Acute cerebellar ataxia and consecutive cerebellitis produced by glutamate receptor delta2 autoantibody

Acute cerebellar ataxia is usually a self-limited benign disease, which may develop in children after certain viral infections or vaccinations. There are several reports of acute cerebellar ataxia associated with autoantibodies. Glutamate receptor delta2, a member of the glutamate receptor family, is predominantly expressed in cerebellar Purkinje cells and plays a crucial role in cerebellar functions. To date anti-GluRdelta2 autoantibody was detected in a patient with chronic cerebellitis. Herein, an 18-month-old boy presented with cerebellar ataxia 9 days following a mild respiratory tract infection. Although cerebellar ataxia gradually improved, it worsened yet again following mumps and varicella virus infection. Cerebro-spinal fluid examination and magnetic resonance imaging of the brain demonstrated pleocytosis and meningeal enhancement, respectively. Furthermore, glutamate receptor delta2 autoantibody was detected in serum and cerebro-spinal fluid. Thus, we believe that the glutamate receptor delta2 autoantibody may play a role in cerebellar ataxia and consecutive cerebellitis.     

Mumps-induced opsoclonus-myoclonus and ataxia

A 9-year-old boy manifested acute cerebellar ataxia associated with mumps infection. He developed opsoclonus, myoclonus, tremor, and truncal ataxia 7 days after mumps infection. Lumbar puncture revealed pleocytosis without elevation of protein; ELISA demonstrated an increased IgM titer of cerebrospinal fluid against mumps virus. From these results it was determined that acute cerebellar ataxia was induced by a direct invasion of mumps virus. Electroencephalography demonstrated normal background activity, although alpha-like activity appeared bilaterally in the frontal regions which was induced by eye closure and decreased by eye opening. Polygraphic electroencephalography revealed that the alpha-like activity corresponded to the ocular movement recorded above or lateral to the eyelids by electro-oculography; therefore, the alpha-like activity was considered to be derived from the opsoclonus which was secondary to cerebellar involvement. His neurologic symptoms improved gradually and resolved completely within 3 months after the onset of acute cerebellar ataxia.     

Epstein-Barr Virus Antibodies in Neurological Diseases

Abstract: Antibody titers to the Epstein-Barr virus (EBV) in the serum and cerebrospinal fluid (CSF) were determined in 57 cases of acute or subacute neurological diseases. As a result, sera from 11 cases (7 Bell's palsy, 2 encephalitis and 2 acute cerebellar ataxia) were found to be positive for antibodies to early antigen. Seven of these 11 cases either seroconverted for IgG antibodies to viral capsid antigen (VCA) or were proven positive for anti-VCA-IgM antibodies in the serum. While 4 were found positive for IgG antibodies to VCA in CSF, 3 tested by the anti-complement immunofluorescence method were all negative for EBV-associated nuclear antigen (EBNA) in CSF. Three of the 11 cases were considered to be of a primary infection with EBV because of a negative serologic test for antibodies to EBNA initially; a reinfection with the virus or a reactivation of the latent infection was suspected in some of the remaining cases.     

