Risk factors for severe hearing loss in Susac syndrome: A national cohort study.

BACKGROUND: Nonreversible hearing loss (HL) is the main sequelae of Susac syndrome (SuS). We aimed to identify risk factors for HL in SuS. METHODS: The CARESS study is a prospective national cohort study that started in December 2011, including all consecutive patients with SuS referred to the French reference center. The CARESS study was designed with a follow-up including fundoscopy, audiometry, and brain magnetic resonance imaging at 1, 3, 6, and 12 months after diagnosis and then annually for 5 years. The primary outcome was the occurrence at last follow-up of severe HL defined as the loss of 70 dB in at least one ear on audiometry or the need for hearing aids. RESULTS: Thirty-six patients (female 66.7%, median age 37.5 [range 24.5-42.5] years) included in the clinical study were analyzed for the primary outcome. Thirty-three patients (91.7%) had cochleovestibular involvement at SuS diagnosis including HL >20 dB in at least one ear in 25 cases. At diagnosis, 32 (88.9%), 11 (30.6%), and 7 (19.4%) patients had received steroids, intravenous immunoglobulin, and/or immunosuppressive (IS) drugs, respectively. After a median follow-up of 51.8 [range 29.2-77.6] months, 19 patients (52.8%) experienced severe HL that occurred a median of 13 [range 1.5-29.5] months after diagnosis. Multivariable analysis showed that the odds of severe HL were lower in patients who received IS drugs at diagnosis (OR 0.15, 95% CI 0.01-1.07, p = 0.058). CONCLUSIONS: Severe HL in SuS is associated with the absence of IS drugs given at diagnosis. Our findings support the systematic use of IS drugs in SuS.

Brain magnetic resonance imaging lesion load at diagnosis, severity at onset and outcomes in Susac syndrome: A prospective cohort study.

BACKGROUND: Susac syndrome (SuS) is a rare occlusive microvessel disease of the brain, retina and inner ear. We aimed to determine whether brain lesion load at the acute phase predicts poor outcomes in SuS. METHODS: A prospective national cohort study was conducted from December 2012 to December 2019 in 20 centres in France. Patients included at the principal investigator's center with available brain magnetic resonance imaging (MRI) at diagnosis were analyzed. MRI was reviewed by an experienced neuroradiologist blinded to clinical status. The size, topography and number of hyperintense lesions on diffusion-weighted imaging (DWI-HL) were analyzed at diagnosis and during follow-up. Outcomes involved descriptive characteristics of patients at onset and last follow-up. RESULTS: Twenty-three patients (38.1 [18.8-56.5] years, 16 females) were prospectively studied. The triad (i.e., brain, eye and ear involvement) was complete at onset in 17 patients. Brain MRI was performed 1.1 (0.1-3.4) months after the first symptom. All patients had DWI-HL at the acute phase. Patients were separated into two groups according to the number of DWI-HL on first MRI: a first group of patients (n=15) displaying low brain lesion load (<50 DWI-HL per patient) and a second group of patients (n=8) displaying high brain lesion load (≥100 DWI-HL). The median follow-up was 57.9 (9.7-98) months. Clinical features, treatment, relapse rate, time to disappearance of DWI-HL, disabilities and professional outcome did not differ according to brain lesion load. CONCLUSION: Brain lesion load assessed by DWI at the acute phase is not associated with risks of disability in SuS.

Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study.

Background Brain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose To describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection. Materials and Methods This was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were (a) positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, (b) severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, (c) neurologic manifestations, and (d) abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student t test or Wilcoxon test. P < .05 represented a significant difference. Results Thirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8-78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], P = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], P = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid. Conclusion Patients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described. © RSNA, 2020.

Factors of Rapid Cognitive Decline in Late Onset Alzheimer's Disease.

