Clinical and neurophysiological patterns of impairments to emotion attention and empathy in multiple sclerosis.

Patients suffering from multiple sclerosis experience various cognitive and affective impairments, resulting in a negative impact on social behavior and personal independence to differing degrees. According to these often clinically subtle but conflicting cognitive-affective impairments, recordings of these socially relevant issues are still of demand to stratifying clinical and social support in a sophisticated way. Therefore, we studied specific cognitive and affective capacities in eleven patients with a predominant relapsing-remitting type of multiple sclerosis by applying paradigms of event-related potentials and a well-selected neuropsychological test protocol. Thus far, distinct cognitive disturbances of executive and attentional domains and the Wechsler Memory Test's four memory indices were found in multiple sclerosis patients. Concerning affective domains, patients showed discrete impairments of affect discrimination and affected naming as proved by specific testing (Tuebinger Affect Battery). Neurophysiologically, event-related potentials recordings in multiple sclerosis patients, were associated with decreased implicit emotion processing to cues of different emotion arousal at the early processing stage depending on attentional capacities and alterations of implicit emotion modulation at late processing stages. These clinical neurophysiological and neuropsychological data were correlated in part to quantitative magnetic resonance imaging brain lesions. Summarizing our data, our data indicate certain neurocognitive and neuroaffective dysfunctions in patients with multiple sclerosis, thus highlighting the validity of sensitive recording of less apparent neurologic disturbances in multiple sclerosis for optimizing the individual care management in patients.

Extending the time window for intravenous thrombolysis in acute ischemic stroke using magnetic resonance imaging-based patient selection.

BACKGROUND: Intravenous thrombolysis with alteplase within a time window up to 4.5 h is the only approved pharmacological treatment for acute ischemic stroke. We studied whether acute ischemic stroke patients with penumbral tissue identified on magnetic resonance imaging 4.5-9 h after symptom onset benefit from intravenous thrombolysis compared to placebo. METHODS: Acute ischemic stroke patients with salvageable brain tissue identified on a magnetic resonance imaging were randomly assigned to receive standard dose alteplase or placebo. The primary end point was disability at 90 days assessed by the modified Rankin scale, which has a range of 0-6 (with 0 indicating no symptoms at all and 6 indicating death). Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. RESULTS: The trial was stopped early for slow recruitment after the enrollment of 119 (61 alteplase, 58 placebo) of 264 patients planned. Median time to intravenous thrombolysis was 7 h 42 min. The primary endpoint showed no significant difference in the modified Rankin scale distribution at day 90 (odds ratio alteplase versus placebo, 1.20; 95% CI, 0.63-2.27, P = 0.58). One symptomatic intracranial hemorrhage occurred in the alteplase group. Mortality at 90 days did not differ significantly between the two groups (11.5 and 6.8%, respectively; P = 0.53). CONCLUSIONS: Intravenous alteplase administered between 4.5 and 9 h after the onset of symptoms in patients with salvageable tissue did not result in a significant benefit over placebo. (Supported by Boehringer Ingelheim, Germany; ISRCTN 71616222).

Dolichoectasia and Small Vessel Disease in Young Patients With Transient Ischemic Attack and Stroke.

BACKGROUND AND PURPOSE: We evaluated whether basilar dolichoectasia is associated with markers of cerebral small vessel disease in younger transient ischemic attack and ischemic stroke patients. METHODS: We used data from the SIFAP1 study (Stroke in Young Fabry Patients), a large prospective, hospital-based, screening study for Fabry disease in young (<55 years) transient ischemic attack/stroke patients in whom detailed clinical data and brain MRI were obtained, and stroke subtyping with TOAST classification (Trial of ORG 10172 in Acute Stroke Treatment) was performed. RESULTS: Dolichoectasia was found in 508 of 3850 (13.2%) of patients. Dolichoectasia was associated with older age (odds ratio per decade, 1.26; 95% confidence interval, 1.09-1.44), male sex (odds ratio, 1.96; 95% confidence interval, 1.59-2.42), and hypertension (odds ratio, 1.39; 95% confidence interval, 1.13-1.70). Dolichoectasia was more common in patients with small infarctions (33.9% versus 29.8% for acute lesions, P=0.065; 29.1% versus 16.5% for old lesions, P<0.001), infarct location in the brain stem (12.4% versus 6.9%, P<0.001), and in white matter (27.8% versus 21.1%, P=0.001). Microbleeds (16.3% versus 4.7%, P=0.001), higher grades of white matter hyperintensities (P<0.001), and small vessel disease subtype (18.1% versus 12.4%, overall P for differences in TOAST (P=0.018) were more often present in patients with dolichoectasia. CONCLUSIONS: Dolichoectasia is associated with imaging markers of small vessel disease and brain stem localization of acute and old infarcts in younger patients with transient ischemic attack and ischemic stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583.

