Paired transcranial magnetic stimulation for the early diagnosis of corticobasal degeneration E. Frasson a , L. Bertolasi a, * , V. Bertasi a , S. Fusina a , L. Bartolomei b , S. Vicentini a , N. Rizzuto a , A. Priori c a Dipartimento di Scienze Neurologiche e della Visione, Sezione di Neurologia, via delle Menegone 6, 37134 Verona, Italy b Divisione di Neurologia, Ospedale di Vicenza, Vicenza, Italy c Istituto di Clinica Neurologica, Universita ` di Milano, IRCCS Ospedale Maggiore Policlinico di Milano, Milan, Italy Accepted 14 October 2002 Abstract Objective: To investigate cortical excitability in patients with corticobasal degeneration (CBD) and to find a reliable diagnostic technique for differentiating CBD from Parkinson’s disease (PD). Methods: Using a paired transcranial magnetic stimulation technique, we studied motor cortex excitability at rest in 6 patients with clinically probable CBD, 10 patients with PD, and 10 normal subjects. The recovery cycle of the motor evoked potentials was tested by delivering paired magnetic stimulation over the hand area of the motor cortex at interstimulus intervals (ISIs) from 1 to 17 ms. Results: In patients with CBD, paired magnetic stimuli delivered at short ISIs invariably elicited enlarged test MEPs. At ISIs of 1–10 ms, the conditioned test MEPs were significantly larger in patients with CBD than in control subjects; and at ISIs of 1, 2, 4, and 6 ms ,they were also larger in patients with CBD than in patients with PD. At the other ISIs tested, patients and control subjects had similar amplitude conditioned test responses. Conclusions: Our findings suggest that the unusual clinical manifestations of CBD might arise partly from motor cortex disinhibition. Paired magnetic stimulation could be a useful diagnostic test particularly in the early stages of the disease. q 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Corticobasal degeneration; Paired transcranial magnetic stimulation; Motor evoked potentials 1. Introduction Corticobasal degeneration (CBD) is a rare neurodegen- erative disease that involves, among several brain struc- tures, the cerebral cortex and basal ganglia. The clinical features of the disease consist of an asymmetric akinesia, rigidity, and apraxia often combined with other movement disorders and cortical dysfunctions (Gibb et al., 1989; Riley et al., 1990; Eidelberg et al., 1991; Blin et al., 1992; Rinne et al., 1994; Schneider et al., 1997; Kompoliti et al., 1998; Wenning et al., 1998; Litvan et al., 1999). In the early stages of the disease, CBD can be difficult to differentiate from other akinetic-rigid syndromes, such as Parkinson’s disease (PD) (Hughes et al., 1992; Brooks et al., 1993; Goetz et al., 1996; Litvan et al., 1997; Schnider et al., 1997). Some investigators suggested that the movement disorder in CBD could arise from abnormal motor cortex (Thompson et al., 1994; Yokota et al., 1995; Strafella et al., 1997; Valls- Sole ´ et al., 2001). One method of assessing intracortical excitability is to deliver paired magnetic shocks at varying interstimulus intervals (ISIs). In normal subjects, a subthres- hold conditioning stimulus suppresses the responses elicited in the relaxed first dorsal interosseous muscle (FDI) by a suprathreshold test stimulus delivered at ISIs of 1–6 ms and facilitates responses at ISIs of 10–15 ms. The suppression is probably due to the action of intracortical inhibitory inter- neurons (Kujirai et al., 1993). Using a paired transcranial magnetic stimulation (TMS) technique, we tested and compared motor cortical excitabil- ity at rest in 6 patients with CBD, in patients with PD, and healthy control subjects to find out a possible neurophysio- logical technique useful in differentiating the two neurolo- gical disorders. Clinical Neurophysiology 114 (2003) 272–278 1388-2457/02/$ - see front matter q 2002 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S1388-2457(02)00340-1 www.elsevier.com/locate/clinph CLINPH 2002521 * Corresponding author. Tel.: 139-045-807-4289; fax: 139-045-585- 933. E-mail address: laurabertolasi@netscape.net (L. Bertolasi).