Introduction

Infantile spasms are epileptic spasms that occur in infancy or early childhood. These spasms are classically characterized clinically by symmetric, brief jerking spells that involve the head, neck, arms, legs, and abdomen which may consist of flexion, extension, or a combination of flexion-extension. Infantile spasms often are associated with a characteristic pattern on electroencephalogram (EEG) called hypsarrhythmia. When the triad of infantile spasms, hypsarrhythmia, and developmental regression occur together, this triad is termed West Syndrome.[1][2][3]

Etiology

Etiologies of possible of infantile spasms vary widely. With modern testing capabilities, the etiology of infantile spasms is identified in approximately two-thirds of patients. A variety of structural abnormalities often visualized on MRI can cause infantile spasms. Additionally, variations of genetic and metabolic problems can cause infantile spasms. However, idiopathic cases of infantile spasms are not infrequent.[4][5][6][7]

Epidemiology

Infantile spasms initially are diagnosed in children younger than 12 months of age in 90% of cases. The peak incidence of new diagnoses is between approximately 4 and 7 months of age. There is no predilection for a specific gender or race. When children who are older than 12 months present with spells resembling infantile spasms, they typically are classified as epileptic spasms. Once spasms begin, the natural history is for continued spasms or an increase in spasms over time. Without treatment, the frequency of spasms typically does not wax and wane, such that the patient has long symptom-free periods, as a patient might with other seizure types.[8][9]

Pathophysiology

The pathophysiology of infantile spasms is not well understood. With an extremely broad range of possible structural, metabolic, and genetic etiologies, there is speculation as to whether a common mechanism exists that results in this unique epilepsy syndrome.

History and Physical

Children with infantile spasms experience brief jerking spells of flexion, extension, or combination of flexion-extension of the head, neck, arms, legs, and trunk that usually last a few seconds or less. These spasms often occur in clusters and clusters often occur during sleep-wake transitions. Spasms also are seen more frequently during waking hours than during sleep. Patients return to a baseline mental state within seconds after the spasm. Some children may appear scared or upset by the clusters of spasm activity. Evidence of developmental delay or regression may be apparent on history and physical exam, although patients who come to medical attention shortly after the onset of spasms may still be developmentally normal. Otherwise, a physical exam is often unremarkable, although a careful skin exam is necessary to screen for possible underlying genetic disorders such as neurocutaneous disorders known to cause infantile spasms. Tuberous sclerosis is one such neurocutaneous disorder that is often associated with infantile spasms.

Evaluation

After identification of a spell that is concerning for infantile spasms, a patient should undergo an EEG evaluation to assess for the classic background of hypsarrhythmia. An EEG which captures the spells of concern, as well as the time between the spells of concern, is ideal. If by history, physical exam, and EEG evaluation, the patient is felt to have a diagnosis of infantile spasms, additional testing is necessary to investigate underlying etiologies. MRI brain scans should be completed first as this is the highest yield tool in identifying an underlying etiology of infantile spasms. If MRI is normal, additional genetic and metabolic screening tests are needed for further evaluation. Typically, these are performed on the blood, urine, and spinal fluid.

Treatment / Management

The two primary treatment options in the United States for infantile spasms are corticotropin (ACTH) and vigabatrin. Other steroid regimens sometimes are administered, and additional steroid regimens are being studied. Other antiepileptic medications are utilized at times; however, these medications are not considered standard first-line treatment. Developmental delay and regression is a significant comorbidity of infantile spasms, and appropriate therapies to maximize development should be utilized. [10][11][12]

Infantile spasms often are difficult to treat with some patients needing a repeat course of therapy or a second therapy. Response to therapy is followed by evaluating for ongoing clinical spasm events and periodically re-evaluating EEG findings. If an underlying etiology for the spasms is identified, treatment of this etiology is important as well. This may include surgical intervention for a focal abnormality identified on imaging or, if available, targeted therapy for an underlying genetic or metabolic disease. The timing of surgical intervention should be discussed among the medical team as such surgeries may delay the use of ACTH and/or other steroid therapies.

Differential Diagnosis

• Benign myoclonus of early infancy

• Congenital infections

• Epilepsy in children with mental retardation

• Epileptic ad epileptiform encephalopathies

• Hydrocephalus

• Hydranencephaly

• Incontinentia pigmenti

• Sturge weber syndrome

• Trisomy 21

• Tuberous sclerosis

Pearls and Other Issues

The overall prognosis of children with infantile spasms is poor. Up to 50% have long-term developmental and neurologic deficits. Many continue to have seizures, although the spasms may evolve into other types of seizures as the patient ages. These seizure types are also often hard to control with standard treatments. Patients with no specific underlying etiology (cryptogenic) tend to have better neurologic and developmental outcomes than patients with other significant underlying etiologies. Observational studies suggest that initiating therapy soon after infantile spasms start confers a better possibility of a good neurologic and developmental outcome.

Close follow-up of a patient with spells concerning for infantile spasms is important. Occasionally, if a patient is evaluated by EEG for spasms early in the clinical course, hypsarrhythmia may not have developed. A repeat EEG a few weeks later may reveal the classic hypsarrhythmia finding. When there is clinical suspicion for infantile spasms, a patient needs close follow-up.

Variants of the classic infantile spasm presentation do exist as well. As above, the classic hips arrhythmia finding may not be present on EEG at the time of initial evaluation. Additionally, this finding may be intermittent. This is more likely to occur early in the clinical course.  Therefore, a longer EEG study may be helpful in identifying if intermittent background changes on EEG exist. Furthermore, a variant of hypsarrhythmia called modified hypsarrhythmia may be seen. In this rare situation, EEG background amplitude is not as high as what is typically seen in hypsarrhythmia. Patients in this situation still merit aggressive treatment as is provided in more typical cases of infantile spasms. Lastly, there are cases reported of clinical infantile spasms where hypsarrhythmia is not seen. Given the high morbidity associated with this condition, it is prudent to use clinical judgment even when unexpected EEG findings occur.

Enhancing Healthcare Team Outcomes

The management of West syndrome is with an interprofessional team that includes neurology nurses and pharmacists. The treatment of West syndrome is not satisfactory and most infants have severe developmental delay and neurological deficits. Many therapies have been tried but none has so far been shown to work with any consistency. Because the infants are frail, surgery should be a last option. Surgery is also associated with many serious complications, which add further morbidity.