Increased human immunodeficiency virus viral load with cerebral infarction due to varicella zoster virus vasculopathy on treatment with bictegravir/emtricitabine/tenofovir alafenamide suspension: a case report and literature review.

BACKGROUND: Varicella-Zoster virus (VZV) vasculopathy occasionally occurs in immunocompromised patients and is difficult to treat. The risk factor and optimal therapy remain unclear. Patients with human immunodeficiency virus (HIV) and dysphagia or difficulty in oral intake receive antiretroviral therapy (ART) suspension. However, there remains little evidence regarding ART suspension. CASE PRESENTATION: We experienced a case of a 55-year-old man diagnosed with HIV and severe multiple cerebral infarctions due to VZV vasculopathy. We started on bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) and acyclovir (ACV), and prednisone. He was started on BIC/TAF/FTC suspension because of deteriorated swallowing. The HIV viral load was increased; however, no drug-resistance genes were detected. We successfully treated him with doltegravir/abacavir/lamibudine suspension. We performed two literature reviews of the administration of BIC/TAF/3TC suspension and VZV vasculopathy in patients with HIV. Three cases of BIC/TAF/3TC suspension were considered treatment failures. Recent history of VZV infection and a CD4 count under 200 µL may be risk factors for VZV vasculopathy. The effective treatment may be using steroid and ACV; however, treatment duration could differ. CONCLUSIONS: BIC/TAF/FTC suspension administration may be unstable, and treating ACV and steroid may be optimal therapy for VZV vasculopathy; however, the evidence level is low.

[Two Cases of Trousseau Syndrome during Chemotherapy].

Case 1 is a 56-year-old man. During postoperative adjuvant chemotherapy for pancreatic cancer, weakness in the right upper and lower limbs appeared, and a head CT scan was performed, but no abnormal findings were noted. Diffusion- weighted MRI scan of the head showed multiple cerebral infarcts, and a diagnosis of Trousseau syndrome was made. Case 2 is an 86-year-old man. During chemotherapy for postoperative recurrence of distal bile duct carcinoma, he developed weakness in the right upper and lower limbs, and a head MRI scan was performed. Diffusion-weighted MRI showed scattered high-signal areas, and a diagnosis of Trousseau syndrome was made. Trousseau syndrome is a condition in which stroke is caused by hypercoagulability associated with malignant tumor. The initial symptoms of cerebral infarction in patients with cancer are similar to those of chemotherapy-induced adverse events and brain metastases, and therefore, a head MRI scan is recommended even if there is no obvious abnormality on head CT scan.

Reversible cerebral vasoconstriction syndrome with cerebral infarction caused by acute high-level vapor exposure of ethylene oxide: a case report.

BACKGROUND: With the increasing production and use of ethylene oxide (EO) worldwide, its explicit bio-toxicity has drawn more and more attention. At present, most studies focus on chronic EO exposure. Studies on acute EO exposure are rare, especially with imaging studies. To our knowledge, this work is the first documented case of reversible cerebral vasoconstriction syndrome (RCVS) with cerebral infarction caused by EO. CASE PRESENTATION: A 58-year-old woman who worked in a capsule production factory got an unprotected acute EO inhalation due to accidental exposure to sterilization gas. She suffered from nausea, vomiting, and severe paroxysmal headaches, but the first brain MRI scan of the patient showed no significant abnormality. Nine days after inhalation, she developed recurrent thunderclap headaches and gradual complete blindness. The follow-up brain MRI, 12 days after inhalation, demonstrated extensive cytotoxic edema. Fifteen days and 21 days after EO (ethylene oxide) inhalation, head MRA and CTA respectively showed diffuse vasoconstriction of cerebral arteries. Fifty-nine days after EO inhalation, head MRA assessed reversibility of the vasoconstriction. According to clinical features and imaging findings, RCVS with cerebral infarction can be diagnosed. The patient was sensitive to light and light reflection but still blind after symptomatic and rehabilitation therapy. CONCLUSIONS: We report an acute EO exposure case in which the patient suffered from RCVS with cerebral infarction, which previous literature has not reported. This article aimed to raise awareness of encephalopathy after EO acute exposure.

