Publications by authors named "Luisa Roveri"

15 Publications

  • Page 1 of 1

The role of CE-MRA of the supraortic vessels in the detection of associated intracranial pathology.

Neurol Sci 2021 Mar 29. Epub 2021 Mar 29.

Department of Neuroradiology, IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Via Olgettina 60, 20132, Milan, Italy.

Background: Contrast-enhanced magnetic resonance angiography (CE-MRA) has become a very popular imaging technique in the evaluation of the extracranial vessels pathology, while it is not commonly used to rule out intracranial vascular pathology. On the contrary, 3D time of flight MRA (TOF-MRA) has a solid role in the study of intracranial arterial vessels disease.

Materials And Methods: One hundred and eight patients were consecutively included in the study. All patients were submitted to a 3 Tesla 3D CE-MRA imaging to rule out extracranial vessels pathology. A comparison was made with a 3D-TOF sequence acquired at the same time in the assessment of intracranial vessels diseases such as steno-occlusion, dissection, and aneurysms.

Results: With regard to steno-occlusive disease, Spearman's rank correlation coefficient was of 0.56 for stenosis detection and of 0.57 for occlusive disease detection. The two techniques shared similar results in the evaluation of anterior circulation, while 3D-TOF found higher grades of stenosis for posterior circulation. With regard to dissection, Spearman's rank correlation coefficient was of 0.7. 3D-TOF depicted more intramural hematoma (Spearman's rank = 0.46), while CE-MRA showed more pseudo-aneurysms (Spearman's rank = 0.56). Both the technique equally evaluated the presence of intracranial aneurysms (Spearman's rank = 1).

Conclusion: CE-MRA can be considered a reliable tool to rule out intracranial pathology associated to supraortic steno-occlusive disease, also allowing time reduction. In the suspicion of dissection a T1-weighted sequence has to be added to detect the presence of a subacute vessel wall hematoma.
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http://dx.doi.org/10.1007/s10072-021-05222-1DOI Listing
March 2021

Cerebral thrombi of cardioembolic etiology have an increased content of neutrophil extracellular traps.

J Neurol Sci 2021 04 21;423:117355. Epub 2021 Feb 21.

Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy; Neurology Department, IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy. Electronic address:

Background: Inflammation is emerging as an essential trigger for thrombosis. In the interplay between innate immunity and coagulation cascade, neutrophils and neutrophil extracellular traps (NETs) can promote thrombus formation and stabilization. In ischemic stroke, it is uncertain whether the involvement of the inflammatory component may differ in thrombi of diverse etiology. We here aimed to evaluate the presence of neutrophils and NETs in cerebral thrombi of diverse etiology retrieved by endovascular thrombectomy (EVT).

Methods: We performed a systematic histological analysis on 80 human cerebral thrombi retrieved through EVT in acute ischemic stroke patients. Thrombus composition was investigated in terms of neutrophils (MPO cells) and NET content (citH3 area), employing specific immunostainings. NET plasma content was determined and compared to NET density in the thrombus.

Results: Neutrophils and NETs were heterogeneously represented within all cerebral thrombi. Thrombi of diverse etiology did not display a statistically significant difference in the number of neutrophils (p = 0.51). However, NET content was significantly increased in cardioembolic compared to large artery atherosclerosis thrombi (p = 0.04), and the association between NET content and stroke etiology remained significant after adjusted analysis (beta coefficient = -6.19, 95%CI = -11.69 to -1.34, p = 0.01). Moreover, NET content in the thrombus was found to correlate with NET content in the plasma (p ≤ 0.001, r = 0.62).

Conclusion: Our study highlights how the analysis of the immune component within the cerebral thrombus, and specifically the NET burden, might provide additional insight for differentiating stroke from diverse etiologies.
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http://dx.doi.org/10.1016/j.jns.2021.117355DOI Listing
April 2021

COVID-19 is associated with clinically significant weight loss and risk of malnutrition, independent of hospitalisation: A post-hoc analysis of a prospective cohort study.

Clin Nutr 2020 Oct 29. Epub 2020 Oct 29.

IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address:

Background & Aims: Coronavirus disease 2019 (COVID-19) may associate with clinical manifestations, ranging from alterations in smell and taste to severe respiratory distress requiring intensive care, that might associate with weight loss and malnutrition. We aimed to assess the incidence of unintentional weight loss and malnutrition in COVID-19 survivors.

