Cerebrospinal Fluid Flow in Patients with Huntington's Disease.

OBJECTIVE: Investigations of cerebrospinal fluid (CSF) flow aberrations in Huntington's disease (HD) are of growing interest, as impaired CSF flow may contribute to mutant Huntington retention and observed heterogeneous responsiveness to intrathecally administered therapies. METHOD: We assessed net cerebral aqueduct CSF flow and velocity in 29 HD participants (17 premanifest and 12 manifest) and 51 age- and sex matched non-HD control participants using 3-Tesla magnetic resonance imaging methods. Regression models were applied to test hypotheses regarding: (i) net CSF flow and cohort, (ii) net CSF flow and disease severity (CAP-score), and (iii) CSF volume after correcting for age and sex. RESULTS: Group-wise analyses support a decrease in net CSF flow in HD (mean 0.14 ± 0.27 mL/min) relative to control (mean 0.32 ± 0.20 mL/min) participants (p = 0.02), with lowest flow in the manifest HD cohort (mean 0.04 ± 0.25 mL/min). This finding was explained by hyperdynamic CSF movement, manifesting as higher caudal systolic CSF flow velocity and higher diastolic cranial CSF flow velocity across the cardiac cycle, in HD (caudal flow: 0.17 ± 0.07 mL/s, cranial flow: 0.14 ± 0.08 mL/s) compared to control (caudal flow: 0.13 ± 0.06 mL/s, cranial flow: 0.11 ± 0.04 mL/s) participants. A positive correlation between cranial diastolic flow and disease severity was observed (p = 0.02). INTERPRETATIONS: Findings support aqueductal CSF flow dynamics changing with disease severity in HD. These accelerated changes are consistent with changes observed over the typical adult lifespan, and may have relevance to mutant Huntington retention and intrathecally administered therapeutics responsiveness. ANN NEUROL 2023;94:885-894.

Structural Correlates of the Sensorimotor Cerebellum in Parkinson's Disease and Essential Tremor.

BACKGROUND: Parkinson's disease (PD) and essential tremor (ET) are commonly encountered movement disorders. Pathophysiologic processes that localize to the cerebellum are described in both. There are limited studies investigating cerebellar structural changes in these conditions, largely because of inherent challenges in the efficiency of segmentation. METHODS: We applied a novel multiatlas cerebellar segmentation method to T1-weighted images in 282 PD and 111 essential tremor patients to define 26 cerebellar lobule volumes. The severity of postural and resting tremor in both populations and gait and postural instability in PD patients were defined using subscores of the UPDRS and Washington Heights-Inwood Genetic Study motor scales. These clinical measurements were related to lobule volume size. Multiple comparisons were controlled using a false discovery rate method. RESULTS: Group differences were identified between ET and PD patients, with reductions in deep cerebellar nucleus volume in ET versus reduced lobule VI volume in PD. In ET patients, lobule VIII was negatively correlated with the severity of postural tremor. In PD patients, lobule IV was positively correlated with resting tremor and total tremor severity. We observed differences in cerebellar structure that localized to sensorimotor lobules of the cerebellum. Lobule volumes appeared to differentially relate to clinical symptoms, suggesting important clinicopathologic distinctions between these conditions. These results emphasize the role of the cerebellum in tremor symptoms and should foster future clinical and pathologic investigations of the sensorimotor lobules of the cerebellum. © 2020 International Parkinson and Movement Disorder Society.

WHIGET and TETRAS Ratings of Action Tremor in Patients with Essential Tremor: Substantial Association and Agreement.

Background: Evaluating tremor severity is a critical component of diagnosing and clinically managing patients with essential tremor (ET). We examined the comparability of tremor severity ratings derived from two frequently used tremor rating scales: the Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET) rating scale and the Tremor Research Group Essential Tremor Rating Scale (TETRAS). Methods: A trained assistant administered and videotaped a neurological examination, including eight items assessing upper limb action tremor (arms outstretched, arms in the wingbeat position, finger-nose-finger maneuver, and drawing of Archimedes spirals). An experienced movement disorders neurologist reviewed the videos and assigned WHIGET and TETRAS ratings. We calculated associations between TETRAS and WHIGET ratings using Spearman rank order correlations. Subsequently, we collapsed these ratings into four tremor severity categories (absent, mild, moderate, severe) and then two broader tremor severity categories (absent/mild, moderate/severe). We calculated weighted Kappa coefficients to assess agreement between category assignments based on the TETRAS and the WHIGET. Results: Spearman's r' s were significant for all items (p's ≤ 0.001, mean r = 0.89). Weighted Kappa's revealed substantial to near perfect agreement for all eight items (mean k = 0.86, range = 0.64 to 1.00). Conclusion: Analyses revealed substantial strength of association and substantial to near perfect agreement between items rated with the WHIGET and TETRAS scales. These data indicated that ratings provided by each scale are highly comparable.