WEST SYNDROME (INFANTILE SPASMS)

Introduction

West Syndrome is a severe epilepsy syndrome of infancy characterized by the triad of symptoms: Infantile spasms, Hypsarrhythmia EEG Pattern, Severe intellectual disability.

History

Infantile Spasms were first described by Dr. W. J West in the early 1840’s. He witnessed what he described as “Bobbing” events noting quick Tonic-Clonic movements of the head occurring in clusters over the span of three minutes.

It wasn’t until nearly 100 years later that the interictal EEG pattern termed Hypsarrhythmia would be connected with the clinical symptoms that Dr. West had described as “Infantile spasms.” The infantile spasms in conjunction with the Hypasarrhythmia EEG pattern would later be termed “West Syndrome.”

Symptoms

As mentioned previously, West Syndrome is classically characterized by the “Triad” of symptoms: Infantile spasms, Hypsarrhythmia EEG pattern, Severe intellectual disability.

Infantile Spasms

Infantile spasms are the characteristic clinical symptom observed during the Ictal period. Infantile spasms are typically broken down into two categories known as the flexor spasm and extensor spasm. The flexor spasm involves the contraction of the flexor muscles in the neck, trunk and limbs that has been described as a “Self-Hugging” motion. The extensor spasm is described as the lateral extension of the neck and truck away from the body. Infantile spasms are also known as Jackknife seizures.

Hypsarrhythmia

The Hypsarrhythmia pattern is observed during interictal-EEG.

The Hypsarrhythmia pattern is described as a

• High voltage (>300μV)
• Multi-focal
• Slow waves with superimposed spike & wave discharges

Ralphelg, CC BY-SA 3.0, via Wikimedia Commons
Figure 1.1 Awake interictal EEG showing disorganized high amplitude spike and wave compatible with Hypsarrhythmia.

From “The Pediatric EEG”, by David Valentine M.D., 2020, (https://www.learningeeg.com/pediatric). Copyright 2020 by David Valentine

Figure 1.2 Hypsarrhythmia pattern showing multifocal discharges.

Severe Intellectual Disability

In West Syndrome, studies have shown that ~70% of patients have significant intellectual delay. Evidence suggests that longer duration of spasms (Increased seizure frequency) is correlated with worse intellectual outcomes. Even in the case of spontaneous remission of West Syndrome, developmental prognosis is often unfavorable.

Classification of disease

West Syndrome tends to have two classifications of diagnoses pertaining to the origin of disease.

Idiopathic: Suspected to account for ~9-14% of diagnosed West Syndrome. This diagnosis is only given if there is normal development prior to onset of seizures, and there is no suspected underlying disorder.

Cryptogenic: Accounts for the majority of West Syndrome diagnoses. Typically in the case of West Syndrome, this diagnosis indicates that an underlying symptomatic cause is at play, but lacks official diagnosis.

Genetic Factors: Certain genes have been identified as being contributory to West Syndrome. These include the:

• TSC 1 & 2 genes (Known to cause Tuberous Sclerosis which is an autosomal dominants disease associated with another epilepsy syndrome, Sturge-Weber)
• ARX & CDKL5 genes (Both located on the X chromosome with evidence to suggest that a higher incidence of West Syndrome is associated with these genes)

Treatments & Prognosis

Prognosis of West Syndrome is poor and directly related to the severity of disease. Severe intellectual disability is present in nearly 70% of patients. Infantile spasms rarely last until adulthood as in ~50-70% of patients develop another seizure disorder. The evolution from West Syndrome to Lennox-Gastaut syndrome being the most common evolution.

Typical anti-epileptic drugs are often ineffective in patients with West Syndrome. The complete reduction of seizures in patients with West Syndrome is rare and treatment usually aims to decrease seizure frequency but rarely aims to keep patients seizure free.

Typical medications used in the treatment of West Syndrome include ACTH, Vigabatrin, and Corticosteroids. Often times multiple medications will be used together to decrease seizure frequency.

Another common treatment in West Syndrome is the Ketogenic diet. Studies have shown that in conjunction with ACTH, the Ketogenic diet reduced seizure frequency in nearly 65% of patients.