R.G. Gonzalez

Posterior leukoencephalopathy without severe hypertension: Utility of diffusion-weighted MRI

Objective: Standard MRI confirms the diagnosis of posterior leukoencephalopathy syndrome (PLES), recently associated with an increasing number of medical conditions. In PLES, T2-weighted MRI demonstrates hyperintensity spreading out from posterior brain regions; the pathophysiology remains mysterious. In the acute setting, diffusion-weighted imaging (DWI), but not standard MR imaging, can distinguish ischemic injury from those conditions known to cause vasogenic brain edema. DWI is potentially valuable in understanding the pathophysiology of PLES and in diagnosing patients who do not have previously known risk factors. Methods: Serial CT and MRI studies (including DWI, apparent diffusion coefficient [ADC] maps, and, in one instance, perfusion-weighted imaging) were performed in three female patients with a neurologic syndrome consistent with PLES while hospitalized for treatment of other conditions. Results: None of the patients had previously described risk factors for PLES; all had only mild elevations in blood pressure. MRI showed large, abnormal, T2 hyperintense regions in the posterior cerebrum with corresponding hyperintensity on ADC maps-signal characteristics predominantly consistent with vasogenic edema. There were also smaller patchy posterior cortical regions with decreased ADC and bright DWI consistent with infarction in one, and dramatic conversion of a large region to an ischemic pattern in another. Conclusions: ADC maps and DWI can successfully differentiate PLES from early cerebral ischemia, thus playing a pivotal role in treatment decisions. PLES is associated with a wider variety of conditions than has been previously reported and is not always reversible. Hyperintense DWI signal in patients with the syndrome likely marks a tissue stage of permanent brain injury.

Normal diffusion-weighted MRI during stroke-like deficits

Background: Diffusion-weighted MRI (DWI) represents a major advance in the early diagnosis of acute ischemic stroke. When abnormal in patients with stroke-like deficit, DWI usually establishes the presence and location of ischemic brain injury. However, this is not always the case. Objective: To investigate patients with stroke-like deficits occurring without DWI abnormalities in brain regions clinically suspected to be responsible. Methods: We identified 27 of 782 consecutive patients scanned when stroke-like neurologic deficits were still present and who had normal DWI in the brain region(s) clinically implicated. Based on all the clinical and radiologic data, we attempted to arrive at a pathophysiologic diagnosis in each. Results: Best final diagnosis was a stroke mimic in 37% and a cerebral ischemic event in 63%. Stroke mimics (10 patients) included migraine, seizures, functional disorder, transient global amnesia, and brain tumor. The remaining patients were considered to have had cerebral ischemic events: lacunar syndrome (7 patients; 3 with infarcts demonstrated subsequently) and hemispheric cortical syndrome (10 patients; 5 with TIA, 2 with prolonged reversible deficits, 3 with infarction on follow-up imaging). In each of the latter three patients, the regions destined to infarct showed decreased perfusion on the initial hemodynamically weighted MRI (HWI). Conclusions: Normal DWI in patients with stroke-like deficits should stimulate a search for nonischemic cause of symptoms. However, more than one-half of such patients have an ischemic cause as the best clinical diagnosis. Small brainstem lacunar infarctions may escape detection. Concomitant HWI can identify some patients with brain ischemia that is symptomatic but not yet to the stage of causing DWI abnormality.

Quantitative Assessment of Core/Penumbra Mismatch in Acute Stroke CT and MR Perfusion Imaging Are Strongly Correlated When Sufficient Brain Volume Is Imaged

Background and Purpose— Our purpose was to determine (1) the correlation between quantitative CT and MR measurements of infarct core, penumbra, and mismatch; and (2) whether the difference between these measurements would alter patient selection for stroke clinical trials. Methods— We studied 45 patients with acute middle cerebral artery stroke imaged a mean of 3.8 hours after onset (range, 0.48 to 8.35 hours) who underwent CT perfusion and MR diffusion (DWI)/perfusion imaging within 3 hours of each other. The DWI and MR-mean transit time (MTT) abnormalities were visually segmented using a semiautomated commercial analysis program. The CT-cerebral blood volume) and CT-MTT lesions were automatically segmented using a relative cerebral blood volume threshold of 0.56 and a relative MTT threshold of 1.50 on commercially available software. Percent mismatch was defined as [(MTT−DWI)/DWI volume]×100. Pearson correlation coefficients were calculated. Results— There were significant correlations for DWI versus CT-cerebral blood volume lesion volumes (r2=0.88, P<0.001), for MR-MTT versus CT-MTT lesion volumes(r2=0.86, P<0.001), and for MR-MTT/DWI versus CT-MTT/CT-cerebral blood volume mismatch lesion volumes(r2=0.81, P<0.001). MR perfusion and CT perfusion agreed for determining: (1) infarct core < versus ≥100 mL in 41 of 45 (91.1%); (2) MTT lesion size < versus >2 cm diameter in 42 of 45 (93.3%); (3) mismatch < versus >20% in 41 of 45 (91.1%); and (4) inclusion versus exclusion from trial enrollment in 38 of 45 (84.4%) patients. Six of 7 disagreements were due to inadequate CT coverage. Conclusion— Advanced MR and CT perfusion imaging measurements of core/penumbra mismatch for patient selection in stroke trials are highly correlated when CT perfusion coverage is sufficient to include most of the ischemic region. Although MR is currently the preferred imaging method for determining core and penumbra, CT perfusion is comparable and potentially more available.

