Brainstem Involvement Research Articles

Exploring Brainstem Structural Abnormalities: Potential Biomarkers for Panic Disorder.

Panic disorder (PD), characterized by recurrent and intense panic attacks, presents a complex interplay between psychological and neurobiological factors. Although the amygdala and hippocampus have been studied extensively in the context of PD, the brainstem's involvement remains relatively underexplored. This study aims to address this gap by examining structural abnormalities within specific brainstem regions, including the medulla, pons, and midbrain. The study sample population comprised twenty-one adult patients diagnosed with PD and an age-gender-education-matched control group. Utilizing rigorous inclusion and exclusion criteria, confounding factors related to comorbid psychiatric conditions and brain structure abnormalities were minimized. Our findings revealed a significant reduction in medulla volume among PD patients, a finding that persisted even after correcting for individual differences in total intracranial volume. The medulla's role in cardiovascular regulation and autonomic function, coupled with its involvement in fear responses, underscores its potential significance in the pathophysiology of PD. This study elucidates the medulla's structural abnormalities as a potential biomarker for PD. Understanding the role of the brainstem in PD could pave the way for more targeted and effective interventions for this condition.

Teaching NeuroImage: Extensive Brainstem and Striatal Involvement in Neuropsychiatric Systemic Lupus Erythematosus.

Teaching NeuroImage: Extensive Brainstem and Striatal Involvement in Neuropsychiatric Systemic Lupus Erythematosus.

Functional Outcomes in Conservatively vs Surgically Treated Cerebellar Infarcts

According to the current American Heart Association/American Stroke Association guidelines, decompressive surgery is indicated in patients with cerebellar infarcts that demonstrate severe cerebellar swelling. However, there is no universal definition of swelling and/or infarct volume(s) available to support a decision for surgery. To evaluate functional outcomes in surgically compared with conservatively managed patients with cerebellar infarcts. In this retrospective multicenter cohort study, patients with cerebellar infarcts treated at 5 tertiary referral hospitals or stroke centers within Germany between 2008 and 2021 were included. Data were analyzed from November 2020 to November 2023. Surgical treatment (ie, posterior fossa decompression plus standard of care) vs conservative management (ie, medical standard of care). The primary outcome examined was functional status evaluated by the modified Rankin Scale (mRS) at discharge and 1-year follow-up. Secondary outcomes included the predicted probabilities for favorable outcome (mRS score of 0 to 3) stratified by infarct volumes or Glasgow Coma Scale score at admission and treatment modality. Analyses included propensity score matching, with adjustments for age, sex, Glasgow Coma Scale score at admission, brainstem involvement, and infarct volume. Of 531 included patients with cerebellar infarcts, 301 (57%) were male, and the mean (SD) age was 68 (14.4) years. After propensity score matching, a total of 71 patients received surgical treatment and 71 patients conservative treatment. There was no significant difference in favorable outcomes (ie, mRS score of 0 to 3) at discharge for those treated surgically vs conservatively (47 [66%] vs 45 [65%]; odds ratio, 1.1; 95% CI, 0.5-2.2; P > .99) or at follow-up (35 [73%] vs 33 [61%]; odds ratio, 1.8; 95% CI, 0.7-4.2; P > .99). In patients with cerebellar infarct volumes of 35 mL or greater, surgical treatment was associated with a significant improvement in favorable outcomes at 1-year follow-up (38 [61%] vs 3 [25%]; odds ratio, 4.8; 95% CI, 1.2-19.3; P = .03), while conservative treatment was associated with favorable outcomes at 1-year follow-up in patients with infarct volumes of less than 25 mL (2 [34%] vs 218 [74%]; odds ratio, 0.2; 95% CI, 0-1.0; P = .047). Overall, surgery was not associated with improved outcomes compared with conservative management in patients with cerebellar infarcts. However, when stratifying based on infarct volume, surgical treatment appeared to be beneficial in patients with larger infarct volumes, while conservative management appeared favorable in patients with smaller infarct volumes.

