Review Question - QID 221322

This patient who presents with infantile spasms, developmental regression, and hypsarrhythmia on video-EEG most likely has West syndrome. West syndrome is caused in part by an excess of corticotropin-releasing hormone, which leads to increased neuronal excitability.

The pathogenesis of West syndrome is incompletely understood. Infantile spasms are often idiopathic, but may also be secondary to tuberous sclerosis, hypoxic-ischemic encephalopathy, congenital brain malformations, aminoacidopathies, and organic acidopathies. Brain insults may activate a neuroendocrine stress response, which in turn leads to abnormalities of the hypothalamic-pituitary-adrenal axis. Disturbed immune activation may also play a role. Patients will present with infantile spasms, developmental regression, and slowing and multifocal epileptiform discharges known as hypsarrhythmia. Many affected infants are responsive to ACTH therapy, with cessation of spasms and resolution of hypsarrhythmia in many cases.

D’Alonzo et al. review the epidemiology, clinical presentation, pathophysiology, and treatment of West syndrome. They discuss how patients will present with the classic symptoms of spasms and regression. They recommend early diagnosis of this syndrome so that patients can be treated appropriately.

Figure/Illustration A is an EEG demonstrating a chaotic pattern of slowing and multifocal epileptiform charges (red circle). This finding of hypsarrhythmia is classically seen in West syndrome.

Incorrect Answers:
Answer 2: Abnormalities in T-type calcium channels may contribute to absence seizures. Absence seizures are generalized seizures that involve brief, sudden lapses of consciousness and are more common in children. This child’s developmental regression, infantile spasms, and EEG findings are more consistent with West syndrome.

Answer 3: Anti-N-methyl-D-aspartate (NMDA) receptor antibodies may cause anti-NMDA encephalitis. Anti-NMDA encephalitis presents with seizures, psychiatric manifestations, and decreased level of consciousness.

Answer 4: Decreased gamma-aminobutyric acid (GABA) levels were once theorized to be the basis of epilepsy syndromes. This theory is less accepted today. Moreover, West syndrome is likely not mediated by disturbances in GABA. Nonetheless, vigabatrin, which in part works by inhibiting GABA metabolism, is an effective medication for patients with West syndrome.

Answer 5: Vitamin B6 deficiency has not been documented in West syndrome. Some studies have suggested vitamin B6 may be of some benefit in the treatment of infantile spasms; however, there is no evidence that response rates to B6 are different from the spontaneous remission rates predicted from natural history data. Therefore, the pathophysiology of West syndrome is more likely CRH-excess mediated rather than due to a deficiency of vitamin B6.

Bullet Summary:
West syndrome, which may be caused by CRH excess, presents with hypsarrhythmia, developmental regression, and infantile spasms.