The term catastrophic epilepsy is applied to children with epilepsy who present with some of the following characteristics:

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  Urgent need for treatments.

  
  
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  Onset in early life.

  
  
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  There is commonly a major loss of cognitive and behavioral functions, which may be profound.

  
  
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  There is relatively high mortality.

The combination of sudden onset of seizures and massive regression may resemble an acute brain illness and be mistakenly diagnosed as having “encephalitis.” Careful review of the history and investigations should show no positive evidence of parenchymal brain disease and the time course may show fluctuations of function relating to seizure severity even if only over a few weeks.

The term “catastrophic” has been particularly useful in the context of potentially surgically treatable epilepsies.^1,2 The term implies that seizures per se are causing the deterioration, that is, it is an epileptic encephalopathy as defined in the 2001 ILAE epilepsy classification³ and that early intervention for seizures, be it medical or surgical, may arrest or even reverse some of the loss of skills.⁴ It may, however, be difficult to accurately define the contribution of seizures and causative pathological process, which serves as the basis for case selection and management (Fig. 56–1). The imperatives for surgical intervention are:

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  The seizure disorder is caused by a focal abnormality, which may be a discrete or hemispheric lesion.

  
  
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  Resistance to antiepileptic drug (AED) treatment.

  
  
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  The lesion is resectable with minimal hazard.

  
  
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  The chances of natural remission are small.

Catastrophic epilepsy surgery should be performed as early as possible with the aim of allowing the child as many seizure-free years of childhood as possible; the ultimate goal is to minimize cognitive and behavioral impairments. Too often, several years pass between the early presentation with epilepsy and surgery.⁵ It is common to successfully surgically treat children of 8 years or more who have presented in the first year of life with infantile spasms, but it may take several years to recognize that the child has a surgically treatable epilepsy.

The reasons for delaying surgical intervention are numerous and include lack of awareness that the child has a surgically treatable epilepsy or temporary seizure remission. There is also a tendency to unsuccessfully try multiple AEDs.⁶ In some cases, accurate localization of the epileptogenic zone may be challenging in the first year of life.

Many children with lesional epilepsy who present with infantile spasms rapidly regress at seizure onset and remain delayed, even with successful treatment. The correlates of epileptic encephalopathy are poorly understood but clearly involve cognitive and behavioral network dysfunction distant from the lesion. Early regression is easily overlooked and a careful history and review of family photographs/movies is often helpful. Assessment instruments appropriate for young regressed children are therefore essential.

The first priority is to identify syndromes that present with early severe seizure onset and regression that are not surgically treatable.

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  Severe (malignant) migratory partial seizures of infancy. This recently described disorder presents with the abrupt onset of focal motor seizures with major autonomic features in the first 6 months of life.⁷ Although seizures initially begin at one focus, other brain regions rapidly become involved leading to widespread shifting focality of seizure semiology and EEG features. Progressive cognitive and motor impairment (hypotonia and pyramidal signs) and acquired microcephaly typically follow. This disorder is usually easy to distinguish from a potentially surgically treatable epilepsy except perhaps at initial presentation.

  
  
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  Severe neonatal epilepsies with suppression—burst EEG/Ohtahara syndrome. Ohtahara syndrome presents with seizures, mostly tonic spasms from the first 2–3 months of life and a suppression-burst EEG.⁸ Partial seizures including hemiconvulsions are common. The course is severe with high seizure frequency, slow development, severe motor delay, and high mortality. It is clear that despite its rarity, this syndrome is the end point for several pathologies, which include malformations and nonketotic hyperglycinemia.⁹ Rarely malformations such as hemimegalencephaly are amenable to surgical treatment. While this occurs rarely, it should be considered in all presenting cases.

  
  
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  Dravet’s syndrome typically presents with complex febrile seizures in the first 6 months of life, followed by multiple seizure types and regression beginning around 1 year of age.¹⁰ About 80% have abnormalities in the SCN1A gene.¹¹ Hippocampal sclerosis is occasionally noted but the seizure semiology, regression, and EEG abnormalities suggest widespread brain involvement.

  
  
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  Metabolic causes of epilepsy, for example, pyridoxine/pyridoxal phosphate dependent,¹² phenylketonuria,¹³ GLUT1 deficiency,¹⁴ biotinidase deficiency.¹⁵ Infants with early onset seizures should be given a trial of pyridoxine/pyridoxal phosphate and biotin (or the enzyme measured) and have their blood glucose, calcium, magnesium, CSF glucose and urinary amino acids and organic acids measured. This group of disorders typically first presents with abnormal development followed by regression at an early age.

The explosive onset of seizures with regression is commonly lesionally based. There are several syndromes that are best dealt with individually as surgery may only be possible in some.

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  Sturge–Weber syndrome. Not uncommonly a baby with a typical port-wine stain naevus presents with repeated or prolonged focal seizures, acquired hemiplegia, and reduced consciousness indicating developmental regression. MRI reveals evidence of cerebral cortical rim ischemia apparently caused by inadequate vascular reserve to cope with the increased metabolic rate of severe seizures.¹⁶ Prolonged seizures typically occur without warning and the stage at which surgery should be offered is not yet agreed.

In a baby with a skin naevus, it seems appropriate to perform gadolinium-enhanced MRI early to see if a pial naevus is present. Unilateral or hemispheric or lobar/multilobar involvement suggests a potential resective surgical option. An antiepilepsy drugs administered prior to clinical seizures, although there is no evidence that it prevents a severe episode and low-dose aspirin is commonly given. The most difficult problem is how to offer surgery early enough to usefully prevent further damage as well as stopping seizures. Many procedures are performed when the child has a dense hemiplegia and severe cognitive impairment. While this outcome is not inevitable, inflicting a hemiplegia and possibly some cognitive impairment by surgery following the onset of seizures is not an easy decision.

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  Hemimegalencephaly. Children with hemimegalencephaly may present with sudden onset of severe hemiepilepsy and regression in which case urgent surgical referral is appropriate, even while AEDs are being tried. Development may not proceed if clinical seizures stop but subclinical seizure activity continues. However, many patients with hemimegalencephaly have intrauterine seizure onset and are already regressed and hemiplegic at birth. Cognitive outcome even after very early surgery is usually poor.²

  
  
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  Infantile spasms/West Syndrome. The characteristic epileptic spasms usually begin between ages 4 and 6 months. In addition to runs of many spasms, there is regression of visual and social behavior. Spasms are sometimes preceded by focal seizures, which may give a clue to the source. Where there is no evidence of underlying pathology with normal MRI and previous development, seizure response to corticosteroids and/or vigabatrin is usually favorable, but cognitive outcome is still often poor.¹⁷ It is important to perform EEG monitoring to ascertain that the EEG has normalized and the spasms have stopped. The results of medical treatment for patients with an abnormal MRI, previous slow development or focal seizures are generally unfavorable and patients typically exhibit a high rate of intractability and psychosocial morbidity.¹⁸ A particularly high rate of autism spectrum disorders is always combined with cognitive impairment.¹⁹ It should not take more than 2–3 weeks of medical treatment with the earlier two drugs to diagnose medical unresponsiveness and begin presurgical investigations.