Fatal cerebral air embolism from atrio-oesophageal fistula following cardiac ablation.

A young woman with Rogers syndrome (thiamine-responsive megaloblastic anaemia, diabetes mellitus and sensorineural deafness) presented with headache, recurrent supraventricular tachycardia and features of an upper gastrointestinal bleed, 1 month after radiofrequency cardiac ablation for supraventricular tachycardia. She deteriorated rapidly after endoscopy and subsequently died. Brain imaging during the acute deterioration showed diffuse intracranial air embolism and hypoxic-ischaemic injury. Postmortem examination showed an atrio-oesophageal fistula, a rare complication of cardiac ablation. Clinicians should suspect this condition in patients with acute neurological deterioration after cardiac ablation who have diffuse air embolism on imaging.

Intraoperative diagnosis of facial schwannomas: a multicenter summation of clinical experience, preoperative avoidance, and intraoperative management protocol.

OBJECTIVE: Preoperative differentiation of facial nerve schwannoma (FNS) from vestibular schwannoma (VS) can be challenging, and failure to differentiate between these two pathologies can result in potentially avoidable facial nerve injury. This study presents the combined experience of two high-volume centers in the management of intraoperatively diagnosed FNSs. The authors highlight clinical and imaging features that can distinguish FNS from VS and provide an algorithm to help manage intraoperatively diagnosed FNS. METHODS: Operative records of 1484 presumed sporadic VS resections between January 2012 and December 2021 were reviewed, and patients with intraoperatively diagnosed FNSs were identified. Clinical data and preoperative imaging were retrospectively reviewed for features suggestive of FNS, and factors associated with good postoperative facial nerve function (House-Brackmann [HB] grade ≤ 2) were identified. A preoperative imaging protocol for suspected VS and recommendations for surgical decision-making following an intraoperative FNS diagnosis were created. RESULTS: Nineteen patients (1.3%) with FNSs were identified. All patients had normal facial motor function preoperatively. In 12 patients (63%), preoperative imaging demonstrated no features suggestive of FNS, with the remainder showing subtle enhancement of the geniculate/labyrinthine facial segment, widening/erosion of the fallopian canal, or multiple tumor nodules in retrospect. Eleven (57.9%) of the 19 patients underwent a retrosigmoid craniotomy, and in the remaining patients, a translabyrinthine (n = 6) or transotic (n = 2) approach was used. Following FNS diagnosis, 6 (32%) of the tumors underwent gross-total resection (GTR) and cable nerve grafting, 6 (32%) underwent subtotal resection (STR) and bony decompression of the meatal facial nerve segment, and 7 (36%) underwent bony decompression only. All patients undergoing subtotal debulking or bony decompression exhibited normal postoperative facial function (HB grade I). At the last clinical follow-up, patients who underwent GTR with a facial nerve graft had HB grade III (3 of 6 patients) or IV facial function. Tumor recurrence/regrowth occurred in 3 patients (16%), all of whom had been treated with either bony decompression or STR. CONCLUSIONS: Intraoperative diagnosis of an FNS during a presumed VS resection is rare, but its incidence can be reduced further by maintaining a high index of suspicion and undertaking further imaging in patients with atypical clinical or imaging features. If an intraoperative diagnosis does occur, conservative surgical management with bony decompression of the facial nerve only is recommended, unless there is significant mass effect on surrounding structures.

Imaging of Petrous Apex Lesions.

The petrous apex may be affected by a range of lesions, commonly encountered as incidental and asymptomatic findings on imaging performed for other clinical reasons. Symptoms associated with petrous apex lesions commonly relate to mass effect and/or direct involvement of closely adjacent structures. Petrous apex lesions are optimally assessed using a combination of high-resolution CT and MRI of the skull base. Management of petrous apex lesions varies widely, reflecting the range of possible pathologies, with imaging playing a key role, including lesion characterization, surveillance, surgical planning, and oncological contouring.

Hyperdense artery sign, symptomatic infarct swelling and effect of alteplase in acute ischaemic stroke.

