Irwin Walot

Cerebral metabolite abnormalities correlate with clinical severity of HIV-1 cognitive motor complex

Objective: To investigate the relation between biochemical alterations and disease severity in HIV–cognitive motor complex (HIV–CMC). Background: HIV–CMC encompasses both the milder form (HIV–minor cognitive motor disorder [HIV–MCMD]) and the more severe form (HIV–dementia). There is no validated marker to monitor disease severity noninvasively. Methods: A total of 54 patients with HIV–CMC (20 with HIV–MCMD, 34 with HIV–dementia) and 29 seronegative healthy volunteers were evaluated for cerebral metabolite abnormalities using proton (1H) MRS in the frontal cortex, frontal white matter, and basal ganglia. Results: The three subject groups showed different concentrations of myoinositol (MI; p = 0.0005) and choline-containing compounds (CHO; p = 0.004) in the frontal white matter. HIV–dementia patients had metabolite changes in all three brain regions whereas HIV–MCMD patients had abnormalities in the frontal white matter only. HIV–CMC patients had elevated MI (p < 0.0001) and CHO (p = 0.004) levels with increasing AIDS dementia complex stage, and N-acetyl compounds (NA) were decreased only in moderate to severe stages of dementia. Furthermore, CD4 count and CSF viral load, but not plasma viral load, showed significant effects on cerebral metabolite concentrations, which in turn showed significant effects on the HIV–dementia scale. Conclusions: In early stages of HIV–CMC, frontal white matter showed evidence of glial proliferation (with elevated MI and CHO levels) and cell membrane injury (with increased CHO levels), but no significant neuronal injury (with normal NA concentrations). HIV–MCMD and HIV–dementia patients have different neurochemical abnormalities. Because these biochemical alterations are related to clinical disease severity, they may be useful surrogate markers for noninvasive quantitative assessment of brain injury in patients with HIV–CMC.

Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild HIV dementia

Objective: To determine whether cerebral metabolite abnormalities normalize with highly active antiretroviral therapy (HAART). Background: Patients with HIV–cognitive motor complex (HIV-CMC) show cerebral metabolite abnormalities in the early stages of dementia. Methods: Sixteen patients with HIV-CMC were evaluated before and after HAART, and compared with 15 HIV-negative healthy volunteers. Cerebral metabolite ratios and concentrations in the frontal lobe and basal ganglia were measured using proton MRS (1H MRS). Results: In 14 of 16 patients who tolerated HAART, CD4 count increased by 133 ± 101 cells/mm3 (p = 0.0003), HIV Dementia Scale score increased by 1.8 ± 2.4 points (p = 0.02), and AIDS dementia complex (ADC) stage decreased by 0.54 ± 0.54 points (p = 0.003). The initially increased choline/creatine (CHO/CR) reversed in the midfrontal cortex (−8.0%; p = 0.02) and in the basal ganglia (−14.7%; p = 0.01). The initially elevated myoinositol (MI)/CR and myoinositol concentration [MI] in the basal ganglia also decreased ( MI/CR: −14.1%; p = 0.005; [MI]: 11.8%; p = 0.02), along with normalization of [MI] in the frontal white matter (11.4%; p = 0.05). Furthermore, the change in [MI] in the frontal white matter correlated with the change in CD4 count (r = −0.67, p = 0.03) and with the change in ADC stage (p = 0.04). Conclusions: HAART improves HIV-CMC in addition to systemic measures of HIV infection. 1H MRS detects improvement of brain injury measured by cerebral metabolites, particularly the glial marker [MI], in patients with early HIV-CMC after HAART. In addition, the degree of improvement in clinical severity of HIV-CMC is related to the degree of recovery with [MI].

Metabolite abnormalities in progressive rnultifocal leukoencephalopathy by proton magnetic resonance spectroscopy

