Brainstem 1H-MR spectroscopy in patients with Parkinson's disease with REM sleep behavior disorder and IPD patients without dream enactment behavior
Introduction
REM sleep behavior disorder (RBD) was first described as a distinct clinical entity by Schenck and colleagues [1]. RBD is characterized by the loss of normal muscle atonia and involves complex motor activity associated with dream mentation occuring in REM sleep period [2]. The behaviors occurred about 60–90 min after sleep onset, the expected time of the first REM period.
Although it is widely accepted that active processes of REM sleep are controlled by brainstem, the underlying cause of RBD is still unknown.
Early findings suggest that atonia resulting from a neuronal loss or disregulation of brainstem nuclei during REM period may be responsible for RBD. In studies made in cats first by Jouvet and then by Morrison, it was observed that atonia during REM period has permanently disappeared by bilaterally symmetric dorsolateral pontine lesions in experimental models and that these animals showed behaviors like RBD in humans [3], [4]. Also, RBD has been described in patients with pontomesencephalic tegmentum lesions [5], [6], [7].
Some recent data suggest that RBD is the result of decreased striatal dopaminergic effect suggesting substantia nigra dysfunction [8], [9].
RBD may be idiopathic and also may accompany neurodegenerative disorders. Recently a close association between RBD and especially synucleinopathies affecting brainstem structures regulating REM sleep, such as IPD, dementia accompanied with Lewy bodies (DLB) and multiple system atrophy (MSA) has been documented [10], [11]. In a prospective study, Schenck et al. reported that 38% of patients with RBD eventually developed IPD [12]. Recently RBD has been suggested as baseline presentation or asymptomatic phase of IPD [9].
If RBD is the direct result of decreased striatal dopaminergic activity, then why do all patients with IPD not have RBD? The answer to this question may be that additional degeneration of brainstem neurons play significant roles in some IPD forms. That is, brainstem degeneration in some patients with IPD in addition to already decreased striatal dopaminergic activity could be resulting in RBD [9]. This hypothesis may be supported by the findings of Plazzi et al. who reported that RBD was present in 44% of patients with MSA 1 year before clinical symptoms have developed [13]. Indeed, additional degeneration of brainstem nuclei is present in IPD [14]. Both findings from postmortem evaluations of IPD and RBD patients demonstrate the presence of alpha-synuclein, Lewy bodies and Lewy neuritis in brainstem nuclei [15].
Recently two studies with contradictory results were reported which evaluated brainstem involvement by 1H-MRS method in idiopathic RBD patients [16], [17]. Miyamoto et al. reported that they have found an increased Cho/Cr ratio in pons compared to normal control values in one patient with idiopathic RBD. They suggested that this finding proved brainstem neuronal dysfunction in this patient and thus, cases with neurodegenerative RBD (such as IPD), demonstrating neuronal loss in 1H-MRS measurements in whom NAA decrease is expected, might be distinguished from idiopathic cases [16]. However, this finding could not be confirmed by Iranzo et al. in a study with 15 idiopathic RBD patients and 15 controls [17].
So, is there a difference between IPD patients with RBD and IPD without dream enactment behavior in brainstem involvement? In this study we aimed to determine whether there is a difference between IPD patients with RBD or without dream enactment behavior in brainstem involvement by 1H-MRS method.
Section snippets
Subjects
We prospectively studied 12 IPD with RBD and 12 IPD without dream enactment behavior. Subjects were recruited from Parkinson's disease and movement disorders outpatient clinic at Haseki Hospital followed during last year, who had been diagnosed with idiopathic PD with at least two of three cardinal features: rigidity, resting tremor and bradykinesia. The 12 patients diagnosed with IPD who were initially diagnosed with RBD and verified by PSG were included in the study, and as the control group:
Results
In PD patients with RBD, mean age was 66.58 ± 7.97 years, mean disease duration was 8.58 ± 3.63 years, mean levodopa dosage was 435.2 ± 190 mg/day and duration of levodopa use was 7.82 ± 4.12 years. In IPD patients without dream enactment behavior, mean age was 67.18 ± 7.35 years, mean disease duration was 6.55 ± 4.16 years, mean levodopa dosage was 463.8 ± 346 mg/day and duration of levodopa use was 5.11 ± 4.99 years. There was no statistically significant difference between groups in these clinical parameters (
Discussion
In Parkinson's disease inclusion body pathology is first developed in the non-catecholaminergic neurons of the dorsal glossopharyngeus–vagus complex, intermediate reticular zone, coeruleus–subcoeruleus complex, caudal raphe nuclei, gigantocelluler reticular nucleus, olfactory bulb, olfactory tract together with anterior olfactory nucleus. During first two presymptomatic stages 1–2, pathology is confined to the medulla oblongata/pontine tegmentum and anterior olfactory structures without
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2019, Handbook of Behavioral NeuroscienceCitation Excerpt :One study did not reveal any differences in NAA/Cr, Cho/Cr, or mI/Cr ratios in the pontine tegmentum and the midbrain (Iranzo et al., 2002). Similarly, another study in 15 PD patients with RBD and 15 PD patients without RBD detected no group differences in these ratios within the pontine region (Hanoglu, Ozer, Meral, & Dincer, 2006). Therefore, it appears that RBD does not involve detectable mesopontine metabolic abnormalities.
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2011, Sleep MedicineCitation Excerpt :Three other reports have also suggested that tumour, ischaemic infarct, or surgery in the pontine region can induce RBD [33–35]. Proton magnetic resonance spectroscopy studies reported no abnormalities in several metabolic measures (N-acetylaspartate, creatine, choline, and myoinositol) in the brain stem of patients with RBD [36] or PD (with or without RBD) [37]. Single-photon emission CT of patients with RBD showed a reduction in striatal dopamine transporters [38] and PET showed a reduced density of striatal dopaminergic terminals [39].