Measles Sclerosing Subacute PanEncephalitis (SSPE), an intriguing and ever-present disease: Data, assumptions and new perspectives.

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a rare, non-treatable and fatal neurological complication of measles, still present due to the return of the epidemic linked to the loosening of vaccination policies. Its mechanism remains unexplained. OBJECTIVE: The main objective was to investigate explanatory variables relating to the risk of developing SSPE and its pathophysiology. METHODS: Literature analysis was focused on different varieties of SSPE: perinatal forms, short-incubation forms similar to acute measles inclusion body encephalitis (MIBE), rapidly evolving forms, forms occurring in the immunosuppressed, adult forms, and family forms. In addition, several studies on the parameters of innate immunity and interferon responses of patients were analyzed. RESULTS: Two main data were highlighted: a relationship between the so-called fulminant forms and the prescription of corticosteroids was established. In familial SSPE, two groups were individualized according to the duration of the latency period, prompting an analysis of patient exomes. CONCLUSION: Treatment with corticosteroids should be banned. Knowledge of the genes involved and epigenetics should be useful for understanding the pathophysiology of SSPE and other late-onset neurological infections with RNA viruses.

Associations among body size across the life course, adult height and endometriosis.

STUDY QUESTION: Are body size across the life course and adult height associated with endometriosis? SUMMARY ANSWER: Endometriosis is associated with lean body size during childhood, adolescence and adulthood; tall total adult height; and tall sitting height. WHAT IS KNOWN ALREADY: The literature suggests that both adult body size and height are associated with endometriosis risk, but few studies have investigated the role of body size across the life course. Additionally, no study has investigated the relationships between components of height and endometriosis. STUDY DESIGN, SIZE, DURATION: We used a nested case-control design within E3N (Etude Epidémiologique auprès de femmes de l'Education Nationale), a prospective cohort of French women. Data were updated every 2-3 years through self-administered questionnaires. Odds ratios (ORs) and 95% CIs were computed using logistic regression models adjusted for a priori confounding factors. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 2416 endometriosis cases were reported as surgically ascertained among the 61 208 included women. MAIN RESULTS AND THE ROLE OF CHANCE: The odds of endometriosis were lower among women who reported having a large versus lean body size at 8 years (P for trend = 0.003), at menarche (P for trend < 0.0001) and at ages 20-25 years (P for trend < 0.0001). Women in the highest quartiles of height had statistically significantly increased odds of endometriosis compared to those in the lowest (<158 cm) (162-164 cm: OR = 1.28, 95% CI = 1.12-1.46; ≥165 cm: OR = 1.33, 95% CI = 1.18-1.49, P for trend < 0.0001). Statistically significantly increased odds were also observed among women with a taller sitting height (OR = 1.24, 95% CI = 1.05-1.47, P for trend = 0.01). Leg length was not statistically significantly associated with endometriosis. LIMITATIONS REASONS FOR CAUTION: Endometriosis cases may be prone to misclassification; however, we restricted our case definition to surgically-confirmed cases, which showed a high validation rate. Body size is based on retrospective self-report, which may be subject to recall bias. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study suggest that endometriosis is positively associated with lean body size across the life course and total adult height. They also suggest that components of height are associated with endometriosis, which should be investigated further. STUDY FUNDING/COMPETING INTEREST(S): The Mutuelle Générale de l'Education Nationale (MGEN); the European Community; the French League against Cancer (LNCC); Gustave Roussy; the French Institute of Health and Medical Research (Inserm). L.V.F. was supported by a T32 grant (#HD060454) in reproductive, perinatal and pediatric epidemiology from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Cancer Institute (3R25CA057711) National Institutes of Health. M.K. was supported by a Marie Curie Fellowship within the seventh European Community Framework Programme (#PIOF-GA-2011-302078). The authors have no conflicts of interest to declare.

Colonic overexpression of the T-type calcium channel Cav 3.2 in a mouse model of visceral hypersensitivity and in irritable bowel syndrome patients.

