Objectives Evidences from either small series or spontaneous reporting are accumulating that SARS-CoV-2 involves the Nervous Systems. The aim of this study is to provide an extensive overview on the major neurological complications in a large cohort of COVID-19 patients. Methods Retrospective, observational analysis on all COVID-19 patients admitted from February 23rd to April 30th, 2020 to ASST Papa Giovanni XXIII, Bergamo, Italy for whom a neurological consultation/neurophysiological assessment/neuroradiologic investigation was requested. Each identified neurologic complication was then classified into main neurologic categories. Results Of 1760 COVID-19 patients, 137 presented neurologic manifestations that manifested after COVID-19 symptoms in 98 pts and was the presenting symptom in 39. Neurological manifestations were classified as: (a) cerebrovascular disease [53 pts (38.7%)] including 37 ischemic and 11 haemorrhagic strokes, 4 transient ischemic attacks, 1 cerebral venous thrombosis; (b) peripheral nervous system diseases [31 (22.6%)] including 17 Guillain-Barrè syndromes; (c) altered mental status [49 (35.8%)] including one necrotizing encephalitis and 2 cases with RT-PCR detection of SARS-Cov-2 RNA in CSF; (d) miscellaneous disorders, among whom 2 patients with myelopathy associated with Ab anti-SARS-CoV-2 in CSF. Patients with peripheral nervous system involvement had more frequently severe ARDS compared to patients with cerebrovascular disease (87.1% vs 42%; difference = 45.1% 95% CI 42.0-48.2; χ 2 = 14.306; p < 0.0002) and with altered mental status (87.1% vs 55.6%; difference = 31.5% 95% CI 27.5-37.5%; χ 2 = 7.055; p < 0.01). Conclusion This study confirms that involvement of nervous system is common in SARS-CoV-2 infection and offers clinicians useful information for prevention and prompt identification in order to set the adequate therapeutic strategies.

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Background Alzheimer's disease (AD) patients often express significant behavioral symptoms: for this reason, accessible related biomarkers could be very useful. Neuroinflammation is a key pathogenic process in both AD and delirium (DEL), a clinical condition with behavioral symptoms resembling those of AD. Methods A total of n = 30 AD patients were recruited together with n = 30 DEL patients and n = 15 healthy controls (CTRL). Serum diazepam binding inhibitor (DBI), IL-17, IL-6, and TNF-α were assessed by ELISA. Results DBI serum levels were increased in AD patients with respect to CTRL (+ 81%), while DEL values were 70% higher than AD. IL-17 was increased in DEL with respect to CTRL (+ 146%), while AD showed dispersed values and failed to reach significant differences. On the other hand, IL-6 showed a more robust increase in DEL with respect to the other two groups (+ 185% and + 205% vs. CTRL and AD, respectively), and TNF-α failed to show any change. Conclusions DBI may be a very promising candidate for AD, perhaps marking psychomotor DEL-like symptoms, in view of developing future helping tool for practicing physicians. Furthermore, DBI rise in DEL offers novel cues for a better comprehension of the pathogenesis of this potentially fatal condition.

At the time of writing, the number of confirmed COVID‐19 cases in Italy has dropped off to less than 150 cases per day. Now we can finally take a breath and think back on what we have experienced during the last months in our hospital Papa Giovanni XXIII in Bergamo, Lombardy, the epicentre of the Italian pandemic.

Objective The purpose of this study was to evaluate cholesterol esterification and HDL subclasses in plasma and cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) patients. Methods The study enrolled 70 AD patients and 74 cognitively normal controls comparable for age and sex. Lipoprotein profile, cholesterol esterification, and cholesterol efflux capacity (CEC) were evaluated in plasma and CSF. Results AD patients have normal plasma lipids but significantly reduced unesterified cholesterol and unesterified/total cholesterol ratio. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate (CER), two measures of the efficiency of the esterification process, were reduced by 29% and 16%, respectively, in the plasma of AD patients. Plasma HDL subclass distribution in AD patients was comparable to that of controls but the content of small discoidal preβ-HDL particles was significantly reduced. In agreement with the reduced preβ-HDL particles, cholesterol efflux capacity mediated by the transporters ABCA1 and ABCG1 was reduced in AD patients’ plasma. The CSF unesterified to total cholesterol ratio was increased in AD patients, and CSF CER and CEC from astrocytes were significantly reduced in AD patients. In the AD group, a significant positive correlation was observed between plasma unesterified cholesterol and unesterified/total cholesterol ratio with Aβ1-42 CSF content. Conclusion Taken together our data indicate that cholesterol esterification is hampered in plasma and CSF of AD patients and that plasma cholesterol esterification biomarkers (unesterified cholesterol and unesterified/total cholesterol ratio) are significantly associated to disease biomarkers (i.e., CSF Aβ1-42).

