Abstract
Background The pathophysiology underlying different types of
dystonia is not yet understood. We report microelectrode data from the globus
pallidus interna (GPi) and globus pallidus externa (GPe) in children undergoing
deep brain stimulation (DBS) for dystonia and investigate whether GPi and GPe
firing rates differ between dystonia types.
Methods Single pass microelectrode data were obtained to
guide electrode position in 44 children (3.3–18.1 years, median 10.7) with the
following dystonia types: 14 primary, 22 secondary Static and 8 progressive
secondary to neuronal brain iron accumulation (NBIA). Preoperative stereotactic
MRI determined coordinates for the GPi target. Digitised spike trains were
analysed offline, blind to clinical data. Electrode placement was confirmed by
a postoperative stereotactic CT scan.
Findings We identified 263 GPi and 87 GPe cells. Both GPi
and GPe firing frequencies differed significantly with dystonia aetiology. The
median GPi firing frequency was higher in the primary group than in the
secondary static group (13.5 Hz vs 9.6 Hz; p=0.002) and higher in the NBIA
group than in either the primary (25 Hz vs 13.5 Hz; p=0.006) or the secondary
static group (25 Hz vs 9.6 Hz; p=0.00004). The median GPe firing frequency was
higher in the NBIA group than in the secondary static group (15.9 Hz vs 7 Hz;
p=0.013). The NBIA group also showed a higher proportion of regularly firing
GPi cells compared with the other groups (p<0.001). A higher proportion of
regular GPi cells was also seen in patients with fixed/tonic dystonia compared
with a phasic/dynamic dystonia phenotype (p<0.001). The GPi firing frequency
showed a positive correlation with 1-year outcome from DBS measured by
improvement in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-m) score
(p=0.030). This association was stronger for the non-progressive patients
(p=0.006).
Interpretation Pallidal firing rates and patterns differ
significantly with dystonia aetiology and phenotype. Identification of specific
firing patterns may help determine targets and patient-specific protocols for
neuromodulation therapy.
Funding National Institute of Health Research, Guy's and St.
Thomas’ Charity, Dystonia Society UK, Action Medical Research, German National
Academic Foundation._____________________________________________________________________________
Dystonia can be primary, where the only feature of the disease is muscle contractions that may cause abnormal, repetitive movements, or it can be secondary to some other disease or brain injury. There are two types of secondary dystonia, including static lesions, and progressive disorders. Static lesions usually occur after hypoxic ischemic encephalopathy (HIE), prematurity, infection, a metabolic disturbance or a vascular event, and progressive disorders include “heredodegenerative dystonias, which are characterized by neurodegeneration,” according to the researchers. Most children have secondary types of dystonia.
One of the most well-established treatments for dystonia is deep brain stimulation (DBS) of the globus pallidus interna (GPi), though it is more effective for people with primary dystonia. In this study, the researchers say they “analyzed microelectrode recordings from the GPi and globus pallidus externa (GPe) in 44 children undergoing DBS for severe generalized dystonia, aiming to test the hypothesis that pallidal firing differs between different dystonia etiologies.”
The researchers report measuring the mean firing rate, the interspike interval distribution, and the instantaneous firing rate, and they classified cells as regular, irregular or bursting based on watching the cells during the firing pattern and the interspike interval distribution, as well as the instantaneous firing rate.
“We identified 263 GPi and 87 GPe cells from 81 electrode trajectories. In three patients, no active cells were identified,” said the researchers. The three with no active cells were excluded due to the possibility of a technical problem, but they also considered the possibility of “silent cells” in those three cases.
The goal of this study was more related to GPi than to GPe, and so, the researchers said, “therefore the path through the GPe was not strongly considered in the targeting of the trajectory. Some paths may have had very little GPe involved.” ...
They suggest that it understanding the different mechanisms involved will help explain why patients with secondary dystonia have a poorer response to DBS, and that further investigations are warranted.
- See more at: http://www.hcplive.com/medical-news/dystonia-why-some-patients-respond-better-to-deep-brain-stimulation#sthash.ugNOJxSy.dpuf
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