Stroke service: how can we improve and measure outcomes? Consensus summary from a global stroke forum.

The success of acute stroke treatment is first and foremost time-dependent, and the need for improvement in acute stroke management is demonstrated by the fact that only a minority of patients gain access to treatment - in particular, intravenous recombinant tissue plasminogen activator (IV tPA) - within the necessary time window. Standards of acute stroke care vary widely both regionally and nationally; consequently, various healthcare organizations have undertaken initiatives to measure and improve quality of care. To date, most quality measures have been process-based, focusing primarily on metrics of patient care in the acute hospital-based setting (e.g., time to recombinant tPA administration). Therefore, there remains a need for metrics designed to assess how improvements in process translate into patient outcomes. A global forum was convened to share best practice and provide consensus recommendations on core metrics for measuring improvements in access to care and patient outcomes. Recommendations for core metrics of patient outcomes include hospital-based outcomes (e.g., neurological status at 24 h, ambulatory status at discharge) and post-discharge outcomes (e.g., modified Rankin Scale score at 30 and/or 90 days). Recommendations for best practice relating to aspects of people, process, and technology involved in the stroke treatment pathway that may help provide improvements in these core outcome measures are also outlined.

Incidental Findings from 16,400 Brain MRI Examinations of Research Volunteers.

BACKGROUND AND PURPOSE: Incidental findings are discovered in neuroimaging research, ranging from trivial to life-threatening. We describe the prevalence and characteristics of incidental findings from 16,400 research brain MRIs, comparing spontaneous detection by nonradiology scanning staff versus formal neuroradiologist interpretation. MATERIALS AND METHODS: We prospectively collected 16,400 brain MRIs (7782 males, 8618 females; younger than 1 to 94 years of age; median age, 38 years) under an institutional review board directive intended to identify clinically relevant incidental findings. The study population included 13,150 presumed healthy volunteers and 3250 individuals with known neurologic diagnoses. Scanning staff were asked to flag concerning imaging findings seen during the scan session, and neuroradiologists produced structured reports after reviewing every scan. RESULTS: Neuroradiologists reported 13,593/16,400 (83%) scans as having normal findings, 2193/16,400 (13.3%) with abnormal findings without follow-up recommended, and 614/16,400 (3.7%) with "abnormal findings with follow-up recommended." The most common abnormalities prompting follow-up were vascular (263/614, 43%), neoplastic (130/614, 21%), and congenital (92/614, 15%). Volunteers older than 65 years of age were significantly more likely to have scans with abnormal findings (P < .001); however, among all volunteers with incidental findings, those younger than 65 years of age were more likely to be recommended for follow-up. Nonradiologists flagged <1% of MRIs containing at least 1 abnormality reported by the neuroradiologists to be concerning enough to warrant further evaluation. CONCLUSIONS: Four percent of individuals who undergo research brain MRIs have an incidental, potentially clinically significant finding. Routine neuroradiologist review of all scans yields a much higher rate of significant lesion detection than selective referral from nonradiologists who perform the examinations. Workflow and scan review processes need to be carefully considered when designing research protocols.

Deep Brain Nuclei T1 Shortening after Gadobenate Dimeglumine in Children: Influence of Radiation and Chemotherapy.

BACKGROUND AND PURPOSE: Intrinsic T1-hyperintense signal has recently been reported in the deep gray nuclei on brain MR imaging after multiple doses of gadolinium-based contrast agents. Most reports have included adult patients and excluded those undergoing radiation or chemotherapy. We investigated whether T1 shortening is also observed in children and tried to determine whether radiochemotherapy is a risk factor for this phenomenon. MATERIALS AND METHODS: In this single-center retrospective study, we reviewed clinical charts and images of all patients 18 years of age or younger with ≥4 gadobenate dimeglumine-enhanced MRIs for 6 years. Seventy-six children (mean age, 9.3 years; 60 unconfounded by treatment, 16 with radiochemotherapy) met the selection criteria (>4 MR imaging examinations; mean, 8). T1 signal intensity ratios for the dentate to pons and globus pallidus to thalamus were calculated and correlated with number of injections, time interval, and therapy. RESULTS: Among the 60 children without radiochemotherapy, only 2 had elevated T1 signal intensity ratios (n = 20 and 16 injections). Twelve of the 16 children with radiochemotherapy showed elevated signal intensity ratios. Statistical analysis demonstrated a significant signal intensity ratio change for the number of injections (P < .001) and amount of gadolinium (P = .008), but not for the interscan time interval (P = .35). There was a significant difference in the average signal intensity ratio change between those with and without radiochemotherapy (P < .001). Chart review revealed no new neurologic deficits in any patients, related to their underlying conditions and prior surgeries. CONCLUSIONS: Compared with published adult series, children show a similar pattern of T1 hyperintense signal changes of the dentate and globus pallidus after multiple gadobenate dimeglumine injections. The T1 signal changes in children may have a later onset but are accelerated by radiochemotherapy.

