Twelve-year neurocognitive decline in HIV is associated with comorbidities, not age: a CHARTER study.

Modern antiretroviral therapy (ART) has increased longevity of people with HIV and shifted the age distribution of the HIV pandemic upward toward that of the general population. This positive development has also led to concerns about premature and/or accelerated neurocognitive and physical ageing due to the combined effects of chronic HIV, accumulating comorbidities, adverse effects or possible toxicities of ART and biological ageing. Here we present results of comprehensive assessments over 12 years of 402 people with HIV in the CNS HIV ART Effects Research (CHARTER) programme, who at follow-up were composed of younger (<60 years) and older (≥60 years) subgroups. Over the 12 years, ART use and viral suppression increased in both subgroups as did systemic and psychiatric comorbidities; participants in both subgroups also evidenced neurocognitive decline beyond what is expected in typical ageing. Contrary to expectations, all these adverse effects were comparable in the younger and older CHARTER subgroups, and unrelated to chronological age. Neurocognitive decline was unrelated to HIV disease or treatment characteristics but was significantly predicted by the presence of comorbid conditions, specifically diabetes, hypertension, chronic pulmonary disease, frailty, neuropathic pain, depression and lifetime history of cannabis use disorder. These results are not consistent with premature or accelerated neurocognitive ageing due to HIV itself but suggest important indirect effects of multiple, potentially treatable comorbidities that are more common among people with HIV than in the general population. Good medical management of HIV disease did not prevent these adverse outcomes, and increased attention to a range of comorbid conditions in people with HIV may be warranted in their care.

Neurologic complications in patients receiving aortic versus subclavian versus femoral arterial cannulation for post-cardiotomy extracorporeal life support: results of the PELS observational multicenter study.

BACKGROUND: Cerebral perfusion may change depending on arterial cannulation site and may affect the incidence of neurologic adverse events in post-cardiotomy extracorporeal life support (ECLS). The current study compares patients' neurologic outcomes with three commonly used arterial cannulation strategies (aortic vs. subclavian/axillary vs. femoral artery) to evaluate if each ECLS configuration is associated with different rates of neurologic complications. METHODS: This retrospective, multicenter (34 centers), observational study included adults requiring post-cardiotomy ECLS between January 2000 and December 2020 present in the Post-Cardiotomy Extracorporeal Life Support (PELS) Study database. Patients with Aortic, Subclavian/Axillary and Femoral cannulation were compared on the incidence of a composite neurological end-point (ischemic stroke, cerebral hemorrhage, brain edema). Secondary outcomes were overall in-hospital mortality, neurologic complications as cause of in-hospital death, and post-operative minor neurologic complications (seizures). Association between cannulation and neurological outcomes were investigated through linear mixed-effects models. RESULTS: This study included 1897 patients comprising 26.5% Aortic (n = 503), 20.9% Subclavian/Axillary (n = 397) and 52.6% Femoral (n = 997) cannulations. The Subclavian/Axillary group featured a more frequent history of hypertension, smoking, diabetes, previous myocardial infarction, dialysis, peripheral artery disease and previous stroke. Neuro-monitoring was used infrequently in all groups. Major neurologic complications were more frequent in Subclavian/Axillary (Aortic: n = 79, 15.8%; Subclavian/Axillary: n = 78, 19.6%; Femoral: n = 118, 11.9%; p < 0.001) also after mixed-effects model adjustment (OR 1.53 [95% CI 1.02-2.31], p = 0.041). Seizures were more common in Subclavian/Axillary (n = 13, 3.4%) than Aortic (n = 9, 1.8%) and Femoral cannulation (n = 12, 1.3%, p = 0.036). In-hospital mortality was higher after Aortic cannulation (Aortic: n = 344, 68.4%, Subclavian/Axillary: n = 223, 56.2%, Femoral: n = 587, 58.9%, p < 0.001), as shown by Kaplan-Meier curves. Anyhow, neurologic cause of death (Aortic: n = 12, 3.9%, Subclavian/Axillary: n = 14, 6.6%, Femoral: n = 28, 5.0%, p = 0.433) was similar. CONCLUSIONS: In this analysis of the PELS Study, Subclavian/Axillary cannulation was associated with higher rates of major neurologic complications and seizures. In-hospital mortality was higher after Aortic cannulation, despite no significant differences in incidence of neurological cause of death in these patients. These results encourage vigilance for neurologic complications and neuromonitoring use in patients on ECLS, especially with Subclavian/Axillary cannulation.