Autoantibodies in childhood post-varicella acute cerebellar ataxia

BACKGROUND: Anti-Purkinje cell antibodies have been reported in cerebellar ataxia following Epstein-Barr virus (EBV) infection. We investigated autoantibody responses, including anti-Purkinje cell antibodies, and the clinical course in eight children who developed post-varicella ataxia, five of their siblings with uncomplicated varicella, one child with post-EBV ataxia, two children with acute disseminated encephalomyelitis (ADEM) and one with neuroblastoma associated ataxia, and in age and gender matched controls. METHODS: Autoantibodies were tested by indirect immunofluorescence (IIF) on cryopreserved cerebrum and cerebellum sections. Other autoantibodies were measured by conventional IIF protocols using HEp-2 cells as a substrate. Antibodies to myelin associated glycoprotein (MAG), asialo-GM1, beta2 glycoprotein 1, cardiolipin and myelin basic protein (MBP) were measured by ELISA. RESULTS: Three of eight children with acute post-varicella ataxia, one child with post-EBV ataxia, one child with ADEM and one child with uncomplicated varicella, had high titer autoantibodies (>1/160) that reacted with cerebrum and cerebellar tissue. This reactivity was not seen in one child with ADEM, in one with neuroblastoma and ataxia, in the remainder of the children with uncomplicated varicella or age and gender matched controls. Autoantibodies were not seen in CSF from two children with post-varicella ataxia. The punctate staining seen on cerebrum and cerebellum sections co-localized with rabbit antibodies to the centrosome protein pericentrin. All patients with strong reactivity with cerebrum and cerebellar tissue by IIF had elevated levels of anti-MAG that was not confirmed by absorption assay. No reactivity was seen with asialo-GM1, MBP, beta2 glycoprotein 1 or cardiolipin. None of the sera had autoantibodies directed against endosomes, the Golgi complex, or the paraneoplastic autoantigens Hu and Yo. CONCLUSION: Some children with post-viral ataxia develop antibodies that have strong reactivity with cerebral and cerebellar tissue. Some of the antigenic reactivity co-localized with the centrosome protein pericentrin.     

Epstein-Barr virus antibodies in neurological diseases

Antibody titers to the Epstein-Barr virus (EBV) in the serum and cerebrospinal fluid (CSF) were determined in 57 cases of acute or subacute neurological diseases. As a result, sera from 11 cases (7 Bell's palsy, 2 encephalitis and 2 acute cerebellar ataxia) were found to be positive for antibodies to early antigen. Seven of these 11 cases either seroconverted for IgG antibodies to viral capsid antigen (VCA) or were proven positive for anti-VCA-IgM antibodies in the serum. While 4 were found positive for IgG antibodies to VCA in CSF, 3 tested by the anti-complement immunofluorescence method were all negative for EBV-associated nuclear antigen (EBNA) in CSF. Three of the 11 cases were considered to be of a primary infection with EBV because of a negative serologic test for antibodies to EBNA initially; a reinfection with the virus or a reactivation of the latent infection was suspected in some of the remaining cases.     

Guillain-Barré syndrome and hemophagocytic lymphohistiocytosis in a patient with severe chronic active Epstein–Barr virus infection syndrome

Epstein–Barr virus (EBV) infection causes a wide range of neurologic and hematologic manifestations. We report a 72-year-old Japanese male patient with severe chronic active EBV infection syndrome (SCAEBV) who presented with Guillain-Barré syndrome (GBS) and developed hemophagocytic lymphohistiocytosis (HLH) several months after the onset of GBS. He showed acute onset of distal muscle weakness, ophthalmoplegia and bulbar palsy. Results of nerve conduction study revealed acute motor-sensory axonal neuropathy (AMSAN). His serum was positive for anti-LM1 IgG and anti-GM1b IgM. Titers of antibodies to EBV-related antigens indicated chronic reactivated EBV infection. Treatment with IVIg resolved the acute ophthalmoplegia, but there was no notable improvement in the AMSAN and bulbar palsy despite repeated. Finally, he developed refractory HLH resulting in a fatal outcome. In the present patient, it seems that SCAEBV was associated with the development of GBS and fatal HLH via parainfectious autoimmunity and direct infectious immune mechanisms, respectively.     

An unusual presentation of varicella zoster virus with acute cerebellitis and SIADH without a rash

We report a case of varicella-zoster virus (VZV) infection with acute cerebellitis and encephalitis with associated Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in an elderly man presenting with acute cerebellar ataxia without antecedent rash. Cerebrospinal fluid examination (CSF) revealed a mononuclear pleocytosis, high protein, normal glucose, positive for VZV polymerase chain reaction (PCR). Early acyclovir treatment is beneficial for acute VZV cerebellitis. Clinicians should consider infectious Central Nervous System (CNS) causes for presentations of acute cerebellar ataxia in adult patients, particularly if there is an accompanying clouded sensorium.     