Objective To evaluate progressive multifocal leukoencephalopathy (PML) lesions using proton magnetic resonance spectroscopy (1H MRS). Design CSF polymerase chain reaction (PCR) detection for JC viral (JCV) DNA; MRI and localized 1H MRS in the PML lesions, normal-appearing contralateral brain regions (CONTRA), and in matched brain regions of normal subjects. Setting University-affiliated medical center. Patients or participants 20 AIDS patients with clinical diagnosis of PML, 16 had tissue and/or CSF evidence of JCV infection; 20 age-matched normal subjects. Main outcome measures Metabolites from 1H MRS: N-acetyl aspartate (NA), creatine (CR), choline-containing compounds (CHO), myoinositol (MI), glutamine/glutamate (GLX), lactate, and lipids. Results CSF PCR for JCV DNA showed 86% sensitivity. MRI showed characteristic demyelinating lesions; commonest locations were frontal lobe and cerebellum. 1H MRS in the lesions showed decreased NA (−35%; p < 0.0001) and CR (−18%; p = 0.003), increased CHO (+28%; p = 0.0005), occasional increased MI, and excess lactate (15/20 lesions) and lipids (18/20). In the CONTRA, MRS showed trends for increased CR (+15%), CHO (+ 15%), MI (+13%), and lower GLX (−9%; p = 0.02). Six patients, studied longitudinally (4–18 months), showed progressive spectroscopic changes; two patients with longest survival showed the highest MI. Conclusions These MRS findings are consistent with neuropathologic observations of neuronal loss, cell membrane and myelin breakdown, and increased glial activity in PML lesions. The CONTRA abnormalities may be due to remote effects of PML or direct HIV-1 infection. 1H MRS may be useful for characterization and follow-up evaluation of PML lesions.

Volume regression of abdominal aortic aneurysms and its relation to successful endoluminal exclusion

OBJECTIVES Evaluating the success of endoluminal repair of abdominal aortic aneurysms (AAAs) is frequently based on diameter measurements and determining the presence of endoleaks. The use of three-dimensional volumetric data and observation of morphologic changes in the aneurysm and device have been proposed to be more appropriate for postdeployment surveillance. The purpose of this study was to analyze the long-term volumetric and morphologic data of 161 patients who underwent endovascular AAA exclusion and to assess the utility of volume measurements for determining successful AAA repair. METHODS Patients with spiral computed tomography scans obtained preoperatively, within the first postoperative month, at 6 months, and annually thereafter, were included in this analysis. Computerized interactive three-dimensional reconstruction of each AAA scan was performed. Total aneurysm sac volume was measured at each time interval (mean preoperative volume 169.0 +/- 78.5 mL), and the significance of volume changes was determined by mixed linear modeling, a form of repeated measures analysis, to account for longitudinal data clustered at the individual level. Sixty-two patients (38%) developed endoleaks at some time during follow-up-15 type I leaks, 45 type II leaks, and 2 type III leaks. The patients with type I and type III leaks were treated with cuffs, and the type II leaks were treated either with observation, side-branch embolization, or required open conversion. RESULTS Aneurysm sac volume increased slightly at 1-month follow-up (+3.3%), and then decreased steadily to -12.9% at 5 years (P <.0001). This effect remained unchanged after controlling for the three device types used in our study population. Patients who did not exhibit an endoleak (n = 99) showed a significant decrease in aneurysm volume across the entire follow-up duration when compared with those who did exhibit an endoleak (n = 62) (P <.0001). The presence of a 10% or greater decrease in volume at 6 months demonstrated a sensitivity of 64%, a specificity of 95%, a positive predictive value of 95%, a negative predictive value of 62%, and an accuracy of 75% for predicting primary clinical success defined by successful deployment of the device; freedom from aneurysm- or procedure-related death; freedom from endoleak, rupture, migration, or device malfunction; or conversion to open repair. CONCLUSIONS Volumetric analysis may be used to predict successful endoluminal exclusion of AAAs. Volume regression appears to be device-independent and should be expected in most clinically successful cases. The presence of volume increases in the first 6 months is suspicious for an endoleak that is pressurizing the aneurysm sac and heralds the need for closer evaluation and possible intervention. A volume decrease of 10% or greater at 6 months and continuing regression over time is associated with successful endovascular repair.

Abdominal aortic aneurysm rupture following endoluminal graft deployment: report of a predictable event.

Purpose: To describe the predictability of an abdominal aortic aneurysm (AAA) rupture secondary to a type II endoleak following stent-graft exclusion. Methods and Results: An 81-year-old man with an enlarging AAA underwent endovascular repair using an AneuRx aortic stent-graft, but a type II endoleak fed by an accessory renal artery was detected at postprocedural computed tomography (CT). Surveillance CT scans at 6 and 16 months showed an increase in the aneurysm diameter and endoleak volume, but the patient refused advised treatment to close the leak. He suffered a fatal aneurysm rupture 24 months after endografting. Retrospective analysis of CT data documented progressive aneurysm enlargement that correctly predicted the rupture. Conclusions: Type II endoleaks can lead to aneurysm rupture. Three-dimensional (3D) spiral CT angiography offers an opportunity to track endoleak volume and the effect of exposure to systemic pressure on the aneurysm sac.

Stent-graft migration following endovascular repair of aneurysms with large proximal necks: anatomical risk factors and long-term sequelae.

