Intravenous immunoglobulin therapy for acute cerebellar ataxia

A case of acute cerebellar ataxia without any prodromal illness showed cerebellar hypoperfusion on 123 I-iodoamphetamine single photon emission computed tomography. The symptoms did not resolve spontaneously or with methylprednisolone pulse therapy but disappeared rapidly with intravenous immunoglobulin therapy.

Conclusion: Intravenous immunoglobulin therapy is worth considering in acute cerebellar ataxia that does not respond to high-dose steroid therapy.     

Haemolytic-uraemic syndrome: an analysis of prognostic features.

Seventy-two children with the haemolytic-uraemic syndrome were seen between 1969 and 1980 at The Hospital for Sick Children and Guy''s Hospital, London. They probably constitute the majority of such cases in south-east England during that period. Boys and girls were affected equally, the mean age at presentation was 3.5 years, and a peak incidence of the disorder in summer months was observed. In 52 (72%) there was a history of diarrhoea at onset. Fifty-seven (78%) were managed by dialysis. Fifty (70%) of the 72 children had a favourable outcome with complete recovery, 3 (4%) died in the acute phase of the illness, 8 (11%) had residual hypertension or chronic renal failure, and 11 (16%) never recovered renal function. The probability of complete recovery of renal function was analysed by logistic regression which indicated that younger age, presentation in the summer months, diarrhoea at onset and, in those patients who were dialysed, a short prodromal illness were associated with a good outcome. Further analysis of the interaction among these variables in the patient group as a whole indicated that diarrhoea favoured a good outcome among boys but not girls.     

Two patients with acute rotavirus encephalitis associated with cerebellar signs and symptoms

Rotavirus, one of the major causes of severe gastroenteritis in children, occasionally causes central nervous system complications. Recently several patients with acute encephalitis/encephalopathy due to rotavirus associated with cerebellar signs and symptoms have been reported. The condition is characterized by disturbances of consciousness at onset and cerebellar signs and symptoms such as hypotonia, ataxia, dysmetria, and speech disorders, including mutism, slow speech, and dysarthria at convalescence. We report two patients (3-year-old girl, 2-year-old boy) who developed acute encephalitis due to rotavirus and showed cerebellar signs and symptoms. Both patients had characteristic history of consciousness disturbances subsequent to several days of diarrhea, vomiting and fever, and cerebellar symptoms such as hypotonia, ataxia, dysmetria, and speech disorders during the recovery period. Electroencephalography showed diffuse high-voltage delta wave activity in each patient. Brain magnetic resonance imaging showed cerebellar edema in the acute phase followed by cerebellar atrophy on follow-up images in both patients. In the first patient, diffusion-weighted images (DWI) revealed high signals at the left cerebellar peduncle region and apparent diffusion coefficient (ADC) maps showed decreased ADC values of the lesion in the acute phase. The first patient had dysmetria at 1-year follow-up. However, she had normal motor and cognitive functions and could lead her daily life without impairment. In the second patient, no further symptoms were apparent at 1-year follow-up. Acute encephalitis/encephalopathy due to rotavirus with cerebellar signs and symptoms might be diagnosed on DWI, by demonstrating decreased ADC values in acute phase.     

Renal function in acute falciparum malaria.

Renal function was assessed in 40 children during the acute illness and after recovery from falciparum malaria. Creatinine clearance was significantly lower during the acute illness than after recovery. Six of 18 children with impaired creatinine clearance (< 50 ml/min/1.73 m2) had evidence of acute tubular dysfunction. Hyponatraemia occurred in 12.5% during the acute phase. Fractional sodium excretion was raised in 27% during the acute illness and continuing sodium wastage occurred in 17% after recovery. Plasma potassium was significantly higher and fractional potassium excretion (FeK) significantly lower during the acute illness than after recovery. There was a positive correlation between FeNa and FeK both during and after recovery from the illness but they did not exactly mirror each other in every individual. Urine sodium:potassium ratios were similar during and after recovery from the illness and was related to FeNa. Fractional glucose excretion was zero. Mild proteinuria occurred in 40% during the acute illness but were not related to creatinine clearance, body temperature at presentation, or peripheral parasite density. Proteinuria was absent after recovery. Acute intrinsic renal impairment occurs during apparently ''uncomplicated'' falciparum malaria in children.     

