The establishment of a molecular diagnostic platform for mitochondrial diseases: from conventional to next-generation sequencing.

Background: The aim of this study was to create a molecular diagnostic platform and establish a diagnostic pipeline for patients highly suspected of mitochondrial disorders. The effectiveness of three methods, namely, traditional restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR), Sanger sequencing for hotspot detection and whole mitochondrial DNA (mtDNA), and third-generation (Nanopore) whole mtDNA sequencing, will be compared in diagnosing patients with suspected primary mitochondrial diseases (PMDs). The strengths and limitations of different methods are also discussed.

Nerve conduction features may serve as a diagnostic clue for neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease is a neurodegenerative disorder with a wide phenotypic spectrum, including peripheral neuropathy. This study aims to characterize the nerve conduction features and proposes an electrophysiological criterion to assist the diagnosis of neuronal intranuclear inclusion disease. In this study, nerve conduction studies were performed in 50 genetically confirmed neuronal intranuclear inclusion disease patients, 200 age- and sex-matched healthy controls and 40 patients with genetically unsolved leukoencephalopathy.

Miro1 improves the exogenous engraftment efficiency and therapeutic potential of mitochondria transfer using Wharton's jelly mesenchymal stem cells.

Mitochondria are important for maintaining cellular energy metabolism and regulating cellular senescence. Mitochondrial DNA (mtDNA) encodes subunits of the OXPHOS complexes which are essential for cellular respiration and energy production. Meanwhile, mtDNA variants have been associated with the pathogenesis of neurodegenerative diseases, including MELAS, for which no effective treatment has been developed.

The Genetics of Primary Familial Brain Calcification: A Literature Review.

Primary familial brain calcification (PFBC), also known as Fahr's disease, is a rare inherited disorder characterized by bilateral calcification in the basal ganglia according to neuroimaging. Other brain regions, such as the thalamus, cerebellum, and subcortical white matter, can also be affected. Among the diverse clinical phenotypes, the most common manifestations are movement disorders, cognitive deficits, and psychiatric disturbances.

Blood neurofilament light chain as a surrogate marker for dystonia.

Background And Purpose: Dystonia is a heterogeneous movement disorder, and it remains unclear whether neurodegeneration is involved. Neurofilament light chain (NfL) is a biosignature of neurodegeneration. We aimed to investigate whether plasma NfL levels were elevated and associated with disease severity in patients with dystonia.

Higher prevalence of idiopathic normal pressure hydrocephalus-like MRI features in progressive supranuclear palsy: An imaging reminder of atypical parkinsonism.

Objectives: The classic triad of idiopathic normal pressure hydrocephalus (NPH) encompass gait disturbance, cognitive impairment, and urinary incontinence. These symptoms overlap with parkinsonism but with distinct treatment. Lacking applicable differentiation also hampers the prediction to therapeutic response.

Telbivudine-Induced Myopathy: Clinical Features, Histopathological Characteristics, and Risk Factors.

Background And Purpose: Oral nucleos(t)ide analogs (NAs) are the mainstay treatment for chronic hepatitis B (CHB). Myotoxicity is an important extrahepatic effect related to NA treatment. Telbivudine is the NA for CHB that is frequently associated with muscle-related side effects.

Iron Brain Menace: The Involvement of Ferroptosis in Parkinson Disease.

Parkinson disease (PD) is the second-most common neurodegenerative disease. The characteristic pathology of progressive dopaminergic neuronal loss in people with PD is associated with iron accumulation and is suggested to be driven in part by the novel cell death pathway, ferroptosis. A unique modality of cell death, ferroptosis is mediated by iron-dependent phospholipid peroxidation.

Clinical and genetic characterization of a Taiwanese cohort with spastic paraparesis combined with cerebellar involvement.

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders clinically characterized by progressive lower-limb spasticity. Cerebellar ataxia commonly co-occurs with complicated HSPs. HSP with concurrent cerebellar ataxia has significant clinical and genetic overlaps with hereditary cerebellar ataxia (HCA) and other inherited neurological diseases, adding to the challenge of planning genetic testing for the disease.

Spontaneous splenic rupture as the first clinical manifestation of Niemann-Pick disease type B: A case report and review of the literature.

