Overlapping Leigh Syndrome/Myoclonic Epilepsy With Ragged Red Fibres in an Adolescent Patient With a Mitochondrial DNA A8344G Mutation

We present the case of a 16-year-old boy with a family history of epilepsy who presented with acute respiratory failure, limb weakness, diabetes mellitus, sinus tachycardia, lactic acidosis, and pneumonia. He went on to develop cranial nerve palsy, myoclonus, generalized seizures, ataxia, recurrent pneumonia, and hypotension. Biochemical investigation revealed elevated lactate, pyruvate, and glucose levels. Cerebral magnetic resonance imaging (MRI) revealed bilateral, symmetric, high-intensity T2-weighted signals in the thalamus, brainstem, and gray matter of the spinal cord. Histochemical analyses revealed ragged red fibers (RRF) and decreased cytochrome oxidase activity. Blood and muscle-derived DNA demonstrated a high level (95% and 96%, respectively) of the m.8344A>G mutation, while almost all of his maternal relatives (n = 17, including his mother) carried the same point mutation. The point mutation level of his mother (who had short stature, high blood lactate levels, and epilepsy) was 77% (blood-derived DNA). Although this mutation has been identified in approximately 30 individuals with these disorders, to our knowledge, this is the first reported case of overlapping Leigh syndrome/myoclonic epilepsy with RRF in an adolescent patient, and the largest reported pedigree of mitochondrial DNA A8344G mutation

Fatigue and long duration of infection are associated with worsen motor and non‐motor symptoms in Parkinson's disease following Omicron COVID‐19 pandemic

Abstract Background Coronavirus disease 2019 (COVID‐19) may influence the clinical course and symptoms of chronic neurological diseases, such as Parkinson's disease (PD), which can persist even after recovery from the infection. This longitudinal study aimed at exploring the impact of the COVID‐19 on motor and non‐motor symptoms and the related risk factors for exacerbation of PD symptoms. Methods One hundred and two PD patients underwent a first assessment between September 2022 and November 2022 (T0) before Omicron COVID‐19 pandemic. They were then contacted again and asked to complete the second assessment between December 2022 and February 2023 (T1) following Omicron infection. Movement Disorders Society Unified PD Rating Scale Part III, Non‐Motor Symptoms Scale, Fatigue Severity Scale (FSS), and quality of life were investigated. Results Ninety‐five PD patients (93.1%) with COVID‐19 for the first time were mild cases. However, 55 patients (55.9%) experienced worsening motor symptoms of PD after recovering from the infectious symptoms. Preinfection FSS score (odds ratios [OR] 2.062, 95% confidence interval [CI] 1.081–3.933, p = .028) and duration of infection (OR 1.232, 95% CI 1.024–1.481, p = .027) were independent risk factors for the worsening of motor symptoms. PD patients with post‐COVID‐19 fatigue were more likely to experience worsened non‐motor symptoms, resulting in an impaired quality of life. Conclusion This study confirms the impact of the Omicron COVID‐19 pandemic on the motor and non‐motor symptoms of PD, suggesting that management of related factors, including fatigue and duration of infection, may be beneficial in preventing or dealing with the exacerbation of PD symptoms after infection

Cognitive Impairments in LRRK2-Related Parkinson’s Disease: A Study in Chinese Individuals

Background. LRRK2 S1647T has been identified as a polymorphic risk variant for Parkinson’s disease (PD) in Chinese individuals. As LRRK2 is the most common genetic cause for PD, it has drawn great interest regarding whether cognitive impairments in PD are related with LRRK2. Purpose. This study aimed to explore the effects of LRRK2 S1647T polymorphism on cognitive function in PD. Method. 90 PD patients were randomly recruited. They underwent a series of clinical evaluations and genetic testing for the LRRK2 S1647T polymorphism. Global intellect and five cognitive domains (language fluency, visuospatial function, attention, memory, and executive function) were compared between S1647T carriers and noncarriers. Results. No differences in motor features were found between two groups, but the executive function evaluation showed that Stroop word colour test time (SWCT-TIME) scores were lower in LRRK2 S1647T carriers than in noncarriers (P=0.017). However, multiple linear regression analysis indicated that the correlation between S1647T polymorphism and SWCT-TIME scores did not reach significant level (P=0.051). Conclusion. Our findings suggest that cognitive impairments are not correlated with different LRRK2 S1647T polymorphisms in Chinese PD individuals

