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Impact on stroke subtype diagnosis of early diffusion-weighted magnetic resonance imaging and magnetic resonance angiography.

BACKGROUND AND PURPOSE: The purpose of the present study was to assess the diagnostic usefulness of early diffusion-weighted MRI (DWI) and MR angiography (MRA) in patients with ischemic stroke. Past approaches to stroke diagnosis required a series of diagnostic tests over several days of hospitalization. New magnetic resonance methodologies that include DWI and MRA may allow more rapid characterization of stroke pathophysiology. However, no previous study has assessed the impact on formal stroke subtype diagnosis of early imaging with DWI/MRA. METHODS: We analyzed 46 consecutive patients with acute ischemic stroke who underwent DWI/MRA within 24 hours of admission. Initial diagnoses were rendered with use of the 2 most widely used formal stroke subtype classification schemes, the TOAST and the Oxfordshire methods, which were applied to patients after CT/conventional MRI but before DWI/MRA. Modified TOAST and Oxfordshire diagnoses were then rendered based on the results of day 1 DWI, MRA, and DWI plus MRA. Final TOAST/Oxfordshire diagnoses at discharge were taken as the gold standard. RESULTS: Compared with final diagnoses, pre-MRI TOAST diagnoses matched final diagnoses in 48%, improving to 83% after DWI alone, 56% after MRA alone, and 94% after DWI plus MRA. For the TOAST diagnostic subtypes of large-vessel atherothromboembolism and small-vessel disease, pre-MRI diagnoses matched final diagnoses in 56% and 35% of patients, respectively, improving to 89% and 100% after DWI/MRA. Pre-MRI Oxfordshire diagnoses matched final diagnoses in 67% of patients, improving to 100% after DWI. CONCLUSIONS: The use of DWI/MRA within 24 hours of hospitalization substantially improves the accuracy of the diagnosis of early ischemic stroke subtype. When initial management and clinical trial eligibility decisions are influenced by stroke subtype, day 1 multimodal MRI is advantageous as a guide to therapy.

Female↗

Old microbleeds are a potential risk factor for cerebral bleeding after ischemic stroke: a gradient-echo T2*-weighted brain MRI study.

BACKGROUND AND PURPOSE: T2*-weighted gradient-echo MRI is known to detect old microbleeds (MBs), considered indicative of microangiopathy. MBs might be a potential risk factor for early cerebral bleeding (CB) after ischemic stroke. Therefore, we assessed the impact of MBs on the occurrence of CB after cerebral infarction. METHODS: We included prospectively stroke patients who had documented ischemic damage. The imaging protocol involved baseline CT scan, T2*-weighted gradient-echo MRI, diffusion-weighted imaging, T2-weighted imaging, and magnetic resonance angiography and had to be performed within 24 hours after symptom onset. The assessment of CB with T2*-weighted gradient-echo sequence necessitated a focal area of signal loss either within the ischemic area revealed by diffusion-weighted imaging or remote from it. Old MBs were defined on T2*-weighted images as homogeneous rounded areas of signal loss without surrounding edema. CT scan was systematically repeated within the first week to verify CB as diagnosed by the T2* weighted sequence. RESULTS: One hundred patients (mean age, 60 +/- 13 years; range, 19 to 83 years; 58 men, 42 women) met the inclusion criteria. MBs were seen in 20 patients on T2*-weighted imaging. Multivariate logistic regression analysis revealed that age, diabetes, previous use of antithrombotic drugs, evidence of an atherothrombotic source of stroke, and lacunar infarct were significantly associated with MBs (P<0.0001). CB was diagnosed in 26 patients: at the acute stage by T2*-gradient echo sequence in 18 patients and with CT scan performed within the first week in 8 patients. Multivariate logistic regression analysis showed that baseline National Institutes of Health Stroke Scale score, diabetes, and MBs were considered significant and independent predictors of CB (P<0.001). CONCLUSIONS: Although the pathogenesis of CB after ischemic stroke is multifactorial, the increased observation of CB in patients with MBs suggests that the associated vascular vulnerability contributes to CB.

Adult↗

Tracking the recovery of consciousness from coma.

Predicting the chances of recovery of consciousness and communication in patients who survive their coma but transit in a vegetative state or minimally conscious state (MCS) remains a major challenge for their medical caregivers. Very few studies have examined the slow neuronal changes underlying functional recovery of consciousness from severe chronic brain damage. A case study in this issue of the JCI reports an extraordinary recovery of functional verbal communication and motor function in a patient who remained in MCS for 19 years (see the related article beginning on page 2005). Diffusion tensor MRI showed increased fractional anisotropy (assumed to reflect myelinated fiber density) in posteromedial cortices, encompassing cuneus and precuneus. These same areas showed increased glucose metabolism as studied by PET scanning, likely reflecting the neuronal regrowth paralleling the patient's clinical recovery. This case shows that old dogmas need to be oppugned, as recovery with meaningful reduction in disability continued in this case for nearly 2 decades after extremely severe traumatic brain injury.

