BACKGROUND: FcRn antagonists have reshaped generalized myasthenia gravis (MG) treatment by enhancing IgG catabolism, complementing traditional antibody-depleting therapy (ADT). However, disrupting IgG homeostasis may par...BACKGROUND: FcRn antagonists have reshaped generalized myasthenia gravis (MG) treatment by enhancing IgG catabolism, complementing traditional antibody-depleting therapy (ADT). However, disrupting IgG homeostasis may paradoxically cause antibody overshoot, potentially worsening MG symptoms. The risk factors and optimal management of antibody overshoot remain inadequately characterized. METHODS: We report two novel cases of anti-acetylcholine receptor (AChR) antibody overshoot and clinical exacerbation following FcRn antagonist efgartigimod treatment. To contextualize these findings, we performed a literature search in PubMed, identifying 10 previously reported cases of antibody overshoot in MG (2 following efgartigimod and 8 following plasma exchange). RESULTS: In the efgartigimod cohort (n=4, including our two novel cases), all patients were anti AChR positive, had thymoma associated MG (TAMG, 100%), and had undergone prior thymectomy (100%). Notably, none had received adequate background immunosuppressive therapy before efgartigimod initiation (75% inadequate, 25% none). All patients (100%) experienced severe clinical exacerbation (MGFA class V in the 3 patients with available data). Rescue therapies-including corticosteroids (75%), eculizumab (50%), IVIG (50%), and tacrolimus (50%)-were effective, with all four patients showing significant improvement. Furthermore, analysis of the plasma exchange cohort (n=8) and the combined cohort (n=12) revealed a distinct and shared clinical risk profile for the development of antibody overshoot. CONCLUSION: Anti AChR antibody overshoot following efgartigimod therapy is a rare but clinically significant adverse event, predominantly affecting patients with TAMG or prior thymectomy who lack adequate baseline immunosuppression. Given the dissociation between total IgG reduction and autoantibody rebound, monitoring should focus specifically on anti-AChR titer rather than total IgG level alone.
BACKGROUND: Total cerebral small-vessel disease (cSVD) score is a well-established predictor of vascular risks. However, the specific type of recurrent stroke associated with cSVD scores remains unclear in hemorrhage-pro...BACKGROUND: Total cerebral small-vessel disease (cSVD) score is a well-established predictor of vascular risks. However, the specific type of recurrent stroke associated with cSVD scores remains unclear in hemorrhage-prone patients-those with cerebral microbleeds (CMBs) or prior intracerebral hemorrhage (ICH). METHODS: This study was a post hoc analysis of 1,454 patients enrolled in a prospective, multicenter, randomized controlled trial. Patients were categorized by modified cSVD (m-cSVD) scores 1-3. One point was awarded for each of the following: white matter hyperintensities (WMH) above the median, ≥2 CMBs or 1 ICH, and ≥1 lacune. The primary outcome was any stroke; secondary outcomes were ischemic and hemorrhagic stroke; the tertiary outcome was major adverse cardiovascular events (MACE). Multivariable Cox regression analysis was used to investigate associations between m-cSVD scores and events. RESULTS: During a mean 1.9-year follow-up, the incidence rate per 100 person-years for ischemic stroke increased significantly with m-cSVD scores (1.9, 2.8, and 5.7, respectively). Compared to score 1, m-cSVD score 3 was associated with a higher risk of ischemic stroke (adjusted HR 2.72; 95% CI 1.03-7.18) and MACE (adjusted HR 2.34; 95% CI 1.08-5.10). While the incidence of hemorrhagic stroke showed a numerical increase (0.5, 0.8, and 1.5), this association did not reach statistical significance (unadjusted HR 3.05; 95% CI 0.66-14.14). CONCLUSION: A high m-cSVD burden was independently associated with recurrent ischemic stroke, but not hemorrhagic stroke, in patients with high bleeding risk. High cSVD burden may reflects elevated ischemic risk, warranting careful consideration of ischemic stroke prevention even in patients with hemorrhagic potential.