Cerebral thromboembolic complications during cerebral angiography and their risk factors in different subgroups: Analysis of 2,457 procedures.

PURPOSE: Diagnostic cerebral digital subtraction angiography (DSA) is an invasive examination that involves catheterization of the major supra-aortic arterial trunks and evaluation of intracranial vessels for diagnostic purposes. Although considered the gold standard method for investigating cerebrovascular diseases, DSA carries measurable and potentially serious complication rates. This report describes the frequency of neurological and non-neurological complications of DSA performed in five hospitals in the state of São Paulo, Brazil, and analyzes them in different disease subgroups. It has a special focus on thromboembolic cerebral complications. METHODS: We retrospectively reviewed clinical records of all adult patients who underwent DSAs between January 2019 and December 2022. Demographic variables, DSA reports, CT/MRI reports, and clinical follow-up notes were reviewed. RESULTS: Twenty-four patients experienced some type of complication among 2,457 diagnostic DSAs (0.97%). Thromboembolic complications were recorded in 9 patients (0.36%), and access site hematomas larger than 5 cm were registered in six patients (0.24%). There was a statistical trend for thromboembolic complications in patients with cervical and/or intracranial atherosclerosis (p = 0.07), but age was not associated with them (p = 0.93). Patients who received heparin had lower rates of embolic complications than those who did not receive it, but there was no statistically significant difference (p = 0.17). Intravenous administration of heparin showed a trend toward significance with groin hematoma (p = 0.10). CONCLUSION: Diagnostic catheter DSAs have low complication rates.

Early Surgery for Infective Endocarditis Complicated With Neurologic Injury.

OBJECTIVES: To estimate the association between early surgery and the risk of mortality in patients with left-sided infective endocarditis in the context of stroke. DESIGN: Retrospective cohort study. SETTING: This study was a multiinstitution study based on the Chang Gung Research Database, which contains electronic medical records from 7 hospitals in northern and southern Taiwan; these include 2 medical centers, 2 regional hospitals, and 3 district hospitals. PARTICIPANTS: Patients with active left-sided infective endocarditis who underwent valve surgery between September 2002 and December 2018. INTERVENTIONS: The authors divided patients into 2 groups, with versus without preoperative neurologic complications, had undergone early (within 7 d) or later surgery, and with brain ischemia or hemorrhage. MEASUREMENTS AND MAIN RESULTS: Three hundred ninety-two patients with a median time from diagnosis to surgery of 6 days were included. No significant differences in postoperative stroke, in-hospital mortality, or follow-up outcomes were observed between the patients with and without neurologic complications. Among the patients with preoperative neurologic complications, patients who underwent early surgery had a lower 30-day postoperative mortality rate (13.1% v 25.8%; hazard ratio, 0.21; 95% CI 0.07-0.67). In the subgroup analysis of the comparison between brain ischemia and hemorrhage groups, there was no significant between-group difference in the in-hospital outcomes or outcomes after discharge. CONCLUSIONS: Early cardiac surgery may be associated with more favorable clinical outcomes in patients with preoperative neurologic complications. Thus, preoperative neurologic complications should not delay surgical interventions.

Comparison of upper extremity and transfemoral access for fenestrated-branched endovascular aortic repair.

