Sex and the migraine brain.

The brain responds differently to environmental and internal signals that relate to the stage of development of neural systems. While genetic and epigenetic factors contribute to a premorbid state, hormonal fluctuations in women may alter the set point of migraine. The cyclic surges of gonadal hormones may directly alter neuronal, glial and astrocyte function throughout the brain. Estrogen is mainly excitatory and progesterone inhibitory on brain neuronal systems. These changes contribute to the allostatic load of the migraine condition that most notably starts at puberty in girls.

Heart rate variability after bariatric surgery: The add-on value of exercise.

PURPOSE: To assess the impact of bariatric surgery and an added supervised exercise training programme on heart rate variability (HRV) in patients with severe obesity. METHODS: Fifty-nine patients who underwent bariatric surgery were randomised in the post-operative period to a 12-week supervised exercise training programme (moderate intensity combination aerobic/resistance exercise training programme) or a control group. Indices of HRV including time-domain, spectral-domain, and nonlinear parameters were measured preoperatively, and at 3, 6, and 12 months. RESULTS: After the surgical procedure, both groups improved anthropometric parameters. Type 2 diabetes, hypertension, and dyslipidemia resolutions were similar between groups. Total body weight loss at 6 and 12 months were also comparable between groups (6 months: 28 ± 6 vs. 30 ± 6%; 12 months: 38 ± 9 vs. 38 ± 10%; control vs. intervention group respectively). Bariatric surgery improved HRV parameters at 12 months compared to the pre-operative values in the intervention group: standard deviation of R-R interval (SDNN) (156.0 ± 46.4 vs. 122.6 ± 33.1 ms), low frequency (LF) (6.3 ± 0.8 vs. 5.8 ± 0.7 ms2), and high frequency (HF) (5.1 ± 0.8 vs. 4.7 ± 0.9 ms2) (all p<0.001). For the control patients, similar improvements in SDNN (150.0 ± 39.4 vs. 118.8 ± 20.1 ms), LF (6.1 ± 0.9 vs. 5.7 ± 0.8 ms2), and HF (5.0 ± 0.9 vs. 4.7 ± 0.9 ms2) were obtained (all p<0.001). However, there was no add-on impact of the supervised exercise training programme on HRV after 12 months (p>0.05 for all HRV parameters). CONCLUSION: Bariatric surgery is associated with an improvement in HRV. A supervised exercise training programme in the post-operative period did not modulate further the benefits of bariatric surgery regarding HRV parameters.

Mapping pain activation and connectivity of the human habenula.

The habenula, located in the posterior thalamus, is implicated in a wide array of functions. Animal anatomical studies have indicated that the structure receives inputs from a number of brain regions (e.g., frontal areas, hypothalamic, basal ganglia) and sends efferent connections predominantly to the brain stem (e.g., periaqueductal gray, raphe, interpeduncular nucleus). The role of the habenula in pain and its anatomical connectivity are well-documented in animals but not in humans. In this study, for the first time, we show how high-field magnetic resonance imaging can be used to detect habenula activation to noxious heat. Functional maps revealed significant, localized, and bilateral habenula responses. During pain processing, functional connectivity analysis demonstrated significant functional correlations between the habenula and the periaqueductal gray and putamen. Probabilistic tractography was used to assess connectivity of afferent (e.g., putamen) and efferent (e.g., periaqueductal gray) pathways previously reported in animals. We believe that this study is the first report of habenula activation by experimental pain in humans. Since the habenula connects forebrain structures with brain stem structures, we suggest that the findings have important implications for understanding sensory and emotional processing in the brain during both acute and chronic pain.

Biological and behavioral markers of pain following nerve injury in humans.

