Multiple system atrophy (MSA) is a rare, rapidly progressive neurodegenerative disorder characterized by varying combinations of Parkinsonian features, cerebellar ataxia, and autonomic dysfunction. The disease is classified into two major subtypes based on predominant symptoms: The Parkinsonian variant (MSA-P) and the cerebellar variant (MSA-C). MSA-C, in particular, presents significant diagnostic challenges due to its overlapping clinical features with other neurodegenerative disorders, such as cerebellar ataxias and atypical Parkinsonian syndromes. Early stages of the disease may not show conclusive findings on conventional imaging, further complicating diagnosis. We report a case of a middle-aged woman who presented with progressive ataxia, dysarthria, orthostatic symptoms, and urinary disturbances. Initial clinical assessment and structural imaging were inconclusive. The patient showed poor response to standard pharmacological therapy, including levodopa. This prompted further evaluation with functional imaging, which demonstrated regional hypometabolism in the brainstem and cerebellum - findings supportive of a diagnosis of MSA-C. Comprehensive autoimmune and metabolic workups were negative, reinforcing the clinical suspicion. This case highlights the importance of a thorough diagnostic approach in patients with progressive cerebellar and autonomic symptoms. While definitive biomarkers for MSA are lacking, advanced imaging techniques such as fluorodeoxyglucose positron emission tomography can provide supportive evidence in challenging cases. Early identification of MSA, even when classic signs like the "hot cross bun" sign are absent on magnetic resonance imaging, is essential to initiate symptomatic treatment, plan supportive care, and guide patient and family counseling.

Immune checkpoint inhibitor-associated myocarditis, myositis, and myasthenia gravis overlap syndrome (IM3OS) is an uncommon immune-related adverse event (irAE) associated with the use of immune checkpoint inhibitors for the treatment of malignancies. We present a case of a 77-year-old woman who received anti-PD1 treatment for high-grade invasive urothelial carcinoma, and subsequently presented with weakness, ptosis, and dysarthria concerning for myositis, myocarditis, and myasthenia gravis overlap syndrome. She was successfully treated with high-dose glucocorticoids, mycophenolate mofetil, and intravenous immunoglobulin with resolution of presenting symptoms. To identify cellular subsets that mediated the disease flare, we performed flow cytometry analysis of peripheral blood mononuclear cells collected at baseline, at hospitalization and after treatment with high-dose glucocorticoids. We found an expansion of the memory CD8[+] T-cell populations at the time of IM3OS presentation. Additionally, we identified a differentiated CD27[-] CD28[-] effector memory (EM) CD4[+] subset that was associated with clinical disease activity and contracted with glucocorticoid use administration. This illustrates a unique case of a patient who was successfully treated for IM3OS and highlights the potential use of flow cytometry to provide insight into the underlying pathophysiology of irAEs, and to guide and gauge response to immunomodulatory therapy, thus facilitating a precision medicine approach within the diagnostic and treatment framework for irAEs.

Background A 27-year-old male with perinatal hypoxia presented with global developmental delay, progressive hearing loss, ataxia, dysarthria, and intellectual disability. Whole-exome sequencing revealed compound heterozygous ACAD9 variants: c.456del (p.Ile153Serfs*46) and c.869G > A (p.Gly290Glu). Brain MRI showed bilateral cerebellar atrophy and a prominent cisterna magna. OCT confirmed optic atrophy. The diagnosis of mitochondrial encephalomyopathy (complex I deficiency type 20) was established. This report expands the known genetic spectrum associated with mitochondrial encephalomyopathy and underscores the critical role of genomic sequencing in diagnosing atypical, slowly progressive multisystem disorders.

Spinocerebellar ataxia 27B (SCA27B) has been recognised as a major cause of sporadic late-onset cerebellar ataxias, accounting for 9-61% of previously unexplained cases. We aimed to describe the clinical, radiological and genetic spectrum of SCA27B through a systematic review of the published literature. A systematic literature search of PubMed, Embase (Ovid), Ovid Medline and Scopus was conducted. Studies including genetically confirmed SCA27B patients were selected. Individual patient and aggregate data were extracted, pooled and summarised. A total of 45 studies including 1267 patients were analysed. The pooled mean age at onset was 53.14±15.23 years. Gait ataxia (pooled prevalence 0.97; 95% CI: 0.93-0.98), oculomotor abnormalities [excluding all nystagmus] (0.79; 95% CI: 0.68-0.87), all nystagmus except downbeat nystagmus(0.57; 95% CI: 0.43-0.70), downbeat nystagmus (0.45; 95% CI: 0.35-0.55), dysarthria (0.51; 95% CI: 0.44-0.59), episodic symptoms (0.44; 95% CI: 0.31-0.58) and vertigo/dizziness (0.37;95% CI: 0.31-0.43) were the most frequent clinical features. Substantial heterogeneity occurred across outcomes. Genotype-phenotype correlation analysis showed that the high-repeat group (≥250 repeats) was associated with significantly higher odds of gait ataxia (3.7 (95% confidence interval 1.9-6.9; p<0.001) and dysarthria (3.5 (1.6-7.7; p<0.001) compared to the low-repeat group (180- 249 repeats). SCA27B is a common and genetically defined cause of late-onset cerebellar ataxia with a heterogeneous clinical phenotype. Recognition of key clinical clues, including gait ataxia, downbeat nystagmus, vestibular features, oculomotor abnormalities and episodic symptoms, is essential to facilitate timely diagnosis and appropriate genetic testing. Repeat size of 250 and above seems to be associated with higher odds of gait ataxia and dysarthria compared to repeat size below 250.

