Transient psychosis in a girl with epilepsy and continuous spikes and waves during slow sleep (CSWS)

A normally developed and healthy 6-year-old girl suffered the onset of epilepsy with generalized tonic-clonic seizures and atypical absences. Initially the EEG showed epileptiform activity over the temporal and parietal regions, later there were episodes of bilateral synchronous spike-wave activity with a frequency of 1.5–2.5 Hz. After a few months, deterioration of cognitive and behavioural functions appeared and gradually increased with the development of a fullblown disintegrative psychosis that went on for several months. Sleep EEG recordings showed the characteristic abnormality described as continuous spikes and waves during slow sleep. Later there was a remarkable improvement of neuropsy chiatric functions but a second outbreak of psychosis seems to have left the girl, who is now 9 years of age, with severe mental impairment.     

A patient with 22q13 deletion syndrome accompanied by epilepsy with continuous spike-waves during slow wave sleep (CSWS) and cerebral infarction

We describe a patient with 22q13 deletion syndrome accompanied by epilepsy with continuous spike-waves during slow wave sleep (CSWS). This patient showed central hypotonia, mental retardation, disappearance of language, multiple facial anomalies, and intractable epilepsy. Overnight EEG showed CSWS (spike & wave index = 99.2%) at seven years of age. Chromosomal analysis using G-banding revealed a deletion at the end of chromosome 22, indicative of 22q13 syndrome. In addition, subsequent magnetic resonance imaging (MRI) demonstrated cerebral infarction in the left posterior temporal area, which was probably caused by recurrent status epilepticus. Unlike previous case reports, a striking feature in this patient was the development of motor deterioration after 15 years of age. The severe EEG abnormalities and frequent status epilepticus might induce this deterioration and brain infarction.     

Rett syndrome associated with continuous spikes and waves during sleep

Major speech impairment is a cardinal feature of Rett syndrome. Epilepsy, of variable presentation, is also frequently described. We report a girl who presented rapid speech regression while EEG showed continuous spikes and waves during slow sleep. The clinical picture was consistent with Rett syndrome, confirmed by MECP2 mutation R133C. We hypothesized that speech regression was partially related to nocturnal epileptic activity. Several antiepileptic drugs were used unsuccessfully but valproic acid was accompanied by improvement of verbal fluency, social interaction and manual abilities as measured by the Quebec Scale of Adaptive Behaviors and the Rett syndrome adapted Kerr scale. Continuous spikes and waves during slow sleep are unexpected in the early stages of Rett syndrome. This report suggests that it might contribute to the clinical impairment, in particular communicative capabilities, and that adequate antiepileptic treatment may be beneficial.     

Treatment with flunitrazepam of continuous spikes and waves during slow wave sleep (CSWS) in children.

We describe our treatment of two boys with continuous spikes and waves during slow wave sleep (CSWS). One of the boys was suffering from non-convulsive status epilepticus and the other from conscious disturbance with automatism. Their ictal EEG readings showed continuous diffuse spike and wave complexes, which were considered to show electrical status. The boys were diagnosed as having CSWS, and were later diagnosed with Landau-Kleffner syndrome (LKS). EEG readings returned to normal on intravenous injection of flunitazepam (FZP) at a dose of 0.02 mg/kg, suggesting that FZP is an effective treatment for CSWS.     

Clinical characteristics of 10 patients with continuous spikes and waves during slow sleep syndrome

Continuous spikes and waves during slow sleep syndrome is characterized by the presence of spike-and-wave discharges in at least 85% of non-rapid eye movement sleep. Associated clinical features vary. Here, features of 10 patients with this syndrome are compared to those in the literature. Patients ranged in age from 4 to 11 years. All patients had predominantly nocturnal partial motor or generalized tonic-clonic seizures; four patients also had daily atonic seizures. All 10 patients had different degrees of neuropsychologic disturbances: 9 patients had low intelligence quotient scores (the 10th, diagnosed attention deficit and hyperactivity disorder, had normal intelligence quotient score); 4 patients had autistic-like features. Apart from mental retardation (7 of 10), physical and neurologic findings were normal. Significant pyramidal signs and microcephaly were detected in two patients, and hypotonia, ataxia, and bilateral pyramidal signs were found in one other. Cranial magnetic resonance imaging findings were normal for 6 patients; the other 4 had some abnormal findings. Continuous spikes and waves during slow sleep syndrome is a rare epileptic syndrome in childhood. A variety of clinical and neurocognitive features were found in patients with continuous spikes and waves during slow sleep syndrome.     

