Ž . Journal of the Neurological Sciences 192 2001 35–40 www.elsevier.comrlocaterjns Excitatory and inhibitory mechanisms in Wilson’s disease: investigation with magnetic motor cortex stimulation Anna Perretti a, ) , Maria Teresa Pellecchia a , Bernardo Lanzillo b , Giuseppe Campanella a , Lucio Santoro a a Department of Neurological Sciences, UniÕersity of Naples A Federico II B , Via Sergio Pansini 5, 80131 Naples, Italy b SalÕatore Maugeri Foundation, IRCCS, Rehabilitation Centre of Campoli-Telese, Italy Received 9 March 2001; received in revised form 8 June 2001; accepted 24 July 2001 Abstract Ž . Ž . We have evaluated cortical excitability in nine patients affected by Wilson’s disease WD using transcranial magnetic TMS and Ž . Ž . electric TES cortical stimulation and central silent period CSP data. A clinical score was derived from the sum of scores assigned to Ž . extrapyramidal, pyramidal and cerebellar signs. All patients underwent TMS. Motor evoked potentials MEPs from abductor pollicis Ž . Ž . Ž . brevis APB and tibialis anterior TA muscles were recorded. MEP threshold and amplitude, central motor conduction time CMCT , Ž . CSP threshold, CSP and peripheral silent period PSP duration were measured. Three patients also underwent transcranial bifocal electric Ž . cortical stimulation TES and MEPs were recorded from the APB muscle, and CMCT, MEP threshold and amplitude were measured. TMS MEPs were absent from relaxed muscles in six patients and from contracted muscles in three. CMCT was prolonged in six patients. APB CMCT correlated with clinical score. In three patients in whom TMS revealed abnormal or no MEP, TES MEPs were of normal threshold and amplitude. The CSP threshold was increased in seven patients, and CSP was absent in one. These results suggest an intracortical presynaptic motor dysfunction in WD. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Wilson’s disease; Transcranial magnetic electric cortical stimulation 1. Introduction Ž . Wilson’s disease WD is a treatable autosomal reces- sive disorder of copper metabolism. Extrapyramidal dys- function is the most frequent neurological feature in WD. Cerebellar dysfunction is seen in approximately 25% of patients, while upper motor neuron syndrome is more rare wx 1 . Neuropathological and brain magnetic resonance imag- Ž . ing MRI studies demonstrated that basal ganglia are more frequently affected, followed by thalamus and brain- w x stem 2,3 . Ž . Transcranial magnetic stimulation TMS of the motor cortex reveals subclinical pyramidal tract impairment in WD, but its use in monitoring treatment efficacy is contro- w x Ž . versial 4,5 . Besides motor evoked potentials MEPs , Ž . TMS evokes a central silent period CSP attributed, at least during its late part, to intracortical inhibitory mecha- w x nisms 6–13 . CSP abnormalities may reflect a derange- ) Corresponding author. Tel.: q 39-81-7462660; fax: q 39-81-7462667. Ž . E-mail address: anperret@unina.it A. Perretti . ment of the intracortical inhibitory pathway in patients w x with basal ganglia dysfunction 14–17 . The aim of this study was to evaluate motor cortical excitability in WD using TMS and transcranial bifocal Ž . electric stimulation TES . To our knowledge, this is the first study to investigate WD using TMS and TES, and to evaluate central silent period in WD. 2. Patients and methods The clinical and MRI findings observed in our patients are shown in Table 1. TMS was performed in nine WD Ž . patients four men and five women aged 32.4 " 11 years Ž . range: 19–55 years . Diagnosis was established by low levels of plasma ceruloplasmin, increased levels of urinary copper and increased liver copper concentrations on needle biopsy. Seven of the nine patients were treated with D- Ž penicillamine daily dosage range: 600–1650 mg; mean . dosage: 1071 " 329 mg and six of these patients also Ž . received zinc sulphate daily dosage: 600 mg . Two pa- tients were untreated at the time of the study. Treatment Ž duration ranged from 3 months to 18 years mean: 6.2 " 0022-510Xr01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. Ž . PII: S0022-510X 01 00594-9