title: Subclinical neurological involvement does not develop if Wilson's disease is treated early.
abstract: OBJECTIVE
  Wilson's disease (WD) is a genetic disorder of copper metabolism causing dysfunctions of various organs, mostly the liver and brain. If untreated, WD is fatal, but early treatment results in a good prognosis, although the long-term neurological outcome has not yet been clarified. To address this issue, we evaluated the neurological status of early-treated WD patients without overt nervous system impairment using neurophysiological, neuropsychological and neuroimaging procedures at least 10 years after treatment onset.
  
  
  METHODS
  Thirty-eight WD patients (18 females, aged 24.47 ± 7.50 years), who received an early diagnosis (in presymptomatic or mild/moderate liver disease stages without neurological involvement) and prompt treatment, were clinically evaluated with the Global Assessment Scale. Presentation was hepatic in 36 subjects (95%), while 2 patients (5%) were presymptomatic. A neurophysiological study was performed to explore the central motor conduction time of the upper and lower limbs, and motor cortex excitability using single pulses and paired-pulse transcranial magnetic stimulation. Neuroimages were obtained with brain magnetic resonance scans. Cognitive abilities, and psychiatric and behavioral disturbances were evaluated with neuropsychological tests.
  
  
  RESULTS
  Patients were undergoing treatment with penicillamine (7 patients) or zinc salts (31 patients) with good adherence. They did not present any neurological signs at clinical evaluation or at specific scale of impairment, the mean Global Assessment Scale score was 0.3 ± 0.7. Magnetic resonance imaging, transcranial magnetic stimulation studies and neuropsychological/neuropsychiatric assessment ruled out subclinical involvement.
  
  
  CONCLUSIONS
  This study suggests that early diagnosis and treatment of WD may prevent the onset of neurologic damage, even at subclinical level.
authors: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Italy.
authors: Raffaele
authors: R
authors: Dubbioso
authors: Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Italy.
authors: Giusy
authors: G
authors: Ranucci
authors: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Italy.
authors: Marcello
authors: M
authors: Esposito
authors: Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Italy.
authors: Fabiola
authors: F
authors: Di Dato
authors: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Italy.
authors: Antonietta
authors: A
authors: Topa
authors: Institute of Biostructure and Bioimaging, National Research Council (CNR), Naples, Italy.
authors: Mario
authors: M
authors: Quarantelli
authors: Department of Translational Medical Sciences, Section of Internal Medicine, University of Naples Federico II, Italy.
authors: Margherita
authors: M
authors: Matarazzo
authors: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Italy.
authors: Lucio
authors: L
authors: Santoro
authors: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Italy.
authors: Fiore
authors: F
authors: Manganelli
authors: Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Italy. Electronic address: riorio@unina.it.
authors: Raffaele
authors: R
authors: Iorio
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D027682:Cation Transport Proteins / Q000235:genetics; D000073840:Copper-Transporting ATPases; D018450:Disease Progression; D005260:Female; D006527:Hepatolenticular Degeneration / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009422:Nervous System Diseases / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D010396:Penicillamine / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D055815:Young Adult; D015032:Zinc / Q000627:therapeutic use
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases; D010396:Penicillamine; D015032:Zinc
keywords: Neurological diagnostic techniques; Outcome; Therapy; Wilson's disease