Cerebrospinal-fluid biomarkers for predicting phenoconversion in patients with isolated rapid-eye movement sleep behavior disorder.

STUDY OBJECTIVES: Patients with isolated rapid-eye-movement sleep behavior disorder (iRBD) have an increased risk of developing neurodegenerative diseases. This study assessed cerebrospinal-fluid (CSF) biomarkers of neurodegeneration and blood-brain barrier (BBB) alteration in patients with iRBD compared to controls and ascertain whether these biomarkers may predict phenoconversion to alpha-synucleinopathies (Parkinson's Disease (PD), Dementia with Lewy bodies (DLB), Multiple System Atrophy (MSA)). METHODS: Patients and controls underwent between 2012 and 2016 a neurological assessment, a lumbar puncture for CSF biomarker analysis (ß-amyloid42 - Aß42; total-tau, and phosphorylated tau), and BBB alteration (CSF/serum albumin ratio). All patients with iRBD were followed until 2021 and then classified into patients who converted to alpha-synucleinopathies (iRBD converters, cRBD) or not (iRBD non-converters, ncRBD). RESULTS: Thirty-four patients with iRBD (mean age 67.12 ±â€…8.14) and 33 controls (mean age 64.97 ±â€…8.91) were included. At follow-up (7.63 ±â€…3.40 years), eight patients were ncRBD and 33 patients were cRBD: eleven converted to PD, 10 to DLB, and two to MSA. Patients with iRBD showed lower CSF Aß42 levels and higher CSF/serum albumin ratio than controls. Cox regression analysis showed that the phenoconversion rate increases with higher motor impairment (hazard ratio [HR] = 1.23, p = 0.032). CSF Aß42 levels predicted phenoconversion to DLB (HR = 0.67, p = 0.038) and BBB alteration predicted phenoconversion to PD (HR = 1.20, p = 0.038). DISCUSSION: This study showed that low CSF Aß42 levels and high BBB alteration may predict the phenoconversion to DLB and PD in patients with iRBD, respectively. These findings highlight the possibility to discriminate phenoconversion in iRBD patients through CSF biomarkers; however, further studies are needed.

Brainstem impairment in obstructive sleep apnoea and the effect of CPAP treatment: an electrophysiological blink reflex study.

PURPOSE: This study aimed to evaluate the functionality of the brainstem structures through the blink reflex (BR) test in patients with obstructive sleep apnoea (OSA) and to assess the effects of continuous positive airway pressure (CPAP) treatment on BR responses. METHODS: Patients with moderate-severe OSA and controls underwent BR testing. Patients with OSA who were adherent to CPAP therapy repeated BR testing at 6 months follow-up. CPAP adherence was defined as CPAP use for ≥ 4 hour per night on > 5 nights per week with residual apnoea-hypopnea index less than 5 events per hour. RESULTS: A total of 22 patients with OSA (86% male, mean age 57.8 ± 10.6 years) and 20 controls (60% male, mean age 55.3 ± 9.3 years) were included. Patients with OSA showed longer right and left R1 latency, as well as delayed right ipsilateral and contralateral R2 latencies compared to controls. Patients with OSA who were compliant with CPAP treatment (n = 16; 88% men, mean age 58.8 ± 9.7 years) showed a significant decrease in latency of the right ipsilateral and contralateral R2 responses at 6 months. CONCLUSION: This study showed an abnormal pattern of BR responses in patients with OSA, consistent with a significant impairment of brainstem functionality in OSA. CPAP treatment partially improved the BR responses, suggesting the importance of treating OSA.

Highly purified cannabidiol improves stability and postural tone in adult patients with Lennox-Gastaut syndrome: A case series.

Lennox-Gastaut syndrome (LGS) is a severe developmental epileptic encephalopathy associated with numerous neurological signs and symptoms. Altered postural tone and the need for a caregiver-assisted wheelchair are features characterizing patients with LGS. Highly purified cannabidiol (CBD) is a novel antiseizure medication (ASM) recommended for seizure treatment, in combination with clobazam, in patients with LGS. Adding CBD to the previous ASM treatment helps in reducing seizure frequency, specifically drop seizures, in patients with LGS in both clinical trials and real-world studies. However, no data about drug effects on postural tone, motor activity, gait, and stability are available. In this case series, three adult patients diagnosed with LGS were treated with CBD as an add-on. During the follow-up, a slight improvement in seizure frequency was observed. Unexpectedly, an amelioration in postural tone and stability, measured using the validated Gross Motor Function Classification System, was also detected. Our case series suggests that CBD may help in managing patients with LGS regarding seizure control and in improving other aspects of the clinical spectrum of the disease, such as postural tone and stability. The mechanisms at the basis of this improvement may be related, other than seizure reduction, to the drug's effect on the brain locomotor centers, as demonstrated in animal model studies.

The effect of lacosamide monotherapy on sleep architecture in patients with epilepsy: a preliminary evidence.

