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1.
Eur J Neurol ; 26(5): 727-732, 2019 05.
Article in English | MEDLINE | ID: mdl-30489673

ABSTRACT

BACKGROUND AND PURPOSE: Information on the prevalence and course of post-stroke cognitive impairment in young stroke patients is limited. The aim was to assess a consecutive sample of acute young ischaemic stroke patients (18-55 years) for the presence and development of neuropsychological deficits. METHODS: Patients prospectively underwent a comprehensive clinical and cognitive assessment, examining general cognitive function, processing speed, attention, flexibility/executive function and word fluency within the first 3 weeks after hospital admission (median assessment at day 6) and at a 3 months' follow-up (FU). Cognitive dysfunction was defined in comparison to age-standardized published norms. RESULTS: At baseline (N = 114), deficits were highly prevalent in processing speed (56.0%), flexibility/executive function (49.5%), attention (46.4%) and general cognitive function (42.1%). These frequencies were comparable for those with FU assessment (N = 87). In most domains, cognitive performance improved within 3 months, except for word fluency. However, in about one-third of patients, cognitive deficits (as defined by 1.5 standard deviations below the standardized mean) were still present 3 months after stroke. At FU, 44.0% were impaired in the domain flexibility/executive function, 35.0% in processing speed and 30.0% in attention. CONCLUSIONS: The high prevalence of cognitive deficits in acute young patients with ischaemic stroke highlights the importance of early post-stroke cognitive assessment to capture a patient's dysfunction in a comprehensive manner and to offer adequate rehabilitation. The role of factors which promote neuropsychological deficits needs further exploration.


Subject(s)
Brain Ischemia/epidemiology , Brain Ischemia/psychology , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/psychology , Stroke/epidemiology , Stroke/psychology , Adolescent , Adult , Age Factors , Attention , Brain Ischemia/complications , Cognition , Cognitive Dysfunction/complications , Disease Progression , Executive Function , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Prevalence , Prospective Studies , Speech , Stroke/complications , Young Adult
2.
Mult Scler ; 22(12): 1560-1568, 2016 10.
Article in English | MEDLINE | ID: mdl-26762671

ABSTRACT

BACKGROUND: Lipocalin 2 (LCN2) may be involved in the immunopathogenesis of multiple sclerosis (MS) and might further impact on iron homoeostasis. Brain iron accumulates in MS; however, the association to iron-related proteins is still unsolved. OBJECTIVE: To investigate cerebrospinal fluid (CSF) and serum LCN2, transferrin (Trf) and ferritin in early MS in relation to disease evolution and longitudinal brain iron accumulation. METHODS: We analysed CSF and serum LCN2 by enzyme-linked immunosorbent assay (ELISA) and Trf and ferritin by nephelometry in 55 patients (45 clinically isolated syndrome (CIS), 10 MS, median clinical follow-up 4.8 years) and 63 controls. In patients, we assessed sub-cortical grey matter iron by 3T magnetic resonance imaging (MRI) R2* relaxometry (median imaging follow-up 2.2 years). RESULTS: Compared to controls serum (p < 0.01), CSF (p < 0.001) LCN2 and CSF Trf (p < 0.001) levels were reduced in the patients. CSF LCN2 correlated with CSF Trf (r = 0.5, p < 0.001). In clinically stable patients, CSF LCN2 levels correlated with basal ganglia iron accumulation (r = 0.5, p < 0.05). In CIS, higher CSF LCN2 levels were associated with conversion to clinically definite MS (p < 0.05). CONCLUSION: We demonstrate altered LCN2 regulation in early MS and provide first evidence for this to be possibly linked to both clinical MS activity and iron accumulation in the basal ganglia.


Subject(s)
Basal Ganglia/metabolism , Demyelinating Diseases/cerebrospinal fluid , Iron/metabolism , Lipocalin-2/cerebrospinal fluid , Multiple Sclerosis/cerebrospinal fluid , Adult , Basal Ganglia/diagnostic imaging , Demyelinating Diseases/blood , Demyelinating Diseases/diagnostic imaging , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multiple Sclerosis/blood , Multiple Sclerosis/diagnostic imaging
3.
Mult Scler ; 22(3): 340-6, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26163072