OBJECTIVE: The use of upper extremity (UE) access is an accepted and often implemented approach for fenestrated/branched endovascular aortic aneurysm repair (F-BEVAR). The advent of steerable sheaths has enabled the performance of F-BEVAR using a total transfemoral (TF) approach without UE access, potentially decreasing the risks of cerebral embolic events. The purpose of the present study was to assess the outcomes of F-BEVAR using UE vs TF access. METHODS: Prospectively collected data from nine physician-sponsored investigational device exemption studies at U.S. centers were analyzed using a standardized database. All patients were treated for complex abdominal aortic aneurysms (CAAAs) and thoracoabdominal aortic aneurysms (TAAAs) using industry-manufactured fenestrated and branched stent grafts between 2005 and 2020. The outcomes were compared between patients who had undergone UE vs total TF access. The primary composite outcome was stroke or transient ischemia attack (TIA) and 30-day or in-patient mortality during the perioperative period. The secondary outcomes included technical success, local access-related complications, and perioperative mortality. RESULTS: Among 1681 patients (71% men; mean age, 73.43 ± 7.8 years) who had undergone F-BEVAR, 502 had had CAAAs (30%), 535 had had extent IV TAAAs (32%), and 644 had had extent I to III TAAAs (38%). UE access was used for 1103 patients (67%). The right side was used for 395 patients (24%) and the left side for 705 patients (42%). UE access was preferentially used for TAAAs (74% vs 47%; P < .001). In contrast, TF access was used more frequently for CAAAs (53% vs 26%; P < .01). A total of 38 perioperative cerebrovascular events (2.5%), including 32 strokes (1.9%) and 6 TIAs (0.4%), had occurred. Perioperative cerebrovascular events had occurred more frequently with UE access than with TF access (2.8% vs 1.2%; P = .036). An individual component analysis of the primary composite outcome revealed a trend for more frequent strokes (2.3% vs 1.2%; P = .13) and TIAs (0.54% vs 0%; P = .10) in the UE access group. On multivariable analysis, total TF access was associated with a 60% reduction in the frequency of perioperative cerebrovascular events (odds ratio, 0.39; P = .029). No significant differences were observed between UE and TF access in the technical success rate (96.5% vs 96.8%; P = .72), perioperative mortality (2.9% vs 2.6%; P = .72), or local access-related complications (6.5% vs 5.5%; P = .43). CONCLUSIONS: In the present large, multicenter, retrospective analysis of prospectively collected data, a total TF approach for F-BEVAR was associated with a lower rate of perioperative cerebrovascular events compared with UE access. Although the cerebrovascular event rate was low with UE access, the TF approach offered a lower risk of stroke and TIA. UE access will continue to play a role for appropriately selected patients requiring more complex repairs with anatomy not amenable to the TF approach.

Adding Fuel to the Fire: Infective Endocarditis and the Challenge of Cerebrovascular Complications.

PURPOSE OF REVIEW: Infective endocarditis is a deadly disease and made more deadly by neurologic complications. We review the cerebrovascular complications of infective endocarditis and focus our discussion on medical and surgical management. RECENT FINDINGS: While management of stroke in the setting of infective endocarditis differs from standard stroke treatment, mechanical thrombectomy has proven safe and successful. Optimal timing of cardiac surgery in the setting of stroke remains an area of debate, but additional observational studies continue to add more detail to the discussion. Cerebrovascular complications in the setting of infective endocarditis remain a high stakes clinical challenge. Timing of cardiac surgery in IE complicated by stroke exemplifies these dilemmas. While more studies have suggested that earlier cardiac surgery is likely safe for those with small ischemic infarcts, there remains a need for more data defining optimal timing of surgery in all forms of cerebrovascular involvement.

Perioperative neurologic outcomes of right versus left upper extremity access for fenestrated-branched endovascular aortic aneurysm repair.

OBJECTIVE: Upper extremity (UE) access is frequently used for fenestrated-branched endovascular aortic aneurysm repair (F-BEVAR), particularly for complex repairs. Traditionally, left-side UE access has been used to avoid crossing the arch and the origin of the supra-aortic vessels, which could potentially result in cerebral embolization and an increased risk of perioperative cerebrovascular events. More recently, right UE has been more frequently used as it is more convenient and ergonomic. The purpose of this study was to assess the outcomes and cerebrovascular events after F-BEVAR with the use of right- vs left-side UE access. METHODS: During an 8-year period, 453 patients (71% male) underwent F-BEVAR at a single institution. UE access was used in more complex repairs. Left UE access was favored in the past, whereas right UE access is currently the preferred UE access side. Brachial artery cutdown was used in all patients for the placement of a 12F sheath. Outcomes were compared between patients undergoing right vs left UE access. End points included cerebrovascular events, perioperative mortality, technical success, and local access-related complications. RESULTS: UE access was used in 361 (80%) patients. The right side was used in 232 (64%) and the left side in 129 (36%) patients for the treatment of 88 (25%) juxtarenal, 135 (38%) suprarenal, and 137 (38%) thoracoabdominal aortic aneurysms. Most procedures were elective (94%). Technical success was achieved in 354 patients (98%). In-patient or 30-day mortality was 3.3%. Five (1%) perioperative strokes occurred in patients undergoing right UE access, of which three were ischemic and two were hemorrhagic. No transient ischemic attacks occurred perioperatively. Two hemorrhagic strokes were associated with permissive hypertension to prevent spinal cord ischemia. No perioperative strokes occurred in patients undergoing left UE access (P = .16). Overall, perioperative strokes occurred with similar frequency in patients undergoing UE (5, 1%) and femoral access only (1, 1%) (P = .99). Arm access-related complications occurred in 15 (5%) patients, 11 (4.8%) on the right side and 4 (6%) on the left side (P = .74). CONCLUSIONS: Right UE access can be used for F-BEVAR with low morbidity and minimal risk of perioperative ischemic stroke or transient ischemic attacks. In general, UE access is not associated with an increased risk of perioperative stroke compared with femoral access only. Tight blood pressure control is, however, critical to avoid intracranial bleeding related to uncontrolled hypertension.

