Case report

A 70 year old woman had a 6 year history of progressive involuntary movements, which worsened at the beginning of the movement disorder and consisted of orobuccolingual dyskinesia, blepharospasm, painful phasic opisthotonic posturing of the neck, and retropulsive twisting movements of both arms. There was no involvement of the legs and only minimal of the trunk. Especially, the left sternocleidomastoid muscle was clearly hypertropic. The remaining neurological status was normal.

Six to 12 months before the onset of the involuntary movements, the patient had been treated with weekly intramuscular injections of 2 mg fluspirilene, a diphenylbutylpiperidinic depot neuroleptic drug with a tranquillising action in neurotic syndromes and anxiety disorders. She received no other neuroleptic agents. There was no family history of psychiatric or neurological disorders and no relevant personal medical or psychiatric history. Paraclinical investigations had been insignificant. Extensive pharmacological treatment trials including baclofen, botulinum toxin, bromocriptine, clonazepam, clozapine, diltiazem, DL-α-tocopherolacetate, gabapentin, pimozide, tetrabenazine, tiapride, trihexyphenidyl, and verapamil had no lasting effect.

Results

After bilateral neurostimulation of the GPi (voltage 3.0 V monopolar, pulse width 210 μs, frequency 150 Hz, Kinetra model 7428, Medtronic Inc), the patient showed and reported a clear and stable improvement of the painful dystonic syndrome within a few hours. The BMFS score decreased from 34.5/120 points to 9.5/120 (-73%) with bilateral Gpi stimulation. The AIMS score improved from 24/40 points to 11/40 (-54%, fig 1). Six months postoperatively she still had slight orofacial dyskinesias and mild dystonic movements resulting in retrocollis, but the pain had subsided completely. Turning off stimulation clearly aggravated the syndrome within 1 to 2 hours with an obvious rebound phenomenon. Electrical stimulation of the VIM using different stimulus parameters did not improve the hyperkinetic movements; furthermore, simultaneous stimulation of both the GPi and the VIM did not result in any additional benefit. Stimulus related side effects such as paraesthesias and a shuffling gait were mild and reversible.

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Figure 1

AIMS scores, disability, and motor scores of the BMFS scale of the preoperative (pre) and 6 month postoperative evaluation in the on and off GPi stimulation condition.

Discussion

This patient presented with tardive dyskinesia which rapidly progressed to severe tardive dystonia (type II according to Adityanjeeet al 3). The clinical picture was consistent with suggested characteristic features of patients with tardive dystonia.5 The development of tardive dystonia with orobuccolingual dyskinesia, severe phasic retrotorticollis, and torticollis as well as asymmetric choreiform involuntary movements of the arms has been reported even after short term use of low dose fluspirilene, a dopamine D₂ receptor antagonist.6 7 There is no recognised specific treatment for tardive dystonia, and treatment trials and strategies reported to be helpful in other cases were without lasting benefit in our patient.

To date there are only a few case reports of effective destructive stereotactic procedures in medically refractory tardive dystonia lesioning different targets. Weetman et al 8 reported on a 31year old schizophrenic man, who first noted 1 year after starting antipsychotic medication dyskinetic movements of his mouth and tongue, rapidly progressing to severe choreiform dyskinesias involving his limbs and trunk, combined with severe dystonia involving his neck and upper limb girdle, who was effectively treated with bilateral posteroventral pallidotomy. Hillieret al 9 performed a two staged ventral thalamotomy on the right side in a 66 year old man with orofacial dyskinesia, torticollis and twisting of the trunk, induced by neuroleptic drugs, who was refractory to pharmacological treatment. Twelve months postoperatively there were only minimal dystonic neck movements, and the patient was off all medication. The lesions were mainly in the VIM and in the ventroposterior medial thalamic nucleus (VPM) extending to the centromedianum-parafascicular (CM-PF) complex. Other authors used thalamotomy in the treatment of tardive dyskinesia and dystonia without exactly specifying the region.10 11Tardive dyskinesia that included facial grimacing, humming, grunting, tongue protrusion, and choreiform limb movements predominantly on the left side had been reduced in a 66 year old man by pallidotomy targeting the ventroposterior globus pallidus on the right side.12 As no single target for deep brain stimulation has been shown to be superior, we decided to target both the VIM nucleus and the GPi. As a result, we could clearly ameliorate the involuntary movements using pallidal stimulation, whereas there was no benefit from stimulating the thalamic VIM nucleus.

The hypothesis of dopamine receptor hypersensitivity used to explain the development of tardive dyskinesia13 may also be applied to tardive dystonia. Trugman et al 14 proposed that repetitive stimulation of the D₁ receptor by endogenous dopamine resulting in sensitisation of the D₁ mediated striatal output in the presence of D₂ receptor blockage is a fundamental mechanism that mediates tardive dyskinesia and dystonia. The hypothesis that sensitisation of the D₁ mediated striatal output is involved in the pathogenesis is consistent with both the delayed onset of dyskinesias after neuroleptic initiation and the persistence of symptoms after neuroleptic withdrawal. The model predicts that D₁ antagonists combined with stimulation of the D₂ receptor will be beneficial in the treatment of both tardive dyskinesia and tardive dystonia, which is in accordance with the observed moderate amelioration of these dyskinesias using bromocriptine, a partial D₁ antagonist and D₂agonist.15-17 Furthermore, the hypothesis is based on a relative segregation of striatal outputs, whereby D₁mediated striatal output is preferentially directed to the GPi and the substantia nigra, pars reticulata, and D₂ mediated output is preferentially directed to the external segment of the globus pallidus.14 By selectively reducing the overactivity of the D₁ mediated direct path of the striatal motor circuits to the GPi, inhibitory neurostimulation of this site might have an effect on tardive dyskinesia and dystonia.

The reason for ineffective thalamic stimulation in this patient could be seen in the more lateral target site in the VIM. Caparros-Lefebvreet al 18 showed that both tremor and drug induced choreiform dyskinesias in Parkinson's disease were abolished by a more posteromedial VIM target. However, only the tremor was relieved by the more anterolateral electrode position, which might point to an antichoreiform dyskinetic effect being secondary to involvement of the CM-PF complex. These results are consistent with neuroanatomical data showing that the CM-PF is included in the motor circuits of the basal ganglia system that receives important input from the GPi and are in accordance with thalamotomy lesions shown to be effective in tardive dyskinesia, which were mainly in the VPM extending to the CM-PF complex.9

The clinical importance of this case report lies in the demonstration that stimulation of a single ventroposterolateral GPi target can achieve a clear amelioration of medically refractory severe tardive dystonia, whereas deep brain stimulation targeting the VIM does not translate into a reduction in tardive dystonia.