Metyrosine in psychosis associated with 22q11.2 deletion syndrome: case report

This report describes the use of metyrosine (Demser) in an adolescent male with psychosis associated with the 22q11.2 deletion syndrome (velocardiofacial syndrome; VCFS), diagnosed by fluorescence in situ hybridization (FISH). He presented with multiple features of 22q11.2 deletion syndrome, including ventricular septal defect, palatal abnormalities, speech and motor delays, attention deficits, mood lability, and psychosis. After a failed trial of an atypical antipsychotic to address the psychosis, metyrosine was initiated, with significant reduction of psychotic symptoms and mood lability. Metyrosine treatment allowed this youth to live at home and to attend school, after months of recurrent psychiatric hospitalizations. The successful treatment of metyrosine for psychosis associated with VCFS represents a first in psychiatry, where a known biochemical abnormality in a psychiatric disorder was corrected by a treatment that targets the biochemical pathway, leading to reduction of psychiatric symptoms and improvement of functioning.     

Reduced NoGo-anteriorisation during continuous performance test in deletion syndrome 22q11.2

Deletion syndrome 22q11.2 (DS22q11.2) is a high-risk factor for psychiatric disorders. Alterations in brain morphology and function including the anterior cingulate cortex (ACC) are suggested to underlie the increased psychiatric disposition. We assessed response-inhibition in patients with DS22q11.2 (n = 13) and healthy controls (n = 13) matched for age, sex, and handedness by means of a Go-NoGo-Task during recording of a multi-channel electroencephalography (EEG). Analysis of event-related potentials (P300) resulted in an aberrant topographical pattern and NoGo-anteriorisation (NGA) as a parameter of medial prefrontal function was significantly reduced in patients with DS22q11.2 compared to controls. Differences in IQ between groups did not account for the findings. Source localization analysis (LORETA) revealed diminished left temporal brain activation during the Go-condition, but no altered ACC activation in DS22q11 during the NoGo-condition. Despite recent reports of structural alterations of the ACC in DS22q11.2 our findings suggest that response-inhibition mediated by the ACC is not impaired in DS22q11.2.     

Electrical status epilepticus in sleep (ESES)/continuous spikes and waves during slow sleep (CSWS) syndrome in children: An electroclinical evaluation according to the EEG patterns

ObjectiveThe aim of this study was to describe the electroclinical spectrum in children with electrical status epilepticus in sleep (ESES)/continuous spikes and waves during slow sleep (CSWS) syndrome according to the EEG patterns.MethodsClinical data of 44 patients with ESES/CSWS syndrome who were treated and followed at least two years were analyzed. Records of EEGs of patients were reevaluated to determine two aspects of the ESES pattern: (1) the spike–wave index (SWI) on the NREM sleep EEG (Group I: typical vs. atypical ESES pattern (33/11 patients)) and (2) the area of maximum amplitude of continuous epileptic activity (Group II: anterior vs. posterior ESES pattern (33/11 patients)).ResultsSymptomatic etiology was more defined in patients with the typical ESES pattern (40%) than the group with the atypical ESES pattern (9%) by a factor of four. All patients were receiving at least two antiepileptic drug (AED) treatments. Eighteen patients (41%) received AEDs plus ACTH therapy. Complete disappearance of the ESES pattern on the EEG was observed in 18 patients (41%), more than 50% reduction was observed in five patients (11%), less than 50% reduction was observed in eight patients (18%), and no response was observed in five patients (11%). No significant difference was found when comparing the groups in terms of reduction of seizures and the SWI. Seizure outcome at the two-year follow-up was similar between the group with ESES treated with AEDs plus ACTH and the group with ESES treated with AEDs without ACTH therapy.SignificanceThis study demonstrated that the rate of the SWI (typical vs. atypical ESES) and the maximum amplitude of the ESES pattern (anterior vs. posterior) have no significant correlation with seizure control and reduction of the SWI on the EEG in children with ESES syndrome.     

SPECT and epilepsy with continuous spike waves during slow-wave sleep

Ten cases of epilepsy with continuous spike waves in slow-wave sleep (CSWS) were evaluated using single photon emission computed tomography (SPECT); in eight patients the EEG paroxysmal abnormalities showed a predominant localization. SPECT carried out using^99mTc-HMPAO allows study of cerebral blood flow (CBF); the examination was performed during phases of drowsiness and the results compared to the EEG data. In four cases SPECT revealed areas of low CBF in sites corresponding to those of the prevalent EEG discharges; in two cases the areas of hypoperfusion did not correspond to those indicated by the EEG; lastly, in four cases SPECT results were negative. The areas of hypoperfusion were predominantly located in the frontal, temporal, and parietal regions. Furthermore, the percentage of positive SPECT results was significantly higher (five cases out of six) in the group in which the CSWS phase was prolonged for at least 1 year, compared to the group in which this phase lasted less than 1 year. Thus, in this type of epilepsy, SPECT reveals focal cortical areas of decreased CBF which correlated generally to the predominant sites of EEG abnormalities. A longer duration of the CSWS phase seems to be associated with a more significant cortical disorder, documented by the presence of areas of hypoperfusion.     

