Cerebral White Matter Lesions Research Articles

Cerebral white matter lesions and silent cerebral infarcts in postmenopausal women with polycystic ovary syndrome

Objectives: The association between polycystic ovary syndrome (PCOS) and cardiovascular disease remains unclear. Our objective was to examine the relation of PCOS with cerebrovascular disease measured by brain magnetic resonance imaging (MRI) as white matter lesions (WMLs) and silent cerebral infarcts (SCIs).Methods: Seventy postmenopausal women with PCOS and 140 controls participated in the case–control, cross-sectional study. Clinical, anthropometric, hormonal and metabolic parameters were measured. WMLs and SCIs were evaluated by brain MRI.Results: Compared with controls, postmenopausal women with PCOS had higher mean body mass index, larger waist hip ratio, higher level of low-density lipoprotein cholesterol, free androgen index and lower sex hormone-binding globulin level. The PCOS group had a significantly higher prevalence of WMLs (40% versus 22%, p = 0.009), and SCIs (17% versus 7%, p = 0.032) compared to the control group.Conclusions: Postmenopausal women with PCOS are associated with WMLs and SCIs.

White Matter Lesions, Carotid and Coronary Atherosclerosis in Late-Onset Depression and Healthy Controls

Cerebral white matter lesions (WMLs) are more common in individuals with late-onset or late-life depression. It has been proposed that carotid atherosclerosis may predispose to WMLs by inducing cerebral hypoperfusion. This hemodynamic effect of carotid atherosclerosis could be important for the formation of WMLs in depression. The case-control study included 29 patients with late-onset major depressive disorder and 27 controls matched for sex, age, and tobacco use. WML volume, carotid intima-media thickness, and coronary plaque volume were assessed using magnetic resonance imaging, ultrasound scan, and coronary computed tomography (CT) angiography, respectively. The mean age for the total sample was 59.7 ± 4.7 years. There was no difference in carotid intima-media thickness between patients and controls (p = 0.164), whereas a higher WML volume in the patients was found (p = 0.051). In both patients and controls, WML volume was associated with carotid but not with coronary atherosclerosis. In adjusted multiple linear regression, a 0.1mm increase in averaged carotid intima-media thickness was associated with a 52% (95% CI: 8.4-112, p = 0.032) increase in WML volume. The association between carotid intima-media thickness and WML volume was, however, similar in patients and controls. In older persons aged between 50 and 70 years, WMLs do not seem to be a part of generalized atherosclerotic disease, but seem to be dependent on atherosclerosis in the carotid arteries. Carotid atherosclerosis, however, could not explain the higher WML load observed in the depressed patients, and thus, studies are needed to establish the mechanisms linking depression and WMLs.

Abstract WP419: Predictors of Post-Discharge Physical Activity in Patients With Mild Ischemic Stroke

Introduction: Low daily physical activity (PA) is a risk for stroke recurrence. However, the predictors of PA have not been well investigated in mild ischemic stroke (MIS). This study aimed to identify the predictors of PA after discharge in MIS. Methods: We performed a single center registry, prospective observational study. Acute MIS with modified Rankin Scale (mRS) of 0-2 were consecutively enrolled. Baseline examination during hospitalization consisted of age, gender, National Institute of Health Stroke Scale, mRS, Mini-Mental State Examination, stroke subtype, cerebral white matter lesions, body mass index, blood pressure, ankle brachial index, blood laboratory tests, metabolic syndrome, handgrip strength, knee extensor isometric muscle strength (KEIMS), 10m maximum walking time, decisional balance for exercise, self-efficacy for walking (SE-W), social support for exercise (SSE), anxiety and depression. PA was measured at 6-months post-discharge by electronic accelerometer. The mean daily step counts and time of moderate to vigorous-intensity (≥3 Metabolic Equivalents) PA (MVPA) were used as an index of PA (total counts over 7 days/7). For multiple logistic regression analysis, step counts and MVPA were categorized into two groups divided by each median value. The baseline variables which had P <0.10 in the univariate analyses of step counts or MVPA were entered into the multiple logistic regression analyses with adjustments of age and gender. Results: 163 MIS (115 male, 69.5±10.1 years) were successfully followed for 6-months post-discharge. After multivariate analyses, KEIMS (increment of 0.1 Nm/kg: OR=0.829, 95%CI=0.717-0.959, p=0.011), SE-W (increment of 1 point: OR=0.917, 95%CI=0.850-0.989, p=0.025) and SSE (increment of 1 point: OR=0.882, 95%CI=0.789-0.987, p=0.029) for step counts, and SE-W (increment of 1 point: OR=0.930, 95%CI=0.867-0.999, p=0.047) for MVPA were selected as independent predictors. Conclusions: The findings of the present study suggest that an appropriate target group of low-PA MIS can be identified by simple measurements/questionnaires during hospitalization.

