Research on the Pathogenesis of Cognitive and Neurofunctional Impairments in Patients with Noonan Syndrome: The Role of Rat Sarcoma-Mitogen Activated Protein Kinase Signaling Pathway Gene Disturbances.

Noonan syndrome (NS) is one of the most common genetic conditions inherited mostly in an autosomal dominant manner with vast heterogeneity in clinical and genetic features. Patients with NS might have speech disturbances, memory and attention deficits, limitations in daily functioning, and decreased overall intelligence. Here, 34 patients with Noonan syndrome and 23 healthy controls were enrolled in a study involving gray and white matter volume evaluation using voxel-based morphometry (VBM), white matter connectivity measurements using diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI). Fractional anisotropy (FA) and mean diffusivity (MD) probability distributions were calculated. Cognitive abilities were assessed using the Stanford Binet Intelligence Scales. Reductions in white matter connectivity were detected using DTI in NS patients. The rs-fMRI revealed hyper-connectivity in NS patients between the sensorimotor network and language network and between the sensorimotor network and salience network in comparison to healthy controls. NS patients exhibited decreased verbal and nonverbal IQ compared to healthy controls. The assessment of the microstructural alterations of white matter as well as the resting-state functional connectivity (rsFC) analysis in patients with NS may shed light on the mechanisms responsible for cognitive and neurofunctional impairments.

Epilepsy and Language Development in 8-36-Month-Old Toddlers with Tuberous Sclerosis Complex.

This paper aimed to assess language development in infants and toddlers with tuberous sclerosis complex (TSC) and epilepsy, which increase the risk of autism spectrum disorder. We assessed language development in 61 patients with TSC at 8-36 months using a standardized Speech Development and Communication Inventory tool. The results showed differences in outcomes due to the duration of the seizures and the number of drugs (pFDR = 0.007 **-pFDR = 0.037 *). Children with TSC with longer epilepsy duration and receiving more antiepileptic drugs have a greater risk of language development delay.

Epilepsy and cognitive deterioration as postoperative complications of the arachnoid cyst fenestration: Case report.

Objective: With the aim of contributing to the discussion on treatment of patients with arachnoid cysts (AC) and their neuropsychological functioning, we present the case of a patient who has undergone surgery of AC located in the left Sylvian fissure. Case description: The patient had no cognitive deficits and no seizures before the cyst's fenestration. After the procedure, however, occurrences of seizures have been observed. Along with the concomitant epileptic seizures, aphasia and serious memory problems also developed. The initial pharmacological treatment of the seizures brought about unsatisfactory results. The treatment was therefore modified a number of times and ultimately, seizures were brought under control to some extent. Despite the varied efforts at neuropsychological rehabilitation, cognitive impairment was still persistent up to a year after the surgery. Conclusions: 1) While referring patients with AC for surgery, one should always consider both the positive outcomes and the unintended and deleterious consequences. A cyst fenestration could in some cases lead to epilepsy and cause neuropsychological symptoms such as anomic aphasia and cognitive deterioration with memory function impairment. 2) Neurological patients, especially the ones qualified for surgery, should always undergo neuropsychological examination. The lack of data from presurgical neuropsychological examination may impact further treatment of neurosurgical patients.

The health-related quality of life in children with arachnoid cysts. Clinical predictors and parent-child perspectives.

BACKGROUND: In clinical practice, arachnoid cysts (AC) are usually detected by coincidence and are frequently considered as clinically mute. Even though an AC does not usually result in serious symptoms, the diagnosis itself can have a significant impact on the patients and their families, especially in terms of psychological functioning and quality of life. METHODS: Participants were 22 children diagnosed with AC and their parents. We analyzed patients' medical records and assessed them using the Stanford Binet Intelligence Scale, fifth edition. Additionally, both children and parents filled in the Polish version of the PedsQL™ 4.0 generic core module. RESULTS: The Health-RelatedQuality of Life (HRQOL) is not related to objective predictors such as radiological predictors and SB 5 results. However, there is a correlation between the HRQOL, and symptoms given in the interview. Secondly, parents assess the HRQOL of their children worse compared to the children's own ratings. Lastly, children with AC assess the HRQOL in a way that is similar to the assessment done by healthy children in the original study describing PedsQL™, whereas parents assess children's HRQOL in a way rather similar to the assessment done by parents of patients. CONCLUSIONS: The results show the impact of the disease's image and understanding on the HRQOL. Basing on our results we conclude the important role of psychological support for patients with AC. We furthermore conclude that parents of children with AC assess the HRQOL of children worse compared to the children's own ratings.