3D time-resolved contrast-enhanced cerebrovascular MR angiography with subsecond frame update times using radial k-space trajectories and highly constrained projection reconstruction.

HYPR TRICKS is an acquisition method that combines radial k-space trajectories, sampling k-space at different rates (TRICKS), and a new strategy for image reconstruction that uses highly constrained backprojection reconstruction (HYPR). This approach provides 3D time-resolved contrast-enhanced MR angiograms of the cerebral vessels with subsecond frame update times and submillimeter in-plane spatial resolution. Artifacts are suppressed, and signal-to-noise ratio is well maintained, by using HYPR reconstruction.

CT angiographic appearance of in-stent restenosis of intracranial arteries treated with the Wingspan stent.

Four patients underwent angioplasty and stenting of medically refractory symptomatic intracranial atherosclerosis with the new Wingspan stent system. In all 4 patients, CT angiography (CTA) showed an abnormality within the stented segment that was suggestive of nonocclusive in-stent thrombus. However, subsequent conventional angiography findings were typical for in-stent restenosis. The CTA imaging features of in-stent restenosis are important to recognize, and the misinterpretation of in-stent restenosis as in-stent thrombus may result in inappropriate management.

Pitfalls in lactate measurements at 3T.

In clinical MR spectroscopy at higher field strengths, lactate may show reduced or absent signal intensity at an echo time of 144 ms. Although this false-negative result may be predicted from theory, experimental verification and clinical impact have not been fully established. Using scanners from 3 major vendors, spectra from phantoms and patients demonstrate the lactate signal loss and potential error in interpretation. Strategies are discussed to overcome, or at least alleviate, this problem.

Thalamomesencephalic strokes after cocaine abuse.

Three young patients developed strokes of rostral midbrain and thalamus shortly following cocaine abuse. Two had infarctions and one had a hemorrhage, but none had clear risk factors other than cocaine for this relatively uncommon type of stroke. Toxicologic analysis confirmed isolated cocaine use in each patient. In the two cases of infarction studied angiographically, one had normal findings and the other had focal narrowing of the P1 segments of the posterior cerebral arteries bilaterally. Since the P1 segment has a uniquely sparse perivascular sympathetic supply, we suggest that direct adrenergic-mediated vasoconstriction is not critical to the production of cocaine-associated stroke.

Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: the PROACT II trial.

OBJECTIVE: To analyze the frequency, clinical characteristics, and predictors of symptomatic intracerebral hemorrhage (ICH) after intraarterial (IA) thrombolysis with recombinant pro-urokinase (r-proUK) in acute ischemic stroke. METHOD: The authors conducted an exploratory analysis of symptomatic ICH from a randomized, controlled clinical trial of IA thrombolysis with r-proUK for patients with angiographically documented occlusion of the middle cerebral artery within 6 hours from stroke onset. Patients (n = 180) were randomized in a ratio of 2:1 to either 9 mg IA r-proUK over 120 minutes plus IV fixed-dose heparin or IV fixed-dose heparin alone. As opposed to intention to treat, this analysis was based on "treatment received" and includes 110 patients given r-proUK and 64 who did not receive any thrombolytic agent. The remaining six patients received out-of-protocol urokinase and were excluded from analysis. The authors analyzed centrally adjudicated ICH with associated neurologic deterioration (increase in NIH Stroke Scale [NIHSS] score of > or =4 points) within 36 hours of treatment initiation. RESULTS: Symptomatic ICH occurred in 12 of 110 patients (10.9%) treated with r-proUK and in two of 64 (3.1%) receiving heparin alone. ICH symptoms in r-proUK-treated patients occurred at a mean of 10.2 +/- 7.4 hours after the start of treatment. Mortality after symptomatic ICH was 83% (10/12 patients). Only blood glucose was significantly associated with symptomatic ICH in r-proUK-treated patients based on univariate analyses of 24 variables: patients with baseline glucose >200 mg/dL experienced a 36% risk of symptomatic ICH compared with 9% for those with < or =200 mg/dL (p = 0.022; relative risk, 4.2; 95% CI, 1.04 to 11.7). CONCLUSIONS: Symptomatic ICH after IA thrombolysis with r-proUK for acute ischemic stroke occurs early after treatment and has high mortality. The risk of symptomatic ICH may be increased in patients with a blood glucose >200 mg/dL at stroke onset.