Association between serum uric acid levels and cerebral white matter lesions in Chinese individuals

Purpose/aim of the study: We aimed to evaluate the association between serum uric acid (SUA) levels and cerebral white matter lesions (WMLs) in Chinese individuals. Material and methods: We prospectively identified patients aged 50 years and older in neurology department from July 2014 to March 2015. Both periventricular WMLs (P-WMLs) and deep WMLs (D-WMLs) were identified on magnetic resonance imanging (MRI) scans and the severity was graded using the Fazekas method. Multivariate logistic regression analyses were performed to examine the association between SUA and WMLs. Results: A total of 480 eligible participants were enrolled in this study. SUA level in severe group was much higher than that in mild group (for P-WMLs: 320.21 ± 79.97 vs. 286.29 ± 70.18, p = 0.000; for D-WMLs: 314.71 ± 74.74 vs. 290.07 ± 74.04, p = 0.031). Subgroup analyses showed that higher SUA level was associated with higher severity of P-WMLs in women, but not in male patients. Multivariate logistic regression analyses showed that SUA was still associated with increased risk of higher severity of P-WMLs (OR = 1.003, 95% = 1.000–1.006), but not D-WMLs. Conclusion: Elevated SUA level was independently associated with greater odds of higher severity of P-WMLs, particularly in women.

Acute Postviral Encephalopathy: Pathologic and Radiologic Correlation in an Atypical Case.

The authors report a case of fatal acute encephalopathy following influenza infection, with slightly atypical pathological and imaging findings. A healthy 8-year-old boy with probable recent influenza A/B infection admitted for refractory seizures was placed on phenobarbital coma and later developed hemodynamic instability. Magnetic resonance imaging revealed bilateral cerebral and cerebellar white matter lesions and microhemorrhages. Following his demise, the autopsy revealed a large area of necrosis in the right centrum semiovale with similar lesions in the temporal and cerebellar regions. Microscopically, there was extensive coagulative necrosis, compatible with necrotizing white matter encephalopathy, and neuronal loss suggesting superimposed hypoxic–ischemia. The acute progressive neurologic deterioration was partly reminiscent on acute necrotizing encephalopathy, a condition recently associated with influenza A. In acute necrotizing encephalopathy, typical brain findings are characterized by bilateral thalamic necrosis/petechiae with variable white matter edema. The somewhat atypical findings in our case can relate to superadded cardiovascular collapse and hypoxic–ischemic effects.

高齢者の平衡障害

The elderly with dizziness and disequilibrium have a higher risk of falls in comparison with the elderly without dizziness or disequilibrium. We should not, therefore, overlook the complaint of dizziness and disequilibrium in the elderly as aging effects. Also, disequilibrium and dizziness in the elderly are often intractable. It may be due to some factors, which are an aging-related functional decline of the sensory and motor organs, deterioration of the postural control system through the central nervous system, and anxiety and depression due to aging: these factors result in the increased morbidity of orthostatic hypotension (OH) with age and, polypharmacy by five or more medications. The score of the functional items on the Dizziness Handicap Inventory (DHI) increased in the late elderly aged more than 80 years old in our department, resulting in a decreased level of activities of daily living, the so-called “frailty”. Those elderly patients with OH showed more severe asymptomatic infarction of cerebral white matter lesions (WMLs) on MRI and most of them have been treated by five or more medications for a variety of diseases. The degree of the WNLs in the elderly patients with OH was correlated with the variance of the subjective visual vertical, which was associated with the spatial cognitional function. If the elderly patients with disequilibrium are frail, or in the prefrail stage, early intervention with vestibular exercise should be considered. When elderly patients meet the criteria for OH in the Schellong test, we should check their polypharmacy and should firstly treat them with non-pharmacologic interventions for the OH. Also, psychologic disorders, such as depression due to aging, often make the disequilibrium symptoms intractable or severe. We should initiate cooperation with other physicians, psychologists, and urologists for the treatment of the elderly with intractable disequilibrium. In conclusion, a holistic treatment approach is necessary for the elderly with intractable disequilibrium.

