Dystonia in neurodegeneration with brain iron accumulation: outcome of bilateral pallidal stimulation

Abstract

Neurodegeneration with brain iron accumulation encompasses a heterogeneous group of rare neurodegenerative disorders that are characterized by iron accumulation in the brain. Severe generalized dystonia is frequently a prominent symptom and can be very disabling, causing gait impairment, difficulty with speech and swallowing, pain and respiratory distress. Several case reports and one case series have been published concerning therapeutic outcome of pallidal deep brain stimulation in dystonia caused by neurodegeneration with brain iron degeneration, reporting mostly favourable outcomes. However, with case studies, there may be a reporting bias towards favourable outcome. Thus, we undertook this multi-centre retrospective study to gather worldwide experiences with bilateral pallidal deep brain stimulation in patients with neurodegeneration with brain iron accumulation. A total of 16 centres contributed 23 patients with confirmed neurodegeneration with brain iron accumulation and bilateral pallidal deep brain stimulation. Patient details including gender, age at onset, age at operation, genetic status, magnetic resonance imaging status, history and clinical findings were requested. Data on severity of dystonia (Burke Fahn Marsden Dystonia Rating Scale—Motor Scale, Barry Albright Dystonia Scale), disability (Burke Fahn Marsden Dystonia Rating Scale—Disability Scale), quality of life (subjective global rating from 1 to 10 obtained retrospectively from patient and caregiver) as well as data on supportive therapy, concurrent pharmacotherapy, stimulation settings, adverse events and side effects were collected. Data were collected once preoperatively and at 2–6 and 9–15 months postoperatively. The primary outcome measure was change in severity of dystonia. The mean improvement in severity of dystonia was 28.5% at 2–6 months and 25.7% at 9–15 months. At 9–15 months postoperatively, 66.7% of patients showed an improvement of 20% or more in severity of dystonia, and 31.3% showed an improvement of 20% or more in disability. Global quality of life ratings showed a median improvement of 83.3% at 9–15 months. Severity of dystonia preoperatively and disease duration predicted improvement in severity of dystonia at 2–6 months; this failed to reach significance at 9–15 months. The study confirms that dystonia in neurodegeneration with brain iron accumulation improves with bilateral pallidal deep brain stimulation, although this improvement is not as great as the benefit reported in patients with primary generalized dystonias or some other secondary dystonias. The patients with more severe dystonia seem to benefit more. A well-controlled, multi-centre prospective study is necessary to enable evidence-based therapeutic decisions and better predict therapeutic outcomes.

Pantothenate Kinase-Associated Neurodegeneration

“…Oral or intrathecal baclofen, stereotactic pallidotomy and anticholinergic treatment may provide symptomatic relief but have no known disease-modifying effects [32,33].…”

Genetics and Pathophysiology of Neurodegeneration with Brain Iron Accumulation (NBIA)

“…However, compared to primary generalized dystonias with most studies showing long-lasting 21-95% improvement in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), the outcomes of DBS GPi in NBIA are more variable and at large less favourable [84][85][86]. In the largest series of 23 PKAN patients, at follow-up 9-15 months postoperatively, dystonia severity assessed by the BFMDRS had improved by 20% or more in two thirds of patients [87]. Although the extent of iron deposits and GP damage seem not to influence the immediate outcome of DBS GPi, benefit gradually diminishes over time due to disease progression.…”

“…Although the extent of iron deposits and GP damage seem not to influence the immediate outcome of DBS GPi, benefit gradually diminishes over time due to disease progression. Some have recommended to operate on patients at an early stage in order to prevent fixed skeletal deformities and improve quality of life [87]. Others have suggested that a beneficial effect can be expected in patients with mobile and axial dystonia rather than fixed and oromandibular dystonia [88].…”

Rechargeable Deep Brain Stimulators in the Management of Paediatric Dystonia: Well Tolerated with a Low Complication Rate

“…Initially used for patients with Parkinson’s disease and idiopathic dystonia, DBS has recently been helpful in treating patients with secondary dystonia [3,4]. Childhood dystonia may be a severe and debilitating condition, frequently of secondary aetiology, where treatment with medication alone often proves unsuccessful.…”

“…The use of monopolar stimulation, high voltage, wide pulse width of 150–450 µs and frequency of stimulation in the 130- to 210-Hz range leads to higher energy consumption and shorter battery life in cases of secondary or primary dystonia [3,8,9,10,11]. We have found a battery longevity between 15 and 33 months (mean 24 months) and observed reduced control of symptoms even prior to neurostimulator end of life, particularly in secondary dystonias which were often the severest cases [11].…”