Infantile epileptic spasms syndrome

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Infantile epileptic spasms syndrome
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Infantile epileptic spasms syndrome(IESS) previously known as West syndrome needs the inclusion of epileptic spasms for diagnosis. [1] Epileptic spasms (also known as infantile spasms) may also occur outside of a syndrome (that is, in the absence of hypsarrhythmia and cognitive regression) - notably in association with severe brain disorders (e.g. lissencephaly). [2]

Contents

IESS is an epileptic encephalopathy, a childhood epilepsy syndrome arising during infancy. [3] It can often arise as a complication of various other medical conditions. [2] [4] It is clinically defined by the occurrence of the characteristic epileptic spasms, episodes of clusters of tonic spasms of the axial and limb musculature. [5] Such spasms are found in association with characteristic abnormal EEG pattern findings (hypsarrhythmia), and cognitive delay or deterioration. [2] [4] The peak age of onset is 4-6 months of age, with 90% of cases presenting during the first year of life. The spasms are usually resistant to conventional antiepileptics. They may persist beyond infancy, or, rarely, commence only later in childhood. Many individuals with the syndrome go on to develop other forms of epilepsy later in life (notably Lennox–Gastaut syndrome), and persisting neurodevelopmental deficits are common; [2] notably, up to about a third of children are subsequently diagnosed with autism. [6] Pharmacotherapy consists of either adrenocorticotropic hormone (ACTH) or glucocorticoids (prednisone), or vigabatrin. Ketogenic diet may be effective as second-line therapy for treatment-resistant cases. Neurosurgery may be indicated in certain cases. [2] [7]

Epileptic spasms are commonly classified as symptomatic when a potential cause can be identified, or as cryptogenic if not (though these designations are used inconsistently). [2] A specific cause can be identified in ~70-75%. Any condition that may cause cerebral insult may give rise to IESS. Causes range from genetic disorders, infections, congenital malformations, malnutrition, to brain trauma. The most commonly identified common cause is tuberous sclerosis complex. Cryptogenic cases entail a more favourable prognosis overall. [4]

West syndrome is named for the English physician William James West who was first to describe the condition in an article in The Lancet in 1841 based on observations of the condition in his son. [1]

Signs and symptoms

Epileptic spasms

Epileptic spasms are a seizure type characteristic for the first year of life. The spasms are typically resistant to conventional pharmacotherapy. There are many episodes per day. [2] Episodes may take place after waking or feeding, [4] or less often before falling asleep. [8] Episode duration, [2] [4] intensity, and muscle groups affected are variable. [4] Mild spasms may involve mere nodding, [8] muscle twitching or eye movements, whereas powerful spasms may result in the infant's body violently bending over (the so-called "salaam" or "jackknife" movements). Individual spasms typically last only seconds, but episodes may last over 20 minutes. [4] An episode is typically followed by exhaustion; [2] [5] episodes are typically followed by over a minute of motionaless and diminished responsiveness. [5]

The spasms present as episodes of brisk (0.2-2s [5] ) neck flexions-extensions and upper limp abductions-adductions, [2] lower limb extension, and trunk musculature contractions, [4] accompanied by upward deviation of the eyes. [2] Nevertheless, individual muscle groups (abdominal, shoulder, neck) may be involved. [5] Most often, there is simultaneous contraction of both flexors and extensors, followed by flexor spasms, and the least frequent extensor spasms. [5] [8] Spasms are usually symmetrical, but up to 30% of cases may exhibit varying degrees of lateralisation. [5] Unilateral brain lesions often (but not always) result in asymmetric spasms; unilateral spasms may progress to generalised spasms. [2] Drop attacks may be the initial presentation of West syndrome of later onset. Altered or absent breathing is common during episodes. [5]

When spontaneous remissions occurs, it is typically gradual. Remission by the age of three is 50%, rising to 90% by the age of five. [2]