BACKGROUND: Among the different mechanisms involved in irritable bowel syndrome (IBS) physiopathology, visceral hypersensitivity seems to play a key role. It involves sensitization of the colonic primary afferent fibers, especially through an overexpression of ion channels. The aims of this translational study were to investigate the colonic expression of Cav 3.2 calcium channels and their involvement in an animal model of colonic hypersensitivity, and to assess their expression in the colonic mucosa of symptomatic IBS patients. METHODS: This bench-to-bed study combined a preclinical experimental study on mice and a case-control clinical study. Preclinical studies were performed on wild-type and Cav 3.2-KO mice. Colonic sensitivity and Cav 3.2 expression were studied after a low-dose treatment of dextran sodium sulfate (DSS 0.5%). Regarding the clinical study, colonic biopsies were performed in 14 IBS patients and 16 controls during a colonoscopy to analyze the mucosal Cav 3.2 expression. KEY RESULTS: Wild-type, but not Cav 3.2-KO, mice developed visceral hypersensitivity without colonic inflammation, after 0.5% DSS treatment. A significant increase of Cav 3.2 mRNA (p = 0.04) was found in the colon of low-dose DSS-treated wild-type (WT) mice compared to their controls. In human colonic biopsies, the Cav 3.2 mRNA level was significantly higher in the IBS group compared to the control group (p = 0.01). The immunofluorescence staining revealed their protein expression in colonic mucosa, particularly in nerve fibers. CONCLUSIONS & INFERENCES: This translational study supports the involvement of the calcium channels Cav 3.2 in abdominal pain, as observed in IBS patients. It opens new therapeutic perspectives based on molecules specifically blocking these channels.

Anti-nociceptive effect of Faecalibacterium prausnitzii in non-inflammatory IBS-like models.

Visceral pain and intestinal dysbiosis are associated with Irritable Bowel Syndrome (IBS), a common functional gastrointestinal disorder without available efficient therapies. In this study, a decrease of Faecalibacterium prausnitzii presence has been observed in an IBS-like rodent model induced by a neonatal maternal separation (NMS) stress. Moreover, it was investigated whether F. prausnitzii may have an impact on colonic sensitivity. The A2-165 reference strain, but not its supernatant, significantly decreased colonic hypersensitivity induced by either NMS in mice or partial restraint stress in rats. This effect was associated with a reinforcement of intestinal epithelial barrier. Thus, F. prausnitzii exhibits anti-nociceptive properties, indicating its potential to treat abdominal pain in IBS patients.

Prenatal features of isolated subependymal pseudocysts associated with adverse pregnancy outcome.

OBJECTIVES: To identify at prenatal ultrasound (US) the features of apparently isolated subependymal pseudocysts (SEPC) that may indicate underlying pathology and should lead to further investigations. METHODS: This was a retrospective study of cases with SEPC detected on prenatal US and/or magnetic resonance imaging (MRI). Those with apparently isolated SEPC at US were classified into two groups as follows: Group 1 (n = 29): normal prenatal US and MRI (except for SEPC) and normal outcome; Group 2 (n = 12): normal prenatal cerebral US (except for SEPC) and abnormal prenatal cerebral MRI with or without abnormal outcome. A third group (n = 9) included cases with abnormal prenatal US and MRI. The latter cases with obvious cerebral abnormalities at US were excluded from the statistical analysis as they do not represent a diagnostic dilemma for clinicians. Groups 1 and 2 were analyzed, comparing them with respect to their SEPC characteristics (size, number, location in relation to the caudothalamic notch and the ventricular horns and morphology) and extracerebral abnormalities. RESULTS: The mean ± SD SEPC great axis was longer in Group 2 (11.67 ± 5.82 mm) than it was in Group 1 (8.00 ± 5.64 mm) (P = 0.021), suggesting an optimal cut-off for size of SEPC of ≥ 9 mm (sensitivity = 75%, specificity = 62%) to maximize sensitivity for predicting pathological outcome. SEPC adjacent to the temporal horns and SEPC located posterior to the caudothalamic notch were observed more frequently in Group 2, indicating their association with poor outcome (P = 0.003 and P = 0.003, respectively). Atypical morphology and extracerebral abnormalities were observed more frequently in Group 2 (P = 0.013 and P = 0.044, respectively). There was no statistically significant difference between groups for either number or location of cysts along the inferior wall or adjacent to the lateral wall of the frontal horns (P = 0.591 and P = 0.156, respectively). CONCLUSION: When apparently isolated SEPC are observed at prenatal US, further investigations should be performed under the following circumstances: (1) SEPC great axis ≥ 9 mm; (2) SEPC adjacent to the occipital and temporal horns; (3) SEPC located posterior to the caudothalamic notch; (4) SEPC with atypical morphology.