The evolution of peripheral and central changes following a peripheral nerve injury imply the onset of afferent signals that affect the brain. Changes to inflammatory processes may contribute to peripheral and central alterations such as altered psychological state and are not well characterized in humans. We focused on four elements that change peripheral and central nervous systems following ankle injury in 24 adolescent patients and 12 age-sex matched controls. Findings include (a) Changes in tibial, fibular, and sciatic nerve divisions consistent with neurodegeneration; (b) Changes within the primary motor and somatosensory areas as well as higher order brain regions implicated in pain processing; (c) Increased expression of fear of pain and pain reporting; and (d) Significant changes in cytokine profiles relating to neuroinflammatory signaling pathways. Findings address how changes resulting from peripheral nerve injury may develop into chronic neuropathic pain through changes in the peripheral and central nervous system.

fMRI reveals distinct CNS processing during symptomatic and recovered complex regional pain syndrome in children.

Complex regional pain syndrome (CRPS) in paediatric patients is clinically distinct from the adult condition in which there is often complete resolution of its signs and symptoms within several months to a few years. The ability to compare the symptomatic and asymptomatic condition in the same individuals makes this population interesting for the investigation of mechanisms underlying pain and other symptoms of CRPS. We used fMRI to evaluate CNS activation in paediatric patients (9-18 years) with CRPS affecting the lower extremity. Each patient underwent two scanning sessions: once during an active period of pain (CRPS(+)), and once after symptomatic recovery (CRPS(-)). In each session, mechanical (brush) and thermal (cold) stimuli were applied to the affected region of the involved limb and the corresponding mirror region of the unaffected limb. Two fundamental fMRI analyses were performed: (i) within-group analysis for CRPS(+) state and CRPS(-) state for brush and cold for the affected and unaffected limbs in each case; (ii) between-group (contrast) analysis for activations in affected and unaffected limbs in CRPS or post-CRPS states. We found: (i) in the CRPS(+) state, stimuli that evoked mechanical or cold allodynia produced patterns of CNS activation similar to those reported in adult CRPS; (ii) in the CRPS(+) state, stimuli that evoked mechanical or cold allodynia produced significant decreases in BOLD signal, suggesting pain-induced activation of endogenous pain modulatory systems; (iii) cold- or brush-induced activations in regions such as the basal ganglia and parietal lobe may explain some CNS-related symptoms in CRPS, including movement disorders and hemineglect/inattention; (iv) in the CRPS(-) state, significant activation differences persisted despite nearly complete elimination of evoked pain; (v) although non-noxious stimuli to the unaffected limb were perceived as equivalent in CRPS(+) and CRPS(-) states, the same stimulus produced different patterns of activation in the two states, suggesting that the 'CRPS brain' responds differently to normal stimuli applied to unaffected regions. Our results suggest significant changes in CNS circuitry in patients with CRPS.

[Management of gestational hypertriglyceridemia by plasmapheresis]. / Prise en charge d'une hypertriglycéridémie gravidique par plasmaphérèse.

We report a case of unexpected severe hypertriglyceridemia (140N) diagnosed at 33 weeks during a second gestation. The risk of acute pancreatitis indicated plasmapheresis (three procedures) with reduction of hypertriglyceridemia (6N) and no impact on fetal well-being. Immediate recurrence led to induction of labour at 34 weeks. Spontaneous regression occurred after delivery. We demonstrated reduced lipoprotein lipase activity with no mutation for apolipoprotein E, nor lipoprotein lipase in favour of a potential pregnancy-induced inhibitor of lipoprotein degradation.

[Colorectal cancer discovered during pregnancy]. / Cancer colique découvert pendant la grossesse.

Colorectal carcinoma during pregnancy is very rare. Prognosis is severe because of the advanced stage due to delay in diagnosis and the aggressiveness of this widespread metastatic disease. We report the case of colon metaststic adenocarcinoma during a twin pregnancy with a good outcome. In the light of epidemiology, pathogeny and immunology, the diagnostic challenge for clinicians is distinguishing pregnancy symptoms from the warning signs of colorectal cancer and, we describe recommended medical and surgical management.

Can c-myc amplification reliably discriminate postradiation from primary angiosarcoma of the breast?

