RESUMEN
Monge's disease, also known as chronic mountain sickness (CMS), is a disease that potentially threatens more than 140 million highlanders during extended time living at high altitudes (over 2500m). The prevalence of CMS in Andeans is about 15-20%, suggesting that the majority of highlanders (non-CMS) are rather healthy at high altitudes; however, CMS subjects experience severe hypoxemia, erythrocytosis and many neurologic manifestations including migraine, headache, mental fatigue, confusion, and memory loss. The underlying mechanisms of CMS neuropathology are not well understood and no ideal treatment is available to prevent or cure CMS, except for phlebotomy. In the current study, we reprogrammed fibroblast cells from both CMS and non-CMS subjects' skin biopsies into the induced pluripotent stem cells (iPSCs), then differentiated into neurons and compared their neuronal properties. We discovered that CMS neurons were much less excitable (higher rheobase) than non-CMS neurons. This decreased excitability was not caused by differences in passive neuronal properties, but instead by a significantly lowered Na(+) channel current density and by a shift of the voltage-conductance curve in the depolarization direction. Our findings provide, for the first time, evidence of a neuronal abnormality in CMS subjects as compared to non-CMS subjects, hoping that such studies can pave the way to a better understanding of the neuropathology in CMS.
Asunto(s)
Mal de Altura/fisiopatología , Células Madre Pluripotentes Inducidas/fisiología , Neuronas/fisiología , Canales de Sodio/metabolismo , Potenciales de Acción/fisiología , Adulto , Técnicas de Cultivo de Célula , Células Cultivadas , Enfermedad Crónica , Fibroblastos/citología , Fibroblastos/fisiología , Humanos , Inmunohistoquímica , Células Madre Pluripotentes Inducidas/citología , Masculino , Células-Madre Neurales/citología , Células-Madre Neurales/fisiología , Neurogénesis/fisiología , Neuronas/citología , Técnicas de Placa-Clamp , Perú , Adulto JovenRESUMEN
OBJECTIVE: To determine the frequency of spinal neurocysticercosis (NCC) in patients with basal subarachnoid NCC compared with that in individuals with viable limited intraparenchymal NCC (≤20 live cysts in the brain). METHODS: We performed a prospective observational case-control study of patients with NCC involving the basal cisterns or patients with only limited intraparenchymal NCC. All patients underwent MRI examinations of the brain and the entire spinal cord to assess spinal involvement. RESULTS: Twenty-seven patients with limited intraparenchymal NCC, and 28 patients with basal subarachnoid NCC were included in the study. Spinal involvement was found in 17 patients with basal subarachnoid NCC and in only one patient with limited intraparenchymal NCC (odds ratio 40.18, 95% confidence interval 4.74-340.31; p < 0.0001). All patients had extramedullary (intradural) spinal NCC, and the lumbosacral region was the most frequently involved (89%). Patients with extensive spinal NCC more frequently had ventriculoperitoneal shunt placement (7 of 7 vs 3 of 11; p = 0.004) and tended to have a longer duration of neurologic symptoms than those with regional involvement (72 months vs 24 months; p = 0.062). CONCLUSIONS: The spinal subarachnoid space is commonly involved in patients with basal subarachnoid NCC, compared with those with only intraparenchymal brain cysts. Spinal cord involvement probably explains serious late complications including chronic meningitis and gait disorders that were described before the introduction of antiparasitic therapy. MRI of the spine should be performed in basal subarachnoid disease to document spinal involvement, prevent complications, and monitor for recurrent disease.