Interferon-beta 1b augments activation-induced T-cell death in multiple sclerosis patients.
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Cell Death↗
Biomedical subjects
F Deisenhammer
Publications and source records attributed to F Deisenhammer.
Bioavailability of interferon beta 1b in MS patients with and without neutralizing antibodies.
BACKGROUND: Neutralizing antibodies (NAB) to interferon beta (IFNbeta) occur in about one-third of MS patients treated with IFNbeta-1b and there is an association with a loss of clinical and MRI efficacy. However, there are no data regarding the bioavailability of IFNbeta-1b in patients with and without NAB. METHODS: The authors measured MxA in whole blood by ELISA, and serum-binding antibodies (SBA) by Western blot and ELISA in 134 samples of MS patients on IFNbeta-1b and 54 control subjects, and correlated the MxA levels and SBA titers with the NAB titer. RESULTS: In the IFNbeta group 84 samples were NAB negative, 21 were NAB positive (i.e., titer of > or =20), and 29 had detectable NAB (i.e., titer between 10 and 20). The median MxA concentration in NAB-negative patients was 4.09 ng/10(5) peripheral blood leukocytes (PBL), 2.37 ng/10(5) PBL in samples with detectable NAB, 0.36 ng/10(5) PBL in NAB-positive samples, and 0.27 ng/10(5) PBL in control subjects. There was no significant difference between NAB-positive samples and control subjects, otherwise the groups differed significantly from each other. SBA occurred in 49% of NAB-negative samples, in 79% of samples with detectable NAB, and in all NAB-positive samples. With regard to the SBA titer, all groups differed significantly from each other. In none of the control samples were SBA detected. CONCLUSION: The conversion of SBA into NAB depends to some degree on the SBA titer, but other mechanisms may be involved. Once NAB have developed, the bioavailability of IFNbeta as measured by MxA is completely inhibited.
Antibodies↗
Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group.
BACKGROUND: Multiple sclerosis is an autoimmune disorder characterised by the repeated occurrence of demyelinating lesions within the central nervous system. Uncontrolled studies and experimental evidence suggest beneficial effects of repeated administration of intravenous immunoglobulin (IVIg) by immunomodulating mechanisms and induction or remyelination. We aimed to investigate the efficacy of IVIg in a randomised double-blind multicentre study. METHODS: Patients with relapsing-remitting multiple sclerosis were randomly assigned a monthly dose of IVIg (0.15-0.2 g/kg bodyweight) or placebo. Duration of treatment was 2 years. The primary outcome measures were the effect of treatment on clinical disability-measured by the absolute change in Kurtzke's expanded disability status scale (EDSS) score- and the proportion of patients with improved, stable, or worse clinical disability (> or = 1.0 grade on EDSS score). FINDINGS: Of the 243 patients screened, 150 met our eligibility criteria and were randomly assigned to IVIg or placebo. Before the start of treatment two patients in the placebo group dropped out, so there were 75 patients in the IVIg group and 73 in the placebo group. Intention-to-treat analysis showed that IVIg treatment had a beneficial effect on the course of clinical disability. The EDSS score decreased in the IVIg-treated patients and increased in the placebo group (-0.23 [95% CI -0.43 to -0.03] vs 0.12 [-0.13 to 0.37], p = 0.008). In the IVIg group, the numbers of patients with improved, stable, or worse clinical disability were 23 (31%), 40 (53%), and 12 (16%) compared with ten (14%), 46 (63%), and 17 (23%) in the placebo group. Side-effects were reported in three (4%) IVIg-treated patients and in four (5%) placebo-group patients, but were not directly linked to study medication. INTERPRETATION: Monthly IVIg is an effective and well-tolerated treatment for patients with relapsing-remitting multiple sclerosis.
Adult↗
Cerebrospinal fluid ferritin in HIV infected patients with acute neurological episodes.