Cerebral autoregulation and white matter lesions in Parkinson's disease and multiple system atrophy

Cerebral autoregulation is a complex homeostatic process which ensures constant brain blood supply, despite continuous blood pressure fluctuations. Recent evidence suggests that in Parkinson's disease (PD) and multiple system atrophy (MSA) this process is maintained in a broadened range of blood pressure values, consistent with an adaptive mechanism to increase tolerance to orthostatic hypotension. In PD and MSA orthostatic hypotension may be accompanied by supine hypertension which has been recently linked with cerebral white matter lesions in these conditions. We hypothesize that cerebral autoregulation adaptation to chronic orthostatic hypotension may be directly related with an increase susceptibility to hypertensive peaks.Evaluation of cerebral autoregulatory behavior may thus represent a novel approach to simultaneously target orthostatic symptoms and silent end-organ damage in alpha-synucleinopathies, with a beneficial impact on cerebrovascular and cognitive outcome.

Vascular Cognitive Impairment

The term vascular cognitive impairment (VCI) has been proposed to encompass all people with cognitive impairment of cerebrovascular origin. VCI is not a single condition, but has several clinical presentations, etiologies, and treatment. VCI forms a spectrum that includes vascular dementia, mixed Alzheimer's disease with a vascular component, and VCI that does not meet dementia criteria. Multiple pathophysiological mechanisms contribute to VCI, accounting for its heterogeneity. Although main changes in the brain in VCI include cerebral infarcts, vascular cognitive impairment is thought to be due to factors beyond acute infarcts. Cerebral white matter lesions and silent brain infarcts are considered to be risk factors for VCI. The prevalence of VCI is high and this entity is poised to become the silent epidemic of the 21st century. Cognitive impairment due to cerebrovascular disease can to some extent be improved, and VCI prevented, if vascular risk factors are brought under control and strokes do not recur. Therefore, strategies that focus on the prevention and treatment of the cognitive impairment associated with cerebrovascular disease are high priority healthcare objectives.

Severe cerebral white matter lesions in ischemic stroke patients are associated with less time spent at home and early institutionalization.

Cerebral white matter lesions are one imaging surrogate for cerebral small vessel disease. These white matter lesions are associated with increased morbidity and mortality in both the general population and ischemic stroke patients. To investigate whether severe white matter lesions in a cohort of ischemic stroke patients are associated with fewer days spent at home and earlier permanent institutionalization. We included 391 consecutive patients aged 55-85 years with ischemic stroke admitted to the Helsinki University Central Hospital (the Stroke Aging Memory cohort) with a 21-year follow-up. Hospitalization and nursing home admissions were reviewed from national registers.white matter lesions were rated using magnetic resonance imaging performed three-months poststroke, dichotomized as none-to-moderate and severe. Kaplan-Meier plots log-rank and binary logistic regression (odds ratio) and Cox multivariable proportional hazards model were used to study the association of white matter lesions with days spent at home and the time of permanent institutionalization. Hazards and odds ratio with their 95% confidence intervals are reported. Severe white matter lesions were associated with fewer days spent at home, and more frequent, and earlier permanent institutionalization (1487 vs. 2354 days; log-rank P < 0·001).After adjusting for significant covariates from univariable analyses, severe white matter lesions were associated with fewer days spent at home (odds ratio 1·62; confidence interval 1·16-2·25), permanent institutionalization within five-years (odds ratio 2·29; confidence interval 1·23-4·29), and increased hazards ratio of permanent institutionalization during 21 years of follow-up (1·64; confidence interval 1·119-2·26). After ischemic stroke, patients with severe white matter lesions spend fewer days at home and become permanently institutionalized earlier, especially within the first five-years.

