Michal Hrdlicka

Not EEG abnormalities but epilepsy is associated with autistic regression and mental functioning in childhood autism

Abstract.The aim of the study was to investigate the potential association of epilepsy and EEG abnormalities with autistic regression and mental retardation. We examined a group of 77 autistic children (61 boys, 16 girls) with an average age of 9.1 ± 5.3 years. Clinical interview, neurological examination focused on the evaluation of epilepsy, IQ testing, and 21-channel EEG (including night sleep EEG recording) were performed. Normal EEGs were observed in 44.4% of the patients, non-epileptiform abnormal EEGs in 17.5%, and abnormal EEGs with epileptiform discharges in 38.1% of the patients. Epilepsy was found in 22.1% of the subjects. A history of regression was reported in 25.8% of the patients, 54.8% of the sample had abnormal development during the first year of life, and 79.7% of the patients were mentally retarded. Autistic regression was significantly more frequent in patients with epilepsy than in non-epileptic patients (p = 0.003). Abnormal development during the first year of life was significantly associated with epileptiform EEG abnormalities (p = 0.014). Epilepsy correlated significantly with mental retardation (p = 0.001). Although the biological basis and possible causal relationships of these associations remain to be explained, they may point to different subgroups of patients with autistic spectrum disorders.

Subtypes of autism by cluster analysis based on structural MRI data

The aim of our study was to subcategorize Autistic Spectrum Disorders (ASD) using a multidisciplinary approach. Sixty four autistic patients (mean age 9.4±5.6 years) were entered into a cluster analysis. The clustering analysis was based on MRI data. The clusters obtained did not differ significantly in the overall severity of autistic symptomatology as measured by the total score on the Childhood Autism Rating Scale (CARS). The clusters could be characterized as showing significant differences: Cluster 1: showed the largest sizes of the genu and splenium of the corpus callosum (CC), the lowest pregnancy order and the lowest frequency of facial dysmorphic features. Cluster 2: showed the largest sizes of the amygdala and hippocampus (HPC), the least abnormal visual response on the CARS, the lowest frequency of epilepsy and the least frequent abnormal psychomotor development during the first year of life. Cluster 3: showed the largest sizes of the caput of the nucleus caudatus (NC), the smallest sizes of the HPC and facial dysmorphic features were always present. Cluster 4: showed the smallest sizes of the genu and splenium of the CC, as well as the amygdala, and caput of the NC, the most abnormal visual response on the CARS, the highest frequency of epilepsy, the highest pregnancy order, abnormal psychomotor development during the first year of life was always present and facial dysmorphic features were always present. This multidisciplinary approach seems to be a promising method for subtyping autism.

Changes of orexin A plasma levels in girls with anorexia nervosa during eight weeks of realimentation.

OBJECTIVE Orexin A (OXA) is a hypothalamic neuropeptide involved in regulation of food intake and nutritional status. There are multiple disturbances of neuropeptide signaling described in girls with anorexia nervosa (AN), but OXA levels have not been addressed in this population to date. Therefore, we analyzed OXA levels of AN girls in this study. METHOD OXA (radioimmunoassay/RIA/method), leptin, insulinlike growth factor-1 (IGF-1), and insulinlike growth factor-1 binding protein-3 (IGFBP-3) levels were measured before and after 8 weeks of realimentation in 36 girls with AN and in 14 healthy controls (control group: CG). RESULTS Average weight increased significantly in AN during the study (p < .0001), while plasma levels of OXA decreased (before realimentation: 56.2 ± 2.4 pg/ml; after realimentation: 47.5 ± 1.4 pg/ml; p = .0025). OXA levels before realimentation differed from levels in the CG (47.15 ± 2.6 pg/ml, p = .034), but not afterward. We did not find any correlation between OXA and age, height, weight, BMI; or IGF-1, IGFBP-3, and leptin levels. DISCUSSION OXA levels in untreated AN patients differ significantly from healthy subjects and decrease during realimentation. These findings indicate that OXA may be involved in the nutritional regulation of malnourished children and adolescents.