Pregnancy and neurologic complications of COVID-19: A scoping review.

While neurologic complications are frequently reported among patients with COVID-19 in the general population, they are unknown in pregnant women. This paper summarizes the case reports of pregnant women with confirmed SARS-CoV-2 infection plus a specified neurologic diagnosis. Until November 2021, 18 case reports were found. Both the central and peripheral nervous systems were equally affected: delirium (n = 1), posterior reversible encephalopathy syndrome (n = 4), cerebrovascular disease (n = 2), acute cerebral demyelinating disease (n = 1), acute necrotizing encephalopathy (n = 1), Guillain-Barré syndrome (n = 5), including one patient who also had vestibular neuritis, Bell's palsy (n = 3), and rhabdomyolysis (n = 1). The median maternal age was 32.5 (25-35) years, the median gestational age was 34 (30-36.5) weeks, and 38.9% presented previous medical conditions. Respiratory symptoms were reported in 76.5%, and 76.5% received immunotherapies to treat the COVID-19 or the neurologic complications. Half the women required admission to ICU and, more often, were those with central nervous system involvement (77.8% vs. 22.2%; Chi-square test, p = .018). For 64.7% of women, the most common method of delivery was surgical, although just one case was due to the neurologic complication. There were reports of one spontaneous abortion, two fetal deaths, and no maternal deaths. Only one case presented a poor neurologic outcome. It is possible that our findings are underestimated, considering that there are thousands of reports regarding neurologic complications in the general population with COVID-19.

Volatile and Intravenous Anesthetics for Brain Protection in Cardiac Surgery: Does the Choice of Anesthesia Matter?

Postoperative neurologic complications have a significant effect on morbidity, mortality, and long-term disability in patients undergoing cardiac surgery. The etiology of brain injury in patients undergoing cardiac surgery is multifactorial and remains unclear. There are several perioperative causative factors for neurologic complications, including microembolization, hypoperfusion, and systemic inflammatory response syndrome. Despite technologic advances and the development of new anesthetic drugs, there remains a high rate of postoperative neurologic complications. Moreover, despite the strong evidence that volatile anesthesia exerts cardioprotective effects in patients undergoing cardiac surgery, the neuroprotective effects of volatile agents remain unclear. Several studies have reported an association of using volatile anesthetics with improvement of biochemical markers of brain injury and postoperative neurocognitive function. However, there is a need for additional studies to define the optimal anesthetic drug for protecting the brain in patients undergoing cardiac surgery.

Neuro-medical manifestations of fluorosis in populations living in the Main Ethiopian Rift Valley.

