Reduced Purkinje cell number in essential tremor: a postmortem study.
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 (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.
Axelrad
Jordan E
JE
Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA.
Louis
Elan D
ED
Honig
Lawrence S
LS
Flores
Ingrid
I
Ross
G Webster
GW
Pahwa
Rajesh
R
Lyons
Kelly E
KE
Faust
Phyllis L
PL
Vonsattel
Jean Paul G
JP
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D018070:Biological Specimen Banks; D001921:Brain / Q000473:pathology; D064026:Calbindins; D002452:Cell Count; D002531:Cerebellum / Q000473:pathology; D020329:Essential Tremor / Q000473:pathology*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000473:pathology; D008297:Male; D016612:Paraffin Embedding; D011689:Purkinje Cells / Q000473:pathology*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D064026:Calbindins; D064030:S100 Calcium Binding Protein G