‘Footprints’ of Transient Ischemic Attacks: A Diffusion-Weighted MRI Study

Objective: Diffusion-weighted imaging (DWI) conveys temporal as well as anatomic information about brain infarction, and is therefore well suited to identify ischemic injury that has occurred simultaneously, or closely linked in time, with a transient ischemic attack (TIA). We aimed to determine the proportion and clinical characteristics of patients with TIA who harbor infarction(s) on DWI. Methods: Using T2-weighted imaging (T2-WI), fast fluid attenuated inversion recovery (FLAIR), and DWI, we studied 57 consecutive patients presenting with acute focal neurologic symptoms lasting less than 24 h. Results: A hyperintense DWI lesion was identified in a vascular territory appropriate to the symptoms in 27 patients (47%). Lesions judged to be clinically appropriate on T2-WI and FLAIR overlapped with a DWI lesion in 41 and 48% of patients, respectively. Independent predictors of infarction on DWI were previous nonstereotypic TIAs, presentation with motor symptoms, and identified stroke mechanism. Conclusion: DWI establishes that recent infarction occurs in almost half of patients with the clinical syndrome of TIA and this subgroup is more likely to harbor an underlying cardiac or cerebrovascular abnormality.

Clinical and radiographic features of peritumoral infarction following resection of glioblastoma

Focal areas of restricted diffusion adjacent to high-grade glioma resection cavities were detected in 70% of patients on immediate postoperative MRI studies. Follow-up studies demonstrated cystic encephalomalacia in 91% of these foci, suggesting the presence of infarction, and the infarcted tissue demonstrated enhancement in 43% of cases. New postoperative deficits correlated well with the anatomic region of infarction in six patients. Enhancement in perioperative infarcts can mimic tumor progression on follow-up imaging studies.

Diffusion-weighted MRI in diffuse axonal injury of the brain

Abstract. The goal of this study was to identify and describe the different types and patterns of tissue injury which are encountered by diffusion-weighted imaging (DWI) in diffuse axonal injury (DAI) of the brain. The DWI data sets of 98 patients who suffered from a closed-head injury were retrospectively evaluated. Medical records were reviewed to rule out pre-existing neurological diseases. Lesions were studied for their DWI signal characteristics and lesion size or extension. Traumatic lesions were classified into three categories depending on their signal characteristica on DWI and apparent diffusion coefficient (ADC) maps: type 1, DWI- and ADC-hyperintense most likely representing lesions with vasogenic edema; type 2, DWI-hyperintense, ADC-hypointense indicating cytotoxic edema; type 3, central hemorrhagic lesion surrounded by an area of increased diffusion. According to the size and extent of lesions, injury was classified into three groups: group A, focal injury; group B, regional/confluent injury; and group C, extensive/diffuse injury. Our study showed that diffusion-weighted imaging differentiates between lesions with decreased and increased diffusion in patients with DAI. Different degrees of tissue injury extent were noticed. Future prospective studies should study if this additional information can be used as a predictor of injury reversibility, final outcome and prognosis.

In vitro 31P NMR spectroscopy detects altered phospholipid metabolism in Alzheimer's disease.

In order to study possible metabolic derangements in Alzheimers disease (AD), we performed phosphorus 31 nuclear magnetic resonance (31P NMR) spectroscopy on brain samples obtained at autopsy from 7 patients with AD and 9 control subjects. Aqueous solutions of brain tissue contained well-defined peaks of intermediate compounds in phospholipid metabolism, including the phosphomonoesters phosphocholine and phosphoethanolamine, and the phosphodiesters glycerophosphorylcholine and glycerophosphorylethanolamine. 31P NMR spectra also displayed the inorganic phosphorus signal, which provides an index to the in vivo concentration of high-energy compounds. We found evidence for altered phospholipid metabolism in that relative levels of phosphomonoesters were decreased, and phosphodiesters increased, in frontal and parietal regions of patients with AD compared to control subjects. The inorganic phosphorus resonance peaks were similar in AD and control subjects, suggesting that energy stores are not diminished in AD. These preliminary data are consistent with the hypothesis that abnormalities in phospholipid metabolism contribute to possible neuronal membrane dysfunction and impaired cholinergic neurotransmission in AD.