Lacosamide (LCM) is a third-generation antiseizure medication (ASM), and its effect on sleep architecture was supported by a few studies in patients with drug-resistant epilepsy in which LCM was used as an add-on treatment. To gather knowledge on ASMs effects on sleep, this study aimed at evaluating the effects of LCM monotherapy on sleep in patients with focal epilepsy. Ten patients diagnosed with epilepsy (mean age 58.00 ± 14.77, 60.0% female, mean monthly seizure frequency 1.20 ± 2.48) starting LCM as monotherapy were included. Sleep architecture was assessed through polysomnography at baseline and at the 6-month follow-up visit. A significant decrease was observed in seizure frequency (p = 0.004), being all patients seizure-free at follow-up. At baseline, eight patients had poor sleep efficiency (< 85%). Sleep efficiency increased at follow-up, with only three patients having an index < 85% (p = 0.022). From baseline to follow-up, a significant decrease was observed in sleep latency (p = 0.022) and wakefulness after sleep onset (p = 0.047). Moreover, a significant decrease was observed in the percentage of stage 1 (Md = 6.70 vs Md = 3.85, p = 0.005) and stage 3 (Md = 27.70 vs Md = 22.35, p = 0.01) of Non-REM sleep. This study suggests that LCM monotherapy may positively impact sleep architecture in patients with epilepsy. The sleep efficiency improvement and the decrease of sleep latency and wakefulness after sleep onset observed at follow-up highlight better sleep stability and continuity in patients treated with LCM. Notably, all patients were seizure-free at follow-up, and seizure freedom may also concur to sleep structure improvement.

Sleep-wake cycle and daytime sleepiness in patients with epilepsy after initiating perampanel as adjunctive therapy.

BACKGROUND: Antiseizure medications (ASMs) may affect nocturnal sleep and daytime vigilance. Perampanel (PER), a third-generation ASM, showed to improve nocturnal sleep in patients with epilepsy (PWE). Although ASMs can have beneficial effects on nocturnal sleep and daytime sleepiness, no study investigated the effect of PER on both sleep-wake cycle and daytime sleepiness. Therefore, this study aimed to objectively evaluate the sleep-wake cycle and daytime sleepiness in PWE treated with PER as adjunctive therapy. METHODS: This prospective study included adult PWE who received PER as add-on treatment. Sleep-wake cycle was assessed through actigraphic monitoring and daytime sleepiness by the multiple sleep latency test (MSLT) performed at the end of the actigraphic recording. All patients performed both tests at baseline and at 6-month follow-up. RESULTS: Ten patients (mean age: 44.50 ± 22.71 years, 50.0% female) were included. The mean monthly seizure frequency was 3.20 ± 5.94. Six of ten patients started PER as a first add-on treatment. The final PER dose was 5.11 ± 2.02 mg/day, and nine of ten patients achieved seizure freedom at follow-up. There was a significant decrease in mean monthly seizure frequency from baseline to follow-up (p = 0.004). No significant changes were found in the sleep-wake cycle parameters. An increase in sleep latency mean was observed at MSLT at 6-month follow-up (p = 0.005). CONCLUSIONS: This study confirms that adjunctive PER is effective on seizures without pathologically change of the sleep-wake cycle in PWE and can even improve daytime sleepiness. This effect can be mediated by the achievement of seizure control. Therefore, PER may be promising in PWE with sleep disturbances and daytime sleepiness.

Sleep architecture in drug-naïve adult patients with epilepsy: Comparison between focal and generalized epilepsy.

OBJECTIVE: Sleep impairment is one of the most common comorbidities affecting people with epilepsy (PWE). The bidirectional relation between epilepsy and sleep has been widely established. Several studies investigated subjective sleep quality and daytime vigilance in PWE, highlighting frequent complaints of sleep fragmentation, difficulties in falling asleep, and daytime sleepiness. The present study aimed to evaluate sleep structure in drug-naive PWE, distributed on the basis of epilepsy type, and compared with controls. METHODS: This observational study included adult patients newly diagnosed with epilepsy and drug-naive as well as a control group of healthy subjects. All PWE and controls underwent a dynamic 24-h EEG with signals for sleep recording to evaluate sleep architecture, structure, continuity, and fragmentation. RESULTS: Twenty-four PWE were included and distributed in two groups based on epilepsy type. Eleven patients were included in the generalized epilepsy group (63.6% male; 34.91 ± 9.80 years) and 13 patients in the focal epilepsy group (53.8% male; 38.69 ± 12.74 years). The control group included 16 subjects (56.3% male; 32.75 ± 12.19 years). Patients with generalized or focal epilepsy had a significantly lower sleep efficiency than controls. Moreover, both patient groups presented the alteration of markers of sleep fragmentation and loss of continuity, with higher indices of sleep stage transitions and arousal. Finally, the two patient groups presented less REM sleep than controls. SIGNIFICANCE: This study highlighted the alteration of sleep quality, continuity, and stability in both patients with focal or generalized epilepsy compared with controls, also in the absence of ictal events. This sleep impairment resulted in the reduction of REM sleep. Therefore, these findings may be explained by the increase in awakenings and sleep stage shifts, which may be attributed to both sleep networks impairment and neurotransmission dysfunction in PWE, and also possibly triggered by paroxysmal interictal abnormalities.