Abstracts

RATIONALE: Patients with progressive myoclonic epilepsy of the Unverricht-Lundborg type (EPM1) experience debilitating seizures and concomitant decline in physical functioning. Despite the nature and severity of the neurological and physical difficulties accompanying the disorder, early group studies indicated relatively slow cognitive decline and normal school functioning prior to onset of seizures and diagnosis. The presence of prominent emotional difficulties have also been described. However, interpretation of past studies is hampered by methodological and sample limitations including a focus on IQ alone and the use of non-genetically verified cases. We describe detailed psychometric data on cognitive and emotional functioining for three genetically verified cases studied from early childhood.
METHODS: The diagnosis was confirmed by molecular genetic testing in all 3 children, who represent all children diagnosed with EPM1 in a province of 4 million people in the past ten years. The patients had been followed clinically from early childhood to the ages of 21, 14, and 19 years, respectively. Cognitive assessments conducted over time were reviewed; Patient 1 had five assessments over 14 years, Patient 2 had three assessments over 6 years, and Patient 3 had two assessments over 1 year. School records were examined for evidence of academic delays prior to diagnosis.
RESULTS: The rate of cognitive deterioration in our cases was much more rapid than that of prior reports, with two cases undergoing a decline of over 5 IQ points per year. Along with a decline in IQ, all children had a pronounced relative drop in attention skills over time. However, one case had prominent attentional/executive dysfunction with intact memory skills, while the other two were primarily affected by memory problems. Psychological/psychiatric manifestations in these patients were mild and appeared to be secondary to the effects of chronic illness. All three children were found to have had learning difficulties in early elementary school prior to the diagnosis of EPM1.
CONCLUSIONS: Our results suggest (1) a more rapid rate of cognitive decline in EPM1 than has been described previously, (2) variability in the cognitive domains affected in EPM1, (3) milder emotional difficulties than those described by prior studies, and (4) early school problems suggesting that development may not be entirely normal prior to diagnosis, as was previously assumed. The results suggest that in some cases, EPM1 may be conceptualized as a progressive childhood dementia syndrome.