CASE PRESENTATION: Mitochondrial complex III deficiency nuclear type 2 (MC3DN2) is a rare inherited neurometabolic disease. A 34-year-old male had neuropsychiatric episodes, progressive cerebellar degeneration, myopathy,...CASE PRESENTATION: Mitochondrial complex III deficiency nuclear type 2 (MC3DN2) is a rare inherited neurometabolic disease. A 34-year-old male had neuropsychiatric episodes, progressive cerebellar degeneration, myopathy, polyneuropathy, and brain stem and basal ganglion lesions since childhood. Muscle biopsy revealed mitochondrial abnormalities. Two novel TTC19 pathogenic variants were detected. LITERATURE REVIEW: To analyze phenotypic characteristics of MC3DN2 related to clinical onset age, neurological presentation and brain MRI regarding infantile and childhood-onset (ICO) and adolescent and adult-onset (AAO) disease in a cohort composed of our patient and the cases reported in the literature were compared. It revealed that, clinically, cerebellar ataxia was common in both groups, nystagmus was more frequently noted in AAO patients, and psychiatric disturbances were more common in ICO patients. Regarding MRI findings, basal ganglion lesions were more prevalent in ICO patients, and inferior olive lesions were more frequent in AAO patients. DISCUSSION: These conspicuous phenotypic features of MC3DN2 may suggest diagnosis of this distinctive disease. The differences in clinical features and brain lesions associated with clinical onset age could provide crucial insights into the phenotypic landscape of MC3DN2.
BACKGROUND: Biallelic variants in SYNJ1 were initially identified in early-onset Parkinson's disease, often accompanied by atypical neurological manifestations. However, their occurrence in patients with a multiple syste...BACKGROUND: Biallelic variants in SYNJ1 were initially identified in early-onset Parkinson's disease, often accompanied by atypical neurological manifestations. However, their occurrence in patients with a multiple system atrophy-mimicking phenotype has not been well described. METHODS: A 71-year-old Chinese woman with gradually worsening motor and autonomic symptoms was assessed. The evaluation included clinical examination, genetic testing, and functional studies. RESULTS: The patient exhibited gait instability, cerebellar ataxia, parkinsonism, urinary autonomic dysfunction, and poor levodopa responsiveness. Genetic analysis identified novel compound heterozygous SYNJ1 variants (c.1574 A > G and c.142G > T). Functional assays evaluating each variant individually showed reduced synaptojanin-1 abundance without altered localization. CONCLUSIONS: This case expands the clinical context in which biallelic SYNJ1 variants may be implicated and suggests that SYNJ1 analysis could be considered in atypical parkinsonism with cerebellar dysfunction.
Muroni A, Velucci V, Martino D
… +21 more, Mascia MM, Belvisi D, Marchet F, Avanzino L, Marchese R, Erro R, Della Valle P, Marinelli L, Villani F, Pisani A, Valentino F, Misceo S, Castagna A, Bono F, Cossu G, Artusi CA, Terranova C, Petracca M, Tambasco N, Defazio G, Bruno V
BACKGROUND: The Pain in Dystonia Scale (PIDS) is a self-administered instrument to assess pain in dystonia, validated in cervical dystonia (CD). OBJECTIVE: To translate and culturally adapt the PIDS into Italian followin...BACKGROUND: The Pain in Dystonia Scale (PIDS) is a self-administered instrument to assess pain in dystonia, validated in cervical dystonia (CD). OBJECTIVE: To translate and culturally adapt the PIDS into Italian following a standardized forward-backward procedure and to validate the resulting Italian version (I-PIDS) in patients with idiopathic adult-onset CD as part of a multicenter effort aimed at evaluating its clinimetric properties across dystonia subtypes. METHODS: I-PIDS was completed by 64 Italian patients with cervical dystonia from 16 centers, three months or more after their last botulinum toxin treatment. Standard clinimetric analyses were performed. RESULTS: Acceptability was optimal, with no missing data. Score distributions met expected criteria, with mean-median differences <10% of the maximum score for all body regions except the jaw, and no floor or ceiling effects. Internal consistency was satisfactory for all pain regions (α = 0.81-0.91) and for functional impact (α = 0.83) and modulating factors (α = 0.73-0.74). Convergent validity was demonstrated by a moderate correlation between neck pain scores and the Global Dystonia Rating Scale (r = 0.39, p = 0.03), while divergent validity was supported by the absence of correlation with the Montreal Cognitive Assessment (r = 0.02, p = 0.90). Exploratory analyses suggested that pain severity in CD was not associated with age, sex, education, age at onset, or dystonia duration, and that pain frequently involved multiple body regions, independently of dystonia distribution. CONCLUSIONS: These findings support the validity of I-PIDS and provide further insight into the pattern of pain in CD.
