COVID-19-Associated Cerebellitis: A Case Report and Rehabilitation Outcome.

INTRODUCTION: The COVID-19 pandemic has brought attention to neurological complications, including cerebellitis, characterized by inflammation of the cerebellum. Despite its rare occurrence, cerebellitis has been associated with COVID-19 infection, albeit the pathogenic mechanisms remain unclear. CASE REPORT: We present the case of a 22-year-old male with acute onset ataxia and dysarthria during a SARS-CoV-2 infection. Diagnostic evaluations ruled out other causes, confirming cerebellitis. Treatment included steroid therapy, vitamin supplementation, physiotherapy, and intravenous immunoglobulins. Rehabilitation focused on enhancing balance, coordination, and daily activities. The patient showed significant improvement in functional abilities, with increased autonomy in daily activities and improved ambulation. Despite persistent mild symptoms, the multidisciplinary rehabilitation approach led to remarkable progress. CONCLUSIONS: This case underscores the importance of recognizing and managing neurological complications, such as cerebellitis, in COVID-19 patients. A comprehensive approach combining medical treatment and rehabilitation is essential for optimizing outcomes. Further research is needed to elucidate the pathogenesis and optimal management strategies for such complications.

Acute Cerebellar Manifestations without Limbic Involvement in GABAB Receptor Autoimmune Encephalitis: Case Report and Literature Review.

Autoimmune encephalitis is a rapidly progressive inflammatory brain disease. Gamma-aminobutyric acid type B (GABAB) receptor autoimmune encephalitis is a rare subtype characterized by distinct clinical features. Diagnosis can be especially challenging when typical limbic symptoms and neuroimaging findings are absent. This case report underscores the importance of identifying this condition and starting immunosuppressive treatment promptly. A 59-year-old man presented with gait disturbances, dysarthria, and severe ataxia without cognitive impairment. Initial examinations, including a brain MRI, were unremarkable, except for an elevated cell count and protein in the cerebrospinal fluid. Despite receiving initial empirical antiviral treatment, his symptoms worsened, prompting the administration of intravenous methylprednisolone and immunoglobulin. After these immunosuppressive therapies, the cerebellar symptoms showed gradual improvement. Subsequent testing for antibodies to the GABAB receptor was positive in both the serum and cerebrospinal fluid. Follow-up MRI revealed cerebellar atrophy, consistent with a diagnosis of GABAB receptor-associated acute cerebellitis. This case illustrates that cerebellar symptoms can occur in the absence of more common limbic manifestations in GABAB receptor autoimmune encephalitis. The progression of cerebellar atrophy following an initially normal MRI is a significant finding that offers supporting evidence for the diagnosis of cerebellitis. A review of the literature identified similar cases of acute cerebellitis without limbic symptoms, although neuroimaging abnormalities in the cerebellum were not reported. Our case underscores the importance of increased clinical awareness and consideration of autoimmune causes, even when neuroimaging appears normal. Early and appropriate immunosuppressive therapy may help change the course of the disease and enhance patient outcomes.

A rare case of acute cerebellitis due to enterovirus treated with therapeutic plasma exchange: Case report and review of the literature.

BACKGROUND: Acute cerebellitis is a rare complication of pediatric infections. There are many reports that viral infections lead to neurological manifestations, including acute cerebellitis. METHODS: A retrospective chart review was conducted for pediatric patients diagnosed with enterovirus cerebellitis between 2000 and 2024. The methods involved reviewing clinical and radiological records and assessing the treatment methods. RESULTS: Case Report We present the case of a 4-year-old immunocompetent child who initially presented with acute encephalopathy followed by truncal ataxia, and eventually received a diagnosis of postinfectious cerebellitis. Enterovirus real-time polymerase chain reaction were positive in the nasopharyngeal swab. Therapeutic plasma exchange (TPE) was started due to neurological deterioration despite IVIG treatment. She improved significantly with TPE, and methylprednisolone treatment and was discharged in good health status. The patient is being followed up as neurologically normal. CONCLUSION: Acute cerebellitis associated with enterovirus is a rare pediatric disorder. Early diagnosis and treatment with TPE in this severe case is thought to be preventive for the potentially fatal complications.

Septin-3 autoimmunity in patients with paraneoplastic cerebellar ataxia.

BACKGROUND: Septins 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. METHODS: Sera 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. RESULTS: Immunoprecipitation 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. CONCLUSIONS: Septin-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.

Immune-mediated cerebellitis following SARS-CoV-2 infection-a case report and review of the literature.