Fatal Cerebral Infarction and Ophthalmic Artery Occlusion After Nasal Augmentation with Hyaluronic Acid-A Case Report and Review of Literature.

BACKGROUND: Cerebral infarction is a rare complication of hyaluronic acid (HA) filler injection, usually presenting with sudden increase in intracranial pressure and loss of vision. METHODS: A 40-year-old Asian woman in a coma was transferred to the emergency intensive care unit of Xijing Hospital, China, 48 h after nasal augmentation with HA. Magnetic resonance imaging indicated cerebral infarction and left optic nerve edema and ischemia. Magnetic resonance angiography did not reveal vessel embolism. RESULTS: The patient developed gastric ulceration, pulmonary infection, respiratory failure, and cerebral herniation, and died 6 days after the HA filler injection. CONCLUSION: Facial cosmetic HA filler injection can cause devastating and even fatal complications. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Trousseau's syndrome triggered by an immune checkpoint blockade in a non-small cell lung cancer patient.

PD-1 blockade therapy activates T cells by blocking the interaction between PD-1 and PD-L1 and promotes IFN-γ and Th1 cytokine production. In turn, IFN-γ and Th1 cytokines produced by activated T cells promote TF synthesis in monocytes/macrophages, which results in hypercoagulability leading to thrombosis.

Features of vascular adverse events in Japanese patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a retrospective study of the CML Cooperative Study Group database.

This study investigated the incidence rate and features of vascular adverse events (VAEs) in Japanese patients with chronic myeloid leukemia (CML) who were treated with tyrosine kinase inhibitors (TKIs). The analysis included 369 CML patients in the chronic or accelerated phases, selected from the CML Cooperative Study Group database; 25 events in 23 (6.2%) of these patients were VAEs. At the time of VAE incidence, nine patients were on treatment with imatinib, 12 with nilotinib, three with dasatinib, and one with bosutinib. VAE incidence comprised 13 cases of ischemic heart disease (IHD), eight of cerebral infarction (CI), and four of peripheral arterial occlusive disease (PAOD). IHD incidence rate in the study population was higher than that in the age-matched general population, particularly in nilotinib-treated patients, while CI incidence rate was almost equivalent. Compared with the Suita score, the SCORE chart and the Framingham score risk assessment tools detected more patients with high or very high risk of VAEs. In conclusion, incidence of IHD requires closer monitoring in nilotinib-treated patients. More detailed investigations for determining the most useful tool to predict VAE incidence and long-term analysis of therapy-related VAE cases are needed for improving safety during TKI therapy.

Would intravitreal bevacizumab injection increase risk of cerebral infarction?

BACKGROUND AND PURPOSE: Although studies have evaluated the relationship between intravitreal bevacizumab (IVB) injection and cerebral infarction (CI), the effects of IVB on CI are still not clear. The aim of this study was to investigate the effects of IVB injection on patients with CI with age-related macular degeneration (AMD). METHODS: We retrospectively reviewed patients with AMD who received IVB injections for 1 year and determined the incidence of CI within 60 days after IVB injection to analyze the possible association between IVB and CI. RESULTS: A total of 263 patients were enrolled over a 12-month period. Six patients (2.28%) were diagnosed with CI within 2 months after receiving an IVB injection. The incidence of CI in patients of 75-84 years of age was 6.38%. These results showed a higher incidence for patients with IVB injections than the results of previous epidemiological studies (0.13% for all age groups, 1.68% for patients of 75-84 years of age). All CIs occurred 21-53 days after the IVB injection (mean: 39.33 ± 14.65 days). Logistic regression analyses showed that age and CI history were factors associated with CI. CONCLUSIONS: Treatment with IVB might be an independent risk factor for CI. These results are useful for planning treatment strategies for patients with AMD and for prevention of CI.

Anabolic androgenic steroids, an easily forgotten cause of polycythaemia and cerebral infarction.

Excessive anabolic androgenic steroids (both exogenous and endogenous) are known causes of polycythaemia and ischaemic cardiovascular events. Despite this, they are commonly forgotten in the workup of patients. We report a case of exogenous anabolic androgenic steroid-induced polycythaemia and stroke and explore possible pitfalls for clinicians.

