Psychosis in Alzheimer's disease is associated with specific changes in brain MRI volume, cognition and neuropathology.

Psychosis in Alzheimer's Disease (AD) is prevalent and indicates poor prognosis. However, the neuropathological, cognitive and brain atrophy patterns underlying these symptoms have not been fully elucidated. In this study, we evaluated 178 patients with AD neuropathological change (ADNC) and ante-mortem volumetric brain magnetic resonance imaging (MRI). Presence of psychosis was determined using the Neuropsychiatric Inventory Questionnaire. Clinical Dementia Rating Sum-of-boxes (CDR-SB) was longitudinally compared between groups with a follow-up of 3000 days using mixed-effects multiple linear regression. Neuropsychological tests closest to the time of MRI and brain regional volumes were cross-sectionally compared. Psychosis was associated with lower age of death, higher longitudinal CDR-SB scores, multi-domain cognitive deficits, higher neuritic plaque severity, Braak stage, Lewy Body pathology (LB) and right temporal lobe regional atrophy. Division according to the presence of LB showed differential patterns of AD-typical pathology, cognitive deficits and regional atrophy. In conclusion, psychosis in ADNC with and without LB has clinical value and associates with subgroup patterns of neuropathology, cognition and regional atrophy.

Divergent magnetic resonance imaging atrophy patterns in Alzheimer's disease and primary age-related tauopathy.

Our study compared brain MRI with neuropathological findings in patients with primary age-related tauopathy (PART) and Alzheimer's disease (AD), while assessing the relationship between brain atrophy and clinical impairment. We analyzed 233 participants: 32 with no plaques ("definite" PART-BRAAK stage higher than 0 and CERAD 0), and 201 cases within the AD spectrum, with 25 with sparse (CERAD 1), 76 with moderate (CERAD 2), and 100 with severe (CERAD 3) degrees of neuritic plaques. Upon correcting for age, sex, and age difference at MRI and death, there were significantly higher levels of atrophy in CERAD 3 compared to CERAD 1-2 and a trend compared to PART (p = 0.06). In the anterior temporal region, there was a trend for higher levels of atrophy in PART compared to Alzheimer's disease spectrum cases with CERAD 1 (p = 0.08). We then assessed the correlation between regional brain atrophy and CDR sum of boxes score for PART and AD, and found that overall cognition deficits are directly correlated with regional atrophy in the AD continuum, but not in definite PART. We further observed correlations between regional brain atrophy with multiple neuropsychological metrics in AD, with PART showing specific correlations between language deficits and anterior temporal atrophy. Overall, these findings support PART as an independent pathologic process from AD.

Incident stroke in patients with Alzheimer's disease: systematic review and meta-analysis.

Vascular mechanisms are increasingly recognized in the pathophysiology of Alzheimer's disease (AD), but less is known about the occurrence of stroke in AD patients. We aimed to quantify the risk of stroke in patients with AD and compare the incidence rates (IR) of stroke in individuals without AD. Systematic search of Embase and MEDLINE between 1970 and 2020. Inclusion criteria: reports with ≥ 50 patients with non-familial AD, which reported the occurrence of stroke (all types) and/or ischemic stroke and/or intracerebral hemorrhage (ICH) during follow-up. Meta-analyses of pooled data using random-effects model were performed. IR were calculated for each study. Incidence rate ratios (IRR) were calculated for studies presenting a control-group without AD. Among 5109 retrieved studies, 29 (0.6%) fulfilled the inclusion criteria, reporting a total of 61,824 AD patients. In AD patients the IR were 15.4/1000 person-years for stroke (all types), 13.0/1000 person-years for ischemic stroke and 3.4/1000 person-years for ICH. When compared to controls without AD, incidence rate for ICH in AD patients was significantly higher (IRR = 1.67, 95%CI 1.43-1.96), but similar for ischemic stroke. Incident stroke is not a rare event in AD population. AD is associated with an increased risk of intracerebral hemorrhage which warrants further clarification.

Intracerebral Hemorrhage Recurrence in Patients with and without Cerebral Amyloid Angiopathy.

