Abstracts

Rationale: Abnormal signaling in the mammalian target of rapamycin (mTOR) pathway is critical for the pathophysiology of Tuberous Sclerosis Complex (TSC) and hemimegalencephaly (HME). TSC is an autosomal dominant multisystem disorder which involved genes are TSC1 and TSC2 - their loss of function leads to hyperactivation of the mTOR pathway. On the other hand, HME is a sporadic, nonfamilial disease without any skin abnormalities or visceral lesions, that is also a consequence of enhanced of the same pathway. The association of these two pathologies is rare and the patients who present it, tend to be a challenge to the physician. Methods: We present a clinical case of a girl with TSC and focal megalencephaly. She has hipocromic macules, right renal cyst, cardiac rhabdomyomas and positive family history for TSC - her mother is also affected. Her magnetic resonance scan (figure 1) demonstrates right frontocentroparietal transmantle dysplasia (focal megalencephaly), bilateral cortical tubers and subependimal nodules. She has begun seizures with 8 hours after birth - clonic movements of the left upper limb and lower limb, head and gaze version to the right with clonic movements of the head, during less than a minute, several times per day, refractory to antiepileptic drugs, until the present moment when she is 12 months-old. The videoelectroencephalogram shows spikes, sharp and slow waves at the right frontocentroparietal region and the same epileptic paroxysms at the left hemisphere, characterizing a multifocal pattern, worse at the right. Her recorded seizures always begin at the right frontocentral region and evolve to the rest of the hemisphere. Results: This association of HME and TSC was first reported in 1988 by Robain et al. More recent studies and reports have confirmed the occurrence of this association. They are both results of an activation of mTOR pathway, but it is still unclear the exact point of intersserction in the mTOR pathway where these two pathologies meet. Patients that present this association tend to be severely affected. They commonly develop epilepsy very early, present developmental delay and autistic features. The treatment of choice for HME is surgical resection. However, patient that has HME and TSC, frequently presents cortical tubers at the other hemisphere. This make this treatment option a difficult decision to the assistant doctor and the family, concerning the risks that are involved in the surgery and the high chance of seizures recurrence. A very important discussion about these patients is if the mTOR inhibitors are another option of treatment. Conclusions: The TSC and HME association is rare and there are no reports about the long-term outcome of patients who had undergone surgery. The treatment of these patients is still a great challenge - is resection indicated in patient that has epileptic lesions on the other hemisphere? Are mTOR inhibitors an option? More genetic studies are important to clarify the mechanisms of this association. Therefore, it is very valuable to open a broad discussion of these cases to better treat them and to improve their quality of life.