Gluten Ataxia and mGluR1 Autoimmune Encephalitis Presenting as Acute Cerebellar Ataxia: A Case Report.

A Caucasian male in his 60s presented with acute onset of dizziness, dysarthria, and gait ataxia. Upon extensive workup, positive findings were cerebrospinal fluid (CSF) showing lymphocytic pleocytosis with oligoclonal bands, positive celiac disease autoantibodies in blood, a duodenal biopsy indicating lymphocytic infiltration, and positive anti-mGluR1 antibody titers in CSF. The patient was started on a strict gluten-free diet and intravenous immunoglobulin therapy for 5 days and showed mild consecutive improvements each day of treatment. He was discharged after 22 days, and was encouraged to continue gluten adherence, physical and speech therapy, and follow up with neuroimmunology. This report demonstrates that autoimmune encephalitis due to anti-mGluR1antibodies and gluten ataxia are both immune-mediated disorders that should be considered in acute cerebellar ataxia cases. By broadening the differential diagnosis and a comprehensive CSF analysis, identification of gluten ataxia and autoimmune encephalitis were beneficial in the management of this particular patient.

[A case of autoimmune glial fibrillary acidic protein astrocytopathy with various symptoms such as optic disc edema and cerebellar ataxia].

A 59-year-old man had developed visual abnormality, nausea, headache, and weight loss since three months before. The ophthalmologist found severe optic disc edema in both eyes, and referred him to our hospital. The patient had mild cerebellar ataxia. Increased cerebrospinal fluid pressure, increased protein and cell counts, positive oligoclonal band, and contrast-enhanced head MRI showed multiple linear perivascular radial gadolinium enhancement around bilateral lateral ventricles. His subjective and objective findings significantly improved with steroid treatment. The cerebrospinal fluid was found to be positive for glial fibrillary acidic protein (GFAP) antibodies, and a diagnosis of GFAP astrocytopathy was obtained. When optic edema or radial contrast effects was observed on contrast-enhanced MRI, GFAP astrocytopathy should be considerd. Prompt immunotherapy is required to circumvent the development of permanent visual impairment.

Case report: Isolated brainstem-cerebellar symptoms in a patient with anti-NMDA receptor encephalitis.

Cerebellar ataxia is an uncommon and atypical manifestation of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, often accompanied by seizures, psychiatric symptoms, and cognitive deficits. Previous cases of isolated brainstem-cerebellar symptoms in patients with anti-NMDAR encephalitis have not been documented. This report presents a case of anti-NMDAR encephalitis in which the patient exhibited cerebellar ataxia, nystagmus, diplopia, positive bilateral pathological signs, and hemiparesthesia with no other accompanying symptoms or signs. The presence of positive CSF anti-NMDAR antibodies further supports the diagnosis. Other autoantibodies were excluded through the use of cell-based assays. Immunotherapy was subsequently administered, leading to a gradual recovery of the patient.

[A case of Holmes tremor in which 123I-IMP SPECT and MRI findings suggest damage to the cerebellothalamic tract and the dentato-rubro-olivary pathway].

A 75-year-old woman was referred to our department in October 2022 with ataxia and involuntary movements of the right upper and lower limbs. She had experienced a left pontine hemorrhage in March 2021, which was managed conservatively. However, she had residual right-sided hemiplegia. In addition, she had cerebellar ataxia and a 2 |Hz resting tremor of the right upper and lower limbs, which was enhanced while maintaining posture and contemplation. Based on her history, and the findings of MRI and nuclear medicine imaging, we diagnosed the patient with Holmes tremor due to pontine hemorrhage. Holmes tremor is a rare movement disorder secondary to brainstem and thalamic lesions, characterized by a unilateral low-frequency tremor. In this case, 123I-IMP SPECT and MRI shows damage to the cerebellothalamic tract and dentaro-rubro-olivary pathway.

[Blood-brain barrier breakdown and autoimmune cerebellar ataxia].

