Neurol. Int., Volume 18, Issue 8 (August 2026) – 18 articles

Background/Objectives: Patients with prolonged disorder of consciousness (PDOC) who regained consciousness in intensive care for consciousness rehabilitation (ICCR) were referred to further brain rehabilitation (FBR). The current retrospective cohort study evaluated the functional and cognitive outcomes of FBR. Methods: We assessed outcomes in 258 PDOC patients during FBR and used multivariate regression analyses to examine the influence of demographic and clinical characteristics on outcomes. Results: During FBR, Functional Independence Measure (FIM) motor, cognitive, and total scores improved from 21 ± 11, 11 ± 10, and 32 ± 15 to 43 ± 26, 18 ± 7, and 61 ± 32, respectively (p < 0.001). Dynamic Lowenstein Occupational Therapy Cognitive Assessment (DLOTCA) total scores increased from 57 ± 29 to 82 ± 36, and the average 6-min-walk (6MW) distances improved from 295 to 374 m (p < 0.001). Higher discharge FIM and DLOTCA scores were associated with younger age, traumatic etiology of the brain injury, shorter time to regaining consciousness, and higher FIM and DLOTCA scores at admission to FBR (p < 0.05). Conclusions: We observed functional and cognitive improvement in the examined patients. The improvement was associated with factors that may mainly reflect the severity of brain damage. The findings support continuing rehabilitation before and after emerging from PDOC. Full article

Background/Objectives: Chronic subdural hematoma (cSDH) is one of the most common neurosurgical disorders in older adults and remains associated with a relevant recurrence rate despite standardized surgical treatment. Identifying postoperative factors that predict recurrence may improve postoperative surveillance and surgical strategy. We therefore investigated whether the density of the residual hematoma on early postoperative computed tomography (CT) is associated with recurrence after burr-hole trepanation. Methods: We retrospectively analyzed all consecutive patients who underwent burr-hole trepanation for cSDH at our institution between 2016 and 2021. Residual hematoma density was measured in Hounsfield units (HU) on postoperative CT scans. Recurrence was defined as symptomatic hematoma reaccumulation requiring reoperation. Results: A total of 223 patients met the inclusion criteria. The overall recurrence rate was 20.2%. Mean residual hematoma density was significantly higher in the recurrence group than in the non-recurrence group (23.2 ± 13.1 HU vs. 19.0 ± 9.1 HU; p = 0.005). ROC analysis identified an optimal cutoff value of 19 HU (AUC 0.578, 95% CI 0.511–0.645; p = 0.022) with sensitivity of 57.8%, and a specificity of 57.9%. Patients with residual hematoma density ≥19 HU had a significantly higher recurrence rate than those with lower density (25.7% vs. 15.6%; p = 0.043). In multivariable logistic regression, higher residual density remained an independent predictor of cSDH recurrence (p = 0.008, OR 1.9; 95% CI 1.2–3.0). Conclusions: Higher postoperative residual hematoma density is an independent predictor of recurrence after burr-hole trepanation for cSDH. Residual density on early postoperative CT may serve as a simple and clinically accessible imaging marker of incomplete hematoma clearance and may help refine postoperative risk assessment. Nevertheless, the low AUC limits interpretation of predictive performance. Full article