PURPOSE: Breast angiosarcomas are rare vascular malignancies that arise secondary to irradiation or de novo as primary tumours. The aim of this study is to know whether c-myc amplification can reliably discriminate these two entities. MATERIEL AND METHODS: Forty-seven patients treated for breast angiosarcomas were studied. Thirty-two patients were diagnosed with postradiation angiosarcomas after breast cancer treatment and 15 patients with primary angiosarcomas. Interphase fluorescence in situ hybridization (FISH) was performed by hybridization of probes covering C-MYC (chromosome 8q24.21) and CEP8 on tissue sections. RESULTS: Amplification (5- to 20-fold) of the c-myc oncogene was found in all breast radiation-induced angiosarcomas (32 tumours) but in none of the 15 primary angiosarcomas except one (7%). CONCLUSION: This study reinforces that there are true pathogenetic differences between the two types of breast angiosarcomas which are morphologically indistinguishable. These data point the pathways preferentially involved in the pathogenesis of post radiation angiosarcomas of the breast and may provide the basis for an additional targeted therapy.

Functional G-CSF pathways in t(8;21) leukemic cells allow for differentiation induction and degradation of AML1-ETO.

INTRODUCTION: Efficacy of differentiating agents requires that their specific cellular targets are still expressed and functional in the leukemic cells. One hypothesis to target sensitive cells is to select leukemic clones which harbor disrupted transcription factors. CBFalpha and CBFbeta are core-binding proteins which have been identified as transcription regulators of hematopoietic genes and shown to be altered in numerous leukemias. In M2 AML, the t(8;21) translocation, CBFalpha (AML1) is altered and produced as the AML1-ETO fusion protein. The fusion protein blocks transcription and differentiation mediated by G-CSF. Interestingly, AML1-ETO leukemic cell lines are sensitive to numerous cytokines in vitro and can be induced to differentiate in the presence of G-CSF and PMA. MATERIALS AND METHODS: As in the APL differentiation model, primary culture provides a useful tool for therapeutic screening of differentiation inducers, we analysed the in vitro sensitivity of 10 fresh M2 AML t(8;21) leukemic samples to G-CSF and the functionality of G-CSF intracellular pathways. In vitro data were compared with in vivo data from four patients treated with rhG-CSF at the dosage of 5 microg/kg/day i.v. for two to three weeks before the initiation of AML induction chemotherapy and immunophenotypic analysis performed weekly to monitor in vivo differentiation. RESULTS: In vitro, an increase in CD34+ cells expressing differentiation antigens (CD11b, CD13 or CD15) was noted along with a decrease of immature CD34+/differentiation antigen negative cells. After two weeks of a daily rhG-CSF administration in vivo, a significant, albeit transient, decrease of blast count was achieved, concomitant with an increase in differentiated leukemic cells suggesting that in vivo differentiation occurs. Fresh t(8;21) leukemic cells possess functional G-CSF signaling pathways as normal activity and kinetics of STAT1 and STAT3 binding was observed. Furthermore, differentiation induction leads to a subsequent degradation of the AML1-ETO oncoprotein. CONCLUSION: The data presented here supports the claim that G-CSF can induce in vitro and in vivo differentiation of M2 AML t(8;21) cells.

[The re-emergence in 1997 of rubella infections during pregnancy. 11 cases in Clermont-Ferrand]. / Recrudescence en 1997 des infections rubéoliques pendant la grossesse. 11 cas à Clermont-Ferrand.

OBJECTIVE: Describe the clinical and laboratory features of rubella observed during the first semester of pregnancy in 11 patients in 1997. PATIENTS AND METHODS: Eleven pregnant women, aged 15-30 years, were referred to the Clermont-Ferrand University Hospital for suspected rubella. Four had had at least 1 prior pregnancy, none had been vaccinated. Rubella serology was obtained for all 11 patients and polymerase chain reaction viral amplification was performed on amniotic fluid in 9 cases. RESULTS: The virology laboratory identified 8 cases of primary rubella (2 prior to 12 weeks gestation) and 3 reinfections (1 prior to 12 weeks gestation). Fetal infection was evidenced in I gravida II patient at 17-18 weeks gestation. All pregnancies were continued to term and no case of congenital rubella malformation was observed. However specific IgM assays were performed at birth in 6 of the 11 infants and revealed infection in 3. CONCLUSION: These observations indicate that a local epidemic of rubella occurred in the general population. They illustrate the risk of a rubella epidemic in France and the lack of sufficient vaccination of the young adult population, finally they emphasize that current anti-rubella vaccination programs should be promoted.

