eMedicine Specialties > Neurology > Pediatric Neurology

Infantile Spasm (West Syndrome): Treatment & Medication

Author: Tracy A Glauser, MD, Professor, Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine, Children's Comprehensive Epilepsy Program, Children's Hospital Medical Center of Cincinnati
Coauthor(s): Diego A Morita, MD, Assistant Professor of Pediatrics and Neurology, Department of Pediatrics, Division of Neurology, Cincinnati Children's Hospital Medical Center, University of Cincinnati; Karen Mary Stannard, MD, FRCPC, Fellow, Pediatric Epilepsy, Cincinnati Childen's Medical Center
Contributor Information and Disclosures

Updated: Dec 7, 2009

Treatment

Medical Care

  • The 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.
  • The various medical treatment options for infants with West syndrome can be divided into 2 major groups:
    • Commonly used first-line treatments (ie, ACTH5,6,7,8 , prednisone, vigabatrin9,10,11,6,12,13 , pyridoxine [vitamin B-6]14,15,16 )
    • Second-line treatments (ie, benzodiazepines, valproic acid, lamotrigine17,18 , topiramate19,20 , zonisamide21,22 , levetiracetam23 )
  • In 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.24,25 Alternative options for symptomatic spasms included ACTH and prednisone.26

Surgical Care

Focal cortical resection: In some patients, resection of a localized region can lead to freedom from seizures.

Consultations

  • Pediatric neuropsychologists can assess intellectual function and educational needs and advise on nonpharmacologic management of behavioral problems.
  • Pediatric psychiatrists can advise on pharmacologic management of behavioral problems.
  • Neurosurgeons can help assess whether the infant is a candidate for focal resection.
  • Dietitians can assist in the institution and maintenance of the ketogenic diet.
  • Cardiologists should be consulted at the initiation of therapy with ACTH or steroids. They can evaluate cardiac function, looking for signs of hypertrophic cardiomyopathy, and aide in the management of hypertension, both of which are potential side effects of these therapies.

Diet

  • The ketogenic diet has been used successfully to treat a variety of seizure types. Recent studies have shown that it can be considered for the medical management of infantile spasms.
  • A 2006 retrospective study showed that the ketogenic diet in a ratio of 4:1 was effective in a small patient population of intractable infantile spasms previously treated with combinations of vigabatrin, topiramate, other AEDs, or prednisolone. A greater than 90% reduction in seizures were seen in 63% of children, and 40% were seizure free at 6 months. Side effects, including gastrointestinal disturbance, infection, and renal stones, were transient.27
  • A 2008 retrospective study showed a similar median time to seizure freedom in infants with new onset infantile spasms treated with either the ketogenic diet or ACTH. There was delay of 2-5 months in normalization of the EEG in those treated with the diet versus a delay of 1 month with ACTH. The side effects of the diet were less than those on ACTH. There was no difference in developmental outcome at 12 months of follow-up between the groups.28


Medication

The 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.

Hormonal agents

These agents cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.


Corticotropin (Acthar, ACTH)

A 2004 American Academy of Neurology and Child Neurology Society practice parameter concluded that (i) "ACTH is probably effective for the short-term treatment of infantile spasms and in resolution of hypsarrhythmia (Level B)" and
(ii) "There is insufficient evidence to recommend the optimum dosage and duration of treatment with ACTH for the treatment of infantile spasms (Level U)."
A 2004 multicenter, randomized, controlled trial in the UK compared hormonal therapy (either oral prednisolone or intramuscular tetracosactide depot, a synthetic analogue of ACTH) to vigabatrin in 107 infants with infantile spasms. More infants assigned hormonal treatments (73%) had no spasms on days 13 and 14 compared to infants assigned vigabatrin (54%, p=0.043). A follow-up study demonstrated that, although hormone treatment controlled spasms better than vigabatrin initially, by age 12-14 months, both groups had similar seizure-free rates. Older studies suggest ACTH's efficacy (percentage of infants with West syndrome reaching seizure freedom) is between 50% and 67%. Associated with serious, potentially life-threatening adverse effects. Must be administered IM, which is painful to infant and unpleasant for parent to perform.
Daily dosages expressed as U/d (most common), U/m2/d, or U/kg/d.
Prospective single-blind study demonstrated no difference in effectiveness of high-dose, long-duration corticotropin (150 U/m2/d for 3 wk, tapering over 9 wk) versus low-dose, short-duration corticotropin (20-30 U/d for 2-6 wk, tapering over 1 wk). With respect to spasm cessation and improvement in patient's EEG; hypertension was more common with larger doses.