Prevalence and outcome of late-onset seizures due to autoimmune etiology: A prospective observational population-based cohort study.

OBJECTIVE: The increasing incidence of new-onset seizures with age is well known. Often, the etiology cannot be clarified. In the present study, patients with unprovoked late-onset seizures and without known neoplasm, who might have had paraneoplastic encephalitis, were investigated for a potentially underlying autoimmunity. METHODS: Sixty-six consecutive patients (36 women; aged ≥55 years) after having at least one seizure or seizures for ≤6 months were prospectively identified over a period of 4.75 years. All patients were tested for serum and cerebrospinal fluid (CSF) antibodies (Abs) to both neural cell-surface and intracellular antigens. Forty-five (68%) underwent brain magnetic resonance imaging (MRI). Follow-up in Ab-positive cases was ≥6 months. RESULTS: Two patients had high titers of anti-CASPR2 (contactin-associated protein-like 2) Abs in serum and CSF and fulfilled the diagnostic criteria of definite limbic encephalitis. Another two patients had bilateral encephalitic temporal MRI abnormalities. They also satisfied the criteria of definite limbic encephalitis, even though they had no Abs in serum or CSF. All four were in the age range of 55-70 years. They received immunotherapy and/or antiepileptic drug treatment and became seizure-free. SIGNIFICANCE: Our findings suggest that autoimmunity should be considered an important etiology in patients with late-onset seizures. Testing for neural antibodies and brain MRI may be worthwhile in this patient group.

Posterior versus Anterior Circulation Stroke in Young Adults: A Comparative Study of Stroke Aetiologies and Risk Factors in Stroke among Young Fabry Patients (sifap1).

BACKGROUND: Although 20-30% of all strokes occur in the posterior circulation, few studies have explored the characteristics of patients with strokes in the posterior compared to the anterior circulation so far. Especially data on young patients is missing. METHODS: In this secondary analysis of data of the prospective multi-centre European sifap1 study that investigated stroke and transient ischemic attack (TIA) patients aged 18-55 years, we compared vascular risk factors, stroke aetiology, presence of white matter hyperintensities (WMH) and cerebral microbleeds (CMB) between patients with ischaemic posterior circulation stroke (PCS) and those having suffered from anterior circulation stroke (ACS) based on cerebral MRI. RESULTS: We diagnosed PCS in 612 patients (29.1%, 407 men, 205 women) and ACS in 1,489 patients (70.9%). Their age (median 46 vs. 47 years, p = 0.205) and stroke severity (modified Rankin Scale: both 2, p = 0.375, Barthel Index 90 vs. 85, p = 0.412) were similar. PCS was found to be more frequent among the male gender (66.5 vs. 60.1% with ACS, p = 0.003). Vertebral artery (VA) dissection was more often the cause of PCS (16.8%) than was carotid artery dissection of ACS (7.9%, p < 0.001). Likewise, small vessel disease (Trial of Org 10172 in Acute Stroke Treatment [TOAST] = 3, PCS: 14.7%, ACS: 11.8%) and stroke of other determined aetiology (TOAST = 4, PCS: 24.5%, ACS: 16.0%) were more frequent in those with PCS. Furthermore, patent foramen ovale (PFO; PCS: 31.1%, ACS: 25.4%, p = 0.029) was more often detected in patients with PCS. In contrast, large-artery atherosclerosis (TOAST = 1, PCS: 15.4%, ACS: 22.2%) and cardio-embolic stroke (TOAST = 2, PCS: 15.6%, ACS: 18.0%) were less frequent in those with PCS (p < 0.001) as were preceding cerebrovascular events (10.1 vs. 14.1%, p = 0.014), TIA (4.8 vs. 7.7%, p = 0.016) and smoking (53.2 vs. 61.0%, p = 0.001). The presence, extent, and location of WMH and CMB did not differ between the 2 groups. CONCLUSIONS: Our data suggested a different pattern of aetiology and risk factors in young patients with PCS compared to those with ACS. These findings especially call for a higher awareness of VA dissection and potentially for more weight of a PFO as a risk factor in young patients with PCS. Clinical trial registration-URL: http://www.clinicaltrials.gov; NCT00414583.

