David L. Coulter

Conceptualizing Supports and the Support Needs of People With Intellectual Disability

This is the third in a series of perspective articles (Schalock et al., 2007; Wehmeyer et al., 2008) from the Terminology and Classification Committee of the American Association on Intellectual and Developmental Disabilities (AAIDD). The purpose of these articles is to share our thoughts on critical issues associated with terminology, definition, and classification in the field of intellectual disability and to seek input from the field as we prepare the 11th edition of AAIDD’s Diagnosis, Classification, and System of Supports Manual (the working title). In the first article (Schalock et al., 2007), we explained the reasons for shifting from the term mental retardation to intellectual disability. Although the two terms cover the same population of individuals, we concluded that intellectual disability was the better term because it

l‐Carnitine Supplementation in Childhood Epilepsy: Current Perspectives

Summary: In November 1996, a panel of pediatric neurologists met to update the consensus statement issued in 1989 by a panel of neurologists and metabolic experts on L‐carnitine supplementation in childhood epilepsy. The panelists agreed that intravenous L‐carnitine supplementation is clearly indicated for valproate (VPA)‐induced hepatotoxicity, overdose, and other acute metabolic crises associated with carnitine deficiency. Oral supplementation is clearly indicated for the primary plasmalemmal carnitine transporter defect. The panelists concurred that oral L‐carnitine supplementation is strongly suggested for the following groups as well: patients with certain secondary carnitine‐deficiency syndromes, symptomatic VPA‐associated hyperammonemia, multiple risk factors for VPA hepatotoxicity, or renal‐associated syndromes; infants and young children taking VPA; patients with epilepsy using the ketogenic diet who have hypocarnitinemia; patients receiving dialysis; and premature infants who are receiving total parenteral nutrition. The panel recommended an oral L‐carnitine dosage of 100 mg/kg/day, up to a maximum of 2 g/day. Intravenous supplementation for medical emergency situations usually exceeds this recommended dosage.

Review Article: Carnitine, Valproate, and Toxicity

Carnitine is an important nutrient that is present in the diet (particularly in meat and dairy products) and is synthesized from dietary amino acids. It functions to assist long-chain fatty acid metabolism and to regulate the ratio of free coenzyme A to acylcoenzyme A in the mitochondrion. Carnitine deficiency occurs in primary inborn errors of metabolism, in nutritional deficiency, and in various other disorders including antiepileptic drug therapy. Valproate therapy is often associated with decreased carnitine levels and occasionally with true carnitine deficiency. Some experimental and clinical evidence links valproate-induced carnitine deficiency with hepatotoxicity, but this evidence is limited and inconclusive. Carnitine supplementation has been useful in some studies, but these data are also limited. Young children with neurologic disabilities taking multiple antiepileptic drugs may have the greatest risk for carnitine deficiency. Measurement of carnitine levels appears warranted in these patients and in patients with symptoms and signs of possible carnitine deficiency. (J Child Neurol 1991;6:7-14).

The Intellectual Disability Construct and Its Relation to Human Functioning

The American Association on Intellectual and Developmental Disabilities’ (AAIDD) Terminology and Classification Committee has two primary purposes in publishing this Perspective: (a) to share our thinking about the construct underlying the term intellectual disability (henceforth the intellectual disability construct) and its relation to human functioning and (b) to ask for input from the field because the committee is preparing a proposal for the upcoming Definition, Classification and Systems of Supports manual, to be published in 2009 or 2010. The article has three sections. In the first section, we make a distinction between an operational definition, which operationalizes the intellectual disability construct and provides the basis for diagnosis and classification, and a constitutive definition, which explains the underlying construct and provides the basis for theory– model development and planning individualized supports. In the second section, we provide an historical overview of how the construct underlying the term mental retardation (henceforth, the mental retardation construct) differs from the construct underlying intellectual disability. In the third section, we describe the parameters to the proposed AAIDD theoretical framework of human functioning that reflects our current understanding of the multidimensionality of human functioning that underlies the intellectual disability construct and the significant role that individualized supports play in human functioning. The article concludes with a brief discussion of the benefits to the field that accrue from a clear understanding of both the differences between an operational and constitutive definition and the fundamental properties of the intellectual disability construct. Operational Versus Constitutive Definitions

Experience with lacosamide in a series of children with drug-resistant focal epilepsy

We report our pediatric experience with lacosamide, a new antiepileptic drug, approved by the US Food and Drug Administration as adjunctive therapy in focal epilepsy in patients more than 17 years old. We retrospectively reviewed charts for lacosamide use and seizure frequency outcome in patients with focal epilepsy (Wilcoxon signed rank test). Sixteen patients (7 boys) were identified (median dose 275 mg daily, 4.7 mg/kg daily; mean age 14.9 years, range 8-21 years). Patients were receiving a median of 2 antiepileptic drugs (interquartile range [IQR] 1.7-3) in addition to having undergone previous epilepsy surgery (n=3), vagus nerve stimulation (n=9), and ketogenic diet (n=3). Causes included structural (encephalomalacia and diffuse encephalitis, 1 each; stroke in 2) and genetic abnormalities (Aarskog and Rett syndromes, 1 each) or cause not known (n=10). Median seizure frequency at baseline was 57 per month (IQR 7-75), and after a median follow-up of 4 months (range 1-13 months) of receiving lacosamide, it was 12.5 per month (IQR 3-75), (P<0.01). Six patients (37.5%; 3 seizure free) were classified as having disease that responded to therapy (≥50% reduction seizure frequency) and 10 as having disease that did not respond to therapy (<50% in 3; increase in 1; unchanged in 6). Adverse events (tics, behavioral disturbance, seizure worsening, and depression with suicidal ideation in 1 patient each) prompted lacosamide discontinuation in 4/16 (25%). This retrospective study of 16 children with drug-resistant focal epilepsy demonstrated good response to adjunctive lacosamide therapy (median seizure reduction of 39.6%; 37.5% with ≥50% seizure reduction) without severe adverse events.

