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- Holmberg, Björn, 1959
(författare)
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The diagnostic challenge of Parkinsonian syndromes. Clinical and laboratory evaluation
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The differentiation between Parkinson's disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) may be difficult, but it is important for prognostic and therapeutic purposes. The aim of this study was to evaluate the differential diagnostic capacity of laboratory tests in a population of patients fulfilling strict clinical criteria for these disorders. Material and methods: 115 patients, diagnosed clinically as having PD, MSA or PSP, were included consecutively and referred for the following tests: 1) Analyses in the cerebrospinal fluid (CSF) of neurofilament protein (NFL), a marker of axonal degeneration, and glial fibrillary acidic protein (GFAP), a marker of gliosis. 2) Assessment of the response to a single levodopa dose, on performance of a complex test movement, using an opto-electronic recording technique. 3) Analyses of cardiovascular autonomic reflexes, including heart rate variability (HRV) at deep breathing and blood pressure responses during orthostatic provocation.Results: The CSF-NFL concentrations were significantly higher in the MSA and PSP groups compared with PD, whereas no significant difference between groups was found for the GFAP levels. High CSF-NFL concentrations were related to the number of degenerative symptoms and to mortality at a 24-month follow-up. Whereas movement time after 12 hours' withdrawal of medication did not differ between groups, movement time after 200 mg of levodopa was significantly shorter in the PD group compared with MSA and PSP. The PSP group showed no impairment of cardiovascular reflexes compared with normal controls, whereas the MSA group showed significant reductions in both HRV and BP responses. Conclusion: The clinical assessment is still most important but the CSF-NFL, levodopa and cardiovascular reflex tests contribute to a more reliable diagnostic process. The high CSF-NFL levels found in MSA and PSP compared with PD indicate a faster and more widespread axonal degeneration. Furthermore, the results of the levodopa test indicate a preserved postsynaptic function in PD compared with MSA and PSP. The sensitivity and specificity to distinguish MSA and PSP patients from PD increased when the NFL and levodopa tests were combined. As we found the autonomic nervous system to be functionally more affected in MSA compared with PSP, adding cardiovascular reflex tests can further differentiate these two disorders.
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