Thrombolysis and adjunct anticoagulation in patients with acute basilar artery occlusion.

BACKGROUND AND PURPOSE: Patients suffering from basilar artery occlusion (BAO) and treated with intravenous thrombolysis are, in some centers, started on adjunct anticoagulation in hyperacute settings. We aimed to assess the outcome of such patients and to compare low-molecular weight heparin (LMWH) and unfractionated heparin (UFH) in this context. METHODS: We examined 211 patients with angiography-proven BAO treated with intravenous thrombolysis and either adjunct UFH or LMWH. Main outcome variables were rate of symptomatic intracranial hemorrhage (sICH) according to European Cooperative Acute Stroke Study II criteria and modified Rankin Scale (mRS) at 3 months. RESULTS: The overall rate of sICH was 11.4% and driven by the UFH group (13.3%). None of the LMWH group developed sICH. Recanalization rate did not significantly differ between the LMWH and UFH groups. An additional propensity analysis was made to balance anticoagulation groups regarding baseline characteristics. Propensity analysis showed a significant difference in sICH rate (0.0% vs. 14.8%, P = 0.044) in favor of LMWH. Independent outcome (mRS score 0-2) was achieved in a total of 31.0% and in 44.8% and 29.1% in the LMWH and UFH group, respectively (P = 0.09). Propensity analysis showed a significant difference in the risk of ending up bedridden or dead (mRS score 5-6; 34.5% vs. 63.0%, P = 0.033) in favor of LMWH. CONCLUSIONS: Our study showed a lower rate of sICH and a shift towards improved outcome in thrombolysed patients with BAO treated with LMWH as compared with UFH.

Media multitasking is associated with distractibility and increased prefrontal activity in adolescents and young adults.

The current generation of young people indulges in more media multitasking behavior (e.g., instant messaging while watching videos) in their everyday lives than older generations. Concerns have been raised about how this might affect their attentional functioning, as previous studies have indicated that extensive media multitasking in everyday life may be associated with decreased attentional control. In the current study, 149 adolescents and young adults (aged 13-24years) performed speech-listening and reading tasks that required maintaining attention in the presence of distractor stimuli in the other modality or dividing attention between two concurrent tasks. Brain activity during task performance was measured using functional magnetic resonance imaging (fMRI). We studied the relationship between self-reported daily media multitasking (MMT), task performance and brain activity during task performance. The results showed that in the presence of distractor stimuli, a higher MMT score was associated with worse performance and increased brain activity in right prefrontal regions. The level of performance during divided attention did not depend on MMT. This suggests that daily media multitasking is associated with behavioral distractibility and increased recruitment of brain areas involved in attentional and inhibitory control, and that media multitasking in everyday life does not translate to performance benefits in multitasking in laboratory settings.

Symptomatic intracranial haemorrhage after thrombolysis with adjuvant anticoagulation in basilar artery occlusion.

BACKGROUND AND PURPOSE: Our aim was to determine factors associated with symptomatic intracranial haemorrhage (sICH) in basilar artery occlusion patients treated with intravenous thrombolysis (IVT) and adjuvant anticoagulant therapy. METHODS: A registry of 176 consecutive patients with angiography-proven basilar artery occlusion who received IVT with alteplase and heparin between 1995 to 2013 was assessed. Post-treatment sICH was evaluated with the European Cooperative Acute Stroke Study II criteria. Unfavourable outcome was defined as a modified Rankin Scale score of 3-6 at 3 months. RESULTS: Twenty-four patients developed sICH (13.6%, sICH+), all of whom had unfavourable outcome and only two (8.3%) sICH+ patients survived. On admission, sICH+ patients more frequently had extensive ischaemic changes defined as posterior circulation Acute Stroke Prognosis Early CT Score (PC-ASPECTS) < 8 (50% vs. 27% in sICH-, P = 0.031) and lower platelet counts (183 vs. 218 E9/l; P = 0.011). They also had higher systolic blood pressure (SBP) (median 160 vs. 147 mmHg, P = 0.034) immediately after IVT. In multivariable regression analysis, lower platelet values [odds ratio (OR) 0.99, 95% confidence interval (CI) 0.97-0.996; P = 0.006], PC-ASPECTS < 8 on admission (OR 3.6, 95% CI 1.3-10.3; P = 0.017) and higher SBP after treatment (OR 1.03, 95% CI 1.01-1.05; P = 0.017) were independently associated with sICH. Ninety per cent of the sICHs occurred within 48 h from IVT/anticoagulation treatment. No differences in activated partial thrompoplastin times prior to or after the treatment were observed between sICH+ and sICH- patients. CONCLUSIONS: The risk of sICH was largely determined by extension of ischaemic changes on admission computed tomography. Clinically relevantly, also higher post-thrombolytic SBP as described earlier and lower perithrombolytic platelet counts do increase the risk, a finding requiring confirmation in other patient series.

