Cerebellar Syndrome Research Articles

Anti-mGluR1 encephalitis: Case illustration and systematic review.

The literature for immune-mediated neurological disorders is evolving like no other field of neurological illnesses. Many new antibodies or disorders have been described in the last decade. The cerebellum is a brain structure susceptible to these immune-mediated pathologies, and anti-metabotropic glutamate receptor 1 (mGluR1) antibody has a predilection to the cerebellar tissue. Anti-mGluR1 encephalitis is a rare autoimmune disease affecting the central and peripheral nervous systems, triggering an acute or subacute cerebellar syndrome with varying degrees of severity. Anti-mGluR1 encephalitis is a rare autoimmune disease affecting the central nervous system. We aimed to systematically review reported cases of anti-mGluR1 encephalitis and summarize their clinical presentation, management, outcomes, and case reports. A search of the PubMed and Google Scholar databases was conducted and included all cases of anti-mGluR1 encephalitis published in English before October 1, 2022. A comprehensive systematic review was conducted using "metabotropic glutamate receptor type 1," "mGluR1," autoantibodies," "autoantibodies," "autoimmunity," and "antibody" as keywords. The risk of bias assessment of the evidence was performed using appropriate tools. The qualitative variables were presented as frequency and percentage. Including our case, 36 cases of anti-mGluR1 encephalitis (19 males, median age 52.5 years, 11.1% pediatric cases) have been reported. The most common clinical manifestations are ataxia, dysarthria, and nystagmus. Initial imaging was normal in 44.4% of patients; however, 75% of patients showed abnormality later in the disease course. The first-line therapy options include glucocorticoids, intravenous immunoglobulin, and plasma exchange. Rituximab is the most commonly used second-line treatment. Complete remission was achieved in only 22.2% of patients, and 61.8% were disabled by the end of their course. Anti-mGluR1 encephalitis manifests as symptoms of cerebellar pathology. Although the natural history has not been completely elucidated, early diagnosis with prompt initiation of immunotherapy could be imperative. Any patient suspected to have autoimmune cerebellitis should be tested for the presence of anti-mGluR1 antibody in the serum and cerebrospinal fluid. Escalation to an aggressive therapy approach should be applied in cases that do not respond to first-line therapies, and extended follow-up durations are required in all cases.

Case Report: Zolpidem's paradoxical restorative action: A case report of functional brain imaging.

Zolpidem is a sedative drug that has been shown to induce a paradoxical effect, restoring brain function in wide range of neurological disorders. The underlying functional mechanism of the effect of zolpidem in the brain in clinical improvement is still poorly understood. Thus, we aimed to investigate rest brain function to study zolpidem-induced symptom improvement in a patient who developed postoperative pediatric cerebellar mutism syndrome, a postoperative complication characterized by delayed onset transient mutism/reduced speech that can occur after medulloblastoma resection. The patient experienced clinical recovery after a single dose of zolpidem. Brain function was investigated using arterial spin labeling MRI and resting-state functional MRI. Imaging was performed at three time-points: preoperative, postoperative during symptoms, and after zolpidem intake when the symptoms regressed. Whole brain rest cerebral blood flow (CBF) and resting state functional connectivity using Pearson coefficient correlations between pairs of regions of interest were investigated two-by-two at the different time points. A comparison between postoperative and preoperative images showed a significant decrease in rest CBF in the left supplementary motor area, Broca's area, and the left striatum and a decrease in functional connectivity within the dentato-thalamo-cortical and cortico-striato-pallido-thalamo-cortical loops. Post-zolpidem images showed increased CBF in the left striatum and increased functional connectivity within the disrupted loops relative to postoperative images. Thus, we observed functional changes within the broader speech network and thalamo-subcortical interactions associated with the paradoxical effect of zolpidem in promoting clinical recovery. This should encourage further functional investigations in the brain to better understand the mechanism of zolpidem in neurological recovery.