Developmental

The onset of epileptic spasms is often associated with developmental regression: autistic withdrawal, and loss of social smiling and of visual attention. [2] A majority of individuals with West syndrome exhibit regression of psychomotor skills. [4] However, developmental delay is noted in up to about two-thirds of infants with West syndrome already before the onset of spasms, [2] [5] whereas only about a third had exhibited normal development prior to spasm onset. [5]

Causes

Based on etiology, cases of IESS are commonly classified as either symptomatic or cryptogenic - although these terms have not been used consistently. Symptomatic cases are most often defined as those in which a clear cause can be identified, though some investigators also use the designation in cases in which there was previous clinical or imaging evidence of brain lesions and/or abnormal development was noted prior to the onset of the syndrome. Cryptogenic cases are thus contrastingly defined as those in which no specific cause can be identified, or where no such lesions or abnormalities were noted prior to syndrome onset. [2]

Down syndrome

Infantile epileptic spasms syndrome appears in 1% to 5% of infants with Down syndrome. IESS in those with Down syndrome is milder, more responsive to treatment (due to unknown reasons), and less likely to evolve into Lennox-Gastaut syndrome or other forms of epilepsy.[ citation needed ] A child with Down syndrome presenting with seizures that are difficult to control should be assessed for autistic spectrum disorder. [9] [ verification needed ]

Genetic

Mutations in several genes have been associated with IESS. These include the Aristaless related homeobox (ARX) and cyclin dependent kinase like 5 (CDKL5) genes. [10] The ARX gene in particular seems to be responsible for at least some of the X linked cases. [11] Variants in the KCNT1 gene can also in rare cases result in West syndrome. [12]

Diagnosis

Infantile spasms can be misdiagnosed as non-epileptic, non-pathological movements such as infantile colic, startle response, or Moro reflex. [2]

Treatment

Pharmacotherapy

There is limited evidence as to which pharmacotherapy approach is optimal. [13] [2] Hormones therapy with either adrenocorticotrophic hormone (ACTH) or oral prednisone is the standard of care (with the two treatments apparently producing equivalent outcomes). ACTH therapy is cost-prohibitive in the US. [13] ACTH therapy produces improvement in spasms within days whereas neurodevelopmental improvements take weeks. ACTH therapy is associated with increased risk of infections (which account for the majority of deaths). [2] Therapy with vigabatrin is also commonly undertaken (though long-term use is associated with a risk of visual field loss); [13] vigabatrin is considered the treatment of choice for infantile spasms associated with tuberous sclerosis complex, and is also favoured in those with serious brain lesions or malformations. [8]

Neurosurgery

Prompt neurosurgery may be indicated in treatment-resistant cases with a demonstrated localised epileptic focus. Some 60% of persons having undergone neurosurgery are subsequently seizure-free. More specifically, these neurosurgical procedures include: hemispherectomy/hemispherotomy and non-hemispheric surgery. [14] Small epileptic foci augur a favourable outcome, however, in most cases, resection of extensive multilobar cortical dysplasias is called for, resulting in limited cognitive improvement. [2]

Ketogenic diet

There is some evidence for the use of the ketogenic diet in cases which have failed to respond to pharmacotherapy. [2]

Prognosis

Prognosis of epileptic spasms and IESS depends predominately upon aetiology, and less so on treatment. Unfavourable prognostic factors include: symptomatic aetiology, early onset (prior to 3 months), presence of other seizure types prior to onset of infantile spasms, poor treatment response, EEG asymmetry, absence of typical hypsarrhythmia, and (prolongued) developmental regression. [2] Premature mortality rates range from 5% to 31%, and depend upon the underlying aetiology of the infantile spasms. [8]

Whereas some 80% of all individuals with IESS will exhibit residual neurodevelopmental impairment, the figure falls to only a third for cryptogenic cases. [2] Brisk initiation of therapy appears to be associated with more favourable neurodevelopmental outcomes - especially in cryptogenic cases. [8]