OBJECTIVES: To measure cerebrospinal fluid (CSF) ferritin in HIV infected patients with acute neurological episodes and to correlate the findings with the type and severity of neurological disease. METHODS: CSF ferritin and the ratio of CSF to serum albumin (QAlb) were prospectively measured in 27 consecutive HIV infected patients admitted to a specialist unit for investigation of acute neurological episodes; the results were compared with their clinical diagnoses. RESULTS: Ten patients had HIV associated dementia complex, six had cryptococcal meningitis, two had primary CNS lymphoma and nine had miscellaneous conditions including herpes simplex virus encephalitis, cytomegalovirus encephalitis, cerebral toxoplasmosis and mononeuritis multiplex. Overall, 16 (59%) patients had raised CSF ferritin levels, ranging from 13.0 to 50.2 micrograms/l, (median = 16.1 micrograms/l: normal range = 1.0-12.0 micrograms/l). Thirteen of the 16 also had normal QAlb values, implying an intact CSF-blood barrier, and thus that local synthesis of ferritin had occurred. Elevated ferritin levels were not associated with particular neurological diagnoses. In those with HIV associated dementia complex there was no correlation between CSF ferritin levels and the severity of clinical cognitive deficit or the extent of magnetic resonance imaging abnormalities. CONCLUSIONS: An elevated CSF ferritin level is a non-specific finding in HIV infected patients presenting with acute neurological episodes.
AIDS Dementia Complex↗
Treatment effects of monthly intravenous immunoglobulin on patients with relapsing-remitting multiple sclerosis: further analyses of the Austrian Immunoglobulin in MS study.
Recently, the Austrian Immunoglobulin in Multiple Sclerosis (AIMS) study showed patients with relapsing-remitting multiple sclerosis to benefit from repeated administration of intravenous immunoglobulin (IVIg). To provide a more detailed understanding of IVIg's action we performed further analyses on the time course of treatment effects and in regard to the impact of clinical disability at study entry on patients' response to medication. The AIMS trial was a randomized, placebo-controlled, double blind, multicenter trial. It included 148 patients (IVIg: 75; placebo 73) who suffered from relapsing-remitting MS, were 15-65 years old and scored from 1-6 on the Expanded Disability Status Score (EDSS). IVIg was given over 2 years in a monthly dosage of 0.15-0.2 g/kg body weight Within the first 6 months of the trial clinical disability of IVIg treated patients improved significantly from a baseline EDSS of 3.33 +/- 1.38 to a score of 3.05 +/- 1.73 (P=0.002). This improvement was retained over the subsequent 18 months of the trial (final EDSS: 3.09 +/- 1.62). In contrast, placebo-treated patients showed a slight trend for deterioration over the study period (baseline EDSS: 3.37 +/- 1.67; final EDSS: 3.49 +/- 1.83). IVIg treatment was associated with a significant reduction of relapses throughout the study which was independent of the patients' disability at baseline. The observation of clinical improvement in the early phase of IVIg medication may suggest the activation of repair mechanisms such as the promotion of remyelination while immunoregulatory effects would be expected as the cause of fewer exacerbations throughout the AIMS study. These hypotheses need to be tested in future trials.
Adolescent↗
Affinity of anti-GM1 antibodies in Guillain-Barré syndrome patients.
In this study, we investigated the affinity of anti-GM1 IgG antibodies as well as their IgG subclass distribution in a series of 38 patients with Guillain-Barré syndrome. In 7 sera elevated titres of IgG anti-GM1 antibodies could be detected. With respect to affinity there were two distinct groups of anti-GM1 antibodies: one group was of high affinity and did not cross-react with other glycolipids; the other group was of low affinity and cross-reacted with asialo-GM1. IgG1 was the predominant and almost exclusive subclass of high affinity anti-GM1 antibodies. Axonal degeneration occurred significantly more frequently in patients with high affinity anti-GM1 antibodies than in patients without anti-GM1 antibodies or in patients with low affinity anti-GM1 antibodies. The presence of anti-Campylobacter jejuni antibodies was not associated with a specific electrophysiological pattern. The prognosis was not dependent on the detection of any of the antibodies, whereas axonal loss and ventilation were associated with a poor prognosis.
Adult↗
[Clinical aspects and diagnosis of multiple sclerosis].
In this article the clinical aspects and the diagnosis of multiple sclerosis are being reviewed. The first part focuses on the different clinical features, the course of the disease, and the differential diagnosis. The second part discusses the value of the diagnostic methods.
Adult↗
Acute cerebellar ataxia after immunisation with recombinant hepatitis B vaccine.