BACKGROUND: Spinal and Bulbar Muscular Atrophy (SBMA) is a rare X-linked polyglutamine disorder characterized by a CAG trinucleotide repeat expansion in the androgen receptor gene. This leads to progressive lower motor n...BACKGROUND: Spinal and Bulbar Muscular Atrophy (SBMA) is a rare X-linked polyglutamine disorder characterized by a CAG trinucleotide repeat expansion in the androgen receptor gene. This leads to progressive lower motor neuron degeneration and skeletal muscle atrophy. Given the need for sensitive outcome measures in clinical trials, this study aimed to perform the linguistic adaptation and psychometric validation of the Adult Myopathy Assessment Tool (AMAT) for the Italian population. METHODS: Following a rigorous forward-back translation protocol to ensure semantic and conceptual equivalence, the Italian AMAT was administered to 29 patients. The validation process assessed internal consistency (Cronbach's alpha), inter-rater and intra-rater reliability, and construct validity. The latter was evaluated through correlations with established clinical markers, including the Six-Minute Walk Test (6MWT), the SBMA Functional Rating Scale (SBMAFRS), and the ALSAQ-40 scale. RESULTS: Psychometric analysis revealed excellent inter- and intra-rater reliability and strong internal consistency (Cronbach's alpha > 0.70). Construct validity was confirmed through significant correlations with established functional markers, including the six-minute walk test (6MWT) and the SBMA Functional Rating Scale (SBMAFRS), while the expected negative correlations with ALSAQ-40 scale physical domains-coupled with a lack of correlation with the communication domain-affirmed divergent validity. CONCLUSIONS: The Italian version of the AMAT is a reliable and valid instrument for quantifying functional impairment and endurance in SBMA. Its implementation facilitates standardized longitudinal assessment and enhances the feasibility of cross-national collaborative research.
INTRODUCTION: Pituitary adenomas are common intracranial neoplasms and postoperative optic neuropathy (PON) is a severe and potentially irreversible complication of pituitary adenoma surgery. OBJECTIVE: PON is a devastat...INTRODUCTION: Pituitary adenomas are common intracranial neoplasms and postoperative optic neuropathy (PON) is a severe and potentially irreversible complication of pituitary adenoma surgery. OBJECTIVE: PON is a devastating complication of pituitary adenoma surgery, leading to irreversible visual loss in severe cases. This multicenter retrospective cohort study aimed to investigate the incidence, independent risk factors, and prognostic factors of PON after pituitary adenoma resection. METHODS: We retrospectively analyzed clinical data of 2000 patients who underwent pituitary adenoma surgery at 5 tertiary hospitals between 2015 and 2023. Baseline characteristics, tumor imaging features, surgical details, postoperative complications, and follow-up data were collected. RESULTS: The overall incidence of PON was 3.2% (64 cases), with a significantly lower incidence in the transsphenoidal surgery group (2.5%, 42/1680) than in the craniotomy group (5.8%, 22/380; χ² = 4.12, p = 0.043). We observed that 82% of PON cases occurred within 24 h postoperatively, presenting as sudden visual acuity decline (65%) or visual field defect (35%). Micro-adenomas (< 1 cm) constituted ~ 8% of the cohort, however, they did not develop PON. Reoperation was not associated with PON risk (OR = 1.32, 95% CI: 0.58-2.99, p = 0.312). Hardy-Wilson Grade II/III + Type D (OR = 2.92, 95% CI = 1.58-5.42, p < 0.001) and Grade III/IV + Type E (OR = 2.56, 95% CI = 1.21-5.42, p = 0.014) as well as intraoperative cerebrospinal fluid (CSF) leakage (OR = 2.15, 95% CI: 1.28-3.62, p = 0.003) are independent risk factors for PON. CONCLUSIONS: Transsphenoidal surgery is associated with a lower risk of PON compared to craniotomy for pituitary adenomas. Hardy-Wilson Grade II/III + Type D and Grade III/IV + Type E as well as intraoperative CSF leakage are independent risk factors for PON.
