Continuous Spike-waves During Slow Sleep Research Articles

Neurobiological effects of CSWS on brain growth: A magnetic resonance imaging volumetric study

Epilepsy with continuous spike-waves during slow sleep (CSWS) is characterized by impairment of neuropsychological abilities, frequently associated with behavioral disorders. These manifestations strongly correlate with frontal lobe dysfunctions. CSWS in childhood may affect the prefrontal cortex and leave residual mental and behavioral abnormalities as profound and permanent as the loss of speech in Landau-Kleffner syndrome. In our previous volumetric studies, frontal and prefrontal lobe volumes revealed growth disturbance in all CSWS patients compared with those of normal subjects. These studies also revealed that in the patients with shorter seizure durations and CSWS periods, developmental abnormalities of the prefrontal lobes were soon restored to a more normal growth ratio, whereas growth disturbances of the prefrontal lobes were persistent in the patients with longer seizure durations and CSWS periods. These findings suggest that seizure and the duration of paroxysmal anomalies may be associated with prefrontal lobe growth abnormalities, which are associated with neuropsychological problems. Thus, the duration of CSWS period seems to be a significant prognostic factor. The urgent suppression of this electroencephalography abnormality may be necessary to prevent the progression of neuropsychological impairments. The best treatment options may be required to remit seizures and electroencephalography abnormalities as soon as possible to achieve optimal prognosis in CSWS.

Frontal Lobe Growth Retardation and Dysfunctions in Children with Epilepsy: A 3-D MRI Volumetric Study

Behavioral abnormalities have been noted in specific epilepsy syndromes involving the frontal lobe. Epilepsies that involve the frontal lobe, such as frontal lobe epilepsy (FLE), atypical evolution of benign childhood epilepsy with centrotemporal spikes (BCECTS), and epilepsy with continuous spike-waves during slow sleep (CSWS), are characterized by impairment of neuropsychological abilities, frequently associated with behavioral disorders. These manifestations correlate strongly with frontal lobe dysfunction. Accordingly, epilepsies in childhood may affect the prefrontal cortex and leave residual mental and behavioral abnormalities. Brain volumetry has shown that frontal and prefrontal lobe volumes show a growth disturbance in patients with FLE, atypical evolution of BCECTS, and CSWS compared with those of normal subjects. These studies also showed that seizures and the duration of paroxysmal anomalies may be associated with prefrontal lobe growth abnormalities, which are associated with neuropsychological problems. Moreover, these studies also showed that the prefrontal lobe appears more highly vulnerable to repeated seizures than other cortical regions. The urgent suppression of these seizure and EEG abnormalities may be necessary to prevent the progression of neuropsychological impairments. Treatment options to remit seizures and EEG abnormalities as soon as possible may be required to achieve the optimal prognosis in frontal lobe epilepsies. Of the new AEDs, levetiracetam (LEV) may be an important addition to the treatments available for refractory childhood epilepsies with cognitive and behavioral problems.

Epilepsy with Continuous Spike-Waves during Slow Sleep: When and How Should We Treat?

Epilepsy with continuous spike-waves during slow sleep (CSWS),which is one of the hallmarks of electrical status epilepticus during slow wave sleep (ESES), is a functional disorder with the following features: severe paroxysmal EEG disturbance; seizures that may be severe but self-limited; behavioral deterioration, with or without premorbid developmental disturbances; no demonstrable brain pathology sufficient to explain the behavioral deterioration; and stabilization or improvement of behavior once the epileptiform EEG abnormalities resolve [1]. Much serious in CSWS are cognitive and behavioral disturbances. In CSWS, paroxysmal activity permanently affects the frontal lobes and higher cognitive functions. At highest risk for permanent sequelae are those with the earliest and longest exposure to the active phase of CSWS. When and how should CSWS be treated?

P-713 - A de novo microdeletion in chromosome 8q12.3q13.2: association with mild intellectual disability and epilepsy?

