Full Parkinsonian Triad Induced by Pallidal High‐Frequency Stimulation in Cervical Dystonia

High-frequency stimulation of the globus pallidus internus (GPi-HFS) is the treatment of choice for patients suffering from generalized or segmental dystonia refractory to conservative medical treatment. Upper-limb bradykinesia or gait freezing have been described as adverse effects of pallidal neurostimulation. Bradykinesia is typically subtle, (e.g., presenting as mild micrographia) and is usually tolerated in return for improved dystonia. Here, we report on a patient with cervical dystonia, in whom GPi-HFS induced a clinically relevant, complete parkinsonian syndrome comprising bradykinesia, hand tremor, and severe freezing of gait (FOG). This 69-year-old man suffered from cervical dystonia since the age of 57. He had no family history of movement disorders, no previous exposure to antidopaminergic drugs, and cervical MRI was normal. After several years of successful botulinum toxine treatment, he became unresponsive as a result of neutralizing antibodies and opted for DBS. Surgical implantation of electrodes for GPi-HFS took place on 16 March 2009 following our published procedure. Intraoperatively, the GPi and its ventral border were identified by microrecordings, and HFS within the target region induced facial muscle contractions at 4 mA current amplitude (120 ls, 130 Hz), indicating a sufficient distance from the pyramidal tract. Permanent electrodes (model 3389; Medtronic Inc., Minneapolis, MN) were bilaterally implanted with the lowest contact at 2 mm below target and connected to an impulse generator (Activa PC; Medtronic). Postoperative MRI confirmed the anatomically correct placement of the electrodes and excluded an asymptomatic intracerebral hemorrhage. Four days later, after a monopolar review session, the most ventral contacts with a threshold for capsular side effects of at least 3 V were chosen for long-term stimulation and programmed to provide monopolar stimulation at an amplitude of approximately 20% below this threshold (GPi left: C+8-, 3.3 V, 120 ls, 130 Hz; GPi right: C+1-, 3.3 V, 120 ls, 130 Hz). After another 2 days of clinical observation, the patient was sent home claiming no adverse effects while the severity of dystonic head rotation was already markedly reduced. A few weeks later, the patient returned complaining about difficulties in walking and handwriting. Clinically, he exhibited clear bradykinesia with slowing and decrement of repetitive movements and a marked resting and kinetic tremor of the right hand, but only mild rigidity. Walking was impaired by difficulties of gait initiation, FOG, and turning difficulties. The video, demonstrating parkinsonian symptoms during stimulation with the initially programmed parameters, was taken 1 year after electrode implantation. Kinematic gait analysis on a motor-driven tread mill (Woodway, Weil am Rhein, Germany) was used to quantify the hypokinetic gait disturbance (Fig. 1C). A cranial MRI revealed no parenchymal abnormalities and a normal DaTSCAN excluded the possiblity of striatal dopaminergic degneration. Oral levodopa did not improve the parkinsonian symptoms. Stopping GPi-HFS or even reducing stimulation intensity led to abrupt worsening of cervical dystonia. Parkinsonian symptoms gradually diminished within days (see Video) after discontinuing HFS, suggesting an effect of stimulation rather than microlesion. Stimulation of dorsal contacts failed to control dystonia, but did not induce parkinsonism. As a compromise, we finally programmed the clinically most effective ventral contacts in bipolar mode with the adjacent contact as anode and titrated stimulation intensity to evoke sufficient dystonia control, but minimal parkinsonian signs (GPi right: 4.5 V, 120 ls, 160 Hz; GPi left: 3.8 V, 90 ls, 160 Hz; Fig. 1A,B). In patients with Parkinson0s disease, HFS of the ventral GPi reduces L-dopa-induced dyskinesias and rigidity, whereas the antiakinetic effect of L-dopa may become antagonized. In contrast, stimulation of the dorsal GPi was found to induce dyskinesia and improve akinesia. This functional segregation may anatomically relate to the two different pallido-fugal fiber tracts, the ansa lenticularis, and the lenticular fasciculus, leaving the nucleus at the ventral or dorsal aspect, respectively. The exact pathophysio-