BACKGROUND: Rapid Cognitive Decline (RCD) in Alzheimer's Disease (AD) is associated with a worse disease progression. There is no consensual predictor of RCD and only a few studies have focused on RCD in late-onset dementia, the most common form of AD. OBJECTIVE: To identify the predictors of RCD, in a population of community-dwelling patients with recently diagnosed late onset AD. METHODS: Community-dwelling subjects aged >75 consulting for the first time in Old Age Memory outpatient center from 2009 to 2012 were considered. All patients underwent a standardized clinical dementia investigation. Patients were classified as rapid decliners when they demonstrated a loss of 3 points or greater in MMSE during the first six months. RESULTS: 130 patients were included (42 males, 88 females, mean ages 82.7±4.58). The average baseline MMSE score was 23.36±3.78. In regression analysis, the Free Recall Scores, categorical fluency scores were the most highly predictive of RCD. CONCLUSION: These results are important for the design of clinical trials and also, in clinical practice, for both physicians and families in planning long-term care.

Usefulness of Subepicardial Hyperemia on Contrast-Enhanced First-Pass Magnetic Resonance Perfusion Imaging for Diagnosis of Acute Myocarditis.

Hyperemia is a major criterion for the diagnosis of acute myocarditis on cardiac magnetic resonance imaging but its assessment is challenging and time consuming. We evaluated the usefulness of the contrast-enhanced first-pass perfusion (FPP) on magnetic resonance imaging for detecting subepicardial hyperemia in acute myocarditis. Forty-seven consecutive patients (mean age: 42 ± 15.6 years; 35 men) with a definite diagnosis of acute myocarditis according to the state-of-the-art guidelines were included and compared with 16 control subjects. FPP was evaluated by 2 blinded observers and compared with the reference late gadolinium enhancement. Detection of hyperemia was performed on both qualitative and quantitative methods. Relative increased signal intensity (SI) in the subepicardial hyperemic layer was measured with SI ratio (SI of the subepicardial layer/SI of the immediately adjacent subendocardial layer). Twenty-four patients (51%) with acute myocarditis exhibited subepicardial hyperemia, detected with a good interobserver reproducibility (kappa coefficient: 0.75). The SI in the myocardium of myocarditis patients was increased compared with controls (1.08 ± 0.03 vs 0.945 ± 0.04, p = 0.03) and the SI in myocarditis patients with hyperemia compared with those without hyperemia (1.22 ± 0.04 vs 0.94 ± 0.04, p <0.0001). Sensitivity, specificity, positive predictive, and negative predictive values of FPP for detecting hyperemia were 85%, 94%, 85%, and 93%, respectively. In conclusion, contrast-enhanced first-pass magnetic resonance imaging is a fast and useful method for assessing myocardial hyperemia in patients with acute myocarditis.

Prognostic value of the infarct- and non-infarct like patterns and cardiovascular magnetic resonance parameters on long-term outcome of patients after acute myocarditis.

BACKGROUND: Prognostic value of the infarct- and non-infarct like patterns and cardiac magnetic resonance (CMR) parameters on long-term outcome of patients after acute myocarditis is not well known. METHODS: Between 2006 and 2015, 112 consecutive patients with CMR-based diagnosis of acute myocarditis were identified in our institution. Of them, 88 were available for clinical follow-up and represented our studied population. Patients were divided into infarct-like group (n=48) (association of acute chest pain, elevated Troponin levels and ST-elevation) and non-infarct-like group (n=40) with any other presentation. The composite primary endpoint of major cardiovascular events (MACE) included: all-cause mortality, cardiac mortality, recurrence of myocarditis, heart failure, and sustained ventricular tachycardia. RESULTS: During follow-up, 21 patients (24%) experienced MACE and infarct-like patients were significantly more at risk for MACE than non-infarct-like patients (HR 2.4, 95% CI [1.01-5.80] p=0.04). Infarct-like patients exhibited in particular a higher risk of sustained ventricular tachycardia and recurrence of myocarditis (p=0.03). They had lower CMR-derived left (p=0.03) and right (p=0.001) ventricular ejection fractions, and exhibited larger areas of late gadolinium enhancement (LGE) (p=0.001). In multivariate analysis, both initial NYHA functional class >II and LGE mass were independent predictors for long-term MACE occurrence (HR 5.8 and 1.07 per gram respectively, p=0.007). Moreover, a threshold of LGE mass >17g provided a high discrimination for MACE occurrence (AUC of 0.81). CONCLUSIONS: The infarct-like pattern of acute myocarditis is associated with MACE occurrence. Initial NYHA functional class >II and LGE are independent predictive factors of MACE during long-term follow-up after acute myocarditis.