Prolonged exposure to higher concentrations of fluoride (> 1.5 mg/L) is associated with dental and skeletal fluorosis. The effects of fluoride on dental and skeletal system have been studied extensively; however, the neurological consequences of fluoride in population-based studies are limited. The study aims to assess the epidemiology of neurological and other manifestations of fluorosis among rural populations living in the Main Ethiopian Rift valley. In this cross-sectional study, we enrolled 316 individuals from 23 rural communities in the Main Ethiopian Rift valley. Fluoride concentration was measured in drinking water samples collected from 23 community wells. Association between fluoride concentrations and clinical features of fluorosis was assessed using student t test, chi square, multivariable regression using adjusted odds ratio (OR). The mean fluoride concentration in the drinking water was 6.8 ± 4.3 mg/L (range: 0.3-15.5 mg/L). At least one clinical sign of skeletal fluorosis was observed in 54.4% (n = 175) of the study participants. Headache and joint pain reported by 67.1% and 56.3% of the participants as the most common neurological manifestation, and skeletal fluorosis symptom, respectively. The mean fluoride level was higher for those individuals who reported paresthesia compared to those with no-paresthesia. Loss of appetite, constipation, and fatigue were reported by 48.0%, 45.6%, and 56.6% of the participants, respectively. Signs of crippling fluorosis were observed in small proportion (1.6%) of the participants. Individuals who reported headache are most likely exposed to higher fluoride concentrations in drinking water compared to those reported no-headache (p < 0.001). The study demonstrates high prevalence of neuro-medical manifestations of fluorosis in population living in the Main Ethiopian Rift valley. Fluoride concentration in drinking water and joint pain were independent predictors of fluorosis.

Clinical characteristics and outcomes of patients admitted to hospitals for posterior reversible encephalopathy syndrome: a retrospective cohort study.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is usually a benign, yet underdiagnosed clinical condition associated with subacute to acute neurological manifestations primarily affecting white matter. PRES is reversible when recognized promptly and treated early by removal of the insulting factor; however, can lead to irreversible and life-threatening complications such as cerebral hemorrhage, cerebellar herniation, and refractory status epilepticus. METHODS: We utilized the National Inpatient Sample database provided by the Healthcare Cost and Utilization Project (HCUP-NIS) 2017 to investigate the demographic variables (age, sex, and race) for patients with PRES, concomitant comorbidities and conditions, inpatient complications, inpatient mortality, length of stay (LOS), and disposition. RESULTS: A total of 635 admissions for patients aged 18 years or older with PRES were identified. The mean age was 57.2 ± 0.6 years old with most encounters for female patients (71.7%, n = 455) and white as the most prevalent race. Half the patients in our study presented with seizures (50.1%, n = 318), sixty-three patients (9.9%) presented with vision loss, and sixty-four patients (10.1%) had speech difficulty. In addition, 45.5% of patients had hypertensive crisis (n = 289). 2.2% of hospitalizations had death as the outcome (n = 14). The mean LOS was 8.2 (±0.3) days, and the mean total charges were $92,503 (±$5758). Inpatient mortality differed between males and females (1.7% vs. 2.4%) and by race (3.6% in black vs. 1.8% in white) but was ultimately determined to be not statistically significant. Most patients who present with vision disturbance have a high risk of intracranial hemorrhage. Furthermore, end-stage renal disease, atrial fibrillation, and malignancy seemed to be linked with a very high risk of mortality. CONCLUSION: PRES, formerly known as reversible posterior leukoencephalopathy, is a neurological disorder with variable presenting symptoms. Although it is generally a reversible condition, some patients suffer significant morbidity and even mortality. To the best of our knowledge, this is the largest retrospective cohort of PRES admissions that raises clinician awareness of clinical characteristics and outcomes of this syndrome.

Primary Stroke and Failure-to-Rescue Following Thoracic Endovascular Aortic Aneurysm Repair.

OBJECTIVE: To characterize the impact, on failure to rescue, of cerebrovascular accident as a first postoperative complication after thoracic endovascular aortic aneurysm repair (TEVAR). DESIGN: A retrospective cohort study using of National Surgical Quality Improvement Program Participants User File. SETTING: United States hospitals taking part in the National Surgical Quality Improvement Program. PARTICIPANTS: Patients >18 years, who underwent TEVAR for nonruptured thoracic aortic aneurysm between 2005 and 2018, and developed one or more major postoperative complications within 30 days after surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 3,937 patients who underwent TEVAR for nonruptured thoracic aneurysm, 1,256 (31.9%) developed major postoperative complications (stroke incidence: 11.4% [143/1256]). In adults <65 years old, the occurrence of stroke as the primary complication, relative to the occurrence of other complications, was associated with ten times greater risk of failure to rescue (29.4% v 4.6%; odds ratio [OR]: 10.10; 95% confidence interval [CI] 2.45-41.56; p < 0.001). The effect size was relatively lower when stroke occurred but was not the primary complication (20.0% v 4.6%; OR: 7.55; 95% CI 1.37-41.71; p = 0.020). In patients ≥65 years, the occurrence of stroke as the primary complication did not carry the similar prognostic value. CONCLUSION: Younger patients who developed stroke were up to ten times more likely to die, relative to patients who developed other major complications. Survival was substantially reduced when stroke was the primary complication. The authors' findings imply that to maximize the survival of patients undergoing TEVAR, efforts may be needed to predict and prevent stroke occurrence as a primary postoperative morbidity event.

