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Epilepsia Jul 2024DYNC1H1 variants are involved on a disease spectrum from neuromuscular disorders to neurodevelopmental disorders. DYNC1H1-related epilepsy has been reported in small...
OBJECTIVE
DYNC1H1 variants are involved on a disease spectrum from neuromuscular disorders to neurodevelopmental disorders. DYNC1H1-related epilepsy has been reported in small cohorts. We dissect the electroclinical features of 34 patients harboring de novo DYNC1H1 pathogenic variants, identify subphenotypes on the DYNC1H1-related epilepsy spectrum, and compare the genotype-phenotype correlations observed in our cohort with the literature.
METHODS
Patients harboring de novo DYNC1H1 pathogenic variants were recruited through international collaborations. Clinical data were retrospectively collected. Latent class analysis was performed to identify subphenotypes. Multivariable binary logistic regression analysis was applied to investigate the association with DYNC1H1 protein domains.
RESULTS
DYNC1H1-related epilepsy presented with infantile epileptic spasms syndrome (IESS) in 17 subjects (50%), and in 25% of these individuals the epileptic phenotype evolved into Lennox-Gastaut syndrome (LGS). In 12 patients (35%), focal onset epilepsy was defined. In two patients, the epileptic phenotype consisted of generalized myoclonic epilepsy, with a progressive phenotype in one individual harboring a frameshift variant. In approximately 60% of our cohort, seizures were drug-resistant. Malformations of cortical development were noticed in 79% of our patients, mostly on the lissencephaly-pachygyria spectrum, particularly with posterior predominance in a half of them. Midline and infratentorial abnormalities were additionally reported in 45% and 27% of subjects. We have identified three main classes of subphenotypes on the DYNC1H1-related epilepsy spectrum.
SIGNIFICANCE
We propose a classification in which pathogenic de novo DYNC1H1 variants feature drug-resistant IESS in half of cases with potential evolution to LGS (Class 1), developmental and epileptic encephalopathy other than IESS and LGS (Class 2), or less severe focal or genetic generalized epilepsy including a progressive phenotype (Class 3). We observed an association between stalk domain variants and Class 1 phenotypes. The variants p.Arg309His and p.Arg1962His were common and associated with Class 1 subphenotype in our cohort. These findings may aid genetic counseling of patients with DYNC1H1-related epilepsy.
PubMed: 38953796
DOI: 10.1111/epi.18054 -
Journal of Cellular and Molecular... Jul 2024Both osteoporosis and tendinopathy are widely prevalent disorders, encountered in diverse medical contexts. Whilst each condition has distinct pathophysiological... (Review)
Review
Both osteoporosis and tendinopathy are widely prevalent disorders, encountered in diverse medical contexts. Whilst each condition has distinct pathophysiological characteristics, they share several risk factors and underlying causes. Notably, oxidative stress emerges as a crucial intersecting factor, playing a pivotal role in the onset and progression of both diseases. This imbalance arises from a dysregulation in generating and neutralising reactive oxygen species (ROS), leading to an abnormal oxidative environment. Elevated levels of ROS can induce multiple cellular disruptions, such as cytotoxicity, apoptosis activation and reduced cell function, contributing to tissue deterioration and weakening the structural integrity of bones and tendons. Antioxidants are substances that can prevent or slow down the oxidation process, including Vitamin C, melatonin, resveratrol, anthocyanins and so on, demonstrating potential in treating these overlapping disorders. This comprehensive review aims to elucidate the complex role of oxidative stress within the interlinked pathways of these comorbid conditions. By integrating contemporary research and empirical findings, our objective is to outline new conceptual models and innovative treatment strategies for effectively managing these prevalent diseases. This review underscores the importance of further in-depth research to validate the efficacy of antioxidants and traditional Chinese medicine in treatment plans, as well as to explore targeted interventions focused on oxidative stress as promising areas for future medical advancements.