Cladosporium trichoides cerebral phaeohyphomycosis in a liver transplant recipient. Report of a case.

Cerebral phaeohyphomycosis (also referred to as cerebral chromomycosis), one of the diseases caused by the dematiaceous (black) fungi, is most commonly caused by Cladosporium trichoides (referred to by some as Xylohypha bantiana) and is a rare disease, with 31 culture-proven cases reported to date. Although most cases have occurred in immunocompetent hosts, recent experimental evidence suggests that host immunosuppression may predispose patients to the disease. The authors report a case of fatal cerebral phaeohyphomycosis in a liver transplant patient, the first to occur in a transplant patient of any type, to the best of the authors' knowledge. This case provides support for the hypothesis that immunosuppressed patients may be at increased risk for development of this disease.

Task-induced asymmetry of the auditory evoked M100 neuromagnetic field elicited by speech sounds.

The auditory evoked neuromagnetic fields elicited by synthesized speech sounds (consonant-vowel syllables) were recorded in six subjects over the left and right temporal cortices using a 37-channel SQUID-based magnetometer. The latencies and amplitudes of the peaks of the M100 evoked responses were bilaterally symmetric for passively presented stimuli. In contrast, when subjects were asked to discriminate among the same syllabic stimuli, the amplitude of the M100 increased in the left and decreased in the right temporal cortices. Single equivalent current dipole modeling of the activity elicited by all stimulus-types localized to a well-circumscribed area in supratemporal auditory cortex. The results suggest that attentional modulation affects the two supratemporal cortices in a differential manner. Task-conditioned attention to speech sounds is reflected in lateralized supratemporal cortical responses possibly concordant with hemispheric language dominance.

Peri-threshold encoding of stimulus frequency and intensity in the M100 latency.

Recent work has suggested that, in addition to spatial tonotopy, pitch and timbre information may be encoded in the temporal activity of the auditory cortex. Specifically, the post-stimulus latency of the maximal cortical evoked neuromagnetic field (M100 or N1m) is a function of stimulus frequency. We investigated the additional effect of varying the stimulus intensity on the M100 response. A 37-channel biomagnetometer recorded neuromagnetic fields over the temporal lobe of healthy volunteers in response to monaurally presented tones. The frequency dependence of the M100 latency remained remarkably invariant even at low stimulus intensity. Thus, for peri-threshold stimuli, frequency information appears encoded in the temporal form of the evoked response.

A hemispherically asymmetrical MEG response to vowels.

Neuromagnetic fields elicited by vowels and tones were recorded and sources were modeled as single equivalent current dipoles (ECDs) in 1 ms steps 80-400 ms post stimulus. To vowels, the left hemisphere (LH) auditory cortex had nearly twice as many satisfactory ECD fits as the right hemisphere (RH). Tones did not evoke such asymmetry. In particular, in the late field (150-400 ms) the LH had more than twice as many ECDs as the RH, and the spatial distribution of LH sources was more clustered than in the RH. An asymmetrical, focal cortical mechanism for vowel processing was identified that intensified in later auditory processing stages. These data suggest that MEG might be used for non-invasive, language laterality determination with simple vowel-like stimuli.

Processing of vowels in supratemporal auditory cortex.

The auditory evoked neuromagnetic fields elicited by synthesized vowels of two different fundamental frequencies F0 were recorded in six subjects over the left and right temporal cortices using a 37-channel biomagnetometer. Single equivalent current dipole modeling of the fields elicited by all vowel types localized activity to a well-circumscribed area in supratemporal auditory cortex in both hemispheres. There were hemisphere asymmetries in the amplitude and latency of the M100 response. We also observed changes in M100 latency related to vowel type, but not to F0. There was no clear effect of vowel type or F0 on dipole localization for the M100, but a possible vowel type by latency interaction. These M100 data provide further evidence that vowels are processed independently of their pitch.

