Infantile spasms is a specific type of epilepsy syndrome, 9-15% are primary and the rest are secondary, with an incidence of about 0.2-0.6%. Most seizures stop spontaneously by the age of 5 years, but other forms of seizures may occur.
The treatment of infantile spasms is a worldwide problem, and over the years, treatment options have been studied and evaluated in the United States, Japan, the United Kingdom, and other European countries. 1994, after a study by the American Child Neurology Association, suggested that ACTH (adrenocorticotropic hormone) should be the drug of choice, followed by valproic acid and oral prednisone. 2000, a study by the Japanese Epilepsy Society showed that vitamin B6 In 2000, a study by the Japanese Epilepsy Association showed that vitamin B6 should be the drug of choice, followed by valproic acid alone or in combination with vitamin B6, and adrenocorticotropic hormone as the third choice.
The following is a brief review of the recent treatment of infantile spasms.
1.ACTH and prednisone
Mechanisms
ACTH may reduce the excitability of nerve cells through two mechanisms: (1) induction of hormone release and (2) direct, non-hormone-dependent effects on the melanocortin-1 receptor. In addition, inhibition of CRH, an excitatory neuropeptide, may also be a mechanism. The mechanism of action, long-term effects and side effects of ACTH and prednisone have been controversial.
Dose, efficacy, and
ACTH: Low dose 20 – 30 U/day or high dose 150 U/m2/day, there is no accepted ideal dose.
Several retrospective and prospective studies have shown no significant differences in spasticity remission rates, recurrence rates, and EEG improvement rates between the two dose regimens. Treatment is effective in starting remission in 7-12 days, with an efficiency rate of 40-87%, and more than one-third of children relapsed after remission, and secondary treatment is often effective.
Treatment with prednisone or prednisolone at 2-3 mg/kg for 2 – 32 weeks resulted in a remission rate of 29% – 59%.
ACTH versus oral prednisone
ACTH 150 IU/m2 was more effective than oral prednisone 2 mg/kg for 2 weeks, while ACTH 20 to 30 units/day was not significantly different from oral prednisone 2 mg/kg/day. ACTH treatment was ineffective, but oral prednisone was effective, and vice versa.
Side effects
Hypertension 0% – 37% (increased risk of hypertension in ACTH high dose group), infection 14%, irritability 37% – 100%, cerebral atrophy 62%, death 5 cases (out of 304 cases).
2.Aminocaproic acid (Xiborin Vigabatrin)
Mechanism
The structure is similar to Γ-aminobutyric acid (GABA), which is an irreversible inhibitor of GABA aminotransferase, and can increase the level of GABA.
Dose and efficacy
18 to 200 mg/kg/day
The remission rate is 23% at 2 weeks and 65% at 3 months, generally better in primary than secondary cases, but best in tuberous sclerosis, 91% -100%. The time to effect is 12 – 35 days.
Side effects
Sedation, irritability, insomnia, hypotonia, etc. Central visual field defects and retinal current map abnormalities have been found in children, and have not been reported under 1 year of age.
3. Valproic acid
Mechanism
Valproic acid increases the function of the GABA inhibitory system at cortical and subcortical levels and blocks sodium channels to inhibit neuronal firing.
Dose, efficacy
40 and 100 mg/kg/day, 73% remission rate and 91% EEG improvement rate at 6 months, but relapse rate reaches 23% at 7 months.
Side effects
General: weight gain, nausea, vomiting, hair loss, bleeding, tremor
Severe: severe skin rash, remitting anemia, leukopenia, liver failure, pancreatitis
4.NitrozepamNitrazepam
Mechanism
May be related to alteration of GABA receptor sensitivity.
Dose, efficacy
0.5 – 3.5 mg/kg/day, remission rate 30% – 54%, EEG improvement rate 15% – 46%.
Side effects
Drowsiness, salivation, dysphagia, aspiration pneumonia.
5.Pyridoxine (VB6)
Mechanism
Pyridoxine is a coenzyme of glutamic acid decarboxylase, which facilitates the synthesis of GABA. Pyridoxine is the preferred treatment for infantile spasms in Japan
Dose, efficacy
Generally 10 to 50 mg/kg/day, with >1 g/day, the remission rate is 35% to 40% for primary, but only 10% for secondary.
Side effects
Appetite, vomiting, irritability at high doses.
Children with pyridoxine dependence have severe, uncontrollable convulsions (some manifesting as infantile spasms), but seizures stop and EEG improves with 100-500 mg of pyridoxine. Children need to be treated with pyridoxine 15 – 20 mg/kg/day for life.
6. Zonisamide
Mechanism
Blocking sodium channels and reducing calcium inward flow
Dose, efficacy
Additive therapy 4 – 20 mg/kg/day, remission rate 33%, but relapse rate 50%.
Monotherapy 3 – 10 mg/kg/day, 36% remission rate in 1 – 5 days, but 50% relapse rate in 4 – 6 weeks.