BACKGROUND: Alteplase improves functional outcomes of patients with acute ischaemic stroke, but its effects on symptomatic infarct swelling, an adverse complication of stroke and the influence of CT hyperdense artery sign (HAS) are unclear. This substudy of the Third International Stroke Trial aimed to investigate the association between HAS and symptomatic infarct swelling and effect of intravenous alteplase on this association. METHODS: We included stroke patients whose prerandomisation scan was non-contrast CT. Raters, masked to clinical information, assessed baseline (prerandomisation) and follow-up (24-48 hours postrandomisation) CT scans for HAS, defined as an intracranial artery appearing denser than contralateral arteries. Symptomatic infarct swelling was defined as clinically significant neurological deterioration ≤7 days after stroke with radiological evidence of midline shift, effacement of basal cisterns or uncal herniation. RESULTS: Among 2961 patients, HAS presence at baseline was associated with higher risk of symptomatic infarct swelling (OR 2.21; 95% CI 1.42 to 3.44). Alteplase increased the risk of swelling (OR 1.69; 95% CI 1.11 to 2.57), with no difference between patients with and those without baseline HAS (p=0.49). In patients with baseline HAS, alteplase reduced the proportion with HAS at follow-up (OR 0.67; 95% CI 0.50 to 0.91), where HAS disappearance was associated with reduced risk of swelling (OR 0.25, 95% CI 0.14 to 0.47). CONCLUSION: Although alteplase was associated with increased risk of symptomatic infarct swelling in patients with or without baseline HAS, it was also associated with accelerated clearance of HAS, which in return reduced swelling, providing further mechanistic insights to underpin the benefits of alteplase.

Effect of IV alteplase on the ischemic brain lesion at 24-48 hours after ischemic stroke.

OBJECTIVE: To determine whether alteplase alters the development of ischemic lesions on brain imaging after stroke. METHODS: The Third International Stroke Trial (IST-3) was a randomized controlled trial of IV alteplase for ischemic stroke. We assessed CT or brain MRI at baseline (pretreatment) and 24 to 48 hours posttreatment for acute lesion visibility, extent, and swelling, masked to all other data. We analyzed associations between treatment allocation, change in brain tissue appearances between baseline and follow-up imaging, and 6-month functional outcome in IST-3. We performed a meta-analysis of randomized trials of alteplase vs control with pre- and postrandomization imaging. RESULTS: Of 3,035 patients recruited in IST-3, 2,916 had baseline and follow-up brain imaging. Progression in either lesion extent or swelling independently predicted poorer 6-month outcome (adjusted odds ratio [OR] = 0.92, 95% confidence interval [CI] 0.88-0.96, p < 0.001; OR = 0.73, 95% CI 0.66-0.79, p < 0.001, respectively). Patients allocated alteplase were less likely than controls to develop increased lesion visibility at follow-up (OR = 0.77, 95% CI 0.67-0.89, p < 0.001), but there was no evidence that alteplase reduced progression of lesion extent or swelling. In meta-analysis of 6 trials including IST-3 (n = 4,757), allocation to alteplase was associated with a reduction in ischemic lesion extent on follow-up imaging (OR = 0.85, 95% CI 0.76-0.95, p = 0.004). CONCLUSION: Alteplase was associated with reduced short-term progression in lesion visibility. In meta-analysis, alteplase reduced lesion extent. These findings may indicate that alteplase improves functional outcome by reducing tissue damage. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that IV alteplase impedes the progression of ischemic brain lesions on imaging after stroke.

Enzyme replacement therapy and white matter hyperintensity progression in Fabry disease.

OBJECTIVE: To explore the association between enzyme replacement therapy (ERT), clinical characteristics, and the rate of progression of white matter hyperintensities (WMH) in patients with Fabry disease (FD). METHODS: Patients with a confirmed diagnosis of FD, aged 18 years or older, participating in an existing FD observational study (NCT00196742), with at least 2 serial MRI brain scans at least 2 years apart for the period between December 2006 and August 2016 were included in this cohort study. Total WMH volume was estimated for each image using a semiautomated procedure. We performed linear regression to calculate the primary outcome measure of WMH change rate for each participant. Associations between ERT, clinical characteristics, and the primary outcome were explored using multiple linear regression. RESULTS: Eight hundred sixty-three MRI time points were analyzed for the 149 included participants. Age (p < 0.0005; increasing age associated with faster WMH progression), total cholesterol (p = 0.03; increasing total cholesterol associated with slower WMH progression), and a history of peripheral pain (p = 0.02; peripheral pain associated with faster WMH progression) were independently associated with WMH change rate in the primary analysis. We did not find an association between "ERT at any point between baseline and final MRI" and WMH change rate (p = 0.22). CONCLUSION: In a large cohort of patients with FD, we did not find an association between ERT and WMH progression, while higher total cholesterol was associated with slower WMH progression. Further research is needed into the pathogenesis and treatment of cerebrovascular disease in this rare condition.