Intravenous thrombolysis in ischemic stroke patients with isolated homonymous hemianopia.

BACKGROUND: Patients with posterior ischemic stroke were usually excluded from thrombolytic treatment in clinical trials and clinical practice, and little is known about effectiveness of thrombolysis treatment in such patients who may end up with severe disability. AIMS OF THE STUDY: We aimed to describe the outcome of acute ischemic stroke patients presenting with isolated homonymous hemianopia and treated with intravenous thrombolysis. METHODS: A case report of three patients presenting with homonymous hemianopia owing to posterior circulation stroke treated with intravenous thrombolysis at the Helsinki University Central Hospital. Main outcome measures were modified Rankin Scale and neuropsychological examination at 3 months after thrombolysis. We further evaluated Goldmann visual field examination at 6 months. RESULTS: No acute findings appeared on admission non-contrast head-computed tomography scan. All patients had a perfusion deficit on admission-computed tomography perfusion imaging. All patients scored 0 on 3-month modified Rankin Scale, and their neuropsychological evaluation was normal. Goldmann examination revealed no visual field deficit in both female patients, and a modest visual field defect was detected in the male patient. CONCLUSIONS: Our experience encourages application of intravenous thrombolytic treatment (especially when supported with multimodality neuroimaging) in patients with homonymous hemianopia, for which rehabilitation options are limited.

HHV-6 infection in multiple sclerosis. A clinical and laboratory analysis.

BACKGROUND AND PURPOSE: To elucidate the role of human herpesvirus-6 (HHV-6) in the development of multiple sclerosis (MS). PATIENTS AND METHODS: Nine patients with MS and with acute or chronic HHV-6 infection were evaluated. RESULTS: Intrathecal antibody production to HHV-6 and oligoclonal IgG bands in the cerebrospinal fluid (CSF) was observed in two patients with a clinically definite MS and chronic HHV-6 infection (based on the presence of HHV-6 specific antibodies in the CSF). A temporal association between the symptoms of clinically possible MS and acute primary HHV-6A infection (based on avidity of HHV-6 specific antibodies) was observed in two patients. CONCLUSIONS: Human herpesvirus-6 infection may be an associated agent in some MS cases. Viral studies are needed to identify a possible viral etiology and give specific therapy.

Viral meningoencephalitis: a review of diagnostic methods and guidelines for management.

BACKGROUND: Viral encephalitis is a medical emergency. The prognosis depends mainly on the pathogen and host immunologic state. Correct immediate diagnosis and introduction of symptomatic and specific therapy has a dramatic influence upon survival and reduces the extent of permanent brain injury. METHODS: We searched the literature from 1966 to 2009. Recommendations were reached by consensus. Where there was lack of evidence but consensus was clear, we have stated our opinion as good practice points. RECOMMENDATIONS: Diagnosis should be based on medical history and examination followed by CSF analysis for protein and glucose levels, cellular analysis, and identification of the pathogen by polymerase chain reaction amplification (recommendation level A) and serology (level B). Neuroimaging, preferably by MRI, is essential (level B). Lumbar puncture can follow neuroimaging when immediately available, but if this cannot be performed immediately, LP should be delayed only under unusual circumstances. Brain biopsy should be reserved only for unusual and diagnostically difficult cases. Patients must be hospitalized with easy access to intensive care units. Specific, evidence-based, antiviral therapy, acyclovir, is available for herpes encephalitis (level A) and may also be effective for varicella-zoster virus encephalitis. Ganciclovir and foscarnet can be given to treat cytomegalovirus encephalitis, and pleconaril for enterovirus encephalitis (IV class evidence). Corticosteroids as an adjunct treatment for acute viral encephalitis are not generally considered to be effective, and their use is controversial, but this important issue is currently being evaluated in a large clinical trial. Surgical decompression is indicated for impending uncal herniation or increased intracranial pressure refractory to medical management.