OBJECTIVE: Autobiographical memory specificity is markedly reduced in behavioral variant frontotemporal dementia (bvFTD). Because emotion is known to facilitate autobiographical memory retrieval in healthy adults, we inv...OBJECTIVE: Autobiographical memory specificity is markedly reduced in behavioral variant frontotemporal dementia (bvFTD). Because emotion is known to facilitate autobiographical memory retrieval in healthy adults, we investigated whether emotional cueing could enhance autobiographical specificity in bvFTD. METHODS: Patients with bvFTD and age-matched healthy control participants were asked to retrieve autobiographical memories in response to positive, negative, and neutral cue words. Participants were also asked to rate the emotional valence of the memories they retrieved. RESULTS: Across all cue conditions, patients with bvFTD demonstrated lower autobiographical specificity than control participants. However, emotional cues did not modulate autobiographical specificity in bvFTD, as memories elicited by positive, negative, and neutral cues were comparable in both specificity and emotional valence. In contrast, control participants showed a strong emotional cueing effect, with positive cues eliciting more specific and emotionally positive memories than neutral or negative cues. Emotional valence ratings further revealed a dissociation between groups, with control participants showing differentiated emotional responses across cue conditions, whereas patients with bvFTD exhibited a flattened emotional profile. CONCLUSION: Together, these findings indicate that emotional cues fail to enhance autobiographical specificity or emotional experience in bvFTD, highlighting a profound disruption in emotion–memory integration that may contribute to altered self-related processing in this condition.
BACKGROUND AND PURPOSE: Miyoshi myopathy is an autosomal recessive distal myopathy resulting from pathogenic variants in the DYSF gene encoding dysferlin. This study aimed to characterize a novel biallelic DYSF gene muta...BACKGROUND AND PURPOSE: Miyoshi myopathy is an autosomal recessive distal myopathy resulting from pathogenic variants in the DYSF gene encoding dysferlin. This study aimed to characterize a novel biallelic DYSF gene mutation as a cause of Miyoshi myopathy through comprehensive clinical, genetic and pathological analysis. METHODS: We evaluated serum muscle enzymes and electromyography for myopathic features and performed muscle magnetic resonance imaging to characterize the pattern of involvement. We then conducted whole-exome sequencing with Sanger validation to identify potential causative variants and obtained a muscle biopsy for pathological confirmation. RESULTS: A 19-year-old male presented with progressive bilateral lower limb weakness and symmetric posterior calf muscles atrophy. Markedly elevated creatine kinase (18053 U/L) and myopathic electromyography supported a diagnosis of distal myopathy. Muscle imaging demonstrated severe gastrocnemius atrophy without inflammation. Whole-exome sequencing identified a novel homozygous nonsense variant in exon 20 of the DYSF gene (c.1851 C > G, p.Tyr617Ter), producing a premature stop codon. Muscle biopsy confirmed absent sarcolemmal dysferlin expression, supporting a loss-of-function mechanism. CONCLUSION: We reported a novel pathogenic variant in the DYSF gene, expanding the mutational spectrum of Miyoshi myopathy and reinforcing the role of biallelic DYSF mutations in disease inheritance.
