Relationship between Prolactin Plasma Levels and White Matter Volume in Women with Multiple Sclerosis.

BACKGROUND: The role of prolactin (PRL) on tissue injury and repair mechanisms in multiple sclerosis (MS) remains unclear. The aim of this work was to investigate the relationship between PRL plasma levels and brain damage as measured by magnetic resonance imaging (MRI). METHODS: We employed a chemiluminescence immunoassay for measuring plasma levels of PRL. We used a 1.5 T scanner to acquire images and Jim 4.0 and SIENAX software to analyse them. RESULTS: We included 106 women with relapsing remitting (RR) MS and stable disease in the last two months. There was no difference in PRL plasma levels between patients with and without gadolinium enhancement on MRI. PRL plasma levels correlated with white matter volume (WMV) (rho = 0.284, p = 0.014) but not with grey matter volume (GMV). Moreover, PRL levels predicted changes in WMV (Beta: 984, p = 0.034). CONCLUSIONS: Our data of a positive association between PRL serum levels and WMV support the role of PRL in promoting myelin repair as documented in animal models of demyelination. The lack of an increase of PRL in the presence of gadolinium enhancement, contrasts with the view considering this hormone as an immune-stimulating and detrimental factor in the inflammatory process associated with MS.

Functional connectivity changes and their relationship with clinical disability and white matter integrity in patients with relapsing-remitting multiple sclerosis.

BACKGROUND AND OBJECTIVE: To define the pathological substrate underlying disability in multiple sclerosis by evaluating the relationship of resting-state functional connectivity with microstructural brain damage, as assessed by diffusion tensor imaging, and clinical impairments. METHODS: Thirty relapsing-remitting patients and 24 controls underwent 3T-MRI; motor abilities were evaluated by using measures of walking speed, hand dexterity and balance capability, while information processing speed was evaluated by a paced auditory serial addiction task. Independent component analysis and tract-based spatial statistics were applied to RS-fMRI and diffusion tensor imaging data using FSL software. Group differences, after dual regression, and clinical correlations were modelled with General-Linear-Model and corrected for multiple comparisons. RESULTS: Patients showed decreased functional connectivity in 5 of 11 resting-state-networks (cerebellar, executive-control, medial-visual, basal ganglia and sensorimotor), changes in inter-network correlations and widespread white matter microstructural damage. In multiple sclerosis, corpus callosum microstructural damage positively correlated with functional connectivity in cerebellar and auditory networks. Moreover, functional connectivity within the medial-visual network inversely correlated with information processing speed. White matter widespread microstructural damage inversely correlated with both the paced auditory serial addiction task and hand dexterity. CONCLUSIONS: Despite the within-network functional connectivity decrease and the widespread microstructural damage, the inter-network functional connectivity changes suggest a global brain functional rearrangement in multiple sclerosis. The correlation between functional connectivity alterations and callosal damage uncovers a link between functional and structural connectivity. Finally, functional connectivity abnormalities affect information processing speed rather than motor abilities.

Disrupted resting-state functional connectivity in progressive supranuclear palsy.

BACKGROUND AND PURPOSE: Studies on functional connectivity in progressive supranuclear palsy have been restricted to the thalamus and midbrain tegmentum. The present study aims to evaluate functional connectivity abnormalities of the subcortical structures in these patients. Functional connectivity will be correlated with motor and nonmotor symptoms of the disease. MATERIALS AND METHODS: Nineteen patients with progressive supranuclear palsy (mean age, 70.93 ± 5.19 years) and 12 age-matched healthy subjects (mean age, 69.17 ± 5.20 years) underwent multimodal MR imaging, including fMRI at rest, 3D T1-weighted imaging, and DTI. fMRI data were processed with fMRI of the Brain Software Library tools by using the dorsal midbrain tegmentum, thalamus, caudate nucleus, putamen, and pallidum as seed regions. RESULTS: Patients had lower functional connectivity than healthy subjects in all 5 resting-state networks, mainly involving the basal ganglia, thalamus, anterior cingulate, dorsolateral prefrontal and temporo-occipital cortices, supramarginal gyrus, supplementary motor area, and cerebellum. Compared with healthy subjects, patients also displayed subcortical atrophy and DTI abnormalities. Decreased thalamic functional connectivity correlated with clinical scores, as assessed by the Hoehn and Yahr Scale and by the bulbar and mentation subitems of the Progressive Supranuclear Palsy Rating Scale. Decreased pallidum functional connectivity correlated with lower Mini-Mental State Examination scores; decreased functional connectivity in the dorsal midbrain tegmentum network correlated with lower scores in the Frontal Assessment Battery. CONCLUSIONS: The present study demonstrates a widespread disruption of cortical-subcortical connectivity in progressive supranuclear palsy and provides further insight into the pathophysiologic mechanisms of motor and cognitive impairment in this condition.

Management of community-acquired pneumonia by trained family general practitioners.