Intravenous Thrombolysis and Passes of Thrombectomy as Predictors for Endovascular Revascularization in Ischemic Stroke.

BACKGROUND: Patient selection for endovascular revascularization treatment (ERT) in acute ischemic stroke depends on the expected benefit-risk ratio. As rapid revascularization is a major determinant of good functional outcome, we aimed to identify its predictors after ERT. METHODS: Consecutive stroke patients from a single stroke center with distal internal carotid artery-, proximal middle cerebral artery- or T-occlusions treated with ERT were retrospectively selected. We assessed admission noncontrast computed tomography and computed tomography angiography for thrombus location, thrombus load (clot burden score), and collateral status. Clinical data were extracted from medical charts. Univariate and multivariate regression analyses were performed to identify predictors of revascularization (thrombolysis in cerebral infarction ≥2b) after ERT. RESULTS: A total of 63 patients were identified (median age, 73 years; interquartile range: 62-77; 40 females). Sixteen patients (25.4%) underwent intravenous thrombolysis (ivT) before ERT. Twenty-two patients (34.9%) had additional intra-arterial application of recombinant tissue plasminogen activator. The overall recanalization rate was 66.7%, and 9.5% had symptomatic intracranial bleeding. In-hospital mortality was 15%, and 30% reached good functional outcome at discharge. In the univariate analysis, preceding ivT and the number of passes for thrombectomy (dichotomized ≤2 versus >2) were associated with recanalization. There was a trend for number of thrombectomy passes (as continuous variable) and multimodal ERT. In the multivariate regression analysis, ivT prior to ERT and passes of thrombectomy were identified as independent predictors for recanalization. CONCLUSION: ivT and lower passes of thrombectomy are associated with recanalization after ERT for ischemic stroke with proximal vessel occlusions.

Reduced Numbers and Impaired Function of Regulatory T Cells in Peripheral Blood of Ischemic Stroke Patients.

BACKGROUND AND PURPOSE: Regulatory T cells (Tregs) have been suggested to modulate stroke-induced immune responses. However, analyses of Tregs in patients and in experimental stroke have yielded contradictory findings. We performed the current study to assess the regulation and function of Tregs in peripheral blood of stroke patients. Age dependent expression of CD39 on Tregs was quantified in mice and men. METHODS: Total FoxP3(+) Tregs and CD39(+)FoxP3(+) Tregs were quantified by flow cytometry in controls and stroke patients on admission and on days 1, 3, 5, and 7 thereafter. Treg function was assessed by quantifying the inhibition of activation-induced expression of CD69 and CD154 on T effector cells (Teffs). RESULTS: Total Tregs accounted for 5.0% of CD4(+) T cells in controls and <2.8% in stroke patients on admission. They remained below control values until day 7. CD39(+) Tregs were most strongly reduced in stroke patients. On day 3 the Treg-mediated inhibition of CD154 upregulation on CD4(+) Teff was impaired in stroke patients. CD39 expression on Treg increased with age in peripheral blood of mice and men. CONCLUSION: We demonstrate a loss of active FoxP3(+)CD39(+) Tregs from stroke patient's peripheral blood. The suppressive Treg function of remaining Tregs is impaired after stroke.

Influence of Recanalization and Time of Cerebral Ischemia on Tissue Outcome after Endovascular Stroke Treatment on Computed Tomography Perfusion.