BACKGROUND: Intracerebral hemorrhage (ICH) recurrence risk is known to be higher in patients with cerebral amyloid angiopathy (CAA) as compared to other causes of ICH. Risk factors for ICH recurrence are not completely understood, and our goal was to study specific imaging microangiopathy markers. METHODS: Retrospective case-control study of patients with non-traumatic ICH admitted to a single center between 2014 and 2017 who underwent magnetic resonance imaging (MRI). Clinical characteristics of the index event and occurrence of death and ICH recurrence were collected from clinical records. MRI images were independently reviewed by 2 neuroradiologists. Groups of patients with CAA-related and CAA-unrelated ICH defined were compared. Presence of CAA was defined according to the Boston modified criteria. Survival analysis with Kaplan-Meier curves and Cox-regression analyses was performed to analyze ICH recurrence-free survival. RESULTS: Among 448 consecutive patients with non-traumatic ICH admitted during the study period, 104 were included in the study, mean age 64 years (±13.5), median follow-up of 27 months (interquartile range, IQR 16-43), corresponding to 272 person-years of total follow-up. CAA-related ICH patients presented higher burden of lobar microbleeds (p < 0.001), higher burden of enlarged perivascular spaces (EPVS) in centrum semiovale (p < 0.001) and more frequently presented cortical superficial siderosis (cSS; p < 0.001). ICH recurrence in patients with CAA was 12.7 per 100 person-years, and no recurrence was observed in patients without CAA. Variables associated with ICH recurrence in the whole population were age (hazard ratio [HR] per 1-year increment = 1.05, 95% CI 1.00-1.11, p = 0.046), presence of disseminated cSS (HR 3.32, 95% CI 1.09-10.15, p = 0.035) and burden of EPVS in the centrum semiovale (HR per 1-point increment = 1.80, 95% CI 1.04-3.12, p = 0.035). CONCLUSIONS: This study confirms a higher ICH recurrence risk in patients with CAA-related ICH and suggests that age, disseminated cSS, and burden of EPVS in the centrum semiovale are associated with ICH recurrence.

Primary Progressive Multiple Sclerosis in a Portuguese Patient With Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a frequent genetic neurocutaneous syndrome and multiple sclerosis (MS) is an acquired demyelinating disease of the central nervous system. The association of both these diseases is rare. In this case report, we describe a 25-year-old man with gait impairment, upper limbs tremor, slurred speech, and urinary symptoms in the form of urinary urgency and incontinence. These symptoms started a year earlier and had a progressive course. Examination revealed scattered café-au-lait spots, right ptosis, bilateral horizontal and vertical nystagmus, mild dysarthria, quadriparesis with generalized hyperreflexia and bilateral Babinski signs, upper limb tremor, bilateral proprioceptive errors, bilateral appendicular dysmetria, and severe gait ataxia. Brain MRI showed lesions involving the deep and subcortical white matter, as well as thalami, with no enhancement after administration of gadolinium, suggestive of focal areas of signal intensity (FASI) in the setting of NF1. There were also oval lesions in the periventricular white matter, perpendicular to the ventricles and involving the corpus callosum, which were atypical for FASI. Spinal MRI also demonstrated several lesions, which mildly enhance after administration of gadolinium. Cerebrospinal fluid (CSF) examination revealed mild lymphocytic pleocytosis (18/µL), mildly elevated protein (0.53 g/L), normal glucose, and positive oligoclonal IgG bands. Extensive laboratory workup, including microbiological CSF studies, aquaporin-4-IgG, myelin-oligodendrocyte glycoprotein-IgG, autoimmune screening, and viral serology, was negative. The genetic study revealed a new mutation in the NF1 gene that was not previously reported. We intend to discuss the genetic and autoimmune mechanisms by which MS and NF1 appear to be related and draw attention to this association because a timely diagnosis of MS is important to prevent further disability in NF1 patients.