Seizures

In about one quarter to one third of children with IESS, seizures will subside completely with time; such resolution is more common when the cause is cryptogenic. In another third, the characteristic epilepstic spasmswill persist in later life. Finally, a third will experience a deterioration with the appearance of additional recalcitrant seizure types - often evolving into Lennox–Gastaut syndrome. [4] About 50% of cases will exhibit other types of epilepsy later in life. [2]

Autism

From 10% to 35% of children with infantile spasms are eventually recognised as autistic. Autism may arise more frequently in those with bilateral temporal lobe epileptic foci. The aetiology of infantile spasms-associated autism may be idiopathic, or an additional comorbidity that itself better explains the autism may be identified. It is believed that early aggressive treatment of infantile spasms can often prevent the later development of autistic features, or lessen their severity. [6]

Epidemiology

Incidence is around 1:3200 to 1:3500 of live births. Statistically, boys are more likely to be affected than girls at a ratio of around 3:2. [15]

See also

Related Research Articles

<span class="mw-page-title-main">Epilepsy</span> Group of neurological disorders causing seizures

Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. An epileptic seizure is the clinical manifestation of an abnormal, excessive, and synchronized electrical discharge in the neurons. The occurrence of two or more unprovoked seizures defines epilepsy. The occurrence of just one seizure may warrant the definition in a more clinical usage where recurrence may be able to be prejudged. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical activity in the brain. These episodes can result in physical injuries, either directly, such as broken bones, or through causing accidents. In epilepsy, seizures tend to recur and may have no detectable underlying cause. Isolated seizures that are provoked by a specific cause such as poisoning are not deemed to represent epilepsy. People with epilepsy may be treated differently in various areas of the world and experience varying degrees of social stigma due to the alarming nature of their symptoms.

Anticonvulsants are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain.

Absence seizures are one of several kinds of generalized seizures. In the past, absence epilepsy was referred to as "pyknolepsy," a term derived from the Greek word "pyknos," signifying "extremely frequent" or "grouped". These seizures are sometimes referred to as petit mal seizures ; however, usage of this terminology is no longer recommended. Absence seizures are characterized by a brief loss and return of consciousness, generally not followed by a period of lethargy. Absence seizures are most common in children. They affect both sides of the brain.

Aicardi syndrome is a rare genetic malformation syndrome characterized by the partial or complete absence of a key structure in the brain called the corpus callosum, the presence of retinal lacunes, and epileptic seizures in the form of infantile spasms. Other malformations of the brain and skeleton may also occur. The syndrome includes intellectual disability that is usually severe or moderate. So far, the syndrome has only been diagnosed in girls and in boys with two X chromosomes.

<span class="mw-page-title-main">Vigabatrin</span> Epilepsy medication

Vigabatrin, sold under the brand name Sabril among others, is a medication used in the management and treatment of infantile spasms and refractory complex partial seizures.

<span class="mw-page-title-main">Lennox–Gastaut syndrome</span> Rare form of childhood-onset epilepsy

Lennox–Gastaut syndrome (LGS) is a complex, rare, and severe childhood-onset epilepsy syndrome. It is characterized by multiple and concurrent seizure types including tonic seizure, cognitive dysfunction, and slow spike waves on electroencephalogram (EEG), which are very abnormal. Typically, it presents in children aged 3–5 years and most of the time persists into adulthood with slight changes in the electroclinical phenotype. It has been associated with perinatal injuries, congenital infections, brain malformations, brain tumors, genetic disorders such as tuberous sclerosis and numerous gene mutations. Sometimes LGS is observed after infantile epileptic spasm syndrome. The prognosis for LGS is marked by a 5% mortality in childhood and persistent seizures into adulthood.

Landau–Kleffner syndrome (LKS)—also called infantile acquired aphasia, acquired epileptic aphasia or aphasia with convulsive disorder—is a rare childhood neurological syndrome.