Thoracoabdominal aortic aneurysm (TAAA) is a complex vascular disorder involving both thoracic and abdominal segments of the aorta and remains associated with substantial morbidity and mortality. One of the most serious complications after thoracoabdominal aortic aneurysm (TAAA) repair is spinal cord ischemia (SCI), which may progress to spinal cord infarction and result in irreversible neurologic deficits including paraplegia, neurogenic bladder dysfunction, and bowel dysfunction. The incidence of SCI after TAAA repair varies with the extent of aneurysmal involvement, operative duration, and patient comorbidities. The primary pathophysiologic mechanism involves interruption of radiculomedullary arterial flow, compounded by systemic hypotension and limited collateral circulation. Because SCI profoundly affects functional recovery and long-term quality of life, prevention and early recognition are central to perioperative management. Established neuroprotective strategies emphasize maintenance of spinal cord perfusion through meticulous hemodynamic optimization, cerebrospinal fluid (CSF) drainage, and temperature modulation. Intraoperative neuromonitoring using motor and somatosensory-evoked potential facilitates early detection, while newer modalities such as near-infrared spectroscopy and CSF lactate monitoring may offer additional insight. When SCI occurs despite prophylaxis, rapid initiation of rescue measures including CSF drainage, hemodynamic augmentation, and other discussed treatments may improve neurologic outcomes. Long-term care focuses on rehabilitation, symptom management, and psychological support. Therefore, this review aims to consolidate medical evidence to improve the prevention, detection, and treatment of spinal cord infarction associated with thoracoabdominal aortic aneurysm repair. Full article

Isolated cortical vein thrombosis is a rare subtype of cerebral venous thrombosis with highly variable clinical and radiologic manifestations that frequently delay diagnosis. Bilateral thrombosis of the veins of Trolard is exceptionally uncommon, with only a few cases reported in the literature. We report a 64-year-old right-handed man who presented after being found unresponsive with suspected seizure. Although his neurological examination was normal at evaluation (NIHSS 0), noncontrast CT demonstrated subtle bilateral cortical vein hyperdensities (cord sign). Subsequent MRI and MR venography confirmed bilateral thrombosis of the veins of Trolard with associated venous congestion and a small sulcal subarachnoid hemorrhage. The patient was treated with therapeutic anticoagulation and levetiracetam. The patient achieved an excellent functional outcome (modified Rankin Scale score of 0). At 3-month follow-up, he remained neurologically intact without recurrent seizures. Follow-up MRI demonstrated improvement of the cortical FLAIR abnormality, and MR venography showed significant interval improvement in the bilateral vein of Trolard thromboses with residual short-segment nonocclusive filling defects, consistent with partial venous recanalization. This case expands the recognized clinical spectrum of the bilateral vein of Trolard thrombosis by demonstrating that extensive bilateral cortical venous involvement may present predominantly with seizure despite a normal neurological examination (NIHSS 0). Early recognition of subtle CT findings, confirmation with dedicated venous imaging, and prompt anticoagulation can result in excellent clinical recovery and favorable radiographic evolution. Full article

Background/Objectives: Brain-derived neurotrophic factor (BDNF) and antioxidant networks mediated by Selenoprotein P (SEPP1) are core drivers of structural neuroplasticity and blood–brain barrier integrity, yet their co-regulatory behavior during subacute stroke neurorehabilitation remains poorly understood. This pilot study quantified concurrent changes in serum BDNF and SEPP1 during rehabilitation. Methods: Sixteen subacute post-stroke patients with mild stroke severity were assigned to an intensive multi-modal neurorehabilitation protocol incorporating high-intensity interval training (Treated, n = 7) or standard care (Control, n = 9); the biomarker sampling window averaged 73.4 days. Fasting venous blood was collected at baseline and post-intervention and analyzed by ELISA. Results: BDNF changes (ΔBDNF) differed significantly between arms (U = 57.0, p = 0.0081): the Treated cohort showed a uniform decrease (mean Δ: −0.240 ± 0.103 ng/mL), while Controls showed stabilization or a slight increase (mean Δ: +0.118 ± 0.339 ng/mL). ΔBDNF and ΔSEPP1 were significantly, positively correlated across the cohort (ρ = 0.596, p = 0.015). Conclusions: The BDNF decline in the Treated group is consistent with the “central sink” hypothesis, but may more plausibly reflect stress/cortisol-mediated suppression induced by the high training intensity, contrasting with increases typically reported after moderate-intensity subacute-phase exercise. The collinear coupling with SEPP1 suggests a link between neurotrophic synthesis and antioxidant buffering during post-stroke tissue remodeling, though this correlational finding does not by itself establish a single, coordinated mechanism. Full article