Guillain-Barré syndrome and hemophagocytic lymphohistiocytosis in a patient with severe chronic active Epstein-Barr virus infection syndrome

Epstein-Barr virus (EBV) infection causes a wide range of neurologic and hematologic manifestations. We report a 72-year-old Japanese male patient with severe chronic active EBV infection syndrome (SCAEBV) who presented with Guillain-Barré syndrome (GBS) and developed hemophagocytic lymphohistiocytosis (HLH) several months after the onset of GBS. He showed acute onset of distal muscle weakness, ophthalmoplegia and bulbar palsy. Results of nerve conduction study revealed acute motor-sensory axonal neuropathy (AMSAN). His serum was positive for anti-LM1 IgG and anti-GM1b IgM. Titers of antibodies to EBV-related antigens indicated chronic reactivated EBV infection. Treatment with IVIg resolved the acute ophthalmoplegia, but there was no notable improvement in the AMSAN and bulbar palsy despite repeated. Finally, he developed refractory HLH resulting in a fatal outcome. In the present patient, it seems that SCAEBV was associated with the development of GBS and fatal HLH via parainfectious autoimmunity and direct infectious immune mechanisms, respectively.     

JC virus granule cell neuronopathy in a child with CD40 ligand deficiency

JC virus infection of the brain typically causes progressive multifocal leukoencephalopathy, a demyelinating disease that rarely involves gray matter. This report presents a case of cerebellar degeneration associated with JC virus infection in a male with CD40 ligand deficiency resulting in hyperimmunoglobulin M type 1. This patient exhibited a progressive cerebellar ataxia with progressive atrophy of the cerebellar cortex in association with the presence of JC virus in the spinal fluid. JC virus infection should be considered in the differential diagnosis of ataxia in children with inherited immunodeficiencies.     

A case of chronic cerebellitis with anti-glutamate receptor delta 2 antibody

A 1-year-8-month-old patient developed cerebellar ataxia following a prodromal infection. Despite initial diagnosis of acute cerebellar ataxia, his symptoms lasted for more than 30 days. High-dose intravenous immunoglobulin and steroid pulse therapy failed to ameliorate his cerebellar symptoms, which fluctuated in association with infections. At the age of 3 years and 8 months, he had mental retardation with cerebellar symptoms. Findings of MR imaging and single photon emission computed tomography were normal. Neuron-specific enolase of cerebrospinal fluid (CSF) ranged from 10.4-17.6 ng/ml, correlating with the cerebellar symptoms. Serum and CSF anti-glutamate receptor delta 2 antibodies were detected in the serum and CSF. We diagnosed him as having chronic cerebellitis associated with anti-glutamate receptor delta 2 antibody.     

Biopsy‐proven case of Epstein–Barr virus (EBV)‐associated vasculitis of the central nervous system

A 75‐year‐old woman was admitted to our hospital with rapidly deteriorating consciousness disturbance. She had a 7‐year history of rheumatoid arthritis (RA), which had been treated with methotrexate (MTX) and prednisolone. Brain T2‐weighted MRI showed diffuse high‐intensity lesions in the cerebral subcortical and deep white matter, bilateral basal ganglia and thalamus. A cerebrospinal fluid examination revealed elevated protein levels and positive Epstein–Barr virus (EBV) DNA. Human immunodeficiency virus was negative. Brain biopsy showed perivascular lymphocytic infiltration in the parenchyma and meninx with EBV‐encoded small RNA (EBER). Since this case did not fulfill the criteria for chronic active EBV infection (CAEBV), she was diagnosed with Epstein–Barr virus (EBV)‐associated vasculitis of the central nervous system. High‐dose methylprednisolone, acyclovir, ganciclovir and foscarnet were not effective. Although EBV is a causative agent of infectious mononucleosis (IM), lymphomas and nasopharyngeal carcinomas, vasculitic pathology of the central nervous system with EBV reactivation in the elderly is rare. Immunosuppressive drugs such as steroids and MTX are widely used to treat autoimmune disorders, but may exacerbate the reactivation of EBV. This is the first case of biopsy‐proven EBV‐positive/HIV‐negative vasculitis during the treatment of RA with MTX and steroids. This case indicates that EBV‐associated vasculitis needs to be considered as a differential diagnosis of CNS vasculitis.     