Mitochondrial haplogroups and cognitive progression in Parkinson's disease

International audienceMitochondria are a culprit in the onset of Parkinson's disease, but their role during disease progression is unclear. Here we used Cox proportional hazards models to exam the effect of variation in the mitochondrial genome on longitudinal cognitive and motor progression over time in 4064 patients with Parkinson's disease. Mitochondrial macro-haplogroup was associated with reduced risk of cognitive disease progression in the discovery and replication population. In the combined analysis, patients with the super macro-haplogroup J, T, U# had a 41% lower risk of cognitive progression with P = 2.42 × 10-6 compared to those with macro-haplogroup H. Exploratory analysis indicated that the common mitochondrial DNA variant, m.2706A>G, was associated with slower cognitive decline with a hazard ratio of 0.68 (95% confidence interval 0.56-0.81) and P = 2.46 × 10-5. Mitochondrial haplogroups were not appreciably linked to motor progression. This initial genetic survival study of the mitochondrial genome suggests that mitochondrial haplogroups may be associated with the pace of cognitive progression in Parkinson's disease over time

Mitochondrial haplogroups and cognitive progression in Parkinson's disease.

Mitochondria are a culprit in the onset of Parkinson's disease, but their role during disease progression is unclear. Here we used Cox proportional hazards models to exam the effect of variation in the mitochondrial genome on longitudinal cognitive and motor progression over time in 4064 patients with Parkinson's disease. Mitochondrial macro-haplogroup was associated with reduced risk of cognitive disease progression in the discovery and replication population. In the combined analysis, patients with the super macro-haplogroup J, T, U# had a 41% lower risk of cognitive progression with P = 2.42 × 10-6 compared to those with macro-haplogroup H. Exploratory analysis indicated that the common mitochondrial DNA variant, m.2706A>G, was associated with slower cognitive decline with a hazard ratio of 0.68 (95% confidence interval 0.56-0.81) and P = 2.46 × 10-5. Mitochondrial haplogroups were not appreciably linked to motor progression. This initial genetic survival study of the mitochondrial genome suggests that mitochondrial haplogroups may be associated with the pace of cognitive progression in Parkinson's disease over time

Evidence of a resonant structure in the e+e−→π+D0D∗−e^+e^-\to \pi^+D^0D^{*-} cross section between 4.05 and 4.60 GeV

The cross section of the process e+e-→π+D0D*- for center-of-mass energies from 4.05 to 4.60 GeV is measured precisely using data samples collected with the BESIII detector operating at the BEPCII storage ring. Two enhancements are clearly visible in the cross section around 4.23 and 4.40 GeV. Using several models to describe the dressed cross section yields stable parameters for the first enhancement, which has a mass of 4228.6±4.1±6.3  MeV/c2 and a width of 77.0±6.8±6.3  MeV, where the first uncertainties are statistical and the second ones are systematic. Our resonant mass is consistent with previous observations of the Y(4220) state and the theoretical prediction of a DD¯1(2420) molecule. This result is the first observation of Y(4220) associated with an open-charm final state. Fits with three resonance functions with additional Y(4260), Y(4320), Y(4360), ψ(4415), or a new resonance do not show significant contributions from either of these resonances. The second enhancement is not from a single known resonance. It could contain contributions from ψ(4415) and other resonances, and a detailed amplitude analysis is required to better understand this enhancement