Objectives: To determine the prevalence of visual deficits among inpatients with acquired brain injury, to examine the agreement between objective screenings and patient-reported visual deficits, and to investigate patient characteristics associated with visual deficits. Methods: This cross-sectional study included data on screened and patient-reported visual deficits in patients with acquired brain injury admitted for inpatient rehabilitation. The screenings were conducted by occupational therapists. Visual acuity and visual field were assessed in 2014–2023, and complemented by assessment of ocular motility and patient-reported deficits in 2021–2023. Predictive values were calculated for the agreement between screening results and patient-reported symptoms. Logistic regression models were applied to investigate the association between clinical characteristics and visual deficits. Results: 2814 patients were screened, 65% were men, the median age was 64 years, and the most common diagnosis was stroke (66%). In screened patients 32% had reduced visual acuity, 18% had ocular motility deficits, and 15% had visual field deficits. Of 975 patients providing self-reports, 38% reported vision problems. A total of 28% of patients who did not report visual deficits, had visual deficits in the objective screening. Lower functional level was associated with greater odds of having any visual deficits. Traumatic and anoxic brain injuries were associated with lower odds of visual field deficits compared with stroke. Conclusions: The high proportion of patients with visual deficits underlines that these are common consequences following acquired brain injury. Objective screening and patient-reported deficits offer overlapping yet distinct insights into visual deficits. Knowledge of clinical characteristics associated with visual deficits may help recognize high-risk subgroups. Full article

Background/Objectives: Ulnar nerve neuropathy at the elbow (UNE) is the second most common focal neuropathy of the upper extremity and often results from entrapment of the ulnar nerve as it traverses the elbow with insidious onset and gradual progression. This study describes the clinical, electrodiagnostic (EDX), and ultrasound (US) findings in a cohort of patients presenting with acute UNE. Methods: This is a review of 103 patients with clinical features of UNE with acute onset who underwent EDX and US studies over a 25-year period (2010–2026) at our Neurodiagnostic Center. Results: Of the 103 patients with acute UNE, all experienced paresthesia in the ulnar nerve distribution. A total of 27 (26.2%) patients had elbow pain, and 99 (96.1%) had decreased pinprick sensation in the ulnar nerve distribution. Weakness of the following muscles was detected: abductor digiti minimi (ADM) (94 [91.3%]), FDI (first dorsal interosseous) (91 [88.3%]), and FDPu (flexor digitorum profundus—ulnar) (76 [73.8%]). Most patients had a clinical grade of 3 (severe: sensory and motor abnormalities as well as atrophy of the FDI and ADM muscles) (93 [90.3%]). Perioperative injuries were the most common etiology of acute UNE, consisting of 65 (63.1%) patients. The perioperative injury was noted after surgical procedures at varied locations, most frequently at the shoulder in 23 (35.4%) followed by coronary artery bypass in 9 (13.8%) and knee joint surgery in 8 (12.3%). Non-iatrogenic injuries affected 11 (10.7%) patients. The US study revealed cysts and tumors such as a Schwannoma in 14/76 (18.4%) patients. Focal demyelination was observed by EDX studies in 95 (92.2%) patients, and a conduction block was detected in 24 (23.3%). Motor and sensory axonal involvement was identified in 81 (78.6%) and 86 (83.5%) patients, respectively. Of the 76 patients who underwent an US study, 68 (90.6%) had an increase in the cross-sectional area of the ulnar nerve and 51 (68.0%) had a hypoechoic ulnar nerve at the elbow. Conclusions: In this study, the most common cause of acute UNE was periprocedural injury, most frequently following shoulder surgery. Acute UNE may also occur without a history of antecedent trauma or a surgical procedure. EDX and US studies provide complementary data to determine the severity and the etiology of acute UNE and guide further management. Full article