Learning transfer and neuronal plasticity in humans trained in tactile discrimination.

Adult humans were unilaterally trained in a tactile discrimination task of sequentially applied multi-finger stimuli. Magnetic source imaging (MSI) was performed before and after the training to evaluate use-dependent neuronal plasticity. All subjects showed fast improvements in performance and complete transfer of the learned task. MSI recordings revealed an unilateral decrease in current dipole strength in the somatosensory system contralateral to the trained hand. Attenuation of sensory evoked fields and a complete learning transfer indicate learning in associative and secondary cortices rather than perceptual plasticity operating on neuronal populations involved in early sensory processing. This findings are discussed with respect to an equivalent animal model and to learning specificity and generalization.

Mapping of the sensorimotor cortex: functional MR and magnetic source imaging.

PURPOSE: To assess the reliability and comparability of functional MR imaging and magnetic source imaging for mapping the somatosensory cortex. METHODS: Parallel studies were performed in eight volunteer subjects in whom both hemispheres were measured with the use of painless tactile stimulation of the tip of each index finger. Magnetic source imaging was performed using a 37-channel biomagnetometer; evoked magnetic fields were analyzed using the single-equivalent dipole representation to ascertain the neuronal source. Functional MR imaging was performed on a 1.5-T MR unit. Blocks of images during periods of rest and activation were acquired using gradient-echo echo-planar imaging. Correlation analysis identified pixels in which signal intensity correlated with the stimulus function. A subsequent requirement for spatial connectivity of activation was imposed to reduce the random occurrence of pixels satisfying the correlation criteria. RESULTS: Using temporal and spatial statistical criteria for activation, we found that functional MR imaging showed activation in 1 of 16 hemispheres. In three cases, this was accompanied by activity either frontally or ipsilateral to the stimulus. Magnetic source imaging showed parietal contralateral location in all 16 cases. Where successful localization was achieved with both methods, the separation between sources appeared to be between 1 and 4 cm. Functional MR imaging localizations tended to lie more superficially than the magnetic source imaging localizations. Performance of a simple motor task, rather than use of somatosensory stimulation, resulted in a cortical signal change detectable with a similar functional MR imaging approach in all cases, suggesting the more robust nature of this stimulus. CONCLUSIONS: Functional mapping of the somatosensory cortex can be achieved with functional MR imaging or magnetic source imaging. Functional MR imaging yields more spurious locations and fails to show localization more often. If neuronal signal propagation pathways are of interest, the temporal resolution of functional MR imaging alone may be inadequate. A combination of magnetic source imaging and functional MR imaging may allow improved sensitivity, fewer false-positive results, and high spatial and temporal resolution.

MR in partial epilepsy: value of high-resolution volumetric techniques.

PURPOSE: To assess the utility of high-resolution volumetric MR examinations with thin partition size for patients with simple partial epilepsies that were well located with electrical and clinical criteria. METHODS: Fifteen patients with normal standard MR findings were studied with three-dimensional Fourier transform volumetric MR examinations using thin (1 to 1.5 mm) partition size. Imaging was done in the coronal plane, then reformatted manually on an independent console with each gyrus analyzed in the planes parallel and perpendicular to its axis. RESULTS: Cortical abnormalities were detected in 8 of the 15 patients in the study. Surgical resection of the affected cortex in 2 patients showed polymicrogyria in one and dysplastic cortical organization in the other. CONCLUSION: In this preliminary study, 3-D Fourier transform volumetric MR examinations with thin partition size appeared to be useful in identifying cortical dysplasias in patients with localized simple partial epilepsies.

Imaging patterns of neonatal hypoglycemia.