Wernicke’s Encephalopathy Complicating Hypermesis Gravidarum: a Rare Case Report

Introduction: Wernicke’s Encephalopathy (WE) is an uncommon neurological disorder due to thiamine deficiency. Its clinical findings are variable steering its high incidence postmortem. Seldom, thiamine deficiency is present in a clinical triad consisting of cognitive disorder, ocular abnormalities and gait ataxia. Most commonly, the clinical picture is not specific leading to late or misdiagnosis. In pregnant woman with Hyperemesis Gravidarum, incoercible vomiting and poor intake paves the path to thiamine deficiency by depleting B1 storage affecting cerebral energy homeostasis. Ergo, HG leads to neurological complications affecting maternal mortality and morbidity. Case Report: We hereby present the uncommon case of WE complicate HG in 18 weeks’ gestation primigravidae. Diagnosis relied on clinical findings as the clinical picture was typical: confusion, disorientation and memory impairment besides static and kinetic cerebellar syndrome and ophthalmological abnormalities such as unequal pupils and horizontal nystagmus. Biological findings were out of normal range as it showed electrolytes imbalance, dehydration and elevated liver and pancreatic enzymes. Imaging investigations were normal. Treatment was based on intravenous thiamine supplementation and vomiting management. Conclusion: We are a preventable neurological disorder. Prompt treatment and correct dosage in light of the appropriate guidelines enlighten the prognosis and may even lead to remission. Whereas late or non-diagnosis leads to dramatic complications such as Korsakoff’s syndrome. This article aims to raise clinician’s suspicion of WE and emphasizes the importance of preventive thiamine supplementation during pregnancies and prophylactic intravenous thiamine administration in pregnancy with Hyperemesis Gravidarum.

Presurgical MRI-Based Radiomics Models for Predicting Cerebellar Mutism Syndrome in Children With Posterior Fossa Tumors.

Current studies have indicated that tumoral morphologic features are associated with cerebellar mutism syndrome (CMS), but the radiomics application in CMS is scarce. To develop a model for CMS discrimination based on multiparametric MRI radiomics in patients with posterior fossa tumors. Retrospective. A total of 218 patients (males 132, females 86) with posterior fossa tumors, 169 of which were included in the MRI radiomics analysis. The MRI radiomics study cohort (169) was split into training (119) and testing (50) sets with a ratio of 7:3. All the MRI were acquired under 1.5/3.0 T scanners. T2-weighted image (T2W), T1-weighted (T1W), fluid attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI). Apparent diffusion coefficient (ADC) maps were generated from DWI. Each MRI dataset generated 1561 radiomics characteristics. Feature selection was performed with univariable logistic analysis, correlation analysis, and least absolute shrinkage and selection operator (LASSO) penalized logistic regression. Significant clinical features were selected with multivariable logistic analysis and used to constructed the clinical model. Radiomics models (based on T1W, T2W, FLAIR, DWI, ADC) were constructed with selected radiomics features. The mix model was based on the multiparametric MRI radiomics features. Multivariable logistic analysis was utilized during clinical features selection. Models' performance was evaluated using the area under the receiver operating characteristic (AUC) curve. Interobserver variability was assessed using Cohen's kappa. Significant threshold was set as P < 0.05. Sex (aOR = 3.72), tumor location (aOR = 2.81), hydrocephalus (aOR = 2.14), and tumor texture (aOR = 5.08) were significant features in the multivariable analysis and were used to construct the clinical model (AUC = 0.79); totally, 33 radiomics features were selected to construct radiomics models (AUC = 0.63-0.93). Seven of the 33 radiomics features were selected for the mix model (AUC = 0.93). Multiparametric MRI radiomics may be better at predicting CMS than single-parameter MRI models and clinical model. 4. 2.