SETTING: Community-acquired pneumonia (CAP) is a respiratory health disease with a high prevalence in the general population. Family general practitioners (GPs) can play an important role in CAP management by reducing unnecessary hospital admissions and, consequently, national health costs. OBJECTIVE: To assess CAP management by trained GPs. DESIGN: A course in CAP management, including a risk classification method based only on clinical criteria, was developed within the framework of an educational programme. GPs who participated in the programme (n = 220) were asked to collect data on their CAP patients. RESULTS: GPs (n = 94, response rate 42.7%) provided information on 370 patients (50% males, aged 18-93 years). The numbers of patients judged to be at low, moderate and high risk were 81%, 13% and 6%, respectively. The admission rate was 19.5%. All home-treated patients had good clinical outcomes. Home treatment was based on quinolones (62%), beta-lactams (23%) and macrolides (15%). The attributable economic mean cost of antibiotic home treatment was euro 96 per episode (standard deviation 71, range 17-445). CONCLUSIONS: The good outcomes suggest that GPs managed their CAP patients well, adhering to the content of the CAP management course. The risk evaluation of patients admitted to hospital, based exclusively on clinical elements, was consistent with more complex classification.

Monthly brain magnetic resonance imaging scans in patients with clinically isolated syndrome.

We investigated if monthly gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) can assist the clinician in anticipating the diagnosis of multiple sclerosis (MS) in the very first few months following a clinically isolated syndrome (CIS). A consecutive series of CIS patients with > or = 3 T2-weighted (T2W) hyperintense brain MRI lesions suggestive of MS were followed up for the first six consecutive months after enrollment with monthly triple-dose Gd-enhanced brain MRI scan. MRI conversion to MS was defined by the presence of either > or = 1 new Gd-enhancing lesion or > or = 1 new T2W lesions in the subsequent MRI scan. Sixty patients were included. Of them, 30 (50%) had at least one Gd-enhancing lesion on the baseline MRI scan. After three months, MRI conversion to MS was observed in 80% and 62% of patients based on the appearance of > or = 1 new T2 lesion and > or = 1 new Gd-enhancing lesions, respectively. The presence of > or = 1 new T2W lesion was observed in 90% and 82% of patients who had, at baseline, a Gd-positive MRI scan and dissemination in space based on the new McDonald's criteria, respectively The rate of MRI conversion remained almost stable in the last two MRI scans. Our study suggests that the majority of CIS patients with an abnormal baseline scan showed an MRI conversion to MS after three months. The model of six months as the optimal interval for repeating MRI exam is not supported by the present data.

Quality of generated diagnosis related groups in Italian Respiratory Intermediate Care Units.

BACKGROUND: To date we lack official data on tipology of Diagnosis Related Groups (DRGs) and their quality in Italian Respiratory Intermediate Care Units (RICUs). AIM: The objective of the study was to collect data on the activity of 26 Italian RICUs and to evaluate the quality of the DRGs generated. METHODS: The primary and secondary diseases, the procedures carried out and their coding using the ICD9 system (valid Italy until 2000) were collected from the discharge forms of patients admitted to RICUs. To obtain the DRG, these codes were automatically recoded in the ICD9-CM classification system by Grouper 10. Afterwards, the same diseases and procedures were directly processed by the ICD9-CM classification system. Finally, in order to evaluate the quality of care, the DRGs generated by the ICD9 classification system were compared to DRGs generated by the ICD9-CM classification system. RESULTS: The average weight of the patients cared for in an Italian RICU was 2.05 using the ICD9 classification system and 2.53 using the ICD9-CM classification system. Some non-complicated DRGs (80-97) or non specific DRGs (101-102) were set to zero; others, like DRG 87 appear due to the ability of the ICD9-CM classification system to recognise and accept the fifth digit of the Respiratory Failure code (518.81). The difference in terms of DRG scores generated by the two codification systems was 360.5 DRG points in favour of ICD9-CM. More than 1 million Euro of reimbursements have been lost, as the average national reimbursement for each DRG score is Euro 2,943.80. CONCLUSION: Severe pulmonary diseases determined the case mix of patients cared for in the Italian RICUs during the observed period. The Italian RICUs offer high quality assistance and are characterised by high mean weight per treated patient. However, the activity has been under-estimated due to the low sensitivity of the ICD9 classification system used in the recognition of the real disease and in the correct generation of relative DRG. The ICD9 classification system penalised the recognition of respiratory failure in particular.

Longitudinal evaluation of depression and anxiety in patients with clinically isolated syndrome at high risk of developing early multiple sclerosis.

We investigated the relationship between emotional changes, brain lesion burden and development of multiple sclerosis (MS). Thirty-seven consecutive patients with clinically isolated syndrome (CIS) were prospectively assessed with the Expanded Disability Status Scale (EDSS), the 21-item Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI) and gadolinium enhanced (Gd+) MRI scans. BDI and STAI were also administered to 36 age-matched controls. Conversion to MS was defined as the occurrence of a clinical relapse. CIS patients were more likely to endorse symptoms of anxiety and depression than controls. Baseline scores for depression and anxiety did not correlate with the total lesion load (i.e., volume of Gd+, T2 and T1 lesions) and the number of Gd+ lesions during the first six months of follow-up. A positive correlation was found between severity of depressive scores and the lesion load in the right temporal region (P = 0.005). After 33+/-6 months of the study entry, patients who had a clinical relapse were more frequently depressed (P = 0.001) than those relapse free. Emotional disturbances are frequently observed in CIS patients and show a tendency towards a normalization in relapse-free patients. The increased rate of depressive symptoms observed in patients who developed MS seems to result from a combination of psychological and organic features. The lesion load in the right temporal region is confirmed as a key area for developing depressive symptoms, even in the early phase of the disease.