Methods: In this post-hoc analysis of a prospective observational cohort study, we enrolled all adult (age ≥18 years) patients with a confirmed diagnosis of COVID-19 who had been discharged home from either a medical ward or the Emergency Department of San Raffaele University Hospital, and were re-evaluated after remission at the Outpatient COVID-19 Follow-Up Clinic of the same Institution from April 7, 2020, to May 11, 2020. Demographic, anthropometric, clinical and biochemical parameters upon admission were prospectively collected. At follow-up, anthropometrics, the mini nutritional assessment screening and a visual analogue scale for appetite were assessed.

Results: A total of 213 patients were included in the analysis (33% females, median age 59.0 [49.5-67.9] years, 70% overweight/obese upon initial assessment, 73% hospitalised). Sixty-one patients (29% of the total, and 31% of hospitalised patients vs. 21% of patients managed at home, p = 0.14) had lost >5% of initial body weight (median weight loss 6.5 [5.0-9.0] kg, or 8.1 [6.1-10.9]%). Patients who lost weight had greater systemic inflammation (C-reactive protein 62.9 [29.0-129.5] vs.48.7 [16.1-96.3] mg/dL; p = 0.02), impaired renal function (23.7% vs. 8.7% of patients; p = 0.003) and longer disease duration (32 [27-41] vs. 24 [21-30] days; p = 0.047) as compared with those who did not lose weight. At multivariate logistic regression analysis, only disease duration independently predicted weight loss (OR 1.05 [1.01-1.10] p = 0.022).

Conclusions: COVID-19 might negatively impact body weight and nutritional status. In COVID-19 patients, nutritional evaluation, counselling and treatment should be implemented at initial assessment, throughout the course of disease, and after clinical remission. CLINICALTRIALS.

Gov Registration: NCT04318366.
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http://dx.doi.org/10.1016/j.clnu.2020.10.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598735PMC
October 2020

Residual clinical damage after COVID-19: A retrospective and prospective observational cohort study.

PLoS One 2020 14;15(10):e0239570. Epub 2020 Oct 14.

School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.

Data on residual clinical damage after Coronavirus disease-2019 (COVID-19) are lacking. The aims of this study were to investigate whether COVID-19 leaves behind residual dysfunction, and identify patients who might benefit from post-discharge monitoring. All patients aged ≥18 years admitted to the Emergency Department (ED) for COVID-19, and evaluated at post-discharge follow-up between 7 April and 7 May, 2020, were enrolled. Primary outcome was need of follow-up, defined as the presence at follow-up of at least one among: respiratory rate (RR) >20 breaths/min, uncontrolled blood pressure (BP) requiring therapeutic change, moderate to very severe dyspnoea, malnutrition, or new-onset cognitive impairment, according to validated scores. Post-traumatic stress disorder (PTSD) served as secondary outcome. 185 patients were included. Median [interquartile range] time from hospital discharge to follow-up was 23 [20-29] days. 109 (58.9%) patients needed follow-up. At follow-up evaluation, 58 (31.3%) patients were dyspnoeic, 41 (22.2%) tachypnoeic, 10 (5.4%) malnourished, 106 (57.3%) at risk for malnutrition. Forty (21.6%) patients had uncontrolled BP requiring therapeutic change, and 47 (25.4%) new-onset cognitive impairment. PTSD was observed in 41 (22.2%) patients. At regression tree analysis, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) and body mass index (BMI) at ED presentation, and age emerged as independent predictors of the need of follow-up. Patients with PaO2/FiO2 <324 and BMI ≥33 Kg/m2 had the highest odds to require follow-up. Among hospitalised patients, age ≥63 years, or age <63 plus non-invasive ventilation or diabetes identified those with the highest probability to need follow-up. PTSD was independently predicted by female gender and hospitalisation, the latter being protective (odds ratio, OR, 4.03, 95% confidence interval, CI, 1.76 to 9.47, p 0.0011; OR 0.37, 95% CI 0.14 to 0.92, p 0.033, respectively). COVID-19 leaves behind physical and psychological dysfunctions. Follow-up programmes should be implemented for selected patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239570PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556454PMC
October 2020

Leukocyte Counts and Ratios Are Predictive of Stroke Outcome and Hemorrhagic Complications Independently of Infections.

Front Neurol 2020 3;11:201. Epub 2020 Apr 3.

Neuroimmunology Unit, Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Hospital, Milan, Italy.

