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1.  Psychotherapy versus usual care in pediatric migraine and tension-type headache: a single-blind controlled pilot study 
Background
Despite growing interest in psychotherapy in child and adolescent headache, efficacy studies in this research field have focused mainly on cognitive-behavioral therapies. Whereas relaxation and cognitive-behavioral techniques, in particular, have been found to reduce the intensity and frequency of headache in children and adolescents, data on psychodynamic psychotherapy in this population are lacking.
Our aim was to explore the effectiveness of a brief psychodynamic psychotherapy program in the treatment of idiopathic headache in childhood and adolescence.
Methods
Thirty-three newly diagnosed idiopathic headache sufferers aged 6–18 years, consecutively referred to our outpatient services, were randomized to receive either a brief cycle of psychodynamic psychotherapy (eight sessions administered at two-week intervals) or usual care (clinical interview, neurological examination, counselling, symptomatic therapy).
The two groups were evaluated at baseline (T0) and at six months (T1) to be assessed for headache characteristics (i.e. frequency, intensity and duration), quality of life (i.e. the EuroQoL score), patient’s global health status (i.e. the Clinical Global Impression score), and emotional-behavioral symptoms (i.e. Child Behavior Checklist scores).
Results
The two groups were fairly similar with reference to the main demographic and clinical variables. The T0/T1 comparison showed a statistically significant improvement in headache frequency (p = 0.005), intensity (p < 0.001) and duration (p = 0.002), a statistically significant improvement in the CGI score (p = 0.018), and a borderline improvement in the EuroQoL score (p = 0.053) in the group receiving psychotherapy.
Conclusions
According to our pilot findings, a brief psychodynamic psychotherapy program may be more effective than usual care in children and adolescents with idiopathic headache.
doi:10.1186/1824-7288-40-6
PMCID: PMC3899919  PMID: 24444140
2.  Headache and comorbidity in children and adolescents 
Headache is one of the most common neurological symptom reported in childhood and adolescence, leading to high levels of school absences and being associated with several comorbid conditions, particularly in neurological, psychiatric and cardiovascular systems. Neurological and psychiatric disorders, that are associated with migraine, are mainly depression, anxiety disorders, epilepsy and sleep disorders, ADHD and Tourette syndrome. It also has been shown an association with atopic disease and cardiovascular disease, especially ischemic stroke and patent foramen ovale (PFO).
doi:10.1186/1129-2377-14-79
PMCID: PMC3849985  PMID: 24063537
Headache; Comorbidity; Children; Adolescents
3.  Molecular Mechanisms Generating and Stabilizing Terminal 22q13 Deletions in 44 Subjects with Phelan/McDermid Syndrome 
PLoS Genetics  2011;7(7):e1002173.
In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome), as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood. We characterized at the molecular level the genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple terminal deletions (72%), ring chromosomes (14%), and unbalanced translocations (7%). We also discovered interstitial deletions between 17–74 kb in 9% of the patients. Haploinsufficiency of the SHANK3 gene, confirmed in all rearrangements, is very likely the cause of the major neurological features associated with PMS. SHANK3 mutations can also result in language and/or social interaction disabilities. We determined the breakpoint junctions in 29 cases, providing a realistic snapshot of the variety of mechanisms driving non-recurrent deletion and repair at chromosome ends. De novo telomere synthesis and telomere capture are used to repair terminal deletions; non-homologous end-joining or microhomology-mediated break-induced replication is probably involved in ring 22 formation and translocations; non-homologous end-joining and fork stalling and template switching prevail in cases with interstitial 22q13.3. For the first time, we also demonstrated that distinct stabilizing events of the same terminal deletion can occur in different early embryonic cells, proving that terminal deletions can be repaired by multistep healing events and supporting the recent hypothesis that rare pathogenic germline rearrangements may have mitotic origin. Finally, the progressive clinical deterioration observed throughout the longitudinal medical history of three subjects over forty years supports the hypothesis of a role for SHANK3 haploinsufficiency in neurological deterioration, in addition to its involvement in the neurobehavioral phenotype of PMS.
