Lesion correlates of secondary paroxysmal dyskinesia in multiple sclerosis

Abstract

Secondary paroxysmal dyskinesia is a rare but life-quality-compromising symptom in multiple sclerosis (MS) and might be associated with particular MS lesions. The present study intended to determine associations between paroxysmal dyskinesia and the MS-associated lesion site using a voxelwise lesion analysis. We conducted a retrospective study and sought MS patients with documented paroxysmal dyskinesia and controls without paroxysmal dyskinesia matched for age, disease severity, and disease duration in a local database. The MS lesions were analysed on T2-weighted magnetic resonance imaging scans (1.5 or 3 T), manually outlined, and transformed into stereotaxic space. We determined the lesion overlap and compared the absence or presence of paroxysmal dyskinesia voxelwise between patients with and without lesions in a given voxel using the Liebermeister test with 4000 permutations. From 15,869 MS patient records screened, we identified 25 patients with paroxysmal dyskinesia. The voxelwise analysis in 22 subjects yielded associations between paroxysmal dyskinesia and MS lesions in the internal capsule, the basal ganglia, and another prominent lesion cluster in the posterior periventricular white matter. Our voxelwise analysis shows associations between paroxysmal dyskinesia and MS lesions in the internal capsule and basal ganglia, areas contributing to motor sequence programming. This association in another lesion site located in the posterior thalamic radiation suggests that lesions in subcortical sensory pathways may also contribute to paroxysmal dyskinesia in MS.

The Phenotypic and Genetic Spectrum of Paroxysmal Kinesigenic Dyskinesia in China

“…On the other hand, if red flags which are not common in primary PKD patients are present, more careful assessment will be needed to differentiate primary PKD from other paroxysmal dyskinesias or secondary PKD. Brain CT/MRI is recommended for all PKD‐suspected patients, because PKD has several secondary etiologies, such as multiple sclerosis, trauma, metabolic derangements, and inadequate brain perfusion . Genetic screening is optional, because PKD is a relatively benign disease with spontaneous remission and effective medications to control attacks.…”

“…Brain CT/MRI is recommended for all PKD-suspected patients, because PKD has several secondary etiologies, such as multiple sclerosis, trauma, metabolic derangements, and inadequate brain perfusion. [29][30][31][32][33][34] Genetic screening is optional, because PKD is a relatively benign disease with spontaneous remission and effective medications to control attacks. For patients who undergo genetic screening, mutations of the following genes reported to be associated with PKD should be initially tested: PRRT2, PNKD, SLC2A1, SCN8A, KCNMA1, KCNA1, and DEPDC5.…”

Clinical and Genetic Overview of Paroxysmal Movement Disorders and Episodic Ataxias

“…In acquired PxDs, onset is usually in adulthood, and interictal neurological abnormalities are commonly found. Multiple sclerosis (MS) is probably the most common cause [41,[337][338][339]. MS is an acquired demyelinating disease of the CNS in which the immune system attacks the protective sheath (myelin) that covers nerve fibers in the brain and spinal cord.…”

Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China

“…In a few cases, PKD may be secondary to other factors [39], such as demyelinating diseases of the central nervous system, cerebrovascular diseases, traumatic brain injury, or metabolic abnormalities [39][40][41]. Multiple sclerosis (MS), particularly the relapsing-remitting MS, is the most common cause of secondary PKD [42][43][44][45][46]. The lesions of MS related to PKD involve the thalamus, the lenticular nucleus, the globus pallidus and the internal capsule [43], and these demyelinating lesions may result in increased axon sensitivity that causes symptoms [43].…”

“…Multiple sclerosis (MS), particularly the relapsing-remitting MS, is the most common cause of secondary PKD [42][43][44][45][46]. The lesions of MS related to PKD involve the thalamus, the lenticular nucleus, the globus pallidus and the internal capsule [43], and these demyelinating lesions may result in increased axon sensitivity that causes symptoms [43]. Calcification of the basal ganglia, including the idiopathic basal ganglial calcification and the basal ganglial calcification secondary to hypoparathyroidism or pseudo-parathyroidism, may also cause the secondary PKD [47][48][49][50][51].…”