Abnormal shape of the cavum septi pellucidi: an indirect sign of partial agenesis of the corpus callosum.

OBJECTIVE: To describe and assess the presence of a new indirect sign of partial agenesis of the corpus callosum (pACC): an abnormally shaped cavum septi pellucidi (CSP). METHODS: We analyzed retrospectively images from all 71 cases of pACC seen at two referral centers between September 2006 and April 2014. Abnormally shaped CSP was diagnosed when its lateral dimension was greater than its anteroposterior dimension in the axial transthalamic plane, and the incidence of this sign was assessed. We also examined the following variables: gestational age at referral, indication for referral, which (if any) of the four corpus callosal segments were abnormal, presence of other, previously established, indirect signs of callosal agenesis (ACC) and presence of additional cerebral or extracerebral anomalies. RESULTS: In 56 of the 71 (79%) cases, the CSP was measurable; it was abnormally shaped in 19 (34%) of these cases, 15 (79%) of which had no other indirect signs of pACC. Of 23 cases with isolated pACC and no other indirect signs, 12 (52%) had an abnormally shaped CSP. CONCLUSIONS: In a significant proportion of cases of pACC detected prenatally, the shape of the CSP is abnormal. This should be considered an additional indirect sign of pACC, and is frequently the only clue to the diagnosis. When observing this sign in a screening context, pACC should be considered, and an attempt to visualize the corpus callosum directly in the midsagittal plane is suggested.

Peripheral contribution of NGF and ASIC1a to colonic hypersensitivity in a rat model of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with idiopathic colonic hypersensitivity (CHS). However, recent studies suggest that low-grade inflammation could underlie CHS in IBS. The pro-inflammatory mediator nerve growth factor (NGF) plays a key role in the sensitization of peripheral pain pathways and several studies have reported its contribution to visceral pain development. NGF modulates the expression of Acid-Sensing Ion Channels (ASICs), which are proton sensors involved in sensory neurons sensitization. This study examined the peripheral contribution of NGF and ASICs to IBS-like CHS induced by butyrate enemas in the rat colon. METHODS: Colorectal distension and immunohistochemical staining of sensory neurons were used to evaluate NGF and ASICs contribution to the development of butyrate-induced CHS. KEY RESULTS: Systemic injection of anti-NGF antibodies or the ASICs inhibitor amiloride prevented the development of butyrate-induced CHS. A significant increase in NGF and ASIC1a protein expression levels was observed in sensory neurons of rats displaying butyrate-induced CHS. This increase was specific of small- and medium-diameter L1 + S1 sensory neurons, where ASIC1a was co-expressed with NGF or trkA in CGRP-immunoreactive somas. ASIC1a was also overexpressed in retrogradely labeled colon sensory neurons. Interestingly, anti-NGF antibody administration prevented ASIC1a overexpression in sensory neurons of butyrate-treated rats. CONCLUSIONS & INFERENCES: Our data suggest that peripheral NGF and ASIC1a concomitantly contribute to the development of butyrate-induced CHS NGF-ASIC1a interplay may have a pivotal role in the sensitization of colonic sensory neurons and as such, could be considered as a potential new therapeutic target for IBS treatment.

Periventricular nodular heterotopia on prenatal ultrasound and magnetic resonance imaging.

