Elsevier

The Lancet Neurology

Volume 8, Issue 8, August 2009, Pages 709-717
The Lancet Neurology

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Bilateral pallidal deep brain stimulation for the treatment of patients with dystonia-choreoathetosis cerebral palsy: a prospective pilot study

https://doi.org/10.1016/S1474-4422(09)70151-6Get rights and content

Summary

Background

Cerebral palsy (CP) with dystonia-choreoathetosis is a common cause of disability in children and in adults, and responds poorly to medical treatment. Bilateral pallidal deep brain stimulation (BP-DBS) of the globus pallidus internus (GPi) is an effective treatment for primary dystonia, but the effect of this reversible surgical procedure on dystonia-choreoathetosis CP, which is a subtype of secondary dystonia, is unknown. Our aim was to test the effectiveness of BP-DBS in adults with dystonia-choreoathetosis CP.

Methods

We did a multicentre prospective pilot study of BP-DBS in 13 adults with dystonia-choreoathetosis CP who had no cognitive impairment, little spasticity, and only slight abnormalities of the basal ganglia on MRI. The primary endpoint was change in the severity of dystonia-choreoathetosis after 1 year of neurostimulation, as assessed with the Burke–Fahn–Marsden dystonia rating scale. The accuracy of surgical targeting to the GPi was assessed masked to the results of neurostimulation. Analysis was by intention to treat.

Findings

The mean Burke–Fahn–Marsden dystonia rating scale movement score improved from 44·2 (SD 21·1) before surgery to 34·7 (21·9) at 1 year post-operatively (p=0·009; mean improvement 24·4 [21·1]%, 95% CI 11·6–37·1). Functional disability, pain, and mental health-related quality of life were significantly improved. There was no worsening of cognition or mood. Adverse events were related to stimulation (arrest of the stimulator in one patient, and an adjustment to the current intensity in four patients). The optimum therapeutic target was the posterolateroventral region of the GPi. Little improvement was seen when the neurostimulation diffused to adjacent structures (mainly to the globus pallidus externus [GPe]).

Interpretation

Bilateral pallidal neurostimulation could be an effective treatment option for patients with dystonia-choreoathetosis CP. However, given the heterogeneity of motor outcomes and the small sample size, results should be interpreted with caution. The optimum placement of the leads seemed to be a crucial, but not exclusive, factor that could affect a good outcome.

Funding

National PHRC; Cerebral Palsy Foundation: Fondation Motrice/APETREIMC; French INSERM Dystonia National Network; Medtronic.

Introduction

Cerebral palsy (CP) is characterised by motor impairment and abnormal movements and postures that result from injury to the developing brain.1 CP, a clinically heterogeneous disorder, is the most common cause of disability in children, affecting 2–3 per 1000 live births;2, 3 about 10–15% of patients present with severe disabling movement disorders (dystonia-choreoathetosis) and little or no impairment of cognitive function. The dystonia-choreoathetosis forms of CP, with basal ganglia dysfunction, are mainly due to neonatal hypoxic ischaemic encephalopathy in term or near-term infants.1, 2 Medical treatments are ineffective, and because the life expectancy of these patients in high-income countries is similar to that of the general population,2 during early adulthood they will have to deal with motor disabilities, limited autonomy, and social difficulties.

A substantial and sustained benefit of bilateral pallidal deep brain stimulation (BP-DBS) has been consistently reported in patients with primary generalised dystonia.4, 5, 6 BP-DBS has therefore raised great expectations among patients with dystonia-choreoathetosis CP because the disease shares most of the features of primary dystonia (eg, involuntary sustained muscle contractions that lead to abnormal movements and postures). However, dystonia-choreoathetosis CP is considered among the causes of secondary dystonia, which are reputed to respond less well to neurostimulation than primary dystonia.4, 7, 8

The few previous reports of neurostimulation in patients with dystonia-choreoathetosis CP have involved small, heterogeneous series and unmasked designs.7, 9, 10, 11, 12, 13 We did a prospective, multicentre, pilot study with standardised and masked assessments to assess the effects of bilateral pallidal stimulation on motor impairment, functional disability, and quality of life in patients with dystonia-choreoathetosis CP.

Section snippets

Patients

13 patients with dystonia-choreoathetosis CP were operated on between September 2003 and March 2006. The inclusion criteria were: disabling dystonia, defined as involuntary sustained muscle contractions that led to abnormal movements and postures, which could be multifocal or generalised, with a combination of segmental crural dystonia (one leg and the trunk) and involvement of any other segment (face, neck, or upper or lower limbs);14 neonatal hypoxic or ischaemic encephalopathy2 and delayed

Results

13 patients (nine women and four men; median age 33 years [range 20–44]; table 1) were included in the study. Table 2 summarises the severity of abnormal movements and motor disability, as assessed with the movement and disability subscales of the Burke–Fahn–Marsden dystonia rating scale, before surgery and after 1 year of continuous stimulation. The mean Burke–Fahn–Marsden dystonia rating scale movement score was significantly lower at 1 year than it was at baseline (p=0·01), with an overall

Discussion

In these adults with CP secondary to neonatal hypoxic or ischaemic encephalopathy, who had severe movement disorders (dystonia-choreoathetosis), little or no cognitive impairment, and no more than slight abnormalities seen on preoperative T1-weighted MRI, BP-DBS resulted in most cases in a sustained improvement in motor symptoms in most segments of the body (neck, trunk, and limbs) over 1 year compared with their preoperative status. Some patients showed an improvement that was similar to that

References (33)

  • HA Eltahawy et al.

    Primary dystonia is more responsive than secondary dystonia to pallidal interventions: outcome after pallidotomy or pallidal deep brain stimulation

    Neurosurgery

    (2004)
  • JK Krauss et al.

    Chronic stimulation of the globus pallidus internus for treatment of non-DYT1 generalized dystonia and choreoathetosis: 2-year follow up

    J Neurosurg

    (2003)
  • VM Tronnier et al.

    Pallidal stimulation for generalized dystonia. Report of three cases

    J Neurosurg

    (2000)
  • M Krause et al.

    Pallidal stimulation for dystonia

    Neurosurgery

    (2004)
  • G Zorzi et al.

    Stimulation of the globus pallidus internus for childhood-onset dystonia

    Mov Disord

    (2005)
  • PA Starr et al.

    Microelectrode-guided implantation of deep brain stimulators into the globus pallidus internus for dystonia: techniques, electrode locations, and outcomes

    J Neurosurg

    (2006)
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