Riboflavin and Histidine Metabolisms Are Two Key Pathways Related to the Clinically Isolated Syndrome (CIS): A WGCNA-based In silico Analysis

Background: As an inflammatory disorder, Multiple Sclerosis (MS) causes demyelination, as well as axonal and neuronal injury in the central nervous system (CNS). Several clinical signs may be the indicators of MS among which, Clinically Isolated Syndrome (CIS) is the first symptom caused by the inflammation and demyelination of CNS. CIS is characterized by symptoms such as optic neuritis, brain stem or cerebellar syndrome, spinal cord syndrome, or sometimes cerebral hemispheric dysfunction. Objective: So far, metabolic pathways involved in the development of CIS are not fully understood. Therefore, in this study, weighted gene co-expression network analysis (WGCNA) has been used to identify differentially expressed genes in CIS disease and the main pathways associated with it. Methods: We grouped differentially expressed genes along with the functionally related genes into large modules to obtain their direct and indirect relationships. Results: The results have identified two new pathways associated with CIS, including riboflavin and histidine metabolism-involved pathways. Conclusion: Riboflavin and histidine metabolism-involved pathways may be considered potential therapeutic goals for CIS management in the future.

Septin-3 autoimmunity in patients with paraneoplastic cerebellar ataxia

BackgroundSeptins are cytoskeletal proteins with filament forming capabilities, which have multiple roles during cell division, cellular polarization, morphogenesis, and membrane trafficking. Autoantibodies against septin-5 are associated with non-paraneoplastic cerebellar ataxia, and autoantibodies against septin-7 with encephalopathy with prominent neuropsychiatric features. Here, we report on newly identified autoantibodies against septin-3 in patients with paraneoplastic cerebellar ataxia. We also propose a strategy for anti-septin autoantibody determination.MethodsSera from three patients producing similar immunofluorescence staining patterns on cerebellar and hippocampal sections were subjected to immunoprecipitation followed by mass spectrometry. The identified candidate antigens, all of which were septins, were expressed recombinantly in HEK293 cells either individually, as complexes, or combinations missing individual septins, for use in recombinant cell-based indirect immunofluorescence assays (RC-IIFA). Specificity for septin-3 was further confirmed by tissue IIFA neutralization experiments. Finally, tumor tissue sections were analyzed immunohistochemically for septin-3 expression.ResultsImmunoprecipitation with rat cerebellum lysate revealed septin-3, -5, -6, -7, and -11 as candidate target antigens. Sera of all three patients reacted with recombinant cells co-expressing septin-3/5/6/7/11, while none of 149 healthy control sera was similarly reactive. In RC-IIFAs the patient sera recognized only cells expressing septin-3, individually and in complexes. Incubation of patient sera with five different septin combinations, each missing one of the five septins, confirmed the autoantibodies’ specificity for septin-3. The tissue IIFA reactivity of patient serum was abolished by pre-incubation with HEK293 cell lysates overexpressing the septin-3/5/6/7/11 complex or septin-3 alone, but not with HEK293 cell lysates overexpressing septin-5 as control. All three patients had cancers (2 × melanoma, 1 × small cell lung cancer), presented with progressive cerebellar syndromes, and responded poorly to immunotherapy. Expression of septin-3 was demonstrated in resected tumor tissue available from one patient.ConclusionsSeptin-3 is a novel autoantibody target in patients with paraneoplastic cerebellar syndromes. Based on our findings, RC-IIFA with HEK293 cells expressing the septin-3/5/6/7/11 complex may serve as a screening tool to investigate anti-septin autoantibodies in serological samples with a characteristic staining pattern on neuronal tissue sections. Autoantibodies against individual septins can then be confirmed by RC-IIFA expressing single septins.

Coordination and Cognition in Pure Nutritional Wernicke's Encephalopathy with Cerebellar Degeneration after COVID-19 Infection: A Unique Case Report.

Alcoholic cerebellar degeneration is a restricted form of cerebellar degeneration, clinically leading to an ataxia of stance and gait and occurring in the context of alcohol misuse in combination with malnutrition and thiamine depletion. However, a similar degeneration may also develop after non-alcoholic malnutrition, but evidence for a lasting ataxia of stance and gait and lasting abnormalities in the cerebellum is lacking in the few patients described with purely nutritional cerebellar degeneration (NCD). We present a case of a 46-year-old woman who developed NCD and Wernicke's encephalopathy (WE) due to COVID-19 and protracted vomiting, resulting in thiamine depletion. We present her clinical course over the first 6 months after the diagnosis of NCD and WE, with thorough neuropsychological and neurological examinations, standardized clinical observations, laboratory investigations, and repeated MRIs. We found a persistent ataxia of stance and gait and evidence for an irreversible restricted cerebellar degeneration. However, the initial cognitive impairments resolved. Our study shows that NCD without involvement of alcohol neurotoxicity and with a characteristic ataxia of stance and gait exists and may be irreversible. We did not find any evidence for lasting cognitive abnormalities or a cerebellar cognitive-affective syndrome (CCAS) in this patient.

