Background and Purpose Carotid Intima-Media Thickness (cIMT) was a widely accepted ultrasound marker of subclinical atherosclerosis in the past. Although traditional risk factors may explain approximately 50% of the variance in plaque burden, they may not explain such a high proportion of the variance in IMT, especially when measured in plaque free-locations. We aimed this study to identify individuals with cIMT unexplained by traditional risk factors for future environmental and genetic research. Methods As part of the Northern Manhattan Study, 1,790 stroke-free individuals (mean age 69±9; 60% women; 61% Hispanic, 19% black, 18% white) were assessed for cIMT using B-mode carotid ultrasound. Multiple linear regression models were evaluated: (1) incorporating pre-specified traditional risk factors; and (2) including less traditional factors, such as inflammation biomarkers, adiponectin, homocysteine and kidney function. Standardized cIMT residual scores were constructed to select individuals with unexplained cIMT. Results Mean total cIMT was 0.92±0.09 mm. The traditional model explained 11% of the variance in cIMT. Age (7%), male sex (3%), glucose (<1%), pack years of smoking (<1%), and LDL-cholesterol (<1%) were significant contributing factors. The model including inflammatory biomarkers explained 16% of the variance in cIMT. Adiponectin was the only additional significant contributor to the variance in cIMT. We identified 358 (20%) individuals with cIMT unexplained by the investigated risk factors. Conclusions Vascular risk factors explain only a small proportion of variance in cIMT. Identification of novel genetic and environmental factors underlying unexplained subclinical atherosclerosis is of outmost importance for future effective prevention of vascular disease.

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Viral encephalitis is a life-threatening condition with prognosis mainly depending on viral pathogenicity, host immunologic state, and availability of virostatic therapy [1]. The Toscana virus (TOSV) is an arthropod-borne virus transmitted by sandflies and typically causes a transient febrile illness [2]. Recently, reports have emerged that TOSV causes not only aseptic meningitis but also serious meningoencephalitis or encephalitis without meningitis [2][3][4][5][6][7][8]. We present a patient who travelled around Tuscany and developed progressive fatal encephalitis. Serological positive TOSV antibodies were detected, and the autopsy revealed lymphocytic viral encephalitis.The general condition of a 73-year-old previously healthy man deteriorated rapidly a couple of days after returning from a 3 week trip to Tuscany. First symptoms were dizziness and disturbance of balance. Internal medical assessment was unremarkable at that time. As symptoms progressed he was transferred to our department of neurology. On admission he was alert but disoriented, and initially psychomotorically retarded, later agitated. Meningeal signs were negative. Cranial nerve functions and reflexes were normal except for hearing impairment on both sides. Walking and standing showed a tendency to fall to the left and were only possible with help. No impairment of the motor nerves and no sensory disturbances were found.Repeated neuroimaging examinations (cCT/cMRI) were unremarkable. EEG-studies showed generally slowed activity, but no epileptiform discharges. The body temperature fluctuated between 37-39.5°C.The laboratory studies revealed a slightly elevated CRP without a rise in WBC count. The CSF showed a slightly elevated cell count (8/3; normal \3/3) with elevated protein (757 mg/dl; normal \450), indicating a disturbance of the blood-CSF barrier. PCR for HSV, VZV and FSME virus were negative; antibody specificity tests for HSV, VZV, and FSME were within normal ranges. Serological studies on Legionella, Treponema pallidum, HIV, Hepatitis C, Borreliose were negative as were blood cultures. Serologically IgG antibodies against TOSV were positive 1:640 and IgM antibodies against TOSV were positive 1:40 using IIFT. In the CSF IgG antibodies against TOSV were tested positive 1:10. With PCR TOSV could not be detected in the CSF.As encephalitis was clinically assumed, an anti-infectious treatment course with broad antibiotics and aciclovir was implemented without clinical benefit. The patient gradually deteriorated and progressed to an akinetic-mutistic state, which persisted 2 weeks after, leading to coma and death. Post-mortem examination revealed a grossly normal brain with no signs of brain swelling. Histologic examination showed dominant perivascular cuffing of mainly lymphocytes in H & E stained sections in various brain regions (neocortex, basal ganglia, hypothalamus, thalamus, limbic areas, brain stem) and sparse infiltration of inflammatory cells in the leptomeninges, typical of viral meningoencephalitis (Fig. 1). Immunohistochemistry (...

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In patients with VAH, the combination of several pathomechanisms of ischemic stroke and the contribution of several risk factors can cause the clinical manifestation of PCS.