Case report of leukoencephalopathy with predominant brainstem and spinal cord involvement and lactate elevation behind the mask of multiple sclerosis

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare or underdiagnosed autosomal-recessive mitochondrial disease that sometimes mimics progressive multiple sclerosis (MS). Difficulties in diagnosing LBSL are due to the possibility of the onset of the disease in adulthood, and the nonspecific clinical picture in the form of slowly progressive neurological symptoms (pyramidal, cerebellar, sensory and cognitive impairments) without the involvement of other organs and systems characteristic of mitochondrial pathology. However, a notable feature of LBSL is its pathognomonic magnetic resonance imaging of the white matter of the brain and spinal cord, which allows a reliable diagnosis when certain criteria are met. Currently, there are no drugs registered for the specific treatment of LBSL, however, correct diagnosis is necessary to complete the epidemiological data, and to prevent the prescription of drugs with side effects that worsen the quality of life of patients. The number of clinical publications about LBSL is small, both in Russian and foreign publications, and therefore each identified case is of great interest. The article presents a brief review of the literature and a case report of a patient with the adult-onset LBSL, who received disease modifying therapy of multiple sclerosis for a long time. The patient’s main problems were progressive lower paraparesis and ataxia. To make clinicians more aware, we have reviewed the difficulties in differential diagnosis between LBSL and MS, we provided detailed medical history, neurological status, and magnetic resonance imaging findings.

Ferritin as an Effective Predictor of Neurological Outcomes in Children With Acute Necrotizing Encephalopathy

BackgroundAcute necrotizing encephalopathy (ANE) is a fulminant disease with poor prognosis. Cytokine storm is the important phenomenon of ANE that affects the brain and multiple organs. The study aimed to identify whether hyperferritinemia was associated with poor prognosis in patients with ANE. MethodsAll patients with ANE had multiple symmetric lesions located in the bilateral thalami and other regions such as brainstem tegmentum, cerebral white matter, and cerebellum. Neurological outcome at discharge was evaluated by pediatric neurologists using the Pediatric Cerebral Performance Category Scale. All risk factors associated with poor prognosis were further analyzed using receiver operating characteristic curve analysis. ResultsTwenty-nine patients with ANE were enrolled in the current study. Nine (31%) patients achieved a favorable neurological outcome, and 20 (69%) patients had poor neurological outcomes. results The group of poor neurological outcome had significantly higher proportion of shock on admission and brainstem involvement. Based on multivariate logistic regression analysis, ferritin, aspartate aminotransferase (AST), and ANE severity score (ANE-SS) were the predictors associated with outcomes. The appropriate cutoff value for predicting neurological outcomes in patients with ANE was 1823 ng/mL for ferritin, 78 U/L for AST, and 4.5 for ANE-SS. Besides, comparison analyses showed that higher level of ferritin and ANE-SS were significantly correlated with brainstem involvement (P < 0.05). ConclusionsFerritin may potentially be a prognostic factor in patients with ANE. Hyperferritinemia is associated with poor neurological outcomes in patients with ANE and ferritin levels more than 1823 ng/mL have about eightfold increased risk of poor neurological outcome.

A retrospective study on the prevalence and risk factors of neurogenic lower urinary tract dysfunction for acute ischemic stroke in China: A case-control study.

This study identified risk factors for neurogenic lower urinary tract dysfunction (NLUTD) in patients with acute ischemic stroke (AIS) through multidimensional analysis of the medical records of patients, aiming to reduce the incidence of NLUTD, improve prognosis, and facilitate rehabilitation. In this case-control study, patients with AIS were recruited from two tertiary general hospitals in Shenzhen, China, from March 2021 to October 2023. Patients were divided into NLUTD and non-NLUTD groups based on the presence and absence of NLUTD, respectively. Comparative analysis was performed using the Mann-Whitney U and chi-square tests, with significant variables being included in logistic regression analysis. Of the 652 participants enrolled in this study, 119 participants (18.3%) developed NLUTD. Bivariate analysis showed that 39 of 54 screened factors exhibited a significant correlation (p<0.05) with the incidence of NLUTD after AIS. Significant variables identified through logistic regression analysis included Glasgow coma scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) scores, anemia, aphasia, pneumonia, brainstem involvement, multiple lesions, urine clarity (CLA), random venous blood glucose (GLU) and hemoglobin (HGB) levels, and white blood cell (WBC) count. A total of 11 risk factors for NLUTD were identified in this study. This finding provides valuable guidance for reducing the incidence of NLUTD after AIS and improving the quality of life of patients.