Background: Flow diverters (FDs) are widely used to treat intracranial aneurysms. Although effective, FD-related thrombosis or progressive stenosis may lead to acute or delayed cerebral hypoperfusion with significant neurological morbidity. Management options are limited when medical or endovascular rescue strategies fail. This study aims to evaluate the role of extracranial–intracranial bypass (EC-IC bypass) as a rescue strategy across the spectrum of FD-related cerebral hypoperfusion. Methods: We retrospectively reviewed all patients who underwent EC-IC bypass for FD-related cerebral hypoperfusion over a 10-year period in our institution. Both acute and chronic presentations were included. Clinical status was assessed using the modified Rankin Scale (mRS). Imaging evaluation included digital subtraction angiography (DSA), computed tomography angiography (CTA), magnetic resonance angiography (MRA) and quantitative magnetic resonance imaging for bypass flow assessment. Surgical technique, antiplatelet therapy, timing of intervention and clinical outcomes were analysed. Results: Five patients with FD-related cerebral hypoperfusion who underwent superficial temporal artery–middle cerebral artery bypass (STA-MCA bypass) were identified. Two distinct patterns emerged. Three patients developed early hypoperfusion within the first month of FD placement, presenting with acute neurological deficits and treated by emergent or urgent bypass under dual antiplatelet therapy. Two patients developed late hypoperfusion years after the procedure, presenting with progressive haemodynamic symptoms and treated by elective flow-augmentation bypass under aspirin monotherapy. At discharge, only one patient had an mRS ≥ 3. At one-year follow-up, a favourable outcome (mRS ≤ 2) was observed in all patients with available data. Follow-up data were missing for one patient. Conclusions: EC-IC bypass represents a feasible rescue strategy for FD-related cerebral hypoperfusion when medical or endovascular treatments fail. In our experience, though limited, STA-MCA bypass can provide sufficient cerebral reperfusion, even in urgent settings and under dual antiplatelet therapy, leading to favourable neurological outcomes. Full article

Background: Isolated hypoglossal nerve palsy is a rare neurological condition with a broad differential diagnosis. Although neoplastic disorders are the most common cause, internal carotid artery dissection (ICAD) is an uncommon but clinically important and potentially reversible vascular etiology that is frequently underrecognized. This systematic review synthesized the available evidence regarding the clinical presentation, imaging findings, pathophysiological mechanisms, treatment, and outcomes of isolated hypoglossal nerve palsy associated with ICAD through a standardized patient-level descriptive analysis. Methods: This systematic review was conducted according to the PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261364863). PubMed, Scopus, Web of Science, and the Cochrane Library were searched from inception to April 2026. Manual reference screening and forward citation tracking were also performed. Studies reporting original, patient-level data on isolated hypoglossal nerve palsy associated with ICAD were eligible. Clinical, imaging, treatment, and outcome data were extracted and synthesized descriptively. In hybrid publications combining original case reporting with a narrative literature review, only eligible, original patient data were included in the quantitative synthesis, whereas the narrative review components were used for citation tracking and contextual comparison. Results: A total of 26 standalone primary publications were included, comprising 23 case reports and 3 case series. Two additional hybrid publications each contributed one eligible patient. One hybrid publication contained an original case-report component, whereas the other reported two original cases and was therefore considered to contain a case-series component, although only one of its patients fulfilled the eligibility criteria. Overall, the 28 publications contributed 32 eligible patients to the patient-level quantitative synthesis. The narrative review components of the two hybrid publications were used solely for citation tracking and contextual comparison. Patients were predominantly male (28/32, 87.5%), with a median age of 47 years. Tongue deviation (28/28, 100%) and tongue weakness (30/30, 100%) were the hallmark clinical features, followed by dysarthria (26/26, 100%) and dysphagia (18/22, 81.8%). All patients presented with isolated hypoglossal nerve palsy at presentation, without Horner syndrome or additional lower cranial nerve involvement. MRI was the most frequently reported imaging modality (29/32, 90.6%), whereas CTA was commonly used to characterize luminal abnormalities. Intramural hematoma (25/26, 96.2%), luminal stenosis (23/26, 88.5%), and external arterial enlargement (22/24, 91.7%) were the most consistent neuroradiological findings. Conservative medical management predominated (31/32, 96.9%). The available evidence was more consistent with a compressive mechanism related to subadventitial arterial wall expansion, although an ischaemic contribution involving the vasa nervorum could not be excluded. A favourable clinical outcome (complete recovery or marked improvement) was observed in 21/30 patients (70.0%). Overall, improvement of any degree, including partial recovery, was documented in 25/30 evaluable patients (83.3%). Outcome data should be interpreted cautiously because they derive predominantly from individual case reports. Conclusions: This systematic review provides an updated standardized synthesis of the available case-level evidence on isolated hypoglossal nerve palsy associated with ICAD. CTA and MRI/MRA provide complementary diagnostic information and may facilitate timely diagnosis when interpreted according to the clinical context. The available evidence identifies recurrent clinico-radiological patterns that may assist clinicians in recognizing this uncommon presentation while highlighting the need for prospective multicentre studies to better inform future diagnostic and therapeutic strategies. Full article