Factor V Leiden mutation triggering four major complications to standard dose cisplatin-chemotherapy for testicular seminoma: a case report.

BACKGROUND: Major life-threatening complications secondary to cisplatin-based chemotherapy are rare in patients with testicular germ cell tumour (GCT). The incidence of complications increases with dosage of chemotherapy and with a variety of patient-related as well as disease-related conditions. We here report the first case of GCT experiencing as many as four major complications most of which can be explained by the conjunction of several predispositions. CASE PRESENTATION: A 48 year old patient with testicular seminoma and bulky retroperitoneal and mediastinal metastases underwent cisplatin based chemotherapy. During the third cycle of chemotherapy, he developed thrombosis of the central venous port device, subtotal splenic infarction, and Bleomycin induced pneumonitis (BIP). Three months after completion of therapy, he was struck by thalamic infarction. Genetic testing then revealed heterozygote mutation of Factor V Leiden (FVL). He received full-dose warfarin anticoagulation treatment and steroid treatment for BIP. 18 months thereafter, the patient is still disease-free, oncologically. Neurological symptoms have disappeared, but pulmonary dysfunction persists with a vital capacity of 50%. CONCLUSION: The unique co-incidence of four major complications occurring in this patient were obviously triggered by the genetically determined predisposition of the patient to thrombotic events (FVL). Additionally, several patient-related and disease-related conditions contributed to the unique pattern of complications, i.e. (1) the slightly advanced age (48 years), (2) the prothrombotic condition caused by the disease of cancer, (3) the central venous port device, (4) retroperitoneal bulky metastasis, and (5) cisplatin chemotherapy. Whether or not FVL contributed to the pulmonary fibrosis as well, remains elusive. Practically, in the case of one major vascular complication during cisplatin chemotherapy at standard dose, genetic testing for hereditary thrombophilia should be considered. Thus, precautions for preventing further complications could be initiated.

Prothrombin complex concentrate (Beriplex P/N)-related renal and cerebral infarctions in a patient with warfarin-associated intracerebral hemorrhage.

A 45-year-old man receiving warfarin treatment suffered from an intracerebral hemorrhage. Four-factor prothrombin complex concentrate (PCC) was administered to correct coagulopathy. However, bilateral renal infarcts and a cerebral infarct developed on day 5 and 7, respectively after PCC administration. Although the occurrence of PCC-related thromboembolism is low, health care practitioners should closely follow-up the symptoms and signs of thrombosis after PCC administration.

[Assessment of risk of cerebral infarction and benefit of anticoagulant therapy in a patient with atrial fibrillation]. / Eteisvärinäpotilaan aivoinfarktin vaaran ja antikoagulaatiohoidon hyödyn arviointi.

The risk of cerebral infarction in patients with atrial fibrillation varies from 0.5% to more than 10% per year. Anticoagulant therapy is recommended today more than before, but to a low-risk patient anticoagulation may cause harm that is larger than the expected benefit. Assessment of the risk of cerebral infarction is therefore essential. Use of the CHA2DS2-VASc risk index enables reliable identification of low-risk patients who do not benefit from anticoagulation. Individual treatment decisions may even be necessary.

Electrophysiological correlations of morphological restructuring in experimental local ischemia of different severity in the rat sensorimotor cortex.

Local cerebrovascular disorders were modeled by reversible photochemical clotting of hemispheric cortical vessels. Mild ischemia led to reversible edema in the surface layers of the cortex: cytotoxic edema of the neuropile, primarily of the distal dendrites. This status led to an increase in the lower delta rhythm frequency band power. After administration of systemic anesthetic, delta rhythm appeared sooner in the ischemic foci than in intact cortical areas. More severe ischemia led to the appearance of dark and pyknotic neurons and reduction of oscillation power in all EEG spectrum bands. Restructuring of primarily dendrites caused by local moderate ischemia of the surface cortical layers at the early stage of neurodegenerative processes stimulated the inhibitory recovery processes.