BACKGROUND: The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) has been proposed as a straightforward alternative to the less reliable visual estimation of tissue at risk. We evaluated the association between admission ASPECTS on computed tomography perfusion (CTP) parameter maps and final infarct ASPECTS in patients with acute ischemic stroke who were treated by endovascular therapy (eT) and compared the results with thrombolysis candidates treated conservatively. METHODS: eT was performed in 26 consecutive ischemic stroke patients within 6 hours of symptom onset. The control group was matched for age and admission National Institutes of Health Stroke Scale having the same admission imaging protocol and a transcranial Doppler sonography within 24 hours. ASPECTS determined from CTP maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and time to peak (TTP) were compared with final infarct ASPECTS on day 5 noncontrast CT. RESULTS: Recanalization rate was 73% in treatment and 50% in control group. ASPECTS for all CTP parameters were significantly lower than ASPECTS-CT in both groups (P < .005). In the treatment group, this applied to patients with successful recanalization. Only controls without recanalization showed a strong correlation between ASPECTS-CTP parameters and ASPECTS-CT (CBV: P = .005; CBF and TTP: P = .028). Patients with early recanalization (≤4 hours) had greater differences between ASPECTS-CTP and ASPECTS-CT than patients with late recanalization (>4 hours; CBF: P = .056; CBV: P = .095; TTP: P = .048). CONCLUSIONS: The initial ASPECTS-CTP lesion was significantly larger than the final infarct determined by ASPECTS in case of recanalization. Initial perfusion lesion, including CBV, is reversible in case of reperfusion, especially in early reperfusion.

Family History in Young Patients With Stroke.

BACKGROUND AND PURPOSE: Family history of stroke is an established risk factor for stroke. We evaluated whether family history of stroke predisposed to certain stroke subtypes and whether it differed by sex in young patients with stroke. METHODS: We used data from the Stroke in Fabry Patients study, a large prospective, hospital-based, screening study for Fabry disease in young patients (aged <55 years) with stroke in whom cardiovascular risk factors and family history of stroke were obtained and detailed stroke subtyping was performed. RESULTS: A family history of stroke was present in 1578 of 4232 transient ischemic attack and ischemic stroke patients (37.3%). Female patients more often had a history of stroke in the maternal lineage (P=0.027) than in the paternal lineage. There was no association with stroke subtype according to Trial of Org 10172 in Acute Stroke Treatment nor with the presence of white matter disease on brain imaging. Patients with dissection less frequently reported a family history of stroke (30.4% versus 36.3%; P=0.018). Patients with a parental history of stroke more commonly had siblings with stroke (3.6% versus 2.6%; P=0.047). CONCLUSIONS: Although present in about a third of patients, a family history of stroke is not specifically related to stroke pathogenic subtypes in patients with young stroke. Young women with stroke more often report stroke in the maternal lineage. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583.

Brain magnetic resonance imaging findings fail to suspect Fabry disease in young patients with an acute cerebrovascular event.

BACKGROUND AND PURPOSE: Fabry disease (FD) may cause stroke and is reportedly associated with typical brain findings on magnetic resonance imaging (MRI). In a large group of young patients with an acute cerebrovascular event, we wanted to test whether brain MRI findings can serve to suggest the presence of FD. METHODS: The Stroke in Young Fabry Patients (SIFAP 1) study prospectively collected clinical, laboratory, and radiological data of 5023 patients (18-55 years) with an acute cerebrovascular event. Their MRI was interpreted centrally and blinded to all other information. Biochemical findings and genetic testing served to diagnose FD in 45 (0.9%) patients. We compared the imaging findings between FD and non-FD patients in patients with at least a T2-weighted MRI of good quality. RESULTS: A total of 3203 (63.8%) patients had the required MRI data set. Among those were 34 patients with a diagnosis of FD (1.1%), which was definite in 21 and probable in 13 cases. The median age of patients with FD was slightly lower (45 versus 46 years) and women prevailed (70.6% versus 40.7%; P<0.001). Presence or extent of white matter hyperintensities, infarct localization, vertebrobasilar artery dilatation, T1-signal hyperintensity of the pulvinar thalami, or any other MRI finding did not distinguish patients with FD from non-FD cerebrovascular event patients. Pulvinar hyperintensity was not present in a single patient with FD but seen in 6 non-FD patients. CONCLUSIONS: Brain MRI findings cannot serve to suspect FD in young patients presenting with an acute cerebrovascular event. This deserves consideration in the search for possible causes of young patients with stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583.

