DTI parameters in neonates with hypoxic-ischemic encephalopathy after total body hypothermia.

BACKGROUND AND PURPOSE: MR imaging provides means for discriminating different patterns of Hypoxic-ischemic encephalopathy (HIE) and may distinguish most severe cases from less severe but is unable to predict long-term outcome. Diffusion tensor imaging (DTI) offers information for a more complete characterization of HIE. The purpose of this study is to compare the modifications of DTI parameters in newborns one week and six months following total-body cooling to healthy controls. METHODS: Forty-seven cooled newborns were studied with MRI, 20 underwent follow-up at 6 months. 12 healthy newborns and nine children at 6 months were enrolled as control groups (HC). Inferior Longitudinal Fasciculus (ILF), Corpus Callosum Fasciculus (CCF), Corticospinal Tract (CST), Optical Tract (OT), Optic Radiation (OR) were generated in all subjects. DTI parameters were evaluated in basal ganglia (BG), thalamus (TH) and tracks. Statistical analysis was performed with MANOVA. RESULTS: In newborns HIE versus HC, there were significantly lower fractional anisotropy (FA) on OR and CST and higher axial diffusivity (AD), apparent diffusion coefficient (ADC) and radial diffusivity (RD) values on CST, BG and TH in HIE-N. At 6 months there were no significant grouping effects. The analysis showed a significant increase of FA, decrease of ADC, AD, RD after 6 months for HIE and HC. CONCLUSIONS: We observed modifications of parameter values in HIE newborns vs HC; however normalization of values at 6 months suggests that changes of parameters cannot be considered early biomarkers for evaluation of therapeutic hypothermia in newborns with moderate HIE and normal conventional MRI.

Clinical applications of dynamic susceptibility contrast perfusion-weighted MR imaging in brain tumours.

Magnetic resonance imaging (MRI) with a dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) sequence to study brain tumours provides information on the haemodynamic characteristics of the neoplastic tissue. Brain perfusion maps and calculation of perfusion parameters, such as relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV) and mean transit time (MTT) allow assessment of vascularity and angiogenesis within tumours of the central nervous system (CNS), thus providing additional information to conventional MRI sequences. Although DSC-PWI has long been used, its clinical use in the study of brain tumours in daily clinical practice is still to be defined. The aim of this review was to analyse the application of perfusion MRI in the study of brain tumours by summarising our personal experience and the main results reported in the literature.

Variations of the perforin gene in patients with multiple sclerosis.

Perforin is involved in cell-mediated cytotoxicity and mutations of its gene (PRF1) cause familial hemophagocytic lymphohistiocytosis (FLH2). PRF1 sequencing in 190 patients with multiple sclerosis and 268 controls detected two FLH2-associated variations (A91V, N252S) in both groups and six novel mutations (C999T, G1065A, G1428A, A1620G, G719A, C1069T) in patients. All together, carriers of these variations were more frequent in patients than in controls (phenotype frequency: 17 vs 9%, P=0.0166; odds ratio (OR)=2.06, 95% confidence interval (CI): 1.13-3.77). Although A91V was the most frequent variation and displayed a trend of association with multiple sclerosis (MS) in the first population of patients and controls (frequency of the 91V allele: 0.076 vs 0.043, P=0.044), we used it as a marker to confirm PRF1 involvement in MS and assessed its frequency in a second population of 966 patients and 1520 controls. Frequency of the 91V allele was significantly higher in patients than in controls also in the second population (0.075 vs 0.058%, P=0.019). In the combined cohorts of 1156 patients and 1788 controls, presence of the 91V allele in single or double dose conferred an OR=1.38 (95% CI=1.10-1.74). These data suggest that A91V and possibly other perforin variations indicate susceptibility to MS.

Multiple sclerosis: pharmacogenomics and personalised drug treatment.

Multiple sclerosis (MS) is a disorder of the central nervous system with an inflammatory and a neurodegenerative component. We do not yet have a definitive therapy for MS. Attempts to develop new treatments are long and costly and should be paralleled by studies aimed at increasing the therapeutic index of the existing treatments, interferon beta and glatiramer acetate. Pharmacogenetics and pharmacogenomics may be of use in this respect though their application may not be straightforward, particularly in MS.

Physiopathology of multiple sclerosis.

Pleiotropy and redundancy are distinctive elements of the immune response. Recent research into the inflammatory component of multiple sclerosis (MS) indicates that, as expected, pleiotropy and redundancy characterize various physiopathological mechanisms of the disease. A certain degree of redundancy is becoming apparent also as far as the degenerative component is concerned. Cumulatively, these data suggest that treatments that target single pathogenetic pathways are unlikely to provide a definitive solution. Combination therapies may offer, in principle, some advantage, although there is a need for more information on the aetiology of the disease.

Hyperthermic syndromes and impairment of the dopaminergic system: a clinical study.

We present 8 cases of centrally-originating hyperthermic syndrome, the initial cause being either neuroleptic malingnant syndrome, hyperthemia after discontinuance of antiparkinsonian therapy or heatstroke. We review the physiological and neurochemical mechanisms involved in thermoregulation, emphasizing the role of dopamine. A single mechanism, consistent with pharmacological or neuropathological impairment of the dopaminergic system, could be responsible for all the cases of hyperthermic syndrome presented.

Hyperthermia after discontinuance of levodopa and bromocriptine therapy: impaired dopamine receptors a possible cause.

Hyperthermia, with no signs of any underlying infection, may occur in the course of neuroleptic malignant syndrome, fatal catatonia, heat stroke, or malignant hyperthermia. We describe hyperthermia as a complication after discontinuance of antiparkinsonian treatment with levodopa/carbidopa and bromocriptine. Impaired nigrostriatal, hypothalamic, and mesolimbic dopaminergic functions could be involved in pathogenesis.

Creutzfeldt-Jakob disease and sheep brain. A report from central and Southern Italy.

The places of origin of 7 out of 8 patients with CJD coincide with the distribution of sheep-rearing in central and southern Italy, confirming the suggested link between this disease and eating and-or handling sheep CNS tissue. Since 6 of the 8 cases were women, it seems more likely that the virus responsible for CJD enters the body through a break in the skin of the hands and forearms in the process of foodhandling rather than via the Digestive tract. This aspect should be borne in mind when investigating the problems of CJD transmission.