RESUMO
X-linked adrenoleukodystrophy (X-ALD) is the most frequent type of inherited demyelinating peroxisomal disease caused by mutations in the ATP binding cassette subfamily D member 1 (ABCD1) gene. The rate of early recognition and genetic diagnosis of X-ALD remains low due to its variable clinical manifestations. The present study summarized the clinical features Chinese X-ALD patients and performed a follow-up study to further precisely characterize this disease. A total of 10 patients diagnosed with X-ALD between 1994 and 2016 at Shandong Provincial Hospital Affiliated to Shandong University (Jinan, China) were included in the present study. Through reviewing their medical records and performing telephone follow-ups, the clinical features, biochemical laboratory data, brain images, treatments and long-term outcomes were retrospectively summarized. Mutation analysis of the ABCD1 gene was performed in certain patients. Most of the patients (8/10) had the childhood cerebral form of X-ALD. One patient presented with the olivo-ponto-cerebellar form, the rarest form of X-ALD. In all patients, brain magnetic resonance images revealed abnormalities with typical T2-weighted hyperintensity. Analysis of very long chain fatty acid revealed high plasma levels of hexacosanoic acid in all patients. Increased adrenocorticotropic hormone, decreased cortisol and neurophysiological manifestations were also observed. Three different mutations of the ABCD1 gene were identified in the 3 patients subjected to genotyping. During the follow-ups, most patients took neurotrophic drugs and received hydrocortisone replacement when required. One patient received a hematopoietic stem cell transplantation, but died 1 year following the transplantation. Chronic myelopathy and peripheral neuropathy progressed with time, gradually leading to a vegetative state or paralysis within several years of clinical symptom onset. In conclusion, male patients with adrenocortical insufficiency should be further investigated for X-ALD. Early detection is critical to prevent the progression of X-ALD with mutation analysis of ABCD1 the most accurate method to confirm diagnosis.
RESUMO
OBJECTIVE: To investigate the expressions of NF-kappaB and TNF-alpha in lumbar spinal cord in a rat model of chronic constrictive injury (CCI). METHODS: Seventy-six male SD rats were randomly divided into 2 groups (n = 38 each): CCI group receiving chronic constriction injury and sham group receiving sham operation as control. The mechanical and thermal nociceptive thresholds were assessed with paw withdrawal latency (PWL) to von Frey filaments and radiant heat at different time points. Five animals were sacrificed at each time point for real-time polymerase chain reaction (real-time PCR) and another three animals sacrificed at 7 d post-operation for double-immunofluorescence histochemical staining. Lumbar segments of spinal cord were removed. The expressions of NF-kappaB and TNF-alpha in spinal cord were examined by real-time PCR and double-immunofluorescence histochemical technique. RESULTS: The post-operative thresholds to mechanical and thermal stimuli decreased obviously. As compared with contralateral side and sham group, the expressions of NF-kappaB and TNF-alpha mRNA increased significantly in ipsilateral spinal dorsal horn. Their expressions began to increase at 4 d post-operation and peaked at 7 d. Then TNF-alpha began to decrease while NF-kappaB maintained at a high level throughout the experiment. Double-immunofluorescence histochemical staining revealed extensive co-localization of NF-kappaB with TNF-alpha on ipsilateral side of dorsal horn. CONCLUSION: The activation of NF-kappaB and its downstream inflammatory mediators may be involved in the regulation of neuropathic pain.