Antigone S. Papavasiliou

Management of motor problems in cerebral palsy: A critical update for the clinician

Currently there is no specific treatment for the brain insults leading to motor dysfunction in cerebral palsy. The available symptomatic therapeutic options place cerebral palsy among the costliest chronic childhood conditions. Therefore, it is necessary to make well-informed decisions in an effort to match cost-effectiveness with patient and family needs. This presentation aims to analyze the efficacy of rehabilitation therapy, orthoses, oral medications, botulinum toxin, intrathecal baclofen, complementary or alternative treatments and discuss guidelines for a goal oriented approach. Despite insufficient reporting of trials, physiotherapy has shifted from traditional to goal oriented approaches, based on principles of motor learning, strength and fitness training. Correct choice and use of orthoses is stressed, yet evidence from primary studies is limited. Pharmacological treatments of spasticity (oral agents, botulinum toxin, intrathecal baclofen) may be alternatives or supplements to orthopaedic surgery. There is evidence that botulinum toxin combined with conservative treatments reduces the number of complex orthopaedic interventions. Intrathecal baclofen effectively reduces spasticity; criteria describing the ideal candidate are needed. Complementary or alternative treatment use is widespread; research needs to determine what factors make these modalities desirable and effective in cerebral palsy. It is concluded that the introduction of new therapies facilitates an individualized management plan. Multimodal treatment is optimized with a multidisciplinary team. Outcome measurement according to the World Health Organizations new International Classification of Functioning, Disability and Health is emphasized.

Written language skills in children with benign childhood epilepsy with centrotemporal spikes

PURPOSE The goal of this work was to study written language skills in children with benign childhood epilepsy with centrotemporal spikes (BCECTS) in the absence of atypical clinical or electroencephalographic (EEG) features (n = 32), as compared with controls (n = 36). METHODS BCECTS patients (7-16 years), attending regular school, without cognitive or behavioral regression, or atypical EEG patterns, completed four tests assessing written language skills and one nonverbal cognitive test. School performance information was recorded. Seizure types, duration, and frequency; awake and sleep interictal EEG findings; and medication status were documented. Epilepsy and educational outcome was recorded for a period of 1-5 years after diagnosis. RESULTS As a group, BCECTS patients performed significantly worse than controls in spelling, reading aloud, and reading comprehension; presented dyslexic-type errors; and frequently had below-average school performance. Among 11 with poor written language performance, 4 had developmental dysfunctions before school and seizure onset and, as a group, demonstrated low performance on a nonverbal cognitive test. Even though 65.6% were on anticonvulsants due to frequent seizures and/or seizures while awake, none belonged to the atypical BCECTS spectrum with respect to clinical or EEG findings. Increased epilepsy duration and seizure frequency were less represented in patients with no or mild written language problems than in those with poor performance. Otherwise, clinical course and EEG findings in this group were no different than those for the 11 children with severe written language problems. Clinical follow-up indicated that learning problems appear persistent and several children require remedial classes and/or tutoring after the epilepsy has resolved. CONCLUSIONS Children with severe but not atypical BCECTS performed, as a group, significantly worse than controls in written language skills, specifically in spelling, reading, aloud and reading comprehension; they also presented many difficulties also found in children with dyslexia. However, poor written language performance was not considered specific to BCECTS because it occurred in children with generally low cognitive capacity and/or preexisting developmental dysfunctions. Moreover, a dissociation between epilepsy outcome and learning problem outcome, in the subgroup with poor performance, casts doubt on the existence of a possible causal link between BCECTS and educational performance.

Myocardial inflammation in Duchenne Muscular Dystrophy as a precipitating factor for heart failure: a prospective study

BackgroundIn patients with Duchenne Muscular Dystrophy (DMD), the absent or diminished dystrophin leads to progressive skeletal muscle and heart failure. We evaluated the role of myocardial inflammation as a precipitating factor in the development of heart failure in DMD.Methods20 DMD patients (aged 15-18 yrs) and 20 age-matched healthy volunteers were studied and followed-up for 2 years. Evaluation of myocarditis with cardiovascular magnetic resonance imaging (CMR) was performed using STIR T2-weighted (T2W), T1-weighted (T1W) before and after contrast media and late enhanced images (LGE). Left ventricular volumes and ejection fraction were also calculated. Myocardial biopsy was performed in patients with positive CMR and immunohistologic and polymerase chain reaction (PCR) analysis was employed.ResultsIn DMD patients, left ventricular end-diastolic volume (LVEDV) was not different compared to controls. Left ventricular end-systolic volume (LVESV) was higher (45.1 ± 6.6 vs. 37.3 ± 3.8 ml, p < 0.001) and left ventricular ejection fraction (LVEF) was lower (53.9 ± 2.1 vs. 63 ± 2.4%, p < 0.001). T2 heart/skeletal muscle ratio and early T1 ratio values in DMD patients presented no difference compared to controls. LGE areas were identified in six DMD patients. In four of them with CMR evidence of myocarditis, myocardial biopsy was performed. Active myocarditis was identified in one and healing myocarditis in three using immunohistology. All six patients with CMR evidence of myocarditis had a rapid deterioration of left ventricular function during the next year.ConclusionsDMD patients with myocardial inflammation documented by CMR had a rigorous progression to heart failure.

