Constipation: an emerging risk factor for Parkinson's disease?

Constipation is the most prominent and disabling manifestation of lower gastrointestinal (GI) dysfunction in Parkinson's disease (PD). The prevalence of constipation in PD patients ranges from 24.6% to 63%; this variability is due to the different criteria used to define constipation and to the type of population enrolled in the studies. In addition, constipation may play an active role in the pathophysiological changes that underlie motor fluctuations in advanced PD through its negative effects on absorption of levodopa. Several clinical studies now consistently suggest that constipation may precede the first occurrence of classical motor features in PD. Studies in vivo, using biopsies of the GI tract and more recently functional imaging investigations, showed the presence of α-synuclein (α-SYN) aggregates and neurotransmitter alterations in enteric tissues. All these findings support the Braak proposed model for the pathophysiology of α-SYN aggregates in PD, with early pathological involvement of the enteric nervous system and dorsal motor nucleus of the vagus. Therefore, constipation could have the potential sensitivity to be used as a clinical biomarker of the prodromal phase of the disease. The use of colonic biopsies to look at α-SYN pathology, once confirmed by larger prospective studies, might eventually represent a feasible, albeit partially invasive, new diagnostic biomarker for PD.

A simplified algorithm may lead to overestimate dementia in PD. A clinical and epidemiological study using criteria for PD-D proposed by the Movement Disorders Task Force.

Making an accurate diagnosis of dementia in Parkinson's disease (PD-D) patients is a challenge that neurologists will have to face in the coming years. In 2007, a Task force of the Movement Disorders Society proposed operational diagnostic criteria for the diagnosis of PD-D, consisting of step I and step II. We assessed the validity of step I with reference to the diagnosis made after a formal neuropsychological evaluation and by applying the current gold standard for the diagnosis of PD-D (DSM IV). Step I had a sensitivity of 78% and a specificity of 95.5%. Step I displayed a positive predictive value of 70%, a negative predictive value of 97%, and an accuracy of 93.4%. The clinimetric properties observed in our setting suggest that step I may be considered as a good screening tool (negative predictive value of 97%); however, using step I alone to make a diagnosis of PD-D may lead to an overestimation of dementia in PD, particularly in patients with considerable dysexecutive deficits (positive predictive value of 70%). In conclusion, formal neuropsychology and longitudinal follow-up are still required for the diagnosis and categorization of dementia in PD.

Inhibition of protein synthesis by ricin: experiments with rat liver mitochondria and nuclei and with ribosomes from Escherichia coli.

1. Ricin, a toxic protein from the seeds of Ricinus communis which inhibits poly(U)-directed polyphenylalanine synthesis by rat liver ribosomes (Montanaro et al., 1973), does not affect protein synthesis by isolated rat liver mitochondria. 2. The toxin is ineffective also on poly(U)-directed polyphenylalanine synthesis in reconstituted systems with ribosomes isolated from rat liver mitochondria or from Escherichia coli. 3. Ricin inhibits protein synthesis by isolated rat liver nuclei, but at concentrations much higher than those affecting rat liver ribosomes.