RESUMEN
BACKGROUND AND AIMS: Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae), an intracellular bacillus that systematically invades the peripheral nerves. Diagnosing leprosy neuropathy is still a defying skill, and late diagnosis and treatment are still a reality. Based on the biological characteristics of M. leprae, particularly its preference for invading the Schwann cells localized at the coldest areas of human body, we hypothesized that these areas have focal demyelination that may escape detection through standard nerve conduction studies (NCSs) protocols. METHODS: Twenty-five patients with confirmed multibacillary leprosy and 14 controls were accessed. A multisegmented NCS protocol (MP) was performed, targeting short segments through the coldest areas, to identify focal areas of slowed conduction velocity. The effectiveness of this multisegmented protocol was compared to the standard protocol (SP) to detect abnormalities. RESULTS: All leprosy patients presented an abnormal study with the MP, contrasting to 19 with the SP. The most frequent NCS pattern was an asymmetric neuropathy with focal slowing of conduction velocity, found in 23 out of 25 leprosy patients. Significant differences favoring the proposed method were observed when comparing the MP with the SP. Notably, the MP increased the sensitivity to detect abnormalities by 122%, 133%, and 257% for the median, peroneal, and tibial nerves, respectively. MP also increases sensitivity to detect focal abnormalities in the ulnar nerve. INTERPRETATION: The MP protocol significantly increases the sensitivity of NCSs to detect neurophysiological abnormalities in leprosy neuropathy.
Asunto(s)
Conducción Nerviosa , Humanos , Conducción Nerviosa/fisiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Lepra/fisiopatología , Lepra/complicaciones , Adulto Joven , Nervios Periféricos/fisiopatología , Lepra Multibacilar/fisiopatología , Lepra Multibacilar/diagnósticoRESUMEN
The most common causes of congenital myasthenic syndromes (CMS) are CHRNE mutations, and some pathogenic allelic variants in this gene are especially frequent in certain ethnic groups. In the southern region of Brazil, a study found the c.130dupG CHRNE mutation in up to 33% of families with CMS. Here, we aimed to verify the frequency of this mutation among individuals with CMS in a larger cohort of CMS patients from different areas of Brazil and to characterize clinical features of these patients. Eighty-four patients with CMS, from 72 families, were clinically evaluated and submitted to direct sequencing of the exon 2 of CHRNE. The c.130dupG mutation was found in 32 patients (23 families), with 26 patients (19 families, 26.3%) in homozygosis, confirming its high prevalence in different regions of Brazil. Among the homozygous patients, the following characteristics were frequent: onset of symptoms before 2 years of age (92.3%), little functional restriction (92.3%), fluctuating symptoms (100%), ocular muscle impairment (96.1%), ptosis (100%), limb weakness (88.4%), response to pyridostigmine (100%), facial involvement (77%), and bulbar symptoms (70.8%). The pretest probability of finding at least one allele harbouring the c.130dupG mutation was 38.1%. Selecting only patients with impaired eye movement together with limb weakness and improvement with pyridostigmine, the probability increases to 72.2%. This clinical pre-selection of patients is likely a useful tool for regions where CHRNE mutations have a founder effect. In conclusion, the CHRNE mutation c.130dupG leads to fairly benign natural course of the disease with relative homogeneity.