Case volumes of intra-arterial and intravenous treatment of ischemic stroke in the USA

Background and purpose Ischemic stroke is a major cause of disability and death in the USA. Intravenous tissue plasminogen activator (t-PA) remains underutilized. With the development of newer intra-arterial reperfusion therapies, there is increased opportunity to address the more devastating large-vessel occlusions. We seek to identify the numbers of patients with stroke treated with intravenous and intra-arterial therapies, as well as to estimate the potential number of intra-arterial cases in the foreseeable future. Methods We performed a literature search to determine case volumes of intravenous t-PA use. We extrapolated the current case volume of intra-arterial stroke therapies from the numbers of cases in which the Merci retrieval device was used. In order to estimate the potential numbers of intra-arterial stroke cases, we characterized the percentage of patients with stroke who received intra-arterial therapy at two leading stroke centers. We applied these percentages to the numbers of patients with stroke seen at the top 100, 200 and 500 stroke centers by volume. Results The rate of intravenous t-PA use is 2.4–3.6%, resulting in 15 000–22 000 cases/year in the USA. The estimated case volume of intra-arterial therapies is 3500–7200 in 2006. Based on data from St. Lukes Brain and Stroke Institute and Massachusetts General Hospital, approximately 5–20% of patients with ischemic stroke can be treated with intra-arterial therapies. Extrapolating this to the top 500 stroke centers by volume, the potential number of intra-arterial cases in the USA is 10 400–41 500/year. Conclusion Based on the current numbers of intra-arterial cases, our theoretical model identifies a potential for significant growth of this stroke therapy.

Dynamic single-section CT demonstrates reduced cerebral blood flow in acute intracerebral hemorrhage.

Optimum blood pressure (BP) management in acute intracerebral hemorrhage (ICH) remains controversial. BP reduction may limit hematoma expansion, but may also exacerbate ischemia. Reduced regional cerebral blood flow (rCBF) has been reported in ICH. Its extent and precise pattern, however, remain uncertain. Dynamic single-section CT perfusion (CTP) is rapid, easily performed and offers superior spatial resolution to PET, SPECT and MRI. It may be the most applicable method for assessing the effects of BP management on rCBF in ICH. We sought to assess whether CTP can identify rCBF abnormalities in acute ICH in 5 patients with ICH who underwent CTP within 24 h of symptom onset. rCBF was measured in serially expanded 2-mm rings around the hematoma and compared with rCBF in the uninvolved hemisphere. Mean time to CTP was 9 h (range 3–23). Mean ICH volume was 25 ml (range 9–64). Perihematoma perfusion was reduced in all patients compared with contralateral hemisphere rCBF. rCBF reduction was most pronounced immediately adjacent to the hematoma (p < 0.05 at 2 mm, p = 0.084 at 4 mm, p > 0.2 at 6 and 8 mm). Perihematoma rCBF increased as a function of the distance from hematoma perimeter. Rate of rCBF increase over distance correlated with time from onset (p = 0.006). We conclude that CTP identifies a rim of reduced rCBF in ICH. A gradient of hypoperfusion appears to extend at least 4 mm beyond the hematoma edge and may be time dependent. Whether reduced CBF is associated with perihematoma ischemia requires additional study.

Increased cerebral blood volume in HIV‐positive patients detected by functional MRI

Objective To study changes in cerebral hemodynamics related to HIV infection. Background Cerebral injury is a well-known manifestation of HIV infection. Physiologic changes in the HIV brain may precede structural changes and may be detected by functional MRI (fMRI). Methods Dynamic contrast fMRI was used to measure the cerebral blood volume (CBV) in 13 patients infected with HIV and in 7 healthy control subjects. Results Significant increases in dynamic CBV were found in the deep (p < 0.001) and cortical gray matter (p < 0.05) of HIV-positive (HIV+) patients. Patients with definite cognitive impairment showed significantly greater increases in CBV in the deep gray matter (DGM) compared with those without impairment. In one patient with rapidly progressive cognitive impairment, these abnormalities reversed and paralleled clinical improvement after initiation of zidovudine monotherapy. Conclusions This study supports the hypothesis that HIV infection is associated with significant cerebral hemodynamic changes, particularly in the DGM, that may contribute to cognitive dysfunction in AIDS. Functional MRI may be useful for early detection of cerebral injury and for the assessment of novel therapies.