. We hypothesized that patients with GBM would show a higher prevalence of metabolic syndrome compared to the general NZ population and that metabolic syndrome may be associated with worsened overall survival (OS) in GBM. METHODS: We performed a retrospective analysis in 170 patients diagnosed and treated for GBM between 2005 and 2020. Clinical and biochemical data were collected with regard to 5 metabolic criteria. OS was determined from the date of initial surgical diagnosis to the date of death or date of data acquisition. RESULTS: Of 170 patients, 31 (18.2%) met the diagnostic criteria for metabolic syndrome. The prevalence of metabolic syndrome in our cohort did not significantly differ from that of the general NZ population. However, OS in patients with metabolic syndrome was significantly worse compared to patients without metabolic syndrome (8.0 vs 13.0 months, P = .016). Patients who received a lower dexamethasone dose had significantly better survival outcomes (15.0 vs 5.0 months, P < .01). Differences in OS did not differ by gender or ethnicity. CONCLUSIONS: We have shown that metabolic syndrome is associated with reduced OS in a NZ cohort of GBM patients. This finding further strengthens the possibility that a metabolic pathogenesis may underpin GBM. However, prospective clinical trials are needed.

Randomized crossover trial of a modified ketogenic diet in Alzheimer's disease.

BACKGROUND: Brain energy metabolism is impaired in Alzheimer's disease (AD), which may be mitigated by a ketogenic diet. We conducted a randomized crossover trial to determine whether a 12-week modified ketogenic diet improved cognition, daily function, or quality of life in a hospital clinic of AD patients. METHODS: We randomly assigned patients with clinically confirmed diagnoses of AD to a modified ketogenic diet or usual diet supplemented with low-fat healthy-eating guidelines and enrolled them in a single-phase, assessor-blinded, two-period crossover trial (two 12-week treatment periods, separated by a 10-week washout period). Primary outcomes were mean within-individual changes in the Addenbrookes Cognitive Examination - III (ACE-III) scale, AD Cooperative Study - Activities of Daily Living (ADCS-ADL) inventory, and Quality of Life in AD (QOL-AD) questionnaire over 12 weeks. Secondary outcomes considered changes in cardiovascular risk factors and adverse effects. RESULTS: We randomized 26 patients, of whom 21 (81%) completed the ketogenic diet; only one withdrawal was attributed to the ketogenic diet. While on the ketogenic diet, patients achieved sustained physiological ketosis (12-week mean beta-hydroxybutyrate level: 0.95 ± 0.34 mmol/L). Compared with usual diet, patients on the ketogenic diet increased their mean within-individual ADCS-ADL (+ 3.13 ± 5.01 points, P = 0.0067) and QOL-AD (+ 3.37 ± 6.86 points, P = 0.023) scores; the ACE-III also increased, but not significantly (+ 2.12 ± 8.70 points, P = 0.24). Changes in cardiovascular risk factors were mostly favourable, and adverse effects were mild. CONCLUSIONS: This is the first randomized trial to investigate the impact of a ketogenic diet in patients with uniform diagnoses of AD. High rates of retention, adherence, and safety appear to be achievable in applying a 12-week modified ketogenic diet to AD patients. Compared with a usual diet supplemented with low-fat healthy-eating guidelines, patients on the ketogenic diet improved in daily function and quality of life, two factors of great importance to people living with dementia. TRIAL REGISTRATION: This trial is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12618001450202 . The trial was registered on August 28, 2018.

Perry syndrome: a case of atypical parkinsonism with confirmed DCTN1 mutation.

Perry syndrome is a rare neurological condition characterised clinically by depression, sleep disturbance, central hypoventilation and parkinsonism. Perry syndrome is a TAR DNA-binding protein 43 (TDP-43) proteinopathy associated with mutated dynactin-1 protein, inherited in an autosomal dominant manner. Several pathogenic mutations in exon 2 in the dynactin 1 gene have been identified; p. F521, p. G67d, p. G71R, p. G71E, p. G71A, p. T72p, p. Q74p and p. Y78C. We present the second known case Perry syndrome with confirmed DCTN1 mutation (p. Y78C) in New Zealand, who initially was thought to have a depressive illness. Perry syndrome should be considered in the differential diagnosis of young parkinsonism, especially if there is family history of sleep disorders, weight loss and/or marked depression.