Faculty Bibliography

Numerous brain imaging studies have demonstrated structural changes in the basal ganglia, thalamus, sensorimotor cortex, and cerebellum across different forms of primary dystonia. However, our understanding of brain abnormalities contributing to the clinically well-described phenomenon of task specificity in dystonia remained limited. We used high-resolution magnetic resonance imaging (MRI) with voxel-based morphometry and diffusion weighted imaging with tract-based spatial statistics of fractional anisotropy to examine gray and white matter organization in two task-specific dystonia forms, writer's cramp and laryngeal dystonia, and two non-task-specific dystonia forms, cervical dystonia and blepharospasm. A direct comparison between both dystonia forms indicated that characteristic gray matter volumetric changes in task-specific dystonia involve the brain regions responsible for sensorimotor control during writing and speaking, such as primary somatosensory cortex, middle frontal gyrus, superior/inferior temporal gyrus, middle/posterior cingulate cortex, and occipital cortex as well as the striatum and cerebellum (lobules VI-VIIa). These gray matter changes were accompanied by white matter abnormalities in the premotor cortex, middle/inferior frontal gyrus, genu of the corpus callosum, anterior limb/genu of the internal capsule, and putamen. Conversely, gray matter volumetric changes in the non-task-specific group were limited to the left cerebellum (lobule VIIa) only, whereas white matter alterations were found to underlie the primary sensorimotor cortex, inferior parietal lobule, and middle cingulate gyrus. Distinct microstructural patterns in task-specific and non-task-specific dystonias may represent neuroimaging markers and provide evidence that these two dystonia subclasses likely follow divergent pathophysiological mechanisms precipitated by different triggers.

BACKGROUND: Leucine-rich glioma inactivated 1 (LGI1) antibody produces a syndrome of limbic encephalitis, hyponatremia, and facio-brachial dystonic seizures that is non-paraneoplastic and responsive to corticosteroids. Parkinsonism, tremor, and generalized chorea are rare manifestations of LGI1, but, when present, commonly accompany other signs of limbic encephalitis. CASE REPORT: We present a case of LGI1-related isolated chorea in a 53-year-old Japanese male. His chorea responded to high-dose steroids, suggesting a potential role for this synaptic antibody in triggering chorea. DISCUSSION: This case highlights a new treatable etiology of chorea.

IMPORTANCE: Data on the long-term cognitive outcomes of patients with PARKIN-associated Parkinson disease (PD) are unknown but may be useful when counseling these patients. OBJECTIVE: Among patients with early-onset PD of long duration, we assessed cognitive and motor performances, comparing homozygotes and compound heterozygotes who carry 2 PARKIN mutations with noncarriers. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 44 participants at 17 different movement disorder centers who were in the Consortium on Risk for Early-Onset PD study with a duration of PD greater than the median duration (>14 years): 4 homozygotes and 17 compound heterozygotes (hereafter referred to as carriers) and 23 noncarriers. MAIN OUTCOMES AND MEASURES: Unified Parkinson Disease Rating Scale Part III (UPDRS-III) and Clinical Dementia Rating scores and neuropsychological performance. Linear regression models were applied to assess the association between PARKIN mutation status and cognitive domain scores and UPDRS-III scores. Models were adjusted for age, education, disease duration, language, and levodopa equivalent daily dose. RESULTS: Carriers had an earlier age at onset of PD (P < .001) and were younger (P = .004) at time of examination than noncarriers. They performed better than noncarriers on the Mini-Mental State Examination (P = .010) and were more likely to receive lower scores on the Clinical Dementia Rating (P = .003). In multivariate analyses, carriers performed better than noncarriers on the UPDRS-III (P = .02) and on tests of attention (P = .03), memory (P = .03), and visuospatial (P = .02) cognitive domains. CONCLUSIONS AND RELEVANCE: In cross-sectional analyses, carriers demonstrated better cognitive and motor performance than did noncarriers with long disease duration, suggesting slower disease progression. A longitudinal follow-up study is required to confirm these findings.

Movement disorder emergencies are defined as clinical scenarios where a movement disorder develops over hours to days, and in which morbidity and even mortality can result from failure to appropriately diagnose and manage the patient. The last decade has seen increasing recognition of various movement disorder emergencies, including acute parkinsonism, neuroleptic malignant syndrome, respiratory compromise in multiple system atrophy, dystonic storm, oculogyric crisis, and hemiballism, among others. This article will review the major movement disorder emergencies encountered in the hospital and office, emphasizing practical management and treatment.

L-2-hydroxyglutaric aciduria (L2HGA) is a neurometabolic disorder characterized by macrocephaly, seizures, progressive mental retardation, pyramidal signs, ataxia and tremor. Dystonia is an under-recognized feature of this entity in the literature. We report two siblings with L2HGA, one of whom presented with writer's cramp followed by dystonia of the other hand. An elevated plasma lysine, highly elevated urine 2-hydroxyglutaric acid, and MRI with characteristic findings (leukoencephalopathy of bilateral subcortical white matter sparing central white matter) suggested the diagnosis, which was confirmed by genetic testing.