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Continuous Spike Wave Discharges in Slow-Wave Sleep – don’t let it catch you napping!

Posted in Paedatric Neurology on 7th Dec 2012

Author

Gautam Ambegaonkar

Dr Gautam Ambegaonkar, MBBS, DCH, MRCPCH is a Paediatric Neurologist based at Addenbrooke’s hospital in Cambridge. He qualified in Medicine from the University of Mumbai and acquired his Diploma in Child Heath from The B.J. Wada Children’s hospital in Mumbai. He came to the UK to specialise in Paediatric Neurology and completed his CCT in Paediatric Neurology from Great Ormond Street hospital in London. He is the lead for Paediatric Neuromuscular services at Addenbrooke’s and supports the paediatric epilepsy service.

Correspondence to:
Email. Gautam Ambegaonkar

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.

History

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.

 

Aetiology

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

Clinical presentation

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.

Antiepileptic drugs:

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.

Steroid treatment:

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).

Alternative treatments:

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).

Outcome

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.

Conclusion

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.

 

Figure 2: MRI Brain showing right side cortical malformation (polymicrogyria) in a child with left hemiparesis, epilepsy and learning difficulties who developed CSWS 3.2 years after onset of epilepsy.

Figure 3: CSWS on sleep EEG in child shown above.

References

1.      Nickels K, Wirrell E. Electrical status epilepticus in sleep. Semin Pediatr Neurol 2008;15(2):50-60.

2.      Guzzetta F, Battaglia D, Veredice C, Donvito V, Pane M, Lettori D, et al. Early thalamic injury associated with epilepsy and continuous spike-wave during slow sleep. Epilepsia 2005;46(6):889-900.

3.      Wang L, Deng YC, Liu YH, Huang YG. Characteristics of continuous spike-and-wave during slow wave sleep syndrome in children. Zhongguo Dang Dai Er Ke Za Zhi;12(2):93-5.

4.      Herguner MO, Incecik F, Altunbasak S, Kiris N. Clinical characteristics of 10 patients with continuous spikes and waves during slow sleep syndrome. Pediatr Neurol 2008;38(6):411-4.

5.      Scholtes FB, Hendriks MP, Renier WO. Cognitive deterioration and electrical status epilepticus during slow sleep. Epilepsy Behav 2005;6(2):167-73.

6.      Seegmuller C, Deonna T, Dubois CM, Valenti-Hirsch MP, Hirsch E, Metz-Lutz MN, et al. Long-term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike-waves during slow-wave sleep. Epilepsia;53(6):1067-76.

7.      Patry G, Lyagoubi S, Tassinari CA. Subclinical “electrical status epilepticus” induced by sleep in children. A clinical and electroencephalographic study of six cases. Arch Neurol 1971;24(3):242-52.

8.      Brazzo D, Pera MC, Fasce M, Papalia G, Balottin U, Veggiotti P. Epileptic Encephalopathies with Status Epilepticus during Sleep: New Techniques for Understanding Pathophysiology and Therapeutic Options. Epilepsy Res Treat;2012:642725.

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13. Tassinari CA, Rubboli G, Volpi L, Meletti S, d’Orsi G, Franca M, et al. Encephalopathy with electrical status epilepticus during slow sleep or ESES syndrome including the acquired aphasia. Clin Neurophysiol 2000;111 Suppl 2:S94-S102.

14.    Nieuwenhuis L, Nicolai J. The pathophysiological mechanisms of cognitive and behavioral disturbances in children with Landau-Kleffner syndrome or epilepsy with continuous spike-and-waves during slow-wave sleep. Seizure 2006;15(4):249-58.

15.    Fernandez IS, Peters JM, Hadjiloizou S, Prabhu SP, Zarowski M, Stannard KM, et al. Clinical staging and electroencephalographic evolution of continuous spikes and waves during sleep. Epilepsia;53(7):1185-95.

16.    Aeby A, Poznanski N, Verheulpen D, Wetzburger C, Van Bogaert P. Levetiracetam efficacy in epileptic syndromes with continuous spikes and waves during slow sleep: experience in 12 cases. Epilepsia 2005;46(12):1937-42.

17.    Inutsuka M, Kobayashi K, Oka M, Hattori J, Ohtsuka Y. Treatment of epilepsy with electrical status epilepticus during slow sleep and its related disorders. Brain Dev 2006;28(5):281-6.

18.    Kawakami Y, Matsumoto Y, Hashimoto K, Kuwabara K, Hirata K, Fujita T, et al. Treatment with flunitrazepam of continuous spikes and waves during slow wave sleep (CSWS) in children. Seizure 2007;16(2):190-2.

19.    Buzatu M, Bulteau C, Altuzarra C, Dulac O, Van Bogaert P. Corticosteroids as treatment of epileptic syndromes with continuous spike-waves during slow-wave sleep. Epilepsia 2009;50 Suppl 7:68-72.

20.    Kramer U, Sagi L, Goldberg-Stern H, Zelnik N, Nissenkorn A, Ben-Zeev B. Clinical spectrum and medical treatment of children with electrical status epilepticus in sleep (ESES). Epilepsia 2009;50(6):1517-24.

21.    Nikanorova M, Miranda MJ, Atkins M, Sahlholdt L. Ketogenic diet in the treatment of refractory continuous spikes and waves during slow sleep. Epilepsia 2009;50(5):1127-31.

22.    Battaglia D, Veggiotti P, Lettori D, Tamburrini G, Tartaglione T, Graziano A, et al. Functional hemispherectomy in children with epilepsy and CSWS due to unilateral early brain injury including thalamus: sudden recovery of CSWS. Epilepsy Res 2009;87(2-3):290-8.

23.    Loddenkemper T, Cosmo G, Kotagal P, Haut J, Klaas P, Gupta A, et al. Epilepsy surgery in children with electrical status epilepticus in sleep. Neurosurgery 2009;64(2):328-37; discussion 337.

24.    Rossi PG, Parmeggiani A, Posar A, Scaduto MC, Chiodo S, Vatti G. Landau-Kleffner syndrome (LKS): long-term follow-up and links with electrical status epilepticus during sleep (ESES). Brain Dev 1999;21(2):90-8.

25.    Praline J, Hommet C, Barthez MA, Brault F, Perrier D, Passage GD, et al. Outcome at adulthood of the continuous spike-waves during slow sleep and Landau-Kleffner syndromes. Epilepsia 2003;44(11):1434-40.

26.    Robinson RO, Baird G, Robinson G, Simonoff E. Landau-Kleffner syndrome: course and correlates with outcome. Dev Med Child Neurol 2001;43(4):243-7.