Red Cell Distribution Width is Associated with 30-day Mortality in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Red cell distribution width (RDW) has been associated with mortality and outcome in a wide variety of non-neurological and neurological diseases, namely in myocardial infarction and acute ischemic stroke, and the reason for this is not completely understood. We aimed to investigate RDW as a potential prognostic marker in patients with intracerebral hemorrhage (ICH). METHODS: This is a retrospective study of consecutive patients with acute non-traumatic ICH admitted to a single center during a 4-year period. We reviewed individual clinical records to collect demographic and baseline information, including RDW at admission, 3-month functional status, and incidence of death during follow-up. Baseline computed tomography imaging was reviewed to classify the location of ICH, and to measure ICH volume and perihematomal edema volume. Patients were divided according to quartile distribution of RDW (RDW-Q1-4). RESULTS: The final study population consisted of 358 patients, median age 71 years (interquartile range [IQR] 60-80), 55% were male, and median Glasgow Coma Scale was 14 (IQR 10-15), with a mean follow-up of 17.6 months. Patients with higher RDW values were older (p = 0.003), more frequently presented with an active malignancy (p = 0.005), atrial fibrillation (p < 0.001), intraventricular hemorrhage (p = 0.048), and were anticoagulated (p < 0.001). Three-month functional independence was similar throughout RDW quartiles. RDW-Q4 was independently associated with increased 30-day mortality (adjusted odds ratio = 3.36, 95%CI = 1.48-7.62, p = 0.004), but not independently associated with increased mortality after 30 days (adjusted hazards ratio = 0.71, 95%CI = 0.29-1.73, p = 0.448). CONCLUSIONS: RDW is a robust and independent predictor of 30-day mortality in non-traumatic ICH patients, and further studies to understand this association are warranted.

Contrast-induced neurotoxicity related to neurological endovascular procedures: a systematic review.

Contrast-induced neurotoxicity (CIN) is an adverse reaction to contrast agents which can occur in the context of diagnostic and therapeutic neurological endovascular procedures. Our goal was to conduct a systematic review of patients reported in the literature diagnosed with CIN after neurological endovascular procedures. A systematic search of EMBASE and MEDLINE databases was conducted. Inclusion criteria were age ≥ 18 years; neurological endovascular procedure performed ≤ 24 h before ictus; new manifestations compatible with encephalic dysfunction; imaging performed < 7 days after ictus; exclusion of other causes and manifestations attributed to pre-existing conditions. Forty-eight patients were included, of which 60.4% were female and 60.4% had arterial hypertension; median age was 63 years. The most frequent procedure was diagnostic cerebral angiography (n = 24, 50.0%) and non-ionic contrast agents were more frequently used (n = 40, 83.3%). Twenty-six patients (54.2%) developed clinical manifestations compatible with CIN during or immediately after the procedure, and the most frequent manifestations were encephalopathy, cortical blindness and motor deficit. The most frequent imaging findings were cortical contrast enhancement on CT (n = 23/42), and cortical sulci effacement (n = 18/48). Most patients presented complete clinical recovery (89.6%) at a median time of 3 days. Among patients with neuroimaging changes who underwent follow-up, complete regression of the abnormalities was shown in 81.5% at a median time of 5 days. CIN is a rare adverse reaction in the context of neurological endovascular procedures. Recognition of clinical manifestations and typical imaging abnormalities, while excluding other causes, is essential for diagnosis.

External carotid artery stenting in symptomatic internal carotid artery occlusion.

We report the case of a patient with an anterior ischemic stroke due to tandem occlusion of the left M2 segment and ipsilateral internal carotid artery (ICA), with concomitant severe stenosis of the ipsilateral external carotid artery (ECA) and contralateral ICA, and moderate stenosis of the left vertebral artery (VA); as thrombectomy was not possible, stenting of the right ICA was performed. Two days after significant recovery, the patient showed neurological deterioration when in upright position, and brain magnetic resonance imaging confirmed decreased cerebral blood flow on the left hemisphere. Stenting of the left ECA and balloon angioplasty of the ipsilateral VA were performed in order to increase collateral flow, with an almost complete resolution of symptoms. This case highlights the importance of assessing the collateralization pattern when an ICA occlusion is present, and the potential need to revascularize an ipsilateral stenotic ECA.