Is it possible to predict the success of non-invasive positive pressure ventilation in acute respiratory failure due to COPD?

There is now sufficient evidence that non-invasive positive pressure ventilation (NIPPV) in selected patients with severe hypercapnic acute respiratory failure due to chronic obstructive pulmonary disease (COPD) is more effective than pharmacological therapy alone. The aim of this study was to identify prognostic factors to predict the success of this technique. Fifty-nine consecutive patients with COPD admitted to a respiratory ward for 75 episodes of acute respiratory failure treated with NIPPV were analysed: success (77%) or failure (23%) were evaluated by survival and the need for endotracheal intubation. There were no significant differences in age, sex, cause of relapse and lung function tests between the two groups. Patients in whom NIPPV was unsuccessful were significantly underweight, had an higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, and a lower serum level of albumin in comparison with those in whom NIPPV was successful. They demonstrated significantly greater abnormalities in pH and PaCO2 at baseline and after 2h of NIPPV. The logistic regression analysis demonstrated that, when all the variables were tested together, a high APACHE II score and a low albumin level continued to have a significant predictive effect. This analysis could predict the outcome in 82% of patients. In conclusion, our study suggests that low albumin serum levels and a high APACHE II score may be important indices in predicting the success of NIPPV.

[Usefulness of selective partial inversion recover (SPIR) sequences in optic nerve diseases]. / Utilità delle sequenze "Selective Partial Inversion Recover" (SPIR) nelle malattie del nervo ottico.

PURPOSE: To evaluate the yield of SPIR sequences with fat suppression in the diagnosis of optic nerve lesions. MATERIAL AND METHODS: Ten patients with suspected optic nerve involvement on the basis of clinical data and abnormalities of visual evoked potentials were examined. MRI was performed with a 1.5 T unit (Philips NT 15) using T1 weighted conventional spin-echo and T1- and T2 weighted SPIR sequences with fat suppression. Axial images were obtained along the optic nerve course, while coronal images throughout the optic nerve axis; slices were 3 mm thick. Axial T2 weighted SPIR sequences were also performed with the volumetric technique (1.5 mm thickness); coronal and parasagittal reconstructions along the nerve axis were obtained too. After paramagnetic contrast medium injection, conventional T1 weighted and SPIR sequences were performed on axial and coronal planes. RESULTS: Optic nerve lesions consistent with the diagnosis of neuritis were demonstrated with T2 weighted images in 4 of 10 patients. No abnormalities and/or nerve enlargement were found on T1 weighted images. An enhancement area was seen after contrast medium injection in only one case. MRI showed a pilocytic astrocytoma in one patient and selective atrophy of the right optic nerve in another. MRI showed normal findings in 4 patients. CONCLUSIONS: T1 and T2 weighted fat-suppressed SPIR imaging of the optic nerve improves anatomical definition, lesion detection and characterization in optic nerve conditions.

Oral vs inhaled asthma therapy. Pros, cons and combinations.

A number of oral and inhaled drugs are available for the long term management of patients with persistent asthma, yet the disease continues to be associated with significant morbidity and mortality. Over the past years, inhaled glucocorticoids have become established as a cornerstone of maintenance therapy because of their demonstrated clinical efficacy, ability to reduce bronchial inflammation and good tolerability. Other inhaled drugs (e.g. sodium cromoglycate, nedocromil, long-acting beta 2 agonists) also play a role in the long term treatment of patients with asthma. However, many patients (especially children and the elderly) find inhalers difficult to use, and poor inhalation technique can affect the amount of drug reaching the lungs and response to therapy. Oral drug administration is simple, but, until recently, oral asthma therapy has primarily consisted of sustained-release theophylline and glucocorticoids. Theophylline has a narrow therapeutic index, necessitating regular monitoring of serum drug concentrations, and long term oral glucocorticoid therapy is associated with potentially serious adverse events including osteoporosis with bone fracture. The recent development of orally administered leukotriene receptor antagonists (e.g. zafirlukast) and 5-lipoxygenase inhibitors (e.g. zileuton) offers novel mechanisms of action and potential solutions to compliance issues associated with regular administration of inhaled asthma therapy. These drugs have demonstrated efficacy as maintenance therapy in patients with asthma and, importantly, lack the adverse effects associated with long term systemic glucocorticoid therapy. Further clinical trials and the increasing use of these new therapies will help to establish the precise role of orally administered leukotriene receptor antagonists and 5-lipoxygenase inhibitors in the long term management of patients with asthma.