Acute Neurological Complications of Brain Tumors and Immune Therapies, a Guideline for the Neuro-hospitalist.

PURPOSE OF REVIEW: Patients with brain tumors presenting to the emergency room with acute neurologic complications may warrant urgent investigations and emergent management. As the neuro-hospitalist will likely encounter this complex patient population, an understanding of the acute neurologic issues will have value. RECENT FINDINGS: We discuss updated information and management regarding various acute neurologic complications among neuro-oncology patients and neurologic complications of immunotherapy. Understanding of the acute neurologic complications associated with central nervous system tumors and with common contemporary cancer treatments will facilitate the neuro-hospitalist management of these patient populations. While there are aspects analogous to the diagnosis and management in the non-oncologic population, a number of unique features discussed in this review should be considered.

Extracorporeal Membrane Oxygenation: The New Jack-of-All-Trades?

The role of extracorporeal membrane oxygenation in the adult patient population still is evolving. Technologic advancements have improved the ability to provide extracorporeal life support. The miniaturization and durability of these systems have made extracorporeal membrane oxygenation more convenient and mobile than ever. Because of these improvements, its use has increased steadily. The indications for use also have diversified. In this review, the authors provide a panoramic view of extracorporeal membrane oxygenation to provide a foundation of knowledge for anesthesiologists.

Neurologic complications after surgical management of complex elbow trauma requiring radial head replacement.

BACKGROUND: Radial head arthroplasty (RHA) has become a successful procedure for addressing acute unreconstructible radial head fractures that compromise elbow stability in complex elbow trauma. The purpose of this study was to investigate the incidence of and risk factors for the development of neurologic complications after surgical treatment of complex elbow fractures that require an RHA. METHODS: Sixty-two patients with an unreconstructible radial head fracture and complex elbow instability treated with RHA were included. There were 33 men and 29 women, with a mean age of 54 years (range, 22-87 years). The average follow-up period was 5.2 years (range, 3-16 years). All patients were neurologically intact before surgery. The arthroplasty was implanted through a Kocher approach in 55 cases, whereas a Kaplan approach was used in 7. An uncemented smooth stem arthroplasty (Evolve) was used in 27 patients, and an anatomic ingrowth system (Anatomic Radial Head), in 35. At the time of surgery, 23 patients underwent fixation of a coronoid fracture and 15 underwent plating of the proximal ulna. All patients were clinically examined immediately after surgery and during follow-up to detect any degree of neurologic deficit. Radial and ulnar nerve injuries were classified according to the Hirachi and McGowan classifications, respectively. Functional outcomes were evaluated with the Mayo Elbow Performance Score. RESULTS: A complete posterior interosseous nerve palsy occurred postoperatively in 2 patients. Hand function had completely recovered in both at 2 months after surgery without sequelae. Nine patients complained of ulnar nerve symptoms (immediately after surgery in 6 and as delayed ulnar neuropathy in 3). Most patients with ulnar nerve deficits had undergone additional surgical procedures to address ulnar fractures. Among patients with ulnar neuropathies, only 3 complained of mild sensory symptoms at the latest follow-up. No significant differences in range of motion and Mayo Elbow Performance Score were found between patients with and without neurologic complications. Associated olecranon or coronoid fixation and a prolonged tourniquet time were identified as risk factors for neurologic complications. CONCLUSION: This study shows that the incidence of neurologic complications associated with the surgical treatment of complex elbow fractures requiring implantation of a radial head prosthesis may be underestimated in the literature. Inappropriate retraction in the anterior aspect of the radial neck, a prolonged ischemia time, and concomitant coronoid or olecranon fracture fixation represent the main risk factors for the development of this complication. Although the great majority of patients have full recovery of their nerve function, they should be advised on the risk of this stressful complication.

Incidence of early intra-cranial bleeding and ischaemia in adult veno-arterial extracorporeal membrane oxygenation and extracorporeal cardiopulmonary resuscitation patients: a retrospective analysis of risk factors.