Adult cervicocerebral artery dissection: a single-center study of 301 Finnish patients.

BACKGROUND AND PURPOSE: There are only few small studies assessing potential risk factors, comorbidity, and prognostic factors in adult spontaneous cervicocerebral artery dissection (CAD). METHODS: We conducted a retrospective, hospital-based analysis on the prognostic factors and association of CAD with vascular risk factors in 301 consecutive Finnish patients, diagnosed from 1994 to 2007. RESULTS: Two thirds of the patients were men (68%). Women were younger than men. Migraine (36% of all patients), especially with visual aura (63% of all migraineurs), and smoking were more common in patients with CAD compared with the general Finnish population. At 3 months, 247 (83%) patients reached a favorable outcome. Occlusion of the dissected artery, internal carotid artery dissection (ICAD), and recent infection in infarction patients were associated with a poorer outcome. ICAD patients had less often brain infarction, but the strokes they had were more severe. Seven (2.3%) patients died during the follow-up (mean 4.0 years, 1186 patient years). Six (2%) patients had verified CAD recurrence. CONCLUSIONS: This study provides evidence for the association of CAD with male sex, and possible association with smoking and migraine. Occlusion of the dissected artery, ICAD, and infection appear to be associated with poorer outcome.

Magnetic resonance imaging of the brain used to detect early post-partum activation of multiple sclerosis.

Post-partum relapses are a frequent phenomenon in multiple sclerosis (MS). The purpose of this study was to evaluate the timing and extent of new or growing T2-lesions after delivery in a cohort of Finnish MS patients. In addition to serial magnetic resonance imaging (MRI), the patients were followed up clinically with determination of relapse rate and expanded disability status scale. The annualized relapse rate was decreased during the last trimester of pregnancy [mean 0.14, standard deviation (SD) 0.14] when compared with the time before pregnancy (mean 0.64, SD 0.14; P = 0.04) and to time post-partum (mean 1.50, SD 0.45; P = 0.0002). New or enlarging lesions were detected in the post-partum images in 14 of 28 patients. Gadolinium-enhancing lesions in post-partum MRI were present in eight of 13 patients. There was a significant increase in the number of T2-lesions (P = 0.0009), in the total volume of MS-lesions measured from fluid-attenuated inversion recovery images (P = 0.0126) and in the number of diffusion weighted imaging hyperintense lesions (P = 0.0098) in the post-partum images. The clinical results support the earlier findings of decreased disease activity in late pregnancy. The clinical and MRI findings indicate that post-partum activation is an early and common phenomenon amongst mothers with MS.

Magnetic resonance imaging correlates of depression after ischemic stroke.

BACKGROUND: Depression affects up to 40% of patients with ischemic stroke. The relationship between site and size of brain infarcts and poststroke depression is still not well characterized. Further possible contribution and interaction of white matter lesions and brain atrophy has not been studied previously. We conducted a magnetic resonance image-based study of the radiologic correlates of depression in a large, well-defined series of patients with ischemic stroke. METHODS: Modified DSM-III-R and DSM-IV criteria were used to diagnose depressive disorders during a comprehensive psychiatric evaluation in 275 of 486 consecutive patients aged 55 to 85 years 3 to 4 months after ischemic stroke. A standardized magnetic resonance imaging protocol detailed side, site, type, and extent of brain infarcts and extent of white matter lesions and brain atrophy. RESULTS: Depressive disorders were diagnosed in 109 patients (40%). Patients with depression had a higher number and larger volume of infarcts affecting the prefrontosubcortical circuits, especially the caudate, pallidum, and genu of internal capsule, with left-sided predominance. Extent of white matter lesions and atrophy did not differ in patients with and without depression. Independent correlates of poststroke depression in a logistic regression model were mean frequency of infarcts in the genu of internal capsule on the left side (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.0-10.1), mean frequency of infarcts in the pallidum of any side (OR, 1.6; 95% CI, 1.1-2.3), and mean volume of infarcts in the right occipital lobe (OR, 0.98; 95% CI, 0.96-0.99). CONCLUSION: Lesions affecting the prefrontosubcortical circuits, especially on the left side, are correlates of depression after ischemic stroke.

Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls.

BACKGROUND: Cortical gray matter volume reductions and cerebrospinal fluid (CSF) volume increases are robust correlates of schizophrenia, but their sources have not been established conclusively. METHODS: Structured diagnostic interviews and magnetic resonance imaging scans of the brain were obtained on 75 psychotic probands (63 with schizophrenia and 12 with schizoaffective disorder), ascertained so as to be representative of all such probands in a Helsinki, Finland, birth cohort; 60 of their nonpsychotic full siblings; and 56 demographically similar control subjects without a personal or family history of treated psychiatric morbidity. RESULTS: Patients with schizophrenia and their siblings exhibited significant reductions in cortical gray matter volume and significant increases in sulcal CSF volume compared with controls. The patients, but not their siblings, also exhibited significant reductions in white matter volume and significant increases in ventricular CSF volume. Regional effects were most robust when component volumes were expressed as percentages of overall regional volumes; in this case, for patient and sibling groups, gray matter volume reductions and sulcal CSF volume increases were significantly more pronounced in the frontal and temporal lobes than in the remainder of the brain. None of the group differences varied significantly by sex or hemisphere. CONCLUSIONS: Structural alterations of the cerebral cortex, particularly in the frontal and temporal lobes, are present in patients with schizophrenia and in some of their siblings without schizophrenia; such changes are thus likely to reflect genetic (or shared environmental) effects. Ventricular enlargement is unique to the clinical phenotype and is thus likely to be affected primarily by nonshared causative factors.

Three-decade neurological and neurocognitive follow-up of HIV-1-infected patients on best-available antiretroviral therapy in Finland.

OBJECTIVES: Is it possible to live without neurocognitive or neurological symptoms after being infected with HIV for a very long time? These study patients with decades-long HIV infection in Finland were observed in this follow-up study during three time periods: 1986-1990, in 1997 and in 2013. SETTING: Patients from greater Helsinki area were selected from outpatient's unit of infectious diseases. PARTICIPANTS: The study included 80 HIV patients. Patients with heavy alcohol consumption, central nervous system disorder or psychiatric disease were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The patients underwent neurological and neuropsychological examinations, MRI of the brain and laboratory tests, including blood CD4 cells and plasma HIV-1 RNA. Neuropsychological examination included several measures: subtests of Wechsler Adult Intelligence Scale, Wechsler Memory Scale-Revised, list learning, Stroop and Trail-Making-B test. The Beck Depression Inventory and Fatigue Severity Scale were also carried out. The obtained data from the three time periods were compared with each other. RESULTS: Owing to high mortality among the original 80 patients, eventually, 17 participated in all three examinations performed between 1986 and 2013. The time from the HIV diagnosis was 27 (23-30) years. Blood CD4 cells at the diagnosis were 610 (29-870) cells/mm(3), and the nadir CD4 168 (4-408) cells/mm(3). The time on combined antiretroviral treatment was 13 (5-17) years. 9 patients suffered from fatigue, 5 had polyneuropathy and 3 had lacunar cerebral infarcts. There was a subtle increase of brain atrophy in 2 patients. Mild depressive symptoms were common. The neuropsychological follow-up showed typical age-related cognitive changes. No HIV-associated dementia features were detected. CONCLUSIONS: Polyneuropathy, fatigue and mild depression were common, but more severe neurological abnormalities were absent. These long-term surviving HIV-seropositive patients, while on best-available treatment, showed no evidence of HIV-associated neurocognitive disorder in neuropsychological and neuroradiological evaluations.

Amnesia in acute herpetic and nonherpetic encephalitis.

