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Frontiers in Aging Neuroscience 2024Parkinson's disease (PD) is the second most common neurodegenerative disease and affects millions of people. Accurate diagnosis and subsequent treatment in the early...
INTRODUCTION
Parkinson's disease (PD) is the second most common neurodegenerative disease and affects millions of people. Accurate diagnosis and subsequent treatment in the early stages can slow down disease progression. However, making an accurate diagnosis of PD at an early stage is challenging. Previous studies have revealed that even for movement disorder specialists, it was difficult to differentiate patients with PD from healthy individuals until the average modified Hoehn-Yahr staging (mH&Y) reached 1.8. Recent researches have shown that dysarthria provides good indicators for computer-assisted diagnosis of patients with PD. However, few studies have focused on diagnosing patients with PD in the early stages, specifically those with mH&Y ≤ 1.5.
METHOD
We used a machine learning algorithm to analyze voice features and developed diagnostic models for differentiating between healthy controls (HCs) and patients with PD, and for differentiating between HCs and patients with mild PD (mH&Y ≤ 1.5). The models were independently validated using separate datasets.
RESULTS
Our results demonstrate that, a remarkable diagnostic performance of the model in identifying patients with mild PD (mH&Y ≤ 1.5) and HCs, with area under the ROC curve 0.93 (95% CI: 0.851.00), accuracy 0.85, sensitivity 0.95, and specificity 0.75.
CONCLUSION
The results of our study are helpful for screening PD in the early stages in the community and primary medical institutions where there is a lack of movement disorder specialists and special equipment.
PubMed: 38765774
DOI: 10.3389/fnagi.2024.1377442 -
Annals of Indian Academy of Neurology 2024Friedreich's ataxia (FRDA) is a common cause of autosomal recessive cerebellar ataxia. The phenotype is dependent on the repeat size and duration of the disease. We...
BACKGROUND AND AIM
Friedreich's ataxia (FRDA) is a common cause of autosomal recessive cerebellar ataxia. The phenotype is dependent on the repeat size and duration of the disease. We aimed to study the clinical, electrophysiologic, and radiologic profiles in a large Indian cohort of genetically proven FRDA patients.
SUBJECTS AND METHODS
A retrospective cross-sectional, descriptive analysis of genetically proven FRDA patients was performed. A detailed review of all the hospital case records was done to analyze the clinical, radiologic, and electrophysiologic details.
RESULTS
A total of 100 FRDA patients were selected for the analysis. Eighty-six patients had an age at onset between 5 and 25 years. Eight patients (8%) were classified as late-onset FRDA and six patients (6%) as early-onset FRDA. The median age at presentation was 19 years. The median age at onset was 14 years, and the median duration of illness was 4 years. All patients had gait ataxia as the initial symptom. Gait ataxia, loss of proprioception, and areflexia were seen in all patients. Dysarthria, nystagmus, amyotrophy, spasticity, extensor plantars, pes cavus, and scoliosis occurred in one-third of patients. Cardiomyopathy (18%) and diabetes (5%) were less common. Sensory polyneuropathy (87.5%) was the most common nerve conduction abnormality. Cortical somatosensory evoked responses were absent in all 43 tested patients (100%). Brainstem auditory evoked response test was done in 24 patients and it showed absent reactions in six patients (25%). Visual evoked potential was tested in 24 patients and it showed absent P100 responses in five patients (21%). Cerebellar and cord atrophy was seen on magnetic resonance imaging in 50% of patients.
CONCLUSION
Most FRDA patients (86%) had an age at onset of less than 25 years, with typical symptoms of gait ataxia, areflexia, and loss of proprioception found in all patients. Dysarthria, nystagmus, amyotrophy, spasticity, extensor plantars, pes cavus, scoliosis, cardiomyopathy, and diabetes were not seen in all patients. Cerebellar atrophy can occur in FRDA patients. Knowledge regarding the clinical, radiologic, and electrophysiologic profile of FRDA will aid in proper phenotypic characterization.
PubMed: 38751907
DOI: 10.4103/aian.aian_1001_23 -
Internal Medicine (Tokyo, Japan) May 2024Introduction Nutritional interventions targeting weight loss are useful for the treatment of amyotrophic lateral sclerosis (ALS). However, the changes in body...
