Clinical correlates of abnormal subcortical volumes in Essential Tremor.

Essential tremor (ET) is considered to be a neurodegenerative disorder and it is plausible that the observed motor and non-motor symptoms may be attributable to functional alterations secondary to abnormalities of subcortical nuclei. This study aims to compare the volumes of subcortical nuclei in patients with ET to ascertain neuroimaging correlates of motor and non-motor features of ET. Forty patients of ET and 40 age- and gender-matched healthy controls (HC) were enrolled in this study. Tremor severity was quantified with the Fahn-Tolosa-Marin tremor rating scale. Patients of ET with and without a rest tremor were also compared. Structural imaging was performed on a 3T scanner, and volumes of subcortical structures were obtained using Freesurfer. There was no difference in total brain volume between ET and HC. However, compared to HC, significantly lower volumes of bilateral thalamus, hippocampus, and ventral diencephalon were observed in patients with ET. A significantly higher volume was observed in the right caudate nucleus, pallidum, amygdala, and bilateral putamen, and nucleus accumbens. No difference was observed between patients of ET with and without a rest tremor. Patients with ET have significant alterations in volumes of subcortical nuclei, which are not limited to the motor domain and include structures involved in cognitive and behavioral functions. These results add to the growing concept of a neurodegenerative pathophysiology of ET with abnormalities extending beyond the cerebellum.

Abnormal hippocampal subfields are associated with cognitive impairment in Essential Tremor.

Multi-domain cognitive impairment (CI) has been frequently described in patients with essential tremor (ET). However, the exact neuroanatomical basis for this impairment is uncertain. This study aims to ascertain the role of the hippocampal formation in cognitive impairment in ET. Forty patients with ET and 40 age, gender and education matched healthy controls (HC) were enrolled. Cognition was assessed using a structured neuropsychological battery and patients were categorized as ET with CI (ETCI) and ET without CI (ETNCI). Automatic segmentation of hippocampal subfields was performed using FreeSurfer 6.0. The obtained volumes were correlated with scores of neuropsychological tests. Significant atrophy of the left subiculum, CA4, granule-cell layer of dentate gyrus, right molecular layer, and hypertrophy of bilateral parasubiculum, right hippocampus-amygdala-transition-area, bilateral hippocampal tail (HT) and widening of right hippocampal fissure was observed in ET. Trends toward atrophy of right subiculum, and widening of left HF was also observed. Comparison of HC and ETCI revealed atrophy of right subiculum, hypertrophy of bilateral parasubiculum, HT, and widening of left HF. ETCI showed a trend toward widening of right HF. ETNCI had isolated left parasubicular hypertrophy and in comparison, to ETNCI the ETCI subgroup had atrophy of bilateral fimbria. Significant correlations were observed between the volumes of HT, HF, fimbria and scores of tests for executive function, working and verbal memory. Patients with ET have significant volumetric abnormalities of several hippocampal subfields and these abnormalities may be important contributors for some forms of cognitive impairment observed in ET.

Phenotypic Variability of Essential Tremor Based on the Age at Onset.

BACKGROUND: Essential tremor (ET) is reported to have a bimodal distribution of age at onset (AAO) with phenotypic variability based on the AAO. This study aims to explore the distribution of AAO based on mathematical modeling and ascertain the differences, if any, in the clinical features of groups. METHODS: A chart review was conducted for 252 patients with ET diagnosed based on the Consensus statement of the Movement Disorder Society on Tremor. Finite mixture modeling was performed to identify groups of the cohort based on the AAO. RESULTS: Three groups were defined: early onset (EO): AAO ≤ 22 years, n = 63, intermediate onset (IO): 23 ≤ AAO ≤ 35 years, n = 43, and late onset (LO): AAO ≥ 36 years, n = 146. There were no significant differences related to family history or responsiveness to alcohol. The EO group had significantly higher prevalence of upper limb and lower limb tremor. Head tremor and voice tremor was more prevalent in the IO and LO groups. Cerebellar signs showed a significant increase with an increase in AAO. CONCLUSIONS: ET shows significant phenotypic variability based on the AAO. Patients with an early AAO are more likely to develop an appendicular tremor, whereas the probability of axial tremor and cerebellar signs increases with increasing AAO.

Role of altered cerebello-thalamo-cortical network in the neurobiology of essential tremor.

