ABSTRACT A 59‐year‐old man developed a right middle cerebral artery infarction involving the insula, resulting in severe contralateral somatosensory impairment and mild motor paresis. Despite preserved sense of limb ownership, he exhibited a reduced sense of agency, reflected in subjective difficulty generating and controlling movement. Rehabilitation consisting of sensory re‐education and visual feedback–based exercise therapy was administered. During rehabilitation, somatosensory function improved, accompanied by partial recovery of the sense of agency. This case suggests that post‐stroke motor dysfunction associated with somatosensory impairment may not be explained solely by sensory deficits but may also reflect a reduced sense of agency related to insular dysfunction. Considering the sense of agency in addition to somatosensory impairment may contribute to a better understanding of post‐stroke motor dysfunction and to more tailored rehabilitation strategies.
ABSTRACT Background Mild cognitive impairment (MCI) is a transitional stage between normal aging and dementia, in which early detection is essential. Urinary amyloid precursor protein (APP) fragments have been proposed as a non‐invasive biomarker, but their diagnostic value in elderly populations remains uncertain. This study evaluated the diagnostic performance of urinary APP fragments, particularly amyloid‐β protein precursor (AβPP), for MCI screening and examined associated sociodemographic and clinical risk factors among adults aged ≥ 65 years. Methods A single‐center, cross‐sectional, case–control study was conducted at Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia. A total of 140 age‐ and gender‐matched participants were recruited (70 MCI, 70 cognitively normal). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Urinary AβPP was measured using a lateral flow immunochromatography kit. Data on comorbidities, body mass index, education level and smoking status were collected. Diagnostic accuracy and logistic regression analyses were performed. Results The urinary AβPP test showed a sensitivity of 74.3%, specificity of 27.1%, and overall accuracy of 50.7%, with no significant association with cognitive status ( p = 0.424). Diabetes mellitus was an independent risk factor predictor for MCI ( p = 0.007, OR = 5.764, 95% CI 1.615–20.572) along with age ( p = 0.001, OR = 1.638, 95% CI 1.234–2.175). Conclusion Urinary AβPP shows high sensitivity but low specificity for MCI screening. Diabetes mellitus is a significant predictor of MCI, highlighting the role of metabolic health in early cognitive decline.
ABSTRACT Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) syndrome is a rare autosomal recessive neurodegenerative disorder caused by biallelic pathogenic variants in ABHD12 . We report a 50‐year‐old Japanese man with childhood‐onset hearing loss and retinitis pigmentosa who subsequently developed action tremor, sensorimotor polyneuropathy, cataracts, and cerebellar atrophy. The action tremor caused greater functional impairment than gait ataxia. Genetic testing identified compound heterozygous ABHD12 variants: the previously reported Japanese splice‐site variant c.316+2T>A and a novel missense variant c.374C>G (p.Thr125Arg). His asymptomatic mother carried only c.316+2T>A, supporting a likely in trans configuration of the two variants, and p.Thr125Arg was classified as likely pathogenic. This case adds a novel ABHD12 missense variant to the genetic spectrum of PHARC syndrome and illustrates that disabling action tremor can occur in ABHD12 ‐related disease, even when gait ataxia is not the dominant source of disability.
ABSTRACT A 38‐year‐old, right‐handed woman presented with transient left hemiplegia and dysarthria. Brain magnetic resonance imaging showed no infarction, but magnetic resonance angiography and computed tomography angiography confirmed right middle cerebral artery (MCA) M1 occlusion. Despite dual antiplatelet therapy, she experienced recurrent transient ischemic attacks. Digital subtraction angiography revealed right M1 occlusion with a twig‐like collateral network to the M2 segment, leading to the diagnosis of aplastic or twig‐like MCA (Ap/T‐MCA). Single‐photon emission computed tomography showed reduced perfusion in the right MCA territory. Superficial temporal artery (STA)‐MCA bypass was performed 38 days after the initial attack and 12 days after diagnosis, resolving her symptoms. Postoperative imaging confirmed bypass patency and blood flow to the MCA cortical branches and suggested reduced perfusion asymmetry. She remained recurrence‐free for 2 years. STA‐MCA bypass may be a treatment option for Ap/T‐MCA patients with recurrent ischemic symptoms despite medical treatment.
ABSTRACT Fatal familial insomnia is an exceedingly rare prion disease that typically presents with intractable insomnia. We report a 73‐year‐old female patient with fatal familial insomnia who exhibited prominent inspiratory stridor. Laryngoscopy revealed paralysis of the bilateral vocal folds, which induced stridor. This case highlights the clinical heterogeneity of fatal familial insomnia, demonstrating that vocal fold paralysis can be a primary clinical manifestation of the disease.