OBJECTIVES: To describe the prenatal ultrasound and magnetic resonance imaging (MRI) findings suggestive of periventricular nodular heterotopia (PNH). METHODS: This retrospective case series included fetuses referred to our institution for brain MRI between 2007 and 2012, which were diagnosed with PNH and confirmed by postnatal MRI or autopsy. The type of PNH, associated ventriculomegaly and associated malformations are reported. RESULTS: We included 11 fetuses (nine female, two male) with a mean gestational age at diagnosis of 31 (range, 23-34) weeks. PNH lesions were small and diffuse (n = 7), large and multiple (n = 1) or single (n = 3). A targeted ultrasound examination performed before fetal MRI missed the diagnosis in four cases (one diffuse and three single); a further ultrasound examination performed after MRI diagnosed PNH in two of these four cases. Ventriculomegaly was present in six cases (four unilateral and two bilateral). PNH appeared in all cases as nodules of intermediate echogenicity protruding into the ventricular lumen. In all cases of diffuse PNH, the frontal horns and bodies of the lateral ventricles appeared square in shape on coronal view, with irregular borders on axial view. Associated cerebral malformations were observed in seven cases and included corpus callosal agenesis (n = 4, with additional malformations in two) and retrocerebellar cyst (n = 3). Extracerebral malformations were also present in two cases. Maternal MRI was performed in five of the six cases of isolated small and diffuse PNH in female fetuses, and demonstrated PNH in two of these. CONCLUSION: PNH is underdiagnosed at prenatal ultrasound, even on targeted scans. Irregular ventricular borders on axial view and irregular square-shaped lateral ventricles on coronal view are suggestive of PNH at prenatal ultrasound.

Review article: Associations between immune activation, intestinal permeability and the irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS), one of the most common gastrointestinal disorders, markedly impairing patients' quality of life. Drug development for IBS treatment has been hampered by the lack of understanding of IBS aetiology. In recent years, numerous data have emerged that suggest the involvement of immune activation in IBS, at least in a subset of patients. AIM: To determine whether immune activation and intestinal permeabilisation are more frequently observed in IBS patients compared with healthy controls. METHODS: The scientific bibliography was searched using the following keywords: irritable bowel syndrome, inflammation, immune activation, permeabilisation, intestine, assay, histology and human. The retrieved studies, including blood, faecal and histological studies, were analysed to provide a comprehensive and structured overview of the available data including the type of assay, type of inflammatory marker investigated or intestinal segment studied. RESULTS: Immune activation was more frequently observed in IBS patients than in healthy controls. An increase in the number of mast cells and lymphocytes, an alteration in cytokine levels and intestinal permeabilisation were reported in IBS patients. No consistent changes in the numbers of B cells or enterochromaffin cells or in mucosal serotonin production were demonstrated. CONCLUSIONS: The changes observed were modest and often heterogeneous among the studied population. Only appropriate interventions improving irritable bowel syndrome symptoms could highlight and confirm the role of immune activation in this pathophysiology.

[Impact of prenatal corpus callosum agenesis diagnosis on pregnancy outcome. Evaluation of 155 cases between 2000 and 2006]. / Impact du dépistage anténatal des agénésies du corps calleux sur le devenir des grossesses. Etude de 155 dossiers de 2000 à 2006.

The purpose of this study was to investigate the changes between 2000 and 2006 in pregnancy outcome when a diagnosis of either isolated or associated fetal corpus callosum agenesis (CCA) was made, given that beginning in 2003, the information provided to couples facing this problem related a good prognosis in nearly 80 % of cases of isolated CCA and a poor prognosis in 20 % of cases. We retrospectively analyzed all pregnancies with a fetal diagnosis of CCA between 2000 and 2006 (n=155) and compared two periods: the first group from 2000 to June 2003, the second from July 2003 to 2006. For each group, we analyzed the type of CCA during pregnancy - either isolated or associated - and the outcome of pregnancy. We compared the rate of pregnancy termination before and after 2003 and analyzed the accuracy of the prenatal CCA diagnosis. Of the 155 patients studied, 62 terminated the pregnancy. The overall rate of termination decreased from 31/70 to 31/85. When CCA was said to be isolated prenatally, the rate of pregnancy termination fell from 13/35 to 9/44 (-17 %) (p<0.05). Nine diagnoses of CCA were corrected after birth or by postmortem examination. Improvement of prenatal diagnosis requires better quality of prenatal screening, with a more systematic study of dysmorphic features, a study of correlations between the type of CCA and the neurological prognosis, and more genetic studies.

Novel neuronal proteolipid protein isoforms encoded by the human myelin proteolipid protein 1 gene.