Screening for autism in preterm children with extremely low and very low birth weight

Background Studies of children with very low birth weight (VLBW, 1,000–1,500 g) and extremely low birth weight (ELBW, less than 1,000 g) indicate that this population seems to be at increased risk of autism spectrum disorder (ASD). Methods Parents of 101 VLBW and ELBW children (age 2 years, corrected for prematurity) agreed to participate in the study and signed informed consents; however, parents of only 75 children (44 boys, 31 girls) completed the screening questionnaires. The screening battery included the Modified Checklist for Autism in Toddlers (M-CHAT), Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist (CSBS-DP-ITC), and the Infant/Toddler Sensory Profile (ITSP). Children with disabilities were excluded. All children who screened positive on any of the screening tools were subsequently invited for a detailed assessment. Results Thirty-two children (42.7%) screened positive on at least one of the screening questionnaires. The screening tool with the most positive results was the CSBS-DP-ITC (26 positive screens), followed by the M-CHAT (19 positive screens) and the ITSP (11 positive screens). Of the 32 children who tested positive, 19 participated in the detailed follow-up assessment. A diagnosis of ASD was confirmed in eight of the 19 children. ASD prevalence, calculated from those 19 children and those with negative screening results (43 children), yielded a prevalence of 12.9% in the sample. The difference in frequency of positive screens between the tests was significant (P=0.011). In pair comparisons, ITSP was found to be significantly less positive than CSBS-DP-ITC (P=0.032). No significant differences were found between the M-CHAT and CSBS-DP-ITC or between the M-CHAT and ITSP. Conclusion The results strongly support the hypothesis of an increased prevalence of autism in children with a birth weight less than 1,500 g.

Olfactory functions are not associated with autism severity in autism spectrum disorders.

Background Changes in olfactory functions have been found in many neurodegenerative and psychiatric disorders, including autism spectrum disorders (ASDs). The aim of the present study was to evaluate the relationship between olfactory functions (odor-detection thresholds, odor identification, and odor preference) and autism severity and sensory-related behavior in children and adolescents with ASD. Subjects and methods Our sample consisted of 35 high-functioning patients with ASD (mean age 10.8±3.6 years, 31 boys). Olfactory testing (threshold and identification) used the Sniffin’ Sticks test. Odor pleasantness was assessed on a 5-point scale using the Identification part of the Sniffin’ Sticks test. The severity of autistic psychopathology was measured using the Childhood Autism Rating Scale (CARS). Results Using Spearman’s correlation, we found no significant correlations between autism severity (as expressed by total CARS score) and odor-detection thresholds (R=0.144, P=0.409), odor identification (R=0.07, P=0.966), or odor pleasantness (R=−0.046, P=0.794). There was also no significant relationship between CARS item 9 (“Taste, smell, and touch response and use”) and odor-detection thresholds (R=0.170, P=0.330), odor identification (R=0.282, P=0.100), or odor pleasantness (R=0.017, P=0.923). Conclusion We did not find any significant relationship between the severity of autistic psychopathology and olfactory functions.

Mirtazapine in the treatment of adolescent anorexia nervosa. Case-control study.

ObjectiveAnorexia nervosa (AN) is a serious and potentially life-threatening psychiatric disorder. Pharmacotherapeutic possibilities still remain limited. We sought to determine if there was a positive effect on body weight and body mass index (BMI) in AN patients being treated for depression or anxiety with mirtazapine.MethodsUsing a case–control design, we found nine female patients with AN who had been treated with mirtazapine for depression or anxiety during hospitalization in our department. We also found nine female controls with AN, who had not received any pharmacotherapy. The two groups of patients were matched according to age and BMI. Case and control groups did not differ significantly in age (15.2 ± 1.9 Vs. 14.7 ± 1.7 years; P = 0.549), or in BMI (15.6 ± 2.3 Vs. 15.6 ± 2.1; P = 0.946) at baseline. Weight and BMI were evaluated at baseline and again after the patients had completed 1, 2, 3 and 4 weeks of treatment.ResultsThe mean dose of mirtazapine was 21.7 ± 1.8 mg at the end of week 4. Using ANOVA Repeated Measures, we found no significant differences between cases and controls with regard to weight (P = 0.981) or BMI (P = 0.576). However, there was a non-significant trend in patients which had been treated with mirtazapine which showed slightly more improvement, in the measured parameters, at the end of weeks 1, 2 and 3, compared to controls.ConclusionResults are limited by small sample size. However, the use of mirtazapine could be useful in the treatment of AN in adolescence.

