title: Neuromuscular abnormality and autonomic dysfunction in patients with cerebrotendinous xanthomatosis.
abstract: BACKGROUND
  Cerebrotendinous xanthomatosis (CTX) is a rare lipid-storage disease. Neuromuscular abnormality and autonomic system (ANS) dysfuction in CTX are rarely examined in large-scale studies in the literature. We studied the peripheral nervous system, myopathology, and autonomic system of four CTX patients and performed a literature review of the reported CTX patients with peripheral neuropathy.
  
  
  METHODS
  Four biochemically and genetically confirmed CTX patients, belonging to two families, were included for study and all received nerve conduction study (NCS), muscle biopsy for histopathologic and ultrastructural study, skin biopsy for intraepidermal nerve fiber (INEF) density measurement, autonomic testings including sympathetic skin response, R-R interval variation and head-up tilt test using an automated tilt table to record the changes of blood pressure and heart rate in different postures. The Q-Sweat test was also applied for the detection of sweat amount and onset time of response. The clinical characteristics, study methods and results of 13 studies of peripheral neuropathy in CTX patients in the literature were also recorded for analysis.
  
  
  RESULTS
  The results of NCS study showed axonal sensory-motor polyneuropathy in three CTX cases and mixed axonal and demyelinating sensor-motor polyneuropathy in one. The myopathological and histopathologic studies revealed mild denervation characteristics, but the ultrastructural study revealed changes of mitochondria and the membranous system, and increased amounts of glycogen, lipofuscin and lipid deposition. The ANS study revealed different degrees of abnormalities in the applied tests and the INEF density measurement showed small fiber neuropathy in three of the four CTX patients. The literature review of peripheral neuropathy in CTX revealed different types of peripheral neuropathy, of which axonal peripheral neuropathy was the most common.
  
  
  CONCLUSIONS
  Peripheral neuropathy, especially the subtype of axonal sensori-motor neuropathy, is common in patients with CTX. Evidence of lipid metabolic derangement in CTX can be reflected in ultrastructural studies of muscles. With an adequate multi-parametric evaluation, a high incidence of ANS abnormalities can be seen in this rare lipid-storage disease, and a high incidence of small fiber involvement is also reflected in the IENF density measurement of skin biopsies.
authors.affiliation: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Shu-Fang
authors.initials: SF
authors.lastname: Chen
authors.forename: Nai-Wen
authors.initials: NW
authors.lastname: Tsai
authors.forename: Chung-Chih
authors.initials: CC
authors.lastname: Chang
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Lu
authors.forename: Chi-Ren
authors.initials: CR
authors.lastname: Huang
authors.forename: Yao-Chung
authors.initials: YC
authors.lastname: Chuang
authors.forename: Wen-Neng
authors.initials: WN
authors.lastname: Chang
mesh_terms: D000328:Adult; D001342:Autonomic Nervous System Diseases / Q000188:drug therapy / Q000209:etiology*; D002635:Chenodeoxycholic Acid / Q000627:therapeutic use; D004576:Electromyography / Q000379:methods; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure; D009412:Nerve Fibers / Q000473:pathology / Q000648:ultrastructure; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D020511:Neuromuscular Junction Diseases / Q000188:drug therapy / Q000209:etiology*; D012867:Skin / Q000294:innervation; D012881:Skin Temperature / Q000187:drug effects; D019294:Xanthomatosis, Cerebrotendinous / Q000150:complications*
chemical_list: D005765:Gastrointestinal Agents; D002635:Chenodeoxycholic Acid