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A Postmortem Study

Jordan E. Axelrad, BS; Elan D. Louis, MD, MSc; Lawrence S. Honig, MD, PhD; Ingrid Flores, MS; G. Webster Ross, MD; Rajesh Pahwa, MD; Kelly E. Lyons, PhD; Phyllis L. Faust, MD, PhD; Jean Paul G. Vonsattel, MD

Arch Neurol. 2008;65(1):101-107.

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 [SD], 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 (β = .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.

Author Affiliations: Gertrude H. Sergievsky Center (Mr Axelrad and Drs Louis and Honig), Department of Neurology (Drs Louis and Honig), Taub Institute for Research on Alzheimer's Disease and the Aging Brain (Drs Louis, Honig, and Vonsattel and Ms Flores), and Department of Pathology, College of Physicians and Surgeons (Drs Faust and Vonsattel), Columbia University, New York, New York; Veterans Affairs Pacific Islands Health Care System, Departments of Medicine and Geriatrics, University of Hawaii John A. Burns School of Medicine, Pacific Health Research Institute, and Kuakini Medical Center/Honolulu-Asia Aging Study, Honolulu, Hawaii (Dr Ross); and Department of Neurology, University of Kansas Medical Center, Kansas City (Drs Pahwa and Lyons).