West syndrome protocol.

Infantile spasms are a rare entity, and the first diagnostic challenge is to differentiate them from non-epileptic paroxysmal disorders of infants. The main tool available for this is home video recordings, so that the movement episodes can be assessed a posteriori by trained personnel.

If PNET is suspected, it is a priority to instruct the family in making video recordings for later review.

1. Process in case of a high degree of suspicion. In order to provide early attention to cases in which there is a high degree of suspicion, it is necessary to undergo hospital admission to perform complementary tests.
2. Diagnostic process in case of low level of suspicion. In those cases in which there is a low degree of suspicion, a telematic/in-person consultation can be requested at the high-resolution consultation, according to our referral criteria, for evaluation within approximately 1 week, accompanied by instructions for home video recording during this period of time, to be able to provide the video clips on the day of the visit.

There is discussion in the scientific community about the differences in the effectiveness of treatment with ACTH vs. corticosteroids.

The gold standard complementary study for diagnostic confirmation is the registry Ictal EEG.

In cases with the presence of hypsarrhythmia, the diagnosis will be immediate.

However, when hypsarrhythmia is not recorded, it is necessary to record at least one clinical event in order to exclude the diagnosis. When the episodes are very frequent, the diagnosis will not be difficult, but if they occur infrequently, it may be necessary to repeat the recording or even request a prolonged EEG recording.

The presence of episodes of jerks that generate muscle artifact are an important technical problem. To differentiate epileptic spasms from those episodes that do not require aggressive treatment, it is necessary to look for the presence of electrodecrement.

In our environment, as long as there are no supply problems, the use of ACTH seems reasonable, since the low prevalence of the disease does not impose a significant economic burden on the health system.

1. Neuroimaging tests: Once it is confirmed that these are infantile spasms, a neuroimaging test is mandatory. The neuroimaging study allows us to guide the etiology (in structural cases), and allows us to select the treatment (in cases secondary to tuberous sclerosis).
2. EClinical examination and directed anamnesis: It is necessary to emphasize the clinical history, carrying out systematic data collection, especially with regard to:
   • Family history.
   • Consanguinity.
   • History of neurodevelopment prior to the onset of spasms.
   • Complete perinatal history.
   • Regarding the clinical examination, it is especially important:
     • Dysmorphological assessment.
     • Skin assessment in search of stigmata of neurocutaneous diseases, including Wood's light.
     • General pediatric assessment that may suggest the presence of congenital errors of metabolism (failure to thrive, thinning hair, ichthyosis, hepatosplenomegaly, etc.).
3. Genetic studies. In the absence of guiding data for a specific pathology (Down syndrome, NF-1, tuberous sclerosis), aCGH is indicated as the first diagnostic step.
4. Other complementary examinations: Metabolic studies have a low diagnostic yield in infantile spasms. However, the existence of some treatable diseases forces them to be considered, especially in the event that there is data suggestive of autosomal recessive inheritance (consanguinity, other affected siblings) or indicative data in the clinical history. It is recommended, at a minimum, to collect urine for 24 hours to determine aminoadipic acid, as well as organic acids, given the ease of access to the sample. It may make sense to carry out acylcarnitines, as a screening for inborn errors of mitochondrial metabolism, especially with a view to the use of valproate later.

ACTH and corticosteroids.

Corticosteroids are the treatment of choice in low-income countries, their main advantage being their low economic cost. Its use at high doses is necessary to achieve an effect equivalent to ACTH. On the other hand, it has been shown that high-dose vs. low-dose ACTH regimens are equivalent, so its use has been standardized at low doses. There are no studies that provide information on the prevalence of adverse effects or the recurrence rate between both treatments.

The ACTH available in Europe is the synthetic one. The presentation of choice is tetracosactide in depot formulation, and there are 2 brands:

– Nuvachten depot 1mg/ml (100 IU) (national manufacturing, with supply problems). It is an oily solution that cannot be administered intravenously. IM administration only.

– Synachten depot 1mg/ml (100 IU) (imported for foreign medication), it is necessary to request through the registration form medications in special situations. It is an oily solution that cannot be administered intravenously. IM administration only.

– Synachten 0.25 mg/ml, it is an immediate release presentation intended for use in endocrinological functional tests. It is IV administration.

The established dose is 0.05 mg/kg/d (usually 0.25 mg= 1/4 of a vial) per day, every 24 hours, IM administration, for 2 weeks, and then wearing off.

1. Vigabatrin.

Vigabatrin is an irreversible inhibitor of GABA-transaminase, an antiepileptic drug used almost exclusively in the context of West syndrome, marketed under the brand name Sabrilex, in 500 mg sachets.

