2DefinitionWest syndrome is composed of the triad of infantile spasms, an interictal EEG pattern termed hypsarrhythmia, and mental retardation, although the diagnosis can be made even if one of the 3 elements is missing (according to the international classification).This severe epilepsy syndrome is an age-dependent expression of a damaged brain. The term infantile spasms has been used to describe the seizure type, the epilepsy syndrome, or both
3the syndrome’s namesake, Dr W J West, gave the first detailed description of infantile spasms, as they occurred in his child.[ in a letter to the editor of The Lancet in 1841,dr West described the events as “bobbings” that “cause a complete heaving of the head forward towards his knees, and then immediately relaxing into the upright position … these bowings and relaxings would be repeated at intervals of a few seconds, and repeated from 10 to 20 or more times at each attack, which would not continue more than 2 or 3 minutes; he sometimes has 2, 3 r more attacks in the day.
4This detailed clinical description was followed 100 years later by the report of the typical interictal EEG pattern termed hypsarrhythmia. Most patients with infantile spasms have some degree of developmentalretardation.The West syndrome was created in the early 1960by Drs. Gastaut, Poirier, and Pampiglione.
5IntroductionWest’s syndrome is a unique, age-specific epilepsy of early infancy.Spasms are:Different from myoclonic and tonic seizuresCharacterized by an initial contraction phase followed by a more sustained tonic phaseDivided into flexor, extensor, and mixed flexor-extensor spasms and they can also be asymmetrical
6Infantile spasms are believed to reflect abnormal interactions between the cortex and brainstem structures. Focal lesions early in life may secondarily affect other sites in the brain, and hypsarrhythmia may represent this abnormal activity arising from multiple brain sites.The frequent onset of infantile spasms in infancy suggests that an immature central nervous system may be important in the pathogenesis. The brain-adrenal axis also may be involved.One theory states that the effect of different stressors in the immature brain produces an abnormal excessive secretion of corticotropin-releasing hormone, causing spasms.
7IncidinceIncidence of infantile spasms is estimated between 0.25 to 0.60 per 1000 live births.Prevalence rate is per 1000 children ten years of age or younger.United StatesInfantile spasm constitutes 2% of childhood epilepsies but 25% of epilepsy with onset in the first year of life.
8Sex Although males are affected slightly more often than females, no significant gender difference is noted.Age 90% of infantile spasms begin in those younger than 12 months. Peak onset is at age 4-6 months.
9ManifestationsSpasms begin with a sudden, rapid, tonic contraction of trunk and limb musculature that gradually relaxes over seconds.Contractions can last 5-10 seconds.The intensity may vary from a subtle head nodding to a powerful contraction of the body.Infantile spasms usually occur in clusters, often several dozens, separated by 5-30 seconds.Spasms frequently occur just before sleep or upon awakening. They can be observed during sleep, although this is rare.
10Spasms can be flexor, extensor, or a mixture of flexion and extension. Flexor spasms consist of brief contractions of the flexor muscles of the neck, trunks, and limbs, resulting in a brief jerk. They may resemble a self-hugging motion and often are associated with a cry. The patient then relaxes, and the jerk repeats. These attacks occur in clusters throughout the day and last anywhere from less than 1 minute to minutes or longer in some patients.
11-Extensor spasms consist of contractions of the extensor muscles with sudden extension of the neck and trunk with extension and abduction of the limbs. Extensor spasms and asymmetric or unilateral spasms often are associated with symptomatic cases.Mixed spasms are the most common type, consisting of flexion of the neck and arms with extension of the legs, or flexion of the legs with extension of the arms.In different series the frequency of the 3 spasm types were 42-50% mixed, 34-42% flexor, and 19-23% ex
12General physical examination Physical examination can be important in helping to identify specific etiologies that may have both systemic and neurological symptoms (eg, tuberous sclerosis complex).Often a patient with infantile spasms has normal findings on general physical examination. No pathognomonic physical findings are present in patients with infantile spasms.If abnormalities in the general physical examination are noted (eg, adenoma sebaceum, ash leaf macules), specific etiologies may be suggested.Patients may exhibit moderate-to-severe growth delay; this is a nonspecific finding and more a reflection of the underlying brain injury than of a specific epilepsy syndrome.
13Neurologic examination The neurologic examination in patients with infantile spasms demonstrates abnormalities in mental status function, specifically deficits in cognitive function consistent with developmental delay or regression.Abnormalities in level of consciousness, cranial nerve function, and motor/sensory/reflex examination are nonspecific findings and more a reflection of the underlying brain injury or effect of anticonvulsant medications than of the syndrome.No pathognomonic findings are present on neurologic examination in patients with infantile spasm
14CausesInfantile spasms (West syndrome) can be classified according to its suspected etiology asSymptomatic:, 70-75%cryptogenic, 8-42%. idiopathic. 9-14%.