Increased basal ganglia volumes in velo-cardio-facial syndrome (deletion 22q11.2).

BACKGROUND: This study evaluated differences in caudate volumes in subjects with velo-cardio-facial syndrome due to a 22q11.2 (22qDS) deletion. Because psychosis is observed in 30% of adult subjects with 22qDS, this neurogenetic disorder could represent a putative model for a genetically mediated subtype of schizophrenia.METHODS: Caudate volumes were measured on high-resolution magnetic resonance images in 30 children and adolescents with 22qDS and 30 gender- and age-matched normal comparison subjects.RESULTS: Caudate head volumes were increased in the 22qDS group independent of neuroleptic medications. Subjects with 22qDS also displayed an abnormal pattern of asymmetry in the anterior caudate, with left side greater than right.CONCLUSIONS: Alterations in the basal ganglia circuitry have been implicated in learning, cognitive, and behavioral problems in children and therefore could be involved in the expression of the neurobehavioral phenotype expressed by subjects with 22qDS. Abnormal caudate volume is a neurodevelopmental feature shared with schizophrenia, further establishing 22qDS as a potential neurodevelopmental model for this disorder.     

Clinical staging and electroencephalographic evolution of continuous spikes and waves during sleep

Purpose: Currently, in continuous spikes and waves during sleep (CSWS) there is a lack of systematic assessments of the clinically relevant stages and the evolution of the electroencephalographic features. The aim of this study is to describe the evolution over time of clinical and electroencephalographic features in CSWS. Methods: We enrolled patients from our video‐electroencephalography (EEG) monitoring unit with CSWS and with overnight EEG studies with at least one overnight assessment per year over a minimum period of 3 years. We studied clinical presentation and electroencephalographic features. We calculated the (1) spike‐wave percentage (SWP) as the percentage of 1‐s bins containing at least one spike‐wave complex and (2) spike frequency (SF) as the number of spikes per 100 s. Key Findings: Nine children (six boys) met the inclusion criteria during a 15‐year period. Seven (78%) had an abnormal development prior to the epilepsy onset, and in two (22%) seizures were the only presenting symptom. Median age at epilepsy onset was 2 years (range 2 days to 4 years), at neuropsychological regression 5.1 years (4–7.7 years), and at seizure freedom 8.6 years (6.5–11.4 years). Median duration and range of clinically relevant stages were as follows: dormant stage (birth‐epilepsy onset median 2 years, range 2 days–4 years), prodromal stage (epilepsy onset‐neuropsychological regression 3.9 years, range 0.9–7.7 years), acute stage (neuropsychological regression‐seizure freedom 2.9 years, range 2.1–6.6 years), and residual stage (after seizure freedom). Seven patients (78%) had a structural lesion on neuroimaging. At last follow‐up (median 11.4 years, range 7.2–20.3 years), eight patients (89%) were receiving antiepileptic treatment, and all patients had residual neurocognitive deficits. During the acute stage, SWP was <85% in 13 (42%) of 31 assessments, and after seizure freedom, 3 of 5 patients (60%) had SWP >85%. Evolution of electroencephalographic patterns included increasing‐decreasing, continuously elevated, and fluctuating patterns (33.3% each). There was good correlation between SWP and SF (Spearman correlation‐coefficient = 0.942; p < 0.0001). SF, which can exceed 100%, reflected changes in electroencephalography pattern in more detail than SWP, which cannot exceed 100% and therefore has a ceiling effect. Significance: Our series systematically studied the age of occurrence of the significant clinical events. These may assist in defining clinical stages, which can provide a useful framework for future clinical trials in patients with CSWS. The severity of the epileptiform discharges on EEG did not always correlate with seizure frequency and severity; epileptiform discharges could be prominent after seizure freedom and fluctuated along the course of the disease. The values of SWP and SF correlated well, but SWP based on 1‐s bins has the potential disadvantage of a ceiling effect.     