Non-pharmacological therapies for inflammatory bowel disease: Recommendations for self-care and physician guidance.

We performed a scoping review on sought-after complementary therapies for patients with inflammatory bowel disease (IBD), specifically diet, physical activity and exercise (PA/E), and psychotherapy. We aim to update patients with IBD on therapies for self-care and provide physicians with guidance on how to direct their patients for the management of IBD. A search of MEDLINE, EMBASE, and PUBMED was completed in Sept 2016. Studies on diet, PA/E, or psychotherapy in patients with IBD were included. Medical Subject Heading terms and Boolean operators were used. The search was limited to full-text English articles describing an adult population. This review included 67 studies: Diet (n = 19); PA/E (n = 19); and psychotherapy (n = 29). We have made the following recommendations: (1) Diet: Consumption of diets rich in vegetables, fruit and soluble fiber may be beneficial in IBD. A trial of a low FODMAP diet can be considered in those patients with functional gastrointestinal symptoms. Restrictive diets are lacking in evidence and should be avoided; (2) PA/E: Regular low-moderate intensity activity, including cardiovascular and resistance exercise, has been shown to improve quality of life (QOL) and may improve inflammation; and (3) psychotherapy: Therapies such as cognitive-behavioural interventions, mindfulness, hypnosis, and stress management have been shown to improve QOL, but evidence is limited on their impact on anxiety, depression, and disease activity. Overall, these complementary therapies are promising and should be used to treat patients with IBD from a more holistic perspective.

Blood pressure variability and leukoaraiosis in acute ischemic stroke.

Higher blood pressure, blood pressure variability, and leukoaraiosis are risk factors for early adverse events and poor functional outcome after ischemic stroke, but prior studies differed on whether leukoaraiosis was associated with blood pressure variability, including in ischemic stroke. In the Third International Stroke Trial, blood pressure was measured in the acute phase of ischemic stroke immediately prior to randomization, and at 0.5, 1, and 24 h after randomization. Masked neuroradiologists rated index infarct, leukoaraiosis, and atrophy on CT using validated methods. We characterized blood pressure variation by coefficient of variance and three other standard methods. We measured associations between blood pressure, blood pressure variability, and leukoaraiosis using generalized estimating equations, adjusting for age, and a number of covariates related to treatment and stroke type/severity. Among 3017 patients, mean (±SD) systolic and diastolic blood pressure decreased from 155(±24)/82(±15) mmHg pre-randomization to 146(±23)/78(±14) mmHg 24 h later ( P < 0.005). Mean within-subject coefficient of variance was 0.09 ± 0.05 for systolic and 0.11 ± 0.06 for diastolic blood pressure. Patients with most leukoaraiosis were older and had higher blood pressure than those with least ( P < 0.0001). Although statistically significant in simple pairwise comparisons, no measures of blood pressure variability were associated with leukoaraiosis when adjusting for confounding variables ( P > 0.05), e.g. age. Our results suggest that blood pressure variability is not a potential mechanism to explain the association between leukoaraiosis and poor outcome after acute stroke.

Effect of alteplase on the CT hyperdense artery sign and outcome after ischemic stroke.