Neural correlates of impaired emotional face recognition in cerebellar lesions.

Clinical and neuroimaging data indicate a cerebellar contribution to emotional processing, which may account for affective-behavioral disturbances in patients with cerebellar lesions. We studied the neurophysiology of cerebellar involvement in recognition of emotional facial expression. Participants comprised eight patients with discrete ischemic cerebellar lesions and eight control patients without any cerebrovascular stroke. Event-related potentials (ERP) were used to measure responses to faces from the Karolinska Directed Emotional Faces Database (KDEF), interspersed in a stream of images with salient contents. Images of faces augmented N170 in both groups, but increased late positive potential (LPP) only in control patients without brain lesions. Dipole analysis revealed altered activation patterns for negative emotions in patients with cerebellar lesions, including activation of the left inferior prefrontal area to images of faces showing fear, contralateral to controls. Correlation analysis indicated that lesions of cerebellar area Crus I contribute to ERP deviations. Overall, our results implicate the cerebellum in integrating emotional information at different higher order stages, suggesting distinct cerebellar contributions to the proposed large-scale cerebral network of emotional face recognition.

Predictive value of EFHC1 variants for the long-term seizure outcome in juvenile myoclonic epilepsy.

OBJECTIVE: This study aimed to determine the contribution of EFHC1 variants to the phenotypic variability of juvenile myoclonic epilepsy (JME) and to evaluate their diagnostic value regarding previously identified clinical long-term seizure outcome predictors in a consecutive cohort of patients with JME. METHODS: Thirty-eight probands and three family members affected with JME were studied at a tertiary epilepsy center with a review of their medical records and a subsequent face-to-face interview. All coding EFHC1 exons and adjacent exon/intron boundaries were directly sequenced. RESULTS: The previously reported EFHC1 mutation F229L was found in two cases who presented with early generalized tonic-clonic seizure (GTCS) onset and appeared to be associated with milder subtypes of JME. Variant R294H was identified in two further probands who had a subtype of JME developing from childhood absence epilepsy. However, segregation of the phenotype with this variant could not be confirmed in one family. CONCLUSIONS: Our findings corroborate the heterogeneity of JME as an electroclinical epilepsy syndrome and provide evidence that genetic factors may influence and help predict the long-term seizure outcome in patients with JME.

Cervical artery dissection in young adults in the stroke in young Fabry patients (sifap1) study.

BACKGROUND: Patients with carotid artery dissection (CAD) have been reported to have different vascular risk factor profiles and clinical outcomes to those with vertebral artery dissection (VAD). However, there are limited data from recent, large international studies comparing risk factors and clinical features in patients with cervical artery dissection (CeAD) with other TIA or ischemic stroke (IS) patients of similar age and sex. METHODS: We analysed demographic, clinical and risk factor profiles in TIA and IS patients ≤55 years of age with and without CeAD in the large European, multi-centre, Stroke In young FAbry Patients 1 (sifap1) study. Patients were further categorised according to age (younger: 18-44 years; middle-aged: 45-55 years), sex, and site of dissection. RESULTS: Data on the presence of dissection were available in 4,208 TIA and IS patients of whom 439 (10.4%) had CeAD: 196 (50.1%) had CAD, 195 (49.9%) had VAD, and 48 had multiple artery dissections or no information regarding the dissected artery. The prevalence of CAD was higher in women than in men (5.9 vs. 3.8%, p < 0.01), whereas the prevalence of VAD was similar in women and men (4.6 vs. 4.7%, n.s.). Patients with VAD were younger than patients with CAD (median = 41 years (IQR = 35-47 years) versus median = 45 years (IQR = 39-49 years); p < 0.01). At stroke onset, about twice as many patients with either CAD (54.0 vs. 23.1%, p < 0.001) or VAD (63.4 vs. 36.6%, p < 0.001) had headache than patients without CeAD and stroke in the anterior or posterior circulation, respectively. Compared to patients without CeAD, hypertension, concomitant cardiovascular diseases and a patent foramen ovale were significantly less prevalent in both CAD and VAD patients, whereas tobacco smoking, physical inactivity, obesity and a family history of cerebrovascular diseases were found less frequently in CAD patients, but not in VAD patients. A history of migraine was observed at a similar frequency in patients with CAD (31%), VAD (27.8%) and in those without CeAD (25.8%). CONCLUSIONS: We identified clinical features and risk factor profiles that are specific to young patients with CeAD, and to subgroups with either CAD or VAD compared to patients without CeAD. Therefore, our data support the concept that certain vascular risk factors differentially affect the risk of CAD and VAD.

