Childhood acute disseminated encephalomyelitis: the role of brain and spinal cord MRI

BACKGROUND: It is recognised that the clinical and radiological spectrum of childhood acute disseminated encephalomyelitis (ADEM) is wide. OBJECTIVE: To determine whether initial MRI features are predictive of clinical outcome and to determine the role of MRI in the management of ADEM. MATERIALS AND METHODS: The MRI scans of ten consecutive children (eight boys, two girls), clinically and radiologically diagnosed to have ADEM, were retrospectively reviewed. Follow-up MRI was available for eight patients. RESULTS: Lesions ranged from small and punctate (<1 cm) to moderate sized and confluent (4-5 cm) to diffuse and extensive. Spinal cord lesions, seen in five of seven children, were contiguous or segmental. Seven children (70%) made good clinical recovery while three children (30%) remained severely handicapped. There was no correlation between the site, extent and pattern of involvement and clinical outcome. However, the evolution of MRI findings on follow-up correlated well with the subsequent clinical course and outcome. CONCLUSIONS: Although the extent and site of lesions on initial MRI scans are not predictive of clinical outcome, early MRI of the brain and spine is useful in aiding clinical diagnosis, and subsequent follow-up MRI is helpful in monitoring disease progression.     

Temporal sequence and functional implications of V beta-specific T cell receptor down-regulation and costimulatory molecule expression following in vitro stimulation with the staphylococcal superantigen Toxic shock syndrome toxin-1

The superantigen toxic shock syndrome toxin-1 (TSST-1) is implicated as the major cause of staphylococcal toxic shock syndrome. The temporal sequence of early signaling events in human peripheral blood mononuclear cells following TSST-1 stimulation was examined. TSST-1 induced rapid and complete down-regulation of V beta 2-specific T cell receptor (TCR), followed by transient CD154 expression on CD4(+) lymphocytes. This was sequentially followed by the up-regulation of CD86, CD80, CD40, and human leukocyte antigen-DR expression on CD14(+) monocytes. In contrast, S14N, a TSST-1 mutant toxin with a single amino acid substitution that is known to be impaired in interleukin (IL)--2, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha secretion, was deficient in both V beta 2-TCR down-regulation and CD154 and CD80/CD86 expression. Furthermore, pretreatment with monoclonal antibodies against V beta 2-TCR, CD80/CD86, and CD154 significantly inhibited TSST-1-induced IL-2, IFN-gamma, and TNF-alpha secretion. Taken together, these results indicate that early V beta-specific TCR activation, along with CD80/CD86 and CD154 costimulation, are key determinants of the TSST-1-induced proinflammatory cytokine response.     

Platelet receptor and clotting factor polymorphisms as genetic risk factors for thromboembolic complications in heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is an immune mediated adverse reaction to heparin treatment often associated with limb- and/or life-threatening thromboembolic complications (TECs). Presently, no prognostic marker has been identified that allows differentiation between mildly (isolated thrombocytopenia) and severely (TECs) affected patients. This study assesses the impact of platelet glycoprotein- and clotting factor polymorphisms in HIT-patients with isolated thrombocytopenia compared to HIT-patients with TECs. Sixty-three HIT-patients with isolated thrombocytopenia and 79 HIT-patients with HIT-related TECs were genotyped for GPIIb-IIIa polymorphisms (HPA-1, HPA-3), GPIa-IIa polymorphisms (HPA-5, GPIaC807T), GPIb-IX-V polymorphisms (HPA-2, Kozak-5, VNTR), and clotting factor polymorphisms (FV-Leiden R506Q, prothrombin PT-G20210A and MTHFR C677T). Women more often presented with TECs than men (P = 0.04). No differences in genotype frequencies could be seen on comparing HIT-patients with and without TECs. Analysing men and women separately, the C allele of the Kozak polymorphism was overrepresented in men who developed TECs (P = 0.034). The enhanced risk of women to develop HIT-associated TECs remains unexplained but it is potentially important in view of recent data on sex-hormone related changes of haemostasis. There was no correlation between platelet glycoprotein- and clotting factor polymorphisms and the risk to develop HIT-associated TECs. An association between the development of TECs and the Kozak-5C allele could be seen among male patients. However, this would need to be assessed in further larger studies. Most likely, the high levels of thrombin generation during acute HIT are so procoagulant that less pronounced risk factors such as polymorphisms are overshadowed.     

Neurocutaneous melanomatosis with a rapidly deteriorating course

Neurocutaneous melanosis is a rare congenital syndrome characterized by large or multiple congenital melanocytic nevi and benign or malignant pigment cell tumors of the leptomeninges. The prognosis is extremely poor for symptomatic patients, even in the absence of malignant melanoma. We present serial MR imaging findings in the brain and spine of a child with congenital giant hairy nevi who developed progressive leptomeningeal melanomatosis and whose neurologic condition rapidly deteriorated.     