The coronavirus disease 2019 (COVID-19) can be associated with a wide variety of neurological manifestations. Some of these manifestations might result from the ongoing systemic inflammatory state, but the pathophysiology of specific neurologic involvement is still unclear. In this article, we report a patient who developed an isolated cerebellar syndrome 9 weeks after an episode of COVID-19. The reverse-transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 was positive on cerebrospinal fluid (CSF). A post-infectious-autoimmune-cerebellitis following COVID-19 was suspected, and the patient was treated with corticosteroids, leading to a complete recovery within a few weeks. We review the other cases of COVID-19-associated cerebellar syndrome reported so far and discuss the potential pathophysiological mechanisms underlying this neurologic manifestation.

Acute cerebellitis following COVID-19 infection associated with autoantibodies to glutamate receptors: a case report.

While COVID-19 infection by the SARS-CoV-2 virus was initially identified as a respiratory disease, mounting evidence suggests its association with various neurological issues as well. Notably, COVID-19 has been linked to acute cerebellitis (AC) and post-infectious cerebellar ataxia. The precise underlying mechanisms behind these neurological effects remain unclear. Our case report describes AC following COVID-19 infection, associated with autoantibodies to glutamate receptors (GluRs), hinting at immunological involvement. The case is a 56-year-old woman who experienced fever and fatigue due to COVID-19 infection. About 2 weeks after these symptoms improved, she showed cerebellar symptoms such as ocular overshoot and ataxia when presenting to our hospital. Her cerebrospinal fluid (CSF) findings were normal. Brain MRI revealed cerebellar abnormalities. Treatment with methylprednisolone led to symptom improvement. Later tests of CSF yielded positive results for autoantibodies to GluRs. Our findings suggest a possible immune-mediated mechanism in the onset of AC following COVID-19 infection. Clinicians should consider the possibility of immunological pathogenesis when diagnosing cerebellar symptoms after COVID-19 infection.

"The Red Flags" in Clinical Approach to Acute Ataxia-the Experience in Cohort of 76 Children.

The aim of our study is to define the most frequent etiology, clinical presentation, and predictive factors of outcome in children with acute ataxia (AA) and to determine "the red flags" in the diagnostic approach to children with AA. The retrospective study included the patients with AA treated in the institute from 2015 to 2021. The inclusion criteria were children aged 1-18 years, evolution time of ataxia within 72 h, and diagnosis made by a physician. The exclusion criteria were anamnestic data about ataxia without confirmation by any physician, chronic/persistent ataxia, and psychogenic or postictal ataxia. Clinical presentation was divided into two categories: (1) isolated cerebellar signs (CS): ataxic gait, dysmetria, dysdiadochokinesia, intention tremor, dysarthria, and nystagmus; (2) CS-plus symptoms which included CS associated with any of other symptoms such as encephalopathy (GCS < 15), awareness disturbances, vomiting, headache, a new onset limb or facial paresis, torticollis, hypotonia, and opsoclonus. The outcome was assessed at the end of hospitalization and was defined as complete or incomplete recovery. The study included 76 children, with a mean age of 5.7 years (IQR 2.1-8.3). The most frequent causes of AA were immune-mediated/infective cerebellar ataxia in 27 (35.5%), and intoxication in 24 (31.6%) cases, followed by vestibular ataxia, opsoclonus-myoclonus-ataxia syndrome, and intracranial expansive process. Forty-two (56%) cases experienced isolated CS, and 35 (46%) cases had CS-plus. Complete recovery was experienced by 62 (81.6%) patients. Analysis of some risk factors (sex, age, presence of previous infection, "cerebellar plus symptoms," and structural abnormalities/neuroimaging abnormalities) and their relation to outcome was performed. Analysis showed that presence of additional symptoms to ataxia, so called "cerebellar plus symptoms" (p = 0.002) and structural abnormalities (p < 0.001), had statistically higher frequency of poor outcome. Statistical significance remained in the univariate analysis. Significant data was included in multivariate logistic regression analysis which also showed that presence of "cerebellar plus symptoms" (p = 0.021) and structural abnormalities (p = 0.002) is related to a poor outcome. Most of the children with AA have "benign" etiology such as intoxication and post/parainfectious cerebellar ataxia with favorable outcomes. On the other hand, AA might be the first manifestation of CNS neoplasm or paraneoplastic phenomena. "The red flags" associated with cerebellar signs are limbs or facial palsy, hypotonia, GCS < 15, vomiting, opsoclonus, headache, myoclonus, visual impairment, torticollis, and vertigo. The presence of those signs and/or structural brain abnormalities was related to poor outcomes in children with AA.