OBJECTIVE: To characterize the clinical and genetic features of 10 paroxysmal kinesigenic dyskinesia (PKD) patients from three Chinese pedigrees, with emphasis on intrafamilial phenotypic variability and the broader PRRT...OBJECTIVE: To characterize the clinical and genetic features of 10 paroxysmal kinesigenic dyskinesia (PKD) patients from three Chinese pedigrees, with emphasis on intrafamilial phenotypic variability and the broader PRRT2-associated disease spectrum. METHODS: Clinical data were collected from PKD patients attending the Department of Neurology, Second Hospital of Hebei Medical University (January 2023 - December 2024). Targeted next-generation sequencing of PKD-associated genes (PRRT2, TMEM151A, SCN8A, KCNA1, etc.) was performed for probands, followed by Sanger sequencing validation and family segregation analysis in available family members. Clinical features were analyzed in conjunction with literature review. RESULTS: Ten PKD cases from three families were identified. All patients exhibited exercise-induced dystonia, chorea, or athetosis without impaired consciousness; each episode lasted < 1 min. Interictal EEG and brain MRI were normal. Inheritance was autosomal dominant. Pathogenic variants were identified in PRRT2 (chromosome 16), including frameshift mutations c.649dup (p.Arg217ProfsTer8) and c.641delC (p.Arg217Glufs*12). Intrafamilial phenotypic variability was notable: the same c.649dup mutation produced clinically silent carriage in one father but severe daily attacks with secondary depression in another family member. In family 3, cold exposure was identified as a novel trigger. CONCLUSION: This study expands the mutational spectrum of PRRT2-associated PKD in the Chinese population by documenting a relatively rare c.641delC variant. The marked intrafamilial variability observed supports the role of additional modifiers influencing clinical expression beyond the primary PRRT2 mutation.
OBJECTIVE: Objective study was the quantification of controlled/inadequately controlled generalized myasthenia gravis (gMG) disease burden, health care resource utilization and costs in MG patients, followed-up at a refe...OBJECTIVE: Objective study was the quantification of controlled/inadequately controlled generalized myasthenia gravis (gMG) disease burden, health care resource utilization and costs in MG patients, followed-up at a reference center for MG in Italy. DESIGN AND SETTING: The study is a 2010 to 2020 retrospective analysis of gMG patients. Clinical and health economics variables were those observed during routine clinical care. Data were anonymized and treated in aggregated forms in compliance with GDPR. PARTICIPANTS: Only patients with gMG were included in the study. RESULTS: Out of 237 patients, 55.3% were males and 44.7% females with a median follow up duration of 4.7 years. Males were older, with a median age at onset of 58.3 years versus 45.7 years for females; an increased representation of late and very late onset patients was recorded. A shorter time from onset to diagnosis was observed in males. The incidence rate per year of exacerbations changed from 0.76 in the first year to 0.23 at the sixth year, with a similar trend for MG crisis; both exacerbations and crisis incidence were higher in inadequately controlled patients. Disease burden and health care resources utilizations were particularly evident in inadequately controlled patients, which showed a 138% increase of costs. CONCLUSIONS: Our data confirmed the observed epidemiological changes occurring in MG population and the high use of health care system resources in uncontrolled patients. The estimates obtained will provide a useful basis for assessing the impact of recently introduced targeted therapies on healthcare expenditure for MG.