We report one woman with acute cerebellar ataxia (ACA), a well-defined clinical syndrome, which occurred 10 days after the second vaccination with recombinant hepatitis B vaccine. The patient had no previous symptoms or signs of neurological disease and there was no evidence of neurologic disease in the family history. Within nine months the symptoms remitted completely according to other reports of ACA. As there was a close temporal connection and no noticeable other cause we assume a causal link between the vaccination and the disease. As far as we known this is the first case of ACA after hepatitis B vaccination.
Acute Disease↗
Childhood immunizations.
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Cerebellar Ataxia↗
Methadone-substitution and driving ability.
A general statement about the driving ability of HIV-positive as well as HIV-negative addicts undergoing methadone-substitution treatment cannot be made with certainty. Even isolated observations are not significant; only an individually performed assessment, free of prejudice and conscientiously done is decisive. The formal assertion that addiction equals driving-inability, which is largely practised at present, is inadmissible and therefore harmful to the therapeutic efforts for rehabilitation.
Austria↗
[Membranous lipodystrophy (Nasu-Hakola disease)].
We present a case-report and review of the literature on membranous lipodystrophy. This is a rare disease characterized by progressive presenile dementia, multiple bone cysts with pathologic fractures, generalized cerebral seizures with abnormal EEG and bilateral calcifications of the basal ganglia. Neuropathological findings are neuroaxonal dystrophy with neurofilaments in the axons, neuronal cell loss and fibrillary gliosis. The disease is usually inherited as an autosomal recessive. The pathogenesis is unknown but is believed to be an enzyme defect of the glycolipid metabolism.
Adult↗
Superficial siderosis of the central nervous system: report of three cases and review of the literature.
We present 3 cases and a review of the literature to demonstrate the current state of clinical diagnosis and therapy of superficial siderosis of the central nervous system. Typical symptoms were progressive cerebellar ataxia, spasticity and hearing loss. Repeated subarachnoid hemorrhage was indicated by persistent xanthochromia of the cerebrospinal fluid and confirmed by the presence of erythrophages, siderophages and iron-containing pigments. Deposition of free iron and hemosiderin in pial and subpial structures leads to intoxication of the central nervous system and represents the pathophysiological mechanism of superficial siderosis. Hypointensity of the marginal zones of the central nervous system on T2 weighted MR images indicates an iron-induced susceptibility effect and seems pathognomonic for superficial siderosis. In 39 of the 43 previously described cases superficial siderosis was verified by biopsy or autopsy. Today magnetic resonance imaging enables diagnosis at an early stage of the disease. Therapeutic management requires the elimination of any potential source of bleeding. In patients with unknown etiology no proofed therapy is yet available.
Aged↗
Double-tracer SPECT in patients with AIDS encephalopathy: a comparison of 123I-IMP with 99Tcm-HMPAO.
Single photon emission computed tomography (SPECT) using N-isopropyl-p-(123I)iodoamphetamine (123I-IMP) and 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) was performed in 25 patients with different clinical stages of AIDS encephalopathy. The average interval between the two examinations was 7 days. In 15 of the 25 cases (60%) 99Tcm-HMPAO scans were different from 123I-IMP scans. Uptake defects of different extent were observed in 8 of 25 cases (32%), of different extent and different location in 3 of 25 cases (12%) and of identical extent but of different location in 4 of 25 cases (16%). Differences in the uptake patterns of 123I-IMP and 99Tcm-HMPAO with regard to extent and/or location were more commonly shown in patients with early acquired immunodeficiency syndrome (AIDS) encephalopathy (P = 0.0372). In this group, 99Tcm-HMPAO showed uptake defects of greater extent more frequently than did 123I-IMP (P = 0.0156). Our data indicate different brain uptake mechanisms of 123I-IMP and 99Tcm-HMPAO in early and advanced AIDS encephalopathy.
AIDS Dementia Complex↗
[Orthostatic tremor].
Two men, aged 57 and 77 years old, reported increasing unsteadiness on standing upright for the past 2 and 5 years, respectively. It had become impossible for them to remain standing for more than 10 seconds, as otherwise they might fall down. Walking, sitting and lying were possible without difficulty. Both patients were found to have a fine tremor in both legs on standing only. There were no other neurological signs or symptoms. Electromyography of the leg muscles demonstrated tremor activity at 14-16 Hz. Propranolol, 40 mg three times daily, in the 57-year-old patient brought no improvement. However, on taking primidone, in slowly increasing doses up to 250 and 500 mg daily, respectively, the condition lastingly improved in both patients.
Aged↗