Biomedical subjects
Publications and source records attributed to M Iivanainen.
EAE in monkeys resulted in CSF OCB appearing 2 to 3 weeks p.i., with BP and complete Freund's adjuvant. Clinical signs appeared close to the time that the bands were first detected. The animals had serum measles antibodies, however, the titers did not change during the development of EAE and no measles antibodies were detected in the CSF.
A rare case of fatal Candida albicans meningitis in a healthy middle-aged woman is reported. The organism did not grow in four of the six cerebrospinal fluid cultures despite clinical meningo-encephalitic symptoms and clear cell reaction in cerebrospinal fluid. Death was unexpected with a generalised tonic-clonic seizure and cardiac arrest. A possible relationship between the coexistent long-standing intra-uterine contraceptive device and Candida meningitis is discussed.
A survey of 15 families in the USA with Baltic myoclonus epilepsy showed that the 27 individuals who were affected had the following clinical picture from about the age of 10: photosensitive, occasionally violent, myoclonus, usually worse upon waking; generalised tonic-clonic seizures, sometimes associated with absence attacks; and light-sensitive, generally synchronous, spike-and-wave discharges on EEG that preceded clinical manifestations. Necropsy revealed marked loss of Purkinje cells of the cerebellum, but no inclusion bodies. Since the disease was confined to sibs and consanguinity was present in two families, autosomal recessive inheritance is probable. The disease progressed more rapidly in these families than it did in the early cases, seen in the Baltic region. This difference could be due to a toxic effect of phenytoin because phenytoin given alone or with other antiepileptic drugs was associated with progressive motor and intellectual deterioration, marked ataxia, and even death. Treatment with valproic acid, and the concomitant reduction or elimination of phenytoin, has been associated with marked improvement in at least 8 patients. Baltic myoclonus epilepsy must be distinguished from Lafora body disease, which is invariably fatal and discernible on clinical grounds.
We studied the frequency of oligoclonal immunoglobulin G bands in the cerebrospinal fluid (CSF) of patients with various neurological diseases. We used a micromethod employing sodium dodecyl sulfate polyacrylamide gel electrophoresis that required only 50 microliters of unconcentrated CSF. Oligoclonal bands were detected in the CSF of 95% of the patients with multiple sclerosis, 90% with subacute sclerosing panencephalitis, and 100% with herpes simplex encephalitis, but less frequently in other central nervous system infections. No oligoclonal bands were detected in the CSF of patients with Parkinson, Huntington, Creutzfeldt-Jakob, or herniated disc diseases. Bands were detected in some patients with Alzheimer disease, cerebrovascular accident, idiopathic vertigo, idiopathic seizures, amyotrophic lateral sclerosis, polyneuropathy, and central nervous system glioma. Patients with other conditions infrequently had positive bands. The determination of oligoclonal bands is a useful aid in the diagnosis of multiple sclerosis, subacute sclerosing panencephalitis, and herpes simplex encephalitis. The presence of oligoclonal bands indicates an immunological response but is not diagnostic for a particular condition.
Increased serum levels of a variety of bacterial antibodies were more common in unselected patients with recent epileptic seizures than in healthy control subjects (17/29 versus 2/31; p less than 0.001). In most of these cases no infections were recognized clinically or bacteriologically. Although infections have been considered as one of the possible provocations for the manifestation of epileptic seizures, the demonstrated strong association may give a new approach to the pathogenetic mechanisms of epileptic seizures or may mean a nonspecific immune response. The explanation for the higher antibody titers in epileptic patients and their etiologic significance are uncertain, but these results also suggest that epileptic seizures may very often be triggered by bacterial infections even when no clinically apparent bacterial infection has been recognized.
Phenobarbital and phenytoin have good antiepileptic effect, but clinically significant untoward effects occur during their long-term use. Phenobarbital may cause hyperactivity, behavioral problems, sedation, and even dementia; these effects are dose related to some extent. Side effects of phenytoin include sedation, a cerebellar syndrome, phenytoin encephalopathy, psychosis, locomotor dysfunction, hyperkinesia, megaloblastic anemia, decreased serum folate level, decreased bone mineral content, liver disease, IgA deficiency, gingival hyperplasia, and a lupus-like hypersensitivity syndrome. Especially susceptible to the neurotoxic effects of phenytoin are epileptic children with severe brain damage who are on multiple drugs. In those children, balance disturbance may develop and be followed by gradual loss of locomotion. Among 131 mentally retarded epileptic patients, phenytoin intoxication occurred in 73 (56%), of whom 18 experienced persistent loss of locomotion. There is experimental evidence that the toxic action of phenytoin lies at the cellular level, predominantly in the cerebellum. Many experts avoid the long-term use of phenytoin because of its insidious and potentially dangerous side effects.
A patient with pontocerebellitis associated with infectious mononucleosis is described. The clinical picture with transitory limb and truncal ataxia was compatible with previous reports of cerebellitis. CT showed wide pontocerebellar cisterns and a hypodense area in the pons.