Adult

Pediatric

Not established; 5-40 U/d IM for 1-6 wk to 40-160 U/d IM for 3-12 mo suggested; some authors recommend 150 U/m2/d IM for 6 wk or 5-8 U/kg/d IM in divided doses for 2-3 wk

Avoid vaccines and immunizations during therapy
Amphotericin B can decrease response; acetazolamide or other carbonic anhydrase inhibitors can cause hypernatremia, hypocalcemia, hypokalemia, and edema; diuretics can reduce natriuretic and diuretic effects; potassium-depleting diuretics can cause hypokalemia; phenytoin, barbiturates, and rifampin can decrease effects; estrogens can potentiate effects; salicylates or NSAIDs can cause GI ulceration; can reduce growth response to growth hormone (somatropin); warfarin can decrease anticoagulation response

Documented hypersensitivity; porcine protein hypersensitivity; scleroderma; recent surgery; congestive heart failure; primary adrenal insufficiency; hypercortisolism; active herpes infection; active tuberculosis; herpes simplex ocular infection; thromboembolic disease; active serious bacterial, viral, or fungal infection

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid vaccines and immunizations during therapy
Because of increased risk of infection, hypertension, hypertrophic cardiomyopathy, and electrolyte disturbances, careful and frequent clinical and laboratory monitoring of patient is essential
Caution in Cushing disease, hypertension, hypokalemia, hypernatremia, diverticulitis, ulcerative colitis or intestinal anastomosis, renal disease, diabetes mellitus, hypothyroidism, hepatic disease


Prednisone (Sterapred)

A 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 (Level U)."
Few comparative studies between ACTH and prednisone have been performed; one double-blind, placebo-controlled, crossover study demonstrated no difference between low-dose ACTH (20-30 U/d) and prednisone (2 mg/kg/d), while second prospective, randomized, single-blinded study demonstrated high-dose ACTH at 150 U/m2/d was superior to prednisone (2 mg/kg/d) in suppressing clinical spasms and hypsarrhythmic EEG in infants with infantile spasms.
A 2004 multicenter, randomized, controlled trial in the UK compared hormonal therapy (either oral prednisolone or intramuscular tetracosactide depot, a synthetic analogue of ACTH) to vigabatrin in 107 infants with infantile spasms. More infants assigned hormonal treatments (73%) had no spasms on days 13 and 14 compared to infants assigned vigabatrin (54%, p=0.043). A follow-up study demonstrated that, although hormone treatment controlled spasms better than vigabatrin initially, by age 12-14 months, both groups had similar seizure-free rates.

Adult

Pediatric

2 mg/kg/d PO for 2-4 wk

Barbiturates, phenytoin, rifabutin, and rifampin can increase metabolism of prednisone; hyperthyroidism can increase metabolism of prednisone; hypothyroidism can decrease metabolism of prednisone; isoproterenol in patients with asthma can increase risk of cardiac toxicity, clinical deterioration, myocardial infarction, congestive heart failure, and death

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Prolonged therapy can affect metabolic, GI, neurologic/behavioral, dermatologic, and endocrine systems; metabolic adverse events can include (but are not limited to) fluid retention and electrolyte disturbances (eg, hypernatremia, hypokalemia, hypokalemic metabolic alkalosis, hypocalcemia), edema, hypertension, and hyperglycemia
GI adverse events can include nausea, vomiting, abdominal pain, anorexia, diarrhea, constipation, gastritis, esophageal ulceration, weight loss, and delayed growth
Neurological and behavioral adverse events reported during prolonged administration can include headache, insomnia, restlessness, mood lability, anxiety, personality changes, and psychosis
Visual adverse events may include exophthalmos, retinopathy, posterior subcapsular cataracts, and ocular hypertension
Dermatological adverse events reported during therapy can include skin atrophy, diaphoresis, impaired wound healing, facial erythema, hirsutism, ecchymosis, and easy bruising
Endocrinological adverse events from prolonged use include hypercorticism and physiologic dependence
Idiosyncratic reactions include pancreatitis and dermatological hypersensitivity reactions (allergic dermatitis, angioedema, urticaria); avoid vaccination with live-virus vaccines; avoid abrupt discontinuation if patient has been on long-term therapy
Caution in congestive heart failure, hypertension, glaucoma, GI disease, diverticulitis, intestinal anastomosis, hepatic disease, hypoalbuminemia, peptic ulcer disease, renal disease, osteoporosis, diabetes mellitus, hypothyroidism, coagulopathy or thromboembolic disease, or potential impending GI perforation

Anticonvulsants

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.


