Cerebrospinal fluid nitric oxide levels in subacute sclerosing panencephalitis.

Oxidative damage plays a role in neurodegenerative diseases. Levels of cerebrospinal fluid nitrite and nitrate levels (oxidation products that provide an indirect estimation of nitric oxide) were investigated in relation to clinical and laboratory features in subacute sclerosing panencephalitis (n = 47) and age-matched control (n = 43) groups. Significantly decreased levels of nitrite (median, 4.91 micromol/L) and nitrate (median, 6.14 micromol/L) were found in the patients. Nitrite and nitrate levels did not correlate with clinical or laboratory findings, except for presence of myoclonus. Cerebrospinal fluid nitrite levels of subacute sclerosing panencephalitis patients without myoclonic jerks were significantly higher than in those with myoclonus (median, 15.63 vs 4.34 micromol/L, respectively). The higher levels of nitrite in these patients can be explained by short disease duration and early stages of disease. Nitrate levels in subacute sclerosing panencephalitis patients with myoclonus (median, 9.26 micromol/L) were higher than in those without myoclonus (median, 4.25 micromol/L). Microbleeding resulting in conversion of nitrite to nitrate and increased production of superoxide can be suggested as possible mechanisms underlying these findings.

Opsoclonus-myoclonus-dysequilibrium syndrome: cytological and immunological dynamics in the serial cerebrospinal fluid in two patients.

A peculiar clinical presentation characterized by the triad of opsoclonus,myoclonus and ataxia, mainly in a form of dysequilibrium, is usually associated with infectious or paraneoplastic processes. Serial cerebrospinal fluid (CSF) analysis in two patients with opsoclonus-myoclonus-dysequilibrium syndrome suggestive of viral encephalitis were performed from disease onset for up to 8 months. A cell count, cytology, total protein and glucose concentrations in CSF, the blood-CSF barrier function, intrathecal synthesis of immunoglobulins (Ig) in class M, G and A expressed as IgM, IgG and IgA indices and oligoclonal IgG bands were monitored. Cellular and humoral alterations in both patients were slight at the onset becoming more pronounced a month later. The kinetics of the CSF changes mirrored the subacute clinical deterioration and subsequent recovery. The delayed response in the CSF measures and the gradual clinical deterioration suggest the development of subacute brain inflammation. A mononuclear pleocytosis, including macrophages and plasma cells, increased within the first month and then normalized during the following weeks. Intrathecally synthesized IgM occurred only transiently after one month of illness, whereas intrathecal IgG production increased during the first month and persisted for at least eight months. An increasing number of oligoclonal IgG bands during the course, indicative of expanding local intrathecal synthesis, was noted. The dynamics of these CSF changes supports the hypothesis that opsoclonus-myoclonus syndrome is a post-infectious immune- mediated condition.

[Paraneoplastic opsoclonus-myoclonus syndrome revealing T-cell lymphoma]. / Syndrome opsoclonus-myoclonus paranéoplasique révélateur d'un lymphome T.

BACKGROUND: Nonrhythmic involuntary ocular oscillations and axial and segmentary myoclonia are associated in the opsoclonus-myoclonus syndrome. In adults, a paraneoplastic origin is generally found. We report the first of opsoclonus-myoclonus associated with non-Hodgkin's lymphoma. CASE REPORT: A 66-year-old woman rapidly developed a typical opsoclonus-myoclonus syndrome within a few hours, presenting vertigo, cerebellous ataxia, multidirectional involuntary ocular movements and non-rhythmic axial and segmentary myoclonia. Brain computed tomography and magnetic resonance imaging demonstrated discrete diffuse anomalies of the white substance predominating in the pons. The cerebrospinal fluid showed discrete lymphocytosis. Antineuron antibodies were negative. No cause could be identified until the development 11 months later of pleomorphic T-cell mediastino-cervical lymphoma. The patient responded moderately to a CHOP regimen which had no effect on the opsoclonus-myoclonus syndrome. Death occurred after a 16-month course due to pulmonary complications. DISCUSSION: Neuroblastoma and infectious causes predominate in opsoclonus-myoclonus syndromes observed in children; in adults, the predominant cause is cancer. Antineuron, anti-Ri and anti-Hu antibodies can be evidenced in some cases, arguing in favor of a paraneoplastic mechanism. Recent reports have evidenced MRI anomalies in the pons and the cerebellum, anatomically well correlated with the opsoclonus-myoclonus syndrome. Besides small-cell bronchogenic anaplastic cancer, the possibility of cancer of the breast and uterus, and both non-Hodgkin and Hodgkin lymphoma should be explored, knowing the cancer develops several month after the opsoclonus-myoclonus syndrome.

