INFANTILE SPASM and INFANTILE SPASM TREATMENT

INFANTILE SPASM and INFANTILE SPASM TREATMENT

INFANTILE SPASM (WEST syndrome):

• Steroids and Vigabatrin are considered as the first line medications for infantile spasms and ACTH injections are not considered superior to oral prednisolone in treatment of infantile spasms.

• For tuberous sclerosis, Vigabatrin should be used as first line, without steroids
• If not tuberous sclerosis: Combination therapy with steroids and vigabatrin has been shown to produce quicker spasm resolution

HIGH DOSE ACTH PROTOCOL IN INFANTILE SPASM:

Schedule	Dose IM
Day 1-14 (week 1 and 2)	75 Units/m2/dose twice a day, may receive only 1 dose on day1
Taper over 2 weeks (weeks 3 and 4)
Day 15-17	30 Units/m2/dose every morning
Day 18-20	15 Units/m2/dose every morning
Day 21-23	10 Units/m2/dose every morning
Day 24-30	10 Units/m2/dose every other morning

Treatment failure: If ACTH treatment has failed after 2 weeks

Then what to do?

• Consider switching to an alternative agent with a different mechanism of action (i.e. vigabatrin). Taper ACTH according to the protocol above, while simultaneously beginning an alternative agent.
• Gastrointestinal prophylaxis: H2 blocker or proton pump inhibitor is required during the full course of ACTH treatment (e.g. ranitidine, omeprazole, or lansoprazole). GI prophylaxis can be stopped when ACTH is stopped.
• PJP prophylaxis: Patients will be immunosuppressed while on ACTH and for weeks after ACTH treatment. PJP prophylaxis is needed with Bactrim 2.5 mg/kg/dose two times a day or BID on three consecutive days each week (preferred practice is Monday, Tuesday and Wednesday) during ACTH treatment and for an additional 4 weeks after ACTH treatment is stopped.
• Immunizations: In general, children receiving high dose systemic corticosteroids (such as ACTH or prednisolone) should NOT receive LIVE-virus vaccines until 4 weeks after discontinuation of steroids. Inactivated vaccines may be temporarily deferred until corticosteroids are discontinued or may be given during corticosteroid treatment if caregiver adherence with follow-up is not likely.
• Stress dose steroids: At the cessation of steroids or with illness, there may be a need for stress dose steroids. Patients will have adrenal insufficiency after the course of ACTH for as long as they received the medication, (e.g. a patient treated with 4 weeks of ACTH will have adrenal insufficiency for 4 weeks following cessation of therapy). They should be evaluated by a physician for any signs of illness including fever, vomiting, diarrhea, or with trauma to assess for hypoglycemia and hypotension.

Monitoring:

• Common side effects from ACTH include hypertension, hyperglycemia, irritability, immunosuppression, stomach irritation, increased appetite, and adrenal crisis (especially if stopped abruptly).
• Hypertension: Blood pressure monitoring is required 2-3 times per week.
• Sustained hypertension is defined as systolic blood pressure (SBP) greater than 95th% (in children 100 is >95th %) on 3 consecutive days.
• Sustained hypertension can be a sign of steroid-induced endocrine dysfunction or cardiomyopathy (septal hypertrophy), which can develop after 5+ days of ACTH treatment. BP monitoring and prompt attention to hypertension is critical.
• Hyperglycemia: Weekly glucose monitoring is required.
• If hyperglycemia occurs (glucose is >200), ensure the patient’s PCP is involved. Draw a BMP to check for hypokalemia. Insulin treatment may be required.

ORAL PREDNISOLONE PROTOCOL:

Low dose 4mg/day vs high dose 8mg/day (max: 60mg/day)

Days	Dose
1-14	2.6mg/kg/day 3 times a day (8mg/kg/day) Maximum dose 60mg/day
15-21	2.6mg/kg/day 2 times a day
22-28	2.6mg/kg/day 1 time a day
29	Stop

Treatment failure: If ACTH treatment has failed after 2 weeks

Then what to do?

Consider switching to an alternative agent with a different mechanism of action (i.e. vigabatrin). Taper ACTH according to the protocol above, while simultaneously beginning an alternative agent.

FOLLOW-UP FOR ALL THERAPIES:

• Following the initiation of any first-line treatment, efficacy of therapy should be assessed by 2 weeks.
• Short-term outcomes include cessation of spasms and EEG confirmation of treatment response showing resolution of hypsarhythmia.
• §  EEG should be used to assess for resolution of spasms and hypsarhythmia at 12-16 days. EEG should be of sufficient duration to include wake and sleep.

If spasms or hypsarhythmia persist at 2 weeks then:

• Many children will respond to an alternative first-line therapy. Consider switching treatment to an alternative first-line treatment with a different mechanism of action. Follow the weaning protocols outlined for the specific first-line agent.
• Efficacy of the alternative therapy should also be assessed at 2 weeks, as above.
• In patients without a clear etiology for IS, consider vitamin B6 diagnostic challenge.
• If spasms or hypsarhythmia persists or recur 2 weeks after treatment with an alternative first-line medication, consider prompt referral to an epileptologist to pursue additional treatment options.
• Consider repeat EEG 1-4 weeks after completion of treatment to confirm sustained efficacy. Also consider repeat EEG if there is concern for developmental plateau/regression or clinical seizures.
• If spasms or hypsarhythmia abnormalities persist or recur in the absence of an established etiology, or if the child does not follow the expected treatment course based on the established etiology, the etiology should be further investigated, to include at least 1 of the following: repeat video EEG monitoring, MRI, or genetic/metabolic studies.
• Neuropsychological testing is recommended within the first two years of life.

VIGABATRIN

Dosing (Infants and children 1 month – 2 years):

• 25 mg/kg/dose twice a day – increase by 25-50 mg/kg/DAY increments every 3 days for spasm control, to max of 75mg/kg/dose twice a day.
• At conclusion of treatment, vigabatrin should be tapered off by 25-50 mg/kg/DAY every 3-4 days.
• Treatment failure: If vigabatrin treatment has failed after 2 weeks, consider switching to an alternative agent with a different mechanism of action (i.e. ACTH or prednisolone).
• Vigabatrin should be weaned by 25-50 mg/kg/DAY every 3-4 days while simultaneously beginning an alternative agent.
• Duration of therapy, if vigabatrin is successful, optimal duration of treatment is unknown. Common practice is 6 months.

Monitoring: 

• Baseline eye exams within 4 weeks of vigabatrin initiation, every 3 months during therapy, and at 3-6 months following discontinuation of therapy are recommended for vigabatrin therapy. Pre-existing visual impairment is not a contraindication for vigabatrin treatment. 
• Baseline MRI is encouraged due to vigabatrin-associated changes on MRI.

Second line treatment may include (in no recommended order as this will depend on the infant’s presentation and possible underlying aetiology):

• Trial of Pyridoxine
• Topiramate or zonisamide
• Sodium valproate
• Nitrazepam
• Ketogenic diet ,
• Evaluation for epilepsy Surgery
• Where prednisolone has been used but ineffective or partially effective, there are occasional children who appear to respond to ACTH