Table 1.
NNIPPS Inclusion and exclusion criteria
| Inclusion criteria | Exclusion criteria | |
|---|---|---|
| BOTH STRATA | All of the following: -Akinetic-rigid syndrome; -Age at disease onset ≥30 years; -Disease duration (12 months to 8 years); -Signed informed consent. | Any of the following: -Idiopathic Parkinson's disease; -Evidence of any other neurological disease that could explain signs; -History of repeated strokes with stepwise progression of parkinsonian features; -History of major stroke; -Any history of severe or repeated head injury; -A history of encephalitis; -A history of neuroleptic use for a prolonged period of time or within the past 6 months; -Street-drug related parkinsonism; -Significant other neurological disease on CT-scan/MRI; -Oculogyric crises; -Signs of corticobasal degeneration; -Signs of lewy body disease; -Other life-threatening disease likely to interfere with the main outcome measure; -Any clinically significant laboratory abnormality, with the exception of cholesterol, triglyceride and glucose; -Renal failure (serum creatinine > 300 μM/l); -Transaminase elevation > 2 time upper limit of normal; -Presence of contra-indicated treatments; -Any previous participation in a therapeutic trial within 3 months prior to entry; -Patient likely to be non-compliant or not easily reached in case of emergency; -Patient under legal guardianship (France only). |
| PSP | All of the following: -Supranuclear ophthalmoplegia; -Postural instability or falls (within 3 years from disease onset). | Any of the following: -Cerebellar ataxia; -Symptomatic autonomic dysfunction; -Tremor at rest. |
| MSA | One or more of the following: -Symptomatic autonomic dysfunction; -Cerebellar ataxia; -Postural instability or falls (within 3 years from disease onset); -Pyramidal signs. | Any of the following: -Supranuclear ophthalmoplegial -Signs of severe dementia. |
According to the NNIPPPS standard operating procedures, for inclusion into the PSP stratum, supranuclear ophthalmoplegia required ‘definite slowness and/or moderate to definite limitation of downward gaze’. For MSA, cerebellar ataxia required a moderate to severe ataxia of trunk and/or limbs. Less marked signs which the investigator nonetheless considered clinically significant were not considered as inclusion criteria but allowed investigators to report the presence or absence of an oculomotor or cerebellar syndrome. The akinetic-rigid syndrome was defined as mild to severe rigidity or slowness of neck or limbs. Significant symptomatic autonomic dysfunction (not treatment induced) was defined as moderate to severe CGI-dysautonomia. A MMSE score of ≤20 was regarded as evidence of severe dementia. Contraindicated treatments included glutamatergic drugs (e.g. amantadine, lamotrigine, dextrometorphan, gabapentin, glutamate containing drugs), free radical scavengers (selegiline, vit-E/ or C at very high dose) or any drug given to treat the disease and not the symptoms; potentially hepatotoxic drugs (e.g. dantrolene); drugs interacting with riluzole metabolism (CYP1A2 inhibitors or inducers); and ropirinole (due to decreased levels of the drug induced by riluzole).