Weight and Muscle Mass Loss Associated with Acute Disease Can be Reversed with Appropriate Nutrition Therapy and Exercise in a Patient with Amyotrophic Lateral Sclerosisa: A Case Report.
Introduction Nutritional interventions targeting weight loss are useful for the treatment of amyotrophic lateral sclerosis (ALS). However, the changes in body composition after nutritional intervention remain unclear. We herein present a patient with ALS who experienced an increased weight and muscle mass owing to nutritional therapy and physical exercise. Case Presentation An 86-year-old man presented with dysphagia and dysarthria. The patient was diagnosed with bulbar-type ALS. As weight loss progressed, a gastrostomy was performed. After 21 months of disease onset, gastrointestinal bleeding due to a bumper ulcer led to further weight loss (from 40.2 kg to 36.8 kg). The patient experienced difficulty walking and ingesting food orally. Although the total daily energy expenditure (TDEE) was estimated to be 1,122 kcal/day, an intake of 1,500 kcal/day beyond the calculated TDEE was administered. The patient continued to perform daily voluntary exercises in addition to his usual rehabilitation. After 5 months, his weight increased from 36.8 kg to 40.4 kg. Muscle mass increased from 25.1 kg to 30.1 kg, as measured using a multifrequency bioelectrical impedance device. Muscle strength improved from 8.5/10.0 kg to 15.0/18.0 kg in grip strength and from 15.2 kPa to 20.4 kPa in tongue pressure. The patient's physical and swallowing functions also improved. Conclusion In patients with ALS, a decreased body weight and muscle mass due to acute disease may be improved by appropriate nutritional therapy and physical exercise.
PubMed: 38749729
DOI: 10.2169/internalmedicine.3622-24 -
Cureus Apr 2024Cerebellar hemispheric enlargement with atypical neurological symptoms poses diagnostic challenges in clinical practice. We present the case of a 57-year-old female with...
Cerebellar hemispheric enlargement with atypical neurological symptoms poses diagnostic challenges in clinical practice. We present the case of a 57-year-old female with persistent headache, left facial paraesthesia, dysarthria, gait ataxia, and longstanding neck swelling. Imaging studies revealed enlargement of the left cerebellar hemisphere with associated mass effect and compression of adjacent structures. The underlying etiology remained uncertain despite extensive evaluation, including magnetic resonance imaging and angiography. Differential diagnoses included neoplastic, vascular, inflammatory, and metabolic etiologies, but none fully accounted for the clinical findings. Management strategies focused on symptomatic relief and close monitoring. This case underscores the complexity of diagnosing and managing patients with rare neurological manifestations and highlights the need for continued research and collaborative approaches in optimising patient care.
PubMed: 38741826
DOI: 10.7759/cureus.58096 -
International Journal of Molecular... Apr 2024Wilson disease is a genetic disorder of the liver characterized by excess accumulation of copper, which is found ubiquitously on earth and normally enters the human body... (Review)
Review
Wilson disease is a genetic disorder of the liver characterized by excess accumulation of copper, which is found ubiquitously on earth and normally enters the human body in small amounts via the food chain. Many interesting disease details were published on the mechanistic steps, such as the generation of reactive oxygen species (ROS) and cuproptosis causing a copper dependent cell death. In the liver of patients with Wilson disease, also, increased iron deposits were found that may lead to iron-related ferroptosis responsible for phospholipid peroxidation within membranes of subcellular organelles. All topics are covered in this review article, in addition to the diagnostic and therapeutic issues of Wilson disease. Excess Cu primarily leads to the generation of reactive oxygen species (ROS), as evidenced by early experimental studies exemplified with the detection of hydroxyl radical formation using the electron spin resonance (ESR) spin-trapping method. The generation of ROS products follows the principles of the Haber-Weiss reaction and the subsequent Fenton reaction leading to copper-related cuproptosis, and is thereby closely connected with ROS. Copper accumulation in the liver is due to impaired biliary excretion of copper caused by the inheritable malfunctioning or missing ATP7B protein. As a result, disturbed cellular homeostasis of copper prevails within the liver. Released from the liver cells due to limited storage capacity, the toxic copper enters the circulation and arrives at other organs, causing local accumulation and cell injury. This explains why copper injures not only the liver, but also the brain, kidneys, eyes, heart, muscles, and bones, explaining the multifaceted clinical features of Wilson disease. Among these are depression, psychosis, dysarthria, ataxia, writing problems, dysphagia, renal tubular dysfunction, Kayser-Fleischer corneal rings, cardiomyopathy, cardiac arrhythmias, rhabdomyolysis, osteoporosis, osteomalacia, arthritis, and arthralgia. In addition, Coombs-negative hemolytic anemia is a key feature of Wilson disease with undetectable serum haptoglobin. The modified Leipzig Scoring System helps diagnose Wilson disease. Patients with Wilson disease are well-treated first-line with copper chelators like D-penicillamine that facilitate the removal of circulating copper bound to albumin and increase in urinary copper excretion. Early chelation therapy improves prognosis. Liver transplantation is an option viewed as ultima ratio in end-stage liver disease with untreatable complications or acute liver failure. Liver transplantation finally may thus be a life-saving approach and curative treatment of the disease by replacing the hepatic gene mutation. In conclusion, Wilson disease is a multifaceted genetic disease representing a molecular and clinical challenge.