Beta-amyloid peptide potentiates inflammatory responses induced by lipopolysaccharide,interferon -gamma and 'advanced glycation endproducts' in a murine microglia cell line

beta-Amyloid (Abeta) plaques are characteristic hallmarks of Alzheimer's disease (AD). In AD, it has been suggested that activation of microglial cells might be the link between Abeta deposition and neuronal degeneration. Activated microglia are associated with senile plaques and produce free radicals and inflammatory cytokines. However, it is still not clear whether Abeta needs a prestimulated environment to exert its proinflammatory potential. Advanced glycation endproducts (AGEs), protein-bound oxidation products of sugars, have been shown to accumulate in senile plaques and could induce a silent but chronic inflammation in the AD brain. We tested whether Abeta acts as an amplifier of a submaximal proinflammatory response initiated by exposure to chicken egg albumin-AGE, lipopolysaccharide or interferon-gamma. Synthetic Abeta was used to produce three different samples (Abeta-fibrilar; Abeta-aggregated; Abeta-AGE), which were characterized for beta-sheeted fibrils by the thioflavin-T test and electron microscopy. As markers of microglial activation, nitric oxide, interleukin-6, macrophage-colony stimulation factor and tumour necrosis factor-alpha production was measured. All three Abeta samples alone could not induce a detectable microglial response. The combination of Abeta preparations, however, with the coinducers provoked a strong microglial response, whereby Abeta-AGE and fibrilar Abeta were more potent inflammatory signals than aggregated Abeta. Thus, Abeta in senile plaques can amplify microglial activation by a coexisting submaximal inflammatory stimulus. Hence, anti-inflammatory therapeutics could either target the primary proinflammatory signal (e.g. by limiting AGE-formation by AGE inhibitors or cross-link breakers) or the amplifyer Abeta (e.g. by limiting Abeta production by beta- or gamma-secretase inhibitors).     

Application of the PRECEDE model to understanding mental health promoting behaviors in Hong Kong.

The burdens related to mental illness have been increasingly recognized in many countries. Nevertheless, research in positive mental health behaviors remains scarce. This study utilizes the Predisposing, Reinforcing, and Enabling Causes in Education Diagnosis and Evaluation (PRECEDE) model to identify factors associated with mental health promoting behaviors and to examine the effects of these behaviors on mental well-being and quality of life among 941 adults in Hong Kong. Structural equation modeling shows that sense of coherence (predisposing factor), social support (reinforcing factor), and daily hassles (enabling factor) are significantly related to mental health promoting behaviors, which are associated with mental well-being and quality of life. Results of bootstrap analyses confirm the mediating role of mental health promoting behaviors on well-being and quality of life. The study supports the application of the PRECEDE model in understanding mental health promoting behaviors and demonstrates its relationships with well-being and quality of life.     

Stellenwert der Radiokephalometrie in der Diagnostik bei OSAS im Erwachsenenalter

Zusammenfassung Untersuchungen zum Zusammenhang zwischen kephalometrischen und polysomnographischen Befunden wurden bisher von mehreren Autoren überwiegend mit linearen statistischen Methoden durchgeführt. Die eigene Arbeitsgruppe interessierte, ob durch den Einsatz mehrdimensionaler statistischer Verfahren der Informationsgehalt der Radiokephalometrie stärker ausgeschöpft werden kann. 77 Patienten mit OSAS (Alter 25 69 Jahre, RDI 3,6 ­ 90,1/h) wurden polysomnographisch und kephalometrisch untersucht. Die Vermessung der knöchernen Parameter erfolgte mit dem Computerprogramm WinCeph und die der Pharynxweichteile in Anlehnung an Hochban et al. (Dtsch Zahnärztl Z 49: 777 782, 1994). Mittels logistischer Regressionen wurde geprüft, ob polysomnographische RDI-Werte > 20 aus dem Röntgenbild vorhergesagt werden können. Die Kopplung der 10 knöchernen Parameter ergab bezüglich der Erkennung erhöhter RDI-Werte eine Sensitivität von 93 % bei einer Spezifität von 44 %. Vier Parameter fielen durch besonders hohe relative Risiken auf. Die alleinige Verwendung der Weichteilparameter zeigte eine Sensitivität von 98 % bei einer Spezifität von 13 %. Die gleichzeitige Betrachtung von Weichteil- und knöchernen Parametern erbrachte eine Sensitivität von 96 % bei einer Spezifität von 40 % in der Erkennung erhöhter RDI-Werte. Die Radiokephalometrie gehört nicht zur Basisdiagnostik des OSAS, sie kann aber bei kieferchirurgischen Operationsentscheidungen einen Beitrag leisten.