Coma↗

Difficulties in assessing brain death in a case of benzodiazepine poisoning with persistent cerebral blood flow.

Assessing brain death may sometimes be difficult, with isoelectric EEG following psychotrope overdoses or normal cerebral blood flow (CBF) persisting despite brain death in the case of ventricular drainage or craniotomy. A 42-year-old man, resuscitated after cardiac arrest following a suicidal ingestion of ethanol, bromazepam and zopiclone, was admitted in deep coma. On day 4, his brainstem reflexes and EEG activity disappeared. On day 5, his serum bromazepam concentration was 817 ng/ml (therapeutic: 80-150). The patient was unresponsive to 1 mg of flumazenil. MRI showed diffuse cerebral swelling. CBF assessed by angiography and Doppler remained normal and EEG isoelectric until he died on day 8 with multiorgan failure. There was a discrepancy between the clinically and EEG-assessed brain death, and CBF persistence. We hypothesized that brain death, resulting from diffuse anoxic injury, may lead, in the absence of major intracranial hypertension, to angiographic misdiagnoses. Therefore, EEG remains useful to assess diagnosis in such unusual cases.

Adult↗

Adult-onset leukoencephalopathy with vanishing white matter with a missense mutation in EIF2B5.

We report of a woman aged 52 years born to consanguineous parents and seeking treatment for progressive dementia and delusion. Neurologic examination revealed dementia and emotional instability, indifference, and confabulation. There was also mild spasticity of the bilateral lower limbs. MRI revealed diffuse white matter hyperintensity on T2-weighted images accompanied by hypointense areas on fluid-attenuated inversion recovery images. A homozygous missense mutation was identified in EIF2B5.

Adult↗

Primary dural lymphomas: a clinicopathologic study of treatment and outcome in eight patients.

The authors report eight patients with primary dural lymphoma (PDL). All patients had extra-axial masses on MRI that diffusely enhanced after gadolinium. Pathology revealed low-grade non-Hodgkin lymphoma (marginal zone lymphoma of MALT [mucosa-associated lymphoid tissue] type) in all patients. All patients underwent radiation therapy, and three received chemotherapy. Complete response was achieved in 100% of patients, but three developed systemic relapse.

Adult↗

Krabbe disease: specific MRI and CT findings.

In three patients with Krabbe disease (galactosylceramide lipidosis), CT and MRI patterns progressed with the evolution of the disease. At first, discrete and symmetric dense areas on CT were found in deep gray matter of hemispheres and brainstem, and also in periventricular and capsular white matter. MRI showed decreased T1 values with normal or slightly decreased T2 values in those areas and large symmetric "plaque-like" lesions with high T1 and T2 values in white matter of the centrum semiovale. Later, both CT and MRI revealed diffuse reduction in gray matter and, more profoundly, in white matter mass. These findings may alert clinicians to the possibility of Krabbe disease in infants with progressive encephalopathy.

Atrophy↗

Infantile CNS spongy degeneration--14 cases: clinical update.

We studied 14 Arab infants with infantile spongy degeneration, 13 of whom were products of consanguineous marriages. They presented in infancy with macrocephaly, poor visual behavior or blindness, and axial hypotonia with appendicular spasticity. Brain CT and MRI showed diffuse symmetric leukoencephalopathy, even before neurologic symptoms. There were relatively normal EEGs. The visual evoked responses (P100) were either absent or delayed early in the course. The brainstem auditory evoked responses showed milder abnormalities, with loss of later components before the earlier ones. Deficient aspartoacylase activity in cultured fibroblasts or brain biopsy confirmed the diagnosis in all patients.

Amidohydrolases↗

Delayed posthypoxic demyelination. Association with arylsulfatase A deficiency and lactic acidosis on proton MR spectroscopy.

