methimazole and Brain-Diseases

Natural prion diseases of ruminants are moderately contagious and while the gastrointestinal tract is the primary site of prion agent entry, other mucosae may be entry sites in a subset of infections. In the current study we examined prion neuroinvasion and disease induction following disruption of the olfactory epithelium in the nasal mucosa since this site contains environmentally exposed olfactory sensory neurons that project directly into the central nervous system. Here we provide evidence for accelerated prion neuroinvasion and clinical onset from the olfactory mucosa after disruption and regeneration of the olfactory epithelium and when prion replication is restricted to neurons. In transgenic mice with neuron restricted replication of prions, there was a reduction in survival when the olfactory epithelium was disrupted prior to intranasal inoculation and there was >25% decrease in the prion incubation period. In a second model, the neurotropic DY strain of transmissible mink encephalopathy was not pathogenic in hamsters by the nasal route, but 50% of animals exhibited brain infection and/or disease when the olfactory epithelium was disrupted prior to intranasal inoculation. A time course analysis of prion deposition in the brain following loss of the olfactory epithelium in models of neuron-restricted prion replication suggests that neuroinvasion from the olfactory mucosa is via the olfactory nerve or brain stem associated cranial nerves. We propose that induction of neurogenesis after damage to the olfactory epithelium can lead to prion infection of immature olfactory sensory neurons and accelerate prion spread to the brain.

Topics: Animals; Brain Diseases; Cranial Nerves; Cricetinae; Disease Models, Animal; Mesocricetus; Methimazole; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Neurological; Neurogenesis; Olfactory Mucosa; Olfactory Nerve; Olfactory Receptor Neurons; Prion Diseases; Prions; PrPSc Proteins; Rats

A report is presented of a girl with Graves' disease, which was diagnosed at the age of 1.7 years. The mother had no thyroid disease. The patient developed signs of hyperthyroidism shortly before her first birthday, and the most prominent manifestations were accelerated skeletal maturation and linear growth, and dilatation of the brain ventricles. The latter manifestation, which has not been reported previously, was reversible upon normalisation of thyroid function with antithyroid treatment for three years.

Topics: Adrenergic beta-Agonists; Antithyroid Agents; Brain Diseases; Cerebral Ventricles; Child, Preschool; Dilatation, Pathologic; Drug Therapy, Combination; Female; Graves Disease; Growth Disorders; Humans; Infant; Methimazole; Propranolol; Treatment Outcome