In recent years, the application of virtual reality (VR) in rehabilitation medicine has gained increasing attention. VR is generally classified into two types: non-immersive and immersive systems. Non-immersive VR allows patients to interact with virtual environments through screens while maintaining a connection with the real world. Several studies have reported that the combined application of non-immersive VR and adjunctive technologies such as transcranial direct current stimulation and hand exoskeleton devices could facilitate functional recovery of hemiparetic limbs after stroke. In contrast, immersive VR is applied with the use of head-mounted displays to encompass the user’s visual field, providing a high level of immersion and an enhanced sense of presence. This enhanced experience has been shown to promote patients’ attention and motivation, which are important factors in motor learning. Emerging evidence suggests that immersive VR is effective for improving upper limb motor function in post-stroke hemiparetic patients. Furthermore, rehabilitative training performed in immersive virtual environments may facilitate the transfer of acquired motor skills to real activities of daily living. Future research should aim to generate high-quality evidence through large-scale, multicenter randomized controlled trials to better establish the clinical efficacy and optimal implementation of VR-based interventions in stroke rehabilitation. Full article

Introduction: Stroke remains a leading cause of mortality and long-term disability worldwide. Coordinated care delivered through protocol-driven multidisciplinary teams enables rapid diagnosis and treatment, both of which are essential for improving clinical outcomes. Objective: Our objective was to analyze care strategies in the emergency management of acute ischemic stroke, focusing on treatment times and influencing factors, interventions implemented in emergency settings and their impact on clinical outcomes, and the contribution of healthcare professionals to optimizing stroke care. Methods: A systematic review was conducted in accordance with the PRISMA 2020 Statement. Current evidence published between 2021 and 2026 was retrieved from five databases: PubMed, Web of Science, Scopus, Cochrane Library, and SciELO. Eligibility criteria were applied, and methodological quality and risk of bias were assessed using validated appraisal tools. Results: Fourteen studies involving a total of 6384 patients were included. Factors such as healthcare system reorganization, multidisciplinary teamwork, early protocol activation, and the use of stroke-specific triage scales significantly influenced treatment times. Coordinated and protocolized care pathways, together with evidence-based clinical interventions, were consistently associated with higher thrombolysis rates and shorter treatment times, while improvements in neurological and functional recovery were reported in several, but not all, studies. The integration of specialized stroke professionals and structured emergency care processes contributed to reducing treatment delays and improving patient outcomes. Conclusions: Critical treatment times in acute ischemic stroke are influenced by multiple factors, and targeted organizational and clinical strategies can accelerate diagnosis and treatment. Although improvements in clinical outcomes were not consistently demonstrated across all included studies, the available evidence consistently supports protocol-driven multidisciplinary emergency care as an effective strategy for reducing treatment delays and optimizing acute ischemic stroke management. Full article