Autoimmune cerebellar ataxia is a disease entity that affects the cerebellum and is induced by autoimmune mechanisms. The disease is classified into several etiologies, including gluten ataxia, anti-glutamate decarboxylase (GAD) ataxia, paraneoplastic cerebellar degeneration, primary autoimmune cerebellar ataxia and postinfectious cerebellar ataxia. The autoimmune response in the periphery cross-reacts with similar antigens in the cerebellum due to molecular mimicry. Breakdown of the blood‒brain barrier (BBB) could potentially explain the vulnerability of the cerebellum during the development of autoimmune cerebellar ataxia, as it gives rise to the entry of pathogenic autoantibodies or lymphocytes into the cerebellum. In this review, the maintenance of the BBB under normal conditions and the molecular basis of BBB disruption under pathological conditions are highlighted. Next, the pathomechanism of BBB breakdown in each subtype of autoimmune cerebellar ataxia is discussed. We recently identified glucose-regulated protein (GRP) 78 antibodies in paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome, and GRP78 antibodies induced by cross-reactivity with tumors can disrupt the BBB and penetrate anti-P/Q type voltage-gated calcium channel (VGCC) antibodies into the cerebellum, thus leading to cerebellar ataxia in this disease.

Etiologies and clinical characteristics of acute ataxia in a single national children's medical center.

OBJECTIVE: To analyze etiologic factors of pediatric acute ataxia and to identify the severity of its underlying causes for urgent medical intervention. METHODS: Clinical data of children diagnosed with acute ataxia between December 2015 and December 2021 from one national medical center were analyzed retrospectively. RESULTS: A total of 99 children (59 boys, 40 girls), median age at disease onset 55 (range: 12-168) months, were enrolled. The median follow period was 46 (range 6-78) months. Eighty-six (86.9 %) children were diagnosed with immune-associated acute ataxia, among which acute post-infectious cerebellar ataxia (APCA) was the most common diagnosis (50.5 %), followed by demyelinating diseases of the central nervous system (18.2 %) and Guillain-Barré syndrome (9.1 %). On cerebrospinal fluid (CSF) examination, 35/73 (47.9 %) patients had pleocytosis (>5 cells/mm3), and 18/73 (24.7 %) had elevated protein levels. Thirty-one patients (31.3 %) had an abnormal cerebral MRI. Children with other immune-associated acute cerebellar ataxia had more extracerebellar symptoms, intracranial MRI lesions, abnormal CSF results, longer hospital stay, higher recurrence rates and incidence of neurological sequelae than children with APCA. CONCLUSION: Immune-associated acute ataxia is the main cause of pediatric acute ataxia, among which APCA is the most common phenotype. However, some immune-associated diseases, especially autoantibody-mediated disease, which has a higher recurrence rate and neurological sequelae account for an increasing proportion of pediatric acute ataxia. When children present with extracerebellar symptoms, abnormal cranial MRI or CSF results, and without prodromal infection, prudent differential diagnosis is recommended.

An atypical case of hypomagnesemia-induced cerebellar syndrome with literature review.

Cerebellar ataxia in adults is always a diagnostic challenge. One of the important causes of late-onset cerebellar ataxia is hypomagnesemia. Hypomagnesemia can have varied manifestations and is attributable to numerous causes. Identification of hypomagnesemia-induced cerebellar syndrome (HiCS) is important as it is reversible but often missed. HiCS has distinct clinical findings and characteristic magnetic resonance imaging (MRI) findings. HiCS presents with distinct clinical, biochemical, and neuroimaging findings, but it cannot be ruled out even in the absence of neuroimaging findings. This condition has to be treated promptly and meticulously to avoid precipitating any serious complications, and a strong suspicion is required for the diagnosis. The underlying cause should be evaluated and managed, as HiCS is a serious but potentially reversible disease with a good prognosis. We present a case of HiCS presenting with a characteristic history of recurrent ataxia, tremor, and vertigo that improved with treatment. Our patient was atypical, as there were no significant MRI findings attributable to hypomagnesemia. Only seven case reports are available throughout the world that show such disparity.

[A case of Seizure-related 6 homolog like 2 (Sez6l2) antibody-associated autoimmune cerebellar ataxia].