Ischemic stroke patients show alterations in peripheral leukocyte counts that may result from the sterile inflammation response as well as the occurrence of early infections. We here aimed to determine whether alterations of circulating leukocytes in acute ischemic stroke are associated with long-term functional outcome and hemorrhagic complications, independently of the occurrence of infections. Blood laboratory values of patients with acute ischemic stroke, presenting within 4.5 h from symptom onset, were collected. Leukocyte subsets were analyzed in relation to 3-month functional outcome, mortality, and parenchymal hemorrhagic transformation (PH). A multivariable logistic regression analysis, considering the occurrence of early post-stroke infections, was performed for each outcome measure. Five-hundred-ten patients were included in the study. Independently of infections, good functional outcome was associated with a lower neutrophil to lymphocyte ratio (NL-R, OR 0.906 [95% CI 0.822-0.998]), a higher lymphocyte count (OR 1.547 [95% CI 1.051-2.277]), a higher eosinophil count (OR 1.027 [95% CI 1.007-1.048]), and a higher eosinophil to leukocyte ratio (EoLeu-R, OR 1.240 [95% CI 1.071-1.436]) at admission. Death within 3 months was associated with higher NL-R (OR 1.103 [95% CI 1.032-1.179]) as well as with lower eosinophil counts (OR 0.909 [95% CI 0.827-0.999]). Patients developing parenchymal hemorrhagic transformation had higher neutrophil counts (OR 1.420 [95% CI 1.197-1.684]) as well as a higher NL-R (OR 1.192 [95% IC 1.088-1.305]). Leukocyte subtype profiles in the acute phase of ischemic stroke represent a predictor of outcome independently of infections. Stroke-evoked sterile inflammation is a pathophysiological relevant mechanism that deserves further investigation.
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http://dx.doi.org/10.3389/fneur.2020.00201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145963PMC
April 2020

Time-domain near-infrared spectroscopy in acute ischemic stroke patients.

Neurophotonics 2019 Jan 7;6(1):015003. Epub 2019 Feb 7.

San Raffaele Scientific Institute, Neurology Department, Via Olgettina, Milan, Italy.

Large vessel occlusion (LVO) stroke might cause different degrees of hemodynamic impairment that affects microcirculation and contributes to metabolic derangement. Time-domain near-infrared spectroscopy (TD-NIRS) estimates the oxygenation of microcirculation of cerebral outer layers. We measure hemoglobin species and tissue oxygen saturation ( ) of anterior circulation stroke patients, classified as LVO or lacunar, and assess the differences compared with controls and according to LVO recanalization status. Fiducial markers categorize the brain region below each TD-NIRS probe as ischemic or nonstroke areas. The study includes 47 consecutive acute ischemic stroke patients and 35 controls. The ischemic area has significantly higher deoxy-hemoglobin (HbR) and total hemoglobin (HbT) compared with controls in both recanalized and nonrecanalized patients but lower only in recanalized patients. Recanalized patients have significantly lower mean in the ipsilateral hemisphere compared with nonrecanalized patients. This is the first study to report TD-NIRS measurements in acute ischemic stroke patients. TD-NIRS is able to detect significant differences in hemoglobin species in LVO stroke compared with controls and according to recanalization status. This preliminary data might suggest that can serve as a surrogate functional marker of the metabolic activity of rescued brain tissue.
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http://dx.doi.org/10.1117/1.NPh.6.1.015003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365799PMC
January 2019

Cerebral time domain-NIRS: reproducibility analysis, optical properties, hemoglobin species and tissue oxygen saturation in a cohort of adult subjects.

Biomed Opt Express 2017 Nov 12;8(11):4987-5000. Epub 2017 Oct 12.

Politecnico di Milano, Dipartimento di Fisica, Piazza Leonardo da Vinci 32, 20133 Milan, Italy.

The reproducibility of cerebral time-domain near-infrared spectroscopy (TD-NIRS) has not been investigated so far. Besides, reference intervals of cerebral optical properties, of absolute concentrations of deoxygenated-hemoglobin (HbR), oxygenated-hemoglobin (HbO), total hemoglobin (HbT) and tissue oxygen saturation (StO) and their variability have not been reported. We have addressed these issues on a sample of 88 adult healthy subjects. TD-NIRS measurements at 690, 785, 830 nm were fitted with the diffusion model for semi-infinite homogenous media. Reproducibility, performed on 3 measurements at 5 minutes intervals, ranges from 1.8 to 6.9% for each of the hemoglobin species. The mean ± SD global values of HbR, HbO, HbT, StO are respectively 24 ± 7 μM, 33.3 ± 9.5 μM, 57.4 ± 15.8 μM, 58 ± 4.2%. StO displays the narrowest range of variability across brain regions.
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http://dx.doi.org/10.1364/BOE.8.004987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695946PMC
November 2017

Todd's post-epileptic paresis and Takotsubo cardiomyopathy: unusual combination of neurological and cardiac disorder. Trigger or triggered?

Neurol Sci 2015 Nov 14;36(11):2157-8. Epub 2015 Jul 14.

