Neuropathology of prodromal Lewy body disease.
BACKGROUND
Current evidence suggests that there is a prodromal stage in Parkinson disease characterized by a variety of nonmotor symptoms.


RESULTS
A 69-year-old man presented to our sleep center with isolated rapid eye movement sleep behavior disorder. During a 10-year follow-up period, longitudinal clinical and laboratory assessments indicated the development of hyposmia, depression, mild cognitive impairment, and constipation. Parkinsonism was absent, but dopamine transporter imaging showed subclinical substantia nigra damage. Postmortem examination demonstrated neuronal loss and Lewy body pathology in the peripheral autonomic nervous system (eg, cardiac and myenteric plexus), olfactory bulb, medulla, pons, substantia nigra pars compacta (estimated cell loss, 20%-30%), nucleus basalis of Meynert, and amygdala, sparing the neocortex.


CONCLUSIONS
Our observations indicate that nonmotor symptoms plus widespread peripheral and central nervous system pathological changes occur before parkinsonism and dementia onset in diseases associated with Lewy pathology. The current diagnostic criteria for Parkinson's disease miss these patients, who present only with nonmotor symptoms.
Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacións Biomédiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
Alex
A
Iranzo
Ellen
E
Gelpi
Eduard
E
Tolosa
José Luis
JL
Molinuevo
Mónica
M
Serradell
Carles
C
Gaig
Joan
J
Santamaria
D000368:Aged; D000369:Aged, 80 and over; D003863:Depression / Q000150:complications / Q000175:diagnosis; D005500:Follow-Up Studies; D006801:Humans; D020961:Lewy Body Disease / Q000150:complications / Q000473:pathology*; D008297:Male; D010300:Parkinson Disease / Q000473:pathology; D020187:REM Sleep Behavior Disorder / Q000209:etiology / Q000473:pathology*
Lewy body disease; Parkinson disease; dementia with Lewy bodies; incidental Lewy body disease; neuropathology; prodromal stage; rapid eye movement sleep behavior disorder