The Psychiatry of Paediatric Movement Disorders

I compared the rate of psychiatric comorbidity in children with Non-tic movement disorders to children with tics and TS. In addition, this PhD explores whether children with Non-tic movement disorders have elevated rates of psychiatry compared to other hospital populations, including Emergency patients and other Neurology patients, as well as a healthy community control group. My hypothesis was that children with Non-tic movement disorders would have rates of psychiatric comorbidities that are similar to children with tics and TS.To examine this hypothesis, I recruited children between the ages of 5 and 16 years from Neurology clinics at The Children’s Hospital at Westmead, Australia, and Great Ormond Street Hospital, United Kingdom, for the following two movement disorder groups: tic movement disorder cohort (consisting of patients with tics and Tourette Syndrome, n=158) and Non-tic movement disorder cohort, (consisting of patients with all other movement disorders, n=102). An additional 137 patients were recruited for two clinical control groups: the Emergency department control cohort (n=100) and the Neurology control cohort including children with peripheral neuropathy or epilepsy (n=37). In addition, data from 10,438 British children were included as a retrospective community control. All patients were screened for psychiatric comorbidities using the Development and Wellbeing Assessment Tool (DAWBA). My primary outcome was that the difference in the rate of psychiatric comorbidity in the Non-tic cohort (39.2%) and the Tic cohort (41.8%) was not statically significant. Importantly, the rate of psychiatric comorbidity in the Non-tic cohort was more than four times the rate of psychiatric diagnosis observed in the large retrospective community cohort (9.5%) (p<0.00001). This is the largest study to date exploring psychiatry in children with paediatric dystonia (n=66) and psychiatric comorbidities occurred in 33.3% of these patients. In conclusion, this study recognises that children with non-tic movement disorders are just as vulnerable to psychiatric comorbidities as children with tics and TS. This new evidence may encourage clinicians to consider screening for psychiatric comorbidities in their movement disorder patients, therefore allowing for earlier diagnosis and treatment

Testamentary capacity assessment tool: μια μελέτη στάθμισης σε ελληνικό πληθυσμό

Το εργαλείο TCAT (Testamentary Capacity Assessment Tool) αποτελεί μια δοκιμασία αδρού ελέγχου (screening) με υψηλή ευαισθησία στην ανίχνευση απώλειας ικανότητας σύνταξης διαθήκης. Στόχος της παρούσας μελέτης ήταν να καταγράψει το εύρος της επίδοσης και να εξάγει νόρμες με βάση την εξίσωση παλινδρόμησης για το εργαλείο στον ελληνικό πληθυσμό, σε νοητικά υγιείς ενήλικες άνω των 40 ετών. Συνολικά το TCAT μαζί με μια σύντομη συστοιχία νευροψυχολογικών δοκιμασιών χορηγήθηκε σε 147 υγιείς ενήλικες. Οι αναλύσεις πολλαπλής παλινδρόμησης έδειξαν πως μόνο η ηλικία και όχι το μορφωτικό επίπεδο ή το φύλο προέβλεψαν στατιστικά σημαντικά την επίδοση στο εργαλείο. Υπήρξε σημαντική επίδραση της ηλικίας και του μορφωτικού επιπέδου στην επίδοση στο εργαλείο σε επίπεδο μέσου όρου. Το εργαλείο παρουσίασε θετική συσχέτιση με δοκιμασίες γενικού επιπέδου γνώσεων αντίληψης κοινωνικών κανόνων και άμεσης μνήμης. Ακόμη υπολογίστηκαν νόρμες με βάση την εξίσωση παλινδρόμησης. Το εργαλείο παρουσιάζει καλές ψυχομετρικές ιδιότητες ωστόσο οι εξαχθείσες νόρμες συνίστανται για ερευνητική χρήση μέχρι τον υπολογισμό τους με μεγαλύτερο δείγμα σε άτομα άνω των 70 ετών.The Testamentary Capacity Assessment Tool (TCAT) is a highly sensitive screening test for the loss of testamentary capacity. The aim of the present research was to examine the psychometric properties of the test, to evaluate the range of performance, and to estimate regression-based norms for the Greek population. In cognitively normal adults over 40 years of age. In all, TCAT along with a battery of neuropsychological tests was administered in 147 healthy adults. MRA analysis indicated that only age and not educational level or gender significantly predicted performance in TCAT. There were significant differences between groups for age and educational level. TCAT was positively correlated with measures of general knowledge, perception of social norms and immediate memory. Regression-based norms were estimated according to the regression equation. The instrument has adequate psychometric properties; however, the present data are considered preliminary, and acquired norms are not suggested for clinical use until the total sample is increased, especially for participants over 70 years of age