Magnetic resonance imaging brain atrophy assessment in primary age-related tauopathy (PART).

Alzheimer disease (AD) is a neurodegenerative disorder characterized pathologically by the accumulation of amyloid-beta (Aß) plaques and tau neurofibrillary tangles (NFTs). Recently, primary age-related tauopathy (PART) has been described as a new anatomopathological disorder where NFTs are the main feature in the absence of neuritic plaques. However, since PART has mainly been studied in post-mortem patient brains, not much is known about the clinical or neuroimaging characteristics of PART. Here, we studied the clinical brain imaging characteristics of PART focusing on neuroanatomical vulnerability by applying a previously validated multiregion visual atrophy scale. We analysed 26 cases with confirmed PART with paired clinical magnetic resonance imaging (MRI) acquisitions. In this selected cohort we found that upon correcting for the effect of age, there is increased atrophy in the medial temporal region with increasing Braak staging (r = 0.3937, p = 0.0466). Upon controlling for Braak staging effect, predominantly two regions, anterior temporal (r = 0.3638, p = 0.0677) and medial temporal (r = 0.3836, p = 0.053), show a trend for increased atrophy with increasing age. Moreover, anterior temporal lobe atrophy was associated with decreased semantic memory/language (r = - 0.5823, p = 0.0056; and r = - 0.6371, p = 0.0019, respectively), as was medial temporal lobe atrophy (r = - 0.4445, p = 0.0435). Overall, these findings support that PART is associated with medial temporal lobe atrophy and predominantly affects semantic memory/language. These findings highlight that other factors associated with aging and beyond NFTs could be involved in PART pathophysiology.

Noncontrast computed tomography markers of outcome in intracerebral hemorrhage patients.

Objectives: The characterization of markers capable of predicting clinically significant hematoma growth (HG) in patients with intracerebral hemorrhage (ICH) may be useful for the selection of patients for clinical trials. The use of several noncontrast computed tomography (NCCT) markers has been suggested to stratify the risk of HG. The aim of this study was to analyze HG prediction using different NCCT markers in patients with spontaneous ICH. Methods: Single-hospital retrospective study of patients with spontaneous ICH, who underwent initial NCCT <24 hours after symptom onset. Clinical characteristics were collected and two independent observers analyzed hemorrhage characteristics, volumes and 8 NCCT markers. HG was defined as a growth of ≥33% or ≥6mL in follow-up CT and 30-day survival was collected. Results: 328 patients were included. The most frequent NCCT marker was 'any hypodensity' (68.0%) and the less frequent was the blend sign (11.6%). HG occurred in 22.1% of patients and the only independent predictors for HG were 'any hypodensity' (OR=3.32, 95%CI=1.18-9.34, p=0.023) and the swirl sign (OR=3.98, 95%CI=1.41-11.21, p=0.009). Although all NCCT markers were more frequent in patients who died within 30 days, the only independent predictors were 'irregular margins' (OR=4.54, 95%CI=1.63-12.66, p=0.004) and the satellite sign (OR=2.49, 95%CI=1.07-5.75, p=0.034). NCCT markers with greater sensitivity for HG were 'any hypodensity' and the swirl sign, although with poor positive predictive values and poor areas under the curve. Conclusion: Even though some NCCT markers are independent predictors of HG and 30-day survival, they have suboptimal diagnostic test performances for such outcomes. Abbreviation: OR: odds ratio; 95%CI: 95% confidence interval.

Magnetic resonance imaging of cerebellar cysts in a neonate with congenital cytomegalovirus infection.

Congenital cytomegalovirus infection is one of the most common congenital viral infections in the world. Brain magnetic resonance imaging plays a key role in evaluating brain involvement and establishing prognosis; several characteristic features have been described. We present a description of cerebellar cysts in a neonate with polymerase chain reaction-confirmed cytomegalovirus congenital infection, and discuss the differential diagnosis and potential pathophysiological mechanisms.