Effect of GBA1 Mutations and APOE Polymorphisms on Survival and Progression Among Ashkenazi Jews with Dementia with Lewy Bodies.

BACKGROUND: Glucocerebrosidase 1 (GBA1) mutations are associated with reduced survival in Parkinson's disease but their effect on survival in dementia with Lewy bodies (DLB) is unclear. OBJECTIVE: To assess the impact of GBA1 mutations on survival among Ashkenazi Jews with DLB, while controlling for APOE status. METHODS: One hundred and forty participants from Tel Aviv Medical Center, Israel were genotyped for GBA1 mutations and APOE polymorphisms. Survival rates and follow-up cognitive screening scores were analyzed. RESULTS: GBA1 mutation carriers had a two-fold increased risk of death (HR = 1.999), while APOE status did not independently affect survival. In a subset of patients with available clinical data (N = 63), carriers of the APOE ε4 allele showed faster cognitive deterioration, while GBA1 mutation carriers also declined more rapidly albeit not significantly. CONCLUSION: Understanding the genetic effects on survival and progression is crucial for patient counseling and inclusion in clinical trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Long-term cognitive outcomes in Susac syndrome: A case series.

Susac syndrome (SuS) presents with encephalopathy, visual disturbances, and hearing loss from immune-mediated microvascular occlusion. While acute SuS is well-described, long-term cognitive outcomes with current treatments are underknown. We assessed ten SuS patients treated in accordance with evidence-based guidelines using immunotherapies targeting humoral and cell-mediated pathways. Patients were followed for a median 3.6 years. Initially, cognition inversely correlated with corpus callosum lesions on MRI. All reported cognitive improvement; 5/10 patients had residual deficits in visual attention and executive function. Early, aggressive treatment was associated with good outcomes; extensive early corpus callosum lesions may identify patients at-risk of persistent cognitive deficits.

Smartphone-based gait assessment for multiple sclerosis.

INTRODUCTION: Multiple Sclerosis causes gait alteration, even in the early stages of the disease. Traditional methods to quantify gait impairment, such as performance-based measures, lab-based motion analyses, and self-report, have limited ecological relevance. The Mon4t® app is a digital tool that uses sensors embedded in standard smartphones to measure various gait parameters. OBJECTIVES: To evaluate the use of Mon4t® technology in monitoring MS patients. METHODS: 100 MS patients and age-matched healthy controls were evaluated using both a human rater and the Mon4t Clinic™ app. Three motor tasks were performed: 3m Timed up and go test (TUG), 10m TUG, and tandem walk. The digital markers were used to compare MS vs. HC, MS with EDSS=0 vs. HC, and MS with EDSS=0 vs. MS with EDSS>0. Within the MS EDSS>0 group, correlations between digital gait markers and the EDSS score were calculated. RESULTS: Significant differences were found between MS patients and HC in multiple gait parameters. When comparing MS patients with minimal disability (EDSS=0) and HC: On the 3m TUG task, MS patients took longer to complete the task (mean difference 0.167seconds, p =0.034), took more steps (mean difference 1.32 steps, p =0.003), and had a weaker ML step-to-step correlation (mean difference 0.1, p = 0.001). The combination of features from the three motor tasks allowed distinguishing a nondisabled MS patient from a HC with high confidence (AUC of 85.65 on the ROC). When comparing MS patients with minimal disability (EDSS=0) to those with higher disability (EDSS>0): On the tandem walk task, patients with EDSS>0 took significantly longer to complete 10 steps than those with EDSS=0 (mean difference 4.63 seconds, p < 0.001), showed greater ML sway (mean difference 0.2, p < 0.001), and had larger angular velocity in the SI axis on average (mean difference 2.31 degrees/sec, p = 0.01). A classification model achieved 81.79 ROC AUC. In the subgroup of patients with EDSS>0, gait features significantly correlated with EDSS score in all three tasks. CONCLUSION: The findings demonstrate the potential of digital gait assessment to augment traditional disease monitoring and support clinical decision making. The Mon4t® app provides a convenient and ecologically relevant tool for monitoring MS patients and detecting early changes in gait impairment.