A review of psychiatric co-morbidity described in genetic and immune mediated movement disorders

Psychiatric symptoms are an increasingly recognised feature of movement disorders. Recent identification of causative genes and autoantibodies has allowed detailed analysis of aetiologically homogenous subgroups, thereby enabling determination of the spectrum of psychiatric symptoms in these disorders. This review evaluates the incidence and type of psychiatric symptoms encountered in patients with movement disorders. A broad spectrum of psychiatric symptoms was identified across all subtypes of movement disorder, with depression, generalised anxiety disorder and obsessive-compulsive disorder being most common. Psychosis, schizophrenia and attention deficit hyperactivity disorder were also identified, with the psychiatric symptoms often predating onset of the motor disorder. The high incidence of psychiatric symptoms across such a wide range of movement disorders suggests a degree of common or overlapping pathogenic mechanisms. Our review demonstrates the need for increased clinical awareness of such co-morbidities, which should facilitate early neuropsychiatric intervention and allied specialist treatment for patients

Tumor control and QoL outcomes of very young children with atypical teratoid/rhabdoid tumor treated with focal only chemo-radiation therapy using pencil beam scanning proton therapy

The aim of this analysis was to assess the early clinical results of pencil beam scanning proton therapy (PT) in the treatment of young children with non-metastatic atypical teratoid/rhabdoid tumor (ATRT) of the CNS. Fifteen children (male, n = 8, 53 %) were treated with PT between May 2008 and January 2013. Mean age at diagnosis was 17.4 ± 7.0 months. The localization was infratentorial in 9 (60 %) patients. Gross total resection of the primary tumors was achieved in 7 (47 %) patients. The dose administered focally under sedation was 54 Gy (RBE). After a median follow-up of 33.4 months (range 9.7-69.2), 3 (20 %), 4 (27 %) and 2 (13 %) patients presented with local failure (LF), distant brain failure (DBF) and spinal failure (SF), respectively. Six patients died, all of tumor progression. The 2-year overall- and progression-free survival was 64.6 and 66.0 %. Tumor location (supratentorial) and the extent of surgical resection (non-gross total resection) were negative prognostic factors for both OS and PFS. PT was well tolerated. No grade >2 acute toxicity was observed. The estimated 2-year toxicity-free survival was 90 %. As assessed by the PedsQoL proxy, no decrease in QoL was observed after PT. We conclude that PBS PT is an effective treatment for young children with ATRT. After PT, with or without concomitant chemotherapy, two third of the patients survived >2 years. Acute toxicity was manageable. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and treatment-induced toxicity

Effectiveness of Real-Time Quantitative PCR Compare to Repeat PCR for the Diagnosis of Charcot-Marie-Tooth Type 1A and Hereditary Neuropathy with Liability to Pressure Palsies

The majority of cases of Charcot-Marie-Tooth type 1A (CMT1A) and of hereditary neuropathy with a liability to pressure palsies (HNPP) are the result of heterozygosity for the duplication or deletion of peripheral myelin protein 22 gene (PMP22) on 17p11.2. Southern blots, pulsed-field gel electrophoresis (PFGE), fluorescence in situ hybridization (FISH) and polymorphic marker analysis are currently used diagnostic methods. But they are time-consuming, labor-intensive and have some significant limitations. We describe a rapid realtime quantitative PCR method for determining gene copy number for the identification of DNA duplication or deletion occurring in CMT1A or HNPP and compare the results obtained with REP-PCR. Six patients with CMT1A and 14 patients with HNPP [confirmed by Repeat (REP)-PCR], and 16 patients with suspicious CMT1A and 13 patients with suspicious HNPP [negative REP-PCR], and 15 normal controls were studied. We performed REP-PCR, which amplified a 3.6 Kb region (including a 1.7 Kb recombination hotspot), using specific CMT1A-REP and real-time quantitative PCR on the LightCycler system. Using a comparative threshold cycle (Ct) method and β-globin as a reference gene, the gene copy number of the PMP22 gene was quantified. The PMP22 duplication ratio ranged from 1.35 to 1.74, and the PMP22 deletion ratio from 0.41 to 0.53. The PMP22 ratio in normal controls ranged from 0.81 to 1.12. All 6 patients with CMT1A and 14 patients with HNPP confirmed by REP-PCR were positive by real-time quantitative PCR. Among the 16 suspicious CMT1A and 13 suspicious HNPP with negative REP-PCR, 2 and 4 samples, respectively, were positive by real-time quantitative PCR. Real-time quantitative PCR is a more sensitive and more accurate method than REP-PCR for the detection of PMP22 duplications or deletions, and it is also faster and easier than currently available methods. Therefore, we believe that the real-time quantitative method is useful for diagnosing CMT1A and HNPP