A 5.5-month-old female infant with tuberous sclerosis complex presented with infantile spasms and was treated with vigabatrin. As her condition did not improve, she was given adrenocorticotropic hormone (ACTH) intramuscularly which stopped the spasms and improved the electroencephalogram (EEG) abnormalities. However, she developed encephalopathy with apathy, drowsiness, and generalized slowing in the EEG. Discontinuation of vigabatrin quickly improved her symptoms and reversed the EEG slowing. A high index of suspicion is required in order to diagnose vigabatrin-induced encephalopathy, especially as the underlying disorders of these patients can be erroneously considered the cause of the observed encephalopathy.
Infantile spasms (IS) is a serious epileptic disorder that often leads to developmental regression and life-long disabilities [
A well-developed 5.5 month-old female infant was admitted in our department with semiology consistent with IS and confirmed on EEG testing which revealed hypsarrythmia. As she bore numerous hypomelanotic macules, brain imaging through Magnetic Resonance (MRI) was carried out revealing several brain hamartomas. She was diagnosed with TSC and was started on vigabatrin. Before initiation of vigabatrin, she was having more than five clusters of spasms per day. Despite her condition, she had reached the anticipated for her age, developmental milestones. Vigabatrin was administered with a starting dose of 50 mg/kg/d, and in two-week period, it was gradually increased to 120 mg/kg/d. The response to treatment was deemed unsatisfactory; therefore, synthetic adrenocorticotropic hormone (ACTH) was added in the treatment regimen and was administered intramuscularly. She remained hospitalized under close medical supervision and regular EEG follow-up. On the new treatment, her spasms gradually improved and the daily seizure count was greatly diminished. However, and despite the improvement in seizure control, she exhibited psychomotor regression along with signs and symptoms of encephalopathy. She was lethargic, unresponsive to acoustic and tactile stimuli, she was not smiling or rolling, and she exhibited head lag as well as head and upper limbs tremor. At that point, a repeat EEG revealed resolution of the hypsarrythmia, remained however significantly abnormal, and was dominated by diffuse slow delta rhythms of medium amplitude. A basic metabolic workup including ammonia, urine organic acids, and serum lactate and pyruvate was conducted with no abnormal findings. The administration of vigabatrin was stopped immediately, as it was considered a possible incriminating factor for the deterioration of the child’s condition. Shortly after the discontinuation of vigabatrin, a substantial clinical improvement was observed and the infant returned to her previous normal developmental status, thus suggesting the encephalopathy was vigabatrin-induced. A repeat EEG showed overall improvement with normal background rhythms and occasional epileptic spikes.
TSC is an autosomal dominant neurocutaneous genetic disorder of cellular differentiation and proliferation which variably affects the brain, skin, kidneys, heart, and other organs through the formation of hamartomas [
The central nervous system is one of the most commonly affected systems in TSC. Epilepsy, neurocognitive dysfunction, and pervasive developmental disorders, such as autism, are perhaps the most devastating and therapeutically challenging manifestations of this condition. Seizures are the most common neurological disorder affecting up to 90% of individuals. They usually manifest during the first year of life in TSC patients and are associated with brain structural abnormalities. A variety of seizure types have been documented, including IS, simple partial, complex partial, and generalized tonic-clonic seizures, with IS being the most common initial seizure subtype [
In conclusion, vigabatrin-induced encephalopathy is a rare complication that can affect infants with IS. It can even occur when the spasms are secondary to TSC where vigabatrin is considered the first-line therapy; therefore, a high index of suspicion for this condition has to be maintained.
Informed consent for the publication of the case was received from the guardians of the child.
An earlier version of the manuscript has been presented as conference abstract in the EPNS 2017—12th European Paediatric Neurology Society Congress, Lyon, France, 20–24 June 2017.
The authors declare that they have no conflicts of interest.
EK and IA drafted the manuscript, and all authors reviewed and approved it.
All authors acknowledge the critical contribution of Dr. G. Vartzelis in the clinical workup of the case.