Autologous haematopoietic stem cell transplantation reduces abnormalities in the expression of immune genes in multiple sclerosis.

Autologous haematopoietic stem-cell transplantation (AHSCT) has been experimented as a treatment in patients affected by severe forms of multiple sclerosis (MS) who failed to respond to standard immunotherapy. The rationale of AHSCT is to 'reboot' the immune system and reconstitute a new adaptive immunity. The aim of our study was to identify, through a robust and unbiased transcriptomic analysis, any changes of gene expression in T-cells potentially underlying the treatment effect in patients who underwent non-myeloablative AHSCT for treatment of MS. We evaluated by microarray DNA-chip technology the gene expression of peripheral CD4+ and CD8+ T-cell subsets sorted from patients with MS patients before AHSCT, at 6 months, 1 year and 2 years after AHSCT and from healthy control subjects. Hierarchical clustering analysis revealed that reconstituted CD8+ T-cells of MS patients at 2 years post-transplantation, aggregated together with healthy controls, suggesting a normalization of gene expression in CD8+ cells post-therapy. When we compared the gene expression in MS patients before and after therapy, we detected a large number of differentially expressed genes (DEG) in both CD8+ and CD4+ T-cell subsets at all time points after transplantation. We catalogued the biological function of DEG and we selected 27 genes known to be involved in immune function for accurate quantification of gene expression by real-time PCR. The analysis confirmed and extended with quantitative data, a number of significant changes in both the CD4+ and CD8+ T-cells subsets from MS post-transplant. Notably, CD8+ T-cells revealed more extensive changes in the expression of genes involved in effector immune responses.

Intracranial teratoma in children: the role of chromosome 21 trisomy.

Teratomas are very rare intracranial tumors and cytogenetic information on this group remains rare. We report a case of a mature teratoma with abnormal +21 trisomy in tumor karyotype ocurring in a non-Down syndrome(DS) infant. Additionally, the evidence for the contribution of chromosome 21 trisomy in this neoplasia are briefly reviewed. The 6-month-old male baby presented with a posterior fossa tumor. Histological evaluation of tumor specimen showed a mature teratoma composed of fully differentiated ectodermal, mesodermal and endodermal components. Although somatic karyotyping of the index case was normal, composite tumor karyotype depicted 47,XY,+21[6]/46,XY[6]. Besides previous reports of children with DS and intracranial teratomas, this is the first report to describe the occurrence of an isolated chromosome 21 trisomy within the tumor of a non-DS child. The participation of chromosome 21 in this rare pediatric tumor, either somatic or restricted to tumor specimen,may deserve special interest and further investigation.

Correlations between changes in the hypothalamic-pituitary-adrenal axis and neurochemistry of the anterior cingulate gyrus in postpartum depression.

BACKGROUND: This study aimed to investigate associations between indicators of hypothalamic-pituitary-adrenal axis (HPA) functioning and metabolite levels in the anterior cingulate gyrus (ACG) of women with postpartum depression (PPD). METHODS: The sample (mean age = 28.5 ±â€¯4.6 years) consisted of 20 women with PPD and 19 postpartum euthymic (PPE) women. Brain metabolites were quantified by proton magnetic resonance spectroscopy (1H-MRS). Salivary cortisol samples were collected upon awakening and 30 min and 12 h later, at 20.6 ±â€¯6.6 (PPD) and 23.0 ±â€¯7.4 (PPE) weeks after childbirth. RESULTS: There were no significant differences between groups in respect to metabolite levels in the ACG. Compared with PPE, PPD women had less diurnal variation (DVr%). In the PPD group, positive correlations were found between DVr% and myo-inositol (mI/Cr) levels, and between cortisol awakening response (CARi%) and glutamate + glutamine (Glx/Cr) levels. The correlation between CARi% and Glx/Cr remained significant even after controlling for the interval, in weeks, from birth and MR spectroscopy and to hormonal data collection, and the use of contraceptives. LIMITATIONS: The limitations of the study include the small sample size and the use of oral contraceptives by around half of the sample. CONCLUSIONS: In the remote postpartum period (mean 21.8 ±â€¯6.9 weeks) and in the presence of depressive episodes, the decreased responsiveness of the HPA axis after awakening and a smaller decrease in cortisol levels over the day were associated with lower levels of metabolites in the ACG. These results may contribute to the development of biological models to explain the etiology of PPD.

