Management of Patients with Cerebellar Ataxia During the COVID-19 Pandemic: Current Concerns and Future Implications.

The current worldwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that causes coronavirus disease 2019 (COVID-19) has brought some medical systems to the brink of collapse. This crisis is also negatively impacting the care of patients with non-COVID-19 conditions, including those with cerebellar ataxia (CA). Older patients with CA and those with immune-mediated ataxias on immunosuppressive medication are potentially at high risk of developing serious complications of the infection, although it is also possible that immunosuppressive agents may provide a defense against cytokine storm. This has implications for even greater attention to preventing contracting the disease through physical distancing and/or isolation. The CA patient population is also at higher risk because of the neurological complexities of their underlying disorder and the comorbid medical illnesses that often accompany the genetic ataxias. As the disruption of social patterns and healthcare delivery in response to the crisis continues, interruption of rehabilitation, speech and language therapy, and face-to-face consultations threatens to have a negative impact on the course and well-being of CA patients. Mental and physical health is also potentially at greater risk because the prevailing uncertainty and anxiety may be superimposed upon cerebellum-specific neuropsychological challenges. We identify and review some of the short- and long-term consequences of this global pandemic for the community of ataxia patients and their families and for the clinical and academic neurologists/ataxiologists caring for these patients. This includes the recognition that telemedicine has emerged as a principle means of caregiver-patient contact and that neurological manifestations of COVID-19 including those specific to cerebellar neurobiology are increasingly recognized and will require close surveillance and monitoring. This COVID-19 Cerebellum Task Force consensus provides some guidance on how we may approach this uncertain time and consider preparing for the new realities we face in CA patient care once this acute crisis has passed.

HIV Presenting as Cerebellar Ataxia.

Presenting features of HIV has always been a Pandora's box largely due to multisystem affection by the virus and a large array of opportunistic infections. We hereby report an extremely rare case of 40 yr old patient presenting as symmetric, progressive cerebellar ataxia later found to be HIV positive. Thorough knowledge of rare presentations of HIV and a high index of suspicion are necessary for early diagnosis and efficient treatment of HIV.

[Clinical significance and the first identification of human parechoviruses in Hungary]. / A humán parechovírusok klinikai jelentosége és elso hazai azonosítása.

UNLABELLED: Human parechoviruses (HPeV) belonging to the family Picornaviridae are widespread enteric pathogens and are associated with various clinical syndromes in human. At present, 16 HPeV genotypes (HPeV1-16) are known. There is no report on the detection of HPeVs in Central Europe. AIMS: The aim of the retrospective study was to detect and characterize HPeVs using molecular methods in cell cultures with "enterovirus-like" cytophatic effect (CPE) archived between 1990 and 2004, in two virology laboratories, in Hungary. MATERIALS AND METHODS: In Laboratory I, fecal samples from children with symptoms of gastroenteritis under the age of 10 years were cultured as a previous routine diagnostic laboratory protocol for "enterovirus". Cell cultures indicating CPE were archived between 1990 and 2000. In Laboratory II, 2 fecal samples, a liquor and a nasopharyngeal aspirate were re-tested which contained an "enterovirus-like" virus in cell cultures and were positive by HPeV1 neutralization immunosera between 2000 and 2004. Specimens were tested retrospectively for HPeV by reverse transcription-PCR (RT-PCR) method using 5'UTR conserved primers. Specific primers were designed to determine the HPeV structural region (VP0-VP3-VP1). RESULTS: 9 of the 66 archived samples (9.1%) from Laboratory I and all the 4 samples from Laboratory II were found to be HPeV-positive. 10 samples were identified as HPeV1, 2 were HPeV4 and 1 could not be determined. 3 HPeV1 clusters were identified in Laboratory I according to the isolation date originated from years 1990/1991, 1992/1995 and 1998. HPeV1 was detected in clinical syndromes: gastroenteritis (in a 24-years-old adult), recurrent stomatitis aphtosa (in a 42-years-old adult), encephalitis and ataxia cerebellaris acuta in infants and children in Laboratory II. CONCLUSIONS: This is the first detection of HPeVs in Central Europe. Detection and genetic characterization of HPeV in available historical samples infected with previously unidentifiable agents with "enterovirus-like" cytopathogenic effect may help to understand the clinical importance and spectrum of the infections and the genetic diversity and evolution of these viruses.

[Varicella is not always benign]. / La varicelle n'est pas toujours bénigne.

Varicella is a rash illness caused by the varicella-zoster virus. It mainly affects children with usually a benign outcome. However, several complications of variable severity can be observed including bacterial infectious complications and neurological complications. We report two cases of complicated varicella. Case 1: 5 month old baby with no previous pathological history presenting with a rash composed of vesicles and pustules lasting for six days. Symptoms worsened the day before his admission to our Department due to respiratory distress. Case 2: 7-Year old girl admitted to our Department due to simple convulsion. Clinical examination showed generalized varicella scars and cerebellar ataxia. Although varicella is a common, in most cases benign viral disease, several studies have recently reported a recrudescence of complications, which appear to be responsible for 0.2-1.5% of the causes of hospitalization in children with varicella.