Olfactory function in Susac syndrome.

OBJECTIVES: Susac syndrome is a rare autoimmune endotheliopathy involving the brain, retina, and inner ear. Olfactory dysfunction is a common early manifestation of several central nervous system diseases, including neurodegenerative diseases and autoimmune-mediated diseases such as Multiple Sclerosis. While the literature is abundant about the Susac syndrome classic triad of encephalopathy, branch retinal artery occlusion, and low-frequency sensorineural hearing loss, little is known about the extent of olfactory sense involvement. METHODS: Using the Sniffin' Sticks test, this study evaluated olfactory function (identification and threshold) in ten recovering Susac syndrome patients under our clinic surveillance with a median of 3.1 (SD=1.53) years post-disease onset. RESULTS: olfactory assessment by threshold and odor identification were within the normal range. No differences between recovering Susac syndrome patients to standard norms of odor identification and threshold were found. CONCLUSIONS: Our findings do not support olfactory dysfunction in Susac syndrome and thereby, do not support olfactory assessment as a reliable biomarker for this condition.

BNT162b2 mRNA COVID-19 vaccine three-dose safety and risk of COVID-19 in patients with myasthenia gravis during the alpha, delta, and omicron waves.

COVID-19 affects the respiratory parenchyma and may potentially contribute to the tendency of myasthenia gravis (MG) patients to develop respiratory failure. It is, therefore, important to study the safety of vaccines against SARS-CoV-2 and to assess the risk of COVID-19 in MG patients. The safety of the three-dose BNT162b2 mRNA vaccine and outcomes of COVID-19 during the alpha, delta, and omicron waves were studied in MG patients as well as the rate of exacerbations and safety for a period of up to 6 weeks from each vaccine dose and patient morbidity and mortality during COVID-19 compared to the general population. 430 vaccine doses were administered across 150 patients. Thirteen patients (8.7%) complained of exacerbation within 6 weeks of each vaccine dose. Both MG onset rate and exacerbation rate were similar to previous years. MG exacerbation rate among fifteen patients who had COVID-19 was significantly higher (40%) compared to the rate following vaccination. During the alpha and delta waves, COVID-19 mortality and severe disease were significantly higher (26.7%) compared to the general population (0.96%). All of them were unvaccinated and had generalized MG. During the omicron wave, all the MG patients who contracted COVID-19 were vaccinated and had mild disease. We concluded that COVID-19 is hazardous for generalized MG patients, while the vaccination did not raise the risk for either exacerbation or new onset of MG and was associated with a reduced risk for severe COVID-19. Hence, it is recommended for generalized MG patients to get vaccinated.

CTGF/CCN2 has a possible detrimental role in the inflammation and the remyelination failure in the early stages of multiple sclerosis.

Connective tissue growth factor (CTGF/CCN2) is a proinflammatory and an oligodendrocyte-differentiating blocking agent. It is found in MS lesions, which raises the possibility of involvement in MS pathogenesis. We found that its CSF and serum levels were higher in RR-MS patients than in controls and for serum compared to PP and SP-MS. Immune cells of both RR-MS and controls secreted CTGF/CCN2, which was enhanced by CD3/CD28 stimulation or by LPS. Anti-CTGF treatment of mice with experimental autoimmune encephalitis ameliorated its clinical severity. CTGF/CCN2 may play a role in the immune pathogenesis of MS and in remyelination failure in early stages of MS.

Neurosyphilis presenting as cranial nerve palsy, an entity which is easy to miss.

Neurosyphilis is a rare disease that until the 2000s was almost eradicated due to population awareness of HIV and efficient treatment. Since then, the prevalence of the entity is rising due to risk-associated behaviour such as unprotected intercourse. Neurosyphilis is still a difficult entity to diagnose especially when combined with acute HIV infection which can influence the usual clinical course of disease. In rare occasions, both acute HIV and early syphilis infection can present as mono or multiple cranial nerve palsies. This case demonstrates a rare manifestation of misdiagnosed early syphilis infection combined with acute HIV infection in a 34-year-old man with prior history of unprotected sex with men.