BACKGROUND: Epilepsy is a frequent feature of genetic neurodevelopmental disorders and is increasingly recognized as a disorder of disrupted neuronal networks rather than isolated focal pathology. DYNC1H1, encoding the h...BACKGROUND: Epilepsy is a frequent feature of genetic neurodevelopmental disorders and is increasingly recognized as a disorder of disrupted neuronal networks rather than isolated focal pathology. DYNC1H1, encoding the heavy chain of cytoplasmic dynein 1, is implicated in a broad spectrum of neuromuscular and central nervous system disorders, including intellectual disability, malformations of cortical development (MCDs), and epilepsy. CASE PRESENTATION: We report a female patient with drug-resistant epilepsy beginning at 9 years of age, normal brain MRI and multiple seizure types, including focal motor, tonic–clonic, epileptic spasms, and atypical absence seizures. She also presented with lower limb hypotrophy, pes cavus, and axonal neuropathy. Genetic testing revealed a heterozygous NM_001376.5(DYNC1H1):c.752G > A(p.Arg251His) variant in the N-terminal tail domain, inherited from her father and shared by two siblings with cognitive and gait difficulties. Motor disability progressed over time, and current therapy reduced but did not eliminate seizures. CONCLUSIONS: This case expands the phenotypic spectrum of DYNC1H1-related disorders, demonstrating that tail-domain variants can cause late-childhood epilepsy even in the absence of cortical malformations. The coexistence of central and peripheral involvement highlights widespread dynein-mediated network disruption, while intrafamilial variability underscores the heterogeneity of these conditions.
Firdous J, Asif AE, Haris HM
… +13 more, Iqbal U, Khalid M, Zahid HF, Mubarika M, Abufatima IO, Amin MHJ, Hafeez S, Jabeen F, Shahzaib M, Fatima N, Kumar N, Sen S, Hassan A
PURPOSE: Glioblastoma (GBM) remains the most common and lethal primary central nervous system tumor, with a median survival of only 14.6 months under standard care. The tumor’s characteristic "Warburg effect"—a dependenc...PURPOSE: Glioblastoma (GBM) remains the most common and lethal primary central nervous system tumor, with a median survival of only 14.6 months under standard care. The tumor’s characteristic "Warburg effect"—a dependency on aerobic glycolysis for energy—creates a metabolic vulnerability. This review evaluates the efficacy and safety of the ketogenic diet (KD) as an adjunctive metabolic therapy aimed at exploiting this glucose dependency. METHODS: This PRISMA-compliant systematic review updates clinical evidence by synthesizing data from databases from 2000 to September 2025. We searched PubMed, Embase, Cochrane, and Web of science for human studies assessing the ketogenic diet (KD) in glioblastoma and high-grade gliomas. Primary outcomes included overall survival (OS), progression-free survival (PFS), feasibility, and adverse events. Study quality was assessed using Joanna Briggs Institute tools. Prospero registration: CRD420251232650. RESULTS: Forty-one studies were included, ranging from randomized trials to case series and abstracts, utilizing interventions such as the classic 4:1 ketogenic diet, Modified Atkins Diet, and calorie restriction. Adherence was high (> 75% maintained nutritional ketosis). Recent data indicate significant survival benefits; adherent cohorts achieved a median OS of 29.4 months vs 14.6 months in historical controls; with 66.7% 3-year survival rate. The diet was well-tolerated, with adverse events limited to mild gastrointestinal symptoms and fatigue. No Grade 3/4 diet-related toxicities reported. CONCLUSION: Current evidence supports the KD as a safe, feasible, and biologically rational adjunct to standard glioblastoma treatment. It demonstrates potential to prolong survival without severe toxicity, highlighting the need for standardized Phase III trials to establish clinical guidelines.