Missense Mutations in MAB21L1: Causation of Novel Autosomal Dominant Ocular BAMD Syndrome.

Biallelic MAB21L1 variants have been reported to cause autosomal recessive cerebellar, ocular, craniofacial, and genital syndrome (COFG), whereas only five heterozygous pathogenic variants have been suspected to cause autosomal dominant (AD) microphthalmia and aniridia in eight families. This study aimed to report an AD ocular syndrome (blepharophimosis plus anterior segment and macular dysgenesis [BAMD]) syndrome based on clinical and genetic findings from patients with monoallelic MAB21L1 pathogenic variants in our cohort and reported cases. Potential pathogenic variants in MAB21L1 were detected from a large in-house exome sequencing dataset. Ocular phenotypes of the patients with potential pathogenic variants in MAB21L1 were summarized, and the genotype-phenotype correlation was analyzed through a comprehensive literature review. Three heterozygous missense variants in MAB21L1, predicted to be damaging, were detected in 5 unrelated families, including c.152G>T in 2, c.152G>A in 2, and c.155T>G in one. All were absent from gnomAD. The variants were de novo in two families, transmitted from affected parents to offspring in two families, and with an unknown origin in the other family, demonstrating strong evidence of AD inheritance. All patients revealed similar BAMD phenotypes, including blepharophimosis, anterior segment dysgenesis, and macular dysgenesis. Genotype-phenotype analysis suggested that patients with monoallelic MAB21L1 missense variants had only ocular anomalies (BAMD), whereas patients with biallelic variants presented both ocular and extraocular symptoms. Heterozygous pathogenic variants in MAB21L1 account for a new AD BAMD syndrome, which is completely different from COFG caused by homozygous variants in MAB21L1. Nucleotide c.152 is likely a mutation hot spot, and the encoded residue of p.Arg51 might be critical for MAB21L1.

Fluorouracil-induced leukoencephalopathy mimicking neuroleptic malignant syndrome: a case report

BackgroundFluorouracil-induced leukoencephalopathy is a rare complication and has been reported to present as confusion, oculomotor abnormality, ataxia, and parkinsonism; however, there is no previous report of a presentation mimicking neuroleptic malignant syndrome. Acute cerebellar syndrome may occur, which can be explained by the extremely high accumulation of the drug in the cerebellum. However, presentation mimicking neuroleptic malignant syndrome similar to our case has never been reported.Case presentationHere, we describe a 68-year-old Thai male presenting with advanced-stage cecal adenocarcinoma, as well as symptoms and signs indicative of neuroleptic malignant syndrome. He received two doses of intravenous metoclopramide 10 mg 6 hours before his symptoms occurred. Magnetic resonance imaging scan revealed signal hyperintensity within the bilateral white matter. Further evaluation showed that his thiamine level was extremely low. Thus, he was diagnosed with fluorouracil-induced leukoencephalopathy mimicking neuroleptic malignant syndrome. The concomitant fluorouracil-induced thiamine deficiency eventually leads to rapid depletion of thiamine and was considered a risk factor for fluorouracil-induced leukoencephalopathy.ConclusionFluorouracil-induced leukoencephalopathy is believed to be caused by insult causing mitochondrial dysfunction. However, the exact mechanism remains unknown, but our finding suggests that thiamine deficiency plays a crucial role in fluorouracil-induced leukoencephalopathy. Diagnosis is usually delayed due to a lack of clinical suspicion and results in significant morbidity requiring unnecessary investigations.

