Lesion Locations Causing Cervical Dystonia Are Part of a Common Brain Network

Cervical dystonia is conventionally attributed to dysfunction of the basal ganglia, but abnormalities have been observed in many other regions of the brain. Accordingly, it's been proposed that cervical dystonia may be a network disorder resulting from dysfunction in multiple brain regions. However, the key nodes of this network have not yet been identified.

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In rare cases, focal brain lesions cause symptoms that are nearly identical to those of idiopathic cervical dystonia. Studying the links between brain lesions and resulting symptoms is a way to investigate cervical dystonia. However, this is complicated; lesions causing cervical dystonia can occur in numerous brain locations, and symptoms can emerge not only from the lesion itself, but also from the effect of the lesion on remote but connected brain regions.

As previously published in the New England Journal of Medicine, researchers at Massachusetts General Hospital have been using lesion network mapping to localize multiple neurological disorders, including Parkinson's disease and other movement disorders. Rather than focusing solely on lesion location, this technique makes use of a database of normal resting-state functional connectivity MRI (rs-fcMRI) scans to identify the network of brain regions connected to each lesion location.

Now, research fellow Juho Joutsa, MD, PhD, Michael D. Fox, MD, PhD, assistant neuroscientist in the Athinoula A. Martinos Center for Biomedical Imaging at Mass General, and colleagues have applied the mapping approach to lesions causing cervical dystonia. Their latest report in Brain goes beyond previous lesion network mapping studies—it demonstrates that the neuroanatomical substrate of cervical dystonia associated with brain lesions is also abnormal in idiopathic cervical dystonia.

Case Selection

The researchers identified case reports on 25 patients ≥10 years of age who had lesion-induced cervical dystonia resulting from one or more brain lesions. The lesions occurred in the cerebellum (n=11), brainstem (n=9), basal ganglia (n=8), thalamus (n=1) and occipital lobe (n=1).

Lesion Network Mapping

The researchers traced the reported location of each lesion onto a standardized brain atlas. Using rs-fcMRI data from a dataset of 1,000 healthy young adults, they identified the brain regions that were functionally connected to all or most lesion locations. They found that the lesions were part of a single, functionally connected brain network:

• All lesion locations were positively correlated with the cerebellar vermis, dentate nucleus, cerebellar cortex and midbrain
• All lesion locations were negatively correlated with the right somatosensory cortex bilaterally, extending slightly into the motor cortex

The researchers compared the lesion locations of the 25 patients with 208 control lesion locations previously found not to cause cervical dystonia. A region of interest (ROI) in lobule IX of the cerebellum and an ROI in the somatosensory cortex/Brodmann's area 1 were specific to lesion locations that caused cervical dystonia.

Relevance to Idiopathic Cervical Dystonia

The team then determined that cerebellar and somatosensory ROI were also abnormal in 37 patients with idiopathic cervical dystonia:

• The ROI in the cerebellum showed abnormal connectivity to regions in the lateral sensorimotor cortex and operculum
• The ROI in the somatosensory cortex showed abnormal connectivity to regions in the basal ganglia, thalamus, anterior cingulate, occipital cortex and sensorimotor cortex

To assess specificity, the researchers compared those two ROI with 19 control ROI identified in previous studies, which covered 11 different neurologic symptoms. Patients with idiopathic cervical dystonia showed significantly greater abnormalities in the two ROI derived from brain lesions causing cervical dystonia than in the 19 control ROI.

Relevance to Treatment

In a previous study, 53 patients with cervical dystonia and 52 patients with generalized or segmented dystonia were categorized as having a good or poor clinical response to deep brain stimulation (DBS). The current researchers identified sites near the globus pallidus that were significantly associated with response in that study, then compared those sites to the two abnormal ROI:

• The cerebellar ROI was positively connected to DBS sites associated with good clinical response in cervical dystonia patients (P < .001) and dystonia patients in general (P < .001)
• The somatosensory ROI was negatively connected to the optimal DBS site for treating cervical dystonia (P < .001) and dystonia in general (P < .001)
• The cerebellar ROI was significantly more positively connected to DBS sites associated with good, compared with poor, clinical response (P = .002)
• The somatosensory ROI was significantly more negatively connected to DBS sites associated with good, compared with poor, responses (P < .001)

These findings of cervical dystonia are additional evidence that mapping brain lesions can guide the search for treatment targets in patients who do not have brain lesions but have similar neurologic symptoms.

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