ABSTRACT Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small‐vessel disease (SVD) caused by pathogenic NOTCH3 gene mutation. We report a case in which a patient was diagnosed with CADASIL after presenting with infarctions in the bilateral middle cerebellar peduncles (MCPs) and bilateral cerebral watershed areas following an influenza A virus infection. In this case, border‐zone ischemia may have resulted from impaired cerebral autoregulation caused by the underlying small‐vessel pathology of CADASIL. Influenza A infection may have served as a triggering factor for the ischemic event.
ABSTRACT Introduction Myasthenia gravis (MG) and demyelinating polyneuropathy affect different components of the peripheral motor system but may both contribute to limb weakness. We report a patient with MG and coexisting demyelinating polyneuropathy and review previously reported MG‐CIDP cases. Methods We described a 68‐year‐old woman with AChR antibody‐positive MG and coexisting demyelinating polyneuropathy and conducted a systematic review in accordance with the PRISMA guidelines. Clinical characteristics, laboratory findings, electrophysiological results, treatments, and outcomes were analyzed. Results The patient presented with fluctuating ocular symptoms and chronic progressive limb weakness. She tested positive for anti‐AChR antibodies. Archived electrophysiological studies showed a demyelinating polyneuropathy pattern, and cerebrospinal fluid analysis revealed albuminocytological dissociation. Marked clinical improvement was achieved with pyridostigmine, intravenous immunoglobulin, and corticosteroids. Twelve previously reported MG‐CIDP cases were analyzed separately. Of these, 50.0% were female and 83.3% were middle‐aged or elderly. MG and CIDP occurred simultaneously in 58.3%, MG preceded CIDP in 33.3%, and CIDP preceded MG in 8.3%. Limb, bulbar, and ocular involvement occurred in 83.3%, 75.0%, and 66.7%, respectively. Nerve conduction abnormalities were present in all patients; RNS and anti‐AChR antibodies were positive in 83.3%. Thymoma occurred in 33.3%. Corticosteroids and intravenous immunoglobulin were each used in 83.3%, and all patients improved. Conclusion Coexisting demyelinating polyneuropathy should be considered in MG patients with persistent limb weakness, generalized areflexia, or nerve conduction abnormalities not fully explained by neuromuscular junction dysfunction.
ABSTRACT Anti‐seizure medications (ASMs) may influence lipid profiles, potentially increasing the risk of cardiovascular diseases. A systematic review and meta‐analysis was conducted following PRISMA guidelines. Five databases were searched up to October 2024. Statistical analysis was performed using fixed and random‐effects models in Comprehensive Meta‐analysis software (CMA). Of the 22 studies included in the systematic review, 17 of them ran for meta‐analysis. Treatment with enzyme‐inducing ASMs, particularly carbamazepine (CBZ) and phenytoin (PHT), was associated with significantly higher lipid parameters compared with healthy controls, including LDL‐C (CBZ: SMD = 0.70, p = 0.01; PHT: SMD = 0.80, p < 0.001), total cholesterol (CBZ: SMD = 0.62, p < 0.01; PHT: SMD = 0.69, p = 0.045), and triglycerides (CBZ: SMD = 0.35, p < 0.01). Differences observed between enzyme‐inducing ASMs and non‐enzyme‐inducing agents such as lamotrigine were derived from indirect comparisons across studies. Our findings suggest that carbamazepine and phenytoin may increase lipid profiles. Further research is needed to confirm these findings and explore long‐term impacts.
This case report described a 75-year-old man with delayed-onset upper limb tremors after cerebral hemorrhagic infarction. Fourteen months prior, the patient had undergone multiple cerebral infarctions, including in the right motor cortex, after percutaneous coronary intervention for acute myocardial infarction. Although the neurological deficits recovered completely afterwards, the patient manifested postural and action tremors of 8 Hz in the left upper limb 10 months later. Brain magnetic resonance imaging revealed cortical superficial siderosis due to chronic hemorrhagic infarction in the right motor cortex with a linear hypointense lesion on the T2*-weighted images. Cerebral cortical infarcts can cause tremors due to damage to the neural loop between the motor cortex and the basal ganglia. Profound damage on the normal neural networks caused by hemorrhagic transformation of infarcts might result in delayed reorganization of the aberrant neural networks leading to the delayed onset of tremors.