ABSTRACT

BACKGROUND: The extent and clinical significance of brain volume changes in different phases of multiple sclerosis (MS) is still under discussion. OBJECTIVE: To determine the rate of global and compartmental brain volume changes in patients with a clinically-isolated syndrome (CIS) compared to patients with definite MS, by long-term follow-up and as a predictor of conversion to MS in a routine clinical setting. METHODS: We investigated 120 patients (63 CIS and 57 MS) at baseline and after a mean follow-up period of 43 months, including detailed clinical examination and 3-Tesla magnetic resonance imaging (MRI). Our imaging analyses comprised the normalized brain volume (NBV), cortical grey matter (cGMV) and white matter (WMV) volumes using SIENA/X, the percentage of brain volume change (PBVC) using SIENA and the change in the volume of the thalami (TV) and basal ganglia (BGV). We also determined the amount and change of T2-lesion load (T2-LL). RESULTS: At baseline, all the brain volume metrics, except cGMV, were significantly lower; and the T2-LL was significantly higher, in patients with MS rather than CIS. During the follow-up, only the PBVC was higher in MS (p = 0.008) and this difference was driven by converters from CIS to MS. Quartiles of PBVC did not allow us to predict conversion to MS, but were associated with the degree of disability. CONCLUSIONS: PBVC is the most sensitive marker of progressing atrophy and a higher PBVC was generally associated with more active disease; however, it did not serve to predict the course of MS on an individual basis, in this study.


Subject(s)
Brain/pathology , Demyelinating Diseases/pathology , Multiple Sclerosis/pathology , Adult , Atrophy/pathology , Disease Progression , Female , Humans , Image Interpretation, Computer-Assisted , Magnetic Resonance Imaging , Male
4.
J Crohns Colitis ; 7(1): 58-69, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22542057

ABSTRACT

BACKGROUND: The incidence of inflammatory bowel disease (IBD) varies widely between different countries. This large variation is also observed for the incidence of its main two forms, ulcerative colitis (UC) and Crohn's disease (CD). Controversy exists whether IBD incidence is increasing, especially in western countries. Currently no data are available for Austria. This study therefore aimed to evaluate for the first time the incidence of IBD over an eleven-year period in Styria, a province of Austria with a population of 1.2 million. METHODS: All patients with an initial diagnosis of IBD between 1997 and 2007, who were Styrian residents, were eligible for this retrospective study. Data were acquired from electronically stored hospital discharge reports and individual reports by patients and physicians. According to population density Styria was divided into two rural and one urban area. RESULTS: Throughout the study period 1527 patients with an initial diagnosis of IBD were identified. The average annual incidence was 6.7 (95% CI 6.2-7.1) per 100,000 persons per year for CD and 4.8 (95% CI 4.5-5.2) for UC. The average annual incidence increased significantly (p<0.01) for both diseases during the 11 year study period. Median age at initial diagnosis was 29 years (range 3-87) for CD and 39 years (range 3-94) for UC. At diagnosis, 8.5% of all IBD patients were <18 years of age. The incidence of both CD and UC was significantly higher in the urban area than in rural areas (CD: 8.8, 95% CI 7.8-9.8 versus 5.5, 95% CI 4.7-6.4 and 5.9, 95% CI 5.3-6.7; [p<0.001]; UC: 5.8, 95% CI 5.1-6.6 versus 4.0, 95% CI 3.4-4.7 and 4.7, 95% CI 4.1-5.4; [p=0.04]). CONCLUSION: We observed an overall increase in the incidence of ulcerative colitis and Crohn's disease in a part of Austria during an eleven year period. IBD was more predominant in the largest urban area than in rural areas.


Subject(s)
Colitis, Ulcerative/epidemiology , Crohn Disease/epidemiology , Rural Population/statistics & numerical data , Urban Population/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Austria/epidemiology , Child , Child, Preschool , Confidence Intervals , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Young Adult
5.
Mult Scler ; 19(4): 436-42, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22917689

ABSTRACT

BACKGROUND: Axonal damage is considered a major cause of disability in multiple sclerosis (MS) and may start early in the disease. Specific biomarkers for this process are of great interest. OBJECTIVE: To study if cerebrospinal fluid (CSF) biomarkers for axonal damage reflect and predict disease progression already in the earliest stages of the disease, that is, in clinically isolated syndrome (CIS). METHODS: We assessed CSF levels of neurofilament heavy (NFH), neurofilament light (NFL) and N-acetylaspartate (NAA) in 67 patients with CIS and 18 controls with neuropsychiatric diseases of non-inflammatory aetiology (NC). Patients with CIS underwent baseline magnetic resonance imaging (MRI) at 3T, and a follow-up MRI after 1 year was obtained in 28 of them. RESULTS: Compared with NC, patients with CIS had higher NFH (p=0.05) and NFL (p<0.001) levels. No significant group differences were found for NAA. Patients' NFH levels correlated with physical disability (r=0.304, p<0.05) and with change in brain volume over 1 year of follow-up (r=-0.518, p<0.01) but not with change in T2 lesion load. CONCLUSION: Our results confirm increased neurofilament levels already in CIS being related to the level of physical disability. The association of NFH levels with brain volume but not lesion volume changes supports the association of these markers with axonal damage.