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Twenty-six adults with severe progressive myoclonus epilepsy (PME) were admitted to a long-term prospective clinical study; 19 were followed up for six years. The previous medication, phenytoin sodium and other antiepileptic drugs, was changed to valproate sodium (Deprakine [Finland]; Depakene Syrup, comparable US product), clonazepam (Clonopin), and phenobarbital, and the patients' conditions improved. After six years of follow-up, the favorable result continued. The mean plasma concentration in 26 patients after four months of follow-up was 27.8 +/- 6.9 mg/L for valproate, 0.053 +/- 0.025 mg/L for clonazepam, and 19.2 +/- 7.9 mg/L for phenobarbital. The clinical response was not in accordance with the plasma drug concentrations when the data of the whole population were statistically analyzed. The classification of disability of patients with PME into five degrees was useful. The longlasting favorable result suggests that the combination of valproate, clonazepam, and phenobarbital is the most effective therapy for severe PME.
The enzyme-linked immunosorbent assay (ELISA) was used to determine levels of specific IgG antibodies against measles, rubella, vaccinia, corona (OC43) and mumps viruses in cerebrospinal fluid (CSF) and serum of 18 patients with clinically definite multiple sclerosis (MS), 8 patients with optic neuritis (ON), 27 patients with other neurological disease (OND), and 88 control subjects without central nervous system disease. Serum antibody levels were not significantly different between the four groups. Differences in the frequency and levels of CSF antibodies between the four groups were observed. Control patients had serum/CSF antibody ratios from 2.0 to 3.0 (log) with an average of 2.5 corresponding to a 320-fold difference between serum and CSF antibody levels. MS patients had ratios from 1.1 to 2.1 with an average of 1.6. The average was 2.0 for the ON patients. The average for the OND patients was similar to the controls. The altered serum/CSF ratios for several viruses within an individual patient was similar. These results suggest that nonspecific immunostimulation is responsible for the increased levels of CSF virus antibodies.
Cerebrospinal fluid (CSF) cells and proteins were determined for 33 patients exposed to industrial organic solvents. A lymphoid reaction, i.e., a pathologically elevated number or percentage of enlarged lymphoid cells was observed in one-third of the patients, more often in patients with chronic intoxication (40%) than in those currently exposed to organic solvents (32%). An almost significant decrease of small lymphocytes in the CSF was observed among patients who had a past history of chronic solvent intoxication but no recent exposure. No cytological evidence of tissue destruction was found. Signs of slight blood--CSF barrier damage occurred in 5 (23%) of the currently exposed patients, but intrathecal IgG synthesis was not observed. Increased cellular activity in the CSF was also accentuated in principal component analysis. The results suggest slight nonspecific immunoactivation in the central nervous system of subjects exposed to organic solvents.
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Three young autopsy and four temporal artery biopsy cases with an arteriographically typical moyamoya syndrome were studied by histologic, electron microscopic, and immunofluorescence methods. In all autopsy cases the intracranial segment of the internal carotid arteries showed concentric intimal thickening with severe stenosis or obstruction of the lumen, folding of the internal elastic lamina, and shrinkage of the external diameter of the vessel. Inflammatory infiltration was absent. Abnormal networks of thin-walled vessels, interpreted as secondary collaterals, were seen at the base and on the convexity of the brain. Degenerative changes, including a ruptured coronary aneurysm in one case, were also noted in the coronary and temporal arteries. In both the intra- and extracranial arteries repeated endothelial damage was indicated by the presence of redundant subendothelial basement membrane-like material. Lipid or calcium deposits were exceptional, and no evidence for the presence of immunoglobulins or components of the complement could be obtained by immunofluorescence. These pathologic alterations, distinct from atherosclerosis, fibromuscular dysplasia, and the established types of arteritis, seem to be identical in children and adults, in spite of different clinical manifestations of the moyamoya syndrome in these age groups. We suggest that a humoral factor, associated with infections, may induce repeated endothelial damage and intimal thickening in the intracranial arteries of genetically predisposed children in analogy with recent observations made in the coronary arteries of young subjects.
We studied CSF and serum samples from 16 patients with progressive myoclonus epilepsy (PME). These patients had juvenile-onset PME with evidence of autosomal recessive inheritance and no Lafora bodies. Twelve of the 16 patients with PME had immunologic abnormalities. Oligoclonal gamma bands were seen in six of the eight patients from whom sufficient CSF was available. The CSF albumin and serum/CSF albumin ratios were normal in all 16 patients, indicating the presence of intact blood-brain barriers. Six of the 16 patients showed increased CSF IgG levels and five had an increased CNS IgG synthesis. All patients had normal serum and CSF IgM and IgA levels. Three patients, all with bands, had reduced measles and/or vaccinia serum/CSF antibody ratios. The findings suggest altered immune response of the CNS of some patients with PME apparently caused by nonspecific immunostimulation.
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Patients with multiple sclerosis and matched controls were tested for lymphocyte stimulation response and induction of suppressor cell activity in response to concanavalin A (Con A) and antigens from axolemma or myelin. Of 17 stable patients, 6 failed to have a suppressor cell response activated by one of these brain cell antigens. Among the patients who lacked these suppressor responses, five had lymphocyte stimulation responses to the same antigens. All matched controls except for one had suppressor cell responses to these antigens and none responded with a positive cellular immune reaction. We found no difference in lymphoproliferative responses to Con A in patients and controls. The level of suppressor cell activity induced by Con A in the stable MS patients varied but did not differ significantly from that of controls.