Adenovirus cerebellitis in an immunocompetent 2-year-old girl.

Acute cerebellitis (AC) is a principal cause of acute cerebellar dysfunction in previously well children. Although the condition is usually benign, fatal complications include obstructive hydrocephalus and brainstem compression; therefore, prompt accurate diagnosis is vital. 1 There are various pathogens reported in the literature as aetiological agents of AC; however, adenovirus is very rarely mentioned, with only one previous case report in the literature to the best of our knowledge. 2 This case demonstrates the importance of recognising adenovirus as a cause of AC, particularly when preceded by a respiratory tract infection in the paediatric age group. Furthermore, we highlight the role of early neuroimaging in differentiating AC from other causes of acute cerebellar dysfunction, which require different management. Our patient made a full recovery with no long-term deficits demonstrating that comprehensive investigation and consideration of atypical pathogens in the context of AC is vital in securing a favourable outcome.

Magnetic resonance imaging of cerebellar cysts in a neonate with congenital cytomegalovirus infection.

Congenital cytomegalovirus infection is one of the most common congenital viral infections in the world. Brain magnetic resonance imaging plays a key role in evaluating brain involvement and establishing prognosis; several characteristic features have been described. We present a description of cerebellar cysts in a neonate with polymerase chain reaction-confirmed cytomegalovirus congenital infection, and discuss the differential diagnosis and potential pathophysiological mechanisms.

JC Virus Granule Cell Neuronopathy as AIDS-Presenting Illness.

JC virus is the etiological agent of progressive multifocal leukoencephalopathy, a white matter demyelinating disease that mostly affects immunocompromised patients. JC virus can also infect neurons and meningeal cells and cause encephalitis, meningitis and granule cell neuronopathy. We report a patient with JC virus granule cell neuronopathy, without concomitant progressive multifocal leukoencephalopathy, presenting as inaugural acquired immune deficiency syndrome-related illness. This patient's human immunodeficiency virus infection remained undiagnosed for several months after neurological symptoms onset. We review JC virus pathophysiology, clinical manifestations, treatment and prognosis, and emphasize the importance of considering human immunodeficiency virus infection and related opportunistic infections in the differential diagnosis of new-onset isolated cerebellar disease.

JC virus granule cell neuronopathy: A cause of infectious cerebellar degeneration.

JC virus (JCV) infection of glial cells can lead to progressive multifocal leukoencephalopathy (PML) in immunocompromised patients. A newly described phenotype of the infection is infection of neurons. This distinct clinical and radiological syndrome is named JCV granule cell neuronopathy, characterized by exclusive or predominant cerebellar atrophy. We report the clinical and radiological longitudinal findings of 5 HIV-infected patients referred to us between September 2004 and November 2011 who exhibited JCV granule cell neuronopathy (4 probable cases and 1 possible). The association of immunocompromised status, progressive cerebellar syndrome, MRI abnormalities with cortical cerebellar atrophy and cerebrospinal fluid positive for JCV on PCR allowed for a highly probable diagnosis. The reversal of the immunocompromised status is the only way to stop the disease evolution. Motor functioning can remain impaired, but the illness itself, unlike progressive multifocal leukoencephalopathy, does not seem to threaten life.

Neurological manifestations of dengue: a cross sectional study.

BACKGROUND: Dengue is an infectious disease caused by a virus of the flaviviridae family. It is a multi systemic illness causing considerable morbidity and mortality. A spectrum of neurological manifestations has been associated with dengue. METHODS: This was a descriptive cross sectional study including patients diagnosed with Dengue fever (DF), Dengue with warning signs and severe dengue with neurological sequale presenting to the Institute of Neurology, National Hospital of Sri Lanka from June 2011 to August 2012. All patients underwent serology testing for Dengue IgM in blood and CSF as confirmation of the diagnosis. RESULTS: Seven patients were included. 1/7 had bilateral optic neuritis (ON), 3/7 had a cerebellar syndrome (CS), 2/7 had transverse myelitis (TM) and 1/7 had cranial nerve palsy. The patient with ON had a post-infectious pattern and protracted recovery. All patients with CS had bilateral involvement. All had a self limiting course with complete recovery. Two were associated with acute infection. Both patients with TM had longitudinally extensive disease with one patient experiencing complete recovery. The patient with cranial nerve involvement had isolated 6th nerve palsy. CONCLUSIONS: Neurological manifestations of dengue are diverse. It is important to consider dengue as a cause for the above neurological presentations in hyper endemic territories for the disease.

Congenital rubella with agenesis of the inferior cerebellar vermis and total anomalous pulmonary venous drainage.