15Symptomatic :-Patients are diagnosed with symptomatic infantile spasms if an identifiable factor is responsible for the syndrome. any disorder that can produce brain damage can be associated with infantile spasms.The list of etiologies can be subdivided into prenatal disorders, perinatal disorders, and postnatal disorders.Prenatal disorders include hydrocephalus, microcephaly, hydranencephaly, schizencephaly, polymicrogyria, Sturge-Weber syndrome, incontinentia pigmenti, tuberous sclerosis, trisomy 21, hypoxic-ischemic encephalopathies, congenital infections, and trauma.
16Perinatal disorders include hypoxic-ischemic encephalopathies, meningitis, encephalitis, trauma, and intracranial hemorrhages.Postnatal disorders include pyridoxine dependency, nonketotic hyperglycinemia, maple syrup urine disease, phenylketonuria, mitochondrial encephalopathies, meningitis, encephalitis, degenerative diseases, biotinidase deficiency, and trauma.
17Cryptogenic:-Patients have cryptogenic infantile spasms if no cause is identified but a cause is suspected and the epilepsy is presumed to be symptomatic.The proportion of cryptogenic cases varies from 8-42%. This wide range may be related to variations in the definition of the term cryptogenic and the age of diagnosis, since assessment of developmental level in early infancy is difficult.
18Idiopathic:-Patients may be considered to have idiopathic infantile spasms if normal psychomotor development occurs prior to the onset of symptoms, no underlying disorders or definite presumptive causes are present, and no neurological or neuroradiological abnormalities exist. Some investigators use the terms idiopathic and cryptogenic interchangeably.The percentage of idiopathic cases reportedly is 9-14%.
19Laboratory workupPrior to initiating therapy, consider obtaining some or all of the following laboratory studies:Complete blood count with differential, liver panel, renal panel with electrolytes and glucose, calcium, magnesium, phosphorus, and urinalysis with microscopic examinationMetabolic workup including glucose, liver panel, serum lactate and pyruvate, plasma ammonia, serum and urine amino acids, urine organic acids, and serum biotinidaseBlood, urine, and cerebrospinal fluid cultures if an infection is suspectedCerebrospinal fluid analysis for cell count, glucose, protein, bacterial and viral culture, lactate, pyruvate, and amino acids
20ImagingAbout 70-80% of patients have abnormal findings on neuroimaging studies.Magnetic resonance imaging (MRI) of the brain provides a more detailed evaluation than does a computed tomography (CT) scan of the brain.Imaging studies should be obtained prior to starting ACTH or steroid therapy, as these therapies are associated with the appearance of apparent brain atrophy as treatment continues.
21CT scanStructural brain anomalies such as hydrocephalus, hydranencephaly, schizencephaly, and agenesis of corpus callosum can be recognized easily by CT scans.In addition, cerebral calcifications can be observed in patients with tuberous sclerosis or congenital infections.MRI scansare superior to CT scans in detecting areas of cortical dysgenesis, disorders of neuronal migration, or disorders of myelination.
22Electroencephalogram(EEG) Interictal electroencephalogramHypsarrhythmia is the characteristic interictal EEG pattern and consists of chaotic, high- to extremely high-voltage polymorphic delta and theta rhythms with superimposed multifocal spikes and wave discharges. Multiple variations of this pattern are possible, including focal or asymmetric hypsarrhythmia.
23Ictal electroencephalogram Eleven different types of ictal patterns have been identified in patients with West syndrome.In one study, the most common pattern found in 38% of patients with seizures was a high-voltage, frontal dominant, generalized slow-wave transient followed by voltage attenuation, also termed an electrodecremental episode. These electrodecremental episodes were a feature in 71% of the seizures.No close correlation exists between the type of seizure and the EEG pattern
24Ophthalmic examination: Ophthalmic examination may reveal chorioretinitis from congenital infections,chorioretinal lacunar defects in patients with Aicardi syndrome,retinal tubers in patients with tuberous sclerosis.
25Wood lamp: Tuberous sclerosis is the single most common recognizable cause of West syndrome. Therefore, a careful examination of the skin for the characteristic hypopigmented lesions of tuberous sclerosis is mandatory. The unaided bedside identification of these lesions may be more difficult in patients with light complexions.