Efficacy and tolerability of oral lacosamide as adjunctive therapy in pediatric patients with pharmacoresistant focal epilepsy

The results of adjunctive lacosamide treatment in 18 pediatric patients with pharmacoresistant focal epilepsy are reported. All had severe forms of focal epilepsy with or without secondary generalization and were concurrently receiving one to three other antiepileptic drugs. Lacosamide was administered orally, and final dose, after slow titration, ranged between 1.7 and 10 mg/kg. Mean treatment duration was 8 months (range=3 weeks-17 months). Treatment efficacy was assessed at two time points with a 1-year interval. The reported greater than 50% reduction in seizure frequency was 36% in the initial short-term and 20% in the following long-term assessment. Side effects, mostly somnolence and irritability, were reported by 39% of patients in both evaluations. Our data suggest that lacosamide treatment in pediatric patients is safe at doses up to 10 mg/kg/day without any major side effects, but studies in larger series are needed to validate and extend these findings.

Safety of Botulinum Toxin A in Children and Adolescents with Cerebral Palsy in a Pragmatic Setting

This retrospective study aimed to examine the safety of botulinum toxin A (BoNT-A) treatment in a paediatric multidisciplinary cerebral palsy clinic. In a sample of 454 patients who had 1515 BoNT-A sessions, data on adverse events were available in 356 patients and 1382 sessions; 51 non-fatal adverse events were reported (3.3% of the total injections number, 8.7% of the patients). On five occasions, the adverse reactions observed in GMFCS V children were attributed to the sedation used (rectal midazolam plus pethidine; buccal midazolam) and resulted in prolongation of hospitalization. Of the reactions attributed to the toxin, 23 involved an excessive reduction of the muscle tone either of the injected limb(s) or generalized; others included local pain, restlessness, lethargy with pallor, disturbance in swallowing and speech production, seizures, strabismus, excessive sweating, constipation, vomiting, a flu-like syndrome and emerging hypertonus in adjacent muscles. Their incidence was associated with GMFCS level and with the presence of epilepsy (Odds ratio (OR) = 2.74 − p = 0.016 and OR = 2.35 − p = 0.046, respectively) but not with BoNT-A dose (either total or per kilogram). In conclusion, treatment with BoNT-A was safe; adverse reactions were mostly mild even for severely affected patients. Their appearance did not necessitate major changes in our practice.

Psychogenic status epilepticus in children

Epilepsy features, psychiatric profile, psychosocial factors, and outcome are described for six children (three males) aged 5-15 years (mean 12.1) with psychogenic status epilepticus (PSE), i.e., prolonged or repetitive psychogenic seizures (PSs), >30 minutes, simulating status epilepticus. They had epilepsy, they were on chronic anticonvulsants (ACVs), and some had other neurological deficits. All received intravenous and/or rectal ACVs prior to suspicion of PSE. PSE was confirmed via video/EEG, demonstrating no epileptogenic activity during alleged seizures. Provocation and placebo therapy techniques were used in two. Psychiatric assessment identified comorbid disorders such as depression, anxiety disorder, obsessive-compulsive disorder, obsessive-compulsive symptoms, and posttraumatic stress disorder. Psychosocial stressors were almost ubiquitous. Psychiatric intervention included psychotherapy, family therapy, and medical treatment in one patient. Outcome was monitored for an average of 3.6 years (3-5 years). PSE did not recur. PSs recurred in three. Psychiatric comorbidity improved in four, who accepted psychiatric intervention and whose epilepsy also improved. In conclusion, the occurrence of PSE in children and adolescents with epilepsy is stressed. Prompt diagnosis was often missed in the acute care setting, and this carries important implications for iatrogenic complications. PSE diagnosis resulted in identification and management of comorbid psychiatric disorders. This was probably important in reducing the predominating anxiety and affective disorders in most patients as well as PSE recurrence. Epilepsy severity and associated deficits were most likely important factors in determining outcome.

