Clinical manifestations and stages of Rett syndrome

The presentation and clinical diagnosis of Rett syndrome at various ages and stages are reviewed. In addition to the classical form, variability in phenotype between different atypical Rett forms is given. Obligatory, supportive, and differential diagnostic criteria are summarized. Long-term follow-up findings in ageing Rett women are addressed.     

Psychometry and regional cerebral blood flow (rCBF) measurements

Summary The relationship between psychometric performance and regional cerebral blood flow (rCBF) measurement in a series of patients suffering from presenile dementia is discussed. An evaluation of central concepts in the late Professor A.R. Luria's dynamic localization model for behavior determination is made. A new indirect measurement of regional cerebral metabolism (rCBF) is used. In general, support is obtained from Luria's model for the interpretation of the relation between psychometric results and the rCBF data.     

Participatory work place intervention for stress prevention in primary health care. A randomized controlled trial

The aim of this study is to explore whether a participatory, organizational intervention can reduce work-related risk factors, and thereby prevent stress-related ill health. We build on the job demand-control and effort-reward imbalance models of stress. It is a two-armed randomized trial, with one primary health care unit receiving the intervention and a two-unit control group. Validated questionnaires for the assessment of psychosocial work environment and health were administered, at the baseline and at 6 and 12-month follow up. The primary outcome was job strain. Secondary outcomes were effort–reward imbalance, exhaustion, sleep, and recovery. Group-level objective data on workload and data about relevant processes during the study were continuously collected. The changes in the intervention group with regard to job strain, effort-reward imbalance, exhaustion, sleep and recovery were not statistically different from changes in the control group. For the non-exhausted employees though, reward was significantly higher at follow up compared to baseline, but only in the intervention group. An important piece of information is that the objective workload was statistically significantly higher in the intervention group throughout the study. Not all the components of the intervention were implemented as intended. Context and process information, such as objective data and implementation fidelity are necessary for a valid interpretation of the results.     

Models of white matter injury: comparison of infectious, hypoxic-ischemic, and excitotoxic insults

White matter damage (WMD) in preterm neonates is strongly associated with adverse outcome. The etiology of white matter injury is not known but clinical data suggest that ischemia-reperfusion and/or infection-inflammation are important factors. Furthermore, antenatal infection seems to be an important risk factor for brain injury in term infants. In order to explore the pathophysiological mechanisms of WMD and to better understand how infectious agents may affect the vulnerability of the immature brain to injury, numerous novel animal models have been developed over the past decade. WMD can be induced by antenatal or postnatal administration of microbes (E. coli or Gardnerella vaginalis), virus (border disease virus) or bacterial products (lipopolysaccharide, LPS). Alternatively, various hypoperfusion paradigms or administration of excitatory amino acid receptor agonists (excitotoxicity models) can be used. Irrespective of which insult is utilized, the maturational age of the CNS and choice of species seem critical. Generally, lesions with similarity to human WMD, with respect to distribution and morphological characteristics, are easier to induce in gyrencephalic species (rabbits, dogs, cats and sheep) than in rodents. Recently, however, models have been developed in rats (PND 1-7), using either bilateral carotid occlusion or combined hypoxia-ischemia, that produce predominantly white matter lesions. LPS is the infectious agent most often used to produce WMD in immature dogs, cats, or fetal sheep. The mechanism whereby LPS induces brain injury is not completely understood but involves activation of toll-like receptor 4 on immune cells with initiation of a generalized inflammatory response resulting in systemic hypoglycemia, perturbation of coagulation, cerebral hypoperfusion, and activation of inflammatory cells in the CNS. LPS and umbilical cord occlusion both produce WMD with quite similar distribution in 65% gestational sheep. The morphological appearance is different, however, with a more pronounced infiltration of inflammatory cells into the brain and focal microglia/macrophage ("inflammatory WMD") in response to LPS compared to hypoperfusion evoking a more diffuse microglial response usually devoid of cellular infiltrates ("ischemic WMD"). Furthermore, low doses of LPS that by themselves have no adverse effects in 7-day-old rats (maturation corresponding to the near term human fetus), dramatically increase brain injury to a subsequent hypoxic-ischemic challenge, implicating that bacterial products can sensitize the immature CNS. Contrary to this finding, other bacterial agents like lipoteichoic acid were recently shown to induce tolerance of the immature brain suggesting that the innate immune system may respond differently to various ligands, which needs to be further explored.     