Vigabatrin (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, 2009. Available only from restricted access program.

A 2004 American Academy of Neurology and Child Neurology Society practice parameter concluded that (i) "Vigabatrin is possibly effective for short-term treatment of infantile spasms (Level C, Class III and IV evidence)." (ii) "Vigabatrin is also possibly effective for short-term treatment of infantile spasms in majority of children with tuberous sclerosis (Level C, Class III and IV evidence)." (iii) "Serious concerns about retinal toxicity in adults suggest that serial ophthalmologic screening is required in patients on vigabatrin. However, data are insufficient to make recommendations regarding the frequency or type of screening that would be of value in reducing the prevalence of this complication in children (Level U, Class IV studies)."29

Multiple studies (both open label and double blind) have reported some effectiveness in stopping seizures in infants with West syndrome, especially when caused by tuberous sclerosis.

A 2004 multicenter, randomized, controlled trial in the UK compared hormonal therapy (either oral prednisolone or intramuscular tetracosactide depot, a synthetic analogue of ACTH) to vigabatrin in 107 infants with infantile spasms. More infants assigned hormonal treatments (73%) had no spasms on days 13 and 14 compared to infants assigned vigabatrin (54%, p=0.043).30 A follow-up study demonstrated that, although hormone treatment controlled spasms better than vigabatrin initially, by age 12-14 months, both groups had similar seizure-free rates.31

In a total of 12 studies, 4 of which were randomized control trials between 1990 and 2005, the percentage of spasm freedom with vigabatrin ranged from 11-78%. The response rate was influenced by etiology of the spasms. Vigabatrin was most effective in patients with tuberous sclerosis and other symptomatic etiologies.

Vigabatrin is not recommended for patients with nonketotic hyperglycinemia. The increase in GABA from vigabatrin, coupled with increased glycine, enhances the epileptic encephalopathy in these patients.

Mechanism of action: selective irreversible inhibition of GABA transaminase.

Adult

Pediatric

<1 month: Not established

1 month to 2 years: 50 mg/kg/d PO divided bid initially; if needed, may increase dose by increments of 25-50 mg/kg/d q3d; not to exceed 150 mg/kg/d

Renal impairment:
CrCl >50-80 mL/min: Decrease dose by 25%
CrCl >30-50 mL/min: Decrease dose by 50%
CrCl >10 to <30 mL/min: Decrease dose by 75%
Hemodialysis: Clearance not adequately studied

P450 CYP2C inducer; coadministration with CYP2C substrates (eg, phenytoin) results in decreased plasma levels (phenytoin levels decreased 16-20% when coadministered and therefore may require dosage adjustments); when coadministered with other AEDs, serum concentration of phenobarbital was reduced 8-16% and sodium valproate concentration was reduced by 8%
Increased clonazepam Cmax by 30% and decreased Tmax by 45%

Documented hypersensitivity; nonketotic hyperglycinemia (increase in GABA from vigabatrin, coupled with increased glycine, enhances the epileptic encephalopathy in these patients)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Boxed warning: Causes permanent vision loss in infants, children, and adults and includes progressive and permanent bilateral concentric visual-field constriction in >30% of patients, which ranges in severity from mild to severe, including tunnel vision to within 10[degree sign]of visual fixation, and can result in disability; reports describe damage to central retina and decreased visual acuity
Vision loss onset is unpredictable and can occur within weeks of starting treatment, sooner, at any time during treatment (even after months or years), and possibly after vigabatrin is discontinued; bilateral concentric visual field defects, involving the nasal fields can be seen within 6 months of exposure, risk is greatest after 1 year of treatment or with a cumulative drug load of 1 kg; periodic vision testing is required, but cannot reliably prevent vision damage; because of this risk, vigabatrin is available only through restricted distribution program
Other precautions: Excreted in breast milk; abnormal MRI signal changes reported in some infants; AEDs may increase risk of suicidal thoughts and behavior; when discontinuing, taper dose gradually to avoid withdrawal seizures; may cause anemia, peripheral neuropathy, and edema
Common adverse effects in addition to permanent vision loss include fatigue, somnolence, nystagmus, tremor, blurred vision, memory impairment, weight gain, arthralgia, abnormal coordination, and confusion
Dose-dependent adverse effects include hyperactivity, agitation, sedation, depression, psychosis, drowsiness, insomnia, facial edema, ataxia, nausea and/or vomiting, stupor, and somnolence; idiosyncratic reactions include visual field constriction; may exacerbate myoclonic and absence seizures in some patients; long-term reactions (ie, cumulative adverse effects) include weight gain; lower doses in patients with renal dysfunction


