Predictive Value of Clinical, CSF and Vessel Wall MRI Variables in Diagnosing Primary Angiitis of the CNS.

Background and Objectives: Without brain biopsy, there are limited diagnostic predictors to differentiate primary angiitis of the CNS (PACNS) from intracranial atherosclerotic disease (ICAD). We examined the utility of clinical, CSF, and quantitative vessel wall magnetic resonance imaging (VWMRI) variables in predicting PACNS from ICAD. Methods: In this cross-sectional design, observational study, we reviewed electronic medical records to identify patients (18 years and older) who presented to our medical center between January 2015 and December 2021 for ischemic stroke due to intracranial vasculopathy. Patients with biopsy-proven PACNS, probable PACNS, or ICAD were included. Patients with secondary CNS vasculitis or no VWMRI data were excluded. On VWMRI, for each patient, a total of 20 vessel wall segments were analyzed for percent concentricity, percent irregularity, and concentricity to eccentricity (C/E) ratios. We also collected several clinical and CSF variables. Using logistic regression models, we assessed the diagnostic value of VWMRI, CSF, and clinical variables in predicting PACNS in patients with biopsy-proven disease. We then performed a sensitivity analysis to assess predictors of biopsy-proven and probable PACNS. Results: Thirty-two patients with ICAD (54.2%) and 27 patients with PACNS (45.8%) were included. Of the patients with PACNS, 21 (77.8%) were not biopsied and considered probable PACNS. Twenty-four patients with ICAD (75%) and 6 biopsy-proven patients with PACNS (22.2%) showed large vessel involvement and were included in the primary analysis. Encephalopathy (odds ratio [OR], 7.60; 95% CI 1.07-54.09) and seizure (OR 23.00; 95% CI 1.77-298.45) were significantly associated with PACNS. All patients were included in the sensitivity analysis, in which headache significantly predicted PACNS (OR 7.60; 95% CI 1.07-54.09). In the primary analysis, for every 1 white blood cell/µL increase in CSF, there was a 47% higher odds of PACNS (OR 1.47; 95% CI 1.04-2.07). On VWMRI, a C/E ratio >1 (OR 115.00; 95% CI 6.11-2165.95), percent concentricity ≥50% (OR 55.00; 95% CI 4.13-732.71), and percent irregularity <50% (OR 55.00; 95% CI 4.13-732.71) indicated significantly higher odds of PACNS compared with ICAD. Discussion: Our results suggest that quantitative VWMRI metrics, CSF pleocytosis, and clinical features of encephalopathy, seizure, and headache significantly predict a diagnosis of probable PACNS when compared with ICAD.

The prevalence of radiological cerebral amyloid angiopathy-related inflammation in patients with cerebral amyloid angiopathy.

OBJECTIVES: Cerebral amyloid angiopathy (CAA) related inflammation (CAA-RI) is an autoimmune inflammatory condition occurring in patients with CAA. We aimed to determine the prevalence of radiological CAA-RI amongst patients with CAA and to describe their presenting clinical features. METHODS: We performed a retrospective review of electronic medical records across multiple centers within a single healthcare network. Patients who met radiological modified Boston 2.0 criteria for CAA and had white matter hyperintensity (WMH) were included. Scans were analyzed by a vascular neurologist and confirmed by a neuroradiologist blinded to clinical information for meeting criteria for possible or probable radiographic CAA-RI. RESULTS: Out of 1100 patients reviewed, 511 patients met radiological modified Boston criteria for CAA and 193 patients had WMH on MRI. A total of 55 (28.5 % of those with CAA and WMH, and 10.8 % of all CAA with or without WMH) patients had MRI brain imaging suggestive of possible or probable radiographic CAA-RI. The diagnosis of CAA-RI was reported in only 10 (18.2 %) patients initially while 20 (36.4 %) were diagnosed up to 74 months later (median 0, IQR 0-9 months). At the time of earliest probable CAA-RI findings on imaging, the most common concurrent findings were cognitive impairment (74.5 %), macro-hemorrhages (52.7 %), headache (30.9 %), seizures (14.5 %), and ischemic infarcts (14.5 %). Only 18 (32.7 %) patients were treated with immunosuppression. CONCLUSIONS: The prevalence of radiographic CAA-RI was high, and most cases were unrecognized and untreated. Further studies are needed to assess if earlier detection and treatment of radiologic CAA-RI may halt disease progression and prevent cognitive decline in these patients.