Cerebellar Mutism Syndrome After Posterior Fossa Tumor Surgery in Children—A Retrospective Single-Center Study

Cerebellar mutism syndrome (CMS) is a well-known complication following posterior fossa tumor surgery in pediatric patients. We evaluated the incidence of CMS in our institute and analyzed association with multiple risk factors, such as tumor entity, surgical approach, and hydrocephalus. All pediatric patients who received an intra-axial tumor resection in the posterior fossa between January 2010 and March 2021 were included for retrospective analysis. Various data points, including demographic, tumor-associated, clinical, radiological, surgery associated, complications and follow-up data were collected and statistically evaluated for association with CMS. 63 surgeries in 60 patients were included with a median age of 8 years. Pilocytic astrocytoma was mostly represented by 50%, followed by medulloblastoma in 28%, and ependymomas in 10%. Complete resection was achieved in 67% versus subtotal in 23%, and partial resection in 10%. Telovelar approach was the most used in 43 % compared to transvermian in 8%. 10 children (17%) developed CMS and showed marked improvement but with residual deficits. Significant risk factors were transvermian approach (p=0.03), vermian splitting whenever added to other approach (p=0.002), initial presentation with acute hydrocephalus (p=0.02), and remaining hydrocephalus after tumor surgery (p=0.004). Our CMS rate compares to those described in literature. Despite the limitations of our study as a retrospective one, we found CMS was not only associated with a transvermian approach, but also occurs after using a telovelar approach, however to a lesser extent. Acute hydrocephalus at initial presentation necessitating urgent management was significantly associated with higher incidence of CMS.

Cerebellar dysfunction and autism spectrum disorders – what do we know?

IntroductionAutism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by impairments in social cognition and repetitive behaviors with onset in early infancy. Deficits in emotion recognition, social perception, and communication have been identified as core symptoms of ASD.Comorbid disorders are frequent, namely psychiatric illness, epilepsy, sleep disruption, and hyperactivity.Immune profile changes during early life may contribute to pathogenesis of ASD. Other risk factors include advanced parental age, fetal environment, fertility treatments, medications, and nutritional and toxic factors.Several brain regions are involved in the pathophysiology of ASD but the cerebellum is the structure most consistently found altered. An increased risk of ASD is associated with cerebellar damage.ObjectivesTo highlight the importance of understanding the key processes of cerebellar development and how altered cerebellar function leads to social and cognitive impairments, and consequently ASD.MethodsNon-systematic review of the literature using Pubmed database. Papers were selected according to their relevance.ResultsFrom imaging studies, we can understand that cerebellum is not just about motor function. Different tasks like adding working memory, emotional and social processing, and language seem to be part of core functions of the cerebellar circuit.Adults with lesions in the cerebellum can develop cerebellar cognitive affective syndrome (CCAS), with core symptoms of impaired executive function, difficulties in spatial cognition, blunted affect, or inappropriate behavior. Some children who have tumor resection surgery for medulloblastomas also exhibit symptoms of CCAS, and some experience posterior fossa syndrome (PFS).The linguistic, cognitive, and behavioral deficits in CCAS and PFS may contribute to explaining how cerebellar alterations are related to ASD, which is a neurodevelopmental disorder characterized by an earlier onset and broader spectrum of these symptoms.ConclusionsThe literature has suggested an important role for cerebellar dysfunction in etiology of ASD, under certain premises: (a) cerebellar expansion temporarily coincides with onset of ASD; (b) cerebellum is prone to lesions during this period; (3) cerebellar lesions contribute to dysfunctional social and language abilities.Disturbances in cerebellar development lead to alterations in higher cognitive functions, due to changes in Purkinje cells. These dysfunctional neurons, once integrated into a brain circuit that controls complex tasks, lead to these functions becoming aberrant.It is therefore fair to say that cerebellum is important for development of the so-called “cognitive and social brain” since it is itself part of this network. So, the cerebellum certainly plays a relevant role in pathophysiology of ASD.Disclosure of InterestNone Declared

Long-term postoperative quality of life in childhood survivors with cerebellar mutism syndrome.