Background and objectives: Cerebrovascular strokes and transient ischemic attacks (TIAs) remain leading causes of global mortality and long-term disability. Emerging evidence suggests that pre-existing structural brain frailty—driven by chronic cerebral small vessel disease (CSVD)—critically limits neuroplastic compensation and determines overall recovery potential. This systematic review aims to synthesize current evidence evaluating brain frailty as an independent determinant of functional and cognitive outcomes. Methods: Following PRISMA and Cochrane SWiM guidelines, a comprehensive literature search was conducted across PubMed, Web of Science, Embase, and Scopus. Methodological quality was evaluated using the Newcastle–Ottawa Scale (NOS). Due to anticipated clinical and methodological heterogeneity, data were synthesized via a structured narrative approach. A total of 15 studies comprising more than 18,000 participants met the inclusion criteria, including prospective cohorts, retrospective cohorts, registry analyses, pooled cohort studies, and post hoc analyses of randomized controlled trials. Results: Structural disconnection burden emerged as one of the strongest predictors of post-stroke cognitive impairment, demonstrating remarkably large effect sizes at both 6 months (OR 9.96, 95% CI 2.21–52.40) and 36 months (OR 12.27, 95% CI 2.80–63.40). Additionally, blood–brain barrier (BBB) leakage was significantly associated with longitudinal cognitive decline (β −3.62 to −0.16, p < 0.001). Pre-existing brain frailty was also consistently associated with poorer functional recovery following acute ischemic stroke, even among patients undergoing advanced reperfusion strategies such as endovascular thrombectomy or intravenous thrombolysis. Conclusions: Brain frailty should be integrated into clinical prognostic frameworks as a key marker for predicting long-term cognitive function and functional independence in stroke patients. However, the substantial methodological and clinical heterogeneity observed across the included literature must be acknowledged as a key limitation of the current evidence base. Large-scale, prospective, multicenter longitudinal studies are required to better standardize brain frailty metrics and validate their utility in clinical practice. Full article

Background/Objective: Status epilepticus (SE) is a life-threatening condition that requires immediate response to effectively control. Although benzodiazepines are the first-line treatment against SE, when treatment is delayed, benzodiazepine pharmacoresistance develops. In preclinical models of benzodiazepine refractory SE, the addition of antiseizure medications (ASMs) as adjunct to midazolam to reduce neuronal excitability and enhance inhibitory function is essential to protect against the neurodegeneration and epileptogenesis that follows prolonged seizure. Brivaracetam is a recently FDA-approved ASM to treat partial onset seizures in pediatric and adult patients as a monotherapy or adjunct therapy. We evaluated the potential of brivaracetam as monotherapy or in combination with midazolam and ketamine for efficacy against organophosphorus nerve agent (OPNA)-induced refractory SE in rats. Methods: Adult male rats were exposed to a seizure-inducing dose of soman and treated with atropine sulfate and the oxime asoxime chloride one minute after soman exposure and with brivaracetam alone or in combination with midazolam and ketamine 40 min after seizure onset. Multiple metrics of protection such as seizure severity, spontaneous recurrent seizure (SRS), neuronal loss, and neuroinflammation were evaluated. Results: Although brivaracetam monotherapy resulted in 100% survival, protection from the development of SRS and neurodegeneration only occurred when brivaracetam was administered as an adjunct to ketamine and midazolam. Initial seizure severity was also reduced by the combination of brivaracetam–midazolam–ketamine over monotherapy. Conclusions: Although further research is needed to determine optimal drug combinations, these preclinical findings provided further evidence that simultaneous polytherapy with ASMs improves OPNA-induced seizure outcomes. Full article

