Orthostatic tremor: Clinical, electrophysiologic, and treatment findings in 184 patients.

OBJECTIVE: To evaluate the clinical, electrophysiologic, and treatment outcome features of orthostatic tremor (OT) in a large case series. METHODS: We performed medical record review of 184 patients who met clinical and electrodiagnostic criteria for OT from 1976 to 2013 at the Mayo Clinic. Demographic, clinical, electrophysiologic, and treatment data were extracted. RESULTS: The majority of OT cases were female (63.6%) and mean age at onset was 59.3 years (range 13-85 years). Diagnosis was delayed by a mean of 7.2 years (range 0-44 years). The average tremor frequency was 15.7 Hz (range 12.5-20 Hz), and transmitted to the arms on weight-bearing (95.5%). Patients reported a spectrum of progressive orthostatic leg symptoms, relieved by sitting or leaning. Falls were reported in 24.1%. Coexistent neurologic disorders included essential tremor (22.8%), other tremor (4.9%), and parkinsonism (8.7%). Family history of OT was noted in 4.9%. Of 46 medications trialed, 24 failed to provide any benefit. Benzodiazepines provided at least mild benefit in 55.9%, and moderate to marked benefit in 31.5%; ß-blockers (31.0%) and anticonvulsants (25.0%) provided mild benefit, and the remainder were largely ineffective. Medication benefit waned over time. Deep brain stimulation (DBS) was effective in 2 cases. CONCLUSION: OT predominantly affects female seniors, and the diagnosis should be considered with any orthostatic-induced leg symptoms, and confirmed by surface EMG. Benzodiazepines are the most efficacious treatment, followed by ß-blockers and anticonvulsants. DBS should be further explored for treatment.

Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson disease.

OBJECTIVE: To determine whether evidence of neuronal dysfunction or demise preceded deposition of Lewy pathology in vulnerable neurons in Parkinson disease (PD). METHODS: We examined the extent of nigral dysfunction and degeneration among 63 normal, incidental Lewy body disease (ILBD), and PD cases based on tyrosine hydroxylase (TH) immunoreactivity and neuron densities, respectively. The relationship between these markers and Lewy pathology (LP) burden in the substantia nigra (SN) and Braak PD stage was assessed. RESULTS: Compared with normal subjects, ILBD cases displayed a significantly higher percentage of TH-negative cells and lower neuronal densities in the SN as early as Braak PD stages 1 and 2, before LP deposition in the nigrostriatal system. ILBD nigral neuron densities were intermediate between normal subjects and PD cases, and TH-negative percentages were higher in ILBD than either normal or PD cases. Furthermore, neuron density and neuronal dysfunction levels remained relatively constant across Braak PD stages in ILBD. CONCLUSIONS: These results suggest that significant neurodegeneration and cellular dysfunction precede LP in the SN, challenging the pathogenic role of LP in PD and the assumption that ILBD always represents preclinical PD.