For its administration, it is necessary to dilute each sachet in 10 ml of SF for subsequent administration in an ascending regimen based on weight.

It is usually started at 50 mg/kg/day. The therapeutic goal is usually 100-150 mg/kg/day, in 2 doses. Maximum daily dose 200 mg/kg/day.

Treatment is maintained for 6 months, and is subsequently suspended, since the drug presents toxicity due to accumulation.

It is a very powerful GABAergic drug, with an irreversible effect, so care must be taken with the concomitant administration of other CNS depressant drugs.

1. Valproic acid.

Treatment with valproic acid is the treatment of choice for maintaining clinical remission. There is no consensus on the time of its introduction. In cases treated with ACTH the introduction will be earlier, in cases treated with vigabatrin, there is more time margin for its introduction. The objective of this treatment is its maintenance between 1 and 2 years after remission, in the event that relapses or other types of epileptic seizures do not appear, once treatment with ACTH or vigabatrin has to be withdrawn.

2. Monitoring of adverse effects:

Treatment with ACTH has multiple adverse effects: Among them:

– Arterial hypertension.

– Metabolic alkalosis.

– Predisposition to serious infections.

– Osteopenia.

– Cushing syndrome (full moon face, hirsutism, acne, etc.).

– Insomnia and irritability.

Treatment with ACTH requires daily administration IM in the morning or by hospital admission.

Taking advantage of the visits to H. de Dia, the following adverse effects are monitored:

– Day 1:

– Blood glucose, EAB, ions, blood count, GOT/GPT, CRP, Ca/P, TSH.

– BP, HR and temperature measurement

– Start prophylaxis with calcium/vitamin D (500 mg/400 IU) and Septrin (8/40 mg): 2.5 ml every 12 hours 3 days a week. Maintain throughout the corticosteroid treatment. – Check vaccination schedule and risk of tuberculosis (TBC)*

– Start ACTH 0.25 mg (0.05 mg/kg/d) IM, every 24 hours, in the morning (after taking constants).

– Days 2 to 7:

– Labstix urine (x glucosuria), temperature, daily BP and HR.

– EAB every 3 days.

– Continue daily ACTH. Monitor for signs of infection.

– Day 7: do basal EEG.

– No clinical or EEG response: maintain the same ACTH dose from day 7 to 14.

– If response, clinical or EEG: maintain the same dose every other day from day 7 to 14. Combine treatment with valproate, progressively up to 25 mg/kg/day.

– Days 8 to 14:

– Labstix daily urine, temperature, BP and HR.

– EAB every 3 days. – Continue ACTH. Monitor for signs of infection.

– Day 14: do basal EEG.

– No clinical or EEG response: introduce vigabatrin and slow decrease in ACTH in 2-3 weeks.

– If clinical or EEG response: start or maintain valproate and slow decrease in ACTH in 2-3 weeks (if daily treatment 2 weeks, decrease every other day for 1 week and 1 dose per week for another 2 weeks). Consider discharge and outpatient treatment.

– Days 15 to 21: labstix, temperature, BP on the day of the ACTH dose.

– Day 28: Control and follow-up EEG in Neuropediatric Consultation according to evolution

1. Complications severe neurological:
   1. Hyperammonemic encephalopathy due to valproate.

It is necessary to take into account that valproic acid may have more hepatic side effects in children under 2 years of age. Furthermore, valproic acid is contraindicated in mitochondrial diseases, which may eventually cause West syndrome, and we will not have an etiological diagnosis at the time of its onset. In case of clinical worsening after starting treatment (worsening of epilepsy, acute encephalopathy, vomiting, sepsis-like, etc.), consider requesting ammonium to rule out hyperammonemic encephalopathy due to valproate.

In some centers, treatment with carnitine supplements is used. There is no firm scientific evidence in this regard.

In some centers, treatment with coenzyme Q10 supplements is used. There is no firm scientific evidence in this regard.

The presence of this complication requires suspension of treatment.

1. Vigabatrin encephalopathy.

Treatment with vigabatrin at high doses or simultaneous treatment with ACTH and vigabatrin can produce progressive lethargy and drowsiness, which can affect vital functions and be life-threatening, associated with the presence of dyskinesias (extrapyramidal movement disorder).

It is necessary to closely monitor the level of consciousness, and if progressive worsening is observed, perform an MRI study, in which lesions characteristic of VABAM (vigabatrin associated brain anomalies on MRI) can be observed.

The presence of this complication requires suspension of treatment.