Defects of immediate memory related to the cerebral blood flow distribution

Different forms of memory defects were studied in 16 patients with organic dementia. The test performance was related to the regional cerebral blood flow (rCBF) in the left (dominant) hemisphere. Verbal memory (Paired Associates) correlated to the blood flow in temporal and parietal regions. Spatial recognition (Memory for Objects, Memory for Geometrical Design) correlated to the temporal and lower frontal regions. One spatial memory test (Visual Retention test) correlated to the temporal region only. Another spatial memory test (Memory for Design) did not show correlations to any regions of the dominant hemisphere. Finally it was found that the hemisphere mean flow values did not correlate to performance. This emphasizes the main finding—the regional correlations. It is concluded that memory performance involves various extratemporal regions depending upon the specific quality of the memory task to be performed.     

Narrative retelling in children with neurodevelopmental disorders: Is there a role for nonverbal temporal‐sequencing skills?

Oral narrative retelling is often problematic for children with communicative and neurodevelopmental disorders. However, beyond a suggested role of language level, little is known about the basis of narrative performance. In this study we examine whether oral narrative retelling might be associated not just with language level but also with skills related to nonverbal narrative temporal sequencing. A diagnostically heterogeneous sample of Swedish‐speaking children with a full scale IQ >70 was included in the study (N = 55; age 6–9 years). Narrative retelling skills were measured using the three subscores from the bus story test (BST). Independent predictors included (1) temporal sequencing skills according to a picture arrangement test and (2) a language skills factor consisting of definitional vocabulary and receptive grammar. Regression analyses show that language skills predicted BST Sentence Length and Subordinate Clauses subscores, while both temporal sequencing and language were independently linked with the BST Information subscore. When subdividing the sample based on nonverbal temporal sequencing level, a significant subgroup difference was found only for BST Information. Finally, a principal component analysis shows that temporal sequencing and BST Information loaded on a common factor, separately from the language measures. It is concluded that language level is an important correlate of narrative performance more generally in this diagnostically heterogeneous sample, and that nonverbal temporal sequencing functions are important especially for conveying story information. Theoretical and clinical implications are discussed.     

More Appreciation of Life or Regretting the Test? Experiences of Living as a Mutation Carrier of Huntington’s Disease

Little is known about how the knowledge of being a mutation carrier for Huntington’s disease (HD) influences lives, emotionally and socially. In this qualitative study 10 interviews were conducted to explore the long term (>5 years) experiences of being a mutation carrier. The results showed a broad variety of both positive and negative impact on the carriers’ lives. The most prominent positive changes reported were a greater appreciation of life and a tendency to bring the family closer together. On the other hand, some participants expressed decisional regrets and discussed the negative impact this knowledge had on their psychological well-being. The knowledge variously served as either a motivator or an obstacle in pursuing further education, career or investment in personal health. Deeper understanding of people’s reactions to the certainty of knowing they will become affected with HD is essential for the genetic counseling team in order to provide appropriate support.     

Speech disturbances in presenile dementia related to local cerebral blood flow abnormalities in the dominant hemisphere

Ten female patients, age 50–70 years, suffering from presenile dementia and showing signs of defective speech function were analyzed. All patients underwent measurements of regional cerebral blood flow (rCBF) by the xenon clearance technique using a 32-detector piece of equipment, and all showed a marked reduction of the hemisphere mean blood flow level. In addition, regional decreases of blood flow of the gray matter was demonstrated. Patients with a marked reduction in the temporo-parieto-occipital regions showed signs of receptive aphasia including alexia and agraphia. Patients with a marked frontal reduction showed signs of expressive aphasia of various types including stereotyped language, voluble speech, echolalia, and mutism in later stages. The results give further support to our previous conclusion that subsymptoms of presenile dementia, apparently also speech disturbances, can be related to local degenerative changes in the brain, which in their turn are accompanied by local reductions of the blood flow of the gray matter. There is pathoanatomical evidence to support this conclusion.     

What to Do with a Second Chance in Life? Long-Term Experiences of Non-carriers of Huntington’s Disease

Little is known about how people’s lives are influenced when going from a 50% risk status of Huntington’s disease (HD) to no risk after performing predictive testing. In this study, 20 interviews were conducted to explore the long-term (>?5 years) experiences after receiving predictive test results as a non-carrier of HD. The results showed a broad variety of both positive and negative reactions. The most prominent positive reaction reported was feelings of relief and gratitude, of not carrying the HD mutation for themselves and for their children. Also, the non-carrier status promoted in some individuals’ significant life changes such as a wishing to have (more) children, pursuing a career or breaking up from an unhappy relationship. However, negative reactions on their psychological well-being were also described. Some had experienced psychological pressure of needing to do something extraordinary in their lives; others expressed feelings of guilt towards affected or untested siblings, resulting in sadness or clinical depression. The new genetic risk status could generate a need of re-orientation, a process that for some persons took several years to accomplish. The results of the present study show the importance of offering long-term post-result counselling for non-carriers in order to deal with the psychological consequences that may follow predictive testing.