Cognitive and functional outcomes after a trial of an mTOR inhibitor in an adolescent with neuropsychiatric sequelae of TSC

Abstract

Tuberous sclerosis complex (TSC) is a genetic autosomal dominant condition with multi-organ involvement and highly variable clinical manifestations. Neurological manifestations (subependymal nodules, cortical tubers, and subependymal giant cell astrocytomas [SEGAs]) are a leading cause of morbidity and mortality leading to cognitive impairment, behavioural disturbances and refractory seizure disorders. Experimental and human evidence suggest that the use of mTOR inhibitors may induce regression of TSC tumor types and provide an alternative to surgical resection of SEGA's. In the EXIST-1 trial everolimus (mTORi) was associated with clinically meaningful increases in the time to progression of subependymal giant cell astrocytomas and skin lesion response rate compared with placebo. We present a case of a 16-year-old girl (MM) referred with neuropsychiatric sequelae including disruptive and dangerous behaviours not responding to outpatient management. Multiple trials of anti-convulsants and antipsychotic treatments achieved poor responses. During admission to a state facility, MM had several seizures followed by aggressive outbursts, inappropriate behaviour and confusion. Her intrusiveness, sexual disinhibition and lack of response inhibition suggested frontal lobe dysfunction impacting on executive functioning. Despite seizure control being optimized to an acceptable rate with anticonvulsants, improvement in social or cognitive functioning was limited. She required individual constant supervision for personal safety and independent functioning. A trial of mTor inhibitor was initiated, and achieved an improvement in cognitive, social and psychiatric functioning. This report will discuss the challenges in this complex case, and report on baseline as well as 6month post medication outcomes measured by radiological, functional and cognitive testing.

Disclosure of interest

The authors have not supplied their declaration of competing interest.