Determinants of prognosis of acute transverse myelitis in children

BACKGROUND: Acute transverse myelitis (ATM) is a severe disorder; recovery requires several months and often leaves neurologic residua. To determine what features of patients with acute transverse myelitis significantly influence prognosis, the authors reviewed reports of ATM in Japanese children published in the last 15 years (from 1987 to 2001). METHODS: The authors studied reports of 50 Japanese patients (17 boys, 26 girls, 7 children of unspecified sex; mean age +/- SD, 8.0 +/- 3.8 years). Acute-phase and demographic features including age, increased deep tendon reflexes, Babinski reflex, sex, preceding infection, decreased deep tendon reflexes, time course of peak neurologic impairment, treatment with prednisolone and/or high-dose methylprednisolone, and the day of illness when treatment was started were used as independent variables in a regression analysis. The dependent variable was long-term persistence of neurologic deficits. RESULTS: Younger patients and those without increased deep tendon reflexes or a Babinski reflex were more likely to have residual neurologic deficits such as paraplegia or tetraplegia, sensory loss and sphincter disturbance. No relationship was seen between prognosis and sex, preceding infections, decreased deep tendon reflexes, time course of peak neurologic impairment, treatment with prednisolone or high-dose methylprednisolone, or timing of treatment initiation. CONCLUSIONS: Age at onset and neurologic features were important for outcome prediction in ATM. Steroid therapy did not associate with better outcome.     

Renal function in acute falciparum malaria

Renal function was assessed in 40 children during the acute illness and after recovery from falciparum malaria. Creatinine clearance was significantly lower during the acute illness than after recovery. Six of 18 children with impaired creatinine clearance (< 50 ml/min/1.73 m2) had evidence of acute tubular dysfunction. Hyponatraemia occurred in 12.5% during the acute phase. Fractional sodium excretion was raised in 27% during the acute illness and continuing sodium wastage occurred in 17% after recovery. Plasma potassium was significantly higher and fractional potassium excretion (FeK) significantly lower during the acute illness than after recovery. There was a positive correlation between FeNa and FeK both during and after recovery from the illness but they did not exactly mirror each other in every individual. Urine sodium:potassium ratios were similar during and after recovery from the illness and was related to FeNa. Fractional glucose excretion was zero. Mild proteinuria occurred in 40% during the acute illness but were not related to creatinine clearance, body temperature at presentation, or peripheral parasite density. Proteinuria was absent after recovery. Acute intrinsic renal impairment occurs during apparently 'uncomplicated' falciparum malaria in children.     

Dancing Eye Syndrome associated with spontaneous recovery and normal neurodevelopment

Five patients with spontaneously recovering Dancing Eye Syndrome/Opsoclonus Myoclonus Syndrome are described. Age at presentation ranged from 4 to 19 months. Four had symptoms of fever and a coryzal illness within days to a few weeks prior to the onset. One of the 4 also had varicella zoster 4 weeks before presentation. All had opsoclonus, myoclonus/ataxia and irritability. Associated infective agents identified were Coxsackie virus and rotavirus. Spontaneous improvement of symptoms started within 9 days of presentation and total duration of illness ranged from 10 to 24 days. Developmental progress at follow-up was normal in all cases. A range of immunomodulatory therapies have been advocated for the treatment of Dancing Eye Syndrome/Opsoclonus Myoclonus Syndrome. However, in some children, early spontaneous recovery may occur, an observation which should be borne in mind when designing therapeutic trials in this condition.     

The use of muscle biopsy in the diagnosis of undefined ataxia with cerebellar atrophy in children

Childhood cerebellar ataxias, and particularly congenital ataxias, are heterogeneous disorders and several remain undefined. We performed a muscle biopsy in patients with congenital ataxia and children with later onset undefined ataxia having neuroimaging evidence of cerebellar atrophy. Significant reduced levels of Coenzyme Q10 (COQ10) were found in the skeletal muscle of 9 out of 34 patients that were consecutively screened. A mutation in the ADCK3/Coq8 gene (R347X) was identified in a female patient with ataxia, seizures and markedly reduced COQ10 levels. In a 2.5-years-old male patient with non syndromic congenital ataxia and autophagic vacuoles in the muscle biopsy we identified a homozygous nonsense mutation R111X mutation in SIL1 gene, leading to early diagnosis of Marinesco-Sjogren syndrome. We think that muscle biopsy is a valuable procedure to improve diagnostic assesement in children with congenital ataxia or other undefined forms of later onset childhood ataxia associated to cerebellar atrophy at MRI.     

Myoclonic encephalopathy of infants or "dancing eyes syndrome". Report of 7 cases with long-term follow-up and review of the literature (cases with and without neuroblastoma).