Congenital rubella infection has been associated with a number of abnormalities including cardiac, central nervous system and placental complications. We present a case with multiple fetal abnormalities detected on prenatal ultrasound, and confirmed postnatally, that included a single umbilical artery, severe tricuspid regurgitation, micrognathia and agenesis of the inferior cerebellar vermis. Postnatal echocardiography additionally revealed unobstructed total anomalous pulmonary venous drainage (TAPVD) into the coronary sinus. Placental examination showed signs of placentitis, and polymerase chain reaction on neonatal serum was positive for rubella. Following a multidisciplinary team review, it was decided to provide only supportive care, and the infant died at 6 months of age owing to a respiratory tract infection. To our knowledge, TAPVD and agenesis of the inferior cerebellar vermis have not been reported previously in association with congenital rubella infection. This case illustrates how congenital infection may present in atypical ways and stresses the importance of considering congenital infection in the differential diagnosis of fetal anomalies when multiple features are present.

JC virus granule cell neuronopathy is associated with VP1 C terminus mutants.

The polyomavirus JC (JCV) infects glial cells and causes progressive multifocal leukoencephalopathy (PML). We described a novel JCV-variant with a 10 bp deletion in the C terminus of the VP1 capsid protein, JCV(GCN1). This mutant was associated with lytic infection of cerebellar granule cell neurons and cerebellar atrophy in an human immunodeficiency virus/PML patient. This condition, also observed independently from PML, was named JCV granule cell neuronopathy (JCV GCN). We characterized JCV mutations in cerebrospinal fluid (CSF) of four other JCV GCN patients, and reviewed the literature on 10 reported cases. The strain from one patient harboured the identical GCN1-deletion, while the other patients had novel mutations in the same area, named JCV(GCN2-4), causing variable changes in VP1 structure. One patient also had wild-type JCV in the CSF. To study the mechanisms leading to JCV GCN, we compared viral replication kinetics from JCV(GCN1) with the prototype JCV(Mad1), the PML isolate JCV(HWM) and the prototype JCV(Mad1D) engineered with the GCN1-deletion. While all strains replicated at low levels in the medulloblastoma cell line DAOY from a cerebellar neuronal tumour, JCV(Mad1) replicated better in astroglial SVG cells than JCV(Mad1D) or JCV(GCN1) and all strains replicated at higher levels in COS-7 kidney cells, suggesting that the GCN1-deletion confers a disadvantage for viral growth in central nervous system white matter. The GCN1-deletion remained stable after 100 days in culture and VP1 protein was produced in all cell lines, indicating that JCV(GCN1) is replication-competent in vitro. These data highlight an important and previously overlooked aspect of JCV-pathogenesis. Detection of GCN-type JCV strains in CSF may help clinicians diagnose JCV GCN.

Chronological diffusion-weighted imaging changes and mutism in the course of rotavirus-associated acute cerebellitis/cerebellopathy concurrent with encephalitis/encephalopathy.

Rotavirus is one of the most common causes of gastroenteritis in children and is known to accompany some neurological disorders such as encephalitis/encephalopathy and seizures. Although cerebellar disorders sometime occur as a complication of rotavirus gastroenteritis in Japan, few reports have addressed these issues. Here, we report three cases of insulted cerebellums in addition to encephalitis/encephalopathy associated with rotavirus. Similar to posterior fossa syndrome after surgery, mutism was a notable symptom that lasted about 1 month. Brain diffusion-weighted imaging (DWI) revealed chronological changes, i.e., marked hyperintensity in the bilateral dentate nucleus followed by the vermis and cerebellar hemisphere. The bilateral dentate nucleus is known to be a key lesion site for mutism, and these clinical and radiological findings may be tightly connected in rotavirus-associated cerebellitis/cerebellopathy.

Persistent adeno-associated virus 2 and parvovirus B19 sequences in post-mortem human cerebellum.

We previously reported in a large cohort (N = 104) of post-mortem tissues the detection of both the non-pathogenic adeno-associated virus (AAV2) in approximately 13% and the pathogenic human parvovirus B19 (B19) in approximately 42% of human brains, particularly the dorsolateral prefrontal cortex. Multiple animal parvoviruses target the developing cerebellum (CBLM) resulting in hypoplasia and ataxia, but very little is known about the human parvoviruses and their ability to infect or cause disease in the CBLM. We have now confirmed in the above cohort the presence of AAV2 and B19 sequences in the CBLM. Our results show that approximately 27% and approximately 70% of human CBLM are positive by nested polymerase chain reaction for AAV2 and B19 sequences, respectively. We also document in a second cohort (N = 10) the presence of AAV2 (50%) and B19 (100%) sequences in the CBLM and correlate our results for B19 with studies from matched sera. Eighty percent (80%) of this cohort was positive for anti-B19 IgG, while none were IgM+, suggesting that most individuals had been previously infected with B19 but none acutely. To our knowledge, this study is the first to demonstrate that both AAV2 and B19 sequences are present at relatively high frequencies in the CBLM and are likely due to persistent rather than acute infection. Further studies will lead to insights into AAV2- and/or B19-CBLM interactions including mechanisms of infection, persistence, and possibly neuropathology, including cerebellar hypoplasia and ataxia.