Are arachnoid cysts actually clinically mute in relation to neuropsychological symptoms? Cognitive functioning in children with AC of middle and cranial fossa.

Aiming at being part of the discussion about the cognitive functioning of patients with arachnoid cysts (AC) and the value of neuropsychological testing in these patients, we present our study in which we investigated the cognitive functioning of 32 children with ACs of the middle cranial fossa. We compared the Stanford Binet 5 (SB 5) results obtained by the patients with the population mean values and analysed the relation between the patients' clinical details and the results of SB 5. The main conclusions of this research are: (1) In SB 5 tasks, the tested group performed worse than the population mean, which could be related to AC of the middle cranial fossa. Deficits concern especially visuospatial reasoning, quantitative reasoning, and knowledge. The obtained results indicate the coexistence of cognitive impairment and AC of the middle cranial fossa. (2) In patients with AC, neuroimaging information has only limited predictive ability regarding cognitive syndromes. (3) The complaints reported in the interview are not necessarily objectively reflected in the clinical assessment. Neuropsychological assessment should be part of the management of all patients with AC. (4) Cognitive deficits in patients with AC may become more pronounced with age. Accordingly, increasing school difficulties in these patients should be expected. In light of the above, there is a clear indication of the need for neuropsychological support and support in school functioning for patients with AC. (5) Neuropsychological control in patients with AC is crucial not only with regard to treatment decisions but primarily for monitoring school performance and providing these patients with adequate neuropsychological and psychological support.

Diagnosis of Fetal Alcohol Spectrum Disorders (FASDs): Guidelines of Interdisciplinary Group of Polish Professionals.

(1) Background: Considerable prevalence in Poland and serious health consequences of prenatal alcohol exposure indicated the need to develop national guidelines for the diagnosis of fetal alcohol spectrum disorders (FASDs). It was assumed that the guidelines must be in line with international standards but adjusted to the Polish context. (2) Methods: Work on recommendations was carried out by an interdisciplinary team of Polish specialists. Its first stage was to assess the usefulness in our country of the U.S. and Canadian guidelines. In the second stage, after several rounds of discussions, a consensus was achieved. (3) Results: The Polish guidelines for diagnosing FASD cover the following issues: 1. distinguished diagnostic categories; 2. diagnostic procedure; 3. assessment of prenatal exposure to alcohol; 4. assessment of sentinel facial dysmorphias; 5. assessment of body weight, height, and head circumference; 6. neurodevelopmental assessment. An important element of the recommendation is appendices containing practical tools that are useful in the diagnostic procedure. (4) Conclusions: National guidelines may improve the quality and standardization of FASD diagnosis in Poland, but their practical utility has to be monitored.

Cognitive Impairment in Children with Arachnoid Cyst of Sylvian Fissure: Does it Justify the Neurosurgical Treatment?

This report discusses the relationship between arachnoid cysts (ACs) and cognitive deficits, and we ask if cognitive impairments could justify neurosurgical treatment. In clinical practice, only AC patients with symptoms of intracranial hypertension or focal neurological deficits are referred to surgery. Occasionally, one might assume that nonspecific problems such as impairment of learning, speech, or cognitive functions are caused by an AC and can be improved by surgery. We describe three patients, in which surgery was indicated on the basis of clinical symptoms such as headaches and the size of the cysts. A neuropsychological examination before AC surgery revealed reduced cognitive potential, and the same examination repeated after surgery showed improvement. We have not found any other reason for this change, except for the decompression of the AC.