A girl with neurofibromatosis type 1, atypical autism and mosaic ring chromosome 17

We describe a girl with neurofibromatosis type 1 (NF1), mild dysmorphic features, growth and mental retardation, autism, and mosaicism of ring chromosome 17 and chromosome 17 monosomy. The extent of genetic material deleted from the ring chromosome was determined using a combination of classical cytogenetics, fluorescence in situ hybridization (FISH) and multiplex ligation‐dependent probe amplification (MLPA) to be 0.6–2.5 Mb on 17p, and up to about 10 Mb on 17q. Based on our observations and on a review of the literature we argue that in addition to a universal “ring syndrome” which is based on ring instability and is less specific for the chromosome involved, various ring chromosomes underlie their own characteristic phenotypes. We propose that the symptoms leading to the diagnosis of NF1 in our patient could be attributed to mosaic hemizygosity for the NF1 gene in some of her somatic cells. A similar mechanism or a direct involvement of respective disease genes in the aberration could possibly influence also the development of autism and other symptoms. We raise a question if the loss of one copy of chromosome 17 from a substantial fraction of somatic cells can have specific consequences also for future risks of the patient, for example, due to the mosaic hemizygosity for the BRCA1 and TP53 genes.

Atypical antipsychotics in the treatment of early-onset schizophrenia

Atypical antipsychotics (AAPs) have been successfully used in early-onset schizophrenia (EOS). This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least.

EEG in Electroconvulsive Therapy: Is More Intensive Paroxysmal Activity Associated with a Higher Therapeutic Response?

EEG records of electroconvulsions were evaluated according to a five-point semiquantitative scale grading the intensity of the paroxysmal activity. A more favorable therapeutic effect of ECT was found to be associated with more pronounced paroxysmal activity on the EEG. The role of this finding for the dosage of energy in the convulsive stimulus is discussed.

Comparison of three screening tests for autism in preterm children with birth weights less than 1,500 grams.

Background Preterm children seem to be at increased risk for autism spectrum disorders (ASD). Methods Parents of 157 children with birth weights less than 1,500 g (age 2 years, corrected for prematurity; 88 boys, 69 girls) completed screening questionnaires. The screening battery included the Modified Checklist for Autism in Toddlers (M-CHAT), Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist (CSBS-DP-ITC), and the Infant/Toddler Sensory Profile (ITSP). Children with disabilities were excluded. All children who screened positive on any of the screening tools were subsequently assessed by clinical examination including the Autism Diagnostic Observation Schedule. Results Fifty-six children (35.7%) screened positive on at least one of the parental screening questionnaires. Of the 56 children who tested positive, 33 participated in the detailed clinical follow-up assessment. A diagnosis of ASD was confirmed in 13 of the 33 children. The ASD prevalence was 9.7% of the sample. Analysis of children with and without an ASD diagnosis found significant differences relative to gestational age (26.9 weeks vs 28.3 weeks, P=0.033) and length of the stay in hospital (89.5 days vs 75.4 days, P=0.042). The screening tool with the most positive results was CSBS-DP-ITC (42 positive screens [PS]), followed by M-CHAT (28 PS), and ITSP (22 PS). Differences in the frequency of PS among the tests were significant (P=0.008). CSBS-DP-ITC had the highest sensitivity (0.846), followed by M-CHAT (0.692) and ITSP (0.462). Conclusion Our results indicate a higher prevalence of autism in children with birth weights <1,500 g at 2 years of age compared to the general population prevalence. The ASD diagnosis was associated with shorter gestation times and longer hospital stays. Our findings support the simultaneous use of more than one screening tests in order to increase screening sensitivity.