"Clock dial pattern", a radiologic clue to neuro-chikungunya diagnosis: a case series.

Chikungunya is a mosquito-borne disease caused by the chikungunya virus (CHIKV) and can lead to neurological complications in severe cases. This study examined neuroimaging patterns in chikungunya cases during two outbreaks in Brazil to identify specific patterns for diagnosis and treatment of neuro-chikungunya. Eight patients with confirmed chikungunya and neurological involvement were included. Clinical examinations and MRI scans were performed, and findings were analyzed by neuroradiologists. Data on age, sex, neurological symptoms, diagnostic tests, MRI findings, and clinical outcomes were recorded. Patients showed different neuroimaging patterns. Six patients exhibited a "clock dial pattern" with hyperintense dotted lesions in the spinal cord periphery. One patient had thickening and enhancement of anterior nerve roots. Brain MRI revealed multiple hyperintense lesions in the white matter, particularly in the medulla oblongata, in six patients. One patient had a normal brain MRI. The "clock dial pattern" observed in spinal cord MRI may be indicative of chikungunya-related nervous system lesions. Isolated involvement of spinal cord white matter in chikungunya can help differentiate it from other viral infections. Additionally, distinct brainstem involvement in chikungunya-associated encephalitis, particularly in the rostral region, sets it apart from other arboviral infections. Recognizing these neuroimaging patterns can contribute to early diagnosis and appropriate management of neuro-chikungunya.

Patient With Gender Dysphoria Diagnosed With Multiple Sclerosis Following Takotsubo Cardiomyopathy and Ventricular Arrhythmia: A Case Report and Systematic Literature Review.

A 34-year-old transgender woman presented with ventricular tachycardia and was diagnosed with takotsubo cardiomyopathy. Further evaluation revealed an underlying diagnosis of multiple sclerosis (MS) with brainstem lesions that may have triggered takotsubo cardiomyopathy. In this report, we also systematically reviewed published cases of takotsubo cardiomyopathy and MS and found that basal type takotsubo cardiomyopathy was the most common, and most patients presented with brainstem involvement of MS. An awareness of these associations by physicians, along with multidisciplinary collaboration, may facilitate the early diagnosis and improve the prognosis of these patients.

A comprehensive study of mutation and phenotypic heterogeneity of childhood mitochondrial leukodystrophies

ObjectiveMitochondrial leukodystrophies (MLs) are mainly caused by impairments of the mitochondrial respiratory chains. This study reports the mutation and phenotypic spectrum of a cohort of 41 pediatric patients from 39 distinct families with MLs among 320 patients with a molecular diagnosis of leukodystrophies. MethodsThis study summarizes the clinical, imaging, and molecular data of these patients for five years. ResultsThe three most common symptoms were neurologic regression (58.5%), pyramidal signs (58.5%), and extrapyramidal signs (43.9%). Because nuclear DNA mutations are responsible for a high percentage of pediatric MLs, whole exome sequencing was performed on all patients. In total, 39 homozygous variants were detected. Additionally, two previously reported mtDNA variants were identified with different levels of heteroplasmy in two patients. Among 41 mutant alleles, 33 (80.4%) were missense, 4 (9.8%) were frameshift (including 3 deletions and one duplication), and 4 (9.8%) were splicing mutations. Oxidative phosphorylation in 27 cases (65.8%) and mtDNA maintenance pathways in 8 patients (19.5%) were the most commonly affected mitochondrial pathways. In total, 5 novel variants in PDSS1, NDUFB9, FXBL4, SURF1, and NDUSF1 were also detected. In silico analyses showed how each novel variant may contribute to ML pathogenesis. ConclusionsThe findings of this study suggest whole-exome sequencing as a strong diagnostic genetic tool to identify the causative variants in pediatric MLs. In comparison between oxidative phosphorylation (OXPHOS) and mtDNA maintenance groups, brain stem and periaqueductal gray matter (PAGM) involvement were more commonly seen in OXPHOS group (P value of 0.002 and 0.009, respectively), and thinning of corpus callosum was observed more frequently in mtDNA maintenance group (P value of 0.042).