Background: Primary intra-axial cerebral schwannomas are exceptionally rare benign tumors that arise within the brain parenchyma without any association with cranial nerves. Their nonspecific clinical and radiological features frequently mimic high-grade gliomas, making preoperative diagnosis challenging. Case Presentation: We report the case of a 17-year-old male who presented with recent-onset right-sided visual disturbance and bilateral early papilledema. Magnetic resonance imaging demonstrated a lobulated, contrast-enhancing left occipitoparietal intra-axial mass with restricted diffusion, hyperperfusion, extensive vasogenic edema, and adjacent calvarial remodeling, raising suspicion for glioblastoma, gliosarcoma, or pleomorphic xanthoastrocytoma. The patient underwent gross-total resection through a left occipital craniotomy. Histopathological examination revealed a well-circumscribed cellular spindle-cell neoplasm with alternating hypercellular and hypocellular areas, perivascular hyalinization, and an absence of mitotic activity or necrosis. Immunohistochemistry demonstrated diffuse positivity for S100 and SOX10, negative Olig2 staining, retained INI-1 expression, and a low Ki-67 proliferation index of approximately 5%, establishing the diagnosis of a WHO grade 1 cellular schwannoma. Conclusions: Intra-axial cerebral schwannoma should be considered in the differential diagnosis of enhancing supratentorial brain lesions in children and adolescents, particularly when imaging suggests a high-grade glioma. Definitive diagnosis relies on histopathological and immunohistochemical evaluation. Gross-total resection is associated with excellent outcomes and durable disease control, although continued radiological surveillance remains advisable given the rarity of the condition. Full article

Neurodegenerative diseases are targets for pridopidine therapy, which aims to improve quality of life through neuroprotective mechanisms that involve sigma-1 receptor (S1R) activation. Neurodegenerative motor and cognitive diseases are influenced by dopamine imbalance, where disruptions in pathways contribute to states that are hyperkinetic or hypokinetic, while current dopaminergic treatments are symptomatic rather than disease-modifying, especially for Huntington’s disease and Amyotrophic lateral sclerosis. This review summarizes the mechanisms underlying pridopidine-mediated neuroprotection and examines the current evidence supporting its therapeutic potential. The S1R is an endoplasmic reticulum-mitochondria-associated chaperone involved in homeostasis of calcium, stress regulation, and mitochondrial function. Pridopidine is a small lipophilic molecule that crosses the blood–brain barrier and acts as an S1R agonist, with minimal dopamine D2 receptor occupancy. Activation of S1R by pridopidine modulates calcium signaling and enhances anti-apoptotic activity. Collectively, available evidence suggests that pridopidine may improve motor outcomes and slow disease progression in Huntington’s disease and amyotrophic lateral sclerosis, supporting its promise as a disease-modifying therapeutic strategy. Full article

Introduction: Stiff-Person Syndrome (SPS) is a rare autoimmune neurological disorder characterized by progressive muscle rigidity and painful spasms, primarily affecting axial and proximal musculature. Its diagnosis can be challenging due to clinical overlap with other neurological conditions such as spasticity, dystonia, or functional movement disorders. The detection of antibodies against glutamic acid decarboxylase (anti-GAD) is a key biomarker that supports diagnosis. Methods: Two clinical cases of patients with manifestations consistent with classic SPS are described, and were evaluated in a specialized neurology service. Both patients underwent detailed clinical assessment, complementary studies, and serum testing for anti-GAD antibodies. Results: Both patients presented with progressive rigidity and fluctuating muscle spasms, predominantly involving axial musculature. After an extensive diagnostic workup, elevated anti-GAD antibody titers were documented in both cases, confirming the diagnosis of classic SPS. Treatment with medications enhancing GABAergic neurotransmission was associated with significant clinical improvement, evidenced by reduced rigidity and the decreased frequency of spasms. Conclusions: These cases highlight the importance of considering SPS in the differential diagnosis of progressive rigidity syndromes. Identification of anti-GAD antibodies is essential for diagnostic confirmation, and treatment that aims to enhance GABAergic neurotransmission can significantly improve symptoms and patient functionality. Full article