Vessel wall MR imaging of aortic arch, cervical carotid and intracranial arteries in patients with embolic stroke of undetermined source: A narrative review.

Despite advancements in multi-modal imaging techniques, a substantial portion of ischemic stroke patients today remain without a diagnosed etiology after conventional workup. Based on existing diagnostic criteria, these ischemic stroke patients are subcategorized into having cryptogenic stroke (CS) or embolic stroke of undetermined source (ESUS). There is growing evidence that in these patients, non-cardiogenic embolic sources, in particular non-stenosing atherosclerotic plaque, may have significant contributory roles in their ischemic strokes. Recent advancements in vessel wall MRI (VW-MRI) have enabled imaging of vessel walls beyond the degree of luminal stenosis, and allows further characterization of atherosclerotic plaque components. Using this imaging technique, we are able to identify potential imaging biomarkers of vulnerable atherosclerotic plaques such as intraplaque hemorrhage, lipid rich necrotic core, and thin or ruptured fibrous caps. This review focuses on the existing evidence on the advantages of utilizing VW-MRI in ischemic stroke patients to identify culprit plaques in key anatomical areas, namely the cervical carotid arteries, intracranial arteries, and the aortic arch. For each anatomical area, the literature on potential imaging biomarkers of vulnerable plaques on VW-MRI as well as the VW-MRI literature in ESUS and CS patients are reviewed. Future directions on further elucidating ESUS and CS by the use of VW-MRI as well as exciting emerging techniques are reviewed.

Case Report of Spinal Cord Involvement in Susac Syndrome Masquerading as a Multiple Sclerosis Mimic.

We present a unique case of a 59-year-old woman with atypical Susac syndrome and prominent involvement of the spinal cord. She initially presented with progressive headaches, lower extremity weakness and hearing loss. Her MRI brain showed multiple enhancing lesions and her MRI spine showed a T8 enhancing lesion as well as a C2 cord infarct. She was treated with IV methylprednisolone with initial stabilization. However, she developed worsening encephalopathy and lower extremity weakness. Her repeat MRI brain showed new bilateral enhancing lesions and subacute infarcts. Given the increased burden of new lesions, she underwent a brain biopsy, which showed perivascular chronic inflammation within a small vessel distribution. Additionally, fluorescein angiography revealed bilateral branch retinal arterial occlusion (BRAO) and an audiogram demonstrated bilateral sensorineural hearing loss. She was diagnosed with Susac syndrome and treated with IV cyclophosphamide with improvement in her clinical exam. Spinal cord involvement is extremely rare for Susac syndrome, which commonly manifests as the classic triad of encephalopathy, BRAO and hearing loss. Her presentation with myelopathy highlights the importance of considering atypical presentations of well-established syndromes for optimal diagnosis and management.

Callosal Diffusion-Restriction in Patients with Intracranial Hemorrhage.

OBJECTIVE: We aim to report the incidence and clinical characteristics of patients who were found to have diffusion restricting lesions of the corpus callosum (CC) on Diffusion-weighted imaging (DWI) on magnetic resonance imaging (MRI) following intracranial hemorrhage (ICH). DESIGN/METHODS: A retrospective cross-sectional analysis was performed of medical records of all adult patients admitted to a single tertiary center with a primary diagnosis of ICH and received nicardipine infusion over a 2-year period. Patients without MRI brain available or patients who underwent digital subtraction angiography (DSA) prior to MRI were excluded. ICH and intraventricular hemorrhage (IVH) volumes and scores were calculated. MRI brain scans were evaluated for presence and locations of DWI lesions. RESULTS: Among 162 patients who met inclusion criteria, 6 patients (4%, median age 53, range 37-71, 100% male, 33% white) were found to have DWI lesions in the CC with a median ICH volume of 17ml (range 1-105ml). The ICH locations were lobar (n=3), deep (n=2) and cerebellum (n=1). All patients (100%) had intraventricular hemorrhage (IVH) with median IVH volume of 25ml (range 2.7-55ml). Four patients were on levetiracetam. No identifiable infections or metabolic abnormalities were found among these patients. All but one patient had normal DSA. Follow up MRI was only available in one patient and showed no reversibility at 14 days. CONCLUSION: Although rare, diffusion restricting corpus callosum lesions can be seen in patients with ICH, especially in patients with IVH. The etiology and clinical significance of these lesions remains unknown and warrant further research.

A 66 Year Old Woman with Recurrent Stroke.