BACKGROUND: Freezing of Gait (FOG) is the most disabling and puzzling symptom of Parkinson’s Disease (PD). FOG is strongly associated with increasing disease severity and longer duration of levodopa treatment. In additio...BACKGROUND: Freezing of Gait (FOG) is the most disabling and puzzling symptom of Parkinson’s Disease (PD). FOG is strongly associated with increasing disease severity and longer duration of levodopa treatment. In addition to FOG in OFF states, there has been a characterization of ON-state freezing of gait (ON-FOG), often described as a “paradoxical” effect of dopaminergic therapy. METHODS: Literature review. RESULTS AND DISCUSSION: In this review, we propose, for the first time, levodopa-induced FOG to be an expected manifestation, rather than a paradox. We first clarify the clinical subtypes of FOG (OFF-FOG, levodopa unresponsive FOG, levodopa-induced FOG and biphasic FOG). We then examine the biomechanical, neurochemical, cognitive and sensori-motor mechanisms that differentiate limb movement from gait control, and explore their differing responses to chronic dopaminergic therapy, while discussing clinical implications of this hypothesis. CONCLUSION: This review provides a distinct phenotype of levodopa induced FOG and posits it to be secondary to expected non-uniform effects of levodopa therapy. The various mechanisms include levodopa-induced spatio-temporal dissociation of gait, disruption of multi-segment coordination and temporal coupling for execution of gait, negative influence on the striatal dopamine-cholinergic balance with maladaptive plasticity affecting the cognitive and sensorimotor networks. Identification of this phenotype is pivotal, since it requires optimal dopaminergic stimulation instead of maximisation, with alternative therapeutic strategies.
BACKGROUND: Stiff-person syndrome (SPS) and stiff-person spectrum disorders (SPSD) are rare, immune-mediated neurological conditions characterized by progressive muscle rigidity, painful spasms, exaggerated startle respo...BACKGROUND: Stiff-person syndrome (SPS) and stiff-person spectrum disorders (SPSD) are rare, immune-mediated neurological conditions characterized by progressive muscle rigidity, painful spasms, exaggerated startle responses, and substantial functional and psychosocial morbidity. Clinical heterogeneity, frequent diagnostic delay, and evolving immunopathogenic insights continue to complicate diagnosis and management. METHODS: This narrative review synthesizes current evidence on the epidemiology, clinical phenotypes, immunopathogenesis, diagnostic strategies, therapeutic approaches, monitoring tools, and psychosocial impact of SPS and SPSD. Evidence from randomized controlled trials, cohort studies, systematic reviews, and recent advances in immunotherapy is integrated, with attention to both adult- and pediatric-onset disease. RESULTS: Classic SPS is most commonly associated with high-titer antibodies against glutamic acid decarboxylase 65 and presents with axial and proximal limb rigidity, stimulus-sensitive spasms, hyperlordosis, and gait impairment. The SPS spectrum includes stiff limb syndrome, SPS-plus, progressive encephalomyelitis with rigidity and myoclonus, paraneoplastic SPS, and seronegative forms, each with distinct clinical and immunological profiles. Impaired GABAergic inhibition represents a central pathophysiological mechanism, although the direct pathogenic role of anti-glutamic acid decarboxylase antibodies remains debated. Diagnosis relies on characteristic clinical features, targeted autoantibody testing, and neurophysiological evidence of continuous motor unit activity. Management is anchored in symptomatic GABAergic agents and immunomodulatory therapies, with intravenous immunoglobulin supported by randomized trial evidence. Emerging treatments—including B-cell–depleting therapies, plasma exchange, autologous hematopoietic stem cell transplantation, neonatal Fc receptor blockade, and chimeric antigen receptor T-cell therapy—offer potential benefit in refractory disease. Standardized clinical scales are essential for monitoring disease burden and treatment response.