Direct electrical stimulation (DES) has long been used in patients undergoing epilepsy surgery for two key purposes: functional brain mapping and seizure triggering. In this review, the findings from DES applications to the opercula are synthesized, with the aim of mapping opercular functions and investigating seizure induction. Clinical responses to opercular DES are frequent and diverse, showing a partial segregation with spatial overlap, and exhibiting topographical differences: Emotion is evoked in the most anterior part of frontal operculum, expressive aphasia is the mid-posterior part, followed by oropharyngeal, dysarthria, and gustatory in the central opercula, somatosensory and vestibular in the posterior opercula, and auditory (or rarely visual) in the temporal opercula. No studies have specifically looked at DES-induced seizures from the opercula. Only a small number of studies about insulo-opercular epilepsy have mentioned that DES of the opercula induced seizures. Overall, opercular DES studies converge on the view that the opercula comprise a complex multimodal cortex integrating especially sensorial perception. Each subdivision had a different dominant response to DES, whose organization helps understand the different subgroups of opercular epilepsy.

Here, we report the case of a 65-year-old man who presented to the emergency department with paresthesia, psychomotor retardation, and dysarthria. Contrast-enhanced brain MRI revealed a solitary, contrast-enhancing mass in the right head of the caudate nucleus with extensive perifocal edema, raising a primary differential diagnosis of glioblastoma versus metastasis, among other possibilities. Prior to surgical removal of the suspected glioblastoma, the patient underwent additional diffusion tensor imaging and research MRI, including multifrequency magnetic resonance elastography (MRE) to generate mechanical property maps of stiffness and tissue viscosity and to potentially differentiate between glioma, brain metastases, and benign masses based on tissue biomechanical properties. MRE revealed abnormally high values of stiffness and viscosity-a mechanical signature known to be associated with brain metastases or meningioma, but not glioblastoma, which typically exhibits soft tissue properties with reduced viscous dissipation. Histopathologic evaluation confirmed MRE by revealing a distant metastasis of squamous cell carcinoma, the primary tumor of which was detected by PET-CT within the right hilus of the lung. This case demonstrates the diagnostic value of the biomechanical properties of brain tumors and raises the prospect of applying MRE as an easy-to-use MRI contrast that can rule out glioma when the suspicious lesion exhibits stiff-viscous material properties.

An 81-year-old woman with follicular lymphoma treated with obinutuzumab and bendamustine developed cognitive impairment and dysarthria. Three months before death, neurological exams showed dysarthria, right hemiparesis, and gait disturbance. Blood tests showed lymphocytopenia (lymphocyte 10.4%). Cerebrospinal fluid (CSF) findings were unremarkable, including with respect to cytology. Brain MRI demonstrated a mass-like hyperintense lesion in the left parietal lobe and band-like abnormalities in the left fronto-temporal white matter that lacked contrast enhancement. Symptoms progressed to hemiplegia and mutism; severe dysphagia eventually necessitated intravenous fluid management. Follow-up MRI one month before death revealed a lesion encompassing nearly the entire left hemisphere, with hyperperfusion observed during arterial spin labeling (ASL). JC virus was detected in CSF (221 copy/mL), confirming that the patient had progressive multifocal leukoencephalopathy (PML). Subsequently, she exhibited poor arousal, followed by death. Here, lymphoma recurrence or PML was suspected due to a post-chemotherapy unilateral expanding brain lesion. These conditions are usually differentiated by contrast-enhancement patterns, but PML can also enhance during immune reconstitution. Moreover, lesions rarely cause a mass effect and more often exhibit hyperperfusion, which may aid in diagnosis. While unilateral PML has been reported, especially in the early stage, such an extensive lesion involving nearly an entire single hemisphere, as seen in our case, is rare.