Natural course and predictors of spontaneous seizure remission in idiopathic generalized epilepsy: 7-27 years of follow-up.

The spontaneous course of idiopathic generalized epilepsy (IGE) is still controversial. The aim of this study was both to investigate the long-term spontaneous course and to identify factors that are predictive for epilepsy remission in a small cohort of 15 IGE patients (9 women) who refused antiepileptic drug (AED) treatment and therefore never have been treated with AED. All of them were reevaluated with a review of their medical records and direct face-to-face interview; the mean duration of follow-up was 15.3 years. Five (33.3%) of them had absence epilepsy (absence seizures, ABS), 5 had IGE with generalized tonic-clonic seizures (GTCS), and another 5 had both seizure types (IGE with ABS/GTCS). Rate of epilepsy remission was 53.3% with a mean time of seizure freedom of 13.1 years; rate of remission was highest among absence epilepsy patients (80%), followed by IGE with GTCS (60%) and IGE with ABS/GTCS (20%). The frequency of spontaneous generalized interictal epileptiform discharges in electroencephalography is not associated with the long-term seizure outcome (p=0.201) and per se does not require AED treatment. Furthermore, the occurrence of photoparoxysmal responses (p=0.020) as well as the occurrence of more than 3 GTCS during the course (p=0.029) were identified as significant predictors for a poor long-term seizure outcome which makes AED treatment indispensable in these patients. This study underlines the heterogenity of the group of IGE. AED treatment has no impact on the spontaneous course of IGE with ABS and/or GTCS. Several predictors for the long-term seizure outcome in patients with IGE were identified in this study.

Stroke alters respiratory burst in neutrophils and monocytes.

BACKGROUND AND PURPOSE: Stroke-induced immune alterations predispose patients to infections. Although the relationship between stroke and the adaptive immune system has been investigated in detail, to date it is unknown whether the innate immune system, which forms the first line of antibacterial defense, is also impaired in patients with stroke. Therefore, we investigated whether chemotaxis, phagocytosis, oxidative burst, degranulation of defensins, and NETosis in monocytes and in neutrophil granulocytes are altered in patients with stroke compared with controls. METHODS: Sixty-three patients having acute ischemic stroke were recruited within 12 hours of symptom onset; blood was sampled on admission and on days 1, 3, 5, and 7. Thirty-seven age-matched controls were also recruited. Cell migration, phagocytosis, and oxidative burst of phagocytes were determined in vitro. Human neutrophil peptides 1 to 3 and serum metanephrine levels were measured by enzyme-linked immunosorbent assay, and NETosis was quantified by immunohistochemistry. RESULTS: The key mechanisms required for bacterial killing, oxidative burst, and NETosis were significantly reduced in samples taken from patients with stroke compared with controls, whereas migration, phagocytic function, and defensin production remained unimpaired in monocytes and granulocytes from patients with stroke. CONCLUSIONS: Stroke-induced immune alterations include impairment of the first-line defense performed by specialized phagocytes against bacteria. The hypothesis that these changes enhance susceptibility to acquired infections is supported by our observation that on admission oxidative burst in monocytes was more impaired in patients with stroke with subsequent stroke-associated infections.

Clinical predictors of the long-term social outcome and quality of life in juvenile myoclonic epilepsy: 20-65 years of follow-up.