Topics: Humans; Oxidative Stress; Osteoporosis; Antioxidants; Tendinopathy; Reactive Oxygen Species; Animals
PubMed: 38953556
DOI: 10.1111/jcmm.18508 -
Epilepsy & Behavior Reports 2024In this patient, now 42 years old, genetic generalized epilepsy (juvenile myoclonic epilepsy) manifested itself at the age of 13. At the age of 39, she experienced a...
In this patient, now 42 years old, genetic generalized epilepsy (juvenile myoclonic epilepsy) manifested itself at the age of 13. At the age of 39, she experienced a status episode with prolonged ICU treatment. She was left with a left-sided hippocampal sclerosis and probably focal seizures. In addition, since the age of 24, the patient also experiences functional seizures on the background of a borderline personality disorder. While generalized epileptic seizures could be controlled with antiseizure medication (ASM), the patient was multiple times admitted to Emergency Departments for her functional seizures with subsequent intensive care treatments, including intubation. As a complication, the patient developed critical illness polyneuropathy and myopathy, resulting in wheelchair dependence. Additionally, she acquired a complex regional pain syndrome after extravasation of ASM. The report demonstrates the uncommon development of hippocampal sclerosis after a generalized tonic-clonic status epilepticus and the poor treatability of functional seizures as compared to generalized and focal seizures.
PubMed: 38953098
DOI: 10.1016/j.ebr.2024.100684 -
Frontiers in Immunology 2024Antiglycine receptor (anti-GlyR) antibody mediates multiple immune-related diseases. This study aimed to summarize the clinical features to enhance our understanding of... (Review)
Review
BACKGROUND AND OBJECTIVES
Antiglycine receptor (anti-GlyR) antibody mediates multiple immune-related diseases. This study aimed to summarize the clinical features to enhance our understanding of anti-GlyR antibody-related disease.
METHODS
By collecting clinical information from admitted patients positive for glycine receptor (GlyR) antibody, the clinical characteristics of a new patient positive for GlyR antibody were reported in this study. To obtain additional information regarding anti-GlyR antibody-linked illness, clinical data and findings on both newly reported instances in this study and previously published cases were merged and analyzed.
RESULTS
A new case of anti-GlyR antibody-related progressive encephalomyelitis with rigidity and myoclonus (PERM) was identified in this study. A 20-year-old man with only positive cerebrospinal fluid anti-GlyR antibody had a good prognosis with first-line immunotherapy. The literature review indicated that the common clinical manifestations of anti-GlyR antibody-related disease included PERM or stiff-person syndrome (SPS) (n = 179, 50.1%), epileptic seizure (n = 94, 26.3%), and other neurological disorders (n = 84, 24.5%). Other neurological issues included demyelination, inflammation, cerebellar ataxia and movement disorders, encephalitis, acute psychosis, cognitive impairment or dementia, celiac disease, Parkinson's disease, neuropathic pain and allodynia, steroid-responsive deafness, hemiballism/tics, laryngeal dystonia, and generalized weakness included respiratory muscles. The group of PERM/SPS exhibited a better response to immunotherapy than others.
CONCLUSIONS
The findings suggest the presence of multiple clinical phenotypes in anti-GlyR antibody-related disease. Common clinical phenotypes include PERM, SPS, epileptic seizure, and paraneoplastic disease. Patients with RERM/SPS respond well to immunotherapy.
Topics: Humans; Male; Receptors, Glycine; Autoantibodies; Young Adult; Encephalomyelitis; Muscle Rigidity; Myoclonus; Stiff-Person Syndrome; Adult
PubMed: 38953026
DOI: 10.3389/fimmu.2024.1387591 -
Nigerian Medical Journal : Journal of... 2023Neurological disorders constitute major causes of morbidity, and globally, they are the leading causes of death. There is a dearth of neurologists in most African...
BACKGROUND
Neurological disorders constitute major causes of morbidity, and globally, they are the leading causes of death. There is a dearth of neurologists in most African countries and the very few available ones are concentrated in urban areas. The cardiovascular and communicable risk factors responsible for most cases of acute and chronic neurological disorders are also prevalent in rural areas. Although patients from the neighbouring states attend the study centre, the majority are indigent. Therefore, there is a need to observe the pattern of these disorders in Ekiti, to appreciate the disease burden as it would help in the judicious allocation of human and other healthcare resources.