OBJECTIVE: To investigate whether the location and extent of the CT hyperdense artery sign (HAS) at presentation affects response to IV alteplase in the randomized controlled Third International Stroke Trial (IST-3). METHODS: All prerandomization and follow-up (24-48 hours) CT brain scans in IST-3 were assessed for HAS presence, location, and extent by masked raters. We assessed whether HAS grew, persisted, shrank, or disappeared at follow-up, the association with 6-month functional outcome, and effect of alteplase. IST-3 is registered (ISRCTN25765518). RESULTS: HAS presence (vs absence) independently predicted poor 6-month outcome (increased Oxford Handicap Scale [OHS]) on adjusted ordinal regression analysis (odds ratio [OR] 0.66, p < 0.001). Outcome was worse in patients with more (vs less) extensive HAS (OR 0.61, p = 0.027) but not in proximal (vs distal) HAS (p = 0.420). Increasing age was associated with more HAS growth at follow-up (OR 1.01, p = 0.013). Treatment with alteplase increased HAS shrinkage/disappearance at follow-up (OR 0.77, p = 0.006). There was no significant difference in HAS shrinkage with alteplase in proximal (vs distal) or more (vs less) extensive HAS (p = 0.516 and p = 0.580, respectively). There was no interaction between presence vs absence of HAS and benefit of alteplase on 6-month OHS (p = 0.167). CONCLUSIONS: IV alteplase promotes measurable reduction in HAS regardless of HAS location or extent. Alteplase increased independence at 6 months in patients with and without HAS. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients within 6 hours of ischemic stroke with a CT hyperdense artery sign, IV alteplase reduced intra-arterial hyperdense thrombus.

Calcifying pseudoneoplasm of the neuraxis (CaPNoN): an unusual cause of third nerve palsy in a teenager.

An 18-year-old part-time teacher presented with headache and diplopia. Physical examination showed partial left oculomotor palsy. Neurology examination was otherwise unremarkable. Cross-sectional imaging was arranged for investigation of third nerve palsy. On CT scan, the lesion was calcified, and on MRI, hypointense on T 1 and T 2 weightedimages with thin rim enhancement, resembling an atypical meningioma. CT angiogram showed no vascular connection. Following worsening diplopia and a slight increase in lesion size on follow-up MRI, the patient was re-reviewed in our regional skull base multidisciplinary team meeting, where a decision for excision was made. Pre-operatively, the absence of a vascular connection was confirmed on catheter angiogram. Histopathological examination demonstrated features typical of calcified pseudoneoplasm of the neuraxis, with extensive metaplastic calcification with stroma containing variable fibrovascular tissue and focal inflammatory cell infiltrates, spindle and epithelioid cells, and psammoma bodies at the rim of the lesion. Following surgery, the patient had persisting diplopia. He remains under clinical review. As surgical resection is considered curative, no further imaging follow-up is planned.

Cerebral perivascular spaces visible on magnetic resonance imaging: development of a qualitative rating scale and its observer reliability.

BACKGROUND: Perivascular spaces (PVS) are an important component of cerebral small vessel disease (SVD), several inflammatory disorders, hypertension and blood-brain barrier breakdown, but are difficult to quantify. A recent international collaboration of SVD experts has highlighted the need for a robust, easy-to-use PVS rating scale for the effective investigation of the diagnostic and prognostic significance of PVS. The purpose of the current study was to develop and extend existing PVS scales to provide a more comprehensive scale for the measurement of PVS in the basal ganglia, centrum semiovale and midbrain, and to test its intra- and inter-rater agreement, assessing reasons for discrepancy. METHODS: We reviewed previously published PVS scales, including site of PVS assessed, rating method, and size and morphological criteria. Retaining key features, we devised a more comprehensive scale in order to improve the reliability of PVS rating. Two neuroradiologists tested the new scale in MRI brain scans of 60 patients from two studies (stroke, ageing population), chosen to represent a full range of PVS, and demonstrating concomitant features of SVD such as lacunes and white matter hyperintensities. We rated basal ganglia, centrum semiovale, and midbrain PVS. Basal ganglia and centrum semiovale PVS were rated 0 (none), 1 (1-10), 2 (11-20), 3 (21-40) and 4 (>40), and midbrain PVS were rated 0 (none visible) or 1 (visible). We calculated kappa statistics for rating, assessed consistency in use of PVS categories (Bhapkar test) and reviewed sources of discrepancy. RESULTS: Intra- and inter-rater kappa statistics were highest for basal ganglia PVS (range 0.76-0.87 and 0.8-0.9, respectively) than for centrum semiovale PVS (range 0.68-0.75 and 0.61-0.8, respectively) or midbrain PVS (inter-rater range 0.51-0.52). Inter-rater consistency was better for basal ganglia compared to centrum semiovale PVS (Bhapkar statistic 2.49-3.72, compared to 6.79-21.08, respectively). Most inter-rater disagreements were due to very faint PVS, coexisting extensive white matter hyperintensities (WMH) or the presence of lacunes. CONCLUSIONS: We developed a more inclusive and robust visual PVS rating scale allowing rating of all grades of PVS severity on structural brain imaging. The revised PVS rating scale has good observer reliability for basal ganglia and centrum semiovale PVS, best for basal ganglia PVS, and moderate reliability for midbrain PVS. Agreement is influenced by PVS severity and the presence of background features of SVD. The current scale can be used in further studies to assess the clinical implications of PVS.