Topics: Humans; Hepatolenticular Degeneration; Copper; Iron; Ferroptosis; Reactive Oxygen Species; Liver; Animals
PubMed: 38731973
DOI: 10.3390/ijms25094753 -
BMC Neurology May 2024Posterior Circulation Syndrome (PCS) presents a diagnostic challenge characterized by its variable and nonspecific symptoms. Timely and accurate diagnosis is crucial for...
BACKGROUND
Posterior Circulation Syndrome (PCS) presents a diagnostic challenge characterized by its variable and nonspecific symptoms. Timely and accurate diagnosis is crucial for improving patient outcomes. This study aims to enhance the early diagnosis of PCS by employing clinical and demographic data and machine learning. This approach targets a significant research gap in the field of stroke diagnosis and management.
METHODS
We collected and analyzed data from a large national Stroke Registry spanning from January 2014 to July 2022. The dataset included 15,859 adult patients admitted with a primary diagnosis of stroke. Five machine learning models were trained: XGBoost, Random Forest, Support Vector Machine, Classification and Regression Trees, and Logistic Regression. Multiple performance metrics, such as accuracy, precision, recall, F1-score, AUC, Matthew's correlation coefficient, log loss, and Brier score, were utilized to evaluate model performance.
RESULTS
The XGBoost model emerged as the top performer with an AUC of 0.81, accuracy of 0.79, precision of 0.5, recall of 0.62, and F1-score of 0.55. SHAP (SHapley Additive exPlanations) analysis identified key variables associated with PCS, including Body Mass Index, Random Blood Sugar, ataxia, dysarthria, and diastolic blood pressure and body temperature. These variables played a significant role in facilitating the early diagnosis of PCS, emphasizing their diagnostic value.
CONCLUSION
This study pioneers the use of clinical data and machine learning models to facilitate the early diagnosis of PCS, filling a crucial gap in stroke research. Using simple clinical metrics such as BMI, RBS, ataxia, dysarthria, DBP, and body temperature will help clinicians diagnose PCS early. Despite limitations, such as data biases and regional specificity, our research contributes to advancing PCS understanding, potentially enhancing clinical decision-making and patient outcomes early in the patient's clinical journey. Further investigations are warranted to elucidate the underlying physiological mechanisms and validate these findings in broader populations and healthcare settings.