An increasing incidence of chickenpox central nervous system complications in children: what's happening in Tuscany?

BACKGROUND: The most frequent noncutaneous site of involvement of chickenpox is the central nervous system (CNS) and complications include cerebellar ataxia, encephalitis, and meningitis. OBJECTIVES: We have recently observed an unusually high number of children with chickenpox CNS complications in our university children's hospital. A study to evaluate the incidence of these complications over time in children living in Tuscany was carried out. STUDY DESIGN: We evaluated all cases of chickenpox and chickenpox complications leading to hospitalization in children aged 1 month-14 years reported to the Tuscany public health centre between 1997 and 2004. The International Classification of Disease Ninth Revision-CM hospital discharge diagnostic codes and medical records were used. RESULTS: The incidence (95% confidence interval) of CNS complications/1000 chickenpox cases was stable between 1997 and 2001 [1997: 0.80 (0.29-1.74); 1998: 0.73 (0.29-1.50); 1999: 0.67 (0.25-1.46); 2000: 0.56 (0.15-1.44); 2001: 0.59 (0.16-1.50)] but increased significantly (chi(2) for trend: 9.401; p=.0021) in 2002 [1.56 (0.83-2.66)], in 2003 [1.73 (0.95-2.90)] and in 2004 [1.51 (0.74-2.27)]. Non-CNS complications remained stable over time. CONCLUSIONS: Possible factors biasing the result were taken into account. Reasons of increased CNS complications remain unknown, but the possible emergence of a particularly neurotropic strain of varicella-zoster virus should be further investigated.

Barr humbug: acute cerebellar ataxia due to Epstein-Barr virus.

Epstein-Barr virus (EBV) infection is associated with neurological sequellae, but rarely there is acute cerebellar ataxia (ACA) in an adult. We present a novel case of a 26-year-old man, who presented with ACA. He had normal MRI and CSF analysis. Serum testing confirmed active EBV. A course of oral prednisolone 1 mg/kg for 4 weeks, with a subsequent taper was started. He made a full recovery within 3 weeks of presentation.

Varicella and its complications as cause of hospitalization.

Varicella is an acute contagious disease that most commonly occurs in childhood. Although normally benign, varicella can occasionally develop into a more serious illness. Moreover, the infection can lead to serious complications, such as Staphylococcus aureus infections, otitis media, endocarditis, pneumonia, and rare central nervous system (CNS) events like cerebellar ataxia and encephalitis. This study was conducted to analyze the hospitalization rate due to varicella or its complications in a tertiary care hospital in Italy, where varicella vaccination has not yet been implemented. The review was carried out on cases of children with varicella identified by ICD9 and ICD9-CM diagnostic codes and admitted to the Giannina Gaslini Children's Research Hospital of Genoa, Italy, from January 1st, 1995 to December 31st, 2004. For each case reporting complications, the clinical report form was extracted and the events recorded. Varicella was recorded in 346 (0,16%) out of 212,647 total hospital discharges. Chickenpox with detailed complications and cerebrovascular diseases accounted for 56 discharges (12.14%), for a total of 728 days. Fifteen patients needed more than one hospitalization because of severe sequelae as result of CNS involvement. We reported three particular cases of invasive infections and four children affected with cerebrovascular diseases following varicella. Our retrospective data regarding a single tertiary care pediatric hospital shows that hospitalization due to varicella or its sequelae may present an important medical and indirect economic problem.

Varicella Zoster Virus Cerebellitis Without a Rash in an Immunocompetent 85-Year-Old Patient.

BACKGROUND: Reactivation of the varicella zoster virus (VZV) in adults rarely presents with neurological symptoms without a rash. To our knowledge, so far, only 3 additional cases of VZV cerebellitis, which presented without a rash and were proven by cerebrospinal fluid analysis, have been reported in the literature. CASE REPORT: An immunocompetent 85-year-old patient presented with a new-onset tremor. He had no rash, had a normal brain computed tomography and magnetic resonance imaging, and had minimal cerebrospinal fluid findings. Eventually, he was diagnosed as having varicella zoster virus cerebellitis only on the basis of a virological examination. CONCLUSIONS: The manifestation of a new-onset tremor and gait ataxia should raise a suspicion of cerebellitis caused by VZV, even in the absence of cutaneous manifestations or typical imaging findings.

A case of Murray Valley encephalitis in a 2-year-old Australian Stock Horse in south-east Queensland.

CASE REPORT: This report summarises the findings from a case of naturally-occurring Murray Valley encephalitis in a 2-year-old filly presenting with acute onset of depression and weakness. Serum samples tested at the onset of clinical signs were negative for Hendra and Kunjin virus antibodies, but positive for Murray Valley encephalitis virus (MVEV) using IgM-capture ELISA (1 : 300 dilution). A virus neutralisation assay performed 4 weeks later confirmed a titre of 1 : 160. Sera collected in the weeks preceding neurological signs returned a negative titre for MVEV 2 weeks prior followed by a titre of 1:80 in the week prior to illness. Serological surveillance conducted on 67 co-located horses returned a positive titre of 1 : 20 in one in-contact horse. There was no history of clinical disease in that horse. At 3 months after the onset of clinical signs in the index case, the filly continued to show mild facial paresis and hypermetria; the owners elected euthanasia and gave permission for necropsy. Histopathological analysis of the brain showed a mild meningoencephalitis. CONCLUSION: The progression of a naturally-occurring MVEV infection in a horse has been documented in this case.

