vitamin-b-12 and Cerebellar-Diseases

Vigabatrin is the drug of choice in resistant epilepsy and infantile spasms. Ataxia, tremors, and abnormal gait have been frequently reported following its use indicating cerebellar involvement. This study aimed, for the first time, to investigate the involvement of necroptosis and apoptosis in the VG-induced cerebellar cell loss and the possible protective role of combined omega-3 and vitamin B12 supplementation. Fifty Sprague-Dawley adult male rats (160-200 g) were divided into equal five groups: the control group received normal saline, VG200 and VG400 groups received VG (200 mg or 400 mg/kg, respectively), VG200 + OB and VG400 + OB groups received combined VG (200 mg or 400 mg/kg, respectively), vitamin B12 (1 mg/kg), and omega-3 (1 g/kg). All medications were given daily by gavage for four weeks. Histopathological changes were examined in H&E and luxol fast blue (LFB) stained sections. Immunohistochemical staining for caspase-3 and receptor-interacting serine/threonine-protein kinase-1 (RIPK1) as well as quantitative real-time polymerase chain reaction (qRT-PCR) for myelin basic protein (MBP), caspase-3, and receptor-interacting serine/threonine-protein kinase-3 (RIPK3) genes were performed. VG caused a decrease in the granular layer thickness and Purkinje cell number, vacuolations, demyelination, suppression of MBP gene expression, and induction of caspases-3, RIPK1, and RIPK3 in a dose-related manner. Combined supplementation with B12 and omega-3 improved the cerebellar histology, increased MBP, and decreased apoptotic and necroptotic markers. In conclusion, VG-induced neuronal cell loss is dose-dependent and related to both apoptosis and necroptosis. This could either be ameliorated (in low-dose VG) or reduced (in high-dose VG) by combined supplementation with B12 and omega-3.

Topics: Animals; Anticonvulsants; Apoptosis; Caspase 3; Cerebellar Diseases; Dose-Response Relationship, Drug; Fatty Acids, Omega-3; Gene Expression Regulation; Male; Myelin Basic Protein; Necroptosis; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Receptor-Interacting Protein Serine-Threonine Kinases; RNA, Messenger; Vigabatrin; Vitamin B 12

A 68-year-old man presenting with chronic intermittent diarrhea and progressive ataxia was found to have idiopathic hypoparathyroidism. Intrinsic factor-resistant vitamin B(12) malabsorption was demonstrated. Both the diarrhea and vitamin malabsorption were reversed by correction of hypocalcemia.His neurological profile was a combination of peripheral nerve, posterior column and cerebellar deficits. He had calcifications in the dentate nuclei of the cerebellum. Possible etiological factors such as vitamin B(12) deficiency, folic acid deficiency and steatorrhea have been excluded. Posterior column and cerebellar abnormalities improved with treatment. It is postulated that hypocalcemia causes functional, reversible spinal cord and cerebellar dysfunction.

Topics: Aged; Calcinosis; Calcium; Cerebellar Diseases; Diarrhea; Humans; Hypocalcemia; Hypoparathyroidism; Male; Peripheral Nervous System Diseases; Phosphorus; Spinal Cord Diseases; Vitamin B 12; Vitamin D

Topics: Adolescent; Cerebellar Diseases; Cerebral Palsy; Child; Corrinoids; Drug Therapy; Electric Stimulation Therapy; Galantamine; Humans; Hyperkinesis; Infant; Movement Disorders; Vitamin B 12