Post-traumatic osteoarthritis progression is diminished by early mechanical unloading and anti-inflammatory treatment in mice.

OBJECTIVE: Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease initiated by injury. Early phase (0-7 days) treatments often include rest (unloading) and anti-inflammatory medications, but how those early interventions impact PTOA progression is unknown. We hypothesized that early unloading and anti-inflammatory treatment would diminish joint inflammation and slow PTOA progression. DESIGN: Mice were injured with non-invasive ACL rupture followed by hindlimb unloading (HLU) or normal cage activity (ground control: GC) for 7 days, after which all mice were allowed normal cage activity. HLU and GC mice were treated with daily celecoxib (CXB; 10 mg/kg IP) or vehicle. Protease activity was evaluated using in vivo fluorescence imaging, osteophyte formation and epiphyseal trabecular bone were quantified using micro-computed tomography, and synovitis and articular cartilage were evaluated using whole-joint histology at 7, 14, 21, and 28 days post-injury. RESULTS: HLU significantly reduced protease activity (-22-30% compared to GC) and synovitis (-24-50% relative to GC) at day 7 post-injury (during unloading), but these differences were not maintained at later timepoints. Similarly, trabecular bone volume was partially preserved in HLU mice at during unloading (-14-15% BV/TV for HLU mice, -21-22% for GC mice relative to uninjured), but these differences were not maintained during reloading. Osteophyte volume was reduced by both HLU and CXB, but there was not an additive effect of these treatments (HLU: -46%, CXB: -30%, HLU + CXB: -35% relative to vehicle GC at day 28). CONCLUSIONS: These data suggest that early unloading following joint injury can reduce inflammation and potentially slow PTOA progression.

Stroke mismatch volume with the use of ABC/2 is equivalent to planimetric stroke mismatch volume.

BACKGROUND AND PURPOSE: In the clinical setting, there is a need to perform mismatch measurements quickly and easily on the MR imaging scanner to determine the specific amount of treatable penumbra. The objective of this study was to quantify the agreement of the ABC/2 method with the established planimetric method. MATERIALS AND METHODS: Patients (n = 193) were selected from the NINDS Natural History Stroke Registry if they 1) were treated with standard intravenous rtPA, 2) had a pretreatment MR imaging with evaluable DWI and PWI, and 3) had an acute ischemic stroke lesion. A rater placed the linear diameters to measure the largest DWI and MTT lesion areas in 3 perpendicular axes-A, B, and C-and then used the ABC/2 formula to calculate lesion volumes. A separate rater measured the planimetric volumes. Multiple mismatch thresholds were used, including MTT volume - DWI volume ≥50 mL versus ≥60 mL and (MTT volume - DWI volume)/MTT volume ≥20% versus MTT/DWI = 1.8. RESULTS: Compared with the planimetric method, the ABC/2 method had high sensitivity (0.91), specificity (0.90), accuracy (0.91), PPV (0.90), and NPV (0.91) to quantify mismatch by use of the ≥50 mL definition. The Spearman correlation coefficients were 0.846 and 0.876, respectively, for the DWI and MTT measurements. The inter-rater Bland-Altman plots demonstrated 95%, 95%, and 97% agreement for the DWI, MTT, and mismatch measurements. CONCLUSIONS: The ABC/2 method is highly reliable and accurate for quantifying the specific amount of MR imaging-determined mismatch and therefore is a potential tool to quickly calculate a treatable mismatch pattern.

MRI guides diagnostic approach for ischaemic stroke.

BACKGROUND AND AIM: Identification of ischaemic stroke subtype currently relies on clinical evaluation supported by various diagnostic studies. The authors sought to determine whether specific diffusion-weighted MRI (DWI) patterns could reliably guide the subsequent work-up for patients presenting with acute ischaemic stroke symptoms. METHODS: 273 consecutive patients with acute ischaemic stroke symptoms were enrolled in this prospective, observational, single-centre NIH-sponsored study. Electrocardiogram, non-contrast head CT, brain MRI, head and neck magnetic resonance angiography (MRA) and transoesophageal echocardiography were performed in this prespecified order. Stroke neurologists determined TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification on admission and on discharge. Initial TOAST stroke subtypes were compared with the final TOAST subtype. If the final subtype differed from the initial assessment, the diagnostic test deemed the principal determinant of change was recorded. These principal determinants of change were compared between a CT-based and an MRI-based classification schema. RESULTS: Among patients with a thromboembolic DWI pattern, transoesophageal echocardiography was the principal determinant of diagnostic change in 8.8% versus 0% for the small vessel group and 1.7% for the other group (p<0.01). Among patients with the combination of a thromboembolic pattern on MRI and a negative cervical MRA, transoesophageal echocardiography led to a change in diagnosis in 12.1%. There was no significant difference between groups using a CT-based scheme. CONCLUSIONS: DWI patterns appear to predict stroke aetiologies better than conventional methods. The study data suggest an MRI-based diagnostic algorithm that can potentially obviate the need for echocardiography in one-third of stroke patients and may limit the number of secondary extracranial vascular imaging studies to approximately 10%.

Distal hyperintense vessels on FLAIR: an MRI marker for collateral circulation in acute stroke?