Recurrent strokes involving various arterial territories can carry a broad differential diagnosis. Multiple progressive infarcts in a patient with clinical signs and symptoms out of proportion to their infarct pattern on imaging should compel the clinician to broaden the differential to include inflammatory causes of stroke also. A stepwise approach, using clinical, imaging and laboratory clues to direct further invasive testing is required for proper diagnosis and management in such cases. We present the case of a 66 year old woman with recurrent strokes over the span of a few weeks with deficits and mental status changes out of proportion to her infarcts on MRI brain and an inflammatory CSF. Since commencement of treatment for the underlying inflammatory cause of her strokes, she has remained stroke free for over two years in follow up.

Spatial Distribution of Intracranial Vessel Wall Enhancement in Hypertension and Primary Angiitis of the CNS.

We hypothesized a difference in the spatial distribution of intracranial vessel wall enhancement between CNS vasculitis and risk factors for intracranial atherosclerotic disease (ICAD). Fifty-five vessel wall MR imaging (VWI) exams were included in this retrospective observational study. Intracranial arteries were evaluated for vessel wall enhancement by branching pattern (e.g., primary, secondary, and tertiary segments). Demographic and laboratory data as well as ICAD risk factors, including a diagnosis of hypertension, were collected. A diagnosis of primary angiitis of the CNS (PACNS) was confirmed by biopsy or clinical assessment by a stroke neurologist. Univariate and multivariate Poisson regression models were fit for the outcomes. In multivariate analyses, hypertension showed significant associations with primary (ß = 1.31, 95% CI 0.78-1.88, p < 0.0001) and secondary (ß = 1.15, 95% CI 0.29-2.18, p = 0.05) segments, contrasting with PACNS which showed a distal spatial distribution with significant associations with secondary (ß = 0.77, 95% CI 0.14-1.39, p = 0.05) and tertiary (ß = 1.34, 95% CI 0.68-2.01, p < 0.0001) segments. Our results suggest the spatial distribution of vessel wall enhancement is an important consideration when interpreting VWI exams, particularly in patients with a comorbid diagnosis of hypertension. Given the global prevalence of hypertension, these results are impactful and may improve image interpretation of VWI in stroke patients.

Peripheral Neuropathies in Infectious Diseases.

Peripheral nerve disorders may be the presenting manifestation of a systemic infection, and early recognition of these syndromes is essential for prompt diagnosis and treatment. Mechanisms associated with infectious disorders of the peripheral nerve are often complex and multiple, with secondary inflammation, direct infectious invasion of nerves, and toxicities of antimicrobial medications playing a role. Here, we provide a complete review of the most common infectious pathogens that can affect the peripheral nerves.

Opportunities for intervention: stroke treatments, disability and mortality in urban Tanzania.

OBJECTIVE: Given the high post-stroke mortality and disability and paucity of data on the quality of stroke care in Sub-Saharan Africa, we sought to characterize the implementation of stroke-focused treatments and 90-day outcomes of neuroimaging-confirmed stroke patients at the largest referral hospital in Tanzania. DESIGN: Prospective cohort study. SETTING: Muhimbili National Hospital (MNH) in Dar es Salaam, July 2016-March 2017. PARTICIPANTS: Adults with new-onset stroke (<14 days), confirmed by head CT, admitted to MNH. MAIN OUTCOMES MEASURES: Modified Rankin scale (mRS) and vital status. RESULTS: Of 149 subjects (mean age 57; 48% female; median NIH stroke scale (NIHSS) 19; 46% ischemic stroke; 54% hemorrhagic), implementation of treatments included: dysphagia screening (80%), deep venous thrombosis prophylaxis (0%), aspirin (83%), antihypertensives (89%) and statins (95%). There was limited ability to detect atrial fibrillation and carotid artery disease and no acute thrombolysis or thrombectomy. Of ischemic subjects, 19% died and 56% had severe disability (mRS 4-5) at discharge; 49% died by 90 days. Of hemorrhagic subjects, 33% died and 49% had severe disability at discharge; 50% died by 90 days. In a multivariable model, higher NIHSS score but not dysphagia, unconsciousness, or patient age was predictive of death by 90 days. CONCLUSIONS: The 90-day mortality of stroke presenting at MNH is 50%, much higher than in higher income settings. Although severe stroke presentations are a major factor, efforts to improve the quality of care and prevent complications of stroke are urgently needed. Acute stroke interventions with low number needed to treat represent challenging long-term goals.