Thrombotic complications are common in COVID-19 patients, but cerebral venous system involvement, timing after infection, optimal treatment, and long-term outcome are uncertain. We report a case of massive cerebral venous thrombosis and concomitant internal iliac vein thrombosis occurring in the late phase of paucisymptomatic COVID-19 infection. Mild respiratory symptoms, without fever, started 3 weeks before headache and acute neurological deficits. The patient had silent hypoxemia and typical COVID-19 associated interstitial pneumonia. Brain CT scan showed a left parietal hypodense lesion with associated sulcal subarachnoid hemorrhage. CT cerebral venography showed a massive cerebral venous thrombosis involving the right transverse sinus, the right jugular bulb, the superior sagittal sinus, the straight sinus, the vein of Galen, and both internal cerebral veins. Abdominal CT scan showed no malignancy but revealed an asymptomatic right internal iliac vein thrombosis. Both cerebral venous thrombosis and pelvic vein thrombosis were effectively treated with unfractionated heparin started on the day of admission, then shifted to low molecular weight heparin, with a favorable clinical course. Nasopharyngel swab, repeated twice, tested negative for SARS-CoV-2. Serological tests confirmed SARS-CoV-2 infection. Our case supports active surveillance and prevention of thrombotic complications associated with COVID-19, which may affect both peripheral and cerebral venous system. Early initiation of unfractionated heparin may lead to good neurologic outcome.

Objective: Cerebral amyloid angiopathy (CAA) is a major cause of spontaneous intracranial hemorrhage in older adults. Epilepsy represents a possible sequela of the disease. To date, studies on epilepsy in CAA are lacking, and the few data available mainly focus on CAA-related inflammation (CAA-ri), the inflammatory form of the disease. Methods:In this retrospective observational study, we consecutively recruited CAA patients observed over a time span of 10 years, collecting demographic, clinical, and instrumental data. Significant baseline characteristics were evaluated as potential risk factors for the development of epilepsy in the CAA population, and in the subgroups of CAA-ri and CAA without inflammatory reaction (CAA-nri).The effect of potential risk factors for epilepsy was measured as odds ratio with 95% confidence interval.Results: Within 96 recruited CAA cases, 33 (34.4%) developed epilepsy during follow-up (median = 13.5 months). The prevalent type of seizure was focal (81.3%); 12.1% of the epileptic patients presented status epilepticus, and 6.1% developed drug-resistant epilepsy. Electroencephalographic traces revealed slow and epileptic discharge activity in the majority of epileptic patients, but also in those without epilepsy. The presence of focal or disseminated cortical superficial siderosis (cSS) was associated with an increased risk of epilepsy in the CAA-nri group, and the association with CAA-ri and epilepsy was present in the overall population.Significance: Epilepsy is a common manifestation during the course of CAA, where CAA-ri and cSS represent predisposing factors for the development of seizures. These data suggest the importance of a deep characterization of CAA patients, to better select those more prone to develop epilepsy.

Background Subcortical vascular dementia (sVAD) is considered the most frequent dementia in old population, and it is due to a small vessel disease. It has a very specific nosography, where the dominant factors are dysexecutive functions, depression, and apathy. Very few studies described visual hallucinations in sVAD, apart from in the final stages of it. Methods This study recruited 577 patients with a diagnosis of sVAD associated with major ocular pathologies and 1118 patients with sVAD without any significant ocular pathology: Patients were followed up for 24 months. We studied the influence of ocular pathologies in precocious visual hallucinations, on behavior disorder (aggressiveness), and gait disorders (instability, fells). We registered the necessity of neuropsychiatric therapies, incidence of hospitalization, and institutionalization. Results What emerges from our study is that the ocular comorbidities might change the behavior profile of dementia, provoking behavioral alterations, and the need for therapies with adverse effects. As far as old age is a complicated status of life, many factors can modify its development. The possible contribution of multiple biological events cannot be neglected, particularly the underlying influence of chronic diseases as well as the geriatric conditions, per se, might compromise the cognitive functions and the pathological conditions. Ocular pathology as a superimposing event in sVAD might worse the outcome. A correct and rapid identification of critical patients might be relevant for the dynamic life events in these patients and their caregivers.