Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042961 (volvulus)
 4,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nodding syndrome is an epileptic disorder of unknown etiology that occurs in children in East Africa. There is an epidemiological association with Onchocerca volvulus, the parasitic worm that causes onchocerciasis (river blindness), but there is limited evidence that the parasite itself is neuroinvasive. We hypothesized that nodding syndrome may be an autoimmune-mediated disease. Using protein chip methodology, we detected autoantibodies to leiomodin-1 more abundantly in patients with nodding syndrome compared to unaffected controls from the same village. Leiomodin-1 autoantibodies were found in both the sera and cerebrospinal fluid of patients with nodding syndrome. Leiomodin-1 was found to be expressed in mature and developing human neurons in vitro and was localized in mouse brain to the CA3 region of the hippocampus, Purkinje cells in the cerebellum, and cortical neurons, structures that also appear to be affected in patients with nodding syndrome. Antibodies targeting leiomodin-1 were neurotoxic in vitro, and leiomodin-1 antibodies purified from patients with nodding syndrome were cross-reactive with O. volvulus antigens. This study provides initial evidence supporting the hypothesis that nodding syndrome is an autoimmune epileptic disorder caused by molecular mimicry with O. volvulus antigens and suggests that patients may benefit from immunomodulatory therapies.
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PMID:Nodding syndrome may be an autoimmune reaction to the parasitic worm Onchocerca volvulus. 2995 Sep 43

Nodding syndrome is an enigmatic neuropsychiatric and epileptiform disorder associated with psychomotor, mental, and physical growth retardation. The disorder affects otherwise previously normal children aged 3-18 years, with a slight preponderance for the male child. Nodding syndrome has been described in rural regions of some low-income countries in sub-Saharan Africa including northern Uganda, South Sudan, and a mountainous region of southern Tanzania. The cause of the disorder has hitherto eluded scientists. Neuroimaging studies show involvement of the nervous system with associated severe cortical atrophy in the affected children. The affected communities have generated a number of perceived causes including some conspiracy theories related to intentional poisoning of water sources and foods, and causes related to fumes and chemicals from ammunitions used during civil wars in the affected regions. From biomedical perspectives, the treatment of the affected children is geared towards symptoms control and rehabilitation. There is evidence that seizures and behavioral problems including wandering and episodes of aggressions are controllable with anticonvulsants, especially sodium valproate and antipsychotics. No treatments have proven effective in reversing the course of the disorder, and cure remains a distant goal. Community members have used indigenous medicines, cleansing rituals, and prayer interventions, but have not perceived any reasonable improvements. A randomized controlled clinical trial is ongoing in northern Uganda to test the efficacy and effectiveness of doxycycline in the treatment of nodding syndrome. The hypothesis underlying the doxycycline trial underscores the role of antigenic mimicry: that antibodies generated against an antigen of a microorganism that resides inside the black fly-transmitted parasite, Onchocerca volvulus becomes directed against nervous tissue in the brain. This paper reviews some of the recent advances in researches on the etiologies, pathophysiology, and treatment of nodding syndrome.
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PMID:Nodding syndrome: recent insights into etiology, pathophysiology, and treatment. 3005 Mar 59