Department of Neurology, INSPE, San Raffaele Scientific Institute, Via Olgettina 48, 20132, Milan, Italy.

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http://dx.doi.org/10.1007/s10072-015-2327-6DOI Listing
November 2015

Defining minor symptoms in acute ischemic stroke.

Cerebrovasc Dis 2015 14;39(3-4):209-15. Epub 2015 Mar 14.

San Raffaele Scientific Institute-Institute of Experimental Neurology, Stroke Unit-Department of Neurology and Neurophysiology, Milan, Italy.

Background: Thrombolysis is often withheld from acute ischemic stroke patients presenting with mild symptoms; however, up to 40% of these patients end up with a poor outcome when left untreated. Since there is lack of consensus on the definition of minor symptoms, we aimed at addressing this issue by looking for features that would better predict functional outcomes at 3 months.

Methods: Among all acute ischemic stroke patients admitted to our Stroke Unit (n = 1,229), we selected a cohort of patients who arrived within 24 hours from symptoms onset, with baseline NIHSS ≤6, not treated with thrombolysis (n = 304). Epidemiological data, comorbidities, radiological features and clinical presentation (NIHSS items) were collected to identify predictors of outcome. Our cohort was tested against minor stroke definitions selected from the literature and a newly proposed one.

Results: Three months after stroke onset, 97 patients (31.9%) had mRS ≥ 2. Independent predictors of poor outcome were age (OR 0.97 [95% CI 0.95-9.99]) and baseline NIHSS score (OR 0.79 [95% CI 0.67-0.94]), while cardioembolic aetiology was negatively associated (OR 3.29 [95% CI 1.51-7.14]). Items of NIHSS associated with poor outcome were impairment of right motor arm (OR 0.49 [95% CI 0.27-0.91]) or the involvement of any of the motor items (OR 0.69 [95% CI 0.48-0.99]). The definition of minor stroke as NIHSS ≤3 and the new proposed definition had the highest sensitivity and accuracy and were independent predictors of outcome.

Conclusions: Our study confirmed that in spite of a low NIHSS score, one third of patients had poor outcome. As already described, age and NIHSS score remained independent predictors of poor outcome even in mild stroke. Also, motor impairment appeared a major determinant of poor outcome. The new proposed definition of minor stroke featured the NIHSS score and the NIHSS items that better predicted functional outcome. Awareness that even minor stroke can yield to poor outcome should sensitize patients to arrive early to the ED and neurologists to administer rt-PA.
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http://dx.doi.org/10.1159/000375151DOI Listing
February 2016

Diagnostic value of IgG4 Indices in IgG4-related hypertrophic pachymeningitis.

J Neuroimmunol 2014 Jan 22;266(1-2):82-6. Epub 2013 Oct 22.

Università Vita-Salute San Raffaele, School of Medicine, San Raffaele Scientific Institute, via Olgettina 58, 20132, Milan, Italy; Unit of Medicine and Clinical Immunology, San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy.

Diagnosis of IgG4-Related Hypertrophic Pachymeningitis (IgG4-HP) relies on meningeal biopsies, because cerebrospinal fluid (CSF) diagnostic biomarkers are lacking. Here, we determined whether IgG4 intrathecal production could distinguish IgG4-HP from other disorders presenting with HP (OHP). In patients with IgG4-HP, the median CSF IgG4 concentration, IgG4 Index and IgG4Loc were significantly higher than in both controls and OHP. CSF IgG4 levels higher than 2.27mg/dL identified 100% of IgG4-HP and 5% of OHP. An IgG4Loc cut-off of 0.47 identified 100% of IgG4-HP and no cases of OHP. Our results support CSF IgG4 quantification and IgG4 Indices as alternatives to meningeal biopsy for the diagnosis of IgG4-HP when this procedure is contraindicated or uninformative.
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http://dx.doi.org/10.1016/j.jneuroim.2013.10.008DOI Listing
January 2014

Cerebrospinal fluid analysis in immunoglobulin G4-related hypertrophic pachymeningitis.

J Rheumatol 2013 Nov;40(11):1927-9

Università Vita-Salute San Raffaele, School of Medicine, and Unit of Medicine and Clinical Immunology, San Raffaele Scientific Institute, Milan;

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http://dx.doi.org/10.3899/jrheum.130678DOI Listing
November 2013

Wake-up stroke within 3 hours of symptom awareness: imaging and clinical features compared to standard recombinant tissue plasminogen activator treated stroke.

J Stroke Cerebrovasc Dis 2013 Aug 30;22(6):703-8. Epub 2011 Nov 30.

Department of Neurology, San Raffaele Scientific Institute, Milan, Italy.

