Tremor dominant parkinsonism: Clinical description and LRRK2 mutation screening.
Tremor dominant parkinsonism (TDP) is characterized by initial prominent resting and action tremor, mild parkinsonism, unpredictable response to medication, and a better prognosis than idiopathic Parkinson's disease (PD). We report on clinical features and longitudinal course of 26 patients suffering from TDP. Mean disease duration was 6.5 +/- 3 years, 61.5% of patients had a positive family history of tremor, 73% did not need drug treatment, performance of 123I-Ioflupane SPECT showed reduced striatal tracer uptake in 65.4% of patients, and odor identification testing was pathologic in all the patients tested (n = 22). Co-occurrence of action and resting tremor were the most annoying and disabling symptoms in all the patients, whereas rigidity and/or bradykinesia were clinically irrelevant in most of them. We also sequenced the full coding region of the Leucine-rich repeat kinase 2 gene (LRRK2) in all patients. We found a novel Val2390Met mutation that was not found in 864 chromosomes. Our results suggest a broader clinical heterogeneity related to LRRK2 mutations and points towards TDP as a subtype within the spectrum of PD, in which disabling tremor but otherwise mild parkinsonian signs and a better prognosis are the main characteristics.
D000368:Aged; D000369:Aged, 80 and over; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009662:Nortropanes / Q000493:pharmacokinetics; D020734:Parkinsonian Disorders / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D017354:Point Mutation / Q000235:genetics*; D011187:Posture; D011379:Prognosis; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012146:Rest; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015899:Tomography, Emission-Computed, Single-Photon; D014202:Tremor / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology
D009662:Nortropanes; D019275:Radiopharmaceuticals; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; C519528:ioflupane