METHODOLOGY
We reviewed the case files of patients seen at the neurology clinic and admitted via the emergency department into the Federal Teaching Hospital, Ido-Ekiti, over a period of 6 years (2016 to 2021).
RESULTS
A total of 881patients were seen during the study period, and they were mostly elderly male patients with chronic disorders in which stroke was the most common neurological disorder (44.9%) followed by seizure disorder (13.1%), and neurodegenerative disorders (9.9%). Tumors and myopathies were the least seen disorders.
CONCLUSION
Health literacy on cardiovascular risk factors and even the distribution of manpower and material resources will help reduce the burden of neurological disorders among the attendees of the Ekiti tertiary health institution.
PubMed: 38952889
DOI: 10.60787/NMJ-64-4-218 -
The American Journal of Case Reports Jul 2024BACKGROUND Rhabdomyolysis, an uncommon but recognized adverse effect of selective serotonin reuptake inhibitor (SSRI) antidepressants, can precipitate acute renal injury...
BACKGROUND Rhabdomyolysis, an uncommon but recognized adverse effect of selective serotonin reuptake inhibitor (SSRI) antidepressants, can precipitate acute renal injury (AKI), especially when combined with risk factors such as alcohol consumption. This report describes a 68-year-old man with acute renal failure due to rhabdomyolysis associated with alcohol intoxication while taking low-dose escitalopram, an SSRI antidepressant. CASE REPORT The patient, with a history of bipolar affective disorder managed with escitalopram, presented with symptoms of general malaise, diarrhea, myalgias, and transient loss of consciousness following substantial ethanol consumption. Laboratory tests indicated severe rhabdomyolysis with a creatine kinase level of 37 672 U/L and myoglobin level >5710 ng/ml, leading to an AKI diagnosis. The discontinuation of escitalopram, along with hydration and renal replacement therapy, facilitated renal recovery. However, the reintroduction of escitalopram resulted in the recurrence of rhabdomyolysis, suggesting a probable causal link, confirmed using the Naranjo Adverse Drug Reaction Probability Scale. CONCLUSIONS This report highlights the importance of identifying the medication history in patients presenting with acute renal failure and rhabdomyolysis and the association with SSRIs, which can be exacerbated by alcohol. This case underscores the importance of vigilant medication history assessment in patients presenting with AKI and rhabdomyolysis, particularly concerning the use of SSRIs like escitalopram, which can pose heightened risks in the context of alcohol use. It highlights the need for clinical caution in managing patients on long-term SSRI therapy, especially when reintroducing such medications after an episode of rhabdomyolysis.
Topics: Humans; Male; Rhabdomyolysis; Acute Kidney Injury; Aged; Citalopram; Selective Serotonin Reuptake Inhibitors; Alcoholic Intoxication
PubMed: 38951999
DOI: 10.12659/AJCR.943422 -
Journal of Clinical Neurology (Seoul,... Jul 2024Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited disorder of fatty acid oxidation that causes lipid storage myopathy (LSM). This is the first report on...
BACKGROUND AND PURPOSE
Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited disorder of fatty acid oxidation that causes lipid storage myopathy (LSM). This is the first report on MADD that describes the phenotypic and genetic features of a Malaysian cohort.
METHODS
Among the >2,500 patients in a local muscle biopsy database, patients with LSM were identified and their genomic DNA were extracted from muscle samples and peripheral blood. All 13 exons of the electron-transfer flavoprotein dehydrogenase gene () were subsequently sequenced. Fifty controls were included to determine the prevalence of identified mutations in the normal population.