BACKGROUND: Hyperintense vessels (HV) on fluid-attenuated inversion recovery imaging are frequently observed in acute ischemic stroke patients. However, the exact mechanism and clinical implications of this sign have not yet been clearly defined. The features of HV and its relevance to other imaging factors are presented here. METHODS: Prominence and location of HV were documented in 52 consecutive patients with middle cerebral artery (MCA) territory infarction, before treatment with IV recombinant tissue plasminogen activator. Pretreatment ischemic lesion volume, perfusion lesion volume, and vessel occlusion were determined in addition to recanalization status and ischemic lesion volume on follow-up imaging. NIH Stroke Scale (NIHSS) was used as a measure of clinical severity. RESULTS: HV distal to arterial occlusion was observed in 73% of patients; more frequent in proximal than distal MCA occlusion patients. Among the 38 patients with proximal MCA occlusion, initial perfusion lesion volume was comparable among patients with different grade distal HV. However, patients with more prominent distal HV had smaller initial, 24-hour, and subacute ischemic lesion volumes and lower initial NIHSS scores. CONCLUSIONS: The presence of distal hyperintense vessels before thrombolytic treatment is associated with large diffusion-perfusion mismatch and smaller subacute ischemic lesion volumes in patients with proximal middle cerebral artery occlusion. DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; GRE = gradient recalled echo; HV = hyperintense vessels; MCA = middle cerebral artery; MRA = magnetic resonance angiography; MTT = mean transit time; NIHSS = NIH Stroke Scale; PWI = perfusion-weighted imaging; rt-PA = recombinant tissue plasminogen activator; TE = echo time; TI = inversion time; TIMI = thrombolysis in myocardial infarction; TR = repetition time.

Racial differences in microbleed prevalence in primary intracerebral hemorrhage.

BACKGROUND: Primary intracerebral hemorrhage is two to three times more common in many racial populations, including black patients. Previous studies have shown that microbleeds, identified on gradient echo MRI (GRE), are present in 50-80% of patients with primary ICH. The objective of this study was to compare, by race, the rates, risk factors, and topography of microbleeds in patients hospitalized for primary ICH. METHODS: Patients diagnosed with primary ICH at two metropolitan stroke centers were included. Clinical and neuroimaging data were recorded for each patient. Analyses were performed to compare baseline characteristics as well as imaging findings by race. RESULTS: A total of 87 patients met inclusion criteria (42 black subjects, 45 white subjects). The black cohort was younger (p < 0.001), and had a greater rate of hypertension (p = 0.001), but not other vascular risk factors. Microbleeds were more prevalent in the black population, with 74% of blacks having one or more microbleeds compared to 42% of whites (p = 0.005). The black population also tended to have a greater frequency of microbleeds in multiple territories than the white population (38% vs 22%, p = 0.106). When adjusting for age, hypertension, and alcohol use, race was an independent predictor of microbleeds (OR 3.308, 95% CI 1.144-9.571, p = 0.027). CONCLUSIONS: These pilot data suggest that significant racial differences exist in the frequency and topography of microbleeds in patients with primary ICH. Microbleeds may be an important emerging imaging biomarker with the potential to provide insights into ICH pathophysiology, prognosis, and disease progression, as well as possible therapeutic strategies, particularly in medically underserved populations.

Efficacy of IV tissue plasminogen activator in acute stroke: does stroke subtype really matter?

BACKGROUND: The National Institute of Neurological Disorders and Stroke (NINDS) trial reported that stroke subtype (e.g., large-artery atherothrombosis, cardioembolism, and lacunae) does not affect response to IV thrombolytic treatment. However, these conclusions were based upon stroke subtypes determined prior to extensive diagnostic evaluation. Because such initial diagnoses are frequently inaccurate, the efficacy of IV recombinant tissue plasminogen activator (rt-PA) based upon verified specific stroke subtypes remains uncertain. METHODS: The records of consecutive acute stroke patients treated with IV rt-PA at two regional stroke centers were retrospectively reviewed. The final stroke subtype after complete diagnostic evaluation was determined. The relationship between final stroke subtype and response to thrombolytic therapy was then investigated and compared with the results reported in the NINDS trial. RESULTS: Ninety consecutive patients were studied. After adjusting for baseline NIH Stroke Scale scores, no significant difference in final outcome based on confirmed stroke mechanism was identified. CONCLUSIONS: These data are consistent with those of the NINDS trial that reported that the efficacy of IV thrombolysis within the 3-hour time window is similar between different stroke subtypes. Based upon these data, allocating treatment of stroke patients with IV rt-PA based upon presumed stroke mechanism may be unnecessary. Such testing may result in time delays that could compromise the efficacy of treatment.

Malnutrition-induced myopathy following Roux-en-Y gastric bypass.

A 42-year-old man developed a myopathy in the setting of malnutrition following Roux-en-Y gastric bypass for the treatment of morbid obesity. No specific vitamin or electrolyte deficiency was identified. Muscle biopsy revealed type II fiber atrophy. He recovered after the initiation of continuous enteral feeding. We suggest that malnutrition was the underlying cause of his myopathy.