A 35-year-old male patient had been repeatedly involved in car accidents since the age of 34 years, had difficulty in tidying his room, and developed speech and gait disorders. At the first examination, he had a hypophonia and poor gait, but he could talk and walk by himself. His Mini-Mental State Examination (MMSE) score was 23 and mild cognitive impairment was observed. Three months later, neurological findings showed subacute progression to loss of speech, and poor right dominant diadochokinesia and finger tapping, poor finger-nose test and heel-knee test, and loss of ability to stand and walk. Cerebellar atrophy was observed on head MRI, and the patient was positive for Seizure-related 6 homolog like 2 (Sez6l2) antibody, leading to a diagnosis of Sez6l2 antibody-associated autoimmune cerebellar ataxia. Immunotherapy halted the progression of symptoms, and the patient showed slight improvement. Sez6l2 antibody measurement and immunotherapy were considered necessary for subacute progressive cerebellar ataxia of unknown cause.

Ataxia cerebelosa aguda y COVID-19: presentación de un caso clínico / Ataxia cerebelosa aguda y COVID-19: presentación de un caso clínico

COVID-19 es una enfermedad viral principalmente respiratoria y/o gastrointestinal. Las manifestaciones neurológicas tienen una frecuencia variable en pediatría. Presentamos un varón de 10 años de edad, previamente sano, que presentó una ataxia cerebelosa durante un cuadro agudo de COVID-19. El SARS-CoV-2 fue detectado por hisopado nasofaríngeo por antígeno y RPC. El LCR fue normal y el cultivo bacteriológico y estudio viral fueron negativos. La TC y RM encefálica fueron normales. No requirió tratamiento específico y tuvo una evolución favorable, con resolución completa de los síntomas neurológicos al mes. Debe considerarse la infección por SARS-CoV-2 como un diagnóstico diferencial entre las causas de ataxia cerebelosa aguda, según la situación epidemiológica.

COVID-19 is a disease that mainly produces respiratory and/or gastrointestinal symptoms. Neurological manifestations occur with a variable frequency in children. We present a previously healthy 10-year-old boy who presented acute cerebellar ataxia during an acute COVID-19. SARS-CoV-2 was detected in a nasopharyngeal sample by antigen and PCR. The CSF was normal, the bacteriological culture and the viral PCR were negative. CT of the brain and gadolinium MRI of the brain were normal. He did not require specific treatment and had a favorable evolution, with complete resolution of neurological symptoms at one month. SARS-CoV-2 infection should be considered as a differential diagnosis between the causes of acute cerebellar ataxia, according to the epidemiological situation.

Immune-mediated ataxias: Guide to clinicians.

Immune-mediated cerebellar ataxias were initially described as a clinical entity in the 1980s, and since then, an expanding body of evidence has contributed to our understanding of this topic. These ataxias encompass various etiologies, including postinfectious cerebellar ataxia, gluten ataxia, paraneoplastic cerebellar degeneration, opsoclonus-myoclonus-ataxia syndrome and primary autoimmune cerebellar ataxia. The increased permeability of the brain-blood barrier could potentially explain the vulnerability of the cerebellum to autoimmune processes. In this manuscript, our objective is to provide a comprehensive review of the most prevalent diseases within this group, emphasizing clinical indicators, pathogenesis, and current treatment approaches.

[Acute cerebellar ataxia in Griscelli syndrome type 2]. / Ataxia cerebelosa aguda en el síndrome de Griscelli de tipo 2.

TITLE: Ataxia cerebelosa aguda en el síndrome de Griscelli de tipo 2.

Novel paraneoplastic mechanism for cerebellar ataxia in Erdheim-Chester disease.

We report a case of BRAF-mutation positive Erdheim-Chester disease presenting with a cerebellar ataxia. This is the first such case to be reported without structural MRI abnormalities but with a single intrathecally produced oligoclonal band. Now that the histiocytoses have been recharacterised as neoplastic, we speculate that the mechanism of the ataxia in our case is paraneoplastic. We highlight the importance of searching for BRAF mutations in this disease, as their presence leads to effective personalised treatments.