OBJECTIVE: The long-term social outcome in patients with juvenile myoclonic epilepsy (JME) is still controversial. The aim of this study was both to investigate the long-term social outcome in relation to clinical variables and to identify epilepsy-related factors that affect the quality of life (QoL) in JME patients with a follow-up of at least 20 years. METHODS: A retrospective selection of 33 of 90 patients (21 female) from a tertiary epilepsy center diagnosed with JME and followed for ≥20 years (mean 37.8 years) was studied. All patients were evaluated with a thorough review of their medical records, and a subsequent face-to-face or telephone interview. QOLIE-31-P questionnaire (QoL In Epilepsy) and Beck Depression Inventory-II were used to assess the QoL and the presence and severity of depressive symptoms, respectively. RESULTS: Of 33 patients, 18 (54.5%) became seizure-free; in 4 of the patients (22.2%), antiepileptic drug (AED) treatment was discontinued. Early and long-term seizure freedom improves both social adjustment (p = 0.02) and occupational integration (p = 0.02) and associates with a better QoL (odds ratio [OR] 2.25). A high seizure burden highly affects both aspects of personal life-family and work; notably the occurrence of frequent and/or late onset generalized tonic-clonic seizures increases the risk of concomitant diseases (p = 0.05) and lifelong AED treatment (p = 0.03), decreases the patient's employability (p = 0.02), increases the rate of employment disability pension (p = 0.05), and considerably increases public/social spending. Seizure freedom significantly increases the QoL (p = 0.001), whereas more severe courses of epilepsy (OR 3.2), AED side effects (p = 0.04), depression (p = 0.02), and sleep disturbances (OR 2.7) considerably decrease the patient's QoL. SIGNIFICANCE: Although patients with JME are a heterogeneous group, several predictors for the long-term social, family, educational, and occupational outcome have been identified in our study and should be considered in the effort to both improve the patient's QoL as well as preserve economic resources.

Impaired recognition of emotional facial expressions in patients with multiple sclerosis.

BACKGROUND: Disturbances that occur in patients with multiple sclerosis (MS) are not restricted to motor, sensory, or urinary functions; they also include cognitive dysfunction, fatigue, and depression. Moreover, people with MS are known to have fewer social activities and a reduced quality of life. One aspect of social interaction is accurate recognition of facial expressions. Several studies have suggested impairment in the processing of facial expressions in patients with multiple sclerosis, but it is not clear if these deficits are based on cognitive, depressive, or other attendant symptoms. OBJECTIVE: To investigate emotion recognition and facial identity recognition abilities and their relation with cognitive functions, depression, and fatigue in a cohort of MS patients. METHODS: Emotion recognition and facial identity recognition abilities were investigated in a cohort of 61 MS patients with unimpaired visual acuity and 53 healthy controls using the Florida Affect Battery. Additionally, we investigated possible relationships between impaired facial expression recognition and other clinical features. RESULTS: MS patients were not impaired in facial identity discrimination, but showed a poor performance in all subtests that required emotion recognition. CONCLUSION: Impaired recognition of facial emotions by patients with MS seems to be associated with both cognitive and affective (depression) aspects of the disease.

MRI in acute cerebral ischemia of the young: the Stroke in Young Fabry Patients (sifap1) Study.

OBJECTIVE: We focused on cerebral imaging findings in a large cohort of young patients with a symptomatic ischemic cerebrovascular event (CVE) to extract relevant pathophysiologic and clinical information. METHODS: We analyzed the scans of 2,979 patients (aged 18-55 years) enrolled in the sifap1 project with clinical evidence of ischemic stroke (IS) or clinically defined TIA in whom MRI, including diffusion-weighted imaging, was obtained within 10 days of the CVE. Age groups were categorized as 18-34, 35-44, and 45-55 years. We compared age- and sex-specific proportions of infarct features, white matter hyperintensities, and old microbleeds. RESULTS: Acute infarcts were identified in 1,914 of 2,264 patients (84.5%) with IS and 101 of 715 patients (14.1%) with TIA. Among patients with IS, younger age was significantly associated with acute infarcts in the posterior circulation, while anterior circulation infarcts and acute lacunar infarcts were more frequent in older age groups. One or more old infarcts were present in 26.8% of IS and 17.1% of TIA patients. This rate remained high even after excluding patients with a prior CVE (IS, 21.7%; TIA, 9.9%). The prevailing type of old infarction was territorial in patients younger than 45 years and lacunar in those aged 45 years or older. The frequency of white matter hyperintensities (46.4%) and their severity was positively associated with age. Old microbleeds were infrequent (7.2%). CONCLUSIONS: Young adults show a high frequency of preexisting and clinically silent infarcts and a relative preference for acute ischemia in the posterior circulation. Findings suggesting small-vessel disease become apparent at age 45 years and older.