Topiramate (Topamax)

A 2004 American Academy of Neurology and Child Neurology Society practice parameter concluded that "there is insufficient evidence to recommend topiramate for the treatment of infantile spasms (Level U, Class III and IV evidence)."29
Topiramate is a sulfamate-substituted monosaccharide with broad spectrum of antiepileptic activity that may have state-dependent sodium channel blocking action, potentiate inhibitory activity of the neurotransmitter GABA, and may block glutamate activity.

A 2005 open label trial of topiramate in 15 infants with infantile spasms demonstrated clinical effectiveness at doses up to 27mg/kg/day. The median seizure rate reduction in the first two months of treatment was 41%. Twenty percent of patients were seizure free, 33% had > 50% reduction in seizures. Other small study series have shown 88% of patients had a >50% seizure reduction in spasms with topiramate.

Adult

Initial starting dose: 2-3 mg/kg/d PO; increment of 2-3 mg/kg q3-4d
Maintenance dose: 15-20 mg/kg/d PO

Pediatric

Initial starting dose: 2-3 mg/kg/d PO; increment of 2-3 mg/kg q3-4d
Maintenance dose: 15-20 mg/kg/d PO

May increase phenytoin plasma levels; may decrease valproate plasma levels; phenytoin and carbamazepine decrease levels

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Dose-dependent adverse effects include irritability, ataxia, dizziness, fatigue, nausea, somnolence, psychomotor slowing, concentration, constipation, and speech problems; if CNS adverse effects occur, reduce concomitant AEDs, slow titration, or reduce dose; no idiosyncratic reactions noted; oligohidrosis and nephrolithiasis reported


Levetiracetam (Keppra, Keppra XR)

Mechanism of action: inhibition of N-type calcium channels, modulation of GABA and glycine receptors and binding to SVA2 protein
One 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 30-60 mg/kg/day.
In another small open label trial of 7 children, 5 with symptomatic infantile spasms, treated with 20-80mg/kg/day of levetriacetam, all responded to therapy. Two patients had > 75% reduction in spasms and one had complete cessation of spasms.

Adult

1000 mg/d PO divided bid (500 mg bid); may increase by 1000 mg/d increments q2wk; not to exceed 3000 mg/d; long-term experience at doses >3000 mg/d is relatively minimal, and there is no evidence that doses >3000 mg/d offer additional benefit

Pediatric

Partial onset seizures:
<4 years: Not established
4-16 years: 20 mg/kg/d PO divided bid; may increase by 20 mg/kg/d increments q2wk; not to exceed 60 mg/kg/d; use oral solution if weight <20 kg
>16 years: Administer as in adults
Myoclonic seizures:
<12 years: Not established
>12 years: Administer as in adults
Tonic-clonic seizures:
<6 years: Not established
6-16 years: 10 mg/kg PO bid; may increase daily dose by 20-mg/kg increments q2wk, not to exceed 30 mg/kg bid
>16 years: Administer as in adults

None reported; does not inhibit CYP450 isoenzymes, epoxide hydrolase, or UDP-glucuronidation; probenecid inhibits renal clearance of ucb L057 (inactive levetiracetam metabolite)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal impairment (reduce dose); major side effects include somnolence, asthenia, incoordination, mild leukopenia (3%) and behavioral changes such as anxiety, hostility, emotional lability, depression and psychosis (1-2%), and depersonalization; seizure frequency may increase following discontinuing drug (discontinue gradually); statistically significant decreases in RBCs and WBCs have been observed


Valproic acid (Depakote, Depakene, Depacon)

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 (Level U, Class III and IV evidence)."
Considered effective second-line AED therapy against spasms associated with West syndrome.