26TreatmentThe goals of treatment for infants with West syndrome are the best quality of life with no seizures, the fewest adverse effects from treatment, and the least number of medications.Medications such as ACTH and conventional antiepileptic medications (AEDs) are the mainstay of therapy for infants with West syndrome. Unfortunately, no one medical treatment gives satisfactory relief for all infants with West syndrome.
27The various medical treatment options for infants with West syndrome can be divided into 2 major groups:Commonly used first-line treatments (ie, ACTH , prednisone, vigabatrin , pyridoxine [vitamin B-6]Second-line treatments (ie, benzodiazepines, valproic acid, lamotrigine , topiramate , zonisamide , levetiracetam
28In 2007, an expert survey concluded that 1-3 trials of monotherapy should be implemented before considering epilepsy surgery. In patients with tuberous sclerosis or symptomatic infantile spasms, vigabatrin was the drug of choice. Alternative options for symptomatic spasms included ACTH and prednisone.Focal cortical resection: In some patients, resection of a localized region can lead to freedom from seizures.
29Vigabatrin (Sabril)Indicated as monotherapy for children aged 1 mo to 2 y with infantile spasms. Precise mechanism unknown. Irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T). GABA-T metabolizes GABA, an inhibitory neurotransmitter, thereby increasing CNS GABA levels. Use must be weighed against risk of permanent vision loss. Approved by the FDA August, Available only from restricted access program.
30ACTHA 2004 American Academy of Neurology and Child Neurology Society practice parameter concluded that "ACTH is probably effective for the short-term treatment of infantile spasms and in resolution of hypsarrhythmia and "There is insufficient evidence to recommend the optimum dosage and duration of treatment with ACTH for the treatment of infantile spasms .
31PrednisoneA 2004 American Academy of Neurology and Child Neurology Society practice parameter concluded that "there is insufficient evidence that oral corticosteroids are effective in the treatment of infantile spasms .
32Levetiracetam (Keppra, Keppra XR) Mechanism of action: inhibition of N-type calcium channels, modulation of GABA and glycine receptors and binding to SVA2 proteinOne small open label trial of 5 infants with new onset cryptogenic infantile spasms showed clinical effectiveness. Two children became seizure free, while 2 others showed a minimum of 50% reduction in seizures. The dose ranged from mg/kg/d.In another small open label trial of 7 children, 5 with symptomatic infantile spasms, treated with mg/kg/d of levetiracetam, all responded to therapy. Two patients had >75% reduction in spasms and one had complete cessation of spasms.
33Valproic acid (Depakene) A 2004 American Academy of Neurology and Child Neurology Society practice parameter concluded that "there is insufficient evidence to recommend valproic acid for treatment of infantile spasms
34Pyridoxine (vitamin B-6) A 2004 American Academy of Neurology and Child Neurology Society practice parameter concluded that "there is insufficient evidence to recommend pyridoxine for the treatment of infantile spasmsTwo distinct treatment situations exist in which pyridoxine is used in patients with West syndrome:(1) IV administration during diagnostic EEG to assess whether patient's seizures and EEG abnormalities are related to pyridoxine deficiency. In this approach, administer mg IV during diagnostic EEG; if dramatic improvement noted in EEG, patient believed to have pyridoxine-dependent seizures
35(2) Long-term oral administration: Effectiveness of long-term oral high-dose pyridoxine in West syndrome has been investigated in multiple open-label studies with promising results; most patients who respond to long-term oral high-dose pyridoxine do so within 1-2 wk of initiation.
36PrognosisThe long-term overall prognosis is poor and is related directly to the etiology.Infants with idiopathic West syndrome have better prognosis than do infants with symptomatic West syndrome. Only 14% of infants with symptomatic West syndrome have normal or borderline normal cognitive development compared with 28-50% of infants with idiopathic West syndrome. Mental retardation is severe in 70% of patients, often with psychiatric problems such as autistic features or hyperactivity. Infrequently spasms may persist in adulthood % of patients develop other seizure types and 18-50% of patients will develop Lennox Gastaut syndrome.
37Favorable prognostic factors include cryptogenic etiology, age of onset >4 months, absence of atypical spasms and partial seizures, absence of asymmetric EEG abnormalities, short time from onset to treatment, and early sustained response to treatment.Infants with symptomatic infantile spasms have been shown to be at higher risk for the development of autism spectrum disorders, compared with those infants with cryptogenic or idiopathic spasms
39This done aty 26-10-2011 (11/2 year child) reveals marked atrophy and volume loss of left temporal and parietal lobe,encephalmalacia .Widenining of the ipsilateral left lateral ventricle is notead”(porencephaly)Conclusion :-chronic sequalae of an old brain insult for clinical correlation