Insomnia and Dysautonomia with Contactin-Associated Protein 2 and Leucine-Rich Glioma Inactivated Protein 1 Antibodies: A "Forme Fruste" of Morvan Syndrome?

Morvan syndrome (MoS) is typically characterized by neuromyotonia, sleep dysfunction, dysautonomia, and cognitive dysfunction. However, MoS patients with mild peripheral nerve hyperexcitability (PNH) or encephalopathy features have been described. A 46-year-old woman presented with a 2-month history of constipation, hyperhidrosis, and insomnia. Neurologic examination revealed muscle twitching and needle electromyography showed myokymic discharges in all limbs. No clinical or electrophysiological features of neuromyotonia were present. Although the patient denied any cognitive symptoms, neuropsychological assessment revealed executive dysfunction, while other cognitive domains were preserved. Cranial and spinal MRIs were unrevealing and tumor investigation proved negative. Polysomnography examination revealed total insomnia, which was partially reversed upon immune-modulatory therapy. Investigation of a broad panel of antibodies revealed serum leucine-rich glioma inactivated protein 1 and contactin-associated protein 2 antibodies. The features of this case indicate that the presentation of PNH syndromes may show significant variability and that MoS patients may not necessarily exhibit full-scale PNH and encephalopathy symptoms.

Predictive value of early serum cytokine changes on long-term interferon beta-1a efficacy in multiple sclerosis.

BACKGROUND: In a previous study, we had evaluated short-term effects of interferon beta-1a (IFNB-1a) 44 µg s.c. three times per week treatment on serum levels of IFN-gamma (IFNG), IL-23, IL-17, IL-10, IL-9, IL-4 and TGF-beta (TGFB) and found a reduction only in IL-17 and IL-23 levels after 2 months of treatment. METHODS: Using the same multiple sclerosis (MS) cohort, we assessed the predictive value of early cytokine level changes (difference between 2nd month and baseline levels as measured by ELISA) on the efficacy of long-term IFNB-1a treatment. RESULTS: The alteration in IFNG levels of patients without any relapse was statistically lower than that of patients having one or more relapses (p = 0.019, Student's t-test). When patients with or without expanded disability severity scale (EDSS) progression were compared, none of the cytokine level changes showed a significant difference between groups. IL-17 and IL-23 level changes did not predict relapse and EDSS progression in IFNB-1a-treated MS patients. CONCLUSION: Our results show that the predictive power of early IFNG measurement on relapse occurrence may potentially extend a time span of several years.

Effect of short-term interferon-ß treatment on cytokines in multiple sclerosis: significant modulation of IL-17 and IL-23.

Therapeutic effect of interferon-ß (IFN-ß) treatment has been associated with modulation of the balance between Th1, Th17, Th2 and regulatory T (Treg) cells, whereas the impact of disease modifying drugs on Th9-immunity in multiple sclerosis (MS) has not been studied. To investigate the short-term effects of IFN-ß treatment on cytokines in MS, we determined serum levels of IL-17, IL-23, IL-10, IL-4, IFN-γ, IL-9 and TGF-ß in relapsing remitting MS patients before and 2 months after IFN-ß treatment by ELISA. MS patients showed increased IL-17, IL-23 and IL-4 levels and decreased IL-9 levels as compared to healthy controls. IFN-ß treatment only reduced IL-17 and IL-23 levels, whereas the levels of other cytokines remained unchanged. IFN-ß treatment appears to exert its earliest therapeutic effect on Th17-immunity. The influence of IL-9 on MS pathogenesis needs to be further studied.

Multiple sclerosis and Hashimoto thyroiditis: two cases.

Multiple sclerosis (MS) occurs with immune-mediated mechanisms, but its pathogenesis is not accurately known. The coexistence of MS with other autoimmune diseases has been reported. The hypothesis that MS coexists with other autoimmune diseases has been supported by the reported association of MS with type I diabetes mellitus and inflammatory disorders. Even though there have been only rare reports of associations between Hashimoto thyroiditis and MS, this association is important for its clinical and therapeutic aspects. Proximal muscle weakness, myalgia, and fatigue are symptoms that are common in both MS and hypothyroidism. When MS patients demonstrate these symptoms, thyroid function tests should be performed. The thyroid hormone levels of MS patients being treated with interferon-beta and Campath-1H also should be monitored. The authors report the clinical data of 2 definite MS patients who also fulfilled criteria for Hashimoto thyroiditis.