Central cholinergic dysfunction has been reported in patients with Parkinson's disease (PD) and hallucinations by evaluating short latency afferent inhibition (SAI), a transcranial magnetic stimulation protocol which gives the possibility to test an inhibitory cholinergic circuit in the human brain. REM sleep behavior disorder (RBD) was also found to be associated with cognitive impairment in PD patients. The objective of the study was to assess the cholinergic function, as measured by SAI, in PD patients with RBD (PD-RBD) and PD patients without RBD (PD-nRBD). We applied the SAI technique in 10 PD-RBD patients, in 13 PD-nRBD patients and in 15 age-matched normal controls. All PD patients and control subjects also underwent a comprehensive battery of neuropsychological tests. Mean SAI was significantly reduced in PD-RBD patients when compared with PD-nRBD patients and controls. Neuropsychological examination showed mild cognitive impairment in 9 out of the 10 PD-RBD patients, and in 5 out of the 13 PD-nRBD. SAI values correlated positively with neuropsychological tests measuring episodic verbal memory, executive functions, visuoconstructional and visuoperceptual abilities. Similar to that previously reported in the idiopathic form of RBD, SAI abnormalities suggest a cholinergic dysfunction in PD patients who develop cognitive impairment, and present findings indicate that RBD is an important determinant of MCI in PD.
Although chronic sleepiness is common after head trauma, the cause remains unclear. Transcranial magnetic stimulation (TMS) represents a useful complementary approach in the study of sleep pathophysiology. We aimed to determine in this study whether post-traumatic sleep-wake disturbances (SWD) are associated with changes in excitability of the cerebral cortex. TMS was performed 3 months after mild to moderate traumatic brain injury (TBI) in 11 patients with subjective excessive daytime sleepiness (EDS; defined by the Epworth Sleepiness Scale ≥10), 12 patients with objective EDS (as defined by mean sleep latency <5 on multiple sleep latency tests), 11 patients with fatigue (defined by daytime tiredness without signs of subjective or objective EDS), 10 patients with post-traumatic hypersomnia "sensu strictu," and 14 control subjects. Measures of cortical excitability included central motor conduction time, resting motor threshold (RMT), short-latency intracortical inhibition (SICI), and intracortical facilitation to paired-TMS. RMT was higher and SICI was more pronounced in the patients with objective EDS than in the control subjects. In the other patients all TMS parameters did not differ significantly from the controls. Similarly to that reported in patients with narcolepsy, the cortical hypoexcitability may reflect the deficiency of the excitatory hypocretin/orexin-neurotransmitter system. These observations may provide new insights into the causes of chronic sleepiness in patients with TBI. A better understanding of the pathophysiology of post-traumatic SWD may also lead to better therapeutic strategies in these patients.
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