Remarkable clinical improvement with bilateral globus pallidus internus deep brain stimulation in a case of Lesch-Nyhan disease: five-year follow-up.

OBJECTIVES: Lesch-Nyhan disease (LND) is a hereditary disorder characterized by hyperuricemia, self-mutilation, developmental retardation, and movement disorders such as spasticity and dystonia. The lack of a precise understanding of the neurological dysfunction has precluded the development of useful conservative therapies. We present our experience treating a LND patient by bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) with improvement in dystonia symptoms and disappearance of self-injurious behavior. METHODS: We present a 29-year-old patient characterized by generalized severe dystonia and self-injurious behavior, both refractory to conservative treatment. The patient underwent a GPi bilateral electrode implant for chronic stimulation. Symptoms were evaluated with the Burke-Fhan-Marsden Dystonia Rating Scale (BFMDRS) and Mean Disability Scale (MDS) preoperatively and during the five-year follow-up. RESULTS: We observed a remarkable improvement in dystonia symptoms and complete disappearance of self-injurious behavior. CONCLUSIONS: This case supports the hypothesis that automutilation in LND might be related to dysfunction of the basal ganglia circuits and the idea that bilateral GPi-DBS is a safe and effective treatment modality for this condition.

Behavioral and motor improvement after deep brain stimulation of the globus pallidus externus in a case of Tourette's syndrome.

OBJECTIVES: The objective of our paper is to show the partial decrease of therapeutic effect with battery exhaustion in a previously successfully treated patient with refractory Tourette's syndrome (TS). MATERIALS AND METHODS: We present a 47-year-old patient diagnosed with TS based on the TS Study Group Criteria and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Surgery was considered based on refractoriness to conservative management. Presurgical evaluation included magnetic resonance imaging (MRI), positron emission tomography scan, and neuropsychologic, neurologic, and psychiatric tests utilizing Yale Brown Obsessive Compulsive Scale, Yale Global Tics Severity Scale, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Global Assessment of Functioning Scale, and Mini-mental State Examination. Target coordinates were obtained from inversion recovery MRI. Quadripolar deep brain stimulation (DBS) electrodes were implanted bilaterally in the globus pallidus externus (GPe) and connected to the pulse generator in the same procedure. To determine the clinical response to DBS, the scores of the scales obtained preoperatively were compared with those obtained postoperatively. RESULTS: No surgical complications were detected and according to the clinical scales the patient experienced a marked improvement of his symptoms, although he never showed obsessive-compulsive disorder components of any type. The battery was exhausted after two years with the subsequent significant partial loss of therapeutic effect. CONCLUSIONS: GPe seems to be a highly promising target of DBS for the treatment of medically refractory TS. After battery exhaustion, the patient experienced a marked partial decrease in the therapeutic effect, which confirms the beneficial action of this method.

New Targets and New Technologies in the Treatment of Parkinson's Disease: A Narrative Review.

Parkinson's disease (PD) is a progressive neurodegenerative disease, whose main neuropathological finding is pars compacta degeneration due to the accumulation of Lewy bodies and Lewy neurites, and subsequent dopamine depletion. This leads to an increase in the activity of the subthalamic nucleus (STN) and the internal globus pallidus (GPi). Understanding functional anatomy is the key to understanding and developing new targets and new technologies that could potentially improve motor and non-motor symptoms in PD. Currently, the classical targets are insufficient to improve the entire wide spectrum of symptoms in PD (especially non-dopaminergic ones) and none are free of the side effects which are not only associated with the procedure, but with the targets themselves. The objective of this narrative review is to show new targets in DBS surgery as well as new technologies that are under study and have shown promising results to date. The aim is to give an overview of these new targets, as well as their limitations, and describe the current studies in this research field in order to review ongoing research that will probably become effective and routine treatments for PD in the near future.

Pallidal surgery for the treatment of primary generalized dystonia: long-term follow-up.

OBJECTIVE: To describe the results and long-term follow-up after functional surgery of the internal segment of the globus pallidus (GPi) in 10 patients with primary generalized dystonia. PATIENTS AND METHODS: Nine of the 10 patients were positive for the DYT1 gene mutation. Bilateral deep brain stimulation (DBS) of the GPi was performed in three cases, bilateral pallidotomy in two, and combined surgery (unilateral GPi lesion with contralateral stimulation) in the remaining five. All patients were evaluated with the Burke-Fahn-Marsden dystonia scale (BFMDS) before, immediately after surgery, at 3 weeks, 3 and 6 months and then yearly. Follow up time ranged from 15 to 105 months (mean: 66.1 months) with six patients having more than 6 years follow up. RESULTS: All patients improved after surgery. All patients with unilateral or bilateral DBS experienced an immediate improvement before starting stimulation. The magnitude of this initial micro lesion effect did not predict the magnitude of the long-term benefit of DBS. The mean decrease in the in the BFMDS was 34%, 55%, and 65% in the movement scale; and 32%, 48%, and 49% in the disability scale for patients with bilateral pallidal DBS, combined unilateral DBS and contralateral pallidotomy, and bilateral pallidotomy, respectively. Worsening of dystonia after a plateau of sustained benefit was observed in three patients. Two patients required multiple pallidal surgeries. Adverse events included: permanent anarthria (1), misplacement of the electrode requiring further surgery (2), scalp infection (1), and hardware related problems (3). CONCLUSIONS: This long-term follow up study confirms the beneficial effect of pallidal DBS or pallidotomy in primary generalized dystonia. In addition, our results extent previous observations by showing that, in these patients, (1) the microlesion effect of DBS is not predictive of long-term benefit; (2) combined DBS with contralateral pallidotomy appears to be more effective than bilateral pallidal DBS; and (3) dystonia can reappear after an initial good response during long term follow up.