Author Summary
Terminal chromosome deletions are among the most commonly observed rearrangements detected by cytogenetics and may result in several well-known genetic syndromes. We used 22q13 deletions to study how these types of chromosome abnormalities arise. Children with Phelan/McDermid syndrome, caused by deletion of the terminal portion of chromosome 22, experience developmental delay, absent or severely delayed speech, and frequent behavioral problems. Lack of one copy of SHANK3, a key gene for the correct development and organization of brain synapses, is very likely the basis of the syndrome's major neurological features. Deletion of additional genes probably causes more complex phenotypes in subjects with larger deletions. We also studied patients who only lack a portion of SHANK3 and demonstrated that small, hard-to-detect deletions of this gene may cause substantial clinical problems. Until now, the 22q distal deletion had been only diagnosed in very young people. We studied a large group of patients of different ages and discovered that all adult patients face progressive cognitive decline. Our study demonstrates that deletion of the terminal portion of chromosome 22, a prototype for terminal deletions in human chromosomes, can occur in several ways. Mosaic deletions of different size can also form in early embryogenesis.
doi:10.1371/journal.pgen.1002173
PMCID: PMC3136441  PMID: 21779178
4.  European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment 
To develop a European guideline on pharmacologic treatment of Tourette syndrome (TS) the available literature was thoroughly screened and extensively discussed by a working group of the European Society for the Study of Tourette syndrome (ESSTS). Although there are many more studies on pharmacotherapy of TS than on behavioral treatment options, only a limited number of studies meets rigorous quality criteria. Therefore, we have devised a two-stage approach. First, we present the highest level of evidence by reporting the findings of existing Cochrane reviews in this field. Subsequently, we provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary of the current consensus on pharmacological treatment options for TS in Europe to guide the clinician in daily practice. This summary is, however, rather a status quo of a clinically helpful but merely low evidence guideline, mainly driven by expert experience and opinion, since rigorous experimental studies are scarce.
doi:10.1007/s00787-011-0163-7
PMCID: PMC3065650  PMID: 21445724
Tics; Tourette; Pharmacologic; Treatment; Guidelines
5.  Overview of diagnosis and management of paediatric headache. Part I: diagnosis 
Headache is the most common somatic complaint in children and adolescents. The evaluation should include detailed history of children and adolescents completed by detailed general and neurological examinations. Moreover, the possible role of psychological factors, life events and excessively stressful lifestyle in influencing recurrent headache need to be checked. The choice of laboratory tests rests on the differential diagnosis suggested by the history, the character and temporal pattern of the headache, and the physical and neurological examinations. Subjects who have any signs or symptoms of focal/progressive neurological disturbances should be investigated by neuroimaging techniques. The electroencephalogram and other neurophysiological examinations are of limited value in the routine evaluation of headaches. In a primary headache disorder, headache itself is the illness and headache is not attributed to any other disorder (e.g. migraine, tension-type headache, cluster headache and other trigeminal autonomic cephalgias). In secondary headache disorders, headache is the symptom of identifiable structural, metabolic or other abnormality. Red flags include the first or worst headache ever in the life, recent headache onset, increasing severity or frequency, occipital location, awakening from sleep because of headache, headache occurring exclusively in the morning associated with severe vomiting and headache associated with straining. Thus, the differential diagnosis between primary and secondary headaches rests mainly on clinical criteria. A thorough evaluation of headache in children and adolescents is necessary to make the correct diagnosis and initiate treatment, bearing in mind that children with headache are more likely to experience psychosocial adversity and to grow up with an excess of both headache and other physical and psychiatric symptoms and this creates an important healthcare problem for their future life.
doi:10.1007/s10194-011-0297-5
PMCID: PMC3056001  PMID: 21359874
Headache; Childhood; Paediatric headaches; Diagnosis; Epidemiology; Defining features
6.  Overview of diagnosis and management of paediatric headache. Part I: diagnosis 
Headache is the most common somatic complaint in children and adolescents. The evaluation should include detailed history of children and adolescents completed by detailed general and neurological examinations. Moreover, the possible role of psychological factors, life events and excessively stressful lifestyle in influencing recurrent headache need to be checked. The choice of laboratory tests rests on the differential diagnosis suggested by the history, the character and temporal pattern of the headache, and the physical and neurological examinations. Subjects who have any signs or symptoms of focal/progressive neurological disturbances should be investigated by neuroimaging techniques. The electroencephalogram and other neurophysiological examinations are of limited value in the routine evaluation of headaches. In a primary headache disorder, headache itself is the illness and headache is not attributed to any other disorder (e.g. migraine, tension-type headache, cluster headache and other trigeminal autonomic cephalgias). In secondary headache disorders, headache is the symptom of identifiable structural, metabolic or other abnormality. Red flags include the first or worst headache ever in the life, recent headache onset, increasing severity or frequency, occipital location, awakening from sleep because of headache, headache occurring exclusively in the morning associated with severe vomiting and headache associated with straining. Thus, the differential diagnosis between primary and secondary headaches rests mainly on clinical criteria. A thorough evaluation of headache in children and adolescents is necessary to make the correct diagnosis and initiate treatment, bearing in mind that children with headache are more likely to experience psychosocial adversity and to grow up with an excess of both headache and other physical and psychiatric symptoms and this creates an important healthcare problem for their future life.
