Eliane Roulet‐Perez

Background: A new monogenic neurodegenerative disease affecting ribosomal metabolism has recently been identified in association with a monoallelicUBTFputative gain of function variant (NM_001076683.1:c.628G>A, hg19). Phenotype is consistent among these probands with progressive motor, cognitive, and behavioural regression in early to middle childhood.Case presentation: We report on a child with this monoallelicUBTFvariant who presented with progressive disease including regression, episodes of subacute deterioration during febrile illnesses and a remarkable EEG pattern with a transient pattern of semi-periodic slow waves.Conclusions: This case further supports the phenotype-genotype correlation of neurodegeneration associated withUBTFc.628G>A. Moreover, it brings new insights into the clinical features and EEG that could possibly serve as diagnostic markers of this otherwise nonspecific phenotype.

Summary: Purpose: To present the long‐term follow‐up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike‐waves during slow wave sleep (CSWS).Methods: Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered.Key Findings: After a mean duration of follow‐up of 15.6 years (range, 8–23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short‐lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long‐term outcome correlated best with duration of CSWS.Significance: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.

Summary: Purpose:  Epilepsy surgery in young children with focal lesions offers a unique opportunity to study the impact of severe seizures on cognitive development during a period of maximal brain plasticity, if immediate control can be obtained. We studied 11 children with early refractory epilepsy (median onset, 7.5 months) due to focal lesion who were rendered seizure‐free after surgery performed before the age of 6 years.Methods:  The children were followed prospectively for a median of 5 years with serial neuropsychological assessments correlated with electroencephalography (EEG) and surgery‐related variables.Results:  Short‐term follow‐up revealed rapid cognitive gains corresponding to cessation of intense and propagated epileptic activity [two with early catastrophic epilepsy; two with regression and continuous spike‐waves during sleep (CSWS) or frontal seizures]; unchanged or slowed velocity of progress in six children (five with complex partial seizures and frontal or temporal cortical malformations). Longer‐term follow‐up showed stabilization of cognitive levels in the impaired range in most children and slow progress up to borderline level in two with initial gains.Discussion:  Cessation of epileptic activity after early surgery can be followed by substantial cognitive gains, but not in all children. In the short term, lack of catch‐up may be explained by loss of retained function in the removed epileptogenic area; in the longer term, by decreased intellectual potential of genetic origin, irreversible epileptic damage to neural networks supporting cognitive functions, or reorganization plasticity after early focal lesions. Cognitive recovery has to be considered as a “bonus,” which can be predicted in some specific circumstances.

Summary: To report the case of a child with short absences and occasional myoclonias since infancy who was first diagnosed with an idiopathic generalized epilepsy, but was documented at follow‐up to have a mild phenotype of glucose transporter type 1 deficiency syndrome. Unlike other reported cases of Glut‐1 DS and epilepsy, this child had a normal development as well as a normal head growth and neurological examination. Early onset of seizures and later recognized episodes of mild confusion before meals together with persistent atypical EEG features and unexpected learning difficulties led to the diagnosis. Seizure control and neuropsychological improvements were obtained with a ketogenic diet.