A case of brainstem encephalitis associated with Epstein-Barr virus infection: differentiation of acute disseminated encephalomyelitis and Bickerstaff's brainstem encephalitis]

A 28-year-old woman initially suffered high fever and headache (day 1). Aseptic meningitis was diagnosed on day 3. Limb ataxia, however, appeared on day 7, and external ophthalmoplegia and drowsiness were recognized on day 8. Urinary disturbance and orthostatic hypotension appeared on day 13. Cerebrospinal fluid showed moderately high cell counts(mononuclear cells, 51/microliter; polynuclear cells, 9/microliter). MRI T2-weighted images showed high intensity lesions in the pons and mesencephalon. No serum anti-GQ1b IgG antibody was detected on day 4. Epstein-Barr virus (EBV) viral capsid antigen-IgG antibody was positive, and EBV determined nuclear antigen antibody was seroconverted. EBV-DNA was detected in the CSF by PCR. These findings indicate prior infection by EBV. After intravenous dexamethasone therapy, these symptoms rapidly disappeared. Our patient showed external ophthalmoplegia, ataxia, and disturbance of consciousness, which are the cardinal signs in Bickerstaff's brainstem encephalitis. The time course of her neurological symptoms, the presence of meningitis, and the MRI findings, however, indicated the pathogenesis of acute disseminated encephalomyelitis rather than Bickerstaff's brainstem encephalitis. We diagnosed this patient as a brainstem encephalitis associated with EBV infection.     

A case of cerebellar meningo-encephalitis caused by Epstein-Barr virus(EBV): usefulness of Gd-enhanced MRI for detection of the lesions]

We report a patient with cerebellar meningo-encephalitis by Epstein-Barr virus(EBV) in which the responsible lesions were detected by Gd-enhanced MRI. A 61-year-old woman with a history of liver cirrhosis and diabetes mellitus presented with cerebellar signs such as ataxia of the trunk, bilateral upper and lower extremities and slurred speech two weeks after the acute upper respiratory inflammation for several days. Serum IgM antibody(Ab) to EBV viral capsid antigen(VCA) was 1:10, Ab to EBV(VCA) IgG was 1:1280, Ab to early antigen diffuse and restricted (EADR) IgG was 1:40, Ab to EBV nuclear antigen (EBNA) was 1:80. Other viral antibody titers were not elevated significantly in serum. Cerebrospinal fluid (CSF) pressure was 195 mmH2O, containing 464 cells/mm3, protein 68 mg/dl and glucose 43 mg/dl. Only CFS Ab to EBV(VCA) IgG elevated significantly (1:16). In acute phase plain MRI was normal except for swelling of the cerebellar hemispheres while Gd-enhanced MRI showed a leptomeningeal enhancement of bilateral cerebellar hemispheres and of vermis disappeared within one month. A homogeneously enhanced lesion in the left dentate nucleus appeared one month after the onset of illness. This lesion had been detected on Gd-enhanced MRI for three months after clinical symptoms were improved. No abnormal finding was shown in the supratentorial region during the whole clinical course. In the literature, EBV encephalitis has a wide range of MR findings which may vary in a short period. We emphasize that frequent MR examinations including Gd-enhanced MRI is useful to evaluate inflammatory or demyelinating diseases in the posterior fossa.     

Benign acute ataxia in an adult with VZV infection

In adults, neurological complications of VZV virus usually occur after herpes zoster infection in patients with AIDS. We report a case of acute and benign cerebellar ataxia after chickenpox in a patient without immunodeficiency.     