Delayed demyelination is a rare and poorly understood complication of hypoxic brain injury. A previous case report has suggested an association with mild-to-moderate deficiency of arylsulfatase A. We describe a 36-year-old man who recovered completely from an episode of hypoxia related to drug overdose, and 2 weeks later progressed from a confusional state to deep coma. MRI showed diffuse white matter signal changes, and brain biopsy demonstrated a noninflammatory demyelinating process. Proton magnetic resonance spectroscopy revealed elevated choline and lactate and reduced N-acetyl aspartate signal in the affected white matter, consistent with demyelination and a shift to anaerobic metabolism. Arylsulfatase A activity from peripheral leukocytes was approximately 50% of normal, consistent with a "pseudodeficiency" phenotype. These findings confirm the hypothesis that relative arylsulfatase A deficiency predisposes susceptible individuals to delayed posthypoxic leukoencephalopathy and implicates lactic acidosis in the pathogenesis of this disorder.

Acidosis, Lactic↗

CADASIL in a North American family: clinical, pathologic, and radiologic findings.

OBJECTIVE: To expand the reported phenotypic range of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). BACKGROUND: Despite numerous patient reports, our knowledge of the phenotypic range of CADASIL remains incomplete. METHOD: We performed clinical, pathologic, and radiologic examinations on members of a family with CADASIL. RESULTS: The proband is a 61-year-old man with a history of migraine and depression who has experienced multiple subcortical infarctions resulting in a stepwise decline. Neuropsychological testing documented a dementia syndrome with frontal lobe features and neurologic examination noted a left hemiparesis and a right-sided palmomental reflex. Brain biopsy with light microscopy revealed a nonatherosclerotic small-vessel angiopathy with periodic acid-Schiff positive granular changes in the media and white matter gliosis, with unremarkable cortex. Genetic testing confirmed a Notch3 mutation. The proband's first cousin has a history of depression, one seizure possibly resulting from an acute stroke, and a learning disorder. Neuropsychological testing demonstrated deficits in executive function and neurologic examination noted persistent extraneous adventitial movements, poor coordination, and primitive reflexes. Skin biopsy with electron microscopy demonstrated granular osmiophilic material within the basement membrane of vascular smooth muscle cells, which is considered to be pathognomonic of CADASIL. The proband's older son and younger son have histories of migraine and depression, respectively, and both also had learning disorders. MRI revealed diffuse white matter disease extending into the temporal lobes, and lacunar infarctions in these four nonhypertensive patients. Other family members have experienced migraine, recurrent stroke, dementia, and depression. CONCLUSIONS: CADASIL is a genetic basis for vascular dementia that may be manifest earlier in life than previously reported.

Adult↗

Cortical dysplasia with angiodysgenesis and chronic inflammation in multifocal partial epilepsy.

A 25-year-old man with a long history of temporal lobe epilepsy developed right occipital lobe seizures and a progressive right homonymous hemianopia. MRI showed diffuse enhancement of the left temporoparieto-occipital white matter and cortical thickening of the left medial temporal lobe. The resected temporal lobe revealed cortical dysplasia and angiodysplasia with foci of more recent ischemic necrosis and chronic inflammation as an explanation for the clinical deterioration.

Adolescent↗

Optic nerve edema as a consequence of respiratory disease.

The authors describe a patient with bilateral papilledema, visual field abnormalities, poorly reactive pupils, meningeal enhancement on cranial MRI, and diffuse brain parenchymal hypervascularity. The opening pressure at the time of lumbar puncture was normal, and results of other CSF studies were normal. All abnormalities resolved with home oxygen therapy.

Diagnosis, Differential↗

Stroke as a complication of cardiac catheterization: risk factors and clinical features.

The authors aimed to delineate the risk factors and radiologic pattern of stroke complicating cardiac catheterization. Twenty-two cases were matched with three control subjects. Stroke was significantly associated with severity of coronary artery disease and length of fluoroscopy time (OR 1.96 and 1.65). The use of MRI with diffusion weighting allowed the identification of multiple asymptomatic lesions and a subset of lacunar-type infarcts (23%), which most likely occurred on an atheroembolic basis.

Aged↗

Advances in intravenous thrombolytic therapy for treatment of acute stroke.

Intravenous tissue plasminogen activator (tPA) is an effective therapy for treatment of acute ischemic stroke when administered within 3 hours of symptom onset. Three large randomized clinical trials that have attempted to extend the time window for tPA treatment beyond 3 hours have failed to demonstrate convincing evidence of efficacy. A recently published prospective, monitored, multicenter study of 389 patients, who were treated with tPA for ischemic stroke at 57 medical centers (24 academic, 33 community) across the United States, demonstrated favorable outcomes and low rates of symptomatic intracerebral hemorrhage. Recent advances in neuroimaging, including diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI), have the potential to differentiate salvageable ischemic brain tissue from irreversibly injured tissue. Preliminary data suggest that acute stroke patients who present with a PWI lesion that is considerably larger than the initial DWI lesion may be good candidates for intravenous thrombolysis, even beyond 3 hours after symptom onset. Additional research is required to clarify the optimal use of these diagnostic techniques and their cost-effectiveness.