Immune reconstitution after potent antiretroviral therapy in AIDS patients with progressive multifocal leukoencephalopathy.

Neurological disease is the initial manifestation of acquired immunodeficiency syndrome (AIDS) in 10-20% of patients with HIV infection. Progressive multifocal leukoencephalopathy (PML) predominantly involves the cerebral hemispheres, with a small subset of patients having lesions predominantly or exclusively confined to the cerebellum. The radiological features of PML are typically non-inflammatory. As a result of potent antiretroviral therapy (ART), however, inflammatory lesions are becoming more common in HIV-infected individuals and are due, in part, to immune reconstitution that occurs in recipients of potent ART. In the majority of such cases, the clinical outcome of immune reconstitution PML has been beneficial to the host, although several case reports have described worsening or fatal outcomes in PML patients as a result of potent ART. The following 2 cases of immune reconstitution PML described in this report illustrate the varied radiological manifestations and clinical outcomes that can develop in AIDS patients with PML receiving potent ART. Moreover, these cases highlight the inflammatory changes observed on neuroimaging in AIDS patients with immune reconstitution PML receiving potent ART and to our knowledge are the first reports of immune reconstitution isolated to the cerebellum in such patients.

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.

Cerebellar hypoplasia associated with an avian leukosis virus inducing fowl glioma.

Fowl glioma-inducing virus (FGV), which belongs to subgroup A of avian leukosis virus (ALV), shows tumorigenicity and pathogenicity, mainly in the nervous system, and causes astrocytoma and perineurioma. Apart from these neoplasms, cerebellar anomaly was found in chickens infected with FGV in ovo. The study reported here describes the morphologic characteristics of the affected cerebellum. Specific-pathogen-free chickens (C/O) were inoculated with FGV through the yolk sac on the 7th day of incubation. The cerebellar anomaly included diffuse depletion of granular cells of the internal granular layer (IGL), remnants of the external granular layer (EGL), and disorganization of the Purkinje cell layer. These cerebellar changes were observed in all birds except one. In the infected embryos, the EGL was thicker and had an irregular arrangement with a thin molecular layer (ML) and IGL, compared with the control. The granular cells were immunohistochemically positive for ALV common antigen. Immunohistochemical analysis for vimentin revealed disarrangement and decreased number of Bergmann's fibers. Use of the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method and electron microscopy indicated that apoptotic granular cells were frequently observed in the EGL and ML. These results suggested that the cerebellar anomaly was hypoplasia, principally resulting from the apoptosis of granular cells in the EGL and ML caused by FGV infection and that the cell loss induced obstruction of granular cell migration and disarrangement of Bergmann's fibers in the ML.

[Acute cerebellitis caused by Epstein-Barr virus: case report]. / Cerebelite aguda causada por vírus Epstein-Barr: relato de caso.

Acute cerebellitis can occur in association with varicella-zoster virus, enterovirus, mumps, mycoplasma, and other infective organisms. Acute cerebellitis is a rare complication of Epstein-Barr virus (EBV) infection. We report the case of a 21-year-old woman with a 12-day history of nausea and vomiting, gait and limbs ataxia, myoclonus, tremor of head and all four limbs, opsoclonus and cutaneous rash. Anti-EBV IgG and IgM antibodies against antiviral capsid were positive and anti-EBV against virus-associated nuclear antigen was also positive. EBV infection in association with neurological findings can occur without the classic signs and symptoms of infectious mononucleosis.

Cerebelite aguda causada por vírus Epstein-Barr: relato de caso / Acute cerebellitis caused by Epstein-Barr virus: case report

A cerebelite aguda pode ocorrer em associação a infecção pelo vírus da varicela-zoster, enterovirus, caxumba, micoplasma e outros agentes infecciosos. A cerebelite aguda é uma complicação rara da infecção pelo vírus Epstein-Barr (EBV). Relatamos o caso de uma mulher de 21 anos com história de 12 dias de evolução com náuseas, vômitos, ataxia de marcha e membros, tremor cefálico e de membros, opsoclono, mioclonias e rash cutâneo. Sorologia para EBV foi positiva. A infecção pelo EBV, com complicações neurológicas, pode não se apresentar com os sinais e sintomas clássicos da mononucleose infeciosa.

[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.