<span class="mw-page-title-main">Ring chromosome 20 syndrome</span> Medical condition

Ring chromosome 20, ring-shaped chromosome 20 or r(20) syndrome is a rare human chromosome abnormality where the two arms of chromosome 20 fuse to form a ring chromosome. The syndrome is associated with epileptic seizures, behaviour disorders and intellectual disability.

<span class="mw-page-title-main">Generalized epilepsy</span> Epilepsy syndrome that is characterised by generalised seizures with no apparent cause

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<span class="mw-page-title-main">CDKL5</span> Protein-coding gene in humans

CDKL5 is a gene that provides instructions for making a protein called cyclin-dependent kinase-like 5 also known as serine/threonine kinase 9 (STK9) that is essential for normal brain development. Mutations in the gene can cause deficiencies in the protein. The gene regulates neuronal morphology through cytoplasmic signaling and controlling gene expression. The CDKL5 protein acts as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of oxygen and phosphorus atoms at specific positions. Researchers are currently working to determine which proteins are targeted by the CDKL5 protein.

Progressive Myoclonic Epilepsies (PME) are a rare group of inherited neurodegenerative diseases characterized by myoclonus, resistance to treatment, and neurological deterioration. The cause of PME depends largely on the type of PME. Most PMEs are caused by autosomal dominant or recessive and mitochondrial mutations. The location of the mutation also affects the inheritance and treatment of PME. Diagnosing PME is difficult due to their genetic heterogeneity and the lack of a genetic mutation identified in some patients. The prognosis depends largely on the worsening symptoms and failure to respond to treatment. There is no current cure for PME and treatment focuses on managing myoclonus and seizures through antiepileptic medication (AED).

Ohtahara syndrome (OS), also known as Early Infantile Developmental & Epileptic Encephalopathy (EIDEE) is a progressive epileptic encephalopathy. The syndrome is outwardly characterized by tonic spasms and partial seizures within the first few months of life, and receives its more elaborate name from the pattern of burst activity on an electroencephalogram (EEG). It is an extremely debilitating progressive neurological disorder, involving intractable seizures and severe intellectual disabilities. No single cause has been identified, although in many cases structural brain damage is present.

<span class="mw-page-title-main">Spike-and-wave</span>

Spike-and-wave is a pattern of the electroencephalogram (EEG) typically observed during epileptic seizures. A spike-and-wave discharge is a regular, symmetrical, generalized EEG pattern seen particularly during absence epilepsy, also known as ‘petit mal’ epilepsy. The basic mechanisms underlying these patterns are complex and involve part of the cerebral cortex, the thalamocortical network, and intrinsic neuronal mechanisms.

Epilepsy-intellectual disability in females also known as PCDH19 gene-related epilepsy or epileptic encephalopathy, early infantile, 9 (EIEE9), is a rare type of epilepsy that affects predominantly females and is characterized by clusters of brief seizures, which start in infancy or early childhood, and is occasionally accompanied by varying degrees of cognitive impairment. The striking pattern of onset seizures at a young age, genetic testing and laboratory results, potential developmental delays or developmental regression and associated disorders, eases diagnosis.

<span class="mw-page-title-main">Mental retardation and microcephaly with pontine and cerebellar hypoplasia</span> Rare X-linked dominant genetic disorder

Mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) – also known as mental retardation, X-linked, syndromic, Najm type (MRXSNA); X-linked intellectual deficit, Najm type; intellectual developmental disorder, X-linked, syndromic, Najm type; X-linked intellectual disability–microcephaly–pontocerebellar hypoplasia syndrome; and by variations of these terms – is a rare X-linked dominant genetic disorder of infants characterised by intellectual disability and pontocerebellar hypoplasia. It usually affects females; many males die before birth or not long after.