Acute Disease↗

Evaluation of cystic ovarian lesions using apparent diffusion coefficient calculated from turboFLASH MR images.

Serial turboFLASH (fast low-angle shot) images with and without diffusion-perfusion (DP) gradients were used to evaluate the contents of cystic ovarian lesions. 19 ovarian cysts seven serous cystadenomas, six mucinous cystadenomas and 13 malignant cystic ovarian tumours were studied. T1 and T2 weighted spin echo images, serial turboFLASH images with and without DP gradients (b = 295.1 and 0 s mm-2, respectively) were obtained. Using these images, the apparent diffusion coefficients (ADCs) were calculated within the cystic contents of these lesions. Approximately corrected ADC (ADC') values were also calculated in order to reduce T1 contamination from ADCs, using results of a phantom study. Ovarian cysts and serous cystadenomas showed larger ADC and ADC' values than the cystic contents of malignant ovarian lesions (p < 0.01). Mucinous cystadenomas show no distinct ADC difference to any other group of cases. However, if the highest ADC' loculus was selected as being representative, mucinous cystadenomas showed a larger ADC' value than malignant cystic neoplasms (p < 0.03). In conclusion, diffusion-weighted MRI is possibly of use in evaluating cystic contents of ovarian lesions.

Adult↗

Short echo-time proton magnetic resonance spectroscopy in regions of severe HIV-related diffuse white matter abnormality on MRI.

The purpose of this study was to determine whether short echo-time proton magnetic resonance spectroscopy (H-MRS) could detect mobile lipid resonances attributable to myelin breakdown products in the deep cerebral white matter of patients with AIDS who have severe diffuse/patchy white matter hyperintensity on T2-weighted magnetic resonance imaging (MRI). Seven patients with AIDS and clinical HIV-associated dementia complex (HADC) and 12 male controls were studied at 1.5T using a single 8 ml voxel, gradient localised, stimulated echo acquisition mode (STEAM) spectroscopy sequence. Spectra were acquired at an echo time of 20 ms with a repetition time of 5000 ms. No spectroscopic peaks were identified at 0.9 ppm and 1.3 ppm (corresponding to lipid resonances) in 6 of the 7 patients with AIDS or in any of the controls. Lipid resonances were identified in 1 patient who had been taking anti-retroviral therapy for 8 weeks. Follow up MRI/H-MRS, performed after a further 14 weeks of anti-retroviral therapy, showed partial resolution of white matter hyperintensity and lipid resonances were not detectable. These data suggest that mobile lipids are only rarely detected by H-MRS in patients with HADC and abnormalities on MRI and that their presence may be transitory.

AIDS Arteritis, Central Nervous System↗

Lissencephaly, abnormal genitalia and refractory epilepsy: case report of XLAG syndrome.

INTRODUCTION: X-linked lissencephaly with ambiguous genitalia (XLAG) is a recently described genetic disorder caused by mutation in the aristaless-related homeobox (ARX) gene (Xp22.13). Patients present with lissencephaly, agenesis of the corpus callosum, refractory epilepsy of neonatal onset, acquired microcephaly and male genotype with ambiguous genitalia. CASE REPORT: Second child born to healthy nonconsanguineous parents, presented with seizures within the first hour of life that remained refractory to phenobarbital, phenytoin and midazolam. Examination identified microcephaly, axial hypotonia, pyramidal signs and ambiguous genitalia. EEG showed disorganized background activity and seizures starting at the right midtemporal, central and occipital regions. MRI showed diffuse pachygyria, moderate thickening of the cortex, enlarged ventricles, agenesis of the corpus callosum and septum pellucidum. Karyotype showed a 46,XY genotype. Additional findings were hypercalciuria, vesicoureteral reflux, patent ductus arteriosus and chronic diarrhea.

Electroencephalography↗

Neuroimaging in human dystonia.

Functional neuroimaging, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), provides a valuable technique for detecting regional changes in brain metabolic activity associated with human disease. These techniques have been applied in different dystonic disorders including primary generalized dystonia and dopa-responsive dystonia (DRD), as well as focal dystonic syndromes such as torticollis, writer's cramp, and blepharospasm. A common finding is abnormality of the basal ganglia and associated outflow pathways to sensorimotor cortex and other regions involved with motor performance. Other recent imaging research has utilized diffusion-based MRI techniques to localize distinct microstructural abnormalities in dystonia patients and gene carriers. This presentation will focus on an integrated approach to understanding the pathophysiology of this genetic and biochemically diverse disorder.

Anisotropy↗