Clinical and radiological guidance in managing facial nerve schwannomas.

OBJECTIVE: To present a review of all patients diagnosed with a facial nerve schwannoma (FNS) managed in our center over almost two decades, and suggest guidelines for their classification and management. STUDY DESIGN: Retrospective case review SETTING: Tertiary referral center PATIENTS: Twenty-eight patients with a facial nerve schwannoma INTERVENTION: Conservative or surgical management depending on clinical and radiological features MAIN OUTCOME MEASURE: Patient demographics, site of tumor, and clinical symptoms, including facial nerve function (House-Brackmann score) at baseline and follow-up. In those managed surgically, operative approach and surgical outcomes were also recorded. RESULTS: Of 28 patients, 16 were male. Mean age at presentation was 46 years. The majority presented with either facial weakness or hearing loss. The internal auditory canal segment of the facial nerve was the most commonly affected (19/28, 68%). Multi-segmental lesions were found in almost half (46%) of patients. Facial weakness was most commonly associated with involvement of the labyrinthine segment (89%). Overall, 16 (57%) patients were managed surgically. CONCLUSION: FNS may be difficult to distinguish on both clinical and imaging grounds from other cerebellopontine pathologies on the basis of audiovestibular symptoms alone. The presence of facial weakness in combination with imaging findings suggestive of FNS is highly suggestive for FNS. In patients with brainstem compression, rapid tumor growth, or House-Brackmann greater than 4, we suggest a surgical approach based on preoperative audiovestibular status, helping optimize long-term facial function and minimize morbidity. Facial nerve reanimation at the time of primary surgery is preferred.

Enlarged perivascular spaces and cerebral small vessel disease.

BACKGROUND AND AIMS: Enlarged perivascular spaces (also known as Virchow-Robin spaces) on T2-weighted brain magnetic resonance imaging are common, but their etiology, and specificity to small vessel as opposed to general cerebrovascular disease or ageing, is unclear. We tested the association between enlarged perivascular spaces and ischemic stroke subtype, other markers of small vessel disease, and common vascular risk factors. METHODS: We prospectively recruited patients with acute stroke, diagnosed and subtyped by a stroke physician using clinical features and brain magnetic resonance imaging. A neuroradiologist rated basal ganglia and centrum semiovale enlarged perivascular spaces on a five-point scale, white matter lesions, recent and old infarcts, and cerebral atrophy. We assessed associations between basal ganglia-, centrum semiovale- and total (combined basal ganglia and centrum semiovale) enlarged perivascular spaces, stroke subtype, white matter lesions, atrophy, and vascular risk factors. RESULTS: Among 298 patients (mean age 68 years), after adjusting for vascular risk factors and white matter lesions, basal ganglia-enlarged perivascular spaces were associated with increasing age (P = 0.001), centrum semiovale-enlarged perivascular spaces (P < 0.001), cerebral atrophy (P = 0.03), and lacunar stroke subtype (P = 0.04). Centrum semiovale-enlarged perivascular spaces were associated mainly with basal ganglia-enlarged perivascular spaces. Total enlarged perivascular spaces were associated with increasing age (P = 0.01), deep white matter lesions (P = 0.005), and previous stroke (P = 0.006). CONCLUSIONS: Enlarged perivascular spaces are associated with age, lacunar stroke subtype and white matter lesions and should be considered as another magnetic resonance imaging marker of cerebral small vessel disease. Further evaluation of enlarged perivascular spaces in studies of ageing, stroke, and dementia is needed to determine their pathophysiological importance.