Adult

Pediatric

Initial dose: 10-15 mg/kg/d PO divided bid/tid
Titration: 5-10 mg/kg/d increments at weekly intervals until therapeutic effect achieved or toxic effects occur
Maintenance dose: 15-60 mg/kg/d PO

Cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may significantly reduce levels; in children, salicylates decrease protein binding and metabolism of valproate; may result in variable changes of carbamazepine concentrations, with possible loss of seizure control; may increase diazepam and ethosuximide toxicity (monitor closely); may increase phenobarbital and phenytoin levels while either one may decrease valproate levels; may displace warfarin from protein binding sites (monitor coagulation tests); may increase zidovudine levels in HIV-seropositive patients

Documented hypersensitivity; history of hepatotoxicity or pancreatitis (patients at high risk for hepatotoxicity include <2 y, multiple concomitant AEDs including phenobarbital, underlying metabolic disease such as defect in fatty acid oxidation, and developmental delay)

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Dose-dependent adverse effects include asthenia, nausea, vomiting, somnolence, tremor, and dizziness; less common adverse effects include thrombocytopenia and parotid swelling; idiosyncratic reactions include hepatotoxicity and pancreatitis; long-term (cumulative) adverse effects include hair loss and weight gain


Lamotrigine (Lamictal)

A 2004 American Academy of Neurology and Child Neurology Society practice parameter concluded that "there is insufficient evidence to recommend lamotrigine for the treatment of infantile spasms (Level U, Class III and IV evidence)."
Lamotrigine inhibits release of glutamate and inhibits voltage-sensitive sodium channels, leading to stabilization of neuronal membrane. Effectiveness in West syndrome has been investigated in open-label studies with promising results.
Initial dose, maintenance dose, titration intervals, and titration increments depend on concomitant medications.

Adult

Pediatric

Combination with AEDs that induce hepatic CYP-450 enzyme system WITHOUT valproate
Initial starting dose: 0.6 mg/kg/d PO for 2 wk; 1.2 mg/kg/d for wk 3-4; 5-15 mg/kg/d thereafter; after week 4, dosage increment not to exceed 1.2 mg/kg/d q1-2wk until maintenance dose achieved; maximum daily dose is 400 mg/d

Combination WITH valproate with or without other AEDs that induce hepatic CYP-450 enzyme system Initial starting dose: 0.15 mg/kg/d PO for 2 wk; 0.3 mg/kg/d for weeks 3-4; 1-5 mg/kg/d thereafter; after week 4, dosage increment not to exceed 0.3 mg/kg/d q1-2wk until maintenance dose achieved; usual maximum daily dose is 200 mg/d

Affected by concomitant AEDs; when used in conjunction with medications that induce hepatic CYP-450 microsomal enzymes (eg, phenobarbital, carbamazepine, phenytoin), clearance enhanced; conversely, when used in conjunction with medications that inhibit hepatic CYP-450 microsomal enzymes (eg, valproate), clearance diminished; lower starting doses, slow titration rate (ie, 2-wk or greater intervals between dosage increases), and smaller increments are needed

Documented hypersensitivity; history of erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis; erythema multiforme; Stevens-Johnson syndrome; toxic epidermal necrolysis

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Dose-dependent adverse effects include ataxia, diplopia, dizziness, headache, nausea, and somnolence; idiosyncratic reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis; no long-term (cumulative) adverse effects noted to date
Risk factors for associated severe dermatologic reactions include younger age (children more than adults), co-medication with valproic acid, rapid rate of titration, and high starting dose; give careful attention to initial starting dose, titration rate, and co-medications; prompt evaluation of any rash is prudent and imperative; approximately 10-12% of patients develop non–life-threatening rash that usually resolves rapidly upon withdrawal and occasionally without changing dosage


Zonisamide (Zonegran)

A 2004 American Academy of Neurology and Child Neurology Society practice parameter concluded that "there is insufficient evidence to recommend zonisamide for the treatment of infantile spasms (Level U, Class III and IV evidence)."
Effectiveness in West syndrome has been investigated in 5 open-label studies with promising results.