OBJECTIVES: To evaluate how often global amnesia syndrome is encountered as a sequel of herpes simplex virus type 1 encephalitis (HSVE) and in other types of acute encephalitides, and to evaluate whether there are qualitative differences in amnesia caused by different encephalitides. SUBJECTS: Forty-five consecutive patients with encephalitis (mean age, 40.8 years) studied prospectively within a 5-year period, 8 of whom had HSVE. There were 24 normal controls. MEASURES: Neuropsychological assessment and memory evaluation after the acute stage of encephalitis, as well as at follow-up after 27.7 +/- 18.6 months. RESULTS: Three patients (6%), including 1 with HSVE, had persistent anterc grade and retrograde memory defects, typical features of global amnesia. Twelve patients had anterograde amnesia in the first assessment. No statistically significant differences in the memory measures were found between the HSVE (n = 4) and the non-HSVE (n = 8) groups. Some patients had predominantly semantic difficulty, some had a "frontal-type" memory disorder, and in some patients rapid forgetting was the prominent feature. CONCLUSIONS: The frequency of amnesia can reliably be evaluated only in consecutive series of patients. Previous literature, mainly case reports, may give the impression that global amnesia is a common consequence of encephalitis. Our findings do not support that view. Furthermore, there are clear differences in the quality of the memory impairment between cases of acute encephalitides. Our findings suggest that amnesia as a consequence of encephalitis, even HSVE, should not be considered a uniform phenomenon.

How complex interactions of ischemic brain infarcts, white matter lesions, and atrophy relate to poststroke dementia.

BACKGROUND: Cerebrovascular disease is a major factor related to cognitive impairment. However, behavioral correlates of ischemic brain lesions are insufficiently characterized. OBJECTIVE: To examine magnetic resonance imaging correlates of dementia in a large, well-defined series of patients with ischemic stroke. METHODS: Detailed medical, neurological, and neuropsychological examinations were conducted 3 months after ischemic stroke for 337 of 486 consecutive patients aged 55 to 85 years. Infarcts (type, site, side, number, and volume), extent of white matter lesions (WMLs), and degree of atrophy were categorized according to magnetic resonance images of the head. The definition for dementia of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) was used. RESULTS: Dementia was diagnosed in 107 (31.8%) of the patients and stroke-related dementia in 87 (25.8%). Volumes, numbers, distinct sites of infarcts, extent of WMLs, and degree of atrophy were different for the demented and nondemented subjects. Particularly, volumes of infarcts in any (right- or left-sided) superior middle cerebral artery territory (27.3 vs 13.7 cm(3), P =. 002) and left thalamocortical connection (14.8 vs 4.0 cm(3), P =. 002) differentiated the 2 groups. Logistic regression analysis showed that the correlates of any dementia included the combination of infarct features (volume of infarcts in any superior middle cerebral artery: odds ratio [OR], 1.11; frequency of left-sided infarcts: OR, 1.21), extent of WMLs (OR, 1.3), medial temporal lobe atrophy (OR, 2.1), and host factors (education; OR, 0.91). In the patients with stroke-related dementia, the main correlate was volume of infarcts in the left anterior corona radiata (OR, 1.68). CONCLUSION: Correlates of poststroke dementia do not include merely 1 feature but a combination of infarct features, extent of WMLs, medial temporal lobe atrophy, and host features.

Unilateral hyperfusion in brain-perfusion SPECT predicts poor prognosis in acute encephalitis.

We studied 88 patients with acute encephalitis using hexamethylpropyleneamine oxime and single photon emission computed tomography (SPECT). All patients had been initially treated with intravenous acyclovir. The etiology could be disclosed in 37 patients (42%), which included 15 patients with herpes simplex encephalitis, 7 with varicella-zoster encephalitis, and 29 with other encephalitides (Mycoplasma, adenovirus, influenza, rotavirus, rubella, Epstein-Barr, arbovirus, syphilis, and tuberculosis). Unilateral hyperperfusion in SPECT was an independent predictor of poor prognosis, whereas neither clinical outcome variables, such as seizures, state of consciousness, and focal neurologic findings, nor CSF or EEG findings were not. Focal unilateral hyperperfusion is an indicator of severe inflammation of the brain tissue and predicts a poor outcome as assessed in terms of activities of daily living after recovery.