BACKGROUND: Functional syncope and vasovagal syncope (VVS) in children both present with transient loss of consciousness (TLOC) and are clinically challenging to differentiate. This study aims to delineate the distinguis...BACKGROUND: Functional syncope and vasovagal syncope (VVS) in children both present with transient loss of consciousness (TLOC) and are clinically challenging to differentiate. This study aims to delineate the distinguishing features among factors associated with TLOC induction in these two conditions. METHODS: A total of 31 children presenting with syncope and diagnosed as functional syncope were enrolled in the functional syncope group; concurrently, 40 children presenting with syncope and diagnosed with VVS were enrolled in the VVS group. Clinical manifestations— including demographic characteristics, precipitating factors, prodromal symptoms, syncope episode characteristics, family history, and psychosocial stressors—were systematically compared between the two groups. RESULTS: Body weight was significantly higher in the functional syncope group than in the VVS group (P < 0.05). No statistically significant differences were observed between the groups in terms of sex distribution, age, body height, or baseline resting heart rate (P > 0.05). Compared with the VVS group, the functional syncope group exhibited significantly fewer identifiable triggers, fewer presyncope symptoms, and a lower prevalence of familial syncope history (all P < 0.05). Conversely, the functional syncope group demonstrated significantly longer syncope duration, higher syncope frequency, and greater exposure to emotional stress events (all P < 0.05). Disease duration did not differ significantly between the two groups (P > 0.05). CONCLUSIONS: Children with functional syncope exhibit distinct clinical profiles relative to those with VVS, characterized by fewer precipitating factors and prodromal symptoms, longer duration and higher frequency of syncope episodes, reduced familial syncope history, and increased association with emotional stress events.
BACKGROUND: Primary central nervous system lymphoma (PCNSL) belongs to the group of the large B-cell lymphomas of immune-privileged sites, confined to the central nervous system. Its heterogeneous clinical and radiologic...BACKGROUND: Primary central nervous system lymphoma (PCNSL) belongs to the group of the large B-cell lymphomas of immune-privileged sites, confined to the central nervous system. Its heterogeneous clinical and radiological presentation often leads to diagnostic delay, particularly in non-specialized centers. This study aimed to characterize the clinical, demographic, imaging, and treatment-related features of patients diagnosed with PCNSL in a tertiary hospital without the needed facilities to manage these patients and to highlight associated diagnostic challenges. METHODS: We performed a retrospective, descriptive, single-centre study including patients diagnosed with histologically confirmed PCNSL between February 2011 and December 2022. Clinical, laboratory, imaging, histology of brain biopsy, treatment, and survival data were collected and analysed. Survival time was defined as the interval from diagnosis to death, and symptom-to-diagnosis time as the interval from symptom onset to pathological confirmation. RESULTS: Twenty-two patients were included (median age 65 years), most of whom were immunocompetent (82%). Neuropsychiatric symptoms and focal neurological deficits were the most common presentations. Imaging revealed predominantly supratentorial (82%) and multifocal (68%) lesions, with homogeneous gadolinium enhancement in most cases and universal diffusion restriction on MRI. Atypical imaging patterns, including ring enhancement in immunocompetent patients, were observed. Histological confirmation was achieved in 21 cases; cerebrospinal fluid flow cytometry was diagnostic in only two patients with spinal or leptomeningeal involvement. Median symptom-to-diagnosis interval was 2.5 months. Younger patients (< 50 years) had longer diagnostic delays but significantly longer survival. Patients receiving targeted therapy had significantly longer median survival than those receiving palliative care (7 vs. 1 month). Overall median survival was 2 months, and six-month mortality was 54.5%. CONCLUSION: PCNSL remains a major diagnostic challenge, particularly in non-specialized hospitals, due to its clinical and radiological heterogeneity. Early suspicion, prompt biopsy, and timely referral to specialized centers are crucial to improve outcomes. Although limited by the small sample size and retrospective design, this study provides relevant real-world data highlighting the impact of diagnostic delay and treatment access on survival.