Adult

Pediatric

Initial dose: 1-2 mg/kg/d PO; increase 1-2 mg/kg/d q2wk
Maintenance dose: 8-12 mg/kg/d PO

Phenytoin, phenobarbital, carbamazepine, and valproate decrease half-life; no effect on steady-state plasma concentrations of other AEDs

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Dose-dependent adverse effects include headache, anorexia, nausea, dizziness, ataxia, paresthesia, difficulty concentrating, irritability, and somnolence; idiosyncratic reactions include severe rash (Stevens-Johnson syndrome, toxic epidermal necrolysis) with reporting rate of 46 per million patient-years of exposure; oligohidrosis and nephrolithiasis reported

Benzodiazepines

A 2004 American Academy of Neurology and Child Neurology Society practice parameter concluded that "there is insufficient evidence to recommend benzodiazepines for the treatment of infantile spasms (Level U, Class III and IV evidence)."29

By binding to specific receptor sites, these agents appear to potentiate the effects of GABA and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.


Clonazepam (Klonopin)

Considered second-line AED therapy against spasms associated with West syndrome. Adverse effects and development of tolerance limit usefulness over time. Nitrazepam and clobazam not approved by FDA in US but are available in many countries worldwide.

Adult

Pediatric

Maintenance dose: 0.01-0.2 mg/kg/d PO

Decreases plasma levels of phenytoin, phenobarbital, and carbamazepine; potentiates CNS depression induced by other anticonvulsants and alcohol; may reduce renal clearance of digoxin; cimetidine and erythromycin decrease clearance

Documented hypersensitivity; significant liver disease; acute narrow-angle glaucoma

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Dose-dependent adverse effects include hyperactivity, sedation, drooling, incoordination, drowsiness, ataxia, fatigue, confusion, vertigo, dizziness, amnesic effect, and encephalopathy; considered least-sedating benzodiazepine; long-term (cumulative) adverse effects include tolerance and dependence; considered to have longest time to development of tolerance; adjust dose or discontinue therapy in presence of renal or liver function impairment, since metabolism occurs in liver and metabolites are excreted in urine

Vitamins

These agents are essential for normal metabolic processes.


Pyridoxine (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 spasms (Level U, Class III and IV evidence)."
Two 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 50-100 mg IV during diagnostic EEG; if dramatic improvement noted in EEG, patient believed to have pyridoxine-dependent seizures
(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.

Adult

Pediatric

Initial dose: 10-20 mg/kg/d PO
Titration: Increase by 10 mg/kg q3d
Maintenance dose: 15-50 mg/kg/d PO (approximately 100-400 mg/d)

Can decrease phenobarbital and phenytoin serum concentrations

Documented hypersensitivity; do not administer IV to infants with cardiac disease

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Usually well tolerated; adverse events include decreased appetite, nausea, vomiting, paresthesias, diarrhea, somnolence, and headache; abnormal liver function tests and low serum folic acid levels have been noted in some patients; long-term (cumulative) adverse effects can include severe sensory peripheral neuropathy, movement disorders, and ataxia

More on Infantile Spasm (West Syndrome)

Overview: Infantile Spasm (West Syndrome)
Differential Diagnoses & Workup: Infantile Spasm (West Syndrome)
Treatment & Medication: Infantile Spasm (West Syndrome)
Follow-up: Infantile Spasm (West Syndrome)
Multimedia: Infantile Spasm (West Syndrome)
References
[ CLOSE WINDOW ]

References

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Further Reading

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Keywords

infantile spasms, West syndrome, hypsarrhythmia, developmental delay, mental retardation, infantile spasms treatment, infantile spasms symptoms, mental retardation, epilepsy syndrome

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Contributor Information and Disclosures

Author

Tracy A Glauser, MD, Professor, Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine, Children's Comprehensive Epilepsy Program, Children's Hospital Medical Center of Cincinnati
Tracy A Glauser, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

Coauthor(s)

Diego A Morita, MD, Assistant Professor of Pediatrics and Neurology, Department of Pediatrics, Division of Neurology, Cincinnati Children's Hospital Medical Center, University of Cincinnati
Diego A Morita, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Karen Mary Stannard, MD, FRCPC, Fellow, Pediatric Epilepsy, Cincinnati Childen's Medical Center
Karen Mary Stannard, MD, FRCPC is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Medical Editor

Robert Baumann, MD, Child Neurology Program Director, Professor, Departments of Neurology and Pediatrics, University of Kentucky
Robert Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, and Child Neurology Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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