BACKGROUND: Cerebral complications in veno-arterial extracorporeal membrane oxygenation are known to have a strong impact on mortality and morbidity. Aim of this study is to investigate the early incidence, risk factors and in-hospital mortality of intra-cranial ischaemia and haemorrhage in adults undergoing veno-arterial extracorporeal membrane oxygenation treatment. METHODS: This study is a single-centre retrospective analysis on adult patients undergoing veno-arterial extracorporeal membrane oxygenation for different indications. The inclusion criterion included patients with early routine cerebral computed tomography imaging during extracorporeal membrane oxygenation, with no clinical evidence of cerebral pathology prior to cannulation. Cerebral complications were grouped by aetiology and the territories of the brain's supplying arteries. RESULTS: One hundred eighty-seven adult patients with a total of 190 veno-arterial extracorporeal membrane oxygenation treatments were included. A total of 16.3% (n = 31) had evidence of either cerebral ischaemia (11.1%) or haemorrhage (5.8%); one patient suffered from both. Cerebral computed tomography scans were performed early in median on the first day after extracorporeal membrane oxygenation cannulation; in-hospital mortality of intra-cranial ischaemia and haemorrhage was 71.4% and 45.5%, respectively. Associated with an increased risk for ischaemic lesions were cannulation of the ascending aorta, higher age, presence of an autoimmune disease and cardiac surgery prior to veno-arterial extracorporeal membrane oxygenation. An association with haemorrhagic lesions was found for a lower blood PaCO2 at 2 hours, lower blood flow through the extracorporeal membrane oxygenation device at 2 hours, higher international normalized ratio and constantly higher activated partial thromboplastin time values as well as higher mean arterial pressures until haemorrhagic lesions were evident. CONCLUSION: Cerebral complications are frequent in patients on veno-arterial extracorporeal membrane oxygenation and may be clinically silent events. Careful monitoring with routine neuroimaging seems to be the most appropriate diagnostic approach at present. Intra-cranial ischaemia occurs more frequent than haemorrhage and is associated with cannulation of the aorta ascendens.

Noninfectious Neurologic Complications after Allogeneic Hematopoietic Stem Cell Transplantation.

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be associated with neurologic complications, data on noninfectious etiologies are scanty. Therefore, we analyzed the incidence, clinical characteristics, risk factors, and influence on outcomes of noninfectious neurologic complications (NCs) in 971 consecutive patients with hematologic malignancies undergoing allo-HSCT at our center between January 2000 and December 2016. We evaluated NCs affecting the central nervous system (CNS) and peripheral nervous system (PNS). The median duration of follow-up of survivors was 71 months (range, 11 to 213 months). A total of 467 patients received a matched sibling donor (MSD) transplant, 381 received umbilical cord blood (UCB), 74 received a haploidentical transplant, and 49 received a matched unrelated donor (MUD) transplant. One hundred forty-nine (15.3%) NCs were documented at a median of 78 days after transplantation (range, 5 days before to 3722 days after). The cumulative incidence risk of developing NC was 7.5% (95% confidence interval, 6% to 8.2%) at day +90 and 13% at 5 years. The 5-year cumulative incidence of NCs was 10.8% after MSD allo-HSCT and 15.3% after alternative donor (UCB, MUD, haploidentical) allo-HSCT (P = .004). There were 101 (68%) CNS complications, including encephalopathy, n = 46 (31%); headache, n = 20 (13%); stroke, n = 15 (10%); seizures, n = 9 (6%), posterior reversible encephalopathy syndrome, n = 6 (4%), and myelopathy, n = 5 (3%). PNS complications (32%) included neuropathies, n = 25 (17%), and myopathies and neuromuscular junction disorders, n = 23 (17%), with 17% of the total PNS complications being immune-related. In multivariable analysis, donor type other than MSD, age ≥40 years, development of acute graft-versus-host disease (GVHD) grade II-IV (hazard ratio [HR], 3.3; P < .00001), and extensive chronic GVHD (HR, 3.2; P = .0002) were independently associated with increased risk of NCs. The 5-year overall survival (OS) was 21% in patients who developed NCs and 41% for those who did not (P < .0001). This difference in OS was observed in patients developing CNS NCs, but not in those developing PNS complications. In conclusion, our study reveals NCs as a frequent and heterogeneous complication that, when affecting CNS, is associated with poor prognosis following allo-HSCT.