Purpose: To evaluate the outcome of aortic endografts deployed in large infrarenal necks and to identify any association of preoperative aneurysm characteristics and postoperative morphological changes with the incidence of neck dilatation and device migration in this patient subset. Methods: The records of 47 patients (41 men; mean age 74, range 55–84) with large aortic neck diameters treated with Talent stent-grafts from 1998 to 2001 were reviewed. Patients with anatomical criteria that precluded aneurysm exclusion with currently available devices were preferentially selected. Mean baseline aneurysm morphology included 27.6-mm (range 18–33.4) suprarenal and 28.1-mm (range 24–34) infrarenal neck diameters; the infrarenal neck length was 26 ± 16 mm with angulation of 37° ± 18°. Computed tomographic (CT) angiograms up to 3 years were analyzed using specialized interactive software; migration was defined as >1-cm change in the distance from the lower renal artery to the top of the device. Pre- and postoperative morphological characteristics of the aneurysm were compared between patients with and without migration. Results: Of the 45 patients successfully treated, 40 had complete CT data for analysis. During a mean 17-month follow-up, 7 (17.5%) of the 40 devices exhibited distal migration. Six patients required secondary procedures; 5 were in the migration cohort. No preoperative anatomical characteristic or degree of neck dilatation over time was predictive of stent-graft migration. Aneurysm sac regression was significant at 1 (–0.09 ± 4.90 mm) and 2 (–1.48 ± 2.56 mm) years in endografts without migration (p<0.001). Distal endograft migration >1 cm predicted the need for secondary interventions (p<0.001), with 83% sensitivity and 94% specificity. Conclusions: Endovascular repair is successful in patients with large infrarenal necks and complex neck morphology. Changes in aneurysm remodeling over time were similar to reported observations in patients with more favorable neck criteria. Although no anatomical factor associated with migration could be identified from this analysis, distal displacement >1 cm correlated with the need for a secondary intervention.

Patient outcomes and thoracic aortic volume and morphologic changes following thoracic endovascular aortic repair in patients with complicated chronic type B aortic dissection.

OBJECTIVE True and false lumen changes and patient outcomes following thoracic endovascular aortic repair (TEVAR) for patients with stable type B dissection have been described by the The Investigation of Stent Grafts in Aortic Dissection (INSTEAD) trial. However, these changes have not been described in TEVAR patients treated for complications of chronic dissection. METHODS A single-institution study was conducted of 73 prospectively evaluated patients treated for complications of chronic type B dissection from 2002 to 2010. Spiral computed tomography reconstructions using M2S (Medical Media Systems, West Lebanon, NH) were analyzed for sequential changes in aortic volume and diameter during patient follow-up. Changes in aortic volume and diameter were tabulated as a percent change from preoperative values. Patient outcomes were determined by sequential evaluations postprocedure. RESULTS TEVAR was successfully performed in 72 out of the 73 patients (99%). Indications for intervention were aortic enlargement (n = 62), failure of medical management (n = 7), and perforation (n = 4). The 30-day all-cause mortality rate was 14%; events were due to retrograde dissection (n = 4), cardiac-related (n = 4), and rupture (n = 2). Eleven out of the 72 patients (15%) required a secondary procedure for endoleak (n = 7) and persistent distal perfusion of the false lumen (n = 4). Mean percentage expansion of the thoracic true lumen was noted during the follow-up period: 38%, 46%, 71%, and 114% at 1-, 3-, 6-, and 12-month follow-up, respectively. Concomitant regression of the thoracic false lumen of -65%, -68%, -84%, and -84% was observed at the same intervals, respectively. Patients with an initial extension of the thoracic dissection into the infrarenal aorta (n = 46) had an increase in mean percentage change of aortic diameter and volume to 21% and 17% at 1 year, respectively. By contrast, in the patient group without infrarenal dissection (n = 14), the infrarenal aortic diameter and volume remained relatively unchanged at 3% and -0.9%, respectively, at 1-year postintervention. CONCLUSIONS TEVAR is a potential treatment option for patients experiencing complications of chronic type B dissection. During follow-up, there is a predictable expansion of the thoracic true lumen and regression of the thoracic false lumen. These findings correlate with those of the INSTEAD trial, which demonstrated false lumen regression and true lumen expansion in a cohort of patients with stable type B dissection. However, many patients with extension of thoracic dissection into the infrarenal aorta demonstrate continued aortic dilation and, on occasion, the need for secondary intervention for persistent distal perfusion. Further analysis is needed in this subgroup of patients so as to better determine potential predictors and the clinical significance of post-TEVAR infrarenal expansion. Moreover, further investigations may support a role for secondary endovascular intervention in remedying persistent infrarenal aortic expansion after TEVAR for chronic dissection.