A Novel Radiological Score System to Assess the Clinical Severity in Patients with Acute Cerebellitis.

To develop a radiological score system to assess the severity of acute cerebellitis (AC) and to compare radiological severity score at the onset to cerebellar atrophy at follow-up. Clinical and MRI findings were recorded in 16 patients with AC. Radiological severity score considering topographic patterns, gray/white matter involvement, enhancement, tonsillar herniation or hydrocephalus development and clinical severity score taking into account clinical symptoms were assessed for each patient at the onset of the symptoms. Radiological and neurological sequelae were assessed at follow-up. At symptoms onset, clinical severity scale ranged from mild to severe and radiological severity score ranged from 3 to 7 with higher scores indicating a greater severity. The cut-off value of 5 for radiological score well segregated severe patients defined by clinical scale. A significant correlation between clinical scale and radiological severity scores (p < 0.001, r = 0.75) was found. At follow-up visit, all children developed cerebellar atrophy and 5 children showed neurologic sequelae while adults showed complete resolution without atrophy. Patients in whom atrophy was not observed had both older ages (p < 0.001) and a focal cerebellar involvement (p = 0.03). In patients with AC, radiological severity score may be a useful tool in evaluating clinical severity, but it is not capable to predict neither neurological sequelae nor evolution towards atrophy. Cerebellar atrophy, observed in children with AC, may be caused by several factors such as the age of patient and the extension of cerebellar involvement and it may be counterbalanced by neuronal restoring processes due to neuroplasticity.

Cerebellar involvement associated with immune checkpoint inhibitors: A systematic review.

BACKGROUND AND PURPOSE: Immune checkpoint inhibitors (ICIs) targeting programmed death receptor 1 (PD-1), cytotoxic T-lymphocyte-associated-4 (CTLA-4) and programmed cell death ligand 1 can be associated with immune-related adverse events (iRAEs). Amongst neurological iRAEs, cerebellar involvement seems to be rare and currently lacks a proper characterization. The aim of this study was to phenotype cerebellar iRAEs. METHODS: A systematic review was performed according to PRISMA guidelines including reported patients with cerebellar involvement related to ICIs and with available individual data. RESULTS: After screening 2765 records, 32 studies with 46 patients were included. Median age was 63 years (20-82), and most patients were male (63.0%). Isolated cerebellitis was observed in 32.6% of cases, whilst the remaining cases had "cerebellitis plus", mostly associated with encephalitis/encephalopathy. Associated tumors included most frequently lung cancer, melanoma and Merkel cell carcinoma. PD-1 inhibitor was the most administered treatment (n = 29, 64.4%), whilst exposure to CTLA-4 inhibitor was rare (n = 2, 4.5%). Magnetic resonance imaging was abnormal in 43.2% of patients and inflammatory cerebrospinal fluid findings were frequently observed. Autoantibodies were detected in 61.9% of patients and included novel reactivities. Amongst treatment strategies, the most common were steroids (n = 36) and ICI discontinuation (n = 28, 90.3%). Relapses were reported in 10% of patients. Most patients showed improvement/remission (n = 31) but, at last follow-up, 12 had died. Isolated cerebellitis versus cerebellitis-plus differed in terms of outcomes, whilst seropositive versus seronegative patients had distinct tumor associations. DISCUSSION: Cerebellar iRAEs are usually multifocal, have heterogeneous tumor associations, are most associated with PD-1 inhibitor exposure and are related to autoantibodies, including novel reactivities.

Fatal fentanyl-associated cerebellitis in a young man.

A 22-year-old man was brought in by EMS for coma and respiratory failure. The initial diagnosis was an opioid overdose but the patient did not respond to naloxone. A head CT revealed findings consistent with cerebellitis. The patient developed obstructive hydrocephalus and herniation. Despite neurosurgical and ICU care, the patient did not recover. Cerebellitis is a seldom-discussed complication of opioid use which may become more common as the opioid and fentanyl epidemic evolves.

Neurological complications of rotavirus infection in children: A systematic review and meta-analysis.