To investigate the long-term quality of life (QoL) of children with cerebellar mutism syndrome (CMS) and explore the risk factors for a low QoL. This cross-sectional study investigated children who underwent posterior fossa surgery using an online Pediatric Quality of Life Inventory questionnaire. CMS and non-CMS patients were included to identify QoL predictors. Sixty-nine patients were included (male, 62.3%), 22 of whom had CMS. The mean follow-up time was 45.2 months. Children with CMS had a significantly lower mean QoL score (65.3 vs. 83.7, p < 0.001) and subdomain mean scores (physical; 57.8 vs. 85.3, p < 0.001; social: 69.5 vs. 85.1, p = 0.001; academic: p = 0.001) than those without CMS, except for the emotional domain (78.0 vs. 83.7, p = 0.062). Multivariable analysis revealed that CMS (coefficient = -14.748.61, p = 0.043), chemotherapy (coefficient = -7.629.82, p = 0.013), ventriculoperitoneal (VP) shunt placement (coefficient = -10.14, p = 0.024), and older age at surgery (coefficient = -1.1830, p = 0.007) were independent predictors of low total QoL scores. Physical scores were independently associated with CMS (coefficient = -27.4815.31, p = 0.005), VP shunt placement (coefficient = -12.86, p = 0.025), and radiotherapy (coefficient = -13.62, p = 0.007). Emotional score was negatively associated with age at surgery (coefficient = -1.92, p = 0.0337) and chemotherapy (coefficient = -9.11, p = 0.003). Social scores were negatively associated with male sex (coefficient = -13.68, p = 0.001) and VP shunt placement (coefficient = -1.36, p = 0.005), whereas academic scores were negatively correlated with chemotherapy (coefficient = -17.45, p < 0.001) and age at surgery (coefficient = -1.92, p = 0.002). Extent of resection (coefficient = 13.16, p = 0.021) was a good predictor of higher academic scores. CMS results in long-term neurological and neuropsychological deficits, negatively affecting QoL, and warranting early rehabilitation.

Cerebellar Cognitive Affective Syndrome in Mexican Pediatric Patients with Ataxia-Telangiectasia.

Ataxia-telangiectasia (A-T) is a disease caused by mutations in the ATM gene (11q22.3-23.1) that induce neurodegeneration Sasihuseyinoglu AS et al. Pediatr Allergy Immunol Pulmonol 31(1):9-14, 2018,Teive HAG et al. Parkinsonism Relat Disord 46:3-8, 2018. Clinically, A-T is characterized by ataxia, mucocutaneous telangiectasia, immunodeficiency, and malignancy. Movement disorders have been the most described and well-studied symptoms of A-T. Other studies have reported visuospatial processing disorders, executive function disorders and emotional regulation disorders, which are clinical manifestations that characterize cerebellar cognitive affective syndrome (CCAS)Choy KR et al. Dev Dyn 247(1):33-46, 2018.To describe the neurocognitive and emotional state of pediatric patients with ataxia-telangiectasia and to discuss whether they have cerebellar cognitive affective syndrome.This observational, cross-sectional, and descriptive study included 9 patients with A-T from May 2019 to May2021. A complete medical history was retrieved, and tests were applied to assess executive functions, visual-motor integration and abilities, language, psychological disorders, and ataxia.Six girls and 3 boys agreed to participate. The age range was 6 to 14years. The participants included five schoolchildren and four teenagers. Eight patients presented impaired executive functioning. All patients showed some type of error in copying and tracing (distortion) in the performance of visual perceptual abilities. Emotional disorders such as anxiety and depression were observed in six patients. Eight patients presented with dyslalia and impairments in word articulation, all patients presented with ataxia, and seven patients used a wheelchair.All patients presented symptoms consistent with CCAS and had variable cognitive performance.