Microduplication 22q11.2 in a child with autism spectrum disorder: clinical and genetic study

Microduplication of the 22q11.2 chromosomal region has been recognized since 1999 and has been associated with a highly variable phenotype. Neurodevelopmental impairment and behavioural problems are very common in patients with 22q11.2 duplication. Autism spectrum disorders (ASDs) have previously been reported in only two patients with 22q11.2 duplication and striking dysmorphic features. We report here on a 4‐year‐old male of healthy consanguineous parents presenting with ASD according to DSMIV, revised, criteria as a primary manifestation. The child walked at 16 months and started to say one word and some sounds. Parents noticed a subsequent developmental arrest. At 4 years his functional development age, evaluated by the Psychoeducational Profile, was roughly 6 months. Mild non‐specific facial dysmorphism was noted. Genetic analyses of the child demonstrated a de novo microduplication of the 22q11.2 chromosomal region. This genetic anomaly was best seen in interphases of blood lymphocytes and in buccal smear nuclei. Our case illustrates once again the clinical heterogeneity of the 22q11.2 duplication as well as the wide genetic complexity of ASD. We suggest that genetic evaluation of ASD should include fluorescence in‐situ hybridization analysis of the 22q11.2 chromosomal region.     

Epileptic encephalopathy of late childhood: Landau-Kleffner syndrome and the syndrome of continuous spikes and waves during slow-wave sleep.

Landau-Kleffner syndrome (LKS) and the syndrome of continuous spikes and waves during slow wave sleep (CSWS) are two points on the spectrum of functional childhood epileptic encephalopathies. They are characterized by a severe paroxysmal EEG disturbance that may permanently alter the critical synaptogenesis by strengthening synaptic contacts that should have been naturally "pruned." The much more common benign epilepsy with centrotemporal spikes is also related to LKS and CSWS by a common pathophysiology. Although prognosis in LKS and CSWS for seizure control is good, cognitive function declines and permanent neuropsychologic dysfunction is seen in many cases. This permanent damage is most evident in those patients who had early-onset EEG abnormality and a prolonged active phase of continuous spike-and-wave discharges during sleep. If the active phase of paroxysmal activity persists for over 2 to 3 years, even successful treatment does not resolve neuropsychologic sequelae. In LKS, the paroxysmal activity permanently affects the posterior temporal area and results in auditory agnosia and language deficits; in CSWS, the frontal lobes are more involved and other cognitive disturbances predominate. Aggressive treatment should include high-dose antiepileptic drugs, corticosteroids, and surgery in specific cases.     

Shyness discriminates between children with 22q11.2 deletion syndrome and Williams syndrome and predicts emergence of psychosis in 22q11.2 deletion syndrome

Background

22q11.2 deletion syndrome (22q11.2DS) is a common neurogenetic syndrome associated with high rates of psychosis. The aims of the present study were to identify the unique temperament traits that characterize children with 22q11.2DS compared to children with Williams syndrome (WS) and typically developing (TD) controls, and to examine temperamental predictors of the emergence of psychosis in 22q11.2DS.

Methods

The temperament of 55 children with 22q11.2DS, 36 with WS, and 280 TD children was assessed using the Emotionality, Activity, Sociability (EAS) Temperament Survey, Parental Ratings. The presence of a psychotic disorder was evaluated in 49 children and adolescents with 22q11.2DS at baseline and again 5.43 ± 2.23 years after baseline temperament assessment.

Results

Children with 22q11.2DS scored higher on Shyness compared to WS and TD controls. Children with 22q11.2DS and WS scored higher on Emotionality and lower on Activity compared to TD controls. Shyness was more severe in older compared to younger children with 22q11.2DS. Baseline Shyness scores significantly predicted the later emergence of a psychotic disorder at follow-up, in children with 22q11.2DS.

Conclusions

Our results suggest that shyness is an early marker associated with the later emergence of psychosis in 22q11.2DS.     

Parental report on socio-communicative behaviours in children with 22q11.2 deletion syndrome

Background Children with 22q11.2 deletion syndrome (22q11.2DS) are reported to have socio-communicative impairments. Although many of these children are diagnosed with intellectual disability (ID) and/or autism spectrum disorder (ASD), these populations are seldom used as control groups. Hence, information regarding syndrome-specific socio-communicative challenges is lacking.

Method Parental concerns regarding everyday communication were investigated by means of the Children’s Communication Checklist-2-NL (Geurts, 2007). Twenty children with 22q11.2DS (chronological age: 6 years–13 years 3 months) were compared to 21 children with idiopathic ID and 23 children with idiopathic ID and comorbid ASD. All groups were matched for fluid intelligence (Gf), chronological age, and core language scores.

Results Neglect or inadequate use of context information was more prevalent in children with 22q11.2DS than in children with idiopathic ID. Nonverbal communication seemed less impaired than in children with idiopathic ID + ASD.

Conclusion Pragmatic language skills and developmental trajectories in children with 22q11.2DS merit further investigation.