Comparative assessment of ascending aortic aneurysms in Marfan patients using ECG-gated computerized tomographic angiography versus trans-thoracic echocardiography.

BACKGROUND: Contrast-enhanced computed tomography (CT) is routinely used as a complementary technique to trans-thoracic echocardiography (TTE) for assessing thoracic aortic aneurysms (TAA). However different measures can be obtained on CT and there are no recommendations on which to use. The objective was to determine which CT measurements most closely match reference TTE measurements in Marfan patients with TAA. METHODS: TTE measurements were obtained using the leading edge-to-leading edge technique in end-diastole on the parasternal longitudinal view. ECG-gated CT measurements were obtained, using the inner-to-inner technique in end-diastole by double oblique reconstruction: on three-cavity view (3C), left ventricle-aorta view (LVAo), and strict transverse plane passing through the maximal diameter "cusp to commissure" and "cusp to cusp" for each cusp. CT and TTE were performed within one month. RESULTS: 44 Marfan patients (39 ± 19 years, 48% men) were included. Dilatation of the ascending aorta was maximal at the level of the sinuses (TTE diameters: mean 47.5 ± 5.3 mm). TTE diameters were similar to 3C, LVAo (mean differences: 2.2 and -0.1 mm, p=NS) and to the three "cusp to cusp" diameters (mean differences ranging from 0 to 1.1mm, p=NS), whereas "cusp to commissure" diameters were all statistically smaller than TTE (3.6 mm, 2.9 mm and 3.7 mm, p ≤ 0.01). CONCLUSIONS: Inner-to-inner "cusp to cusp" diameter measured on an ECG-gated CT should be used for comparison with 2D TTE aortic diameter at the level of the sinuses of Valsalva in patients with thoracic aortic aneurysms.

The Lawton Instrumental Activities Daily Living/Activities Daily Living Scales: A Sensitive Test to Alzheimer Disease in Community-Dwelling Elderly People?

OBJECTIVE: To examine the diagnostic ability of the Lawton Instrumental Activities Daily Living (IADLs) scale and the Activities Daily Living (ADLs) scale as a sensitive tool to Alzheimer's disease (AD) in community-dwelling elderly people. DESIGN: In an old age memory outpatient center, among patients with a clinical diagnosis of AD dementia or no dementia supported by at least 6 months of follow-up, we looked back at the baseline Lawton IADL scale (short version IADL-4 item), ADL scale, Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MOCA) values. RESULTS: There were 109 patients with AD and 53 nondemented individuals (81.4 ± 4.6 years). The sensitivity of ADL scale or IADL-4 item or the MMSE was low (52%-57%). The most efficient AD classification used both the IADLs-4 item and the MOCA with a threshold score of 20. Besides age and memory scores, the main correlates of IADLs scale or ADLs scale were executive, neuropsychiatric, vascular, and extrapyramidal scores. CONCLUSION: Our results suggest that the Lawton IADLs-4 item scale and ADLs scale lack sensitivity to AD dementia in elderly people and support a better sensitivity of MOCA rather than MMSE and IADLs-4 item/ADLs at the expense of specificity.

Cerebral vascular aging: extending the concept of pulse wave encephalopathy through capillaries to the cerebral veins.