ABSTRACT Background Nearly one‐third of patients with epilepsy fail to achieve seizure remission despite appropriate anti‐seizure medications. Lacosamide has emerged as a potential adjunctive therapy for drug‐resistant partial‐onset seizures. Objective To evaluate the efficacy and safety of adjunctive lacosamide in patients with partial‐onset seizures. Methods PubMed, Embase, and Cochrane databases were searched for randomized controlled trials evaluating adjunctive lacosamide. Efficacy outcomes included ≥ 50% and ≥ 75% reductions in seizure frequency. Safety outcomes included treatment‐emergent adverse events (TEAEs) and discontinuation due to TEAEs. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using the Mantel–Haenszel method. Heterogeneity was assessed with the I 2 statistic, and risk of bias was evaluated using the Cochrane RoB 2 tool. Results Of 3273 records identified, seven RCTs met inclusion criteria. Adjunctive lacosamide significantly increased the likelihood of achieving a ≥ 50% reduction in seizure frequency (RR 1.72, 95% CI 1.45–2.05; p < 0.00001; I 2 = 37%) and a ≥ 75% reduction (RR 2.01, 95% CI 1.57–2.57; p < 0.00001; I 2 = 0%). Lacosamide was associated with a non‐significant increase in TEAEs (RR 1.06, 95% CI 0.99–1.15; p = 0.09; I 2 = 42%) but a significant increase in discontinuations due to TEAEs (RR 1.83, 95% CI 1.23–2.71; p = 0.003; I 2 = 26%). Most studies were judged to have a low risk of bias. Conclusion Adjunctive lacosamide improves seizure control in patients with drug‐resistant partial‐onset seizures. However, its increased risk of treatment discontinuation should be considered when selecting therapy.
ABSTRACT Parkinson's disease (PD) is a complex, multifactorial neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra and widespread involvement of multiple neurotransmitter systems. Traditionally recognized for its motor manifestations including bradykinesia, tremor, rigidity, and postural instability, PD also encompasses an array of non‐motor symptoms including cognitive impairment, neuropsychiatric disturbances, sleep disorders, and autonomic dysfunction. Recent insights have expanded PD pathophysiology beyond dopaminergic deficiency to include α‐synuclein aggregation, mitochondrial dysfunction, oxidative stress, neuroinflammation, and gut–brain axis disruption. Growing evidence links insulin resistance and metabolic dysregulation to neuronal vulnerability, suggesting PD as part of a broader metabolic–neurodegenerative continuum. Emerging evidence further indicates that progressive bioenergetic failure, impaired mitochondrial resilience, and disrupted neuronal energy homeostasis may represent central mechanisms linking α‐synuclein aggregation, oxidative stress, neuroinflammation, and multisystem neurodegeneration in PD. This review specifically emphasizes an integrated energy failure–centered framework that connects molecular pathology with clinical heterogeneity and therapeutic vulnerability. Current therapeutic strategies such as levodopa‐based pharmacotherapy, dopamine agonists, MAO‐B/COMT inhibitors, and adjunct agents provide symptomatic relief but fail to modify disease progression. Surgical and device‐assisted interventions such as deep brain stimulation and continuous infusion therapies improve motor control yet remain limited by non‐motor efficacy and invasiveness. Emerging therapies targeting molecular and metabolic pathways, including gene and cell‐based approaches, GLP‐1 receptor agonists, and microbiome modulation, represent promising avenues for neuroprotection and disease modification. This review integrates molecular, metabolic, and clinical insights to emphasize the need for a holistic, multi‐target therapeutic paradigm in advancing the management of PD.
ABSTRACT Zonisamide is an antiepileptic agent used as adjunctive therapy for Parkinson's Disease in Japan and studied more selectively elsewhere. Preclinical and early translational studies suggest that zonisamide may modulate several pathways relevant to Parkinson's Disease pathobiology, including dopaminergic neurotransmission, oxidative stress, neuroinflammation, and apoptosis. This systematic review critically appraises and synthesizes the existing evidence of the molecular and cellular neuroprotective pathways zonisamide exerts in Parkinson's Disease across human, animal, and in vitro studies. The review protocol was registered on PROSPERO (CRD420251274891). A literature search of PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science using MeSH terms and keywords for Parkinson's Disease and zonisamide limited to English‐language was employed. Clinical trials, mechanistic studies, and pre‐clinical models were included, with case reports and reviews excluded. Thirty‐six studies met the eligibility criteria and were included. Out of the 36 studies, most were beneficial; however, two studies were non‐beneficial (1 harmful, 1 mixed/dose‐dependent), indicating potential context‐ and dose‐sensitivity pertaining to the effect of zonisamide. Across the mechanistic domains, neurotransmission, oxidative stress, and neuroinflammation reduction, as well as anti‐apoptosis, were identified as the key drivers of neuroprotection. Overall, zonisamide demonstrates mechanistic promise, but interpretation is constrained by the predominantly preclinical, geographically concentrated evidence base, heterogeneity across models and endpoints, and limited human mechanistic data.