When the brain looks imperfect: An example of neuroplasticity as seen in a patient with arachnoid cysts - a case study.

Objective: This study presents a case of a teenager (J.J.) prenatally diagnosed with large arachnoid cysts which did not allow parts of his brain to develop correctly. It aims to establish whether the congenital malformation affected the boy's cognitive development.Method: In order to assess his cognitive development, the authors analyzed J.J.'s medical history, interviewed him and his parents and conducted neuropsychological examination.Results: Despite major parts of his brain undeveloped, the boy achieved average to outstanding scores in all tests.Conclusions: The scores achieved by J.J. suggest that normal development of cognitive abilities is possible even for a person whose central nervous system differs structurally from what is expected in a healthy subject.

Cognitive and social function in girls with congenital adrenal hyperplasia -- influence of prenatally administered dexamethasone.

OBJECTIVES: To assess the cognitive, social, and emotional function in girls prenatally treated with dexamethasone (Dex) due to congenital adrenal hyperplasia (CAH), compared to CAH female patients not treated prenatally. PATIENTS AND METHODS: 33 girls from CAH families were studied: 17 girls treated prenatally with Dex (9 CAH-affected and 8 non-CAH-affected) and 16 CAH-affected females prenatally untre-ated. Standardized tests to assess cognitive function, tests of memory and learning process, and the Child Behavior Checklist (CBCL) were used. RESULTS: There were few statistically significant differences between the results of treated girls (CAH-affected and unaffected) and CAH untreated patients, with a tendency for better results in all tests by Dex treated girls. Among three groups- "CAH-unaffected treated," "CAH-affected treated," and "CAH-affected untreated"- the best results were found in "CAH-affected treated" in almost all tests. The Wechsler test performance scale was significantly higher in treated CAH-affected girls. The comparison between treated and untreated CAH-affected girls revealed better results in all tasks involving the cognitive function in Dex-treated patients. Poor performance in visual perception, analysis of spatial material, and visual memory tasks were obtained in CAH-unaffected treated girls. CONCLUSIONS: Prenatal treatment with Dex creates for CAH-affected females better conditions for cognitive development. The prenatal Dex in CAH-unaffected girls can cause the risk of unfavorable influences on the development of some cognitive functions. Therefore, it is recommended that prenatal treatment in CAH-unaffected female fetuses should be stopped as soon as possible after the exclusion of the disease.

Cephalic index in the evaluation of surgical treatment of children with sagittal synostosis. Preliminary report.

AIM OF THE STUDY: To analyze changes of the cephalic index (CI) values in patients with sagittal synostosis operated on in the Department of Surgery of Children and Adolescents of the Institute of Mother and Child in Warsaw. MATERIAL AND METHODS: The study group consisted of 14 consecutive cases (11 boys and 3 girls). In 8 patients younger than 3 months of age (1st subgroup) the modified reversed-pi technique (craniotomy in the shape of the reversed Greek π letter) was utilized. In 6 older infants and in patients with severe head deformity - the radical cranial vault reconstructions were performed (2nd subgroup). The statistical analysis of the preoperative (preop) and postoperative (postop) cephalic index (CI) values was done. RESULTS: For the entire study group the preop CI values ranged from 61 to 77 (mean 68.14, median 68.5) and postop CIs from 73 to 89 (mean 77.64, median 76). In the 1st subgroup the preop CIs ranged from 63 to 77 (mean 69.625, median 69) whereas the postop CIs from 69 to 89 (mean 78.125, median 76.5). In the 2nd subgroup the preop CI values ranged from 61 to 72 (mean 66.1667, median 66) and postop from 73 to 81 (mean 77, median 77). All the differences were statistically significant. CONCLUSION: The values of cephalic index increased after both types of procedures. It signifies the correction of dolichocephaly in both subgroups of the patients. However, because of the small number of operated children, further studies are necessary.

Ventricular fibrillation risk factors in over one thousand patients with accessory pathways.