This systematic review and meta-analysis synthesizes evidence on cerebrospinal fluid (CSF) proteomic alterations in patients with spinal muscular atrophy (SMA) treated with nusinersen. Across 21 studies, consistent post-...This systematic review and meta-analysis synthesizes evidence on cerebrospinal fluid (CSF) proteomic alterations in patients with spinal muscular atrophy (SMA) treated with nusinersen. Across 21 studies, consistent post-treatment decreases were observed in neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNF-H), and tau protein, which correlated with motor improvement, particularly in younger patients. Synaptic stress markers (e.g., α-synuclein, DJ-1) and metabolic proteins (e.g., apolipoprotein A1, transthyretin) demonstrated dynamic responses, suggesting systemic effects of therapy, while inflammatory cytokines and glial markers showed inconsistent trends. Extracellular matrix proteins and muscle-specific microRNAs emerged as promising indicators of musculoskeletal remodeling and treatment response. To evaluate clinical outcomes, a meta-analysis of 12 studies (n = 195 pre-treatment; n = 175 post-treatment) revealed a statistically significant mean improvement of 3.33 points in Hammersmith Functional Motor Scale Expanded (HFMSE) scores following nusinersen therapy (95% CI: –6.22 to –0.43; p = 0.02), with no heterogeneity (I² = 0%), indicating consistent functional gains across SMA populations. Overall, these findings suggest that HFMSE is a responsive clinical outcome measure in nusinersen-treated patients with SMA and that CSF proteomic profiling may provide complementary insights into biological treatment effects. However, given the heterogeneity in study design, patient characteristics, and proteomic platforms, the current evidence should be interpreted cautiously. Further large-scale, standardized, and longitudinal studies are required to validate candidate biomarkers and to clarify their integration with motor function assessments in monitoring treatment response in SMA.
BACKGROUND: Post-stroke patients often suffer from impaired postural stability and a heightened risk of falls due to neu- romuscular deficits. Russian current stimulation, a medium-frequency neuromuscular electrical stim...BACKGROUND: Post-stroke patients often suffer from impaired postural stability and a heightened risk of falls due to neu- romuscular deficits. Russian current stimulation, a medium-frequency neuromuscular electrical stimulation technique, has shown promise in enhancing muscle strength and mo- tor control. PURPOSE: This study aimed to investigate the effect of Russian current stimulation applied to the ante-rior tibial muscle group, in conjunction with a structured physiotherapy program, on postural stability and fall risk in stroke survivors. METHODS: A randomized controlled trial was conducted with 40 stroke patients aged 40–60 years (BMI < 30 kg/m²), divided equally into study (n=20) and control (n=20) groups. Both groups received a standard 40-minute physiotherapy regimen three times weekly for six weeks. The study group also received Russian current stimulation (2.5 kHz, 50 bursts/sec, 20 min/session) target- ing the anterior tibial group. Outcomes were assessed pre- and post-intervention using the Biodex Balance System in- dices (overall, anterior-posterior, and medial-lateral stabil- ity), and fall risk index RESULTS: Significant improvements were observed in the study group compared to controls as reductions in overall stability index, anterior-posterior and medial-lateral sway indices (all p < 0.05). No significant dif- ference was noted between groups in fall risk under eyes- closed conditions (p > 0.05). CONCLUSION: The addition of Russian current stimulation to conventional physical therapy significantly improves postural stability and reduces fall risk in stroke patients under eyes-open conditions. These findings support the integration of neuromuscular electrical stimulation into stroke rehabilitation protocols targeting the anterior tibial muscle group. TRIAL REGISTRATION: Clinical-Trials.gov Identifier: NCT06793865