Journal
ARCHIVES OF NEUROLOGY
Volume 65, Issue 1, Pages 101-107Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/archneurol.2007.8
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Funding
- NIA NIH HHS [R01 AG017155, P50 AG008702, P01 AG007232, P50 AG08702, 5R01 AG017155, P50 AG008702-11A19002, P01 AG07232] Funding Source: Medline
- NINDS NIH HHS [R01 NS42859, R01 NS042859] Funding Source: Medline
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS042859] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [P01AG007232, P50AG008702, R01AG017155] Funding Source: NIH RePORTER
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Background: Clinical and functional imaging evidence suggests that cerebellar dysfunction occurs in essential tremor (ET). In recent postmortem studies, we documented increased numbers of torpedoes (Purkinje cell axonal swellings) in ET patients without Lewy bodies. Purkinje cell loss, however, has never been rigorously assessed. Objective: To quantitatively assess the number of Purkinje cells in brains of ET patients and similarly aged controls. Methods: Postmortem cerebellar tissue was available in 14 ET cases (6 with Lewy bodies and 8 without Lewy bodies) and 11 controls. Calbindin immunohistochemistry was performed on paraffin sections of the cerebellum. Images were digitally recorded and blinded measurements of the number of Purkinje cells per millimeter of cell layer (linear density) were made. Results: Purkinje cell linear density was inversely correlated with age (r=-0.53, P=.006) and number of torpedoes (r=-0.42, P=.04). Purkinje cell linear density differed by diagnosis (mean [SDI, controls, 3.46 [1.27] cells/mm; ET cases with Lewy bodies, 3.33 [1.06] cells/mm; and ET cases without Lewy bodies, 2.14 [0.82] cells/mm; P=.04), with the most significant difference between ET cases without Lewy bodies and controls, where the reduction was 38.2% (P=.04). In an adjusted linear regression analysis that compared ET cases without Lewy bodies with controls, decreased linear density (outcome variable) was associated with ET ([beta=.56, P=.03). Conclusions: We demonstrated a reduction in Purkinje cell number in the brains of patients with ET who do not have Lewy bodies. These data further support the view that the cerebellum is anatomically, as well as functionally, abnormal in these ET cases.
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