Whole genome microarray techniques are a primary tool for the etiological assessment in patients with intellectual disabilities. As a result, several novel microdeletions have been demonstrated that could be causatively related to the disorder. Interpretation of array results is facilitated through the use of databases such as the European Cytogeneticists Association of Unbalanced Chromosome Abberations (ECARUCA; http://www.ecaruca.net ). Clinical interpration of rare de novo microdeletions. Detailed evaluation of a young female with unexplained intellectual disability. Extensive neuropsychological, neurological, and genetic workup in a 9-years-old female patient with a history characterized by delay of psychomotor and speech development, mild to moderate intellectual disability and persistent sleep disturbances since the age of two. Several dysmorphic features were noticed including hypertelorism, downslanting palpebral fissures, a long, pear shaped nose, and low set, posteriorly rotated ears. Furthermore, she had a pectus excavatum, bilateral flat feet, and a sandal gap. Besides lowered intelligence, neuropsychological functioning disclosed impaired attentional capacities and executive control as well as weak motor skills. MRI of the brain disclosed no abnormalities. EEG demonstrated frequent epileptiform activity centroparietal bilaterally with marked increase during sleep, corresponding with continuous spike-waves during slow sleep (CSWS) syndrome. Array-CGH demonstrated a 3.57 Mb de novo microdeletion in chromosome 8q12.3. This de novo 8q12.3q13.2 microdeletion syndrome is characterized by a specific combination of a rare form of juvenile epilepsy (CSWS), neuropsychological dysfunction, impaired language and motor skills.

A de novo 3.57 Mb microdeletion in 8q12.3q13.2 in a patient with mild intellectual disability and epilepsy

A female patient, nine years of age, is reported with a history characterized by delay of psychomotor and speech development, mild to moderate intellectual disability and persistent sleep disturbances since the age of two. The patient showed facial dysmorphisms, a pectus excavatum and a sandal gap. Apart from lowered intelligence, neuropsychological functioning disclosed impaired attentional capacities and executive control as well as weak motor skills. Genome wide SNP array analysis revealed a 3.57 Mb de novo microdeletion in band q12.3 of chromosome 8. The long lasting sleep disorders turned out to originate from a rare juvenile epilepsy, continuous spike-waves during slow sleep (CSWS) syndrome, that includes the electrical status epilepticus in sleep (ESES) phenomenon. MRI-scanning of the brain showed no abnormalities.To the authors knowledge, this is the first report of a de novo 8q12.3q13.2 microdeletion syndrome that presents with ESES/CSWS.

Epilepsy in Children – Brain Growth and Behavior

The degree of behavioral problems associated with epilepsy in children is greater than would be expected on the basis of the existence of a chronic illness alone. Involvement of the frontal lobe such as atypical evolution of benign childhood epilepsy with centrotemporal spikes (BCECTS), epilepsy with continuous spike-waves during slow sleep (CSWS), and frontal lobe epilepsy (FLE) are characterized by impairment of neuropsychological abilities, and are frequently associated with behavioral disorders. In volumetric studies using three-dimensional (3D) magnetic resonance imaging (MRI), frontal and prefrontal lobe volumes revealed growth disturbance in patients with atypical evolution of BCECTS, CSWS, and FLE compared with those of normal subjects. These studies also revealed that in patients with shorter seizure durations and abnormal EEG periods, developmental abnormalities of the frontal lobe were soon restored to a more normal growth ratio. Conversely, growth disturbances of the prefrontal lobes were persistent in the patients with longer seizure durations and abnormal EEG periods. These findings suggest that seizure and the duration of paroxysmal anomalies may be associated with prefrontal lobe growth abnormalities, which are associated with neuropsychological problems. The urgent suppression of these seizure and EEG abnormalities may be necessary to prevent the progression of neuropsychological impairments.

Prefrontal Lobe Growth in a Patient with Continuous Spike-Waves during Slow Sleep

Epilepsy with continuous spike-waves during slow sleep (CSWS) is characterized by impairment of neuropsychological abilities, frequently associated with behavioral d isorders. These manifestations strongly correlate with frontal lobe dysfunctions. In the present case, an 11-year-old girl presented with progressive behavioral deteriorations after the appearance of electrical status epilepticus in sleep. The duration of CSWS period was 5 months. Serial measurements (at the appearance of the EEG pattern, and 6 months and 1, 2, 3 and 4 years thereafter) of frontal and prefrontal lobe volumes by 3-dimensional magnetic resonance imaging-based volumetry showed growth disturbance of prefrontal lobe volume, particularly prefrontal-to-frontal lobe volume ratio, after the appearance of the EEG pattern when compared with two frontal lobe epilepsy subjects without neuropsychological disorders and 13 control subjects. However, the ratio was restored to the growth ratio and seen to reach control levels, after improvement of the clinical manifestations of CSWS. These results suggest that children with CSWS may be prone to frontal lobe dysfunctions, and that the duration of CSWS period seems to be a significant prognostic factor. The urgent suppression of this EEG abnormality may be necessary to prevent the progression of neuropsychological impairments.