Risk of recurrent stroke in patients with atrial fibrillation treated with oral anticoagulants alone or in combination with anti-platelet therapy.

INTRODUCTION: Ischaemic stroke patients with atrial fibrillation (AF) are at high risk of stroke recurrence despite oral anticoagulation therapy. Patients with cardiovascular comorbidities may take both antiplatelet and oral anticoagulation therapy (OAC/AP). Our study aims to evaluate the safety and efficacy of OAC/AP therapy as secondary prevention in people with AF and ischaemic stroke. PATIENTS AND METHODS: We performed a post-hoc analysis of pooled individual data from multicenter prospective cohort studies and compared outcomes in the OAC/AP cohort and patients on DOAC/VKA anticoagulation alone (OAC cohort). Primary outcome was a composite of ischaemic stroke, systemic embolism, intracranial bleeding, and major extracranial bleeding, while secondary outcomes were ischaemic and haemorrhagic events considered separately. A multivariable logistic regression analysis was performed to identify independent predictors for outcome events. To compare the risk of outcome events between the two cohorts, the relation between the survival function and the set of explanatory variables were calculated by Cox proportional hazard models and the results were reported as adjusted hazard ratios (HR). Finally another analysis was performed to compare the overall risk of outcome events in both OAC/AP and OAC cohorts after propensity score matching (PSM). RESULTS: During a mean follow-up time of 7.5 ± 9.1 months (median follow-up time 3.5 months, interquartile range ±3), 2284 stroke patients were on oral anticoagulants and 215 were on combined therapy. The multivariable model demonstrated that the composite outcome is associated with age (OR: 1.03, 95% CI: 1.01-1.04 for each year increase) and concomitant antiplatelet therapy (OR: 2.2, 95% CI: 1.48-3.27), the ischaemic outcome with congestive heart failure (OR: 1.55, 95% CI: 1.02-2.36) and concomitant antiplatelet therapy (OR: 1.93, 95% CI: 1.19-3.13) and the haemorrhagic outcome with age (OR: 1.03, 95% CI: 1.01-1.06 for each year increase), alcoholism (OR: 2.15, 95% CI: 1.06-4.39) and concomitant antiplatelet therapy (OR: 2.22, 95% CI: 1.23-4.02). Cox regression demonstrated a higher rate of the composite outcome (hazard ratio of 1.93 [95% CI, 1.35-2.76]), ischaemic events (HR: 2.05 [95% CI: 1.45-2.87]) and bleeding outcomes (HR: 1.90 [95% CI, 1.06-3.40]) in OAC/AP cohort. After PSM analysis, the composite outcome remained more frequent in people treated with OAC + AP (RR: 1.70 [95% CI, 1.05-2.74]). DISCUSSION: Secondary prevention with combination of oral anticoagulant and antiplatelet therapy after ischaemic stroke was associated with worse outcomes in our cohort. CONCLUSION: Further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischaemic stroke in patients with atrial fibrillation.

Cerebral infarction after treatment with dabrafenib plus trametinib for BRAF-V600E-positive non-small cell lung cancer: A case report.

Dabrafenib plus trametinib is the standard treatment for BRAF V600E-mutated non-small cell lung cancer. No treatment-related cerebral infarction (CI) has been reported in previous clinical trials. Here, we described a 61-year-old Japanese man with BRAF V600E-mutated lung adenocarcinoma treated with dabrafenib plus trametinib as a third-line treatment. On the 10th day of dabrafenib plus trametinib treatment, the patient developed fever and was urgently hospitalized on the 18th day owing to impaired consciousness. The patient had disseminated intravascular coagulation because of infection, was treated with thrombomodulin and ceftriaxone, and subsequently improved. On the 44th day, dabrafenib plus trametinib was resumed with a one-step dose reduction. Three hours after the first oral administration, the patient developed chills, fever, and hypotension. He received intravenous fluids. On the 64th day, 20 mg prednisolone was administered from the previous day, and dabrafenib plus trametinib was resumed with a further one-step reduction in dose. Five hours after the first oral administration, the patient developed fever, hypotension, paralysis of the right upper and lower limbs, and dysarthria appeared. Head magnetic resonance imaging revealed multiple cerebral infarcts. Hemoconcentration because of intravascular dehydration may have caused CI. In conclusion, CI should be taken into consideration during treatment with dabrafenib plus trametinib.