The recent concept of pulse wave encephalopathy helps understanding the cerebral venous remodeling in aging. This so-called periventricular venous collagenosis is an expected mechanical consequence of the age-related changes in arterial pulsations and the mechanical fatigue of vascular smooth muscles. Unlike arteriolar mechanical stress, venular mechanical stress depends on both the blood pulse wave amplitude and the mechanical properties of the environment tissue. Thereby, there is a preferential periventricular location of venous collagenosis and a mechanistic link between venous collagenosis and foci of white matter rarefaction or leukoaraiosis. The recent concept of pulse wave encephalopathy also helps understanding the widening of retinal venules, the "mirror" of cerebral venules, in various manifestations of pulse wave encephalopathy, including progressive leukoara�osis, lacunar and hemorrhagic "pulse wave" strokes, and dementia. Indeed, the age-related chronic increase in arterial pulsations explains subsequent arteriolar myogenic "fatigue", marked attenuation in the arteriolar myogenic tone and abnormal penetration of the insufficiently dampened arterial pulse wave into the venules. Thus, retinal venular widening, a biomarker of advanced pulse wave encephalopathy, is also increasingly recognized as a biomarker for high cardiovascular risk. All these data support a shift in the concept of chronic cerebrovascular disease, from the classical model which is restricted to steno-occlusive cerebrovascular diseases to an enlarged model which would include the pulse wave encephalopathy concept. Thereby, preventing damage to the cerebral microvasculature by an undampened arterial pulse wave will become a logical target for the prevention and treatment of late-onset cognitive decline.

Intracranial MR dynamics in clinically diagnosed Alzheimer's disease: the emerging concept of "pulse wave encephalopathy".

As increasingly shown in neuropathological and predementia clinical studies, cognitive decline with altered intracranial dynamics can fulfill current clinical criteria of dementia of the Alzheimer's type (DAT) and there is a marked pathogenic complexity of this epidemic syndrome. Whereas structural studies only suggest the unexpected frequency of cerebrovascular changes in late life DAT, flow quantification MR sequences now offer a great opportunity of in vivo accurate analysis of cerebrovascular function. Their first applications have allowed development of a modern concept of the intracranial dynamics; a complex windkessel system allows two processes that are crucial to insure brain oxygenation and nutrition, a periodic systolic marked expansion of the intracranial blood compartment within the rigid cranial cavity on the one hand, a marked dampening of the arterial pulse wave before it reaches capillary level on the other hand. This modern concept has allowed better understanding of two archetypes of windkessel failure or so-called pulse wave encephalopathy, normal pressure hydrocephalus and subcortical arteriosclerotic encephalopathy. Dynamic MRI may now help to detect and classify distinct patterns of cerebrovascular dysfunction in DAT. This dynamic approach helps to understand the major association between aging and DAT as well as the increasingly recognized overlap between Alzheimer's pathology, normal pressure hydrocephalus and arteriosclerotic neurodegeneration. Evidence of such a great variety of disturbances in intracranial dynamics behind a single clinical syndrome of DAT can greatly impact therapeutic research on this devastating disorder.

Assessing cerebrovascular contribution to late dementia of the Alzheimer's type: the role of combined hemodynamic and structural MR analysis.

The critical question as to the respective role of Alzheimer's disease (AD) and cerebrovascular disease in dementia of the Alzheimer's type (DAT), the most common form of dementia, is still debated. But there has been considerable progress in understanding cerebral hemodynamics and the relationship between structural brain damage and cognitive decline, in routine neuro imaging techniques. These advances now allow the proposition of a novel MR classification of DAT including indicators of both cerebrovascular function and regional brain atrophy. MR indicators of windkessel function include the arterial pulsatility index, the intracranial blood stroke volume, the cerebral relative venous outflow rates and a relative index of craniospinal compliance. MR indicators of vascular conduct function include total arterial and superficial venous flow rates that are closely related to brain metabolism. Structural MR sequences allow the detection of structural markers of windkessel dysfunction and, beyond the non specific hippocampal atrophy, a more extensive AD-like MR pattern of atrophy. The first illustration of this MR classification in elderly patients that later progressed to dementia converges with recent neuropathological observations to suggest that the major enemy to combat in late-life dementia is not AD but cerebrovascular dysfunction.