Side effects
General: anorexia, dizziness, ataxia, fatigue, drowsiness, confusion
Rare: kidney stones, hyperthermia
7.Topiramate
Mechanism
Blocking sodium channels, increasing GABA activity, decreasing glutamate activity
Dose, efficacy
3 to 27 mg/kg/day, the maximum amount has been used to 50 mg/kg/day
Remission rate 20%-45%.
Side effects
Common: anorexia, weight loss, word finding difficulties, ataxia, concentration disorders, dizziness, fatigue, sensory abnormalities, sleepiness
Rare: kidney stones, sweating less, acute glaucoma
8.Felbamate of felbamate
Mechanism
Increase GABA-mediated inhibition and block sodium channels.
Dose, efficacy
15 – 45 mg/kg/day 75% remission in a small sample of refractory infantile spasms (4 cases) and 75% reduction in seizures in another observation (6 cases).
Side effects
General: nausea, vomiting, anorexia, weight loss, dizziness, headache, ataxia, insomnia
Severe: remittance, liver failure
9.Lamotrigine
Mechanism
Acts on sodium channels, stabilizes cell membranes, and inhibits the release of excitatory neurotransmitters
Dose, efficacy
In combination with valproic acid, increase to 5 mg/kg/day
Not combined with valproic acid, increase to 15 mg/kg/day
Refractory infantile spasms remission rate of 17% with add-on therapy.
Side effects
General: rash, nausea, dizziness, sleepiness
Severe: StevensCJohnson syndrome
10. Levetiracetam (Kaipuran) Levetiracetam
Mechanism
Linked to synaptic vesicle proteins, exact mechanism is unclear
Dose, efficacy
10 to 60 mg/kg/day Several cases of remission have been reported. Low relapse rate after remission.
Side effects
General: sleepiness, headache, anorexia, nervousness
Rare: irritability, anxiety, depression, aggressive behavior
11.Thyrotropin-releasing hormone
Mechanism
Increases cerebrospinal fluid kynurenine levels. Kynurenine is an antagonist of N-methyl-D-aspartate receptor. In addition, it also increases the release of GABA
Dosage, efficacy
0.5 – 1 mg daily, intramuscular or intravenous for 1 – 4 weeks, 53.7% remission rate and 61.5% EEG improvement at 3 – 12 months follow-up.
12.Ganaxolone
Mechanism
Allosteric modulator of GABA receptors.
Dose, efficacy
Refractory infantile spasmodic seizures reduced by 50% up to 33% -50% with 36 mg/kg/day
Side effects
Well tolerated, mild side effects, sleepiness, diarrhea, vomiting, nervousness
13. Dexamethasone palmitate (liposteroid)
Dose, efficacy
0.25 mg/kg, refractory secondary infantile spasms in a study of 7 injections over 3 months, with complete remission in 5 cases after 4 doses. In another study, 12 injections over 1 month resulted in 1 remission in 4 cases and a 50% reduction in seizures in 2 cases.
Side effects
No significant side effects were observed.
14. Sulthiame Sulthiazide
Mechanism
Carbonic anhydrase inhibitor
Dose, efficacy
5 to 10 mg/kg/day, complete remission in 6 (30%) of 20 cases.
Side effects
vomiting, anorexia, diarrhea, sleepiness, irritability
15. Gammaglobulin
Dose, efficacy
100 – 200 mg/kg once every 2-3 weeks for 6-10 times. 6 cases of primary remission, one of 5 cases of secondary remission, and 2 cases of relapse after short-term remission were treated.
The treated cases remitted in 5 out of 23 cases after 1g/kg for 2 days and once every 3 weeks for 6 months.
16.Ketogenic diet therapy
Mechanism
Unknown, ketogenic diet restricts carbohydrate and energy intake. The ratio of fat to carbohydrate and protein is 2:1 to 5:1.
Usage, efficacy
In a four-year study of 23 patients with refractory epilepsy, there were 38%, 39%, 53%, and 46% seizure reductions of 90% or more at 3, 6, 9, and 12 months, respectively, and 3 remissions at 12 months; 67%, 72%, 93%, and 100% seizure reductions of 50% or more, respectively. Another observed remission rate reached 53.5% (23/43) and a 90% reduction in seizures reached 62.8% (27/43).
Side effects
Within 4 weeks of treatment initiation, there was transient dehydration, nausea, vomiting, diarrhea, constipation, malaise, hypoglycemia, hypercholesterolemia, hypertriglyceridemia, hyperuricemia, hypoproteinemia, hypomagnesemia, hyponatremia, decreased HDL concentration, hepatitis, acute pancreatitis, metabolic acidosis, hemolytic anemia, and Fanconi glomerular acidosis.
Late side effects include osteoporosis, renal calculi, cardiomyopathy, and iron deficiency anemia.
17. Biotin
Infantile spasms are occasionally associated with biotinase deficiency, and biotin therapy is effective; infantile spasms are occasionally associated with phenylketonuria, and low-phenylalanine diet and valproic acid or nitrovaline therapy are effective.
18.Surgery
Four cases of children with cortical dysplasia remitted after surgery. In another case, 15 out of 23 cases remitted, and the level of mental development was also improved.