We describe 7 children with myoclonic encephalopathy of infants (MEI). MEI is a clinical entity characterized by an acute or subacute onset of polymyoclonia, cerebellar ataxia and opsoclonus ("dancing eyes"). It occurs either spontaneously, following an infectiuos illness or in association with an occult neuroblastoma. It is likely that immunological factors play a role in the pathogenesis. Steroid therapy resulted in rapid dramatic improvement of the neurological symptoms in 4 cases. However, this initial response did not correlate with the eventual outcome. We reviewed the literature to compare 45 reported cases of MEI associated with a neuroblastoma with 48 children without such a tumor to identify possible differences in clinical presentation, response to steroid medication and long-term prognosis of the neurological syndrome. In this respect we found no differences. Impairment of motor, verbal or intellectual performance were reported in at least half the cases. Although an immediate and marked response to steroids occurs in many cases of both groups, it remains unclear whether the long-term outcome is favourably influenced by this medication. The two-year-survival rate (90%) in the neuroblastoma group and the percentage of mediastinal localisation of the tumor (49%) are much higher compared with neuroblastomas without MEI. The reasons for these remarkable differences are not known. Diagnostic, therapeutic and prognostic implications justify the separation of MEI from the more common and benign syndrome known as acute cerebellar ataxia of childhood.     

Acute urinary retention in a child with acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory demyelinating encephalomyelitis with often monosymptomatic abrupt onset, followed by multifocal neurologic symptomatology depending on lesion-site. Diagnosis is made on the basis of characteristic magnetic resonance imaging (MRI) signal alterations. ADEM is sensitive to steroid therapy, immunoglobulins and plasmapheresis, presents usually a monophasic course and disappears completely after 2 or 3 weeks. Resolution of MRI lesions appears usually within 6 months of presentation. We report on a 14-year-old male, admitted to our Emergency Unit because of fever and acute urinary retention with a normal neurological examination. Urinary tract ultrasonography and mictional cystography were normal; electrophysiology showed a mild involvement of the peripheral nervous system and brain and spine MRI revealed disseminated areas of increased signal on T2-weighted sequences suggestive of ADEM. Steroid therapy brought about clinical recovery in a few days. Resolution of lesions on MRI after 4 months and absence of relapses during four-year clinical follow-up confirmed definitive diagnosis. Our case is interesting because, to our knowledge, this is the first literature report with acute urinary retention as predominant symptom in monosymptomatic forms. Another peculiar feature is the absence of associated neurologic symptomatology despite MRI evidence of important brain and spine alterations.     

Atypical presentations of SSPE: a clinical study in four cases

Subacute sclerosing panencephalitis (SSPE) is a progressive, fatal disease of the central nervous system caused by a persistent measles virus. It is clinically characterized by insidious onset of intellectual deterioration and behavioral changes followed by myoclonias and eventually complete neurologic deterioration. The diagnosis is based on characteristic clinical features, periodic electroencephalography (EEG) complexes of high slow waves and increased antibody titer against measles in cerebrospinal fluid. Here, we report four SSPE cases, two of whom manifested with hemiparesis; in the third and fourth cases, cerebellar ataxia and acute encephalopathy with focal seizures were the presenting symptoms at the onset of disease, respectively. The typical periodic EEG complexes in our patients led to the diagnosis of SSPE. Our findings show that SSPE should be considered in the differential diagnosis of hemiparesis, cerebellar ataxia and acute encephalopathy, and highlight the diagnostic significance of EEG in unidentified cases.     

Description and prognostic value of cerebellar MRI lesions in children with severe acute ataxia]

The aim of this work was to evaluate NMR cerebellar abnormalities in children with severe acute ataxia. Among 8 consecutively observed children, NMR performed in 6 during the acute phase was pathological in 4, demonstrating hyperintense signal in the T2-weighed sequences of dentate nuclei (2 cases, associated in 1 with hyperintense signal in the medium cerebellar peduncle) or of the cerebellar cortex associated with cerebellar swelling (2 cases). NMR performed in 7 cases after at least 1 month of evolution showed cerebellar atrophy in 4 cases. After 1 to 6 years of clinical follow-up, 4/8 children had clinical sequellae, including 3 of the 4 children with initially abnormal NMR. Conversely, the 2 patients with initially normal NMR had a good clinical recovery. NMR during the acute phase gives informations on prognosis in patients with severe acute ataxia.     