RESULTS
Fourteen (82%) of the 17 LSM patients had MADD with mutations. Twelve (86%) were Chinese and two were Malay sisters. Other unrelated patients reported that they had no relevant family history. Nine (64%) were females. The median age at onset was 18.5 years (interquartile range=16-37 years). All 14 demonstrated proximal limb weakness, elevated serum creatine kinase levels, and myopathic changes in electromyography. Three patients experienced a metabolic crisis at their presentation. Sanger sequencing of revealed nine different variants/mutations, one of which was novel: c.998A>G (p.Y333C) in exon 9. Notably, 12 (86%) patients, including the 2 Malay sisters, carried a common c.250G>A (p.A84T) variant, consistent with the hotspot mutation reported in southern China. All of the patients responded well to riboflavin therapy.
CONCLUSIONS
Most of our Malaysian cohort with LSM had late-onset, riboflavin-responsive MADD with mutations, and they demonstrated phenotypic and genetic features similar to those of cases reported in southern China. Furthermore, we report a novel mutation and possibly the first ever MADD patients of Malay descent.
PubMed: 38951975
DOI: 10.3988/jcn.2023.0265 -
Archives of Dermatological Research Jul 2024
Topics: Humans; Dermatomyositis; Hypothyroidism; Female; Male; Middle Aged; Adult; Thyroid Gland; Aged; Risk Factors
PubMed: 38951280
DOI: 10.1007/s00403-024-03183-x -
Zhonghua Nei Ke Za Zhi Jul 2024
Topics: Humans; Hypokalemic Periodic Paralysis; Diabetes Mellitus, Type 2; Pedigree; Male; Adult; Female; Mutation; Insulin
PubMed: 38951094
DOI: 10.3760/cma.j.cn112138-20231019-00230 -
Zhonghua Nei Ke Za Zhi Jul 2024To summarize the clinical, imaging, and pathological characteristics of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS) to...
To summarize the clinical, imaging, and pathological characteristics of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS) to improve the diagnosis of this rare disease. A retrospective case series was conducted to collect the clinical data and results of genetic testing, muscle biopsy, and imaging studies including computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance spectroscopy (MRS) of 35 patients with MELAS admitted to the Nanjing Drum Tower Hospital from 2012 to 2021. Descriptive statistical analysis including mean, standard deviation, and frequency percentage were carried out. The average age of onset of the patients was 30.2±2.3 years; the prevalence of family history was 20%. The two main initial symptoms were limb weakness and convulsions. The clinical manifestations of the neuromuscular system were proximal muscle weakness and exercise intolerance. The endocrine system is the most affected outside the neuromuscular system, with diabetes being the most common condition. Among the five patients who underwent brain CT, four showed hypodense lesions and two had calcified lesions. Brain MRI in 26 patients showed that the lesions more often affected the parietal lobe, basal ganglia, temporal lobe, occipital lobe, and frontal lobe than the infratentorial areas. Twelve of these individuals exhibited different levels of brain atrophy. Among the 10 patients who underwent H-MRS, nine showed a decrease in N-acetylaspartate (NAA) levels, eight exhibited abnormal lactate elevation (Lac peaks), whereas six had both reduced NAA levels and the presence of Lac peaks. Thirty-one patients underwent genetic testing; among them, 25 were found to have the mt.3243A>G mutation, while the remaining six exhibited rare gene alterations. Muscle biopsies were performed in 21 patients, and 15 showed abnormal mitochondrial proliferation manifested by ragged red fibers and defective oxidative phosphorylation manifested by cytochrome C oxidase (COX) enzyme-deficient muscle fibers. The clinical manifestations of MELAS syndrome are variable and complex, and early atypical symptoms could be missed or misdiagnosed. A detailed clinical history, imaging MRS analysis, muscle biopsy, and genetic testing are necessary to confirm the accurate diagnosis of MELAS.
Topics: Humans; MELAS Syndrome; Retrospective Studies; Adult; Magnetic Resonance Imaging; Brain; Tomography, X-Ray Computed; Male; Female; Magnetic Resonance Spectroscopy
PubMed: 38951091
DOI: 10.3760/cma.j.cn112138-20231227-00411