BACKGROUND: Published data concerning risk factors of VF in WPW patients are inconsistent or contradictory. METHODS AND RESULTS: We included 1007 patient (pts) (mean age 35 years; 45% female) with an accessory pathway (AP) referred for non pharmacological treatment. Group 1 consisted of 56 pts (42M, aged 34 ± 15 yrs) with an AP and documented VF and Group 2-951 pts (513M, aged 35 ± 15 yrs) with an AP and without VF. Univariate predictors of VF were: overt pre-excitation, male gender, multiple AP, large AP. Multivariate predictors were: overt pre-excitation, male gender and MAP. The mean shortest pre-excited RR interval during AF was significantly shorter in Group 1: 205 ± 27 vs. 243 ± 64, P=0.019. VF as an end point of the first arrhythmia episode (AVRT or AF) was observed in 20 pts (15M, 5F). Primary VF (no documented arrhythmia prior to aborted SCD) occurred in 16 pts (13M, 3F). The mean age of primary VF pts was significantly lower than of pts with history of AVRT or AVRT and/or AF (24.5 vs. 36.5 vs. 38 yrs., P<0.005 and P=0.002, respectively). Age at VF occurrence shows a bi-modal distribution with peak occurrences in the 2-nd/3-rd and 5-th decades. CONCLUSION: In patients with an accessory pathway, overt pre-excitation, male gender and multiple AP constitute independent risk factors of VF episodes. Young patients in the 2-nd/3-rd and older patients in the 5-th decade might be at higher risk of VF occurrence.

Does atrioventricular reentry tachycardia (AVRT) or atrioventricular nodal reentry tachycardia (AVNRT) in children affect their cognitive and emotional development?

The current study sought to assess cognitive and emotional functions among children and adolescents with atrioventricular reentry tachycardia (AVRT) and atrioventricular nodal reentry tachycardia (AVNRT). 113 patients (62 girls and 51 boys ages, 9-18 years) scheduled for radiofrequency ablation due to AVRT or AVNRT underwent neuropsychologic examination. The study excluded patients who had experienced cardiac arrest, congenital heart defects, neurologic disorders, or other diseases affecting cognitive or emotional development. Standardized tests for examining verbal and visual memory as well as visual-spatial functioning were performed. For patients exhibiting deficits in two or more tests, a diagnosis of "cognitive deficits" was determined. Levels of anxiety were tested using the State-Trait Anxiety Inventory. Cognitive deficits were found in 47.8 % of the patients. The age at first arrhythmia attack was related to memory dysfunction. The mean age at which the first symptoms occurred was significantly lower for patients with deficits (8.3 years) than for patients who had no deficit (10.2 years) (t = 2.15; p = 0.03). Boys exhibited a significantly higher level of trait anxiety than girls (t = 3.42; p = 0.0009). A significant negative correlation was found between anxiety and the age at appearance of the first symptoms (r = -0.26; p = 0.005). These findings led us to conclude that cognitive and emotional developments can be negatively affected by AVNRT and AVRT, particularly if tachycardia appears early in life.

Two-year follow-up of Sanfilippo Disease patients treated with a genistein-rich isoflavone extract: assessment of effects on cognitive functions and general status of patients.