Management of cerebellopontine angle lipomas: need for long-term radiologic surveillance?

OBJECTIVE: To date, only a very limited number of lipomas of the cerebellopontine angle (CPA) have been reported. Our objective was to examine clinical and radiologic features of CPA lipomas and determine the most appropriate management plan. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Patients with CPA lipomas were identified through the skull base multidisciplinary meeting database. INTERVENTIONS: Radiologic surveillance and clinical assessment. MAIN OUTCOME MEASURES: Tumor growth, assessed through radiologic measurements on serial magnetic resonance imaging, demographics, presenting symptoms, and any correlation between weight gain and lipoma growth were among the examined factors. RESULTS: Of the 15 patients with CPA lipomas, six were female and nine were male, with an average age at presentation of 50.2 years (range, 31.7-76.4 yr) and an average follow-up time of 51.7 months (range, 6-216 mo). The lipomas were unilateral in all cases, nine on the right (60%) and six on the left (40%) side. None of the lipomas increased in size. All patients were treated conservatively. Sensorineural hearing loss was the main presenting symptom (80%) followed by tinnitus (46.7%) and vertigo (20%). None of the patients suffered from facial nerve dysfunction. There was no correlation between weight gain and tumor growth. CONCLUSION: CPA lipomas can be diagnosed accurately with appropriate magnetic resonance imaging techniques and be managed conservatively with safety. Cochleovestibular are the most common presenting symptoms, whereas facial nerve involvement is rare. CPA lipomas do not tend to grow and can be monitored on a less regular basis.

Lack of association of white matter lesions with ipsilateral carotid artery stenosis.

BACKGROUND: White matter lesions (WML) are commonly seen on brain MRI and are generally considered a marker of tissue damage from cerebral small vessel disease. WML are associated with increasing age and vascular risk factors, but their precise cause is unknown. A role for carotid artery atherothromboemboli has been suggested. If this is the case, more WML would be expected ipsilateral to increasing degrees of carotid stenosis. METHODS: We recruited patients with ischaemic stroke from two large, separate prospective stroke studies, assessed with brain MRI and carotid Doppler ultrasound. We scored hemispheric WML visually in periventricular and deep locations. We assessed the association between carotid stenosis asymmetry and WML asymmetry, and vice versa. Further, we assessed the association between carotid stenosis and ipsilateral WML, before and after adjusting for vascular risk factors, and tested associations between ipsilateral and contralateral stenoses and WML. RESULTS: We recruited 247 (Study 1) and 253 (Study 2) patients. In Study 1 and Study 2, 36 (15%) and 29 (11%) patients had ≥50% carotid stenosis, and 27 (11%) and 15 (6%) had ≥70% stenosis, respectively. Carotid stenosis was asymmetric in 28 (11%) and 26 (10%) patients and WML were asymmetric in 22 (9%) and 11 (4%) patients in Study 1 and Study 2, respectively. We found no association between carotid stenosis and ipsilateral WML score, before or after adjusting for vascular risk factors or sidedness, but WML were strongly associated with increasing age (p < 0.001). CONCLUSION: In two large cohorts of ischaemic stroke patients, we found no association between carotid stenosis and ipsi- or contralateral WML. There is now substantial evidence that atherothromboemboli are unlikely to cause most WML or other forms of cerebral small vessel lesions. Future studies should focus on determining what causes the intrinsic small vessel pathological changes that appear to underlie most WML.

Wide variation in definition, detection, and description of lacunar lesions on imaging.

