Low M, Nicholls K, Tubridy N, Hand P, Velakoulis D, Kiers L, Mitchell P, Becker G
Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Intern Med J. 2007 Jul;37(7):436-47. doi: 10.1111/j.1445-5994.2007.01366.x.
Fabry disease has diverse neurological manifestations, many of which influence morbidity and quality of life.
The aim of the study was to document the clinical and subclinical neurological manifestations in a cohort of Australian patients with Fabry disease, using multiple clinical tools and a multidisciplinary approach.
Participants completed focused questionnaires and underwent clinical neurological examination, Neurocognitive testing using Mini Mental State Examination and Neuropsychiatry Unit Cognitive Screen, Quantitative Sensory Testing (QST), autonomic assessment using RR interval variation, intracranial magnetic resonance imaging (MRI) and audiology. In subsets of patients who had previously undergone QST and/or prospective serial quality-of-life assessments over the previous 5 years, results before and after enzyme replacement therapy were compared.
Twenty hemizygotes and two heterozygotes were recruited. The age (mean +/- standard deviation (SD)) of male participants was 40.4 +/- 11.9 years (range 20-62 years); the women were aged between 20 and 56 years. Increasing age was strongly associated with increasing neurological disability. Clinical peripheral neuropathy predominantly affected thermal sensation in all patients, with variable involvement of pinprick and light touch. QST confirmed these findings. Clinical cerebellar tests were commonly abnormal: this has not been previously reported in the absence of symptomatic cerebrovascular disease. There was hearing loss was in 90% of patients and no patient older than 44 years had normal hearing. MRI lesion prevalence increased with age. Despite neurological complications being common, formal cognitive testing was basically normal. QST thresholds for pain showed a significant change after enzyme replacement therapy.
Neurological complications in Fabry disease are common, complex and may be devastating. All patients studied had neurological involvement, with protean and diverse manifestations.
法布里病具有多种神经学表现，其中许多会影响发病率和生活质量。
本研究旨在通过多种临床工具和多学科方法，记录一组澳大利亚法布里病患者的临床和亚临床神经学表现。
参与者完成针对性问卷，并接受临床神经学检查、使用简易精神状态检查表和神经精神病科认知筛查进行的神经认知测试、定量感觉测试（QST）、使用RR间期变异性进行的自主神经评估、颅内磁共振成像（MRI）和听力检查。在过去5年中曾接受过QST和/或前瞻性系列生活质量评估的患者亚组中，比较了酶替代治疗前后的结果。
招募了20名半合子和2名杂合子。男性参与者的年龄（均值±标准差[SD]）为40.4±11.9岁（范围20 - 62岁）；女性年龄在20至56岁之间。年龄增长与神经功能障碍加剧密切相关。临床周围神经病变在所有患者中主要影响温度感觉，针刺觉和轻触觉受累情况不一。QST证实了这些发现。临床小脑测试通常异常：在无有症状脑血管疾病的情况下，此前尚无此类报道。90%的患者存在听力损失，44岁以上患者无听力正常者。MRI病变患病率随年龄增加。尽管神经并发症很常见，但正式的认知测试基本正常。酶替代治疗后，疼痛的QST阈值有显著变化。
法布里病的神经并发症常见、复杂且可能具有毁灭性。所有研究患者均有神经受累，表现形式多样。
