Clinical Features, Neuroimaging, and Levodopa-Responsiveness in Holmes' Tremor: A Video-Based Case-Series with a Review of the Literature

Abstract

Background: Holmes' tremor (HT) is a low-frequency tremor characterized by a combination of rest, posture, and action components. We are reporting the clinical features, neuroimaging findings, and levodopa responsiveness in 12 patients with HT.

Cases: The majority of the patients were male (11/12). Dystonia was observed in 10 patients and the remaining two patients had head tremor, a "forme-fruste" of cervical dystonia. The underlying etiologies were vascular (n = 8), head trauma (n = 2), and tumor resection (n = 2). Neuroimaging showed isolated involvement of the midbrain in four, thalamus in two, and basal ganglia and cerebellum in one patient each. A combination of the lesion (thalamus and cerebellum = 2; cerebellopontine angle = 1, and cortical/subcortical = 1) was present in four patients. Levodopa responsiveness was seen in 75% of patients including one with levodopa-induced dyskinesia.

Literature review: Of 139 patients from 49 studies, levodopa was tried in 123 patients. Improvement with levodopa was seen in 71 patients (57.72%). No improvement with levodopa was observed in 33 patients (26.82%) and details regarding therapeutic response were unavailable in 19 patients (15.44%).

Conclusions: Dystonia is an important clinical manifestation of HT. Levodopa responsiveness seen in the majority of the patients is consistent with the hypothesis that nigrostriatal pathway damage is crucial for the pathophysiology of HT.

Keywords: dystonia; levodopa; tremor.

FIG. 1

Case 1: axial sections of T2‐weighted (A) and gradient‐recall echo (GRE) images (B) of magnetic resonance imaging (MRI) brain show right midbrain hemorrhage. Case 2: axial fluid‐attenuated inversion recovery (FLAIR) (C) and T2‐weighted sections (D) of MRI brain showed ischemic infarct in the right thalamus and occipital region. Case 3: axial diffusion‐weighted (DWI) (E,F) and apparent diffusion coefficient (ADC) sequences (G,H) of MRI brain show bilateral acute thalamic and cerebellar infarcts. Case 4: axial FLAIR MRI brain (I) shows left mesencephalic hemorrhage. MR angiography (J) shows the causative left midbrain arteriovenous malformation. Case 5: axial GRE MRI brain (K) shows multiple bilateral cortical hemorrhagic areas admixed with infarctions because of cortical venous thrombosis. FLAIR MRI (L) is showing bilateral subcortical and periventricular white‐matter changes. MR venography (M) shows attenuated right transverse and superior sagittal sinuses. Case 6: axial T2‐weighted axial MRI brain (N) shows multiple chronic lacunar infarcts in the bilateral midbrain. Case 7: axial T2‐weighted MRI brain images show left temporal lobe encephalomalacia with gliosis (O) and left thalamic infarct (P). Case 8: axial sections of non‐contrast computerized tomography (NCCT) of the head (Q) shows multiple areas of hypodensity in the left basal ganglia region suggestive of a chronic infarct. Case 9: axial FLAIR MRI shows hyperintensities in the left cerebellar region suggestive of gliosis (R) and GRE MRI shows microbleeds in the right thalamus (S). Case 10: axial sections of NCCT head (T) and T2‐GRE MRI brain show right mesencephalic hemorrhage (U). Case 11: pre‐operative (V) and post‐operative (W) axial FLAIR MRI brain images show left cerebellopontine angle schwannoma. Case 12: coronal pre‐operative FLAIR MRI (X) shows medulloblastoma.