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.

Neurological manifestations of West Nile virus infection.

BACKGROUND: Over the past four years, West Nile virus (WNV) has become a significant health issue in North America. In 2002, WNV infection made its first appearance in the human population in Canada. METHODS: Patients who presented to the University Health Network and Mount Sinai Hospital in Toronto with neurological disease attributed to WNV infection were identified and followed by the neurology service. Clinical features and results of laboratory, electrodiagnostic, radiological and pathological studies are presented. RESULTS: In August and September 2002, 26 patients were admitted with WNV infection; 14 presented with neurological illness. Encephalitis was the most common presentation (11 patients). Eleven patients developed neuromuscular disease; two at presentation and nine after encephalitis. While the majority had a motor process that localized to the anterior horn cell and/or motor neuron, two patients had evidence of a demyelinating neuropathy and one a sensorimotor axonal neuropathy. Less common manifestations included rhombencephalitis, ataxia, myelopathy and parkinsonism. Death occurred in four patients; two > 75 years of age, and two who were immunocompromised. CONCLUSIONS: The most common neurological manifestation of WNV infection was encephalitis with subsequent neuromuscular involvement. The diversity of clinical and pathological findings, however, suggests widespread involvement of the central and peripheral nervous system. A poorer prognosis for neurological recovery and overall survival was seen in older and immunocompromised patients.

Pre-eruptive varicella cerebellitis confirmed by PCR.

The diagnosis of pre-eruptive varicella cerebellitis is usually based on a history of exposure and thus depends on a subjective clinical assessment. The confirmation of the diagnosis has traditionally depended on the development of skin manifestations of varicella and on varicella-zoster antibody seroconversion. Confirming the diagnosis of pre-eruptive cerebellar ataxia or encephalitis early in the course of a viral infection may save the patient unnecessary tests, procedures, or attempts at therapeutic intervention. A patient is reported in whom, after clinically suspecting a diagnosis of pre-eruptive varicella cerebellitis, the diagnosis was confirmed by performing polymerase chain reaction analysis of varicella-zoster virus DNA in peripheral blood leukocytes and cerebrospinal fluid. The patient developed skin manifestations of varicella 5 days after the onset of neurologic symptoms and 15 days after known exposure. In some patients with preeruptive varicella cerebellitis, polymerase chain reaction may be extremely useful for rapid confirmation of the diagnosis.

Complicated varicella zoster infection in 8 paediatric patients and review of literature.

BACKGROUND: This is a study of complicated varicella zoster infection in paediatric patients. AIM: To find out the number of patients with such complications, the types of complications and their outcome. METHOD: This involved a retrospective review of the case records of 8 patients who presented to our unit over a 12-month period (Jan-Dec 96). All patients were previously well without any underlying immunodeficiency. Varicella zoster (VZ) infection was confirmed by VZ immunofluorescence from vesicular fluid. RESULTS: CMS complications accounted for 6 of the 8 cases. Of these, 3 presented with encephalitis, 2 with cerebella ataxia and 1 with aseptic meningitis and cerebella ataxia. Of the non-CNS cases, 1 presented with glomerulonephritis with superimposed staphylococcus infection of skin ulcers; the other had disseminated VZ infection with haemorrhagic vesicles, hepatitis, ileus with mesenteric adenitis and disseminated intravascular coagulation. OUTCOME: The patient with disseminated VZ infection and multiple organ involvement died 5 days after a stormy course. One patient with encephalitis who had status epilepticus for 2 hours had behavioural problems and poor memory. The remaining 6 patients had no sequelae. CONCLUSION: VZ infection usually a minor illness, can result in serious life-threatening complications in previously healthy patients.

[Neurologic complications of varicella in adults]. / Les complications neurologiques de la varicelle chez l'adulte.

Three patients aged 32, 30 and 36 years, had chicken pox then developed acute cerebellar ataxia (for two) and acute polyradiculoneuritis. Cerebrospinal fluid (CSF) protein content was increased and varicella virus serology was positive in both blood and CSF. All three patients improved with aciclovir.

[Acute cerebellar ataxia in a 5-year-old boy. Clinical warnings]. / Ostra ataksja mózdzkowa u 5-letniego chlopca. Spostrzezenia kliniczne.

A case of acute cerebellar ataxia caused by ECHO virus 30.5-year-old boy admitted to the Clinic of Gastroenterology and Nutrition in Warsaw, in September, 1996, complaining of headache, dizziness, weakness, somnolence, dysarthria and an unsteady walk. On neurological examination he had imparied coordination, rombergism, generalized hypotonia. There was no history of exposure to contagious diseases, ear discharge, convulsions, trauma. Parents suggested that the child could have swallowed an unidentified pill--toxicological tests ruled out poisoning. The diagnosis is based on the clinical examination and amplification ECHO virus from CSF.