Cerebral white matter lesions and microcirculation retinal in stroke lacunar

Background: The blood vessels in the retina are available for viewing in a noninvasive way and have similar anatomical, physiological as features small vessel brain. Also the white matter lesions (WMLs) brain are most frequently associated with lacunar stroke Objective: To determine the relationship between cerebral white matter lesions and retinal microvascular alteration in lacunar stroke. Material and methods: Cross-sectional study, patients with acute stroke was evaluated. Arteriovenous crossings, focal or diffuse arteriolar narrowing, retinal hemorrhages, cotton wool spots, alteration in vascular path, microaneurysms, the presence of retinal microvascular abnormalities was assessed. The WMLs were evaluated with a ranking of 1 to 9. Lacunar Stroke was classified by the score of TOAST. Results: A total of 67 patients were evaluated, classified as lacunar stroke 23.88% (n:16), the average age was 70.06 years, 50% were men, the main risk factors hypertension 68.75%, hypercholesterolemia 50%, diabetes 31.25%. In reference to the degree of WMLs grade 4-9 was superior to no lacunar stroke with 68.75% vs. 56.86%, the presence of retinopathy was also higher in lacunar stroke with 68.75% vs. 52.94%, but we found the presence of retinopathy in patients without diabetes and hypertension. Conclusion: WMLs and altering of retinal microcirculation are more prevalence in patients with lacunar stroke. Likewise, the retinopathy may be present in these patients despite not having recognized cardiovascular risk factors.

Cortical tau load is associated with white matter hyperintensities.

IntroductionCerebral white matter lesions (WML), visualized as white matter hyperintensities (WMH) on T2-weighted MRI, encompass structural damage and loss of integrity of the cerebral white matter (WM) and are commonly assumed to be associated with small vessel disease (SVD). However, it has been suggested that WM damage may also be the result of degenerative axonal loss that is secondary to cortical Alzheimer’s disease (AD) pathologies i.e., hyperphosphorylated tau (HPτ) and amyloid-beta (Aβ). Here we investigate the influence of HPτ, Aβ and SVD on WMH severity.Results36 human post-mortem right fixed cerebral hemispheres (mean age 84.4 ± 7.7 years; male: 16, female: 20) containing varying amounts of AD-pathology (AD: 23, controls: 13) underwent T2- weighted MRI with WMH assessed according to the age related white matter change scale (ARWMC). After dissection, using tissue samples from the frontal, temporal, parietal and occipital regions from the right hemisphere, we quantitatively assessed cortical HPτ and Aβ pathology burden by measuring the percentage area covered by AT8 immunoreactivity (HPτ-IR) and 4G8 immunoreactivity (Aβ-IR), and assessed the severity of WM SVD by calculating the sclerotic index (SI) of WM arteries/arterioles. HPτ-IR, Aβ-IR, and SI were compared with ARWMC scores. HPτ-IR, Aβ-IR and WM ARWMC scores were all significantly higher in AD cases compared to controls, while SI values were similar between groups. ARWMC scores correlated with HPτ-IR, Aβ-IR and SI in various regions, however, linear regression revealed that only HPτ-IR was a significant independent predictor of ARWMC scores.ConclusionsHere we have shown that increasing cortical HPτ burden independently predicted the severity of WMH indicating its potentially important role in the pathogenesis of WM damage. Moreover, our findings suggest that in AD patients the presence of WMH may indicate cortical AD-associated pathology rather than SVD. Further studies are warranted to elucidate the pathological processes that lead to WM damage and to clarify if WMH may serve as a general biomarker for cortical AD-associated pathology.

Influence of cerebral white matter lesions on the activities of daily living of older patients with mild stroke.

Neurological symptom severity is a prognostic factor for post-stroke activities of daily living (ADL). Recently, it has been reported that white matter lesions indicate poor functional prognosis in patients with stroke. The present study investigated the influence of white matter lesions on the ADL of older patients with stroke who have mild neurological symptoms. We investigated ADL at discharge in 44 patients with stroke (men, n = 27; women, n = 17; mean age 78 years [range 71-85 years]) aged ≥65 years with National Institutes of Health Stroke Scale scores of ≤5 (cerebral infarction, n = 37; cerebral hemorrhage, n = 7). We used single correlation analysis and multiple regression analysis to investigate factors that correlated with ADL at discharge. ADL at discharge was also evaluated on the basis of white matter lesion severity (Fazekas classification, grades 0-3). Single correlation analysis showed that age (r = -0.36, P = 0.016), male sex (r = 0.362, P = 0.016), neurological symptom severity (r = -0.361, P = 0.016), ADL on starting rehabilitation (r = 0.685, P < 0.001) and white matter lesion severity (r = -0.361, P = 0.016) significantly correlated with ADL at discharge. Multiple regression analysis showed that ADL on starting rehabilitation (β = 0.519, t = 4.723, P < 0.001) and white matter lesion severity (β = -0.309, t = -3.057, P < 0.01) were statistically significant prognostic factors for ADL at discharge. ADL at discharge score was significantly lower in the group with high white matter lesion severity (Fazekas, grade 2) than in the other two groups (Fazekas, grade 0, P < 0.01; Fazekas, grade 1, P < 0.05). Severe white matter lesions are a prognostic factor for poor ADL at discharge in older patients with stroke who have mild neurological symptoms. Geriatr Gerontol Int 2016; 16: 942-947.