Splenomegaly is the most common phenotype for Niemann-Pick disease type B (NPD-B), an autosomal recessive lipid storage disease caused by deficiency of the lysosomal enzyme acid sphingomyelinase. Although a spleen of massive volume is common in NPD-B, splenic rupture in this disease is rarely reported. We describe a patient with NPD-B who initially presented with spontaneous splenic rupture.

Two Birds One Stone: The Neuroprotective Effect of Antidiabetic Agents on Parkinson Disease-Focus on Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors.

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease affecting more than 1% of the population over 65 years old. The etiology of the disease is unknown and there are only symptomatic managements available with no known disease-modifying treatment. Aging, genes, and environmental factors contribute to PD development and key players involved in the pathophysiology of the disease include oxidative stress, mitochondrial dysfunction, autophagic-lysosomal imbalance, and neuroinflammation.

Glucagon-Like Peptide-1 Receptor Agonist Ameliorates 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Neurotoxicity Through Enhancing Mitophagy Flux and Reducing α-Synuclein and Oxidative Stress.

Parkinson disease (PD) is the second most common neurodegenerative disease without known disease modification therapy to slow down disease progression. This disease has pathological features of Lewy bodies with α-synuclein aggregation being the major component and selective dopaminergic neuronal loss over the substantia nigra. Although the exact etiology is still unknown, mitochondrial dysfunction has been shown to be central in PD pathophysiology.

Investigating DYT1 in a Taiwanese dystonia cohort.

Background/purpose: A heterozygous three-nucleotide (GAG) in-frame deletion in the TOR1A gene causes the rare disease, dystonia (DYT1), which typically presents as focal limb dystonia during adolescence, then spreads to other limbs. This study investigated the frequency and clinical features of DYT1 in a Taiwanese dystonia cohort.

Methods: We performed targeted next generation sequencing in 318 patients with primary dystonia.

Clinical and genetic characterization of hereditary spastic paraplegia type 3A in Taiwan.

Aim: To investigate the clinical and genetic features of hereditary spastic paraplegia (HSP) type 3A (SPG3A) in Taiwan.

Methods: Mutational analysis of the ATL1 gene was performed for 274 unrelated Taiwanese HSP patients. The diagnosis of SPG3A was ascertained by the presence of a heterozygous pathogenic mutation in ATL1.

Brain hypoperfusion and nigrostriatal dopaminergic dysfunction in primary familial brain calcification caused by novel MYORG variants: case report.

Background: Primary familial brain calcification (PFBC) is a rare inherited disease characterized by multiple calcified foci in the brain parenchyma. MYORG is the first gene found to be associated with autosomal recessive PFBC. The precise pathogenic mechanism of neurodegeneration in PFBC remains unclear.

Nutritional Status Associated with Molecular Biomarkers, Physiological Indices, and Clinical Severity in Parkinson's Disease Patients.

This study is intended to explore the associations between nutritional status and molecular biomarkers and the clinical severity of Parkinson's disease (PD), as well as to examine the differences in related factors between PD patients with normal nutrition and those with at risk for malnutrition. A cross-sectional assessment of 82 consecutive outpatients with PD was conducted using the mini nutritional assessment (MNA), Unified Parkinson's Disease Rating Scale (UPDRS), and the Hoehn and Yahr scale to determine the nutritional status, the clinical severity of PD, and the stage of the disease. Recordings of blood samples collected after 12 h of overnight fasting were also assessed in terms of serum levels of glycated hemoglobin (HbA1c), blood urea nitrogen (BUN), creatinine, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), hemoglobin (Hgb), folate, and vitamin B12.

Recessively-Inherited Adult-Onset Alexander Disease Caused by a Homozygous Mutation in the GFAP Gene.

Background: Alexander disease (AxD) is an autosomal-dominant leukodystrophy caused by heterozygous mutations in the glial fibrillary acidic protein (GFAP) gene.

Objectives: The objective of this report is to characterize the clinical phenotype and identify the genetic mutation associated with adult-onset AxD.

Methods: A man presented with progressive unsteadiness since age 16.

Spastic paraparesis as the first manifestation of Machado-Joseph disease: A case report and review of the literature.

Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3, is characterized by remarkable clinical heterogeneity. We present a MJD family in which variable phenotypes were noted in affected members, including one presenting predominantly with spastic paraparesis. A review of the literature revealed that MJD with the initial presentation of spastic paraparesis is more frequently observed in cases of eastern Asian origin who carry a greater CAG expansions in the ATXN3 gene.