Elena Zambrelli

Epilepsy in TSC: Certain etiology does not mean certain prognosis

Prevalence and long‐term outcome of epilepsy in tuberous sclerosis complex (TSC) is reported to be variable, and the reasons for this variability are still controversial.

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.

Hallucinations and sleep-wake cycle in Alzheimer's disease: a questionnaire-based study in 218 patients.

The aim was to evaluate the relationship between hallucinations and the sleep-wake cycle in a sample of Alzheimers disease (AD) patients in the early-moderate stage. Two hundred and eighteen AD patients (66 males, 152 females, mean age 74.3±6.85) were administered a sleep questionnaire in the presence of a care-giver. Twenty-six out of 218 (12%) reported the occurrence of hallucinations, mainly visual. In 18/28 (69%) hallucinations occurred when the patient was awake and in 8 (31%) hallucinations were reported to occur close to a specific phase of the sleep-wake cycle. Vivid dreams were reported in 25/218 (11%) and violent sleep-related and dream-related behaviours (probable REM behaviour episodes) in 22/218 (10%). Both REM phenomena were more frequent in AD hallucinators than in AD non-hallucinators (26.9% vs. 9.3%, and 26.9% vs. 7.8%, p<0.007). Our data indicate a lower incidence of hallucinations and presumable REM behaviour disorder (RBD) in AD, at least in the early-moderate phase, than that observed in synucleinopathies. However, the higher occurrence of vivid dreams and RBD in AD patients with hallucinations compared to those without hallucinations indicates a potential role of disordered REM sleep in influencing the occurrence of hallucinations in AD, similar to what has been observed in synucleinopathies.

Laryngeal motility alteration: A missing link between sleep apnea and vagus nerve stimulation for epilepsy.

This study aimed to evaluate the prevalence and the relationship of sleep breathing disorders (SBDs) and laryngeal motility alterations in patients with drug‐resistant epilepsy after vagus nerve stimulator (VNS) implantation. Twenty‐three consecutive patients with medically refractory epilepsy underwent out‐of‐center sleep testing before and after VNS implantation. Eighteen eligible subjects underwent endoscopic laryngeal examination post‐VNS implantation. Statistical analysis was carried out to assess an association between laryngeal motility alterations and the onset/worsening of SBDs. After VNS implantation, 11 patients showed a new‐onset mild/moderate SBD. Half of the patients already affected by obstructive sleep apnea (OSA) showed worsening of SBD. All of the patients with a new‐onset OSA had a laryngeal pattern with left vocal cord adduction (LVCA) during VNS stimulation. The association between VNS‐induced LVCA and SBD was statistically significant. This study suggests an association between VNS and SBD, hinting to a pivotal role of laryngeal motility alterations. The relationship between SBD and VNS‐induced LVCA supports the need to routinely investigate sleep respiratory and laryngeal motility patterns before and after VNS implantation.

Epilepsy in adult patients with Down syndrome: a clinical-video EEG study

Patients with Down syndrome are now living longer and the overall prevalence of epilepsy is increasing, however, full characterisation of epilepsy in adult age is still incomplete. We describe the electroclinical characteristics of epilepsy in 22 adult patients with Down syndrome (11 males, 11 females), with a mean age of 46 years (range: 28–64 years), followed at the Epilepsy Centre, San Paolo Hospital in Milan. Mean age at epilepsy onset was 36.8 years (range: 6–60 years). Nine out of 22 patients had focal epilepsy, while nine had late-onset myoclonic epilepsy. In four patients, epilepsy was unclassified. The EEG pattern of our patients was characterised by a progressive slowing of the background activity with sharp-and-slowwaves with frontal predominance. In the patients diagnosed with late-onsetmyoclonic epilepsy, the EEGs showed generalised polyspike waves. Three subjects had an episode ofmyoclonic status epilepticus at the beginning or in the course of the disorder. After the first descriptions of lateonset myoclonic epilepsy by Genton and Paglia (1994), this is one of the largest patient cohorts reported. Our data confirm that epilepsy in adult patients with Down syndrome presents peculiar electroclinical characteristics which should be recognized early as prompt, effective treatment may be beneficial.