Acquired cognitive dysfunction with focal sleep spiking activity

The syndrome of continuous spike-waves during slow sleep (CSWS) is considered an epileptic encephalopathy in which the epileptiform abnormalities may contribute to progressive cognitive dysfunction. The characteristic electroencephalographic feature of the syndrome occurs during non-REM sleep, and takes the form of continuous bilateral and diffuse slow spike-waves that persist through all slow sleep stages. Using a case study design including clinical, neuropsychological, electroencephalographic, and positron emission tomography with 18F-fluorodeoxyglucose (PET-FDG) investigations, we describe the clinical and electroencephalographic findings in two patients who presented with nonsymptomatic epilepsy with unilateral spike-waves during sleep. Both patients presented with a left unilateral motor neglect of the upper limb that was associated with unilateral CSWS activity over the right hemisphere, predominantly in the centrotemporal region. PET-FDG studies during the active phase of CSWS showed right centrotemporal hypermetabolism in both cases. After treatment, a regression of the CSWS activity and an improvement of the cerebral FDG pattern were paralleled by a remission of the motor neglect. These cases demonstrate that the electroencephalographic pattern of CSWS in nonsymptomatic epilepsies is not necessarily diffuse and bilateral, and that focal unilateral CSWS activity can be associated with focal neuropsychological deficits. These findings add further evidence that the spectrum of clinical conditions associated with the electroencephalographic pattern of CSWS can include different forms of acquired cognitive disturbances that may be focal in nature.

Electrophysiological characterisation of myoclonicatonic seizures in symptomatic continuous spike‐waves during slow sleep syndrome

Sudden epileptic falls are frequently reported in continuous spike-waves during slow sleep (CSWS) syndrome. Inhibitory seizures are usually considered as the underlying mechanism. However, published polygraphic recordings are rare. We report the case of a 22 month-old boy suffering from a symptomatic CSWS syndrome associated with a perinatal stroke involving the right middle cerebral artery territory. He presented with psychomotor regression and daily multiple falls related to myoclonic-atonic seizures. Neurophysiological examination showed secondary generalized myoclonus systematically correlated with a bilateral spike spreading from the right central area. This confirms that positive myoclonus, in addition to negative myoclonus, may be responsible for epileptic falls in CSWS syndrome. [Published with video sequences].

Investigators' Workshop Saturday Evening Session I 6:00 p.m.‐7:30 p.m.

Ronit M. Pressler*, Massimo Avoli†, Solomon L. Moshe‡ and Shlomo Shinnar§ *Clinical Neurophysiology, Telemetry Unit, Great Ormond Street Hospital, London, United Kingdom; †Departments of Neurology, Neurosurgery and Physiology, McGill University, Montreal, QC, Canada; ‡Pediatric Neurology, Albert Einstein College of Medicine, Bronx, NY and §Pediatric Neurology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY Summary: Epileptiform discharges not accompanied by obvious clinical events are regarded as subclinical or interictal. They are found in up to 80% of patients with epilepsy but are only weakly related to seizure frequency or seizure severity. Indeed their clinical relevance in highly controversial and a principle of treatment is to avoid over‐interpretation of epileptiform activity. Experimental data shows that interictal spikes and ictal discharges are generated by different populations of neuron through different cellular and network mechanisms and may represent a condition that delays or prevents seizure onset. However, in the immature brain seizure discharges may cause neuronal cell loss. In older children and adults interictal discharges can be accompanied by brief interruption of cognitive function even in the absence of overt seizures (transitory cognitive impairment). In children with Landau‐Kleffner syndrome and CSWS (continuous spike‐waves during slow sleep) prolonged nocturnal discharges can have devastating effects on language and / or behavior. This multi‐disciplinary workshop will discuss the pathophysiology of interictal discharges and the significance of epileptiform activity in neonates and in older children.

