Increased concentration of interferon lambda-3, interferon beta and interleukin-10 in the cerebrospinal fluid of patients with tick-borne encephalitis.

Tick-borne encephalitis (TBE) has a wide clinical spectrum, from asymptomatic to severe encephalitis, and host-dependent factors determining the outcome remain elusive. We have measured concentrations of pro-inflammatory/Th1 interferon-γ (IFNγ), immunomodulatory/Th2 interleukin-10 (IL-10), anti-viral type I (IFNß) and type III (IFNλ3) interferons in cerebrospinal fluid (csf) and serum of 18 TBE patients, simultaneously genotyped for polymorphisms associated with the expression of genes IFNL3 (coding IFNλ3), IL10, CD209 and CCR5. IL-10, IFNß and IFNλ3 were up-regulated in csf, with IFNλ3 level higher in patients with the milder clinical presentation (meningitis) than in meningoencephalitis. There was an increased serum IFNß and a tendency for increased serum IL-10 in meningitis patients. Genotype in rs12979860 locus upstream of IFNL3 was associated with IFNλ3 expression and in rs287886 (CD209) - IL-10 expression. IL-10, IFNß and IFNλ3 are expressed and play a protective role in TBE and their expression in TBE patients is associated with genetic polymorphisms.

A coincidental case of young-onset Parkinson disease and multiple sclerosis.

BACKGROUND: Parkinsonism in patients with multiple sclerosis is rare. Some patients have 2 coincidental diseases, whereas others have a Parkinsonian syndrome symptomatic to demyelinating lesions. CASE REPORT: We describe a 42-year-old female patient who developed left akinetic-rigid Parkinsonian syndrome at the age of 38 years. Brain magnetic resonance imaging revealed multiple white matter hyperintense T2-weighted lesions. DaTSCAN revealed reduced uptake of dopamine transporter in the right striatum. Intravenous corticosteroids were inefficacious. She had major clinical improvement with levodopa and 6 months later developed peak-dose dyskinesias. At the age of 41 years, she presented with a brainstem attack, with complete symptom resolution after intravenous corticosteroids. Subsequent brain magnetic resonance imagings disclosed new inflammatory lesions. Immunomodulatory treatment was started with ß-interferon. COMMENTS: In this patient, the presence of an asymmetrical Parkinsonian syndrome, with good response to levodopa, peak-dose dyskinesias, and abnormal DaTSCAN, supports the diagnosis of young-onset Parkinson disease. The multiple sclerosis diagnosis was established based on clinical evidence of time and space dissemination of demyelinating lesions.

Biological markers for multiple sclerosis.

Multiple sclerosis (MS) is the most common disabling neurological disease in young adults and is thought to result from an autoimmune attack against autoantigens within the myelin sheath. A characteristic feature of MS is the broad heterogeneity of clinical, histopathological and immunological phenotypes, which urges a more differentiated defining of patients by biological markers that reflect the underlying disease process and allow the prediction of disease courses and treatment responses. Here we review the current research on the identification of biomarkers for MS in cerebrospinal fluid and/or blood. We will focus on antibodies to myelin and non-myelin antigens, cells and soluble molecules of the immune system and the brain as biomarkers for 1) the diagnosis and prediction of clinical courses, 2) disease activity and 3) treatment response in MS.

The historical development of interferons as multiple sclerosis therapies.

Human interferon (IFN) beta is the first therapeutic agent to convincingly reduce the multiple sclerosis relapse rate and retard disability. To achieve this significant treatment advance over 15 years of preliminary work was necessary, encompassing over 15 controlled trials which employed each of the three human interferons. Important insights into the pathogenesis of multiple sclerosis (MS) were gained, especially from the findings of the single IFN-gamma trial. This short history describes the unfolding of our current understanding of the place for IFNs in the management of MS. The contribution of the patients who have participated is recognized and their courage acknowledged. The final role for IFN treatment of MS is unclear, but future studies will be required to define the best IFN, optimal dose, and route of administration and patient selection for long-term management of MS.