Tanjala T Gipson1, Gwendolyn Gerner2, Siddharth Srivastava3, Andrea Poretti4, Rebecca Vaurio5, Adam Hartman6, Michael V Johnston7. 1. Tuberous Sclerosis Clinic, Kennedy Krieger Institute, Baltimore, Maryland; Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland; Clinical Trials Unit, Hugo W. Moser Research Institute, Inc., Kennedy Krieger Institute, Baltimore, Maryland; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: tsclinic@kennedykrieger.org. 2. Tuberous Sclerosis Clinic, Kennedy Krieger Institute, Baltimore, Maryland; Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland; Clinical Trials Unit, Hugo W. Moser Research Institute, Inc., Kennedy Krieger Institute, Baltimore, Maryland. 3. Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland. 4. Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland. 5. Department of Neuropsychology, Kennedy Krieger Institute, Baltimore, Maryland; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland. 6. Department of Neurology, The John M. Freeman Pediatric Epilepsy Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. 7. Tuberous Sclerosis Clinic, Kennedy Krieger Institute, Baltimore, Maryland; Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland; Clinical Trials Unit, Hugo W. Moser Research Institute, Inc., Kennedy Krieger Institute, Baltimore, Maryland; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abstract
BACKGROUND: Infants born with tuberous sclerosis complex, a genetic condition resulting from a mutation in TSC1 or TSC2, are at increased risk for intellectual disability and/or autism. Features of epilepsy, neuropathology, genetics, as well as timing and type of mechanism-based medications have been proposed as risk factors. Neurodevelopmental outcomes have been reported among these studies; however, few include data about the individuals' early neurodevelopmental profile, a factor that may contribute significantly to these outcomes. Further, there is no clinical standard for the neurodevelopmental assessment of these infants. The paucity of data regarding the natural history of neurodevelopment in infants with tuberous sclerosis complex and the lack of a gold standard for neurodevelopmental evaluation present a significant challenge for clinicians and researchers. METHOD: During the first year of life, we tracked the onset of infantile spasms, the type and timing of antiepileptic treatments, and the associated response of two age-matched infants with tuberous sclerosis complex. We also employed Capute Scales as a part of a structured neurodevelopmental evaluation to characterize and compare their neurodevelopmental profiles. RESULTS: Infant 1 developed infantile spasms with confirmed hypsarrhythmia at 4 months of age. Treatment with vigabatrin was initiated within 24 hours with near immediate cessation of seizures and no further seizures to date. Expressive language delay was detected at 12 months and treated with speech and/or language therapy. Infant 2 developed complex partial seizures at 1 month. Treatment included levetiracetam, oxcarbazepine, and the ketogenic diet. Vigabatrin was initiated on detection of hypsarrhythmia after 4 months. Intractable epilepsy persists to date. Global developmental delay was evident by 8 months and treated with physical, occupational, and speech and/or language therapy. CONCLUSION: Many risk factors have been associated with intellectual disability and/or autism in individuals with tuberous sclerosis complex; however, few data are available regarding practical clinical tools for early identification. In our case series, inclusion of the Capute Scales as a part of routine medical care led to the identification of developmental delays in the first 12 months of life and selection of targeted neurodevelopmental interventions. Development of a risk-based assessment using this approach will be the focus of future studies as it may provide a potential window of opportunity for both research and clinical purposes. In research, it may serve as an objective outcome measure. Clinically, this type of assessment has potential for informing clinical treatment decisions and serving as a prognostic indicator of long-term cognitive and psychiatric outcomes.
BACKGROUND:Infants born with tuberous sclerosis complex, a genetic condition resulting from a mutation in TSC1 or TSC2, are at increased risk for intellectual disability and/or autism. Features of epilepsy, neuropathology, genetics, as well as timing and type of mechanism-based medications have been proposed as risk factors. Neurodevelopmental outcomes have been reported among these studies; however, few include data about the individuals' early neurodevelopmental profile, a factor that may contribute significantly to these outcomes. Further, there is no clinical standard for the neurodevelopmental assessment of these infants. The paucity of data regarding the natural history of neurodevelopment in infants with tuberous sclerosis complex and the lack of a gold standard for neurodevelopmental evaluation present a significant challenge for clinicians and researchers. METHOD: During the first year of life, we tracked the onset of infantile spasms, the type and timing of antiepileptic treatments, and the associated response of two age-matched infants with tuberous sclerosis complex. We also employed Capute Scales as a part of a structured neurodevelopmental evaluation to characterize and compare their neurodevelopmental profiles. RESULTS:Infant 1 developed infantile spasms with confirmed hypsarrhythmia at 4 months of age. Treatment with vigabatrin was initiated within 24 hours with near immediate cessation of seizures and no further seizures to date. Expressive language delay was detected at 12 months and treated with speech and/or language therapy. Infant 2 developed complex partial seizures at 1 month. Treatment included levetiracetam, oxcarbazepine, and the ketogenic diet. Vigabatrin was initiated on detection of hypsarrhythmia after 4 months. Intractable epilepsy persists to date. Global developmental delay was evident by 8 months and treated with physical, occupational, and speech and/or language therapy. CONCLUSION: Many risk factors have been associated with intellectual disability and/or autism in individuals with tuberous sclerosis complex; however, few data are available regarding practical clinical tools for early identification. In our case series, inclusion of the Capute Scales as a part of routine medical care led to the identification of developmental delays in the first 12 months of life and selection of targeted neurodevelopmental interventions. Development of a risk-based assessment using this approach will be the focus of future studies as it may provide a potential window of opportunity for both research and clinical purposes. In research, it may serve as an objective outcome measure. Clinically, this type of assessment has potential for informing clinical treatment decisions and serving as a prognostic indicator of long-term cognitive and psychiatric outcomes.
Authors: Ayla Humphrey; Cathy MacLean; George B Ploubidis; Yael Granader; Michelle Clifford; Maisy Haslop; Brian G R Neville; John R W Yates; Patrick F Bolton Journal: Epilepsia Date: 2014-01-13 Impact factor: 5.864
Authors: Kit Sing Au; Aimee T Williams; E Steve Roach; Lori Batchelor; Steven P Sparagana; Mauricio R Delgado; James W Wheless; James E Baumgartner; Benjamin B Roa; Carolyn M Wilson; Teresa K Smith-Knuppel; Min-Yuen C Cheung; Vicky H Whittemore; Terri M King; Hope Northrup Journal: Genet Med Date: 2007-02 Impact factor: 8.822