Clinical characteristics and prognostic analysis of acute necrotizing encephalopathy of childhood: a retrospective study at a single center in China over 3 years.

Acute Necrotizing Encephalopathy of Childhood (ANEC) is a rare, fulminant neurological disease in children with unknown mechanisms and etiology. This study summarized the clinical characteristics, treatment, and prognosis of ANEC through a retrospective analysis, providing insights into the ANEC early diagnosis and prognosis assessment. Clinical data of children diagnosed with ANEC at the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University from July 1, 2020, to June 30, 2023, were retrospectively analyzed. There were 25 cases, 14 males and 11 females, with a median age of 3 years. Hospital admissions were mainly in the winter (14/25, 56%) and spring (9/25, 36%). All patients presented with varying degrees of fever and altered consciousness, with 92% (23/25) experiencing high body temperatures (>39.1°C) and 88% (22/25) having a Glasgow coma scale (GCS) score of ≤8. Seizures were observed in 88% (22/25) of patients. Laboratory findings indicated 100% B lymphocyte activation (14/14), and 78% (14/18) of patients showed cytokine storm (interleukin (IL)-6, IL-8, IL-10, interferon (IFN)-α). Neuroimaging showed symmetrical thalamus involvement, commonly involving basal ganglia and brainstem regions. Viral infection (23/24, 96%) was the predominant etiological finding, with 42% (10/24) of cases due to SARS-CoV-2 infection and 42% (10/24) to influenza A virus infection. Multi-organ dysfunction occurred in 68% (17/25) of patients, and 52% (13/25) died. Correlation analysis revealed the death group exhibited higher proportion of male, lower GCS scores, higher IL-6 level and a greater likelihood of associated brainstem impairment (p < 0.05). ANEC is more prevalent in the winter and spring, and its etiology may be associated with B lymphocyte activation and cytokine storm following viral infections. Clinical manifestations lack specific features, with fever, consciousness disturbances, and seizures being the main presentations, particularly in cases of high fever and hyperpyrexia. ANEC progresses rapidly and has a high mortality rate. The child's gender, GCS score, IL-6 levels, and the presence of brainstem involvement can serve as important risk factors for assessing the risk of mortality.

A Case of Ramsay Hunt Syndrome Showing Central Findings due to Brainstem Involvement

Ramsay Hunt syndrome occurs when the varicella zoster virus reactivates. Classic findings include the triad of facial paralysis, otic pain and herpetic lesions due to the pathogenesis associated with anterograde axonal reactivation of the varicella zoster virus in the geniculate ganglion. In addition to the classic triad, rare features such as a central type of vestibular function test may be observed due to the retrograde spread of the varicella zoster virus from the geniculate ganglion into the brain stem, including involvement of the vestibular nucleus. We present a case of Ramsay Hunt syndrome in a 57-year-old male patients, manifesting not only the typical triad of symptoms but also the unique features associated with brain stem involvement. This presented as direction-changing gaze-evoked nystagmus and a decrease in gain on both sides on video head impulse test. And brain magnetic resonance imaging showed a lesion in the vestibular nucleus of the brain stem.

The main forms of leukodystrophies. Lecture and clinical cases

Leukodystrophies are genetically determined diseases characterised by primary damage to the white matter of the central nervous system, irrespective of the genetic defect and structural component involved. This paper classification is presented based on the identification of typical patterns characteristic of certain forms of leukodystrophy. Clinical examples are given for each of the identified patterns. The parieto-occipital pattern is considered in a clinical case of a 9-year-old boy with X-linked adrenoleukodystrophy. Frontal pattern there is an example of a genetically verified juvenile form of Alexander’s disease in a 16-year-old female patient. The periventricular pattern reflects leukoencephalopathy with brain stem and spinal cord involvement and increased lactate in a 9-year-old female patient. A subcortical pattern is considered within L-2-hydroxyglutoric aciduria in a 29-year-old patient. As examples of brainstem and cerebellar involvement patterns, autosomal dominant leukodystrophy with adult onset due to tandem duplication of the lamin B gene, identified in a 40-year-old patient, is considered. In conclusion, we present additional diagnostic methods for the differential diagnosis of brain white matter diseases and a brief overview of treatment.

