ABSTRACT
Objective:To study the neurophysiological features of Kennedy disease (KD) and to figure out the function of the nervous system.Methods:Subjects were recruited from the outpatient and the ward of Peking University Third Hospital from November 2010 to November 2022. Sixty patients with KD (29 patients with KD alone, 31 KD cases with the complication of diabetes mellitus) and 60 patients with diabetic polyneuropathy (DPN) were included in this study. Electrophysiological tests were performed in all subjects, including electromyogram, nerve conduction study, somaosensory evoked potential (SEP), contact heat evoked potential (CHEP) and triple stimulation technique (TST). Student′s t-tests were conducted to compare differences intra or inter groups of nerve conduction velocity and action potential of nerve conduction study, latency and interphase of SEP, initial peak latency of CHEP and other parameters. Results:Compared with the normative value, the amplitude of the sensory nerve action potential (SNAP) declined by 30%-80% in KD patients [median nerve (0.7±0.4) μV, ulnar nerve (0.8±0.3) μV, sural nerve (1.8±0.1) μV], the amplitude of the median and ulnar nerves was lower than the sural nerves ( t=2.43, P=0.010; t=2.40, P=0.010). The conduction time of peripheral segments of SEP and CHEP was prolonged by 115%-130%, while that of the central segments was prolonged by 104%-115% in SEP. TST test/TST control declined by 40%-60% in 17 patients with KD. The amplitude of SNAP declined by 30%-50% in patients with DPN [median nerve (2.9±0.5) μV, ulnar nerve (2.6±0.6) μV, sural nerve (1.6±0.2) μV], the amplitude of the sural nerves was lower than the median and ulnar nerves ( t=2.52, P=0.006; t=2.47, P=0.007). The conduction time of peripheral segments of SEP and CHEP was prolonged by 75%-112%, while that of the central segments was normal in both SEP and CHEP in DPN patients. Compared with DPN patients, the upper limb SNAP amplitude was lower in KD patients with the complication of diabetes mellitus [median nerve (0.7±0.3) μV, t=3.18, P=0.001; ulnar nerve (0.8±0.4) μV, t=3.20, P=0.001]. Conclusions:Sensory nerve is involved in patients with KD, including the large fiber and the small one. The central segments was abnormal in the deep sensory pathway, and the pyramid tract may be involved besides the anterior horn cell.
ABSTRACT
ABSTRACT The X-linked spinal and bulbar muscular atrophy (Kennedy's disease) is a rare X-linked, recessive, lower motor neuron disease, characterized by weakness, atrophy, and fasciculations of the appendicular and bulbar muscle. The disease is caused by an expansion of the CAG repetition in the androgen receptor gene. Patients with Kennedy's disease have more than 39 CAG repetitions. We report a case of 57-year-old man, resident of Monte Dourado (PA, Brazil) who complained of brachiocrural paresis evolving for 3 years along with fasciculations and tremors of extremities. In addition, he also developed dysarthria, dysphagia, and sexual dysfunction. The patient clinical picture included gait impairment, global hyporeflexia, proximal muscle atrophy of upper limbs, deviation of the uvula to right during phonation and tongue atrophy with fasciculations. The patient reported that about 30 years ago he had undergone gynecomastia surgery. His electroneuromyography suggested spinal muscular atrophy, and nuclear magnetic resonance imaging showed tapering of the cervical and thoracic spinal cord. Patient's creatine kinase level was elevated. In view of the findings, an exam was requested to investigate Kennedy's disease. The exam identified 46 CAG repetitions in the androgen receptor gene, which confirmed the diagnostic suspicion. This was the first case of Kennedy's disease diagnosed and described in the Brazilian Amazon. To our knowledge only other four papers were published on this disease in Brazilian patients. A brief review is also provided on etiopathogenic, clinical and diagnostic aspects.
RESUMO A atrofia muscular bulboespinhal ligada ao cromossomo X (doença de Kennedy) é uma rara doença de neurônio motor inferior, recessiva, ligada ao X, e caracterizada por fraqueza, atrofia e fasciculações da musculatura apendicular e bulbar. É causada por uma expansão da repetição CAG no gene do receptor de androgênio. Pacientes com doença de Kennedy apresentam mais de 39 repetições CAG. O paciente deste relato era do sexo masculino, 57 anos, morador de Monte Dourado (PA, Brasil), com queixa de paresia braquiocrural há 3 anos, acompanhada de fasciculações e tremores de extremidades. Em seguida, ele desenvolveu disartria, disfagia e disfunção sexual. Também apresentava comprometimento da marcha, hiporreflexia global, atrofia muscular proximal dos membros superiores, desvio da úvula para direita à fonação e atrofia de língua com fasciculações. Foi realizada cirurgia para tratamento de ginecomastia há 30 anos. A eletroneuromiografia sugeriu quadro de atrofia muscular espinhal. Imagens de ressonância magnética demonstraram afilamento da medula espinhal cervical e torácica. A creatina quinase estava elevada. Diante dos achados, solicitou-se investigação para doença de Kennedy, e foram identificadas 46 repetições CAG no gene do receptor de androgênio, o que confirmou a suspeita diagnóstica. Este foi o primeiro caso de doença de Kennedy diagnosticado e descrito na Amazônia brasileira. Existem, além deste relato, apenas outros quatro trabalhos publicados sobre a doença em pacientes do Brasil. Também realizamos breve revisão de aspectos etiopatogênicos, clínicos e diagnósticos.
Subject(s)
Humans , Male , Middle Aged , Bulbo-Spinal Atrophy, X-Linked/diagnosis , Brazil/epidemiology , Family , Forests , Bulbo-Spinal Atrophy, X-Linked/genetics , Bulbo-Spinal Atrophy, X-Linked/epidemiology , Asymptomatic DiseasesABSTRACT
La enfermedad de Kennedy es un trastorno neurodegenerativo de herencia recesiva ligada al cromosoma X, de inicio en la adultez, caracterizado por degeneración progresiva de las neuronas motoras espinales, debido a una mutación dinámica del gen del receptor de andrógeno. Se presentan tres familias (cinco casos) con temblor, calambres, debilidad muscular generalizada lentamente progresiva con atrofia, afectación de músculos bulbares y alteraciones endocrinas. El estudio neurofisiológico demostró compromiso de segunda motoneurona. El análisis molecular mostró una expansión anormal de tripletes citosina-adenina-guanina en el gen de receptor de andrógeno en todos los casos. Todos los pacientes cursaron con una presentación clínica típica de la enfermedad siendo los primeros casos de enfermedad de Kennedy con diagnóstico molecular realizado en el Perú.
Kennedy’s disease is an X-linked recessive disorder with onset in adulthood, characterized by progressive degeneration of spinal motor neurons due to a dynamic mutation in the androgen receptor gene. We report three families (five cases) characterized by progressive weakness involving both limbs and bulbar muscles, atrophy, tremor, cramps and endocrinologic disturbances; the neurophysiological studies demonstrated second motor neuron impairment. The molecular analysis identified abnormal CAG repeats expansion in the androgen receptor gene (AR) in all cases. Clinical features were consistent with other previous reports. These are the first Peruvian cases of Kennedy´s disease with confirmed molecular diagnosis.