Protean Neurologic Manifestations of Two Rare Dermatologic Disorders: Sweet Disease and Localized Craniofacial Scleroderma.

PURPOSE OF REVIEW: To describe diverse neurologic and neuroradiologic presentations of two rare, immunologically mediated skin conditions: Sweet disease and localized scleroderma (morphea). RECENT FINDINGS: Core syndromes of neuro-Sweet disease (NSD) are steroid responsiveness, recurrent meningitis, and encephalitis. Focal neurologic, neuro-vascular, and neuro-ophthalmologic syndromes have been reported recently in NSD. A variety of steroid-sparing treatments and biologics have been used for relapsing NSD. Localized craniofacial scleroderma is associated with seizures, headaches, and, less commonly, focal deficits and cognitive decline. Immunosuppressive therapy may be required in patients with disease progression; some refractory cases have responded to IL-6 inhibition. Our review provides an up-to-date reference for neurologists faced with a patient with a history or skin findings consistent with Sweet disease or localized scleroderma. We hope that it will stimulate collaborative studies aimed at unraveling the pathogenesis of these disorders, better characterization of their neurologic manifestations, and discovery of optimal therapeutic solutions.

Extra-renal manifestations of atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare and complex disease resulting from abnormal alternative complement activation with a wide range of clinical presentations. Extra-renal manifestations of aHUS can involve many organ systems, including the peripheral and central nervous, gastrointestinal, cardiovascular, integumentary, pulmonary, as well as the eye. While some of these extra-renal manifestations occur in the acute phase of aHUS, some can also occur as long-term sequelae of unopposed complement activation. Extra-renal symptoms are observed in approximately 20% of patients with aHUS, with the incidence of specific organ system complications ranging from a few case reports to 50% of described patients. Careful monitoring for extra-renal involvement is critical in patients with aHUS, as prompt evaluation and management may decrease the risk of high morbidity and mortality associated with aHUS.

Fungal infections of the central nervous system and paranasal sinuses in onco-haematologic patients. Epidemiological study reporting the diagnostic-therapeutic approach and outcome in 89 cases.

Invasive fungal infections (IFI) of the Central Nervous System (IFI-CNS) and Paranasal Sinuses (IFI-PS) are rare, life-threatening infections in haematologic patients, and their management remains a challenge despite the availability of new diagnostic techniques and novel antifungal agents. In addition, analyses of large cohorts of patients focusing on these rare IFI are still lacking. Between January 2010 and December 2016, 89 consecutive cases of Proven (53) or Probable (36) IFI-CNS (71/89) and IFI-PS (18/89) were collected in 34 haematological centres. The median age was 40 years (range 5-79); acute leukaemia was the most common underlying disease (69%) and 29% of cases received a previous allogeneic stem cell transplant. Aspergillus spp. were the most common pathogens (69%), followed by mucormycetes (22%), Cryptococcus spp. (4%) and Fusarium spp. (2%). The lung was the primary focus of fungal infection (48% of cases). The nervous system biopsy was performed in 10% of IFI-CNS, and a sinus biopsy was performed in 56% of IFI-PS (P = 0.03). The Galactomannan test on cerebrospinal fluid has been performed in 42% of IFI-CNS (30/71), and it was positive in 67%. Eighty-four pts received a first-line antifungal therapy with Amphotericine B in 58% of cases, Voriconazole in 31% and both in 11%. Moreover, 58% of patients received 2 or more lines of therapy and 38% were treated with a combination of 2 or more antifungal drugs. The median duration of antifungal therapy was 60 days (range 5-835). A surgical intervention was performed in 26% of cases but only 10% of IFI-CNS underwent neurosurgical intervention. The overall response rate to antifungal therapy (complete or partial response) was 57%, and 1-year overall survival was 32% without significant differences between IFI-CNS and IFI-PS. The overall mortality was 69% but the IFI attributable mortality was 33%. Mortality of IFI-CNS/PS remains high but, compared to previous historical data, it seems to be reduced probably due to the availability of newer antifungal drugs. The results arising from this large contemporary cohort of cases may allow a more effective diagnostic and therapeutic management of these very rare IFI complications in haematologic patients.