Leukoencephalopathy with Brain stem and Spinal cord involvement and Lactate elevation (LBSL): Report of a new family and a novel DARS2 mutation

BackgroundLBSL is a mitochondrial disorder caused by mutations in the mitochondrial aspartyl-tRNA synthetase gene DARS2, resulting in a distinctive pattern on brain magnetic resonance imaging (MRI) and spectroscopy. Clinical presentation varies from severe infantile to chronic, slowly progressive neuronal deterioration in adolescents or adults. Most individuals with LBSL are compound heterozygous for one splicing defect in an intron 2 mutational hotspot and a second defect that could be a missense, non-sense, or splice site mutation or deletion resulting in decreased expression of the full-length protein. AimTo present a new family with two affected members with LBSL and report a novel DARS2 mutation. ResultsAn 8-year-old boy (Patient 1) was referred due to headaches and abnormal MRI, suggestive of LBSL. Genetic testing revealed a previously reported c.492 + 2 T > C mutation in the DARS2 gene. Sanger sequencing uncovered a novel variant c.228-17C > G in the intron 2 hotspot. Family studies found the same genetic changes in an asymptomatic 4-year-old younger brother (Patient 2), who was found on follow-up to have an abnormal MRI. mRNA extracted from patients' fibroblasts showed that the c.228-17C > G mutation caused skipping of exon 3 resulting in lower DARS2 mRNA level. Complete absence of DARS2 protein was also found in both patients. SummaryWe present a new family with two children affected with LBSL and describe a novel mutation in the DARS2 intron 2 hotspot. Despite findings of extensive white matter disease in the brain and spine, the proband in this family presented only with headaches, while the younger sibling, who also had extensive white matter changes, was asymptomatic. Our in-vitro results confirmed skipping of exon 3 in patients and family members carrying the intron 2 variant, which is consistent with previous reported mutations in intron 2 hotspots. DARS2 mRNA and protein levels were also reduced in both patients, further supporting the pathogenicity of the novel variant.

Patterns of Adult Neuromyelitis Optica Spectrum Disorder Patients Compared to Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Neuromyelitis optica spectrum disorders (NMOSDs) are central nervous system inflammatory conditions, now recognized to involve the brain, often identified by aquaporin-4 (AQP4) antibodies. We aimed to summarize the characteristics of adult NMOSD patients compared to multiple sclerosis (MS). A computerized search was conducted on MEDLINE via PubMed, Web of Science, and ProQuest using the relevant keywords. Three independent reviewers performed two-stage screening and data extraction. The Review Manager 5.4 program (Cochrane Collaboration, Windows, London, UK) was used for the analysis. The Joanna Briggs Institute (JIB) tool was used for the quality of included studies. Twenty-three articles were included. NMOSD patients were associated with older age at presentation and higher Expanded Disability Status Scale (MD = 3.88, 95% CI: 1.80 to 5.97, P = 0.0003) and (MD = 1.15, 95% CI: 0.58 to 1.72, P < 0.0001), respectively. The risk of NMOSD in females was significantly higher than MS (OR = 2.21, 95% CI: 1.41 to 3.46, P = 0.0005). Patients with NMOSD were associated with a lower risk of extrapyramidal symptoms (OR = 0.26, 95% CI: 0.11 to 0.60, P < 0.01), brainstem involvement symptoms (OR = 0.32, 95% CI: 0.16 to 0.64, P < 0.01), and developing brain lesions compared to MS (OR = 0.08, 95% CI: 0.03 to 0.18, P < 0.00001). The current evidence suggests that both NMOSD and MS have different demographic, clinical, and lesion characteristics. There is a need for additional validation of the identified differences compared with MS due to the lack of long-term systematic imaging investigations in NMOSD.

The spectrum of central nervous system manifestations in leprosy: a systematic review of published case reports and case series.

