Progressive multifocal leukoencephalopathy in multiple myeloma: a case report of a patient with SARS-CoV-2 infection and an updated systematic literature review.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by a reactivation of the human polyomavirus 2 (HPyV-2, previously known as JCV) in immunosuppressed individuals. Few cases of PML have been described in multiple myeloma (MM) patients. METHODS: We described a case of PML in a patient with MM with fatal worsening that occurred during SARS-CoV-2 infection. We also performed a literature review to update the 16 cases series of MM patients with PML already collected until April 2020. RESULTS: A 79-year-old female patient with refractory IgA lambda MM in Pomalidomide- Cyclophosphamide-Dexamethasone regimen developed gradual lower limbs and left arm paresis along with a decreased consciousness 3.5 years after the MM diagnosis. Symptoms developed shortly after the recognition of hypogammaglobulinemia. After SARS-CoV-2 infection, her neurological status quickly worsened until she deceased. MRI features and JCV-positive PCR on CSF confirmed the PML diagnosis. Our literature review adds sixteen clinical cases of PML in MM published between May 2020 and March 2023 to the 16 cases already collected in the previously published review by Koutsavlis. DISCUSSION: PML has been increasingly described in MM patients. It remains questionable if the HPyV-2 reactivation is determined by the severity of MM itself, by the effect of drugs or by a combination of both. SARS-CoV-2 infection may have a role in worsening PML in affected patients.

Angioedema after rt-PA infusion led to airway emergency: a case report of rescue treatment with fresh frozen plasma

Abstract The authors report the case of a 71-year-old woman presented to the Emergency Department with acute ischemic stroke. She was treated with rt-PA and interventional endovascular revascularization and developed rapidly progressing angioedema that led to emergency intubation. The standard treatment was not very effective and the swelling improved after infusion of fresh frozen plasma. Angioedema after rt-PA infusion could be a life-threatening emergency that requires quick airway management by skilled professionals. As this condition is triggered by several factors, such as unregulated histamine and bradykinin production, the traditional treatment recommended by the guidelines may not be sufficient and the use of FFP can be considered as a safe and valuable aid.

Imaging features and ultraearly hematoma growth in intracerebral hemorrhage associated with COVID-19.

PURPOSE: Intracerebral hemorrhage (ICH) is an uncommon but deadly event in patients with COVID-19 and its imaging features remain poorly characterized. We aimed to describe the clinical and imaging features of COVID-19-associated ICH. METHODS: Multicenter, retrospective, case-control analysis comparing ICH in COVID-19 patients (COV19 +) versus controls without COVID-19 (COV19 -). Clinical presentation, laboratory markers, and severity of COVID-19 disease were recorded. Non-contrast computed tomography (NCCT) markers (intrahematoma hypodensity, heterogeneous density, blend sign, irregular shape fluid level), ICH location, and hematoma volume (ABC/2 method) were analyzed. The outcome of interest was ultraearly hematoma growth (uHG) (defined as NCCT baseline ICH volume/onset-to-imaging time), whose predictors were explored with multivariable linear regression. RESULTS: A total of 33 COV19 + patients and 321 COV19 - controls with ICH were included. Demographic characteristics and vascular risk factors were similar in the two groups. Multifocal ICH and NCCT markers were significantly more common in the COV19 + population. uHG was significantly higher among COV19 + patients (median 6.2 mL/h vs 3.1 mL/h, p = 0.027), and this finding remained significant after adjustment for confounding factors (systolic blood pressure, antiplatelet and anticoagulant therapy), in linear regression (B(SE) = 0.31 (0.11), p = 0.005). This association remained consistent also after the exclusion of patients under anticoagulant treatment (B(SE) = 0.29 (0.13), p = 0.026). CONCLUSIONS: ICH in COV19 + patients has distinct NCCT imaging features and a higher speed of bleeding. This association is not mediated by antithrombotic therapy and deserves further research to characterize the underlying biological mechanisms.

Clinical Features of Patients With Cervical Artery Dissection and Fibromuscular Dysplasia.