The effect of a psycho-educational program on CARS scores and short sensory profile in autistic children

UNLABELLED There is great demand for effective management of children with Autistic Spectrum Disorders (ASD). This study aimed to investigate the effect of an individually tailored psycho-educational program for autistic children on the scores of the Childhood Autism Rating Scale (CARS) and the Short Sensory Profile (SSP). METHODS Forty children (36 males) were enrolled into an intervention program which consisted of occupational therapy including sensory integration techniques, speech therapy, social skills therapy and parent-directed approaches. Autism severity was assessed using CARS; sensory response capability with the SSP pre- and post-treatment. RESULTS Eight children were intellectually normal; 12 borderline and 20 of low intelligence. Pre-treatment CARS showed that 8 were mildly autistic, 32 moderately-severely autistic. Post-treatment, 24 children changed category; 11 were no longer autistic. The percentage of children performing in the definitive difference region, according to total SSP score, changed slightly (45% vs 32.5%). Comparison of the pre- and post-treatment values revealed that CARS decreased significantly (p < 0.001), whereas total SSP did not (p = 0.294). Tactile sensitivity and low energy/weakness sections, though, were significantly different pre- and post-treatment. Longitudinal analysis, taking into account other confounding factors besides time, further revealed a significant decrement for CARS score with time but not for SSP score (p < 0.001 and p = 0.288, respectively). Similarly, intelligence levels affected CARS but not SSP values (p < 0.001 and p = 0.813, respectively). CONCLUSION Individually tailored psycho-educational therapy had a significant effect on autism severity according to CARS. Changes in the SSP scores were not significant.

Intravenous midazolam in convulsive status epilepticus in children with pharmacoresistant epilepsy.

Although the efficacy of midazolam in refractory status epilepticus and as a first-line agent in children with established status epilepticus has been reported, differences in starting doses, continuation method, timing of efficacy assessment, and discontinuation pose limitations in deriving a specific protocol for midazolam use. An audit of clinical experience with a protocol of midazolam as first-line agent for impending status epilepticus (defined as a continuous, generalized, convulsive seizure lasting >5 minutes) in 76 episodes of unprovoked convulsive status epilepticus in children 1-15 years old with treatment-refractory epilepsy demonstrated that: (1) repeated bolus midazolam 0.1mg/kg (every 5 minutes, maximum 5) controlled 91% of events; (2) three bolus doses controlled 89% of the episodes, with minimal chance of response beyond that; (3) treating impending status resulted in lower doses (mean 0.17 mg/kg) than reported and infrequent utilization of additional anticonvulsants (9%); and (4) adverse events were infrequent (respiratory depression 13%, assisted ventilation 3%).

Illness perceptions determine psychological distress and quality of life in youngsters with epilepsy

The aim of this cross-sectional study was to explore the extent to which gender, epilepsy severity, and self-regulation concepts (illness perceptions, autonomous treatment regulation, perceived autonomy support by parents) predict psychological distress and quality of life (QoL) in young patients with epilepsy. Structured interviews were conducted in 100 patients (Mage=13.9, SD=2.21, 41% girls), and data were analyzed by means of multiple hierarchical regression analyses. Seizures of most patients (91%) were well controlled by antiepileptics, 3% of the patients had infrequent seizures, and seizures in 6% were pharmacoresistant. At a multivariate level, it appeared that youngsters with epilepsy who expect that their disease will last for a long time, who believe that they have less personal control over their illness, and who expect the illness to have a high emotional impact reported higher levels of distress. In addition, a better QoL was reported by youngsters who believed that treatment did not control their illness and who thought that their epilepsy would not affect them emotionally. Findings indicate the importance of illness perceptions, and it is suggested that they should be targeted in future interventions in youngsters with epilepsy.

Botulinum toxin treatment in upper limb spasticity: Treatment consistency

This study assessed treatment consistency of botulinum toxin administration in spastic upper limbs under pragmatic conditions, as derived through stability of dosages and between injections intervals. Over a period of 8 years, 153 children (81 with bilateral spastic cerebral palsy, 72 with unilateral) were treated according to accepted, experience-based guidelines with Botox and Dysport. Treatment response was based on assessment of spasticity and attainment of pre-determined goals at 3, 6 and 12 months post each treatment. Mean age at treatment onset was 6y 4mo (SD: 4y 10mo), median F/U, 2.5 years (4 months-6 8/12 years). Number of injection sessions was 1-10; few had more than 6 sessions. In 106 (69.28%) children, more than one anatomic regions of the limb were injected. Most (56.2%), had at least two injection sessions; median time interval between the sessions was 9 months (IQR: 4-35 months, similar for unilateral and bilateral cerebral palsy, p = 0.874). Children >4 years old at the first treatment had longer intervals between sessions (25.8%) compared to younger ones (p = 0.010). The mixed effects models demonstrated that botulinum toxin dosage was stable over subsequent visits (p = 0.144) and that intermediate intervals for subsequent visits were similar to the first one (p = 0.279).