Genetic aspects of congenital cerebellar ataxia

Congenital cerebellar ataxia comprises a heterogeneous group of birth defects involving brain stem and cerebellum, characterised by ataxia, spasticity, choreoathetoid movements and mental retardation. Three children with congenital cerebellar malformations are described. The presenting features were benign enlargement of head, myoclonic jerks, episodes of hypernoia, nystagmus, ataxia, motor delay and mental retardation. Computerised tomography revealed Dandy-Walker cyst in one case and in two cases cerebellar vermis agenesis was associated with a variable degree of brain stem involvement. Retinal dysplasia and post-axial polydactyly were associated abnormalities in one case as reported in Joubert's syndrome, an autosomal recessive type of familial cerebellar vermis dysgenesis. Genetic factors in the pathogenesis of congenital cerebellar ataxia are reviewed. The relevance of computerised tomography, electroretinography and prenatal diagnosis by fetal ultrasound is discussed. Genetic counselling in congenital cerebellar ataxia presenting in the first year of life is important because of the high risk of recurrence.     

Serum autoantibodies in childhood opsoclonus-myoclonus syndrome: An analysis of antigenic targets in neural tissues

Objective: Opsoclonus-myoclonus (OM) is a rare neurologic syndrome affecting children and adults. In children it occurs as a parainfectious process or a paraneoplastic syndrome in association with neuroblastoma. Evidence for an immune mechanism includes the presence of serum autoantibodies to several neural antigens and improvement of symptoms with immunosuppressive therapy. We studied the neural antigenic targets of serum IgM and IgG autoantibodies from nine children with OM.Design: We studied sera from nine children with OM, three with associated neuroblastoma and six with a prodromal viral illness. Control subjects (n = 77) included four children with neuroblastoma but not OM, 32 children with other neurologic disorders, and 41 with nonneurologic illnesses. We studied the neural antigenic targets of serum IgM and IgG autoantibodies by the following methods: (1) immunostaining of human cerebellar sections and peripheral nerve, and (2) Western blot analysis with human brain fractions including white matter, gray matter, and cerebellar Purkinje cells and nuclei.Results: Sera from all nine children with OM had IgM and IgG binding to the cytoplasm of cerebellar Purkinje cells and to some axons in white matter. In peripheral nerve, IgM and IgG from all nine OM sera bound to large and small axons. Western blot analysis showed a distinctive pattern of binding to several neural proteins, including a 210 kd antigen identified as the high molecular weight subunit of neurofilament. No control serum showed a similar pattern of reactivity.Conclusion: Opsoclonus-myoclonus syndrome in childhood is associated with a distinctive pattern of serum IgM and IgG binding to neural tissues and antigens.     

Articular and cutaneous prodromal manifestations of viral hepatitis.

The association of arthritis, arthralgia, and various types of skin rashes, as a prodrome to viral hepatitis, although well recognized in adults, has not been well described in children. In an 18-month period, three children presented with this serum sickness-like illness before the onset of evident liver involvement. In one case, the prodromal symptoms occurred four weeks before biochemical or clinical evidence of hepatitis. The SSLI tended to subside with the onset of clinically evident liver disease. Hepatitis B surface antigen (HBsAg, Australia antigen) was detected in the sera of two patients, but free antibody to the antigen was not demonstrable in either one. Serum complement levels were low during the prodromal phase and tended to return to normal value at the onset of extensive liver involvement. The diagnosis of viral hepatitis should be considered in children presenting with polyarthritis, polyarthralgia, and a rash (serum sickness-like illness) of uncertain etiology.     

Pseudotumoral acute hemicerebellitis in a child

Acute cerebellitis is an inflammatory disorder usually involving both sides of the cerebellum and presenting with localized signs such as ataxia. Hemicerebellitis is extremely rare in children and may clinically and radiologically resemble a tumor. There are very few reports of hemicerebellitis needing decompressive surgery. We report a case of hemicerebellitis in a 15 year old child presenting with severe headache but no cerebellar symptoms whose brain CT revealed an ill-defined mass compressing the fourth ventricle (pseudotumoral). MRI of the posterior fossa revealed a swollen left cerebellar hemisphere, supra-tentorial hydrocephalus and tonsil herniation, without any cerebral or brain stem lesions. Due to worsening symptoms she required a decompressive craniectomy, and the biopsy revealed an inflammatory process, possibly viral. At follow-up she was asymptomatic and the MRI revealed only slight cerebellar atrophy. This case had an atypical clinical presentation and illustrates that though a self-limited evolution is expected, surgical intervention may be needed in acute cerebellitis.     

Acute encephalitis in Swiss children: aetiology and outcome.