The responsive amygdala: treatment-induced alterations in functional connectivity in pediatric complex regional pain syndrome.

The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear, and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-sex matched control subjects before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared with control subjects, with differences predominantly in the left amygdala in the pretreated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy control subjects from time 1 to time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores; and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity after an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response.

7th SOSORT consensus paper: conservative treatment of idiopathic & Scheuermann's kyphosis.

UNLABELLED: : Thoracic hyperkyphosis is a frequent problem and can impact greatly on patient's quality of life during adolescence. This condition can be idiopathic or secondary to Scheuermann disease, a disease disturbing vertebral growth. To date, there is no sound scientific data available on the management of this condition. Some studies discuss the effects of bracing, however no guidelines, protocols or indication's of treatment for this condition were found. The aim of this paper was to develop and verify the consensus on managing thoracic hyperkyphosis patients treated with braces and/or physiotherapy. METHODS: The Delphi process was utilised in four steps gradually modified according to the results of a set of recommendations: we involved the SOSORT Board twice, then all SOSORT members twice, with a Pre-Meeting Questionnaire (PMQ), and during a Consensus Session at the SOSORT Lyon Meeting with a Meeting Questionnaire (MQ). RESULTS: There was an unanimous agreement on the general efficacy of bracing and physiotherapy for this condition. Most experts suggested the use of 4-5 point bracing systems, however there was some controversy with regards to physiotherapeutic aims and modalities. CONCLUSION: The SOSORT panel of experts suggest the use of rigid braces and physiotherapy to correct thoracic hyperkyphosis during adolescence. The evaluation of specific braces and physiotherapy techniques has been recommended.

[Utilization of thought stopping in the treatment of obsessive- compulsive disorder in a 9 year old girl]. / Utilisation de "l'arrêt des pensées" dans le traitement d'un trouble obsessionnel-compulsif chez une fillette de neuf ans.

OBJECTIVE: To use a pharmacobehavioural approach employing modified techniques of exposure, prevention of the response, and thought stopping in the treatment of obsessive-compulsive disorder in a 9-year-old girl. METHODS: The diagnosis of obsessive-compulsive disorder (OCD) was made based on the DSM-IV criteria. The patient was seen over 15 sessions, during which clomipramine was introduced and modified techniques of exposure, prevention of the response, and thought stopping were successively used. Follow-up extended over more than 18 months after the end of the therapy. RESULTS: The patient learned and used the behavioural techniques easily, and we observed a rapid, complete, and sustained disappearance of the obsessive-compulsive symptomatology. CONCLUSIONS: Use of a pharmacobehavioural approach in treating OCD in young children remains limited. Techniques used with adults and slightly modified to adapt them for children are, in our view, an avenue of treatment worth exploring.

[Child psychiatric day treatment centers in Quebec for children 0-12 years of age]. / Les centres de jour pédopsychiatriques pour la clientèle des 0-12 ans au Québec.

OBJECTIVES: The review lists the child psychiatry day-care centres in Quebec, evaluates their capacity, and describes them according to the age range for admission, the psychopathologies treated, and the parent involvement required. METHOD: The 26 programs selected, which are all associated with a hospital centre, assess and treat children aged 0 to 12 years on a day-care basis. Organization, clinical operation, and research are addressed during a semisupervised interview. RESULTS: The average capacity is 18 children (4 to 40), with a total capacity of 454 children. The number of preschool patients can be compared with the number of school patients. Few programs are dedicated to invasive development disorders, and one-third treat behavioural or emotional disorders. The larger capacity programs treat patients of both genders. Most programs are eclectic and encourage but do not require parental involvement. CONCLUSIONS: Results take into account different theoretical influences, the controversy about integration criteria and parent involvement, and the specificity of the child psychiatry mission.