Neuroimaging of major depression in Parkinson's disease: Cortical thickness, cortical and subcortical volume, and spectroscopy findings.

Depression is the most common psychiatric disorder in Parkinson's disease (PD). The aim of this study was to compare PD patients with current Major Depressive Disorder (MDD), lifetime MDD, and no MDD using three neuroimaging techniques. A total of 43 PD patients were selected and divided into three groups: (i) current MDD (n = 15), (ii) previous MDD without current MDD (n = 10); and (iii) control group (no current or lifetime MDD; n = 18). All participants underwent magnetic resonance imaging to evaluate cortical thickness, cortical and subcortical volume, and spectroscopy in the bilateral putamen and cingulate cortex. Volumetric analysis showed volume decreases in frontal and temporal areas, bilateral amygdala, and left cerebellar white matter in the lifetime MDD group compared to the control group. Furthermore, the volumes of the anterior cingulate cortex, right amygdala, and left cerebellar white matter were smaller in the group with current MDD compared to the control group. Regarding cortical thickness, the left rostral anterior cingulate gyrus of the group with previous MDD was thinner compared to the control group. There was a weak negative correlation between the NAA/Cre ratio in the right putamen and depressive symptoms. The results suggested current and lifetime MDD have a negative impact on the neurodegenerative process of PD, with decreased volume and/or reduction of cortical thickness in temporal and frontal areas, anterior cingulate cortex, amygdala, and cerebellar white matter.

Polyarteritis nodosa with central nervous system involvement mimicking meningoencephalitis.

OBJECTIVE: To describe a patient who had polyarteritis nodosa with central nervous system involvement mimicking infectious meningoencephalitis. DESIGN: Case report. SETTING: Pediatric intensive care unit of a university hospital. PATIENT: A 9-yr-old boy with prolonged fever, headache, decreased level of consciousness, neck stiffness, and papilledema. RESULTS: Cerebrospinal fluid examination showed pleocytosis and a high protein level. After neurologic deterioration resulted from the initial treatment with antibiotic, the combination of clinical and laboratory findings with neuroradiologic features led to suspected systemic vasculitis. The patient was treated subsequently with corticosteroid, which resulted in great improvement. Biopsy of a skin lesion confirmed the diagnosis of polyarteritis nodosa. CONCLUSIONS: Critical care physicians must recognize neurologic manifestation patterns of systemic vasculitides because appropriate diagnosis and therapy result in significantly improved morbidity and mortality.

Ictal chronology and interictal spikes predict perfusion patterns in temporal lobe epilepsy: a multivariate study.

Typical (TPP) and atypical (APP) perfusion patterns (PP) may be seen in ictal SPECT of patients with temporal lobe epilepsy (TLE). APP may pose problem in the lateralization of the epileptogenic zone (EZ). We aimed to investigate predictive variables for the occurrence of TPP and APP. Fifty-one TLE patients were submitted to successful anterior-mesial temporal lobectomy. Univariate (UVA) and multivariate (MVA) analysis were performed upon clinical data, distribution of interictal spikes, and ictal chronology of seizures. From MVA, a final predictive model (FPM) was determined to better predict TPP and APP. Forty patients showed TPP (78.5%) and 11 patients APP (21.5%). Accuracy of ictal SPECT was higher in the unilateral (UIS) than in the bilateral (BIS) interictal spikes group (P = 0.05). FPM showed that patients exhibiting BIS, with shorter proportion of the electrographic seizure occurring after completion of tracer injection, and longer clinical than EEG seizure duration had more APP (P = 0.003). Generalized tonic-clonic seizures did not result in more APP. We concluded that analysis of ictal SPECT in TLE requires the knowledge of TPP and APP, the distribution of interictal spikes on temporal lobes and the ictal chronology of seizures. BIS showed that beyond a more complex epileptogenicity and seizure propagation, they may also lead to APP.

Disseminated cysticercosis with pulmonary involvement.

Cysticercosis is an important public health problem in developing countries. The central nervous system is the major site of involvement, although striated muscles and subcutaneous tissue are frequently involved in the disseminated form of disease. We describe a recent case in which pulmonary nodules due to cysticercosis were detected on CT and MRI.