Presymptomatic DNA and MRI diagnosis of neurofibromatosis 2 with mild clinical course in an extended pedigree.

Neurofibromatosis 2 (NF2), a dominantly inherited disorder, typically manifests as bilateral vestibular schwannomas and predisposes to other nervous system tumors. In this study, we present a large pedigree with a benign course of NF2 (mild Gardner type) characterized by slowly growing vestibular schwannomas but few other manifestations. The family was thoroughly investigated with neurologic, ophthalmologic, and neuro-otologic methods including gadolinium-enhanced MRI of the head and spine and DNA linkage analysis. In the clinical analysis of 22 family members, MRI was superior to neuro-otologic methods in the detection of asymptomatic tumors. Based on the DNA linkage analyses we identified the NF2 mutation carriers with a high degree of certainty. These DNA markers (CRYB2, NEFH, D22S268, and D22S280) can also be used for presymptomatic diagnosis in other NF2 families. Early detection of NF2 gene mutation carriers has become possible using linkage analysis in familial NF2. MRI screening of carriers will reveal presymptomatic vestibular schwannomas (and other CNS tumors), making early intervention possible, but an efficient treatment strategy to prevent deafness has not yet been established.

CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts.

BACKGROUND: Nasu-Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is a genetically heterogeneous disease characterized by a combination of systemic bone cysts and dementia. OBJECTIVE: The authors present a neurologic, neuroradiologic, and neuropathologic analysis of a series of PLOSL patients in which the diagnosis has been confirmed by molecular genetic methods. METHODS: Clinical, neurophysiologic, and imaging follow-up data on eight patients as well as autopsy samples of three patients were analyzed in this study. All eight patients were homozygous for a loss-of-function mutation in the DAP12 gene. RESULTS: In most patients, the disease debuted with pain in ankles and wrists after strain during the third decade, followed by fractures caused by cystic lesions in the bones of the extremities. Frontal lobe syndrome and dementia began to develop by age 30, leading to death by age 40. Neuroimaging disclosed abnormally high and progressively increasing bicaudate ratios and calcifications in the basal ganglia as well as increased signal intensities of the white matter on T2-weighted MR images even before the appearance of clinical neurologic symptoms. Three patients who had undergone autopsies showed an advanced sclerosing leukoencephalopathy with frontal accentuation, widespread activation of microglia, and microvascular changes. CONCLUSIONS: Although PLOSL in most patients manifests by bone fractures, some patients do not show any osseous symptoms and signs before the onset of neurologic manifestations. Consequently, patients with frontal-type dementia of unknown origin should be investigated by x-ray of ankles and wrists. The current results suggest early basal ganglia involvement in PLOSL.

Adverse long-term effects of brain radiotherapy in adult low-grade glioma patients.

OBJECTIVE: To study the long-term effects of radiotherapy on cognitive function in adult patients operated on for low-grade glioma. METHODS: A cohort of 160 patients who underwent surgery for low-grade gliomas of cerebral hemisphere between 1980 and 1992 in a single institution serving a defined population was studied. At a mean follow-up time of 7 years, 28 of the 101 patients who had postoperative irradiation (and no second surgery or chemotherapy) were still alive and eligible for MRI and neuropsychological study. Twenty-three of 59 patients who did not have radiotherapy, second surgery, or chemotherapy were alive and eligible at a mean of 10 years. RESULTS: The group that had postoperative irradiation performed significantly worse than the group that did not in cognitive tests. This difference was not accounted for by histologic diagnosis; location, extent of removal, or progression of the tumor; or any patient factor. Leukoencephalopathy was more severe in the group that had postoperative irradiation than in the group without radiotherapy, and correlated to poor memory performances only in the postoperative radiotherapy group. Average Karnofsky performance scale score was significantly lower in the group that had postoperative irradiation than in the group that did not. CONCLUSION: In adults with low-grade glioma, postoperative radiotherapy poses a significant risk of long-term leukoencephalopathy and cognitive impairment.

The effect of IFNbeta-1b on the evolution of enhancing lesions in secondary progressive MS.