Background: Virtual reality (VR) is increasingly being explored as a tool for upper limb (UL) assessment in adults with neurological disorders. This review synthesizes the available evidence on VR-based UL assessments by analyzing their psychometric properties and potential role in clinical and research settings. Methods: This systematic review followed the Guideline for reporting systematic reviews of outcome measurement instruments (PRISMA-COSMIN) and was prospectively registered in PROSPERO. Data extraction was independently performed by two reviewers, with disagreements resolved by consensus or a third reviewer. Psychometric evidence was evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology, including risk of bias assessment, evaluation and synthesis of measurement properties, and evidence grading according to GRADE. Additionally, the clinical application context of each VR assessment was examined, and a strengths, weaknesses, opportunities and threats analysis was conducted to explore factors affecting implementation and future development in neurorehabilitation. Results: Twenty VR-based UL assessments were identified. VR-Box and Blocks Test represented the largest body of evidence and was the only assessment implemented across all immersion levels, with promising findings in both stroke and Parkinson’s disease populations (Grade B recommendation). Immersive Action Research Arm Test demonstrated the strongest psychometric profile among the stroke sample (Grade B recommendation). Additionally, the Virtual Occupational Therapy Assistant and SaeboVR^® incorporated the most ecologically valid tasks, reflecting activities closer to daily life performance. Test–retest reliability and construct validity were the most frequently evaluated measurement properties. Conclusions: VR-based assessments represent promising tools for UL assessment. However, despite most systems receiving a Grade B recommendation, the supporting evidence remained low or very low certainty due to methodological shortcomings and incomplete psychometric evaluation. Therefore, more rigorous and methodologically robust research is needed to strengthen the evidence supporting their implementation in clinical practice as a complementary tool for UL assessment. Full article

Background: Post-stroke recovery varies widely, and pharmacological options to enhance rehabilitation outcomes remain limited. MLC601/MLC901 (NeuroAiD), a natural neurorestorative product, has been evaluated as an adjunct to standard care to improve functional and motor recovery after ischaemic stroke. This systematic review and meta-analysis assessed its efficacy using validated outcome measures. Methods: A systematic PubMed search identified randomised controlled trials comparing MLC601/MLC901 with placebo or active comparators in adults with ischaemic stroke. Functional outcomes included modified Rankin Scale (mRS), Barthel Index (BI), and Diagnostic Therapeutic Effects of Apoplexy (DTER) item 8 scores. Motor outcomes included Fugl–Meyer Assessment (FMA), DTER motor items, and National Institutes of Health Stroke Scale (NIHSS) motor scores. Data were pooled using fixed- and random-effects models. Odds ratios (ORs) and standardised mean differences (SMDs) were calculated. Risk of bias was assessed using the Cochrane RoB 1.0 tool. Results: Six publications reporting seven randomised clinical studies were included in the meta-analysis. Of the 7 studies, 5 were assessed as having a low risk of bias, while 2 were assessed as having an unclear risk. Altogether, 1535 participants for functional outcomes and 1774 for motor outcomes were analysed. Functional recovery significantly favoured MLC601/MLC901 at 1 month (OR 2.61; p = 0.004), 6 months (OR 1.38; p = 0.002), 12 months (OR 1.33; p = 0.03), and end-of-study (OR 1.40; p = 0.007), with benefits persisting up to 24 months. Motor recovery was assessed at months 1, 2 and 3 and at the end of the study. It also improved consistently over time, with the greatest effects during the first two months. Benefits were most evident in patients with moderately severe stroke (NIHSS 8–14). Clinical studies consistently indicate that NeuroAiD is safe and well-tolerated as an adjunct to standard ischaemic stroke care. Conclusions: MLC601/MLC901 is associated with improved functional independence and motor recovery after ischaemic stroke. Benefits appear within 1 month and may persist for up to 2 years, supporting early use alongside rehabilitation to optimise recovery. Full article