Opsoclono-Myoclonic Syndrome Revealing a Neuroblastoma in an Infant: A Rare and Unusual Case Report

Introduction Opsoclonomyoclonic syndrome (OMS) is an uncommon childhood illness. Opsoclonus, myoclonus, ataxia, and behavioral abnormalities are all symptoms. Long-term prognosis is dismal, however the introduction of novel immunotherapy regimens may improve it. Case report We present the case of an 18-month-old previously healthy newborn who was hospitalised for gait problem and widespread tremors that lasted four days, along with food vomiting and photophobia. A conscious patient with a 38°C temperature, a cerebellar syndrome, and aberrant palpebral and ocular myoclonic movements led us to suspect an opsoclonomyoclonic syndrome. The biological examination and brain CT were both normal, however the cerebral-medullary MRI revealed a signal anomaly. Given the close link between OMS and neuroblastoma, a thoraco-abdominal CT scan revealed a neuroblastoma. The child was transported to the paediatric oncology department, where he received surgical resection with chemotherapy, as well as corticosteroids, clonazepam, and antiepileptic medication. Oncologically and neurologically, the evolution was favorable. Conclusion : Although OMS is an uncommon condition in children, the fact that it has a significant connection with neuroblastoma allowed us to identify the diagnosis and begin therapy early, resulting in a positive patient outcome.

Hemorrhagic Wallenberg Syndrome Accompanied by Horner Syndrome at Young Age

Highlight: Wallenberg syndrome caused by medulla oblongata hemorrhage with good functional outcome. Wallenberg syndrome is accompanied by Horner's syndrome, which occurs at a young age. In patients with Wallenberg syndrom, conservative management and medical rehabilitation are used. ABSTRACT Introduction: Wallenberg syndrome is a rare syndrome involving the medulla oblongata, an uncommon hemorrhage site. It is also known as lateral medullary syndrome or posterior inferior cerebellar artery syndrome. Wallenberg syndrome has several symptoms that can be divided into vestibulo-cerebellar, bulbar, autonomic, sensory, and atypical. Case: A 27-year-old man came to the emergency unit complaining of dizziness and swinging, as well as a left eyelid that did not open completely, a lack of sweat on the left side of the face, a hoarse voice, swallowing disturbances, hiccups, decreased hearing in the left ear, and a lack of sensation on the left side of the face and the right side of the body. The patient tended to fall to the left and was unsteady when standing. Physical examination revealed Horner syndrome, bidirectional nystagmus, left dysdiadochokinesia, and left ataxia. A CT scan of the head showed a left-sided medulla oblongata hemorrhage. The patient was given conservative therapy, feeding through a nasogastric tube, and medical rehabilitation. A repeat CT scan of the head was done one week later, and it was discovered that the hemorrhage in the medulla oblongata had begun to absorb. Conclusion: Wallenberg syndrome, with a manifestation of hemorrhagic stroke in the medulla oblongata, can occur at a young age with various clinical symptoms. The diagnosis of Wallenberg syndrome is made based on clinical symptoms and imaging findings. Conservative therapy using medicines and medical rehabilitation can provide a speedy recovery. An incorrect diagnosis is a major hazard to patient safety and can have serious consequences, including permanent disability or death.

Cerebellar ataxia after a single day of metronidazole use: Case report

Cerebellar ataxic syndromes, although uncommon, have been reported previously in patients taking metronidazole. However, almost all cases describe instances where patients were taking prolonged or high doses of the drug. We report a 65-year-old man who consumed 400 mg of metronidazole 3 times over 1 day and presented with slurring of speech, imbalance while walking and diplopia. The symptoms developed the day after consumption of metronidazole. Examination showed slurring of speech, gaze-evoked nystagmus, and dysmetria in all limbs. MRI brain revealed symmetric hyperintense lesions in the dentate nucleus and pons on T2-weighted imaging and FLAIR, which have a well-established association with metronidazole-induced central nervous system (CNS) toxicity. On discontinuation of the drug, symptoms improved, and complete recovery was noted at follow-up 2 weeks later. This case indicates that CNS side effects of metronidazole may not necessarily occur only at high doses or after prolonged courses of metronidazole, but may occur as an idiosyncratic reaction to the drug. Reasons for variable susceptibility require further investigation.

Creutzfeldt-Jakob Disease Misdiagnosed as Multiple System Atrophy.

