Continuous Spike Wave Discharges in Slow-Wave Sleep – don’t let it catch you napping!
Posted in Paedatric Neurology on 7th Dec 2012
Continuous Spike Wave discharges in slow wave Sleep (CSWS) is a clinical encephalopathy characterised by neurocognitive regression, motor impairment and an EEG pattern of Electrical Status Epilepticus in Sleep (ESES). It is a rare disorder comprising 0.2-0.5% of all childhood epilepsies1 and usually reported in children with epilepsy secondary to pre-existing brain pathology such as cortical malformations or acquired brain injury.2,3 Children with CSWS usually present with non-specific motor and behavioural symptoms.4 The diagnosis can easily be missed unless a sleep EEG is obtained which typically shows a high spike-wave index in slow wave sleep. Treatment options include specific antiepileptic drugs (often in combination), oral steroids, IV Immunoglobulin, Ketogenic diet and Epilepsy surgery. A longer duration of CSWS correlates with poor neuropsychological outcome5,6 therefore a high degree of clinical suspicion is essential and may significantly alter prognosis.
CSWS was first described by Patry et al in 1971 in six children with epilepsy who had ‘subclinical electrical status epilepticus’ induced by sleep.7 Over the past 40 years, there has been much progress in our understanding about it and CSWS is now recognised as a separate entity by the ILAE.8-10 There exists, however, confusion over terminology and specifically the terms ESES (Electrical Status Epilepticus in Sleep) and CSWS are often incorrectly used interchangeably. ESES merely represents an electrophysiological pattern of ‘near–continuous’ spike-wave discharges observed in sleep; the accompanying clinical signs and symptoms may differ with different syndromes for example, ESES is seen in both Landau Kleffner syndrome and CSWS – which are two different entities.10 Table 1 represents the different clinical syndromes which can be associated with ESES.
The exact aetiology of CSWS is unknown but there is an apparent relationship between CSWS and underlying structural brain abnormalities, both inherited and acquired.1 Up to 1/3rd of children who develop CSWS have had a preceding neurological insult such as meningitis or neonatal encephalopathy.11 Radiological abnormalities such as cortical atrophy and neuronal migrational abnormalities are often found in children with CSWS.12,13 The pathophysiology of CSWS has been attributed to disruption of physiologic thalamocortical rhythms by some authors6 and activation of reticulo-thalamic-cortical system with secondary bilateral synchronisation by others.9
Children who develop CSWS present to medical services with increasing seizure frequency14 accompanied by a history of slowly progressive motor impairment such as ataxia, dyspraxia and increased ‘clumsiness’. There is often a history of loss of language and temporo-spatial skills, hyperactivity, short-term memory deficits and behavioural problems. The child may be perceived to have recently ‘become challenging’ or to be ‘misbehaving’ which often results in difficulties at school leading to short and long-term exclusions. Parents complain of increased aggressiveness towards family members and that the child is ‘not himself’. The clinical changes during the evolution of CSWS have been well described in the literature along with detailed description of the accompanying electrophysiological features15 and it is important to recognise that CSWS develops over a period of time.
Diagnosis and differential diagnoses
When presented with a child with symptomatic epilepsy who has recently had an increase in seizure frequency, it is necessary to ask for a history of regression of skills, language and behavioural difficulties. A report from school is essential. This should be complemented by a careful clinical examination to exclude possible differential diagnoses (Table 2). Early discussion about the patient with the regional paediatric neurologist is often useful. An urgent sleep/sleep-deprived EEG must be requested to look for ESES in slow-wave sleep. The diagnosis is confirmed if the spike wave index is > 85%. (Spike wave Index = total number of minutes of all spike and slow wave abnormalities X 100 divided by total number of NREM sleep minutes).
Treatment of CSWS
There are no controlled trials for the treatment of CSWS, only large cohort studies. The goal of treatment is not only to control seizures but also improve neurocognitive function which requires a significant improvement or amelioration of the electrophysiological abnormalities. An aggressive approach is indicated, supported by neuropsychological treatment wherever possible.
Specific anti-epileptic drugs (AEDs) have been reported to be efficacious in treating CSWS including traditional AEDs such as Sodium Valproate (VPA) and Ethosuximide (ETX); in the past decade newer AEDs such as Levetiracetam (Keppra) and Sulthiame (STM) have also been shown to be effective.16 Benzodiazepines (BZDs) play a key role in treating CSWS. Clobazam remains the first choice owing to its safer side effect profile and tolerability but other BZDs such as short courses of oral diazepam17 and IV flunitrazepam18 have also been used. In line with good practice for treatment, AEDs should be used at the maximum doses possible without side effects for four to six weeks before being considered ineffective.
Oral Prednisolone (2-5mg/kg/day), IV Methylprednisolone (30mg/kg/day for three days), ACTH (80 IU/day) and Hydrocortisone (5mg/kg/day) have been shown to be extremely effective and safe in the treatment of CSWS19 with a positive outcome in over two thirds of patients. A combination of AEDs and steroids is often necessary for four to six weeks following the diagnosis following which a repeat EEG is recommended to look for resolution of ESES (personal practice).
IV immunoglobulins (IVIGs 2gm/kg/day for two days) and the ketogenic diet have both been used with limited success.20,21 Epilepsy surgery should be considered early if the patient has a structural brain malformation.22,23 Figure 1 is a Therapeutic approach to treatment of CSWS (Veggiotti et al; Epileptic Disorders 2012).
Children who develop CSWS have a poor long-term neuropsychological outcome despite resolution of seizures and electrophysiological abnormalities.5,24,25 Treatment for co morbidities such as attention deficit hyperactive disorder and behavioural difficulties is also essential. Pharmacological treatment such as Methylphenidate and behavioural/ family therapy may often be necessary.
CSWS is an often under-recognised entity in children with symptomatic epilepsy and diagnosis is often delayed unless a sleep EEG is requested. Duration of ESES appears to be a particularly important predictive factor for poor outcome.26 A high index of suspicion and early aggressive treatment with AEDs and/or steroids supported by neuropsychiatric management is needed to offer this vulnerable group of patients the best chance of a good recovery.
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