An epilepsy syndrome is defined as "a characteristic cluster of clinical and Electroencephalography (EEG) features, often supported by specific etiological findings ."

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SLC6A1 epileptic encephalopathy is a genetic disorder characterised by the loss-of-function of one copy of the human SLC6A1 gene. SLC6A1 epileptic encephalopathy can typically manifest itself with early onset seizures and it can also be characterised by mild to severe learning disability. Not all manifestations of the conditions are present in one given patient.

References

  1. 1 2 "Infantile epileptic spasms syndrome". Epilepsy Action.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 Shorvon, S. D.; Guerrini, Renzo; Cook, Mark; Lhatoo, Samden D., eds. (2013). Oxford Textbook of Epilepsy and Epileptic Seizures. Oxford Textbooks in Clinical Neurology. Oxford, United Kingdom: Oxford University Press. pp. 63, 140, 177–179. ISBN   978-0-19-965904-3. OCLC   806014746.
  3. ↑ "Infantile Epileptic Spasms Syndrome (IESS)". www.epilepsydiagnosis.org.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 "West Syndrome - Symptoms, Causes, Treatment | NORD". rarediseases.org. Retrieved 2024-09-28.
  5. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Panayiotopoulos, C. P. (2007). A Clinical Guide to Epileptic Syndromes and Their Treatment (2nd ed.). London: Springer. pp. 276–283. ISBN   978-1-84628-643-8. OCLC   173238208.
  6. 1 2 Coleman, Mary; Gillberg, Christopher; Gillberg, Christopher (2012). "17. Prevention, Reversible Autism, and Medical Therapies". The Autisms (4th ed.). New York: Oxford University Press. pp. 315–316. ISBN   978-0-19-973212-8. OCLC   711828867.
  7. ↑ Treadwell, Jonathan R.; Wu, Mingche; Tsou, Amy Y. (2022-10-25). Management of Infantile Epilepsies (Report). Agency for Healthcare Research and Quality (AHRQ). doi:10.23970/ahrqepccer252.
  8. 1 2 3 4 5 6 "Infantile Spasms". MSD Manual Professional Edition. Retrieved 2024-09-29.
  9. ↑ Goldberg-Stern et al., 2001 & Eisermann et al. 2003 in: American Journal of Medical Genetics part C, 2006, S. 163: Neurobehavioral disorders in children, adolescents and young adults with down syndrome
  10. ↑ Bahi-Buisson N, Bienvenu T (2012) CDKL5-related disorders: from clinical description to molecular genetics. Mol Syndromol 2(3-5):137-152
  11. ↑ Sherr EH (2003) The ARX story (epilepsy, mental retardation, autism, and cerebral malformations): one gene leads to many phenotypes. Curr Opin Pediatr 15(6):567-571
  12. ↑ Gertler, T.; Bearden, D.; Bhattacharjee, A.; Carvill, G.; Adam, M. P.; Mirzaa, G. M.; Pagon, R. A.; Wallace, S. E.; Bean LJH; Gripp, K. W.; Amemiya, A. (1993). "KCNT1-Related Epilepsy". KCNT1-Related Epilepsy - GeneReviews® - NCBI Bookshelf. University of Washington, Seattle. PMID   30234941.
  13. 1 2 3 Wilmshurst JM, Ibekwe RC, O'Callaghan FJK (January 2017). "Epileptic spasms - 175 years on: Trying to teach an old dog new tricks" (PDF). Seizure. 44: 81–86. doi: 10.1016/j.seizure.2016.11.021 . PMID   27989601. S2CID   4977080.
  14. ↑ "Maternal and Child Outcomes Associated With the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)". effectivehealthcare.ahrq.gov. doi:10.23970/ahrqepccer253 . Retrieved 2024-10-21.
  15. ↑ Johnston, Michael V.; Adams, Harold P.; Fatemi, Ali (2016-08-18). Neurobiology of Disease. Oxford University Press. ISBN   9780190219086.
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