Ictal SPECT in patients with rapid eye movement sleep behaviour disorder

Abstract

Rapid eye movement sleep behaviour disorder is a rapid eye movement parasomnia clinically characterized by acting out dreams due to disinhibition of muscle tone in rapid eye movement sleep. Up to 80-90% of the patients with rapid eye movement sleep behaviour disorder develop neurodegenerative disorders within 10-15 years after symptom onset. The disorder is reported in 45-60% of all narcoleptic patients. Whether rapid eye movement sleep behaviour disorder is also a predictor for neurodegeneration in narcolepsy is not known. Although the pathophysiology causing the disinhibition of muscle tone in rapid eye movement sleep behaviour disorder has been studied extensively in animals, little is known about the mechanisms in humans. Most of the human data are from imaging or post-mortem studies. Recent studies show altered functional connectivity between substantia nigra and striatum in patients with rapid eye movement sleep behaviour disorder. We were interested to study which regions are activated in rapid eye movement sleep behaviour disorder during actual episodes by performing ictal single photon emission tomography. We studied one patient with idiopathic rapid eye movement sleep behaviour disorder, one with Parkinson's disease and rapid eye movement sleep behaviour disorder, and two patients with narcolepsy and rapid eye movement sleep behaviour disorder. All patients underwent extended video polysomnography. The tracer was injected after at least 10 s of consecutive rapid eye movement sleep and 10 s of disinhibited muscle tone accompanied by movements registered by an experienced sleep technician. Ictal single photon emission tomography displayed the same activation in the bilateral premotor areas, the interhemispheric cleft, the periaqueductal area, the dorsal and ventral pons and the anterior lobe of the cerebellum in all patients. Our study shows that in patients with Parkinson's disease and rapid eye movement sleep behaviour disorder-in contrast to wakefulness-the neural activity generating movement during episodes of rapid eye movement sleep behaviour disorder bypasses the basal ganglia, a mechanism that is shared by patients with idiopathic rapid eye movement sleep behaviour disorder and narcolepsy patients with rapid eye movement sleep behaviour disorder.

Keywords: REM sleep behaviour disorder; basal ganglia; ictal SPECT; muscle atonia; sublaterodorsal nucleus.

REM sleep behaviour disorder is characterised by dream enactment. Using ‘ictal’ SPECT, Mayer et al. reveal activation in cortical, cerebellar and brainstem regions — but not the basal ganglia — in four patients. The same pathway is activated in individuals with idiopathic disease as in those with comorbid Parkinson’s disease or narcolepsy.

Figure 1

Polysomnography before, at and after tracer injection. Muscle activity of musculus mentalis started 12 epochs prior to injection of ECD tracer (blue line) and was accompanied by intermittent muscle activity of musculus mentalis (>50%/epoch) and kicking movements of the left, followed by the right leg. F8–P3 = scalp electrodes for EEG recordings; VER1/2 = vertical eye movements; HOR1/2 = horizontal eye movements; NASAL = nasal flow; THORAKAL = thoracal excursion; ABDOMINA = abdominal excursion; EMG and EMG3 = mentalis muscle; EXT1/2 = musculus extensor digitorum brevis; FLEX1/2 = musculus flexor digitorum brevis; TA1/2 = musculus tibialis anterior; GAST1/2 = musculus gastrocnemius.

Figure 2

Ictal SPECT of Patient CR, female with Parkinson’s disease with REM sleep behaviour disorder. Difference images of cerebral perfusion, measured by Tc-99m ECD SPECT (in colour), overlaid on T₁-MRI (greyscale). The colour of the SPECT indicates the degree of ictal hyperperfusion, ranging from weak (blue and green) to strong (orange and red). The arrows indicate hyperperfusion in brain regions. Median, precentral activation (premotor area), activation of left brainstem and right anterior cerebellum. A =anterior; H =head; P =posterior; F =foot; R=right; L =left.

Figure 3

Ictal SPECT of Patient RD, male with idiopathic REM sleep behaviour disorder. Difference images of cerebral perfusion, measured by Tc-99m ECD SPECT (in colour), overlaid on T₁-MRI (greyscale). The colour of the SPECT indicates the degree of ictal hyperperfusion, ranging from weak (blue and green) to strong (orange and red). The arrows indicate hyperperfusion in brain regions. Bifrontal activation in premotor area, pons and anterior cerebellum. A =anterior; H =head; P =posterior; F =foot; R =right; L=left.

Figure 4

Ictal SPECT Patient MH, female with narcolepsy with REM sleep behaviour disorder. Difference images of cerebral perfusion, measured by Tc-99m ECD SPECT (in colour), overlaid on T₁-MRI (greyscale). The colour of the SPECT indicates the degree of ictal hyperperfusion, ranging from weak (blue and green) to strong (orange and red). The arrows indicate hyperperfusion in brain regions. Activation of median interhemispheric cleft, bilateral activation of brainstem and left vermis. A =anterior; H =head; P =posterior; F =foot; R =right; L=left.

Figure 5

Ictal SPECT Patient CF, female with narcolepsy with REM sleep behaviour disorder. Difference images of cerebral perfusion, measured by Tc-99m ECD SPECT (in colour), overlaid on T₁-MRI (greyscale). The colour of the SPECT indicates the degree of ictal hyperperfusion, ranging from weak (blue and green) to strong (orange and red). The arrows indicate hyperperfusion in brain regions. Activation of median interhemispheric cleft, asymmetric activation of brainstem, activation of thalamus. A =anterior; H =head; P =posterior; F =foot; R =right; L=left.