BACKGROUND: After the resolution of contrast enhancement, the majority of new MS lesions become isointense with surrounding white matter on T1-weighted MRI. Less commonly, a hypointense T1 lesion develops, representing the development of more severe focal tissue damage. Interferon beta (IFNbeta) reduces both the number of new enhancing lesions and the duration of contrast enhancement. OBJECTIVE: To determine if IFNbeta affects the degree of tissue damage within new lesions and if its effects are related to lesion size. METHODS: One hundred twenty-five patients with secondary progressive MS from seven European sites were randomized to receive either IFNbeta-1b or placebo. Monthly, contrast-enhanced T1-weighted MR images were acquired at baseline, at months 1 to 6, and at months 19 to 24. The size of all new enhancing lesions developing between months 1 and 6 was recorded and their appearance at follow-up documented. RESULTS: In the first 6 months, fewer new enhancing lesions occurred in the IFNbeta-1b arm. This difference was greater for small (70% decrease) than for large (46% decrease) lesions. Hypointense T1 lesions were more likely to form from large (25%) than from small (9%) enhancing lesions in both treatment arms. Patients taking IFNbeta-1b developed fewer hypointense T1 lesions; however, the proportion of enhancing lesions developing into hypointense T1 lesions was similar in both arms. CONCLUSION: IFNbeta-1b reduced the number of new enhancing lesions, with a greater effect on small lesions. However, when a new enhancing lesion did become established, treatment with IFNbeta-1b did not alter its subsequent course.

MRI enhancement and microvascular density in gliomas. Correlation with tumor cell proliferation.

RATIONALE AND OBJECTIVES: Angiogenesis and proliferation activity are important indicators of tumor behavior in human gliomas. The authors studied how tumor enhancement in MR imaging and intratumoral vascular density were correlated with cell proliferation in cerebral gliomas. METHODS: The authors studied retrospectively 62 cerebral gliomas. Patients were examined before surgery with contrast-enhanced MR imaging. Microvessel density and the cell proliferation rate of tumor specimens were measured immunohistochemically using factor VIII and MIB-1 antibodies. Contrast enhancement of the tumors was evaluated by two radiologists. RESULTS: Contrast enhancement was observed in 45 tumors and was correlated with histologic cell proliferation (P = 0.0007) and microvessel density (P = 0.01). There was also a correlation between tumor vascular density and the cell proliferation rate (r = 0.51, P < 0.0001). Histologic tumor grade was associated with vascular density (P = 0.001). CONCLUSIONS: Lesion enhancement on preoperative contrast-enhanced MR imaging correlates with vascularity and proliferation activity of gliomas. The additional correlation between tumor vascularity and proliferation suggests that intratumoral microvessel density could be useful in estimating tumor proliferation.

Central nervous system aspergillosis in allogeneic stem cell transplant recipients.

Invasive aspergillosis (IA) is relatively common in allogeneic stem cell transplant (SCT) recipients. Although lungs are the most common site, central nervous system (CNS) involvement is also observed in this setting. We have retrospectively studied 14 cases of CNS aspergillosis found in a cohort of 455 allogeneic SCT recipients (incidence 3%). All patients, except one, had experienced acute graft-versus-host disease treated with high-dose methylprednisolone, and eight patients (57%) had also received ATG. The median time to the diagnosis of CNS aspergillosis was 124 days (range 49-347 days) from SCT. Pulmonary aspergillosis had been diagnosed earlier in four patients (29%). The most common initial symptoms of CNS aspergillosis were convulsions, hemiparesis, and mental alteration. Neuroradiological studies revealed single (two patients) or multiple (seven patients) focal lesions of 0.2-9 cm in diameter. Despite clinical suspicion in many patients, a confirmed diagnosis of CNS aspergillosis was made during life in only one patient. A total of 12 patients (86%) received amphotericin B. Despite therapy, all patients died 0-27 days (median seven days) after the initial CNS symptoms. CNS aspergillosis is not uncommon in allogeneic SCT recipients. Clinical manifestations are usually dramatic and progress quickly. Earlier and more effective treatment of IA is needed to prevent dissemination of infection into the CNS.