Michele Terzaghi

Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: A multicenter study

To assess whether risk factors for Parkinson disease and dementia with Lewy bodies increase rate of defined neurodegenerative disease in idiopathic rapid eye movement (REM) sleep behavior disorder (RBD).

Comorbidity between epilepsy and sleep disorders

Despite being relatively common and potentially able to have clinical and pathophysiological consequences, the comorbidity between epilepsy and sleep disorders is poorly investigated in the literature and rarely taken into consideration by clinicians in general practice. There is increasing evidence that obstructive sleep apnoea (OSA) coexists in epilepsy (in 10% of unselected adult epilepsy patients, 20% of children with epilepsy and up to 30% of drug-resistant epilepsy patients). A few lines of evidence suggest that continuous positive airway pressure treatment of OSA in epilepsy patients improves seizure control, cognitive performance and quality of life. Parasomnias and epileptic seizures can coexist in the same subject making the differential diagnosis of these conditions particularly challenging. In childhood, a frequent association between epilepsy and NREM arousal parasomnias, enuresis and rhythmic movement disorder has been documented. A particular pattern of association has been found between nocturnal frontal lobe epilepsy (NFLE) and NREM arousal parasomnias, the latter being found in the personal or family history of up to one third of NFLE patients. As far as REM parasomnias are concerned, REM sleep behaviour disorder, unrecognised or misdiagnosed, has been found to co-occur in 12% of elderly epilepsy patients. Patients with epilepsy often complain of poor, non-restorative sleep; however, insomnia in epilepsy is poorly investigated, with the literature giving conflicting prevalence data and no information on the impact of this disorder on seizure control, or on the best therapeutic approach to insomnia in this particular group of patients. A greater awareness, among clinicians, of the comorbidities between sleep disorders and epilepsy may help to prevent misdiagnosis and mistreatment. Sleep hygiene measures in epilepsy need to be more comprehensive, taking into account the various pathologies that may underlie disordered sleep in epilepsy patients.

The FLEP scale in diagnosing nocturnal frontal lobe epilepsy, NREM and REM parasomnias: Data from a tertiary sleep and epilepsy unit

Purpose: To test the usefulness of the FLEP scale in diagnosing nocturnal frontal lobe epilepsy (NFLE), arousal parasomnias, and REM sleep behavior disorder (RBD).

Comorbidity and medication in REM sleep behavior disorder A multicenter case-control study

Objective: This controlled study investigated associations between comorbidity and medication in patients with polysomnographically confirmed idiopathic REM sleep behavior disorder (iRBD), using a large multicenter clinic-based cohort. Methods: Data of a self-administered questionnaire on comorbidity and medication use of 318 patients with iRBD and 318 matched controls were analyzed. Comparisons between cases and controls were made using logistic regression analysis. Results: Patients with iRBD were more likely to report depression (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.3–2.9) and concomitant antidepressant use (OR 2.2, 95% CI 1.4–3.6). Subanalysis of antidepressant agents revealed that the increased use of antidepressants in iRBD was due to selective serotoninergic reuptake inhibitors (OR 3.6, 95% CI 1.8–7.0) and not due to other antidepressant classes. Patients with iRBD reported more lifetime antidepressant use than comorbid depression (antidepressant use: OR 1.9, 95% CI 1.1–3.3; depression: OR 1.6, 95% CI 1.0–2.5). Patients with iRBD reported more ischemic heart disease (OR 1.9, 95% CI 1.1–3.1). This association did not change substantially when adjusting for cardiovascular risk factors (OR 2.3, 95% CI 1.3–3.9). The use of inhaled glucocorticoids was higher in patients with iRBD compared to controls (OR 5.3, 95% CI 1.8–15.8), likely reflecting the higher smoking rate in iRBD (smoking: OR 15.3, 95% CI 2.0–118.8; nonsmoking: OR 2.4, 95% CI 0.4–13.2) and consequent pulmonary disease. Conclusions: This large study confirms the association between comorbid depression and antidepressant use in iRBD. In addition, there was an unexpected association of iRBD with ischemic heart disease that was not explained by cardiovascular risk factors.

Dissociated local arousal states underlying essential clinical features of non-rapid eye movement arousal parasomnia: an intracerebral stereo-electroencephalographic study

Sleep has been shown to be a global phenomenon in which the presence of local processes of both activation and deactivation are finely orchestrated. Dysfunctional and independent action of the systems involved in non‐rapid eye movement (NREM) sleep and wakefulness is deemed to be at the basis of arousal parasomnias. We show, in a patient with confusional arousals, persistence of sleep in the hippocampal and frontal associative cortices in contrast to the presence of awakening in the motor, cingulate, insular, amygdalar and temporopolar cortices. The clinical features of the confusional arousals in this patient are highly consistent with a dysfunctional coexistence of local cortical arousal and local cortical sleep.