Monoaminergic effects of high-dose corticotropin in corticotropin-responsive pediatric opsoclonus-myoclonus.

Children with the opsoclonus-myoclonus syndrome (OMS) usually respond to corticotropin (adrenocorticotrophic hormone, ACTH) treatment but the mechanism of benefit is unknown. We previously showed that both cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) concentrations are low in pediatric OMS. In this study, we measured levels of CSF Dopa, catecholamines, deaminated metabolites of catecholamines, as well as HVA and 5-HIAA in eight patients before and during treatment with ACTH. All the children were ACTH-responsive with 50-70% improvement in multiple clinical features of OMS. ACTH treatment reduced the HVA concentration in every child by a mean of 21% (p < 0.001). Treatment with ACTH was associated with significant correlations between dopaminergic markers such as HVA, dihydroxyphenylacetic acid (DOPAC), and Dopa. There were no significant changes in the CSF concentrations of the noradrenergic markers norepinephrine (NE) and dihydroxyphenylglycol (DHPG), or the serotonergic marker 5-HIAA. The only child with a marked inflammatory pattern in CSF, which was reversed by ACTH, was atypical for a large increase in NE and decrease in 5-HIAA during ACTH treatment. Beneficial effects of ACTH in OMS are not associated with normalization of HVA or 5-HIAA levels. The pattern of decreased HVA and unchanged DOPAC levels could reflect decreased extraneuronal uptake of catecholamines (which steroids inhibit) or decreased 0-methylation of catecholamines in nonneuronal cells.

Cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid in the pediatric opsoclonus-myoclonus syndrome.

To study the purported role of central monoamine disturbances in the pathophysiology of the opsoclonus-myoclonus syndrome, the serotonin metabolite 5-hydroxyindoleacetic acid and the dopamine metabolite homovanillic acid were measured in cerebrospinal fluid samples from 27 affected children and 47 age- and gender-matched control subjects by high-pressure liquid chromatography with electrochemical detection. 5-Hydroxyindoleacetic acid and homovanillic acid concentrations in the cerebrospinal fluid were approximately 30 to 40% lower in opsoclonus-myoclonus patients compared to control subjects, and the normal inverse correlation between age and monoamine metabolite concentrations in the cerebrospinal fluid of control subjects was not found in opsoclonus-myoclonus patients. Patients with the lowest values were less than 4 years old, and a subgroup had extremely low levels, but differences in older children were not significant. Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid and homovanillic acid were more positively correlated in control subjects than in opsoclonus-myoclonus patients. None of the patients exhibited high levels of monoamine metabolites. Homovanillic acid levels were slightly lower in the cerebrospinal fluid of patients receiving corticotropin or steroids at the time of lumbar puncture. Clinical variables that could be excluded were paraneoplastic etiology, anesthetic for lumbar puncture, syndrome duration, age at onset, gender, response to steroids, length of time until initiation of corticotropin or steroids, presence of seizures, opsoclonus, and functional impairment. These data suggest a disturbance and possible altered ontogeny of serotonin or dopamine neurotransmission in a subpopulation of children with opsoclonus-myoclonus with low cerebrospinal fluid levels of 5-hydroxyindoleacetic acid and homovanillic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Syndrome of opsoclonus-myoclonus caused by Coxsackie B3 infection.

Coxsackie B3 was cultured from 2 children who presented within two weeks of each other from the Cape Cod, Massachusetts, area showing opsoclonus and myoclonus. The organism was recovered from the cerebrospinal fluid of 1 patient and from the stools of both. Both children had cerebrospinal fluid pleocytosis and gradual, spontaneous resolution of their symptoms.