Since published data on the course and prognosis of encephalitis in Central Europe is limited, we retrospectively evaluated 104 children with either acute strict sense encephalitis (n = 80) or acute cerebellar ataxia (n = 24) treated at the Department of Pediatrics, University of Bern, Switzerland, between 1980 and 1991. Of the 80 patients with strict sense encephalitis, four (5%) died acutely and 28 (36%) of 78 followed up had sequelae - eight patients with severe, six with moderate and 14 with mild sequelae. Young age and seizures were shown to correlate with poor outcome. Among the 24 patients with acute cerebellar ataxia, there was no fatal outcome and none developed severe residua, but six had mild and one had moderate sequelae. Initial cerebrospinal fluid white cell count was significantly higher in these children with sequelae compared with those without any sequelae after acute cerebellar ataxia.     

Acute childhood encephalitis and encephalopathy associated with influenza: a prospective 11-year review

BACKGROUND: Influenza virus infection has been associated with a variety of neurologic complications. The objective of this study was to evaluate prospectively the role of influenza viruses in acute childhood encephalitis/encephalopathy (ACE). METHODS: All children admitted to the Hospital for Sick Children, Toronto, during an 11-year period with ACE and evidence of acute influenza virus infection were included. Acute influenza virus infection was defined by detection of the organism in the nasopharynx by direct immunofluorescence microscopy or viral culture and/or by a 4-fold or greater rise in complement fixation titer. RESULTS: A total of 311 children with ACE were evaluated; evidence of influenza infection was detected in 7% (22 of 311). Eight were excluded from the main analysis because of evidence implicating other potential pathogens. Eleven of the 14 included subjects were <5 years of age. A respiratory prodrome was documented in 93% of subjects. In 64% neurologic manifestations developed within 5 days of onset of respiratory symptoms. Neuroimaging abnormalities were more common in children <2 years of age. Neurologic sequelae occurred in more than one-half of subjects. CONCLUSIONS: In this prospective registry, influenza virus infection was associated with 5% of ACE cases. The majority of children were <5 years of age and the prevalence of neuroimaging abnormalities was higher in children <2 years of age suggesting that younger children are predisposed to the neurologic complications of influenza. An acute rather than a postinfectious process was suggested by the briefness of the respiratory prodrome in most cases.     

Isolated deafness following recovery from neurologic injury and adult respiratory distress syndrome. A sequela of intercurrent aminoglycoside and diuretic use

We report two children who survived neurologic injury (near-drowning and Reye's syndrome) and adult respiratory distress syndrome and who required prolonged ventilatory support. Follow-up examination in both children showed steady neurologic recovery, but five months following discharge from their acute illness, profound hearing loss was diagnosed in both children. A review of the literature is reported and the hypothesis that combined aminoglycoside antibiotic and loop diuretic therapy caused the hearing loss is presented. Recommendation is made for audiologic assessment within six months of recovery from critical illness of pediatric patients in whom therapy has included loop diuretic and aminoglycoside antibiotic therapy.     

The CSF-protein pattern in acute cerebellar ataxia of childhood and intracranial midline tumours

CSF-protein profiles of 25 children with acute cerebellar ataxia and of 39 children with intracranial midline tumours at diagnosis were examined by quantitative zone electrophoresis in agarose gel. The profiles were compared with those obtained from a control group of 86 cases, and those from 61 patients with aseptic meningitis and 40 children with bacterial meningitis. The data from the latter groups demonstrated the CSF-protein pattern of moderate or severe disturbance of the blood-CSF barrier (B-CSF-B), respectively. The children with acute cerebellar ataxia showed minor signs of a B-CSF-B impairment and no increase of -globulin. These findings point to a slight acute vascular lesion. CSF changes indicative of a moderate-to-severe dysfunction of the B-CSF-B occurred in the majority of the patients with cerebellar astrocytomas, pontine gliomas, tumours around the 3rd ventricle, and medulloblastomas. Therefore acute cerebellar ataxia can be differentiated from intracranial midline tumours in most cases by means of CSF-protein electrophoresis. A striking finding was that 12 out of 14 children with medulloblastomas revealed a marked increase of -globulin. Since in 5 of these cases oligoclonal -globulin could be detected, this finding means local immunoglobulin synthesis within the CNS. The marked increase of -globulin which almost exclusively occurred in association with medullo-blastomas allows their seperation from acute cerebellar ataxia and the other tumour groups. Quantitative agarose gel electrophoresis can be a complementary diagnostic test in children with acute ataxia and suspected of having a CNS infection, or in cases with a negative CT brain scan in which intracranial midline tumour is a likely possibility.