Asymptomatic Cerebral White Matter Lesions Predict Future Cognitive Decline in Japanese Elderly.

Asymptomatic Cerebral White Matter Lesions Predict Future Cognitive Decline in Japanese Elderly.

CD62-mediated activation of platelets in cerebral white matter lesions in patients with cognitive decline

BackgroundVascular dementia is related to intracranial arteriosclerosis associated with deep white matter lesions (DWMLs). DWMLs have been linked to thrombogenesis due to sustained platelet activation; therefore, an accurate hematological marker is needed. This study was done to evaluate the usefulness of a new method to examine the function of activated platelets in order to assess DWMLs associated with cognitive decline. MethodsA total of 143 individuals (70.4±6.1 years old) who underwent hospital-based health screening using head MRI were evaluated. DWLs were evaluated on T2-weighted and FLAIR images by semi-quantitatively grading them from Grade 0 (none) to Grade 3 (severe) using the Fazekas classification. Cognitive function was evaluated using the MMSE and the word fluency test. Platelet activation was assessed using fluorescence-labeled anti-human platelet monoclonal antibodies and semi-quantitatively determining PAC-1- and CD62P-positive rates by flow cytometry. ResultsSignificant increases in hypertension and CD62P levels were observed with increasing DWML grade (2.6% in Group 0, 3.1% in Group 1, 4.1% in Group 2, and 5.0% in Group 3). CD62P levels were defined as elevated when they were above the mean+2SD of the Grade 0 group, and the odds ratio of the Grade 2+3 group was 3.03. A significant negative correlation was observed between CD62P levels and word fluency tests or the MMSE score. ConclusionElevations in CD62P levels, which reflect platelet function activation, were associated with white matter lesions accompanied by a decline in cognitive function. CD62P levels may be useful as a sensitive clinical marker for the early detection of DWMLs with cognitive decline.

Cerebral White Matter Lesions and Affective Episodes Correlate in Male Individuals with Bipolar Disorder.

BackgroundCerebral white matter lesions (WML) have been found in normal aging, vascular disease and several neuropsychiatric conditions. Correlations of WML with clinical parameters in BD have been described, but not with the number of affective episodes, illness duration, age of onset and Body Mass Index in a well characterized group of euthymic bipolar adults. Herein, we aimed to evaluate the associations between bipolar course of illness parameters and WML measured with volumetric analysis.MethodsIn a cross-sectional study 100 euthymic individuals with BD as well as 54 healthy controls (HC) were enrolled to undergo brain magnetic resonance imaging using 3T including a FLAIR sequence for volumetric assessment of WML-load using FSL-software. Additionally, clinical characteristics and psychometric measures including Structured Clinical Interview according to DSM-IV, Hamilton-Depression, Young Mania Rating Scale and Beck’s Depression Inventory were evaluated.ResultsIndividuals with BD had significantly more (F = 3.968, p < .05) WML (Mdn = 3710mm3; IQR = 2961mm3) than HC (Mdn = 2185mm3; IQR = 1665mm3). BD men (Mdn = 4095mm3; IQR = 3295mm3) and BD women (Mdn = 3032mm3; IQR = 2816mm3) did not significantly differ as to the WML-load or the number and type of risk factors for WML. However, in men only, the number of manic/hypomanic episodes (r = 0.72; p < .001) as well as depressive episodes (r = 0.51; p < .001) correlated positively with WML-load.ConclusionsWML-load strongly correlated with the number of manic episodes in male BD patients, suggesting that men might be more vulnerable to mania in the context of cerebral white matter changes.

Contribution of Schwann Cells to Remyelination in a Naturally Occurring Canine Model of CNS Neuroinflammation.

Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide evidence for regeneration promoting cells recruitable for therapeutic purposes. There is evidence that neurotrophin receptor p75 (p75NTR)-expressing cells emerge in the lesioned CNS. However, the phenotype and identity of these cells, and signals triggering their in situ generation under normal conditions and certain pathological situations has remained enigmatic. In the present study, we used a spontaneous, idiopathic and inflammatory CNS condition in dogs with prominent lympho-histiocytic infiltration as a model to study the phenotype of Schwann cells and their relation to Schwann cell remyelination within the CNS. Furthermore, the phenotype of p75NTR-expressing cells within the injured CNS was compared to their counter-part in control sciatic nerve and after peripheral nerve injury. In addition, organotypic slice cultures were used to further elucidate the origin of p75NTR-positive cells. In cerebral and cerebellar white and grey matter lesions as well as in the brain stem, p75NTR-positive cells co-expressed the transcription factor Sox2, but not GAP-43, GFAP, Egr2/Krox20, periaxin and PDGFR-α. Interestingly, and contrary to the findings in control sciatic nerves, p75NTR-expressing cells only co-localized with Sox2 in degenerative neuropathy, thus suggesting that such cells might represent dedifferentiated Schwann cells both in the injured CNS and PNS. Moreover, effective Schwann cell remyelination represented by periaxin- and P0-positive mature myelinating Schwann cells, was strikingly associated with the presence of p75NTR/Sox2-expressing Schwann cells. Intriguingly, the emergence of dedifferentiated Schwann cells was not affected by astrocytes, and a macrophage-dominated inflammatory response provided an adequate environment for Schwann cells plasticity within the injured CNS. Furthermore, axonal damage was reduced in brain stem areas with p75NTR/Sox2-positive cells. This study provides novel insights into the involvement of Schwann cells in CNS remyelination under natural occurring CNS inflammation. Targeting p75NTR/Sox2-expressing Schwann cells to enhance their differentiation into competent remyelinating cells appears to be a promising therapeutic approach for inflammatory/demyelinating CNS diseases.

Study of proton magnetic resonance spectrum on cerebral white matter lesions in patients with Alzheimer's disease and vascular dementia

Objective To evaluate the value of proton magnetic resonance spectrum (1H-MRS) in the differential diagnosis of Alzheimer's disease (AD) and vascular dementia (VD) patients with white matter lesions(WMLs). Methods Multi voxel 1H-MRS were performed to 30 patients with AD, 30 patients with VD, and 30 normal control volunteers. The levels of the N-acetylaspartate (NAA), myo-inositol (mI), glutamate (Glu), and creatine (Cr) were measured in the white matter adjacent to the lateral ventricles. The ratios of NAA/Cr, mI/Cr and Glu/Cr were calculated and compared among the group. Comparisons of the 1H-MRS indexes among AD, VD and NC group were conducted by one-way ANOVA. Results NAA/Cr ratios of the region of interesting in AD (1.59±0.15)and VD(1.53±0.12) group were significantly decreased compared with NC (1.79±0.22)group (P 0.05), and Glu/Cr ratios in AD and VD groups were significantly different (P 0.05). Conclusion Multi-voxel 1H-MRS is an effective method in the differential diagnosis of dementia, and changes of the mI/Cr and Glu/Cr ratios of the white matter adjacent to the lateral ventricles may help to identify the AD and VD patients. Key words: Alzheimer disease; Vascular dementia; White matter lesions; Magnetic resonance spectroscopy

Renal dysfunction is associated with deep cerebral microbleeds but not white matter hyperintensities in patients with acute intracerebral hemorrhage.

Kidney disease is a risk factor for cerebral microangiopathy and spontaneous intracerebral hemorrhage (ICH). We aimed to determine the association of renal dysfunction (RD) with MRI correlates of different patterns of cerebral microangiopathies including cerebral microbleeds (CMB) and white matter lesions (WML) in patients with ICH. In a prospectively collected, single-center cohort of ICH patients, glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease equation. We classified the renal function in five categories: category 1 (eGFR ≥ 90 mL/min/1.73 m(2)), category 2 (eGFR 60-89), category 3 (eGFR 30-59), category 4 (eGFR 15-29), and category 5 (eGFR <15) and dichotomized at an eGFR of 60. Number, location, and extent of CMB and WML were measured on MRI. ICH and CMB locations were classified as lobar or deep. 97 ICH patients with MRI (mean age 65.9 ± 13.9 years) were included. Intracerebral hemorrhage was lobar in 52.6 %. Median eGFR was 85.8 mL/min/1.73 m(2) (IQR 34.3). Renal dysfunction was present in 12.4 % of the patients. At least one CMB was present in 57.7 % of patients, WML were even more frequent (97.7 %). Age and impaired renal function were factors independently associated with the presence of CMB. The presence of CMB was independently associated with the number and extent of WML. RD is a frequent comorbidity in patients with ICH. Associations of RD with hypertension and with CMB in deep location suggest a predominant impact of RD on deep rather than on lobar microangiopathy.