doi:10.1007/s10194-011-0297-5
PMCID: PMC3056001  PMID: 21359874
Headache; Childhood; Paediatric headaches; Diagnosis; Epidemiology; Defining features
7.  Overview of diagnosis and management of paediatric headache. Part II: therapeutic management 
A thorough evaluation of headache in children and adolescents is necessary to make the correct diagnosis and initiate treatment. In part 1 of this article (Özge et al. in J Headache Pain, 2010), we reviewed the diagnosis of headache in children and adolescents. In the present part, we will discuss therapeutic management of primary headaches. An appropriate management requires an individually tailored strategy giving due consideration to both non-pharmacological and pharmacological measures. Non-pharmacological treatments include relaxation training, biofeedback training, cognitive-behavioural therapy, different psychotherapeutic approaches or combinations of these treatments. The data supporting the effectiveness of these therapies are less clear-cut in children than in adults, but that is also true for the data supporting medical treatment. Management of migraine and TTH should include strategies relating to daily living activities, family relationships, school, friends and leisure time activities. In the pharmacological treatment age and gender of children, headache diagnosis, comorbidities and side effects of medication must be considered. The goal of symptomatic treatment should be a quick response with return to normal activity and without relapse. The drug should be taken as early as possible and in the appropriate dosage. Supplementary measures such as rest in a quiet, darkened room is recommended. Pharmaco-prophylaxis is only indicated if lifestyle modification and non-pharmacological prophylaxis alone are not effective. Although many prophylactic medications have been tried in paediatric migraine, there are only a few medications that have been studied in controlled trials. Multidisciplinary treatment is an effective strategy for children and adolescents with improvement of multiple outcome variants including frequency and severity of headache and school days missed because of headache. As a growing problem both children and families should be informed about medication overuse and the children’s drug-taking should be checked.
doi:10.1007/s10194-010-0256-6
PMCID: PMC3072476  PMID: 21170567
Migraine; Tension-type headache; Symptomatic treatment; Pharmacological prophylaxis; Non-pharmacological treatment
8.  Overview of diagnosis and management of paediatric headache. Part II: therapeutic management 
A thorough evaluation of headache in children and adolescents is necessary to make the correct diagnosis and initiate treatment. In part 1 of this article (Özge et al. in J Headache Pain, 2010), we reviewed the diagnosis of headache in children and adolescents. In the present part, we will discuss therapeutic management of primary headaches. An appropriate management requires an individually tailored strategy giving due consideration to both non-pharmacological and pharmacological measures. Non-pharmacological treatments include relaxation training, biofeedback training, cognitive-behavioural therapy, different psychotherapeutic approaches or combinations of these treatments. The data supporting the effectiveness of these therapies are less clear-cut in children than in adults, but that is also true for the data supporting medical treatment. Management of migraine and TTH should include strategies relating to daily living activities, family relationships, school, friends and leisure time activities. In the pharmacological treatment age and gender of children, headache diagnosis, comorbidities and side effects of medication must be considered. The goal of symptomatic treatment should be a quick response with return to normal activity and without relapse. The drug should be taken as early as possible and in the appropriate dosage. Supplementary measures such as rest in a quiet, darkened room is recommended. Pharmaco-prophylaxis is only indicated if lifestyle modification and non-pharmacological prophylaxis alone are not effective. Although many prophylactic medications have been tried in paediatric migraine, there are only a few medications that have been studied in controlled trials. Multidisciplinary treatment is an effective strategy for children and adolescents with improvement of multiple outcome variants including frequency and severity of headache and school days missed because of headache. As a growing problem both children and families should be informed about medication overuse and the children’s drug-taking should be checked.
doi:10.1007/s10194-010-0256-6
PMCID: PMC3072476  PMID: 21170567
Migraine; Tension-type headache; Symptomatic treatment; Pharmacological prophylaxis; Non-pharmacological treatment

Results 1-8 (8)