Electro-clinical and neurodevelopmental outcome in six children with early diagnosis of tuberous sclerosis complex and role of the genetic background.

BACKGROUND: Seizures in individuals affected by tuberous sclerosis complex (TSC) commonly develop in the first year of life, are often preceded by a progressive deterioration of the electroencephalogram (EEG), and likely influence developmental outcome. Although early diagnosis of TSC has offered a tremendous opportunity to monitor affected patients before seizure onset, reports of the neurological manifestations of TSC in infants before seizure onset are still scarce. Here we describe early EEG activity, clinical and genetic data and developmental assessment in a group of TSC infants, with the aim of identifying possible prognostic factors for neurodevelopmental outcome. METHODS: We report on six infants diagnosed with TSC pre- or perinatally, who underwent serial Video-EEG recordings during the first two years of life. EEGs were classified based on distribution and intensity of interictal epileptiform discharges, and Vigabatrin was introduced in case of ictal discharges. Psychomotor development, cognitive functioning and behavioral problems were assessed through standardized scales. Molecular testing included analysis for point mutations and deletions/duplications in TSC1 and TSC2. RESULTS: EEG abnormalities appeared at a mean age of 4 months. Four of the six patients developed seizures. EEG abnormalities preceded the onset of clinical seizures in all of them. The two individuals with good seizure control showed normal development, while the other two exhibited psychomotor delays. The patients who did not develop seizures had normal development. A pathogenic variant in the TSC2 gene was detected in all patients but one. The one without a mutation identified did not develop seizures and showed normal neurodevelopment. Of note, the two patients presenting with the worst outcome (that is, poor seizure control and intellectual/behavioral disability) both carried pathogenic variants in the GAP domain of TSC2. CONCLUSION: Our report supports the importance of EEG monitoring before seizure onset in patients with TSC, and the correlation between prompt seizure control and positive neurodevelopmental outcome, regardless of seizure type. Our results also indicate a possible role of the genetic background in influencing the outcome.

Alexithymia partly predicts pain, poor health and social difficulties in patients with temporomandibular disorders.

Temporomandibular disorders (TMD) are functional diseases of the masticatory system; their symptoms are clicking, difficulty opening the mouth wide, ear pain, facial pain and headaches. The relationships among distress, emotional factors and TMD are well known. It was shown that patients with TMD have little awareness of their inner states and emotions, and it was found that those reporting oro-facial pain presented higher alexithymia than did asymptomatic people. Other authors confirmed that alexithymia was higher in the painful TMD group than controls. This study was aimed to evaluate whether alexithymia and its components can be considered as predisposing factors for pain severity, poor health and greater social difficulties in patients with TMD. One hundred thirty-three patients received a diagnosis of TMD and completed the 20-item Toronto Alexithymia Scale. Multiple stepwise regressions showed that alexithymia and age explained 10% of the pain and 31% of poor health and also that alexithymia explained 7% of social difficulty. A direct comparison of patients with TMD based on alexithymia revealed a higher presence of pain in alexithymic patients with TMD than in those characterised by moderate or no alexithymia. In conclusion, alexithymia partly predicts pain, poor health and social difficulties in patients with TMD. Furthermore, alexithymic patients have more pain than those with moderate or low alexithymia.