Background: Patients with wake-up stroke (WUS) are excluded from thrombolysis because of unknown time of symptom onset. Previous studies have reported similar stroke severity and early ischemic changes (EICs) in patients with WUS and stroke of known onset. These studies, however, included patients within a large timeframe to imaging or did not quantify EICs. The aim of our study was to quantify EICs of patients with WUS presenting within 3 hours of symptom recognition compared to standard 3-hours recombinant tissue plasminogen activator (rt-PA)-treated patients and assess the extent of ischemic lesion and functional independence at follow-up.

Methods: Patients were selected from our prospectively collected stroke database. Baseline and follow-up computed tomographic scans were graded with Alberta Stroke Program Early Computed Tomography Score (ASPECTS). Clinical outcome measures were modified Rankin Scale score, mortality, and symptomatic intracerebral hemorrhage.

Results: Demographic features, risk factors, stroke severity, and baseline ASPECTS were similar in both groups. WUS and rt-PA-treated patients had similar tissue outcome (median ASPECTS 7.0 vs 7.5; P = .202). Functional outcome was more favorable in rt-PA-treated patients (61.6% vs 43.1%; odds ratio [OR] 2.12; 95% confidence interval [CI] 1.05-4.28; P = .037). After adjusting for age, stroke severity, treatment, and EICs in less than one-third of middle cerebral artery territory, rt-PA and National Institutes of Health Stroke Scale scores remained the only significant predictors of outcome (OR 7.76; 95% CI 2.40-25.05; P = .001 and OR 0.74; 95% CI 0.67-0.82; P < .001, respectively).

Conclusions: Within 3 hours of symptom recognition, patients with WUS have EICs similar to rt-PA-treated patients. It is reasonable to expect that selected WUS patients might benefit from thrombolysis within 3 hours of symptom awareness.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2011.10.003DOI Listing
August 2013

Loss of bipolar cells resulting from the expression of bcl-2 directed by the IRBP promoter.

Exp Eye Res 2003 Oct;77(4):477-83

Cole Eye Institute, (i-31), Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

We have recently noted marked reductions in the electroretinographic (ERG) b-wave in HIBA transgenic mice expressing bcl-2 under control of the human IRBP promoter. These electrophysiological results are unexpected as this promoter has been shown to specifically target transgene expression to the rod and cone photoreceptors. Here, we have carried out a series of studies to better understand this result. ERGs were recorded from three lines of HIBA transgenic mice. Mice with higher levels of transgene expression developed progressive photoreceptor degeneration, and an associated reduction in the ERG a-wave. These higher-expressing lines also exhibited a severe reduction in the ERG b-wave that affected both rod- and cone-mediated responses. These mice were mated to L7 transgenic mice, which express beta-galactosidase in bipolar cells. In double transgenic mice, the ERG b-wave reduction was associated with a decrease in the number of bipolar cells in the inner retina. These results indicate that bcl-2, targeted to photoreceptors, can induce bipolar cell degeneration, and indicate that the potential benefit for bcl-2 in treating hereditary retinal disease appears limited.
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http://dx.doi.org/10.1016/s0014-4835(03)00149-0DOI Listing
October 2003

A randomised controlled trial of intravenous immunoglobulin in IgM paraprotein associated demyelinating neuropathy.

J Neurol 2002 Oct;249(10):1370-7

Department of Neurology, Ospedale San Raffaele, Via Olgettina 60, 20132 Milan, Italy.

This multicentre randomised double blind crossover trial tested the short term efficacy of intravenous immunoglobulin (IVIg) 2.0 g/kg given over 24 or 48 hours in patients with paraproteinaemic demyelinating neuropathy (PDN). Twenty-two patients were randomised and completed the trial. After 2 weeks, the overall disability grade decreased during both IVIg treatment and placebo but neither change was significant nor was the mean difference between the treatment effects. After 4 weeks the overall disability decreased by a mean of 0.55 [0.67] grades during the IVIg period (p = 0.001) while it was substantially unmodified during the placebo period. The mean difference between the treatment effects was significant (p = 0.05). Overall during the IVIg period 10 patients improved and 11 were stable and one got worse. During the placebo period 4 patients improved, 4 deteriorated and 14 were stable. Many secondary outcome measures, including Rankin scale, time to walk 10 metres, grip strength, sensory symptoms score were significantly better during IVIg treatment. Two serious adverse events occurred during the trial, both during placebo treatment. In conclusion the trial showed some short-term benefit of IVIg in about half of the patients confirming previous observation.
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http://dx.doi.org/10.1007/s00415-002-0808-zDOI Listing
October 2002