This systematic review aimed to investigate central nervous system (CNS) involvement in leprosy by analysing multiple cohort studies, individual cases and case series. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. PubMed, Scopus and Embase databases were searched up to 8 July 2023, using a predefined search strategy. Inclusion criteria included patients diagnosed with leprosy with evidence of CNS involvement. The quality of the included cases was evaluated using the Joanna Briggs Institute checklist. A total of 34 records were identified, including 18 cohort studies and 16 reports describing 27 isolated cases. Autopsies revealed macroscopic changes in the spinal cord, neurofibrillary tangles and senile plaques. Mycobacterium leprae was detected in neurons of the medulla oblongata and spinal cord using PCR and phenolic glycolipid 1 staining. Cerebrospinal fluid (CSF) analysis showed inflammatory changes, increased gamma globulins and detection of Mycobacterium leprae antigens and antibodies. In 21 patients (78%), spinal cord/brachial plexus abnormities were detected. In the majority, MRI revealed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity in the cervical cord. In patients with brainstem involvement, T2/FLAIR hyperintensity was noted in the cerebellar peduncles, facial nerve nuclei and/or other cranial nerve nuclei. Brain parenchymal involvement was noted in three patients. This systematic review provides evidence of CNS involvement in leprosy, based on autopsy findings, neuroimaging, CSF analysis and neurophysiological studies.

Recurrent petit mal seizures in Erdheim-Chester disease mimicking an intra-axial brain tumor: illustrative case.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized histologically by foamy histiocytes and Touton giant cells in a background of fibrosis. Bone pain with long bone osteosclerosis is highly specific for ECD. Central nervous system involvement is rare, although dural, hypothalamic, cerebellar, brainstem, and sellar region involvement has been described. A 59-year-old man with a history of ureteral obstruction, medically managed petit mal seizures, and a left temporal lesion followed with serial magnetic resonance imaging (MRI) presented with worsening seizure control. Repeat MRI identified bilateral amygdala region lesions. Gradual growth of the left temporal lesion over 1 year with increasing seizure frequency prompted resection. A non-Langerhans cell histiocytosis with a BRAF V600E mutation was identified on pathology. Imaging findings demonstrated retroperitoneal fibrosis and long bone osteosclerosis with increased fluorodeoxyglucose uptake that, together with the neuropathologic findings, were diagnostic of ECD. This case of biopsy-proven ECD is unique in that the singular symptom was seizures well controlled with medical management in the presence of similarly located bilateral anterior mesial temporal lobe lesions. Although ECD is rare intracranially, its variable imaging presentation, including the potential to mimic seizure-associated medial temporal lobe tumors, emphasizes the need for a wide differential diagnosis.

Rombo encephalitis and cerebellar abscess due to Listeria monocytogenes with fulminant course in an immunocompetent elderly patient: A case report

Listeria Monocytogenes (LM) is an opportunistic bacterium that can cause from mild infections to severe clinical pictures with neurological involvement, being responsible for sporadic cases, epidemic outbreaks and a high mortality and case fatality rate. Neurolisteriosis may present as meningitis, meningoencephalitis, rhomboencephalitis or brain abscesses. LM rhomboencephalitis is a rare disease for which advanced age and cellular immunosuppression are common risk factors, although it may occur in patients without prior immunosuppression. Spread to the CNS occurs haematogenously through the blood-brain barrier, by direct invasion or by retrograde brain migration through nerve tracts. Different diagnostic subtyping methods are available, although DNA sequencing is the technique of choice for epidemiological studies. The combination of ampicillin with gentamicin for 6-8 weeks is usually the recommended treatment, and neurosurgery may improve the prognosis in patients with brain abscess, although there are no clinical practice guidelines available with a high level of evidence. The diagnosis of LM rhomboencephalitis should be suspected in any patient with an infectious condition with evidence of meningeal or brainstem involvement. Mortality from neurolisteriosis is increasing in Europe due to the ageing population and the increase in immunocompromised patients, and can reach up to 51%. The case described in this article is exceptional, presenting acute rhomboencephalitis with cerebellar abscesses in a healthy patient with no risk factors and a fulminant course.

