Acute Dystonia with Thalamic and Brainstem Lesions after Initial Penicillamine Treatment in Wilson’s Disease

Abstract

Dystonia is a common manifestation in Wilson’s disease (WD). The striatum, especially the putamen, has been considered to be responsible for dystonia. We reported 3 patients who developed acute generalized dystonia and akinetic rigid syndrome following an initial therapy with d-penicillamine 125–500 mg daily. Brain MRI revealed lesions in the thalamus and the brainstem, particularly the tegmentum, and the basis pontis in addition to the basal ganglion lesions. After the episode, 1 patient continued to receive d-penicillamine therapy and 2 changed to zinc sulfate treatment. The generalized dystonia improved in the following 3 months and 3 years respectively in 2 patients. Follow-up brain MRI of these 2 patients revealed that the lesions in the thalamus and brainstem disappeared or resolved almost completely. From these data, acute generalized dystonia with brainstem and thalamic lesions may occur in WD patients after an initial d-penicillamine therapy. Furthermore, the dystonia may resolve following the disappearance of the brainstem and thalamic lesions.

Early neurological worsening in patients with Wilson's disease

“…scored using UWDRS parts II and III; 3) initial damage to the brain, as visualized on brain MRI (especially lesions located in the thalamus and brain stem); and 4) concomitant treatment with agents that blocking dopamine neurotransmission. Our observations are partially in line with previous reports about the worse prognosis for WD patients who have advanced neurological symptoms and corresponding severe brain lesions on MRI [26,29]. The worsened long-term treatment outcome in this patient group may also be due to irreversible neurological brain damage through the disease course.…”

“…The mechanism of this effect, however, is poorly understood. The high total amount of free copper in the blood and CSF is suggested to increase copper-related oxidative stress and lead to brain damage and neurological worsening [9,12,[27][28][29][30]. Therefore, it is possible that rapid introduction of chelators in full dose may result in mobilization of free copper from different tissues (not bound to ceruloplasmin or chelator).…”

Gabapentin as a rescue drug in D-penicillamine-induced status dystonicus in patients with Wilson disease

“…[1][2][3] Similar aggravation of dystonia is also known with Trientine and zinc [4] monotherapies; the condition is however more severe with D-penicillamine. D-penicillamine does not produce dystonia when used in other disorders, like rheumatoid arthritis, copper sulfate or arsenic poisoning.…”

“…The signal changes in thalamus and brainstem observed on MRI during D-penicillamineinduced increase in dystonia may reverse back to normal on discontinuation of D-penicillamine. [3] D-penicillamine-induced status dystonicus responds poorly to anti-dystonia drugs. All our patients responded well to gabapentin after failing to respond to other anti-dystonia drugs.…”

Zerebrale Bildgebung bei Morbus Wilson

“…So kann eine Regredienz des hyperintensen Signals der Basalganglien, des Thalamus und des Pons unter suffizienter Therapie beobachtet werden [51,55]. Gleiches gilt für die mesencephalen Signalanhebungen innerhalb des Signalmusters des "Pandazeichens" [56].…”