The human myelin proteolipid protein 1 gene (hPLP1), which encodes the major structural myelin proteins of the central nervous system (CNS), is classically described as expressed in the oligodendrocytes, the CNS myelinating cells. We identified two new exons in the intron 1 of the hPLP1 gene that lead to the expression of additional mRNA and protein isoforms mainly expressed in neurons instead of oligodendrocytes. Those novel neuronal PLP isoforms are detected as soon as human fetal development and their concomitant expression is specific of the human species. As classical PLP proteins, the novel protein isoforms seem to be addressed to the plasma membrane. These results suggest for the first time that PLP may have functions in humans not only in oligodendrocytes but also in neurons and could be implicated in axono-glial communication. Moreover, this neuronal expression of the hPLP1 gene might explain the neuronal dysfunctions in patients carrying hPLP1 gene mutations.

Prenatal ultrasonographic diagnosis of polymicrogyria.

We report a rare case of polymicrogyria diagnosed at 27 weeks' gestation on ultrasound examination and associated with cytomegalovirus (CMV) infection. The ultrasound finding suggesting this diagnosis was the direct visibility of the overfolded cortical ribbon. The cerebral surface was clearly visible because of a markedly enlarged pericerebral space associated with micrencephaly secondary to CMV infection. Bilateral opercular dysplasia was also present. Very few sonographic markers of infectious fetopathy were observed other than periventricular cysts located behind both ventricular horns. Magnetic resonance imaging (MRI) of the fetal brain confirmed the ultrasound findings and also showed the presence of marked micrencephaly, whereas cephalic measurements acquired on ultrasound examination (biparietal diameter and head circumference) were within the normal range. This case emphasizes the complementary roles of sonography and MRI in the prenatal diagnosis of cerebral abnormalities. Moreover, it illustrates the fact that polymicrogyria is easier to diagnose on ultrasound examination during the second trimester, before the development of secondary sulci.

Interactive involvement of brain derived neurotrophic factor, nerve growth factor, and calcitonin gene related peptide in colonic hypersensitivity in the rat.

BACKGROUND AND AIMS: Neutrophins are involved in somatic and visceral hypersensitivity. The action of nerve growth factor (NGF) on sensory neurones contributes to the development of referred colonic hypersensitivity induced by trinitrobenzene sulfonic acid (TNBS). Based on data on brain derived neurotrophic factor (BDNF) and calcitonin gene related peptide (CGRP) in pain, the aims of the present study were: (1) to investigate the involvement of BDNF and CGRP in this model of referred colonic hypersensitivity, (2) to test the effect of exogenous BDNF and CGRP on the colonic pain threshold, and (3) to investigate the relationship between BDNF, NGF, and CGRP by testing antineurotrophin antibodies or h-CGRP 8-37 (a CGRP antagonist) on bowel hypersensitivity induced by these peptides. METHODS: Colonic sensitivity was assessed using a colonic distension procedure. RESULTS: Anti-BDNF antibody and h-CGRP 8-37 reversed the induced decrease in colonic threshold (33.4 (2.1) and 40.3 (4.1) mm Hg, respectively, compared with a vehicle score of approximately 18 mm Hg; p<0.001). BDNF (1-100 ng/rat intraperitoneally) induced a significant dose dependent decrease in colonic reaction threshold in healthy rats. This effect was reversed by an anti-BDNF antibody and an anti-NGF antibody (33.4 (0.6) v 18.7 (0.7) mm Hg (p<0.001), anti-NGF v vehicle). NGF induced colonic hypersensitivity was reversed by h-CGRP 8-37 but not by the anti-BDNF antibody. Finally, antineurotrophin antibody could not reverse CGRP induced colonic hypersensitivity (at a dose of 1 microg/kg intraperitoneally). CONCLUSION: Systemic BDNF, NGF, and CGRP can induce visceral hypersensitivity alone and interactively. This cascade might be involved in TNBS induced referred colonic hypersensitivity in which each of these peptides is involved.

[Parry-Romberg's syndrome and epilepsy]. / Syndrome de Parry-Romberg et épilepsie.

INTRODUCTION: Parry-Romberg's syndrome or progressive facial hemiatrophy is a rare disorder of unknown etiology which may be accompanied by neurological complications, frequently epilepsy, usually focal refractory epilepsy. The associated brain lesions are located on the same side as the half face atrophy and may progress. OBSERVATION: We report the cases of two patients with Parry-Romberg's syndrome and epilepsy. Neurosurgery was performed in one patient, enabling a histological study. CONCLUSION: The link between Parry-Romberg's syndrome and epilepsy is discussed and the neurodevelopmental theory with vascular dysgenesis is suggested.