P58. Primary hyperparathyroidism mimicking multiple sclerosis? A case report

A 46-year-old Caucasian female patient was admitted to our hospital with suspected relapse of multiple sclerosis (MS). Diagnosis was made 2 years ago by unspecific white matter lesions, oligoclonal bands in the cerebrospinal fluid and a first episode with a slight hemiparesis left, which remitted in a few weeks. A treatment with interferon beta 1a was introduced. Since that there were no relapses noted. Since a few days she suffered fluctuating muscle weakness, dysarthria, fatigue and mood changes. Clinical examination revealed brisk tendon reflexes, no paresis but severe hypalgesia of both arms. After a 20 m walk she was not able to walk fast and she reported a feeling like a lead weight in her legs. A prednisolone pulse was given for 5 days. Brain MRI showed a new small single contrast enhancing lesion parieto-occipital. Patient shows a slight improvement, mainly concerning their fatigue. Few days after completed prednisolone treatment, the fluctuating muscle weakness progressed. She reported cognitive impairment and paroxysmal panic attacks. Repeated MRI (3 Tesla) oft he brain and cervical spine showed no new lesions. Prednisolone pulse was initiated repeatedly. Laboratory investigations revealed slight elevation of serum calcium. Therefore parathyroid hormone level was evaluated and showed 3-fold elevation. Further evaluations by endocrinologists showed a large adenoma oft he right caudal parathyroid gland. Surgery was planned. Retrospectively serum calcium showed elevated values 4 years ago, when patient was first admitted to a neurology department because of cerebral MRI white matter lesions without clinical symptoms. This case raises the question wether primary hyparathyroidism is a MS mimic? A recent study showed an association between plasma parathyroid hormone and white matter lesions (Hagstroem et al., 2014). Non focal muscle weakness is sometimes reported in primary hyperparathyroidism (pHPT), but severe sensory symptoms are not reported to our knowledge. In a series of pHPT patients subclinical changes of sensory nerve conduction velocity has been showed (Diniz ET, 2013). In our patient sensory electroneurography was normal, but hypalgesia was consistent in the quantitative sensory testing (QST). Our report present further neurophysiologic tests and will discuss possible underlying mechanisms oft he clinical symptoms in detail.

White Matter Lesions Double the Risk of Post-Thrombolytic Intracerebral Hemorrhage

Cerebral white matter lesions (WMLs), a surrogate for small-vessel disease, are common in patients with stroke and may be related to an increased intracranial bleeding risk after intravenous thrombolysis in acute ischemic stroke. We aimed to investigate the risk of symptomatic intracerebral hemorrhage (sICH) in the presence of WMLs in a large cohort of ischemic stroke patients treated with intravenous thrombolysis. We included 2485 consecutive patients treated with intravenous thrombolysis at the Helsinki University Central Hospital. WMLs were scored according to 4 previously published computed tomography visual rating scales from all baseline head scans. A sICH was classified according to the European Cooperative Acute Stroke Study II criteria. The associations of sICH with nominal, ordinal, and continuous variables were analyzed in a univariate binary regression model and adjusted in multivariate binary regression models. In univariate and multivariate regression analyses, all 4 tested visual WML rating scales (as continuous variables or dichotomized at different cutoff points) were associated with increased risk of sICH. In binary analyses, WML doubled the bleeding risk: the odds ratios of all 4 visual rating scales ranged from 2.22 (95% confidence interval, 1.49-3.30) to 2.70 (1.87-3.90) in univariable and from 2.00 (1.26-3.16) to 2.62 (1.71-4.02) in multivariable analyses. The multivariable-adjusted odds ratio for the association of high load of WMLs with remote parenchymal hemorrhage was 4.11 (2.38-7.10). WMLs visible on computed tomography are associated with a more than doubled risk of sICH in patients treated with intravenous thrombolysis for acute ischemic stroke.