INTRODUCTION: Essential tremor (ET) is the most common movement disorder among adults. Although ET has been recognized as a mono-symptomatic benign illness, reports of non-motor symptoms and non-tremor motor symptoms have increased its clinical heterogeneity. The neural correlates of ET are not clearly understood. The aim of this study was to understand the neurobiology of ET using resting state fMRI. METHODS: Resting state functional MR images of 30 patients with ET and 30 age- and gender-matched healthy controls were obtained. The functional connectivity of the two groups was compared using whole-brain seed-to-voxel-based analysis. RESULTS: The ET group had decreased connectivity of several cortical regions especially of the primary motor cortex and the primary somatosensory cortex with several right cerebellar lobules compared to the controls. The thalamus on both hemispheres had increased connectivity with multiple posterior cerebellar lobules and vermis. Connectivity of several right cerebellar seeds with the cortical and thalamic seeds had significant correlation with an overall score of Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) as well as the subscores for head tremor and limb tremor. CONCLUSION: Seed-to-voxel resting state connectivity analysis revealed significant alterations in the cerebello-thalamo-cortical network in patients with ET. These alterations correlated with the overall FTM scores as well as the subscores for limb tremor and head tremor in patients with ET. These results further support the previous evidence of cerebellar pathology in ET.

Prescribing Pattern for Parkinson's Disease in Indian Community before Referral to Tertiary Center.

BACKGROUND: Several factors determine the choice of medications in patients with Parkinson's disease (PD). We aimed to analyze the pattern of prescription of drugs in patients with PD before attending a tertiary-care center. METHODS: The study included chart review of 800 PD patients attending the Department of Neurology of the National Institute of Mental Health and Neurosciences in Bangalore, India. RESULTS: The mean age at onset was 51.1±11.8 years. The mean duration of illness was 41.7±43.6 months. At first visit, 79.4% (group 1, n=635) of patients were on medications, 10% (group 2, n=80) were on medications but later discontinued, and 10.6% (group 3, n=85) were drug-naïve. Overall, levodopa was prescribed in 94.8%, trihexyphenidyl in 40.4%, dopamine agonists in 23.2%, and amantadine in 17.2% either as monotherapy or in combination. In group 1, 37.8% were on monotherapy, with levodopa being the most commonly used agent (33.1%), followed by trihexyphenidyl (2.2%), dopamine agonists (1.6%), and amantadine (0.6%). Among those on polytherapy, levodopa plus trihexyphenidyl was the preferred combination (23.9%). In group 2, levodopa monotherapy was also most common (72.5%), followed by trihexyphenidyl monotherapy (7.5%). CONCLUSIONS: Levodopa and trihexyphenidyl were the most commonly prescribed drugs in our patients. A higher use of trihexyphenidyl could be due to its easy availability, low cost, and better tolerability in our patients, who were relatively young at the time of onset of their disease. The choice of antiparkinsonian medications at the primary and secondary care levels in India may be inappropriate, and newer guidelines tailored to the Indian context are warranted.

Are patients with limb and head tremor a clinically distinct subtype of essential tremor?

BACKGROUND: Essential tremor (ET) is the most common tremor disorder in adults. In addition to upper limbs, the tremor in ET may also involve head, jaw, voice, tongue, and trunk. Though head tremor (HT) is commonly present in patients with ET, large comparative studies of ET patients with HT (HT+) and without HT (HT-) are few. METHODS: To determine whether ET with HT is a distinct clinical subtype by comparing ET patients with and without HT, a chart review of 234 consecutive patients with ET attending the neurology clinics of the National Institute of Mental Health and Neurosciences, India, was done. A movement disorder specialist confirmed the diagnosis of ET in all patients using the National Institutes of Health collaborative genetic criteria. RESULTS: HT was present in 44.4% of the patients. Comparison between HT+ and HT- showed that the HT+ group patients: (1) were older, (2) had later onset of tremor, (3) had unimodal distribution of age at onset with a single peak in the fifth decade, (4) had more frequent voice tremor, and (5) were more likely to have mild cervical dystonia. HT was part of presenting symptoms in nearly two thirds of the ET patients and in the rest it was detected during clinical examination. CONCLUSIONS: Several demographic and clinical variables suggest that ET patients with HT have a distinct clinical phenotype.