The Pathology of Essential Tremor
November 1, 2006 3 minutes read
The Pathology of Essential Tremor
Abstract & Commentary
By John J. Caronna, MD, Vice-Chairman, Department of Neurology, Cornell University Medical Center, Professor of Clinical Neurology, NewYork-Presbyterian Hospital. Dr. Caronna reports no financial relationships relevant to this field of study.
Synopsis: Patients with essential tremor may have degenerative changes in the Purkinje-dentate-thalamic pathways.
Source: Louis ED, et al. Essential tremor associated with pathologic changes in the cerebellum. Arch Neurol. 2006;63:1189-1193.
Essential tremor (ET) usually is a monosymptomatic disorder, although the manifestations of the tremor may be varied. Essential tremor can affect arms, head, eyelids, lips, voice, jaw, tongue, trunk, and legs. In some patients with typical ET, clinicians have described signs of cerebellar dysfunction, such as dysmetria and ataxia, but the association has been thought to be coincidental.1,2 The histopathological characteristics of the brain in cases of ET have remained unclear. In a previous report, Louis and colleagues3 reported the pathologic findings in 10 patients with ET. ET patients could be divided into 2 groups: those with brainstem Lewy bodies (n = 6) and those with mild cerebellar changes (n = 4). Now, they've reported a case of ET in which cerebellar involvement was marked. The patient, a 90-year-old woman, had a 30-year history of ET, characterized by head tremor and gradually, worsening action tremor of both arms. There were no clinical signs of Parkinsonism or cerebellar disorder.
At postmortem examination, there were mild degenerative changes in the cerebellar cortex (segmental loss of Purkinje cells, torpedoes, and Bergmann gliosis), as described previously.3 There were previously unreported extensive changes in the dentate nucleus that included marked neuronal loss, with atrophy of the remaining neurons, microglial clusters, and pallor of the dentate hilum. These changes were absent in 3 control subjects who were older than 90 years of age and 3 who were ages 85 to 90 years old. The brain of the patient with ET had no Lewy bodies and only mild changes of Alzheimer disease.
Commentary
ET is hypothesized to be caused by oscillatory activity in a cerebellum-dentate-brainstem pathway. Clinical studies1 have associated ET with higher-level gait disorders in the elderly.4 PET studies have demonstrated increased cerebellar activity in ET patients.5 Louis and colleagues have studied pathological specimens in the Essential Tremor Centralized Brain Repository at Columbia University to describe the cerebellar features of ET. The present report extends those findings. The neurons of the dentate nucleus receive synaptic input from Purkinje cells. Efferent fibers leave the dentate nucleus via the hilum, exit the cerebellum through the superior cerebellar peduncle, and pass rostrally in the brainstem to synapses in the contralateral ventrolateral nucleus of the thalamus. Therefore, patients with lesions in this pathway, whether in the cerebellum, dentate nucleus, or brainstem, could be expected to have some type of tremor, either that associated with essential tremor or a more cerebellar-like intention tremor. Such patients also would be expected to benefit from deep brain stimulation in the region of the ventrolateral nucleus of the thalamus. Louis et al have promised to continue to catalogue and describe the pathological changes in cases of essential tremor; therefore, one can look forward to future publications in which further clinicopathological correlations are provided.
References
1. Stolze H, et al. The gait disorder of advanced essential tremor. Brain. 2001;124:2278-2286.
2. Caronna JJ. Disturbed cerebellar functions in patients with essential tremor. Neurology Alert 2002;20:42-43.
3. Louis ED, et al. Essential tremor associated with focal nonnigral Lewy bodies: A clinicopathologic study. Arch Neurol. 2005;62:1004-1007.
4. Nutt JG, et al. Human walking and higher-level gait disorders, particularly in the elderly. Neurology. 1993; 43:268-279.
5. Hallet M, Dubinsky RM. Glucose metabolism in the brain of patients with essential tremor. J Neurol Sci. 1993;114: 45-48.
Patients with essential tremor may have degenerative changes in the Purkinje-dentate-thalamic pathways.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content