INTRODUCTION: Although motor symptoms are the defining feature of dystonia, increasing evidence indicates that non-motor symptoms substantially affect patients' quality of life. Among these, social cognition remains insu...INTRODUCTION: Although motor symptoms are the defining feature of dystonia, increasing evidence indicates that non-motor symptoms substantially affect patients' quality of life. Among these, social cognition remains insufficiently explored, particularly in relation to global cognitive functioning and affective-behavioral dimensions. METHODS: In this study, 25 patients diagnosed with Idiopathic Focal Dystonia (IFD) and 25 healthy controls (HCs) underwent assessments of social cognition (cognitive and affective Theory of Mind [ToM] and empathy), global cognitive functioning (MoCA), depression (BDI) and apathy (DAS). RESULTS: Patients diagnosed with IFD performed significantly worse than HCs on cognitive and affective ToM tasks, whereas no group differences were observed for the remaining measures. Within the IFD group, cognitive ToM performance correlated with global cognitive functioning, and affective ToM correlated with apathy but not with depression. CONCLUSION: These findings demonstrate specific impairments in social cognition and suggest links between ToM deficits, cognitive dysfunction and motivational disturbance. By identifying a pattern of social cognition deficit in IFD patients, this study advances understanding of its non-motor symptoms and underscores the need for further research on its impact on daily functioning and quality of life.
BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting millions of people worldwide. It severely impairs patients' mobility. For effective treatment strategies, it is essential to dete...BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting millions of people worldwide. It severely impairs patients' mobility. For effective treatment strategies, it is essential to determine the severity of the disease at an early stage. METHODS: In this study, an optimized feature-fusion framework is developed to detect the severity of Parkinson's disease using gait data via an Optimized Fuzzy Neural Network (OPtFuzNet). This feature-fusion framework can be categorized into three stages: pre-processing, feature extraction, and classification. In the pre-processing stage, a median filter is employed to reduce noise present in the gait images. During feature extraction, local and global features of the gait images are captured using SAE and IDCN, respectively. Subsequently, these features are fused and fed into the OPtFuzNet classifier, where parameter optimization is performed using IGWO-Lévy. RESULTS: The proposed model is evaluated on the GAIT-IT and GAIT-IST benchmark datasets using standard metrics, achieving superior performance with accuracies of 98.08% and 98.12%, respectively. Furthermore, a feature importance analysis is conducted to identify the most influential gait characteristics that contribute to determining the severity of the impairment, thereby enhancing the clinical interpretability of the model.The proposed model is evaluated on the GAIT-IT and GAIT-IST benchmark datasets using standard metrics, achieving superior performance with accuracies of 98.08% and 98.12%, respectively. Furthermore, a feature importance analysis is conducted to identify the most influential gait characteristics that contribute to determining the severity of the impairment, thereby enhancing the clinical interpretability of the model. CONCLUSION: These results validate the efficacy of the proposed feature fusion and optimization strategy in identifying discriminative gait patterns associated with the severity of Parkinson's disease. However, as the datasets are based on simulated gait patterns rather than real clinical data, further validation on real-world datasets is necessary for practical applicability.
BACKGROUND: Dopa-responsive dystonia (DRD) is an underdiagnosed inherited movement disorder characterized by childhood-onset progressive dystonia, diurnal symptom luctuation, and exquisite responsiveness to low-dose levo...BACKGROUND: Dopa-responsive dystonia (DRD) is an underdiagnosed inherited movement disorder characterized by childhood-onset progressive dystonia, diurnal symptom luctuation, and exquisite responsiveness to low-dose levodopa. Misdiagnosis as epilepsy, cerebral palsy, or juvenile Parkinsonism is common due to overlapping phenotypes and non-specific auxiliary examinations. CASE PRESENTATION: A 22-year-old Chinese female presented with an 18-year history of right-sided limb and perioral involuntary movements, slurred speech, and progressive hypertonia. She was misdiagnosed with epilepsy for over a decade with no response to antiepileptic therapy. Brain MRI, EEG, and routine laboratory tests were unremarkable. Whole-exome sequencing (WES) identiied a heterozygous guanosine triphosphate cyclohydrolase-1 (GCH1) variant c.579C>G (p.Ile193Met), classified as a variant of uncertain signiicance (VUS) per American College of Medical Genetics and Genomics (ACMG) guidelines. Low-dose levodopa/benserazide (Madopar 0.125 g tid) induced dramatic symptomatic improvement, with sustained remission at 6-month follow-up. CONCLUSION: This case expands the GCH1 mutational spectrum of DRD and highlights the critical role of levodopa trial in unexplained dystonia, even in the absence of diurnal luctuation. Early recognition and intervention are pivotal for favorable prognosis.