Prevalence of stenoses and occlusions of brain-supplying arteries in young stroke patients.

OBJECTIVE: Atherosclerosis is believed to be a minor cause of TIA and stroke in younger and middle-aged patients. However, data from large cohorts are limited. This study investigates the prevalence of extracranial and intracranial atherosclerosis in stroke and TIA patients aged 18-55 years in the multinational sifap1 study. METHODS: From the sifap1 cohort (n = 5,023), we analyzed a subset of patients with complete data from carotid ultrasound studies. Patients with arterial dissections, vasculitis, and mobile thrombi were excluded. Among the remaining 2,187 patients (men: n = 1,319; 18-44 years: n = 744), intracranial arteries were additionally examined with ultrasonography in 1,612 patients (73.7%). Patients were stratified by sex and age groups (younger: 18-44 years; middle-aged: 45-55 years). RESULTS: In patients with ischemic stroke, the overall prevalence of carotid artery stenoses and occlusions was 8.9% (younger: 4.9%; middle-aged: 11.0%), of which 81% were symptomatic. Nonstenotic carotid plaques were more common in men than in women (15.8% vs. 7.7%; p < 0.001), and in middle-aged than in younger patients (17.0% vs. 4.9%; p < 0.001). Supratentorial intracranial artery stenoses and occlusions amounted to 11.8%. Supratentorial stenoses occurred more frequently in middle-aged patients (13.0% vs. 7.8%; p < 0.001), whereas occlusions were equally common (both 3.2%; not significant). CONCLUSIONS: We observed a substantial proportion of atherosclerotic carotid artery stenoses and occlusions in younger stroke patients. Intracranial stenoses and occlusions were even more prevalent than extracranial carotid artery disease. Together with nonstenotic plaques, one-fifth of patients (21.2%) had symptomatic or asymptomatic large-artery atherosclerosis, which should encourage future stroke prevention campaigns to target risk factor modification in young people.

Acute cerebrovascular disease in the young: the Stroke in Young Fabry Patients study.

BACKGROUND AND PURPOSE: Strokes have especially devastating implications if they occur early in life; however, only limited information exists on the characteristics of acute cerebrovascular disease in young adults. Although risk factors and manifestation of atherosclerosis are commonly associated with stroke in the elderly, recent data suggests different causes for stroke in the young. We initiated the prospective, multinational European study Stroke in Young Fabry Patients (sifap) to characterize a cohort of young stroke patients. METHODS: Overall, 5023 patients aged 18 to 55 years with the diagnosis of ischemic stroke (3396), hemorrhagic stroke (271), transient ischemic attack (1071) were enrolled in 15 European countries and 47 centers between April 2007 and January 2010 undergoing a detailed, standardized, clinical, laboratory, and radiological protocol. RESULTS: Median age in the overall cohort was 46 years. Definite Fabry disease was diagnosed in 0.5% (95% confidence interval, 0.4%-0.8%; n=27) of all patients; and probable Fabry disease in additional 18 patients. Males dominated the study population (2962/59%) whereas females outnumbered men (65.3%) among the youngest patients (18-24 years). About 80.5% of the patients had a first stroke. Silent infarcts on magnetic resonance imaging were seen in 20% of patients with a first-ever stroke, and in 11.4% of patients with transient ischemic attack and no history of a previous cerebrovascular event. The most common causes of ischemic stroke were large artery atherosclerosis (18.6%) and dissection (9.9%). CONCLUSIONS: Definite Fabry disease occurs in 0.5% and probable Fabry disease in further 0.4% of young stroke patients. Silent infarcts, white matter intensities, and classical risk factors were highly prevalent, emphasizing the need for new early preventive strategies. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov.Unique identifier: NCT00414583.