Distinct phenotypes in a cohort of anti-CASPR2 associated neurological syndromes

IntroductionAnti-contactin-associated protein-like 2 (CASPR2) is classically associated with limbic encephalitis (LE), Morvan syndrome and peripheral nerve hyperexcitability (PNH). Additional clinical features have been previously recognized. ObjectiveTo describe a cohort of patients with anti-CASPR2-associated neurological syndromes from a tertiary referral centre. MethodsRetrospective analysis of patients with positive serum anti-CASPR2 antibodies in the period between 2014 and 2021. ResultsNineteen patients were identified, 11 (57.9%) male, with a median age at symptom onset of 49.0 (31.3–63.0) years and a median time to diagnosis of 1.0 (0.0–1.8) years. The most common clinical syndromes were LE (7 cases, 36.8%), Morvan syndrome (4, 21.1%) and PNH (2, 10.5%). Six patients presented with atypical phenotypes (31.6%), comprising dysautonomia (orthostatic hypotension and Adie’s Pupil), motor tics/stereotypies, obsessive-compulsive disorder, and brainstem involvement. The most common presenting symptoms were seizures (31.6%), PNH (21.1%) and cognitive dysfunction (15.8%). One LE patient had a disease duration of 2,5 years and was initially diagnosed with dementia. CSF was normal in most cases. Brain MRI showed temporal lobe hyperintensities in 4 LE cases (57.1%). All PNH cases had myokymic discharges of fasciculations in the electromyography. Two patients had associated thymoma and 1 had lung adenocarcinoma. Eight patients (42.1%) received treatment during the acute phase and 26.3% maintenance treatment. Approximately half of the treated cases improved or stabilised, with 4 (21.1%) deaths in the whole cohort. ConclusionAnti-CASPR2-associated neurological disorders may present with isolated atypical phenotypes, a slowly progressive clinical course, and with normal CSF or imaging findings.

Phenotypic Heterogeneity in Patients with Mutations in the Mitochondrial Complex I Assembly Gene NDUFAF5.

Rare mutations in NADH:ubiquinone oxidoreductase complex assembly factor 5 (NDUFAF5) are linked to Leigh syndrome. We aimed to describe clinical characteristics and functional findings in a patient cohort with NDUFAF5 mutations. Patients with biallelic NDUFAF5 mutations were recruited from multi-centers in Taiwan. Clinical, laboratory, radiological, and follow-up features were recorded and mitochondrial assays were performed in patients' skin fibroblasts. Nine patients from seven unrelated pedigrees were enrolled, eight homozygous for c.836 T > G (p.Met279Arg) in NDUFAF5 and one compound heterozygous for p.Met279Arg. Onset age had a bimodal distribution. The early-onset group (age <3 years) presented with psychomotor delay, seizure, respiratory failure, and hyponatremia. The late-onset group (age ≥5 years) presented with normal development, but slowly progressive dystonia. Combing 25 previously described patients, the p.Met279Arg variant was exclusively identified in Chinese ancestry. Compared with other groups, patients with late-onset homozygous p.Met279Arg were older at onset (P = 0.008), had less developmental delay (P = 0.01), less hyponatremia (P = 0.01), and better prognosis with preserved ambulatory function into early adulthood (P = 0.01). Bilateral basal ganglia necrosis was a common radiological feature, but brainstem and spinal cord involvement was more common with early-onset patients (P = 0.02). A modifier gene analysis showed higher concomitant mutation burden in early-versus late-onset p.Met279Arg homozygous cases (P = 0.04), consistent with more impaired mitochondrial function in fibroblasts from an early-onset case than a late-onset patient. The p.Met279Arg variant is a common mutation in our population with phenotypic heterogeneity and divergent prognosis based on age at onset. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Evaluating the diagnosis and treatment of neuro-Behçet’s disease with cascade sign appearance in brainstem: a case report

This study aimed to investigate a case of neuro-Behçet’s disease misdiagnosed as acute ischemic stroke or multiple sclerosis (MS). The studied case was a 29-year-old man with subacute onset of hemiparesis, dysarthria, and ataxia who was diagnosed as acute ischemic stroke at first. Due to no significant improvement, the patient was managed as an MS case, but he did not experience any improvements again. We noticed a history of oral and genital aphthous and cascade sign appearance in his brain MRI. Then, Behçet’s disease with secondary parenchymal involvement of brainstem was confirmed. The patient received infliximab, which resulted in clinico-radiological recovery. Practical Implications. Given the prevalence of Behçet’s disease in the Middle East, the possibility of its diagnosis should be considered in patients with atypical history or imaging for ischemic stroke or MS.