Cilostazol reduces the risk of hemorrhagic infarction after administration of tissue-type plasminogen activator in a murine stroke model.

BACKGROUND AND PURPOSE: Prior use of antiplatelet agents improves stroke outcome in patients undergoing thrombolytic therapy as shown by reduced arterial reocclusion, although the risk of cerebral hemorrhage can be increased. METHODS: The effect of cilostazol, an antiplatelet drug that improves endothelial function through upregulation of intracellular cAMP, on cerebral hemorrhage after thrombolytic therapy was investigated using a highly reproducible transient ischemia model. RESULTS: Treatment with cilostazol for 7 days before ischemia significantly suppressed the risk and severity of cerebral hemorrhage after injection of tissue-type plasminogen activator, although treatment with aspirin had no such protective effect compared with nontreated mice. Immunohistological analysis revealed that treatment with cilostazol suppressed disruption of the microvasculature in the ischemic area associated with reduced matrix metalloproteinase-9 activity. CONCLUSIONS: Our results suggest that patients treated with cilostazol before onset of stroke could have a lower risk of cerebral hemorrhage after thrombolytic therapy and might also have a longer therapeutic time window for thrombolysis. Furthermore, the risk of cerebral hemorrhage can be significantly altered by prestroke therapies, and analysis of the effects of multiple drugs on tissue-type plasminogen activator-induced cerebral hemorrhage in animal models is essential for the extending safe and effective thrombolytic therapy to a wider group of patients.

Influence of constraint-induced movement therapy upon evoked potentials in rats with cerebral infarction.

Constraint-induced movement therapy (CIMT) is an effective treatment promoting motor recovery of upper extremity function in stroke patients. The objective of the present study was to determine the effect of CIMT on the evoked potentials in rats with focal cerebral cortical ischemia induced by endothelin-1 (ET-1). Thirty rats were randomly assigned to the sham, infarct or CIMT groups. ET-1 was injected stereotaxically into the forelimb area of the cerebral cortex in the dominant hemisphere. Custom-made constraint jackets were applied to limit movement of the unaffected forelimb in the CIMT group. Motor and sensory function of the forelimb was evaluated by a pellet retrieval task and forearm asymmetry test. Electrophysiologic changes were evaluated by motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SEPs). The location and extent of cerebral ischemia were confirmed and compared histologically. The CIMT group showed better recovery in the pellet retrieval task. Forelimb use was more symmetrical in the CIMT group. The waveform of the SEP was reversed and delayed in the infarct group, but it was preserved in the CIMT group with amplitude decrease only. The estimated volume of infarction was smaller in the CIMT group, although statistically not significant. The results demonstrate that CIMT can promote recovery of motor function in focal cerebral cortical infarcts, and that recovery may be related to reorganization of the cerebral neuronal network in the somatosensory pathway.

Ambient air pollutants and acute case-fatality of cerebro-cardiovascular events: Takashima Stroke and AMI Registry, Japan (1988-2004).