AIM: To systematically review the clinical features and outcomes of paediatric patients developing neurological complications associated with a rotavirus infection. METHODS: A systematic literature review and meta-analysis was performed, including articles published from 1984 to 2020. Neurological complications were classified into four groups: encephalitis, cerebellitis, encephalo-cerebellitis and benign convulsions with mild gastroenteritis (CwG). RESULTS: Out of 68 reports that fulfilled the research criteria, 99 cases of CwG, 39 cases of encephalitis, 18 cases of encephalo-cerebellitis and five cases of cerebellitis were collected. Ninety-five patients were from Asia. Median age was 22 (IQR 14-29) months, and the children who developed CwG were significantly younger (19, IQR 12-24 months, p < 0.0001) than the others. Status epilepticus was observed in 23% and 5% of the encephalitis and CwG groups respectively. The most frequently described neuroimaging finding were lesions of the splenium of corpus callosum. Four deaths were reported in the encephalitis group, whereas no fatal events were described in the other groups. Among the surviving children, the encephalo-cerebellitis group showed the most severe long-term outcome. All cases of CwG recovered completely. CONCLUSION: Older age at diagnosis and the development of encephalo-cerebellitis are associated with a higher risk of long-term complications.

Central nervous system manifestations of dengue infection: data from a tertiary care Centre in South India.

BACKGROUND: Dengue fever is the second most common mosquito-borne disease affecting human beings and neurological manifestations (NMs) of this arboviral infection are increasingly being reported. METHODS: In this retrospective study, conducted in a tertiary care centre in south India, we sought to describe the spectrum of NMs of dengue fever. The records of all patients admitted in the Department of Internal Medicine over 8 years, with a diagnosis of dengue-based on clinical symptoms and the detection of dengue IgM antibodies or detection of NS1 antigen or nucleic acid by reverse transcriptase-polymerase chain reaction (RT-PCR); with Glasgow coma score (GCS) ≤14, neck stiffness, focal neurological signs, seizures, or visual disturbances-were explored. RESULTS: Of 1121 patients admitted with dengue fever, 341 (30%) had severe dengue and 23 (2%) had NMs. Encephalopathy was seen in 9 patients (39%), encephalitis in 6 (27%), cerebellitis in 4 (17%), acute disseminated encephalomyelitis (ADEM) in 2 (9%), ischaemic stroke in 1 (4%) patient, and neuro-ophthalmological manifestations in 1 (4%) patient. The median duration of hospital stay was 7 days. Nine (39% of) patients required intensive care unit (ICU) admission and 5 (22%) had fatal outcomes. There was no association between thrombocytopenia, metabolic acidosis, transaminitis, hyponatremia, the type of dengue infection, and the various NMs described. CONCLUSIONS: The NMs of dengue infection are varied, and a high index of suspicion is needed to identify them in patients who present with lethargy or altered sensorium on the background of an acute febrile illness suggestive of dengue.

CD8 T-cell-mediated cerebellitis directed against Purkinje cell antigen after ipilimumab for small cell lung cancer.

We report a rapidly progressive and fatal CD8 T-cell-mediated cerebellitis after ipilimumab (cytotoxic T-lymphocyte-associated protein 4 inhibitor) for small cell lung cancer. Clinical features and histopathology were consistent with an accelerated form of paraneoplastic cerebellar degeneration. A patchy CD8 T-cell infiltrate spatially corresponded to areas of Purkinje cell loss, with occasional CD8 polarisation towards Purkinje cells. CD20-positive B cells were sparse. CD8 T-cell-mediated cerebellitis after immune checkpoint inhibitor treatment may recapitulate the early stages of paraneoplastic cerebellar degeneration.

Acute Coxsackievirus B3-induced meningo-cerebellitis in an immunocompetent adult patient.

We report an acute Coxsackievirus B3 (CVB3)-induced meningo-cerebellitis in an immunocompetent adult patient. CVB3 has a global distribution and is the most common Enteroviruses cause of myocarditis and sudden cardiac death. To our knowledge, CVB3 is exceedingly rare as causes of meningo-encephalitis in immunocompetent adults, whereas some cases have been reported in neonates due to perinatal acquired infections or in immunocompromised patients.

Acute cerebellitis following SARS-CoV-2 infection: A case report and review of the literature.

Novel coronavirus disease (COVID-19) first described in Wuhan, China in December 2019, has rapidly spread across the world and become a global public health emergency. Literature on the neurological manifestations of COVID-19 is limited. We report a 24-year-old male, who presented with vertigo, dysarthria, and bradyphrenia 3 weeks after being diagnosed with COVID-19 on nasopharyngeal reverse transcription polymerase chain reaction. The patient was diagnosed with acute cerebellitis based on magnetic resonance imaging features and showed improvement posttreatment with intravenous methylprednisone for 5 days. The scope of this article is to highlight the importance of early identification of neurological symptoms and timely management as the outcomes may be catastrophic.