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by various combinations of autonomic failure, parkinsonism, and cerebellar syndromes. Although consensus criteria have been widely used to diagnose MSA, accurate clinical diagnosis remains challenging. Other neurodegenerative disorders, such as Lewy body disease, can mimic MSA. We described clinical and neuropathologic findings of two patients with Creutzfeldt-Jakob disease (CJD) who had antemortem clinical diagnoses of MSA. The brain bank for neurodegenerative disorders was queried for cases with a clinical diagnosis of MSA, but neuropathologic findings of CJD. Case 1 was a 55-year-old man with a 6-month history of orthostatic hypotension, parkinsonism, cerebellar ataxia, bradyphrenia, and memory impairment. Case 2 was a 65-year-old man who had a 5-year history of cerebellar ataxia, parkinsonism, and cognitive impairment, as well as a 7-year history of dream enactment behavior. Neither case had characteristic α-synuclein immunoreactive neuronal or glial inclusions typical of MSA. Instead, they had spongiform encephalopathy with neuronal loss and gliosis with prion protein-immunoreactive kuru-like plaques. Genetic analyses in case 1 had wild-type PRNP, whereas case 2 revealed a 4-octapeptide repeat insertion in PRNP. Even when clinical features suggest MSA, CJD should also be considered if the progression is rapid or the disease course is atypical, such as the absence of autonomic dysfunction for an extended period.

Chapter 8 - Cerebellum: From the identification of the cerebellar motor syndrome to the internal models

Cerebellar circuitry is topographically arranged in closed loops with the cerebral cortex. The three cornerstones of clinical ataxia have emerged from studies on connectional anatomy and from clinical/neuropsychological observations, leading to the definition of clinical syndromes encountered in daily practice: (a) the cerebellar motor syndrome (CMS), (b) the vestibulocerebellar syndrome (VCS), and (c) the cerebellar cognitive affective syndrome/Schmahmann syndrome (CCAS/SS). These syndromes are either isolated or coexist, depending on the underlying pathological process and its degree of extension within the cerebellum. Dysmetria is the core feature of cerebellar deficits, encompassing motor dysmetria (hypermetria, hypometria) in CMS, oculomotor dysmetria in VCS, and dysmetria of thought in CCAS/SS. The leading hypothesis is that dysmetria results from errors in building or maintaining internal models, which are inherent to predictive behavior. Errors in prediction would lead to clumsiness and incoordination of limbs, oculomotor impairments, and aberrant cognitive/affective behavior. The cerebellum is currently viewed as a learning machine enriched with multiple plasticity mechanisms, allowing the permanent adaptation to the external world by generating and maintaining predictive operations, from motor to cognitive, affective, emotional, and social operations essential for daily human life.

Multiple system atrophy

The article presents a progressive neurodegenerative disease - multisystem atrophy, characterized by a combination of autonomic failure and various motor disorders, including parkinsonism and/or cerebellar ataxia; etiopathogenetic factors and variants of the clinical picture are described. We describe own clinical observation of a 59-old patient with cerebellar and bulbar syndromes, parkinsonism, pyramidal insufficiency, cognitive deficits, and autonomic dysfunction. The differential diagnosis included a whole range of neurodegenerative and hereditary diseases: Parkinson's disease, vascular parkinsonism, progressive supranuclear palsy, spinocerebellar ataxia, FXTAS, mitochondrial encephalopathies. The moderate severity of parkinsonism and the significant predominance of cerebellar symptoms and autonomic dysfunction make this clinical case difficult to diagnose. However, based on the life and disease history, clinical picture and research methods, a diagnosis of multiple system atrophy, cerebellar type (cerebellar, autonomic, bulbar syndrome, parkinsonism, pyramidal insufficiency and moderate cognitive impairment) was established. Differential search in such patients is a difficult task and includes a whole range of neurodegenerative and hereditary diseases due to the similarity of individual clinical and neuroimaging features and, unfortunately, the limited availability of molecular genetic diagnostic methods. However, earlier diagnosis is necessary to focus in time on the development of a personalized approach to the management of each such patient, taking into account the rate of symptoms development and steady progression, in order to ensure the longest possible survival time with an acceptable level of quality of life.

Classical Infratentorial Superficial Siderosis Related to Spinal Abnormalities as a Cause of Cerebellar Cognitive Affective Syndrome.

Classical Infratentorial Superficial Siderosis Related to Spinal Abnormalities as a Cause of Cerebellar Cognitive Affective Syndrome.