Barbanti P, Tassorelli C, Vernieri F
… +14 more, De Cesaris F, De Icco R, Di Lorenzo C, Finocchi C, Grazzi L, Guerzoni S, Mampreso E, Mastronuzzi T, Messina R, Ornello R, Rao R, Taddeo D, De Tommaso M, Rainero I
INTRODUCTION: Migraine is a disabling neurological disorder often mismanaged, with only a minority of individuals receiving a timely correct diagnosis and appropriate treatment. The aim of this work was to establish cons...INTRODUCTION: Migraine is a disabling neurological disorder often mismanaged, with only a minority of individuals receiving a timely correct diagnosis and appropriate treatment. The aim of this work was to establish consensus-based indications for improving the management of individuals with migraine and optimizing their journey from general practice to specialist care. METHODS: A panel of 17 Italian experts, including neurologists, pharmacologists, and general practitioners (GPs) assessed a total of 36 statements addressing migraine diagnosis and management in primary care, referral pathways, and long-term care through the Delphi methodology. RESULTS: The panel endorsed the role of GPs in the early identification and management of migraine, emphasizing the use of validated screening tools and headache diaries as well as the adoption of structured care pathways, where available, to ensure consistent and effective management. Specialist referral was emphasized for chronic migraine, medication overuse, or for individuals with inadequate response to preventive therapies. The panel advocated for a shared, long-term care model grounded in dynamic, bidirectional collaboration across healthcare levels to reduce the burden on tertiary headache centers. CONCLUSION: This consensus provides practical, context-specific guidance to facilitate care of migraine across primary and specialist care. Proper implementation of this model may streamline the management of individuals with migraine, reduce diagnostic delays, prevent unnecessary costs, and ultimately guide the development of a coordinated migraine care model in Italy.
INTRODUCTION: ATP1A3-related neurological disorders show a broad spectrum of manifestations, usually with autosomal dominant transmission. Classical phenotypes include alternating hemiplegia of childhood (AHC), rapid-ons...INTRODUCTION: ATP1A3-related neurological disorders show a broad spectrum of manifestations, usually with autosomal dominant transmission. Classical phenotypes include alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism (RDP), and syndrome characterized by cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss (CAPOS). Additional rarer forms include childhood-onset-schizophrenia (COS), encephalopathy with MRI abnormalities without hemiplegia (D-DEMØ), fever-induced paroxysmal weakness and encephalopathy (FIPWE), and relapsing encephalopathy with cerebellar ataxia (RECA). These conditions often overlap, sharing core symptoms due to dysfunction of the Na⁺/K⁺-ATPase α3 subunit. Some mutations result in a thermolabile enzyme, which impairs its function under stress, leading to weakness' episodes, encephalopathy and ataxia. CASE SERIES: We report a patients' cohort with ATP1A3 mutations followed at Santobono-Pausilipon Children's Hospital in Naples. The first family includes three siblings with RECA (p.Arg756Cys). The second cluster comprises a mother and son with FIPWE (p.Arg756His). We also describe one case of AHC (p.Asp801Asn) and one of CAPOS (p.Arg756Cys). All patients showed marked susceptibility to infection and fever. DISCUSSION AND CONCLUSION: Our case series confirms the complex clinical scenarios in ATP1A3-related disorders, with symptoms overlapping and possible interfamilial variability, contributing to the diagnostic challenge posed by a rare genetic disorder, already observed in individuals with ATP1A3 gene mutations. The ongoing effort to characterize the clinical phenotype and identify "core" symptoms is necessary to expand our knowledge of the genotype-phenotype correlation, which is currently unclear. More importantly, our series highlights the molecular fragility of mutant ATP1A3, particularly its sensitivity to fever. Proactive prevention of fever and time management may be crucial to reducing the risk of neurological deterioration in affected individuals.