BACKGROUND AND PURPOSE: Variation in the definition of lacunar lesions on imaging and difficulties in their detection may be hampering lacunar stroke research. We assessed literature definitions of imaging lacunar lesions and the definitions and detection of lacunar lesions among small-vessel disease researchers. METHODS: We assessed definitions of imaging lacunar lesion in 50 randomly selected articles from 3 stroke-related journals and an online survey of small-vessel disease researchers. In the literature review, we assessed clinical/imaging definitions of lacunar stroke. In the survey, we assessed lacunar lesion detection, effects of lesion appearance, background white matter lesions, and provision of relevant data. RESULTS: Among 50 articles, imaging definitions were varied and often limited; size was stated in 21 of 43 (49%) studies of acute and in 9 of 20 (45%) studies of old lesions and site in 18 (42%) and 4 (20%), respectively. Clinical definitions also varied, and images were read mostly by nonradiologists. Among 56 survey respondents, multiple descriptions were used for recent and old, symptomatic and asymptomatic, lesions on imaging. Most agreed on definitions for site (98%) and "old lacunar infarct" (61%) size. Cavitated (vs noncavitated) lesions were usually identified as lacunar lesions; with increasing white matter lesions, however, noncavitated lesions were very unlikely to be identified, even with prior imaging available (7.8%). CONCLUSIONS: Imaging definitions of lacunar lesions vary widely, in part due to variation in lesion detection and classification. A consensus for imaging definitions of small-vessel disease features would be helpful.

Associations of clinical stroke misclassification ('clinical-imaging dissociation') in acute ischemic stroke.

BACKGROUND: Up to 20% of lacunar infarcts are clinically misdiagnosed as cortical infarcts and vice versa. The reasons for this discrepancy are unclear. We assessed clinical and imaging features which might explain this 'clinical-imaging dissociation' (C-ID). METHODS: Patients with an acute stroke syndrome (cortical or lacunar) underwent magnetic resonance imaging including diffusion-weighted imaging (DWI). We recorded DWI-positive infarcts and proximity to cortex for small subcortical infarcts. We examined factors associated with C-ID. RESULTS: 137 patients with a mild cortical or lacunar syndrome had an acute ischemic lesion on DWI. Of these, 21/93 (23%) with a cortical syndrome had an acute lacunar infarct and 7/44 (16%) with a lacunar syndrome had an acute cortical infarct. From 72 patients with an acute lacunar infarct on DWI, lesion proximity to cortex (odds ratio (OR) 14.5, 95% confidence interval (CI) 1.61-130.1), left hemisphere location (OR 8.95, 95% CI 1.23-64.99) and diabetes (OR 17.1, 95% CI 1.49-196.16) predicted C-ID. On multivariate analysis of all 137 patients, C-ID was associated with diabetes (OR 7.12, 95% CI 1.86-27.2). CONCLUSIONS: C-ID occurs in a fifth of patients with mild stroke. Lacunar infarcts lying close to cortex are more likely to cause cortical symptoms. Diabetes is associated with any clinical-imaging mismatch. Stroke misclassification which can arise with clinical classification alone should be minimized in research by verification with high-sensitivity imaging.

Counting cavitating lacunes underestimates the burden of lacunar infarction.

BACKGROUND AND PURPOSE: On brain imaging, lacunes, or cerebrospinal fluid-containing cavities, are common and are often counted in epidemiological studies as old lacunar infarcts. The proportion of symptomatic lacunar infarcts that progress to lacunes is unknown. Noncavitating lacunar infarcts may continue to resemble white matter lesions. METHODS: We identified patients with acute lacunar stroke, with or without an acute lacunar infarct on computed tomography or MRI, who had follow-up imaging. A neuroradiologist classified lacunar infarcts progressing to definite or possible cavities on follow-up imaging. We tested associations between cavitation and patient-related, stroke-related, and imaging-related features, including other features of small vessel disease. RESULTS: Among 90 patients (mean age 67 years), any cavitation was present on follow-up imaging in 25 (28%), and definite cavitation in 18 (20%). Definite cavitation was associated with increasing time to follow-up imaging (median 228 days, range 54 to 1722, versus no cavitation 72 days, range 6 to 1440; P=0.0003) and deep cerebral atrophy (P=0.03) but not with age, stroke severity, larger initial infarct size, or other features of small vessel disease. Hypertension and diabetes were negatively associated with cavitation (P=0.01 and 0.02, respectively). CONCLUSIONS: Definite cavitation occurs in one fifth of symptomatic lacunar ischemic strokes, implying that most continue to resemble white matter lesions. Epidemiology and pathophysiology studies of lacunar stroke, which have only counted lacunes as lacunar infarcts, may have substantially underestimated by as much as 5 times the true burden of lacunar stroke disease.