Efficacy and safety of noninvasive brain stimulation for patients with cerebellar ataxia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: With the development of noninvasive brain stimulation (NIBS) techniques, many researchers have turned their attention to NIBS as a promising treatment for cerebellar ataxia. Therefore, we conducted a systematic review and meta-analysis to investigate the efficacy and safety of NIBS in treating patients with cerebellar ataxia. METHODS: Databases, including PubMed, Embase, Web of Science, Medline, and Cochrane Library, were retrieved for relevant randomized controlled trials (RCTs). Two researchers conducted literature screening, data extraction, literature quality assessment, and heterogeneity analysis between RCTs. According to the magnitude of heterogeneity I2, an appropriate data analysis model was selected for meta-analysis. RESULTS: A total of 14 RCTs including 406 patients with cerebellar ataxia met the inclusion criteria. The included RCTs had an overall low-risk bias and an intermediate level of evidence recommendation for key outcome indicators, such as the scale for the assessment and rating of ataxia (SARA) and international cooperative ataxia rating scale (ICARS). The results of meta-analysis showed that cerebellar NIBS, including transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), was effective in reducing the SARA scores (MD = - 3.45, 95%CI = [- 4.85, - 2.50], P < 0.05) and ICARS scores (MD = - 10.87, 95%CI = [- 14.46, - 7.28], P < 0.05) in patients with cerebellar ataxia compared to controls. Subgroup analysis showed that the efficacy of tDCS and rTMS was statistically different in patients with cerebellar ataxia as assessed by the SARA scores, but not by the ICARS scores. There was statistically significant difference in the efficacy of NIBS for the treatment of cerebellar ataxia caused by different etiologies. As for safety, 8 of 14 included studies documented the adverse effects of NIBS, and only two studies reported the mild adverse events of NIBS. CONCLUSIONS: Cerebellar NIBS was safe and effective in improving the motor coordination of patients with cerebellar ataxia, and tDCS was better than rTMS in the treatment of cerebellar ataxia. In addition, the efficacy of NIBS was different in the treatment of different types of cerebellar ataxia.

Pediatric de novo movement disorders and ataxia in the context of SARS-CoV-2.

OBJECTIVE: In the fourth year of the COVID-19 pandemic, mortality rates decreased, but the risk of neuropsychiatric disorders remained the same, with a prevalence of 3.8% of pediatric cases, including movement disorders (MD) and ataxia. METHODS: In this study, we report on a 10-year-old girl with hemichorea after SARS-CoV-2 infection and immunostained murine brain with patient CSF to identify intrathecal antibodies. Additionally, we conducted a scoping review of children with MD and ataxia after SARS-CoV-2 infection. RESULTS: We detected antibodies in the patient's CSF binding unknown antigens in murine basal ganglia. The child received immunosuppression and recovered completely. In a scoping review, we identified further 32 children with de novo MD or ataxia after COVID-19. While in a minority of cases, MD or ataxia were a symptom of known clinical entities (e.g. ADEM, Sydenham's chorea), in most children, the etiology was suspected to be of autoimmune origin without further assigned diagnosis. (i) Children either presented with ataxia (79%), but different from the well-known postinfectious acute cerebellar ataxia (older age, less favorable outcome, or (ii) had hypo-/hyperkinetic MD (21%), which were choreatic in most cases. Besides 14% of spontaneous recovery, immunosuppression was necessary in 79%. Approximately one third of children only partially recovered. CONCLUSIONS: Infection with SARS-CoV-2 can trigger de novo MD in children. Most patients showed COVID-19-associated-ataxia and fewer-chorea. Our data suggest that patients benefit from immunosuppression, especially steroids. Despite treatment, one third of patients recovered only partially, which makes up an increasing cohort with neurological sequelae.

Hypomagnesemia, a Rare Cause of Reversible Ataxia.

Background: A 61-year-old male patient presented with cerebellar syndrome, which had progressively worsened for 10 days, followed by a tonic-clonic seizure. Phenomenology Shown: Blood analysis showed severe hypomagnesemia and a brain MRI showed T2 hyperintensity in the cerebellar hemispheres (Figure 1). Therefore, the final diagnosis was cerebellar syndrome and epileptic seizures secondary to severe hypomagnesemia. Educational Value: In cases of subacute onset of ataxia, the possibility of ataxia secondary to hypomagnesemia should be considered, as it can be diagnosed with a basic blood test and there are potentially life-threatening outcomes in the absence of treatment, with a reversible course following early supplementation.