BACKGROUND: More than 70% of stroke survivors suffer from upper extremity paresis, which limits the ability to perform activities of daily living. To guide rehabilitation, specific tools that accurately evaluate upper li...BACKGROUND: More than 70% of stroke survivors suffer from upper extremity paresis, which limits the ability to perform activities of daily living. To guide rehabilitation, specific tools that accurately evaluate upper limb function are essential. The Stroke Upper Limb Capacity Scale (SULCS) is a stroke-specific assessment tool that evaluates functional capacity of the upper limb. It is quick to administer, requires no specialized equipment, and is a cost-effective option for routine clinical use. OBJECTIVE: The aims of this study were to adapt the SULCS transculturally to Spanish and to examine its clinimetric properties. METHODS: For cross-cultural adaptation to Spanish, we employed a "translation/back-translation" approach and evaluated its feasibility in routine neurorehabilitation. A multicenter study was conducted in Spanish post-stroke patients (n = 56) to validate the clinimetric properties of the instrument. RESULTS: The translation into Spanish was completed without major difficulties. Reliability analysis, including test-retest and inter-operator, demonstrated almost perfect agreement for the Spanish SULCS, with weighted Cohen's kappa values of 0.8755 (95% CI: 0.5991-1.1519) and 0.8988 (95% CI: 0.7343-1.0632) respectively. The minimal detectable change indicated high sensitivity (0.72 at the 95% confidence level). The SULCS showed excellent concurrent validity with the Fugl-Meyer Assessment (r = 0.9533), the Action Research Arm Test (r = 0.9730), and the Box and Block Test (r = 0.9247). No floor or ceiling effects were observed. CONCLUSIONS: The Spanish version of the SULCS presented excellent clinimetric properties. Its characteristics make it a useful tool for assessing upper limb functional capacity in the Spanish post-stroke population.
BACKGROUND: Epilepsy may affect cardiac function early due to seizure and pathophysiology-related autonomic changes. Strain echocardiography is a valuable method that reveals myocardial deformity with high sensitivity in...BACKGROUND: Epilepsy may affect cardiac function early due to seizure and pathophysiology-related autonomic changes. Strain echocardiography is a valuable method that reveals myocardial deformity with high sensitivity in these patients. This study aims to identify subclinical cardiac involvement in the epilepsy population using this method and to examine the contribution of the obtained data to cardiac risk assessment. METHODS: In this cross-sectional observational study, 49 epilepsy patients who underwent electroencephalography (EEG) examination, and 57 age and sex-matched healthy controls were examined. Standard transthoracic echocardiography (TTE) measurements, including tissue doppler indices, left and right ventricular global longitudinal strain (LVGLS, RVGLS), left atrial strain (LAS), and electrocardiography (ECG) parameters were compared between groups. RESULTS: Conventional systolic indices were partially preserved; however, patients with epilepsy exhibited significantly reduced LVGLS, RVGLS, and LAS values compared with controls (p < 0.05). Some diastolic functions such as isovolumetric relaxation and contraction time and medial e' velocities were significantly affected (p < 0.05). ECG abnormalities, particularly conduction and repolarization disturbances, were more frequent in the epilepsy group. Notably, left ventricular ejection fraction (within normal range in both group) was significantly lower in epilepsy group, suggesting early systolic vulnerability. CONCLUSION: Despite preserved some conventional echocardiographic findings, patients with epilepsy demonstrate significant subclinical myocardial deformation abnormalities detectable by strain imaging. Incorporation of speckle-tracking echocardiography into routine cardiovascular evaluation may facilitate early identification of myocardial involvement and improve cardiovascular risk stratification in this population.
We reported the case of 55 years-old man with an unilateral tegmental primary pontine hemorrhage (PPH) with a follow-up brain Magnetic Resonance Imaging (MRI) showing the residual hemorrhagic scar within pontine bundles...We reported the case of 55 years-old man with an unilateral tegmental primary pontine hemorrhage (PPH) with a follow-up brain Magnetic Resonance Imaging (MRI) showing the residual hemorrhagic scar within pontine bundles similar to the symbols of the mahjong tile. We named this appearance the "Mahjong sign".