Topics: Humans; Machine Learning; Early Diagnosis; Male; Female; Middle Aged; Aged; Stroke; Registries; Adult
PubMed: 38714968
DOI: 10.1186/s12883-024-03638-8 -
Brain Communications 2024Bilateral perisylvian polymicrogyria is the most common form of regional polymicrogyria within malformations of cortical development, constituting 20% of all... (Review)
Review
Bilateral perisylvian polymicrogyria is the most common form of regional polymicrogyria within malformations of cortical development, constituting 20% of all malformations of cortical development. Bilateral perisylvian polymicrogyria is characterized by an excessive folding of the cerebral cortex and abnormal cortical layering. Notable clinical features include upper motoneuron dysfunction, dysarthria and asymmetric quadriparesis. Cognitive impairment and epilepsy are frequently observed. To identify genetic variants underlying bilateral perisylvian polymicrogyria in Finland, we examined 21 families using standard exome sequencing, complemented by optical genome mapping and/or deep exome sequencing. Pathogenic or likely pathogenic variants were identified in 5/21 (24%) of families, of which all were confirmed as These variants were identified in five genes, i.e. , , , and , with and being associated with bilateral perisylvian polymicrogyria for the first time. In conclusion, our results confirm the previously reported genetic heterogeneity of bilateral perisylvian polymicrogyria and underscore the necessity of more advanced methods to elucidate the genetic background of bilateral perisylvian polymicrogyria.
PubMed: 38712318
DOI: 10.1093/braincomms/fcae142 -
Therapeutic Advances in Infectious... 2024Powassan virus (POWV), a tick-borne flavivirus transmitted primarily by Ixodes ticks, poses a significant threat as it can lead to severe neuroinvasive illness. This... (Review)
Review
Powassan virus (POWV), a tick-borne flavivirus transmitted primarily by Ixodes ticks, poses a significant threat as it can lead to severe neuroinvasive illness. This review delves into the nuanced clinical presentation of Powassan infection, a challenge in diagnosis exacerbated by the absence of an available vaccine. Over the past decade, the prevalence of POWV has surged in North America, necessitating a thorough examination of its neurological manifestations alongside tick-borne encephalitis virus (TBEV). A comprehensive literature search conducted up to January 2024 revealed 135 cases of neurological symptoms associated with either Powassan or TBEV infection. Notably, severe occipital headache emerged as the most prevalent symptom (22.75%), followed by meningoencephalitis (10.34%), seizures (8.27%), and flaccid paresis (6.8%). Additional manifestations included poor balance, wide gait, dysarthria, facial nerve palsy, seizure, slurred speech, and absent deep tendon reflexes. Tragically, nine cases resulted in fatal outcomes attributed to POWV infection. This analysis highlights the intricate spectrum of neurological symptoms associated with Powassan infection and underscores the necessity for heightened awareness among medical practitioners, particularly in regions with a higher prevalence of the virus. The complexity of symptoms emphasizes the need for further research to unravel the factors contributing to this diversity. Additionally, exploring potential treatment avenues and vaccine development is crucial in addressing the rising threat posed by POWV, ultimately enhancing our ability to manage and prevent severe neurological outcomes.
PubMed: 38693969
DOI: 10.1177/20499361241247470 -
Frontiers in Neurology 2024Epilepsy, characterized by recurrent seizures, impacts 70-80% of patients, leading to cognitive deficits. The intricate relationship between seizure control and...
Epilepsy, characterized by recurrent seizures, impacts 70-80% of patients, leading to cognitive deficits. The intricate relationship between seizure control and cognitive impairment remains complex. Epileptic encephalopathy (EE), an intensified form often rooted in genetic factors, is detectable through next-generation sequencing, aiding in precise diagnoses, family counseling, and potential treatment strategies. We present a case involving two sisters with refractory generalized seizures evolving into dysarthria, dysphagia, ataxia, and cognitive decline. Despite normal physical exams, abnormal electroencephalogram results consistent with epilepsy were noted. Whole Exome Sequencing identified heterozygous variants in the alanyl-tRNA synthetase (AARS) and Calcium Voltage-Gated Channel Subunit Alpha 1 (CACNA1A) genes. The AARS variant (c.C2083T, p.R695*) was maternal, while the CACNA1A variant (c.G7400C, p.R2467P) was paternal. Patients A and B exhibited a unique blend of neurological and psychiatric conditions, distinct from common disorders that begin adolescence, like Juvenile Myoclonic Epilepsy. Whole Exome Sequencing uncovered an AARS gene and CACNA1A gene, linked to various autosomal dominant phenotypes. Presence in both parents, coupled with familial reports of migraines and seizures, provides insight into accelerated symptom progression. This study underscores the importance of genetic testing in decoding complex phenotypes and emphasizes the value of documenting family history for anticipating related symptoms and future health risks.
PubMed: 38689878
DOI: 10.3389/fneur.2024.1376643