BACKGROUND: Apart from the conventional risk factors, cerebro-cardiovascular disease (CVD) are also reported to be associated with air pollution, thus lowering the level of exposure might contribute in prevention activities to reduce the associated adverse outcomes. Though few studies conducted in Japan have reported on the CVD mortality but none have explored the effect of air pollutant exposure on the acute case-fatality of CVD. We investigated the effects of air pollution exposure on acute case-fatality of stroke and acute myocardial infarction (AMI) in a setting where pollutant levels are rather low. METHODS: We leveraged the data from the Takashima Stroke and AMI Registry, which covers a population of approximately 55,000 in Takashima County located in central Japan. The study period of 6,210 days (16 years, leap years also taken into account) were divided into quartiles of daily average pollutant concentration; suspended particulate matter (SPM), sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)), and photochemical oxidants (Ox). The stroke and AMI events were categorized to corresponding quartiles based on the pollution levels of the onset day. To study the effects of air pollutants, we estimated the fatality rate ratio across quartiles of the pollutants where the lowest quartile served as the reference. RESULTS: There were 307 (men: 153 and women: 154) fatal stroke cases within 28 days of onset among the 2,038 first ever stroke during 1988-2004. In the same period, there were 142 (men: 94 and women: 54) fatal AMI cases within 28 days of onset among the 429 first ever AMI events. The mean of the measured pollutant levels were as follows: SPM 26.9 µg/m(3), SO(2) 3.9 ppb, NO(2) 16.0 ppb, and Ox 28.4 ppb. Among the pollutants, higher levels of NO(2) showed increased fatality risk. In multi-pollutant model, the highest quartile of NO(2) was associated with 60% higher stroke case-fatality risk in comparison to lowest quartile of NO(2). In the fully adjusted model the fatality-rate ratio was 1.65 (95% CI 1.06-2.57). This association was more prominent among stroke subtype of cerebral infarction. Other pollutant levels did not show any association with stroke or AMI case-fatality. CONCLUSION: We observed association between NO(2) levels, an index of traffic related air pollution, with the acute case-fatality of stroke, especially cerebral infarction in our study population. Further studies are needed in different regions to determine the association between ambient air pollutants and acute cardiovascular fatalities.

Cerebral infarction in a young man using high-dose anabolic steroids.

Anabolic androgenic steroid (AAS) abuse has increased among athletes in recent years. However, AAS abuse can increase hypercoagulopathy and cause cerebrovascular disease. We report a case of a 27-year-old man who had right hemiparalysis, hemianopia, dysarthria, and double vision in the middle of muscle training. He suspected acute disseminated encephalomyelitis at first, because of a preceding respiratory infection. However, extensive work-up was performed, including brain magnetic resonance imaging, transcranial Doppler and transesophageal echocardiography, confirming the final diagnosis of cardioembolic stroke. Physicians should be aware that cerebrovascular disease may be a side effect of AAS, even in younger populations.

[Neurological adverse events under anti-TNF alpha therapy]. / Évènements neurologiques sous traitement par anti-TNF alpha.

INTRODUCTION: Anti-TNF alpha treatments are increasingly prescribed in various rheumatological or gastroenterological inflammatory diseases. Several adverse events, including neurological episodes have been reported in the literature. Relation to treatment is a major concern and guidelines for management of those patients are not available. The aim of our study is to collect and analyze neurological adverse events occurring during anti-TNF alpha therapy, and to propose guidelines for diagnosis of demyelinating-induced diseases. METHODS: All patients treated with anti-TNF alpha drug, who were addressed in our department following a neurological event, were collected. We gathered clinical data including previous neurological history and immunosuppressive treatments. Paraclinical data included brain and spinal MRI, CSF study and outcome after anti-TNF therapy was collected. RESULTS: Nine patients were included in this study. Sex ratio was eight and mean age was 49±9 years. One patient had previous history of subarachnoïdian hemorrage. All the patients previously received immunosuppressive drugs, including methotrexate (nine) and leflunomide (four). Three patients had a brain MRI before initiation of anti-TNF treatment, which was normal. Clinical episode was stroke-like in three cases, clinically isolated syndrome (CIS) in five cases, and peripheral neuropathy in one case. MRI showed lesions suggestive of demyelinating T2 hyperintensities in four cases, vascular infarcts in two cases, and non-specific T2 hyperintensities in three cases. Barkhof and Tintore criteria were fulfilled in one of the four CIS cases. CSF study was available for six patients. It was normal (four cases), showed oligoclonal bands (one case) and lymphocytic meningitis (one case). Anti-TNF alpha discontinuation was decided in five cases. Outcome was favorable for eight patients. One patient, whom MRI fulfilled Barkhof and Tintore criteria, and CSF showed oligoclonal bands, further developed relapsing remitting multiple sclerosis. CONCLUSION: Our study is compatible with data found in the literature. Barkhof and Tintore criteria and CSF study are useful in clinical practice to diagnose a first demyelinating event. Standardized paraclinical neurological explorations should be proposed to physicians who are in charge of anti-TNF treated patients.