Neuropathological findings in benign tremulous parkinsonism

Mov Disord. 2013 Feb;28(2):145-52. doi: 10.1002/mds.25220. Epub 2012 Dec 12.

Abstract

Benign tremulous parkinsonism, a tremor dominant syndrome with a relatively slow rate of deterioration, is recognized by clinicians although its pathological basis is not well understood. A systematic review of Queen Square Brain Bank donors was carried out to determine the natural history and pathology of individuals who had tremor dominant parkinsonism with mild non-tremor components and minimal gait disability for at least 8 years. We identified 16 cases of pathologically proved benign tremulous Parkinson's disease (PD); another 5 individuals conformed to the definition but did not have the pathology of PD. Patients with verified benign tremulous PD had less severe neuronal loss in the substantia nigra than controls (χ(2): P = .003). Twelve of these had been correctly diagnosed with PD at their first neurological evaluation, whereas the other 4 were originally thought to have another tremor disorder. The only consistent distinguishing feature of the 5 pathologically disproved cases, who may have had either essential tremor with associated rest tremor or dystonic tremor, was a failure to develop unequivocal bradykinesia within a decade of onset of tremor at rest. Our findings support the existence of a distinct subgroup of benign tremulous PD. The slower rate of clinical progression correlates with less severe nigral cell loss at postmortem, although many of these patients transgress the benign tremulous parkinsonism definition by the final third of their disease course and develop the common features of advanced PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Brain / pathology*
  • Databases, Factual
  • Essential Tremor
  • Female
  • Humans
  • Hypokinesia / etiology
  • Hypokinesia / physiopathology
  • Lewy Bodies / pathology
  • Male
  • Middle Aged
  • Parkinson Disease / genetics
  • Parkinson Disease / pathology*
  • Phenotype
  • Substantia Nigra / pathology
  • Tissue Banks
  • Ubiquitin-Protein Ligases / genetics

Substances

  • Ubiquitin-Protein Ligases
  • parkin protein