GAD65抗体相关性小脑性共济失调一例报道及文献复习

目的探讨抗谷氨酸脱羧酶65(glutamic acid decarboxylase,GAD65)抗体相关性小脑性共济失调的临床表现、治疗及预后。方法报道一例抗GAD65抗体相关性小脑性共济失调患者的临床资料,进行诊断、鉴别诊断、治疗及预后分析。结果患者为中老年男性,急性起病,缓慢进展,主要表现为步态不稳并渐出现复视、不能独立行走;神经系统体检发现双眼上视受限、双侧跟膝胫试验及双手轮替试验欠稳准;血清及脑脊液抗GAD65抗体阳性;头颅MRI未见异常萎缩及责任病灶;大剂量甲强龙冲击后症状明显减轻。结论抗GAD65抗体相关性小脑性共济失调可有脑干及小脑受累症状,是一种可以治疗性疾病,早期诊断并积极治疗有望改善预后。     

A 19-year-old male with cerebellar ataxia and cognitive impairment following glandular fever

A 19-year-old male, who was previously functionally independent, presented with cerebellar ataxia and cognitive impairment following glandular fever. This case highlights the importance of considering an Epstein-Barr virus aetiology in children or young adults with acute cerebellar ataxia.     

Autoantibodies in postinfectious acute cerebellar ataxia

The authors found serum immunoglobulin M (IgM) autoantibody in a patient with typical acute cerebellar ataxia (ACA) and identified the antigen molecule as triosephosphate isomerase (TPI). TPI antigenicity to the patient's antibody was the highest in the cerebellar tissue. Eight of 23 patients with ACA had increased IgM anti-TPI antibody titers vs those of healthy controls. Preceding Epstein-Barr virus infection was confirmed serologically in all 8 patients. Anti-TPI antibody decreased with clinical improvement.     

An adult case of peripheral facial nerve palsy following acute cerebellitis associated with high antibody titers against varicella-zoster virus]

Here we report a case of acute cerebellitis, in which the patient developed right peripheral facial palsy during the recovery phase of cerebellar ataxia. A 67-year-old man developed truncal and limb ataxia following a fever, general fatigue and anorexia. He was diagnosed to have acute cerebellitis. While the ataxia symptoms were improving without any treatment, right peripheral facial nerve palsy developed and an MRI revealed an enhancement of the right facial nerve proximal to the geniculate ganglion. After treatment with acyclovir and corticosteroids, his facial nerve palsy and ataxia both gradually improved. There has been no previous report of an adult case who developed peripheral facial nerve palsy during the recovery phase of acute cerebellitis. This case indicates that a wide spectrum of neurological complications may develop in association with a varicella-zoster virus infection.     

Neoplastic meningitis presenting with acute cerebellar ataxia

Acute cerebellar ataxia is a rare initial presenting feature of neoplastic meningitis (NM), particularly in gastric cancer. The authors report a 61-year-old woman with acute cerebellar ataxia secondary to NM from gastric cancer, which was not accompanied by other symptoms commonly associated with NM at initial presentation. It is suggested that NM should be considered in the differential diagnosis of cancer patients with acute cerebellar ataxia.     

HIV-related opsoclonus–myoclonus–ataxia syndrome: Report on two cases

Opsoclonus–myoclonus–ataxia (OMA) syndrome is a rare neurological disorder, characterized by a rapid onset of generalized myoclonus in association with chaotic multi-directional eye movements and, less frequently, cerebellar ataxia. OMA is commonly related to a paraneoplastic process, specifically neuroblastoma in children and lung or breast cancer in adults. Nevertheless, OMA may occur in association with various infectious agents, such as Coxsackie virus B3, Epstein-Barr virus, mumps, enterovirus, and streptococcus. We recently encountered two cases of HIV-related OMA syndrome. The first patient developed a sudden onset of OMA at the time of HIV seroconversion. The second patient experienced severe ataxia with a mild degree of myoclonus and opsoclonus, associated with an elevated CD4 count following the initiation of highly active antiretroviral therapy (HAART). We suggest that OMA syndrome may be another rare manifestation of HIV infection at the time of seroconversion or during an immune restoration period.