BACKGROUND AND PURPOSE: Observational studies have suggested a link between fibromuscular dysplasia and spontaneous cervical artery dissection (sCeAD). However, whether patients with coexistence of the two conditions have distinctive clinical characteristics has not been extensively investigated. METHODS: In a cohort of consecutive patients with first-ever sCeAD, enrolled in the setting of the multicenter IPSYS CeAD study (Italian Project on Stroke in Young Adults Cervical Artery Dissection) between January 2000 and June 2019, we compared demographic and clinical characteristics, risk factor profile, vascular pathology, and midterm outcome of patients with coexistent cerebrovascular fibromuscular dysplasia (cFMD; cFMD+) with those of patients without cFMD (cFMD-). RESULTS: A total of 1283 sCeAD patients (mean age, 47.8±11.4 years; women, 545 [42.5%]) qualified for the analysis, of whom 103 (8.0%) were diagnosed with cFMD+. In multivariable analysis, history of migraine (odds ratio, 1.78 [95% CI, 1.13-2.79]), the presence of intracranial aneurysms (odds ratio, 8.71 [95% CI, 4.06-18.68]), and the occurrence of minor traumas before the event (odds ratio, 0.48 [95% CI, 0.26-0.89]) were associated with cFMD. After a median follow-up of 34.0 months (25th to 75th percentile, 60.0), 39 (3.3%) patients had recurrent sCeAD events. cFMD+ and history of migraine predicted independently the risk of recurrent sCeAD (hazard ratio, 3.40 [95% CI, 1.58-7.31] and 2.07 [95% CI, 1.06-4.03], respectively) in multivariable Cox proportional hazards analysis. CONCLUSIONS: Risk factor profile of sCeAD patients with cFMD differs from that of patients without cFMD. cFMD and migraine are independent predictors of midterm risk of sCeAD recurrence.

Significant low prevalence of antibodies reacting with simian virus 40 mimotopes in serum samples from patients affected by inflammatory neurologic diseases, including multiple sclerosis.

Many investigations were carried out on the association between viruses and multiple sclerosis (MS). Indeed, early studies reported the detections of neurotropic virus footprints in the CNS of patients with MS. In this study, sera from patients affected by MS, other inflammatory (OIND) and non-inflammatory neurologic diseases (NIND) were analyzed for antibodies against the polyomavirus, Simian Virus 40 (SV40). An indirect enzyme-linked immunosorbent assay (ELISA), with two synthetic peptides, which mimic SV40 antigens, was employed to detect specific antibodies in sera from patients affected by MS, OIND, NIND and healthy subjects (HS). Immunologic data indicate that in sera from MS patients antibodies against SV40 mimotopes are detectable with a low prevalence, 6%, whereas in HS of the same mean age, 40 yrs, the prevalence was 22%. The difference is statistically significant (P = 0.001). Significant is also the difference between MS vs. NIND patients (6% vs. 17%; P = 0.0254), whereas no significant difference was detected between MS vs OIND (6% vs 10%; P>0.05). The prevalence of SV40 antibodies in MS patients is 70% lower than that revealed in HS.

Multiple sclerosis lymphocytes upregulate A2A adenosine receptors that are antiinflammatory when stimulated.

Multiple sclerosis (MS) is an autoimmune-mediated inflammatory disease characterized by multifocal areas of demyelination. Experimental evidence indicates that A2A adenosine receptors (ARs) play a pivotal role in the inhibition of inflammatory processes. The aim of this study was to investigate the contribution of A2A ARs in the inhibition of key pro-inflammatory mediators for the pathogenesis of MS. In lymphocytes from MS patients, A1, A2A, A2B, and A3 ARs were analyzed by using RT-PCR, Western blotting, immunofluorescence, and binding assays. Moreover the effect of A2A AR stimulation on proinflammatory cytokine release such as TNF-α, IFN-γ, IL-6, IL-1ß, IL-17, and on lymphocyte proliferation was evaluated. The capability of an A2A AR agonist on the modulation of very late antigen (VLA)-4 expression and NF-κB was also explored. A2A AR upregulation was observed in lymphocytes from MS patients in comparison with healthy subjects. The stimulation of these receptors mediated a significant inhibition of TNF-α, IFN-γ, IL-6, IL-1ß, IL-17, and cell proliferation as well as VLA-4 expression and NF-κB activation. This new evidence highlights that A2A AR agonists could represent a novel therapeutic tool for MS treatment as suggested by the antiinflammatory role of A2A ARs in lymphocytes from MS patients.

A2A adenosine receptors are up-regulated in lymphocytes from amyotrophic lateral sclerosis patients.

Adenosine, a purine nucleoside interacting with A1, A2A, A2B and A3 adenosine receptors (ARs), is a potent endogenous modulator of inflammatory and neuronal processes involved in the pathophysiology of several neurodegenerative diseases. In the present study, ARs were investigated in lymphocytes from patients with amyotrophic lateral sclerosis (ALS) and compared with age-matched healthy subjects. In ALS patients A2AARs were analysed by using RT-PCR, Western blotting and saturation binding experiments. The effect of A2AAR stimulation on cyclic AMP levels was evaluated in lymphocytes from ALS patients and healthy subjects. An up-regulation of A2AARs was observed in ALS patients with respect to healthy subjects while A1, A2B and A3AR affinity and density did not change. In ALS patients, the A2AAR density values correlated with the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Furthermore, the stimulation of A2AARs mediated a significant increase in cyclic AMP levels in lymphocytes from ALS patients, with a higher potency than in lymphocytes from healthy subjects. In conclusion, the positive correlation between A2AAR density and ALSFRS-R scores could indicate a possible protective effect of this receptor subtype, representing an interesting starting point for the study of alternative therapeutic approaches for ALS based on A2AAR modulation.