Physiologic MRI of a tumefactive multiple sclerosis lesion

Structural and physiologic MRI were performed after subacute onset of left hemiparesis in a patient with MS. MRI showed a large ring-enhancing lesion with surrounding edema and mass effect; differential diagnosis included a neoplasm or a large MS plaque. Physiologic MRI showed reduced blood flow and magnetization transfer, as well as increased diffusion, in the large lesion. Because these findings suggested a tumefactive MS plaque rather than a neoplasm, the patient received steroid treatment for acute MS exacerbation. Three months later the patient improved clinically and on MRI.

Intravascular Ultrasound: The Ultimate Tool for Abdominal Aortic Aneurysm Assessment and Endovascular Graft Delivery

Intravascular ultrasound (IVUS) imaging is a relatively new, rapidly evolving technology that enables precise catheter-based assessment of the dimensions and morphology of vascular structures and lesions. In extensive preclinical laboratory developmental studies and in clinical cases of endograft deployment for treatment of abdominal aortic aneurysms, we have found IVUS invaluable for determining key parameters of aortic morphology before and during interventions and for assessing the accuracy of deployment after device placement. By combining the IVUS data with information obtained from angiography, magnetic resonance imaging, and computed tomography (axial and three-dimensional reconstructions), we have been able to size devices and choose optimal fixation sites to prevent endoleaks and maintain luminal patency acutely and in the long term.

Preliminary clinical outcome and imaging criterion for endovascular prosthesis development in high-risk patients who have aortoiliac and traumatic arterial lesions

PURPOSE This report reviews our preliminary experience of prospective treatment of arterial lesions with endoluminal grafts in a Food and Drug Administration (FDA)-approved, investigator-sponsored Investigation Device Exemptions study. The utility and accuracy of various imaging methods, including angiography, cinefluoroscopy, computed tomography (CT), intravascular ultrasonography (IVUS), and duplex scanning, in performing the procedures was also assessed. METHODS Thirty-one patients were evaluated; 17 patients were treated, including 11 with abdominal aortic aneurysms, one with an aortic occlusive lesion, two with iliac artery aneurysms, and three with traumatic arteriovenous fistulas. Twelve of the 14 patients who had aorta and iliac artery lesions were high-risk. The mean follow-up of patients treated was 9 months (range, 6 to 15 months). RESULTS Aortoaortic endoluminal interposition procedures were not successful for treating abdominal aortic aneurysms early in the study (n = 3). Aortoiliac endoluminal bypass, contralateral iliac artery occlusion, and femorofemoral bypass procedures were successful in seven of eight subsequent cases (88%), with no incidence of endoleaks at either the proximal or distal fixation sites using the deployment methods described in this report. The 30-day operative mortality rate on follow-up evaluations for patients who underwent aortoiliac procedures was 14% (two of 14). Other major complications included transient renal failure in three patients that required short-term (two to eight times) dialysis, one arterial perforation and one dissection, and one prolonged intubation. No myocardial infarctions or strokes occurred. After major complications or identification of limitations in the study, the protocol was modified with the approval of the FDA to help avoid the recurrence of the same problems. There were no deaths or complications in the trauma cases. CONCLUSIONS Contrast-enhanced CT (axial images and spiral reconstructions) was the most accurate method to determine candidacy for aortoiliac procedures and to choose the site for deployment of the devices. Angiographic scans were misleading in several patients regarding the critical determinants of patient candidacy and device deployment, particularly regarding the presence of a distal aortic neck. Cinefluoroscopy was used in all patient and was particularly useful for determining the continuity of vascular structures and the anatomy of branch arteries and for enabling precise positioning of stent devices. Determination of fixation sites and assessing dimensional information by cinefluoroscopy and angiography were limited by inaccuracies produced by image magnification, parallax, and uniplanar views. IVUS was used to determine the morphologic features of vascular structures (i.e., calcium, thrombus), to perform real-time observation of the expansion of devices, and to assure firm fixation of balloon-expanded stents before the procedures were completed. Duplex scanning was very helpful in assessing and identifying precisely the location of arteriovenous fistulas before intervention and provided assessment at follow-up intervals. Three-dimensional reconstruction imaging technologies such as spiral CT were particularly helpful for assessing the morphologic features of vascular anatomy before the intervention and at follow-up intervals, whereas 3-D IVUS provided a similar real-time perspective during the procedure.