t.i.d. was started and valproate was stopped. Over the next few weeks, however, no improvement was noted.
At that time, the hypothesis of parkinsonism due to lamotrigine was raised. To investigate this hypothesis, the treatment with lamotrigine was stopped, which resulted in clear improvements over the next few days. The Unified Parkinson's Disease Rating Scale (UPDRS) Motor score before stopping lamotrigine ran up to 31. One month later, the UPDRS Motor score was 5, with a total disappearance of the postural tremor and rest tremor. Cogwheel rigidity as well as bradykinesia of movements was no longer present. Only facial hypokinesia and slight but atypical general bradykinesia persisted.
To further elaborate our hypothesis, we charged the patient with a single 200-mg dose of lamotrigine and evaluated him 3 hours later. At that time, his UPDRS Motor score was 19. The previously present signs of Parkinsonism re-occurred with increase of generalized bradykinesia, resting and postural tremor of the hands, rigidity of the upper limbs, impairment of finger tapping and hand pro-supination, and postural instability. At present, more than 1 year later, parkinsonian signs remain notably absent, even though the treatment with sodium valproate 500 mg t.i.d. was restarted.
There are several reports on movement disorders, such as tremor, dystonia, and tourettism, associated with lamotrigine, especially in children. [2][3][4] This case suggests that Parkinsonism can also occur in patients treated with this drug. The pathophysiological mechanisms involved in the development of movement disorders and parkinsonism in patients treated with lamotrigine are unknown. Its mechanism of action seems to involve the stabilization of presynaptic cell membranes by blockage of voltage-sensitive sodium channels and subsequent inhibition of L-glutamate and L-aspartate release. 5 There are clear interactions between glutamatergic and dopaminergic transmission. Initially, it was even thought that lamotrigine might have antiparkinsonian effects. This finding, however, has never been confirmed in animal models. 6 On the contrary, lamotrigine administered in high doses (Ͼ40 mg/kg) decreased spontaneous locomotor activity in normal mice, causing impairment of posture and gait. 7 . Whether this finding results from locoregional differences in glutamatergic neurotransmission 8 or a decrease of dopamine turnover, 9 as suggested by in vitro studies, remains a matter of speculation. The latter hypothesis, however, seems an attractive one for explaining the development of parkinsonism in our patient.