Subject(s)
Biomarkers/cerebrospinal fluid , Brain/pathology , Demyelinating Diseases/cerebrospinal fluid , Neurofilament Proteins/cerebrospinal fluid , Adult , Aspartic Acid/analogs & derivatives , Aspartic Acid/cerebrospinal fluid , Demyelinating Diseases/pathology , Female , Humans , Magnetic Resonance Imaging , Male
6.
Neurology ; 77(18): 1691-7, 2011 Nov 01.
Article in English | MEDLINE | ID: mdl-21975210

ABSTRACT

OBJECTIVES: Abnormal high cerebral iron deposition may be implicated in chronic neurologic disorders, including multiple sclerosis (MS). R2* relaxometry has been recently validated in a postmortem study to indicate brain iron accumulation in a quantitative manner. We used this technique to assess brain iron levels in different stages of MS and healthy controls (HC) and determined their relation with demographic, clinical, neuropsychological, and other imaging variables. METHODS: We studied 113 consecutive patients (35 clinically isolated syndrome [CIS], 78 MS) and 35 HC with 3 T MRI and clinical and neuropsychological examination. Iron deposition in subcortical gray matter structures was assessed by automated, regional calculation of R2* rates. RESULTS: Basal ganglia (BG) R2* levels were significantly increased in MS compared to CIS (p < 0.001) and HC (p < 0.005). They were correlated with age (r = 0.5, p < 0.001), disease duration (r = 0.5, p < 0.001), Expanded Disability Status Scale (r = 0.3, p < 0.005), and the z values of mental processing speed (r = -0.3, p < 0.01). Stepwise linear regression analysis revealed gray matter atrophy as the strongest independent predictor of BG R2* levels (p < 0.001), followed by age (p < 0.001) and T2 lesion load (p < 0.005). CONCLUSION: BG iron accumulation in MS occurs with advancing disease and is related to the extent of morphologic brain damage, which argues for iron deposition as an epiphenomenon. The absence of increased iron levels in patients with CIS indicates that iron accumulation does not precede the development of MS.


Subject(s)
Brain/metabolism , Brain/pathology , Iron/metabolism , Magnetic Resonance Imaging/methods , Multiple Sclerosis/pathology , Multiple Sclerosis/physiopathology , Adult , Brain/anatomy & histology , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Young Adult
7.
Mult Scler ; 17(2): 173-80, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20956399

ABSTRACT

BACKGROUND: Cognitive deficits are frequent in multiple sclerosis (MS) and have been associated with morphologic brain changes. Less information exists on their extent and relation to MRI findings in clinically isolated syndrome (CIS). It is also unclear if structural changes as detected by magnetization transfer (MT) imaging may provide an additional explanation for cognitive dysfunction. OBJECTIVE: To analyse the extent of cognitive deficits and their relation to MRI metrics including MT imaging in CIS compared to relapsing-remitting MS (RRMS). METHODS: Forty-four CIS and 80 RRMS patients underwent the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) and a 3 T MRI scan. RESULTS: BRB-N subtests revealed similar results in CIS and RRMS. Impaired mental processing speed was most prevalent in both groups (CIS 13.6%; RRMS 16.3%) and thus served for correlation with MRI metrics. Using stepwise linear regression analyses, the strongest predictor for decreased mental processing speed was normalized cortex volume (p < 0.001) followed by T2-lesion load (p < 0.05) in RRMS, whereas cortical MT ratio was the only MRI parameter associated with decreased mental processing speed in CIS (p < 0.005). CONCLUSION: Cognitive dysfunction occurs in CIS in a pattern similar to RRMS, with impaired mental processing speed being most prevalent. Cortical MT-ratio changes may be an early sign for tissue changes related to impaired mental processing speed in CIS while this association shifts to increased signs of cortical atrophy and lesion load in RRMS.


Subject(s)
Brain/pathology , Cognition Disorders/diagnosis , Cognition , Demyelinating Diseases/diagnosis , Magnetic Resonance Imaging , Multiple Sclerosis, Relapsing-Remitting/diagnosis , Adult , Atrophy , Austria , Chi-Square Distribution , Cognition Disorders/etiology , Cognition Disorders/pathology , Demyelinating Diseases/pathology , Demyelinating Diseases/psychology , Disability Evaluation , Executive Function , Female , Humans , Linear Models , Male , Memory , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/pathology , Multiple Sclerosis, Relapsing-Remitting/psychology , Neuropsychological Tests , Prospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Young Adult
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