Coupling of minor motor events and epileptiform discharges with arousal fluctuations in NFLE

Purpose: We recently demonstrated that in nocturnal frontal lobe epilepsy (NFLE) highly stereotyped minor motor events (MMEs, in the form of short‐lasting stereotyped movements involving the limbs, the axial musculature, and/or the head), could occur in either the presence or absence of an epileptiform discharge (ED). In lack of a systematic analysis, both MMEs and EDs were frequently observed to occur in association with arousal fluctuations. Hereby, in the same group of refractory NFLE subjects, we report a methodical neurophysiolgical investigation set out to investigate whether, and how, the arousal mechanism, monitored through visual scoring of the cyclic alternating pattern, modulates the expression of MMEs and EDs.

Sleep-related Minor Motor Events in Nocturnal Frontal Lobe Epilepsy

Summary:  Purpose: Nocturnal frontal lobe epilepsy (NFLE) is characterized by a wide spectrum of sleep‐related motor manifestations of increasing complexity, ranging from major episodes to brief motor events (minor motor events, MMEs). NFLE patients may exhibit a large quantity of MMEs in the form of short‐lasting stereotyped movements. Whereas major episodes are considered epileptiform manifestations, it remains unclear whether the MMEs are related to epileptiform discharges (EDs).

Family history of idiopathic REM behavior disorder: A multicenter case-control study

Objective: To compare the frequency of proxy-reported REM sleep behavior disorder (RBD) among relatives of patients with polysomnogram-diagnosed idiopathic RBD (iRBD) in comparison to controls using a large multicenter clinic-based cohort. Methods: A total of 316 patients with polysomnography-confirmed iRBD were recruited from 12 RBD study group centers, along with 316 controls matched on sex and age group. All subjects completed a self-administered questionnaire that collected proxy-reported information on family history of tremor, gait trouble, balance trouble, Parkinson disease, memory loss, and Alzheimer disease. The questionnaire also included a single question that asked about possible symptoms of RBD among first-degree relatives (siblings, parents, and children). Results: A positive family history of dream enactment was reported in 13.8% of iRBD cases compared to 4.8% of controls (odds ratio [OR] = 3.9, 95% confidence interval [CI] 2.0–7.7). ORs were increased for both siblings (OR = 6.1, 95% CI 2.1–18.1) and parents (OR = 3.2, 95% CI 1.4–7.8). We found no significant difference in sex, current age (65.3 ± 10.2 vs 66.9 ± 10.2 years), or age at self-reported RBD onset (55.2 ± 11.7 vs 56.6 ± 15.1 years) in possible familial vs sporadic iRBD. No differences were found in family history of tremor, walking and balance troubles, Parkinson disease, memory loss, or Alzheimer disease. Conclusion: We found increased odds of proxy-reported family history of presumed RBD among individuals with confirmed iRBD. This suggests the possibility of a genetic contribution to RBD.

REM Sleep Behavior Disorder and Epileptic Phenomena: Clinical Aspects of the Comorbidity

Summary:  Purpose: To document the occurrence of REM sleep behavior disorder (RBD) episodes in patients with epilepsy, and of interictal EEG epileptiform abnormalities (IEA) in patients with idiopathic RBD.

Analysis of video‐polysomnographic sleep findings in dementia with Lewy bodies

Knowledge of sleep architecture and disorders of nocturnal sleep in dementia with Lewy bodies (DLB) is limited by a lack of systematic video‐polysomnographic (video‐PSG) investigations. We describe video‐PSG findings in 29 consecutive subjects diagnosed with DLB. All the patients underwent a clinical interview and overnight video‐PSG monitoring. Twenty‐nine nondemented patients with Parkinsons disease (PD) matched for age and sex with the DLB cases were selected for comparison. The DLB subjects showed less 1NREM sleep (P = .000) and more 2NREM sleep (P = .000) than the PD subjects. Sleep apnea (30.7% vs. 34.8%) and periodic limb movements (60.9% versus 50.0%) were frequent in both groups. Disruptive motor behavioral manifestations were more frequent in subjects with DLB (69.6% vs. 26.9%, P = .008) and consisted of not only REM sleep behavior disorder (RBD) but also confusional events (30.3% vs. 3.8%, P = .020) and arousal‐related episodes mimicking RBD. Subjects with DLB in whom a sleep disturbance had been the presenting symptom performed better than those with other onset symptoms on both the Mini–Mental State Examination (22.2 ± 4.1 vs. 18.1 ± 4.6, P = .019) and the Frontal Assessment Battery (15.8 vs. 10.3, P = .010). Polysomnographic findings in DLB show a complex mix of overlapping sleep alterations: impaired sleep structure, sleep comorbidities, and various motor‐behavioral events (not restricted to RBD). Clinicians should be aware of the possibility of misleading symptoms and of the risk of overlooking sleep comorbidities, and consider performing polysomnographic sleep investigations in selected cases. We found evidence that a sleep disturbance as the presenting symptom might indicate a different phenotype of the disease, characterized by milder cognitive impairment.