Anti-GAD associated post-infectious cerebellitis after COVID-19 infection.

The coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread rapidly all over the world. Besides severe pneumonia, it causes multisystemic disease, including neurological findings. Here, we present a patient with anti-glutamic acid decarboxylase (anti-GAD) antibody-associated cerebellitis developed after COVID-19 infection. The patient responded well to the immune treatments. Our knowledge about SARS-CoV-2 infection-related neurological disorders is limited. New data are needed to recognize the clinical spectrum of autoimmune neurological disorders that emerges after SARS-CoV-2 infection.

Acute Cerebellar Ataxia in COVID-19 Infection: A Case Report.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has been widely reported to cause symptoms such as fever, cough, sore throat, fatigue, and shortness of breath. Neurologic complications have not been widely reported without associated respiratory symptoms. These neurologic manifestations have been found mostly in the elderly. There has been no report of ataxia or COVID-19 cerebellitis in the young adult population without associated respiratory symptoms. CASE REPORT: Here we report the case of a 30-year-old patient who presented with isolated cerebellar symptoms and was diagnosed with COVID-19 cerebellitis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is important for emergency physicians to know that COVID-19 can have many clinical manifestations and to have a high level of suspicion with acute neurologic symptoms.

Herpes simplex virus-1 as a rare etiology of isolated acute cerebellitis: case report and literature review.

Acute cerebellitis is one of the most common cerebellar disorders and occurs due to para-infectious, post-infectious, or post-vaccination cerebellar inflammation. Herpes simplex virus-1 (HSV-1) is known as a common infectious cause of sporadic encephalitis. Cerebellar involvement of HSV-1 is rare and almost always associated with meningoencephalitis. To date, HSV-1 has been identified as the cause of acute isolated cerebellitis in only two patients. Here we report another case of isolated acute cerebellitis caused by HSV-1 in a 20-month-old boy.

A First Case of Acute Cerebellitis Associated with Coronavirus Disease (COVID-19): a Case Report and Literature Review.

Novel coronavirus (severe acute respiratory syndrome-coronavirus-2: SARS-CoV-2), which originated from Wuhan, China, has spread to the other countries in a short period of time. We report a 47-year-old male who was admitted to our hospital due to suffering from progressive vertigo and ataxia for 7 days prior to the admission. Neurological examination revealed cerebellar dysfunction, and brain magnetic resonance imaging (MRI) depicted edema of the cerebellar hemisphere associated with leptomeningeal enhancement. Cerebrospinal fluid (CSF) analysis showed mild lymphocytic pleocytosis, elevated protein, and lactate dehydrogenase. SARS-CoV-2 RNA was detected in the oropharyngeal/nasopharyngeal and CSF specimens. As a result, treatment with lopinavir/ritonavir was initiated, and patient symptoms and signs improved significantly during the course of hospitalization. To the best of our knowledge, this is the first case of acute cerebellitis associated with COVID-19 disease which is reported in the literature so far.

A case of fulminant Epstein-Barr virus encephalitis in an immune-competent adult.

A 21-year-old female presented with headache, nausea and vomiting, dysarthria, difficulty finding words, vertigo, episodical diplopia and an abnormal gait since 2 days. Additionally, we found marked ataxia and disturbed liver chemistry whilst her infection parameters were low. Her head CT scan was unremarkable, but her MRI scan showed leptomeningeal enhancement along the cerebellar folia. A lumbar punction revealed mononuclear leucocytosis and increased protein in her cerebrospinal fluid. She was admitted on a working diagnosis of herpes simplex encephalitis. Shortly after admission, she had a generalised seizure. She was tested for a wide range of viruses, bacteria and auto-immune antibodies and treated empirically with aciclovir, ceftriaxone, doxycycline and intravenous immunoglobulins. All tests continued to come back negative until the fifth day of admission, when repeat Epstein-Barr virus (EBV) serology showed evidence of an acute EBV infection, even though negative tests were acquired at admission. EBV encephalitis is a rare complication of EBV infection that is usually restricted to children and immune-compromised individuals. This is only the fifth case describing EBV encephalitis in an immune-competent adult, presenting with unique clinical features including a lack of fever and leptomeningeal enhancement on MRI investigation. Most interestingly, she tested negative for EBV until a few days after admission, underlining the need for repeated investigations in suspected virological encepahlitis. Even though our patient did not receive the often recommended glucocorticosteroids, she made a good neurological recovery.