Epilepsy in ring chromosome 20 syndrome

OBJECTIVE Ring chromosome 20 syndrome is characterized by severe, drug resistant childhood onset epilepsy, often accompanied by cognitive impairment. We characterized the electro-clinical phenotype and the long-term course of epilepsy in a large series. METHODS We reviewed the electro-clinical phenotype of 25 patients (aged 8-59 years), and assessed the relationship between epilepsy severity and clinical and/or genetic variables. We also searched for reports of patients diagnosed with r(20) syndrome in the literature, included those whose clinical information was sufficiently accurate, and compared their clinical features with the ones of our patients. RESULTS Epilepsy exhibited an age dependent course. When seizure onset occurred in childhood (21 patients), terrifying hallucinations associated with focal motor seizures, often sleep-related (8 patients), or dyscognitive seizures (13 patients), were prominent features, often evolving into epileptic encephalopathy associated with non-convulsive status epilepticus (11 patients). In the long-term, progressive stabilization of drug resistant epilepsy associated with non-convulsive status epilepticus, focal seizures with motor and autonomic features, and eyelid myoclonia were noticed. Epilepsy onset in adolescence (3 patients) was accompanied by a milder developmental course, dyscognitive seizures and non-convulsive status epilepticus, and no cognitive decline. Only three older patients became seizure free (>5 years) We found statistically significant correlations between age at epilepsy onset and cognitive level. Although in the study cohort the relationship between r(20) ratio, age at epilepsy onset and cognitive level was non-statistically significant, it reached significance evaluating the larger cohort of patients previously published. SIGNIFICANCE In ring(20) syndrome, epilepsy has an age dependent course and a worse outcome when age at seizure onset is earlier. The r(20) ratio and severity of cognitive impairment appear to be directly related to each other and inversely correlated with the age at epilepsy onset.

Pre- and post-dormitum epilepsies: Idiopathic generalized epilepsies

Epilepsy and sleep have a profound bidirectional influence. Idiopathic generalized epilepsy (IGE) comprises a fascinating group of syndromes that constitute nearly one-third of all epilepsies. These syndromes are genetically determined and affect otherwise normal people of both sexes and all races. IGE manifests with typical absences, myoclonic jerks, and generalized tonic-clonic seizures, alone or in varying combinations and severity. IGE syndromes are typically modulated by the sleep-wake cycle, and particularly by the sleep-wake transition process, both in terms of the occurrence of seizures and interictal epileptiform discharges (IED), with pronounced susceptibility to sleep deprivation. IGE analysis from the point of view of arousal modulation enhances the concept of a biological continuum existing among IGE syndromes. At the same time, this analysis broaches the problem of syndromic diagnosis and identification of the factors influencing the phenotypic expression of some epileptic phenomena over the course of life with potential bidirectional influences between epileptic manifestations and sleep-wake processes.

Narcolepsy Type 1 and Idiopathic Generalized Epilepsy: Diagnostic and Therapeutic Challenges in Dual Cases.

STUDY OBJECTIVES The aim of this study is to describe the possible co-occurrence of narcolepsy type 1 and generalized epilepsy, focusing on diagnostic challenge and safety of dual treatments. METHODS AND RESULTS Four patients with comorbidity for narcolepsy type 1 and idiopathic generalized epilepsy are reported: in three cases the onset of epilepsy preceded narcolepsy type 1 appearance, whereas in one case epileptic spells onset was subsequent. Patients presented with absences, myoclonic and tonic-clonic seizure type: in the patient with tonic-clonic seizures the dual pathology was easily recognized, in the other cases the first diagnosis caused the comorbid disease to be overlooked, independent of the time-course sequence. All four patients underwent neurological examination, video-electroencephalogram during which ictal and interictal epileptic discharges were recorded, and sleep polysomnographic studies. Repeated sleep onset rapid eye movement periods (SOREMPs) were documented with the multiple sleep latency test (MLST) in all the four cases. All patients had unremarkable brain magnetic resonance imaging studies and cerebrospinal hypocretin-1 was assessed in two patients, revealing undetectable levels. The association of antiepileptic drugs and substances currently used to treat narcolepsy type 1, including sodium oxybate, was effective in improving seizures, sleep disturbance, and cataplexy. CONCLUSIONS Narcolepsy type 1 may occur in association with idiopathic generalized epilepsy, leading to remarkable diagnostic and therapeutic challenges. Electrophysiological studies as well as a comprehensive somnologic interview can help confirm the diagnosis in patients with ambiguous neurological history. Sodium oxybate in combination with antiepileptic drugs is safe and effective in treating cataplexy and excessive daytime sleepiness.

