Subjects and methods
Subjects
The data from three HT patients who consecutively visited the Department of Neurology, Affiliated Hospital of Chengdu University of TCM from August 2018 to April 2021 were retrospectively analyzed. In particular, their clinical and imaging characteristics were investigated. The diagnostic criteria for HT in this work complied with the Consensus Statement on the Classification of Tremors established by the International Parkinson and Movement Disorder Society in 1998 [3], as were as follows: (1) rest and intention tremors, mostly accompanied by postural tremors; (2) usually lower than 4.5 Hz; (3) mostly occurring in 1 to 24 months after the primary disease onset.
Clinical information
Clinical information was collected from the patients, and included gender, age of onset, etiology, delay in HT onset time after primary disease onset, side of tremor (left/right), affected limb (upper/lower limb), presence or absence of hemiplegia, aphasia or paresthesia, involvement of cranial nerves, treatment methods, and outcome.
Neurophysiological testing
Electromyography (EMG) tremor analysis was performed in the patients using the Nicolet EDX 6-channel EMG system with 4 pairs of EMG surface electrodes and 2 piezoresistive accelerometers. Recording parameters were as follows: sensitivity: 100 μV/D, specific scanning speed: 100 ms/ D, EMG low frequency band pass filter: 10.0 Hz, high frequency band pass filter: 10.0 kHz; accelerometer low frequency band pass filter: 0.5 Hz, high frequency band pass filter: 30 Hz. The recording electrodes were placed on the muscle belly of the flexor carpi ulnaris and extensor carpi ulnaris on both forearms, the reference electrodes were placed on the corresponding distal tendons, and the 2 accelerometers were placed 2 cm proximal to the third metacarpophalangeal joint on the dorsal side of both hands. Measurements were recorded at several states, including stillness, posture, intention, and the holding of a load of 1000 g. Stillness was defined as the patient sitting on a chair with both forearms resting on the chair armrests, with the wrists naturally hanging down and fully relaxed. Posture was defined as when the patient’s hands were stretched forward flat with the wrists straight. Intention was defined as when the patient slowly repeated the finger-to-nose movement with the bilateral upper limbs. Finally, holding a load of 1000 g was performed with the hands being stretched forward flat while holding a 1000-g sandbag with the wrists straight. The tremor peak frequency, flexor and extensor tremor half-width power, as well as types of agonist and antagonist muscle contractions were recorded.
Multimodal 3D medical imaging
The cranial MRI information of the patients was collected, and included T1-weighted images (T1WI), T2-weighted images (T2WI), FLAIR and diffusion weighted imaging (DWI) sequences, and functional MRI and diffusion tensor imaging (DTI) data. The 3D reconstruction and visualization of multimodal 3D medical images were adopted to reconstruct and analyze the damaged brain sites and related nerve conduction bundles. This technique involves thalamus subfield parcellation and subfield-based tractography. Specifically, the thalamus from the T1WI was parcellated into 25 different subfields using FreeSurfer [4] with a probabilistic atlas built from histological data [5]. The T1WI was then linearly registered to the b0 image of the diffusion series. The generated transformation matrix was used to map the parcellated thalamus to the diffusion data space. The diffusion tensors throughout the brain of the subject were calculated using the “dtifit” function in FSL. The deterministic tractography was performed on the calculated tensors using each subfield of the thalamus as seeds.