Carnitine Deficiency in Epilepsy: Risk Factors and Treatment:

16. Murakawa H, Bland CE, Willis WT, Dallman PR: Iron deficiency and neutrophil function: Different rates of correction of the depressions in oxidative burst and myeloperoxidase activity after iron treatment. Blood 1987;69:1464-1468. 17. Walter T, Arrendondo S, Arevalo M, Stekel A: Effects of iron therapy on phagocytosis and bactericidal activity in neutrophils or iron-deficient infants. Am J Clin Nutr 1986;44:877-882. 18. Gruener N, Gozlan O, Goldstein P, et al: Iron, transferrin and ferritin in cerebrospinal fluid in children. Clin Chem 1991;37: 263-265.

Neurotrichosis: Hair‐shaft Abnormalities associated with Neurological Diseases

Six children with morphological hair‐shaft abnormalities and neurological disease are presented, including two with Pollitt syndrome, one with biotin deficiency, two with Menkes diseases and one with argininosuccinic aciduria. The child with biotin deficiency grew normal hair following oral biotin therapy. Although the hair‐shaft abnormalities may be seen with light microscopy (LM), they are best visualised with scanning electron‐microscopy (SEM). Pili torti may be mistaken for monilethrix by LM, but SEM shows the true defect. A review of the literature shows that these hair‐shaft abnormalities (trichorrhexis nodosa, monilethrix and pili torti) are not specific or pathognomonic, but do indicate a group of neurological disorders, including potentially treatable inborn errors of metabolism. The term ‘neurotrichosis’ is suggested to classify this group of disorders.

Rufinamide for the treatment of epileptic spasms

OBJECTIVE The purpose of this study was to determine the safety and efficacy of rufinamide for treatment of epileptic spasms. METHODS We retrospectively reviewed patients treated with rufinamide for epileptic spasms from January 2009 to March 2010. Age, presence of hypsarrhythmia, change in seizure frequency following rufinamide initiation, and side effects were assessed. Patients who had a ≥ 50% reduction in spasm frequency were considered responders. RESULTS Of all 107 children treated with rufinamide during the study period, 38 (36%) had epileptic spasms. Median patient age was 7 years (range: 17 months to 23). One patient had hypsarrhythmia at the time of treatment with rufinamide, and 9 other patients had a history of hypsarrhythmia. Median starting dose of rufinamide was 9 mg/kg/day (range: 2-18) and median final treatment dose was 39 mg/kg/day (range: 8-92). All patients were receiving concurrent antiepileptic drug therapy, with the median number of antiepileptic drugs being 3 (range: 2-6). Median duration of follow-up since starting rufinamide was 171 days (range: 10-408). Responder rate was 53%. Median reduction in spasm frequency was 50% (interquartile range=-56 to 85%, P<0.05). Two patients (5%) achieved a >99% reduction in spasms. Rufinamide was discontinued in 7 of 38 patients (18%) because of lack of efficacy, worsening seizures, or other side effects. Minor side effects were reported in 14 of 38 patients (37%). CONCLUSIONS Rufinamide appears to be a well-tolerated and efficacious adjunctive therapeutic option for children with epileptic spasms. A prospective study is warranted to validate our observations.

Comprehensive Management of Epilepsy in Persons with Mental Retardation

Summary: Epilepsy is a common occurrence in persons with mental retardation. The application of recent advances in epilepsy research to patients with mental retardation has shown that well‐accepted principles of management are as relevant for multiply handicapped people as for those with epilepsy alone. Quality enhancement is emphasized as the overarching concept that determines the quality of care provided to patients with epilepsy and mental retardation. This article reviews the comprehensive management of epilepsy, discusses what is known at present, and indicates what is not known and needs further research.

CARDIAC MANIFESTATIONS IN A CHILD WITH A NOVEL MUTATION IN CREATINE TRANSPORTER GENE SLC6A8

The creatine-phosphocreatine shuttle serves to maintain a high-energy phosphate supply for normal cellular function. Most creatine is derived from the diet; the rest is synthesized primarily in the liver, pancreas, and kidneys. The transport of creatine in tissues is accomplished by the Na+-dependent transporter SLC6A8. Expression of the SLC6A8 gene is high in skeletal muscle, heart, and kidney, moderate in brain, and extremely low in liver and pancreas. X-linked creatine transporter (Crt) defect (OMIM 300352), originally described in 2001,1 has been linked to mutations in the SL6CA8 gene at Xq28. SLC6A8 deficiency may comprise up to 1% of cases of mental retardation of unknown etiology in males.2 Intellectual disability is the uniform feature in patients with creatine-deficiency syndromes.3,4 Some patients also have epilepsy, extrapyramidal movement disorder, failure to thrive, and sometimes autism and other behavioral problems.4 We report a novel mutation in the SLC6A8 gene in an 11-year-old boy with Crt defect, who presented with multiple premature ventricular contractions (PVCs) in the second year of life. ### Case report. This male child had poor weight gain since birth. By 18 months of age his weight dropped below the fifth percentile and he was admitted for investigation. When given midazolam IV and topical lidocaine before an endoscopy, he immediately developed frequent PVCs (bigeminy …