Circadian phase typing in idiopathic generalized epilepsy: dim light melatonin onset and patterns of melatonin secretion : semicurve findings in adult patients

OBJECTIVE/BACKGROUND It has been debated in the literature whether patients with idiopathic generalized epilepsy (IGE) have a distinctive, evening-oriented chronotype. The few questionnaire-based studies that are available in the literature have conflicting results. The aim of our study was to define chronotype in patients with IGE by determining dim light melatonin onset (DLMO). PATIENTS/METHODS Twenty adults diagnosed with IGE (grand mal on awakening [GM] in 7 cases and juvenile myoclonic epilepsy in 13 cases) were investigated by means of a face-to-face semistructured sleep interview, Morningness-Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI) questionnaire, and a melatonin salivary test with DLMO determination. Eighteen healthy subjects (HC) and 28 patients affected with cryptogenic focal epilepsy (FE) served as controls. RESULTS The mean MEQ score was significantly lower in patients with IGE than that in patients with FE (49.1±5.9 versus 56.1±8.7 P<0.01) but not significantly lower than that in HC (49.1±5.9 versus 49.3±8.6). Midsleep on free days corrected for sleep duration did not differ significantly between the three subject groups (04:59±01:21h, 04:37±01:17h, 04:29±00:52h). The mean DLMO time in patients with IGE (22:13±01:34h) occurred 49min later than that in HC (21.24±1h), and the melatonin surge within the 30-minute time interval after DLMO in patients with IGE was significantly lower than that in HC (1.51±2.7 versus 3.8±3.6pg/mL P=0.045). CONCLUSIONS Subjective measures of chronotype do not indicate a definite evening-oriented chronotype in patients with IGE. However, the data concerning endogenous melatonin secretion indicate that patients with IGE tend to have a late circadian phase. Further studies are warranted in order to better define the late pattern of endogenous melatonin secretion in patients with IGE and to ascertain the role of this pattern in influencing behavioral chronotype in these subjects.

Sleep disorders in Cornelia de Lange syndrome.

Cornelia de Lange syndrome (CdLS) is a rare genetic disorder characterized by growth retardation, intellectual disability, limb defects, typical facial dysmorphism, and other systemic involvement. Sleep disturbances have been frequently reported in CdLS, but these have not been completely characterized, and prevalence data are conflicting. The aim of this paper is to characterize and determine the prevalence of sleep disorders in CdLS patients by means of a validated questionnaire. From November 2012 to November 2013, we asked 46 consecutive parents/caregivers of CdLS patients aged more than 3 years old to fill out the sleep disturbances scale for children (SDSC). The subjects were also characterized by the presence of epilepsy, intellectual disability (ID), behavioral problems, CdLS severity score, gastroesophageal reflux disease (GERD), and genetic test results. An abnormal total sleep score was found in 7 patients (15.2%), 26 (56.5%) showed a borderline total score, and 18 (39.1%) had an abnormal score for at least one SDSC factor. In our study sleep disorders were found to be positively associated to presence of epilepsy, GERD, ID, and behavioral disturbances. No correlation was evident with specific mutations of the different genes, BMI, and severity score. Our results confirm that sleep disorders represent a common problem in CdLS, with higher incidence than in the normal population. In these patients sleep disorders seem to be more prevalent in comorbid settings, representing a clinical indicator for different medical and neuropsychiatric disorders. Better knowledge and characterization of typology of sleep disorders in CdLS patients could permit a more specific therapeutic approach.