Atypical language impairment in two siblings: Relationship with electrical status epilepticus during slow wave sleep

We report the case of a young girl who presented severe learning disabilities in oral and written language related to a continuous spike-waves during slow sleep (CSWS) syndrome. A sleep EEG recording obtained in her younger brother, who presented a clinical pattern suggesting developmental dysphasia, also showed a CSWS syndrome. These two clinical cases underscore the need to look for this syndrome in the siblings of an affected child when learning difficulties appear in a child who previously had normal psychomotor development.

Outcome at adulthood of the continuous spike-waves during slow sleep and Landau-Kleffner syndromes.

The aim of this study was to determine the clinical, social, and/or professional and cognitive outcomes in adulthood of the continuous spike-waves during slow sleep (CSWS) and Landau-Kleffner syndromes, which are two rare epileptic syndromes occurring in children. We enrolled seven young adults, five who had a CSWS syndrome, and two, a Landau-Kleffner syndrome in childhood. We evaluated their intellectual level as well as their oral and written language and executive functions. This study confirmed that the epilepsy associated with these syndromes has a good prognosis. Only one patient still had active epilepsy. However, the neuropsychological disorders particular to each syndrome persisted. Only two patients had followed a normal pathway in school. Three of the five patients with a CSWS syndrome during childhood remained globally and nonselectively mentally deficient. We found no evidence of the persistence of a dysexecutive syndrome in this study group. The intellectual functions of the two patients with Landau-Kleffner syndrome were normal; however, their everyday lives were disrupted by severe, disabling language disturbances. We discuss the role of some prognostic factors such as the location of the interictal electric focus and the age at onset of CSWS. These two epileptic syndromes of childhood are very similar in many respects, but their clinical outcomes in adulthood are different.

Atypical evolution in childhood epilepsy with occipital paroxysms (Panayiotopoulos type)

ABSTRACT We report, on two, school‐age girls with clinical and electroencephalographic features of early onset childhood epilepsy with occipital paroxysms (CEOP) of the “Panayiotopoulos type” that showed atypical evolution. Neurological examination and brain imaging were normal in both. One child presented at age 2.5 years episodes of oculocephalic deviation, and ictal vomiting during nocturnal sleep. The EEG showed left occipital spikes during wakefulness and sleep. One year later, frequent inhibitory seizures appeared in the lower limbs causing, “pseudoataxic gait”. At the same time she presented with behavioral disturbances and aphasia. EEG showed bilateral spike‐waves while awake and continuous spike‐waves during slow sleep (CSWSS). After switching AEDs to benzodiazepines, control of seizures along with improvement of behavior, and partial restoration of cognitive functions were achieved. The CSWSS disappeared and the last EEG at age 8 years only showed only isolated right occipital spikes. The other girl had a personal and familial history of febrile seizures. At 4 years of age she presented the first non‐febrile seizures during sleep, with oculocephalic deviation and ictal vomiting, followed by a generalized tonic‐clonic seizure. Partial control of seizures was obtained with antiepileptic drugs. At age 7, the child began to have weekly episodes of oculocephalic version, occasionally with secondary generalization. Repeated inhibitory seizures and absences also appeared. EEG showed frequent bilateral spikes occupying predominantly the posterior regions while awake, and CSWSS. At 7.5 years the same electro‐clinical picture persisted. Ethosuximide was added to sodim valproate and clobazam. Fifteen days later, the seizures disappeared and the EEG showed less frequent bilateral occipital spikes. She is now 9 years old and she has been seizure‐free for 18 months. Her present neuropsychological profile shows mild mental retardation. The two children with typical electroclinical features of “Panayiotopoulos Type” CEOP developed an atypical evolution which, to our knowledge, has not been described previously.

ＣＳＷＳあるいは頻発する全般性発作波に関連した神経心理学的な問題について 急速な脳波および臨床上の改善がみられた３例について

ＣＳＷＳあるいは頻発する全般性発作波に関連した神経心理学的な問題について 急速な脳波および臨床上の改善がみられた３例について