RESUMEN
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) may involve many target organs with relevant variability among affected individuals. We performed a multi-organ assessment tapping nervous system, skeletal muscle and cardiovascular system in thirty-nine individuals belonging to 16 families from Central Italy sharing the same R1006C CADASIL mutation. Stroke prevalence was larger in female patients (66.7%) than in males (23.8%); high levels of CKemia were quite frequent (21.6%) and were related to a myopathy without mitochondrial alterations; several individuals had atrial septal aneurysm (10.3%). No specific relationships between common cardiovascular risk factors and clinical manifestations were found. The present systematic study thus identified several gender-related, myopathic and cardiovascular peculiarities of R1006C mutation. This kind of comprehensive approach is necessary to define clinical course, prognosis and treatment options for a multi-organ disease such as CADASIL.
Asunto(s)
Arginina/genética , CADASIL/genética , Cisteína/genética , Salud de la Familia , Mutación/genética , Receptores Notch/genética , Adulto , Anciano , Anciano de 80 o más Años , CADASIL/sangre , CADASIL/complicaciones , CADASIL/diagnóstico , Anomalías Cardiovasculares/etiología , Colesterol/metabolismo , Creatina Quinasa/sangre , Progresión de la Enfermedad , Electromiografía , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Italia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Músculo Esquelético/fisiopatología , Conducción Nerviosa , Neurofisiología , Pruebas Neuropsicológicas , Fenotipo , Receptor Notch3 , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary small vessel disease responsible for an early onset cognitive impairment. Aim of our study was to test the cortical cholinergic innervation in CADASIL by short latency afferent inhibition (SAI) technique. METHODS: We applied SAI in ten CADASIL patients and in ten age-matched normal controls. SAI is a phenomenon observed on motor evoked potential when transcranial magnetic stimulation is delivered after a time ranging from 2 to 8 ms longer than the time needed by the peripheral nerve afferent input to reach the somatosensory cortex. RESULTS: The amount of short latency afferent inhibition was significantly smaller in CADASIL patients than in controls (79.5+/-21.7% Vs 42.7+/-14.1% of test size; p<0.001, two tailed Mann-Whitney test). The mean resting motor threshold (RMT) was significantly lower in CADASIL patients than in controls (49.4+/-14.4% Vs 65.6+/-15.4%; p=0.02). CONCLUSIONS: We demonstrated by SAI technique a central cholinergic impairment in CADASIL. SIGNIFICANCE: SAI could be used to evaluate the cholinergic dysfunction and potentially the efficacy of cholinomimetic therapy in CADASIL.