BACKGROUND: Mucopolysaccharidoses (MPS) are inherited metabolic disorders caused by deficiencies in enzymes involved in degradation of glycosaminoglycans. MPS type III (Sanfilippo disease) is clinically characterized mainly by progressive and severe behavioral disturbances and cognitive dysfunction. Recent 1-year experimental treatment of 10 patients with a genistein (4', 5, 7-trihydroxyisoflavone)-rich extract resulted in improvement of tested parameters, including cognitive and behavioral functions. MATERIAL/METHODS: Eight pediatric patients with Sanfilippo disease were enrolled into the study. The modified version of the Brief Assessment Examination was used to assess cognitive functions. Moreover, 18 different parameters concerning changes in conditions of patients were assessed by their parents. RESULTS: During the first year of the treatment, an improvement of cognitive functions in 7 patients and stabilization in 1 patient were assessed, while after the third year (2-year follow-up) further improvement was observed in 2 patients, stabilization in 3 patients and some deterioration in 3 patients. Monitoring of general and behavioral symptoms revealed improvement in all patients after the first year of the treatment, further improvement in 5 patients, and deterioration in 3 patients during the next 2 years. CONCLUSIONS: We conclude that the treatment of Sanfilippo patients with a genistein-rich soy isoflavone extract (called gene expression-targeted isoflavone therapy [GET IT]) may be effective in either inhibition (in some patients) or slowing down (in other patients) of behavioral and cognitive problems over a longer period. An increased dose of genistein may improve the efficacy of the treatment.

Cognitive and social functioning in children and adolescents after the removal of craniopharyngioma.

PURPOSE: The aim of this study is to assess cognitive, emotional and social functioning in children and adolescents after the removal of craniopharyngioma. METHODS: Twenty-seven children operated for craniopharyngioma and their parents participated in the study. Cognitive functions were assessed with WISC-R/WAIS-R-PL and Rey-Osterrieth Complex Figure Test. Parents completed Achenbach's Child Behaviour Checklist (CBCL) questionnaires on problems in functioning and psychopathological symptoms and took part in an interview on children coping in everyday life. RESULTS: Eighty-two percent of patients were diagnosed with an average level of intellectual functioning. No child received results indicating mental disability. In half of the children, effectiveness of visual memory was reduced, despite normal visual-spatial abilities. The results in the CBCL scale indicated more frequent presence of psychopathological symptoms-especially social problems, depression, anxiety and withdrawal. The most frequent problems in children's everyday functioning included inability to control emotions, difficulties in learning, unsatisfactory peer relationships, and unattractive appearance resulting from hormonal disorders (short height and obesity). One third of parents also reported problems with pathological appetite in their children. CONCLUSIONS: Despite normal intellectual abilities and relatively good physical condition, children after removal of craniopharyngioma experience many difficulties in everyday life regarding social relationships, emotion control and learning. The analogy between the above-mentioned symptoms and symptoms observed in patients after infantile damage in the frontal area leads to an observation that, apart from endocrine disorders, damage to the frontal lobe caused by the growth of tumour and operational intervention is of crucial importance to the further development of children with craniopharyngioma.

Long-term functional outcome of surgical treatment of juvenile pilocytic astrocytoma of the cerebellum in children.

PURPOSE: Increasing incidence of pediatric brain tumors and improving survival rates encouraged us to assess long-term functional outcome of patients with cerebellar juvenile pilocytic astrocytoma (JPA). MATERIALS AND METHODS: Our study encompassed 105 children treated since 1980-2005 and consisted in analysis of mailed, custom-designed questionnaires. RESULTS: Mean follow-up time was 8.3 years. Sixty out of 104 patients presented permanent neurological deficits and 47/104 presented significant behavioral disorders. Eighty-nine children continued their education at primary, secondary or high school level. Most patients and their parents were satisfied with treatment outcome. Patients' and parents' notes were usually concordant. CONCLUSIONS: Long-term functional treatment outcome of cerebellar JPA is relatively favorable, in spite of permanent neurological deficits and emotional disorders in over half of the patients. Vermian tumors are associated with worse long-term functional outcome. Neurological deficits and emotional disorders do not preclude further education and independent functioning.

[Next cardioversion or RF ablation in professional driver with recurrent typical atrial flutter and MAS syndromes]. / Nastepna elektrowersja czy ablacja RF podloza typowego trzepotania przedsionków u zawodowego kierowcy z napadami MAS.

We describe a 42-year-old professional driver with hypertension, obesity and recurrent episodes of highly symptomatic typical atrial flutter. Despite chronic sotalol treatment, 1:1 AV conduction with RBBB-morphology was observed. After excluding of thrombus in the heart chambers, the 'urgent' and successful RF ablation was performed.