PURPOSE: Our purpose was to report the patterns of injury observed in five patients who suffered brain damage consequent to neonatal hypoglycemia. METHODS: The imaging studies and clinical records of five patients with brain damage caused by neonatal hypoglycemia were reviewed retrospectively. Patterns of injury were compared with those described in the literature and those seen in neonatal hypoxic-ischemic injury. RESULTS: Diffuse cortical and subcortical white matter damage was seen, with the parietal and occipital lobes affected most severely. Globus pallidus injury was present in one patient who had the most severe cortical injury. CONCLUSION: We found a specific pattern of injury that correlates well with the sparse pathologic and imaging reports on neonatal hypoglycemia. We speculate that the patterns of damage are the result of regional hypoperfusion and excitatory toxicity with cell-type-specific injury.

Quantification and reproducibility of tracking cortical extent of activation by use of functional MR imaging and magnetoencephalography.

BACKGROUND AND PURPOSE: Functional MR imaging and magnetoencephalography are commonly used to study normal cortical sensory and cognitive processing as well as a variety of disease states. The usefulness of these techniques is dependent on the reproducibility and sensitivity to change of derived measures of brain function. The purpose of this study was to compare the efficacy of functional MR imaging and magnetoencephalography as measures of the extent of cortical activity in response to a graded stimulus. METHODS: Five participants underwent functional MR imaging and magnetoencephalography involving stimulation of one, two, three, and four digits of the left hand. Measurements of activation were repeated three times per participant. The cortical extent of activation was assessed for functional MR imaging by observing the number of "activated" pixels and the "amount of activation": the product of the number of activated pixels and the mean signal change. Activation was quantified for magnetoencephalography as the magnitude of the evoked magnetic field peak and as the strength of the modeled current source, Q. RESULTS: For functional MR imaging, the number of activated pixels tended to increase with the increasing number of stimulated digits. High intra- and interparticipant variability (66% and 85% variation, respectively) did not, however, allow statistical resolution of this trend. The amount of activation was similarly variable (interparticipant, 89%). Magnetoencephalography was more robust regarding quantification. The evoked field amplitude varied linearly with the number of digits stimulated; intra- and interparticipant variability was 18% and 41%, respectively, permitting resolution of significant differences between any combination of stimulated digits, except two versus three (P < .05). CONCLUSION: Although functional MR imaging and magnetoencephalography show measurable evoked responses with somatosensory stimulation, in this study, functional MR imaging did not permit robust quantification of increasing cortical areas of activation.

Radiologic-pathologic findings in raccoon roundworm (Baylisascaris procyonis) encephalitis.

A 13-month-old boy developed eosinophilic meningoencephalitis, retinitis, and a protracted encephalopathy with severe residual deficits. The initial MR examination revealed diffuse periventricular white matter disease, and follow-up images showed atrophy. Brain biopsy, serology, and epidemiologic studies lead to the diagnosis of Baylisascaris procyonis infection, a parasitic disease contracted through exposure to soil contaminated by the eggs of a common raccoon intestinal roundworm. The pathologic, epidemiologic, and imaging features of this disease are herein reviewed.

Functional activity within brain tumors: a magnetic source imaging study.

OBJECTIVE: To determine whether low-grade gliomas contain functional cortical activity more often than high-grade gliomas within radiologically defined abnormal tissue. METHODS: Patients with intra-axial cerebral lesions located in the vicinity of eloquent brain cortex preoperatively underwent magnetic source imaging. A dual 37-channel biomagnetometer was used to perform the imaging. Evoked magnetic fields were analyzed using the single-equivalent dipole representation to ascertain the neuronal source. Stimuli included painless tactile somatosensory stimulation of fingers, toes, and lips and auditory presentation of pure sinusoidal tones. RESULTS: A retrospective analysis of 106 nonconsecutively treated patients, who had undergone preoperative magnetic source imaging between February 1996 and December 1999, revealed that 24.5% of the patients had been at risk for neurological deficits, because functionally active tissue was located within or at the border of the tumor. Functional activity was found within the radiologically defined lesion in 18% of Grade 2 tumors, in 17% of Grade 3 tumors, and in 8% of Grade 4 tumors. CONCLUSION: The results confirm that, regardless of tumor grade, intra-axial brain tumors may involve or directly border on functional cortex. The degree of involvement of functionally viable cortex appeared greater for low-grade tumors than for high-grade lesions. On the other hand, high-grade lesions were more likely to be associated with functional cortex at their margins or within peritumoral edema. To safely maximize tumor resection, preoperative functional imaging and intraoperative electrophysiological mapping of the cerebral cortex and the white matter tracts are deemed necessary.