Bilateral Non-Arteritic Anterior Ischaemic Optic Neuropathy in a Patient with a COL4A2 Mutation.

Non-arteritic anterior ischaemic optic neuropathy (NAION) is a common cause of vision loss in adults and is thought to be due to compromised perfusion to the optic nerve head. Patients with NAION in one eye are at risk of recurrence in the fellow eye. We report a case of sequential, bilateral NAION in a patient who was found to have a COL4A2 mutation. COL4A2 encodes a subunit of the collagen 4 protein, the major component of the human basement membranes, and has several known cerebrovascular and ocular associations.

Outflow graft obstruction in patients with the HM 3 LVAD: A percutaneous approach.

BACKGROUND: The use of the HeartMate 3 (HM3) left ventricular assist device (LVAD) is expanding. Despite being associated with lower rates of adverse events and increased survival, outflow graft obstruction (OGO) has been reported in patients with HM3. The incidence and best management of this serious complication remain unclear. METHODS: We describe six cases of HM3 OGO occurring in five patients in our institutional HM3 cohort. Four cases underwent computed tomography angiography and in two percutaneous angiography was directly performed to confirm the diagnosis. In four cases, percutaneous repair of the OG was performed using common interventional cardiology (IC) techniques. RESULTS: Our institutional incidence of OGO was 7% (event rate of 0.05 per patient year); much higher than the previously reported incidence of 1.6%. All cases occurred in the bend relief covered segment. Only two patients had apparent OG twisting, and in two, OGO occurred despite placement of an anti-twist clip at the time of implant. External compression seems to play a role in most cases. Balloon "graftoplasty" and stent deployment via the femoral artery alleviated the obstruction and normalized LVAD flow in all patients who underwent percutaneous repair. The use of self-expanding stents allowed for downsizing of the procedural access site to 10 Fr. No serious procedure-related complications occurred. CONCLUSION: OGO is common in HM3 patients, external compression due to biomaterial accumulated surrounding the OG is a common etiology. Percutaneous repair using standard IC techniques is safe and feasible in cases of compression with or without partial twisting.

An exploratory study of the electronic medical record and outpatient vascular neurology consultations.

We carried out a quality improvement project utilizing the electronic medical record (EMR) to determine (1) the quality of vascular neurologists' recommendations for recurrent stroke prevention and (2) primary care provider (PCP) acknowledgement of the vascular neurologists' recurrent stroke prevention recommendations and their frequency of meeting the recommended metrics for risk factor control and lifestyle modification. We conducted a retrospective EMR chart review on a convenience sample of ischemic stroke patients during two epochs. Data collected included risk factors, stroke subtype, and process and outcome guidance metrics for recurrent ischemic stroke prevention according to American Heart Association/American Stroke Association (AHA/ASA) recommendations. Overall, vascular neurologists commonly recommended appropriate AHA/ASA risk factor management standards, but were less likely to do so for lifestyle management. Improvements in the EMR system over time, including the establishment of guideline-driven importable recurrent stroke prevention templates, led to a high frequency of proper risk factor and lifestyle recommendations made by vascular neurologists. Statistical analysis provided further evidence that the EMR positively influenced the delivery of proper recurrent stroke prevention guidance. Although PCPs infrequently acknowledged receipt of vascular neurology consultations, there was a relatively high frequency of achieved risk factor control. The latter may be attributed at least in part to pre-existent quality improvement programs implemented at primary care offices. Our exploratory findings suggest that proper use of the EMR may heighten efforts to provide appropriate and consistent recurrent stroke prevention recommendations in a primary care setting.

Population-based approaches for reducing stroke risk: an update on their success and the challenges ahead.

INTRODUCTION: Stroke is a significant public health challenge as it is the second most common cause of death and the third leading cause of disability globally. Additionally, stroke incidence and the number of stroke deaths have been rising. Efforts to prevent stroke have been made, including high-risk approaches where patients are screened for cardiovascular risk factors, and population-based approaches which attempt to reduce stroke rates by improving overall population health. AREAS COVERED: We summarize studies of population-based approaches to stroke prevention involving greater than 1,000 participants identified on a PubMed database search. Based on these programs, challenges of population-based stroke prevention programs are discussed and potential keys to success are highlighted. EXPERT OPINION: Population-based stroke prevention programs face challenges including cost and interest of the public and certain stakeholders. Additionally, secular trends for improvement in risk factors and catastrophic adverse environmental circumstances add to the complexity of analyzing program success. Factors leading to successful programs include validated digital solutions for self-monitoring of risks, backing by global policy and legislation, flexibility to the needs of the population, intersectoral programs, community engagement, information dissemination back to the populations, and high-risk screening to develop a complementary combination approach to stroke prevention.

Safety and efficacy evaluation of carnosine, an endogenous neuroprotective agent for ischemic stroke.

BACKGROUND AND PURPOSE: An urgent need exists to develop therapies for stroke that have high efficacy, long therapeutic time windows, and acceptable toxicity. We undertook preclinical investigations of a novel therapeutic approach involving supplementation with carnosine, an endogenous pleiotropic dipeptide. METHODS: Efficacy and safety of carnosine treatment was evaluated in rat models of permanent or transient middle cerebral artery occlusion. Mechanistic studies used primary neuronal/astrocytic cultures and ex vivo brain homogenates. RESULTS: Intravenous treatment with carnosine exhibited robust cerebroprotection in a dose-dependent manner, with long clinically relevant therapeutic time windows of 6 hours and 9 hours in transient and permanent models, respectively. Histological outcomes and functional improvements including motor and sensory deficits were sustained on 14th day poststroke onset. In safety and tolerability assessments, carnosine did not exhibit any evidence of adverse effects or toxicity. Moreover, histological evaluation of organs, complete blood count, coagulation tests, and the serum chemistry did not reveal any abnormalities. In primary neuronal cell cultures and ex vivo brain homogenates, carnosine exhibited robust antiexcitotoxic, antioxidant, and mitochondria protecting activity. CONCLUSIONS: In both permanent and transient ischemic models, carnosine treatment exhibited significant cerebroprotection against histological and functional damage, with wide therapeutic and clinically relevant time windows. Carnosine was well tolerated and exhibited no toxicity. Mechanistic data show that it influences multiple deleterious processes. Taken together, our data suggest that this endogenous pleiotropic dipeptide is a strong candidate for further development as a stroke treatment.

Vascular cognitive impairment.

Vascular cognitive impairment (VCI) is a term used to capture the entire spectrum of cognitive impairment from mild to more severe forms and includes all forms of stroke (e.g., ischemic and hemorrhagic forms) associated and underlying cognitive impairment related with subclinical vascular brain injury. Vascular contributions to cognitive impairment are common, especially as one ages. Therefore, both stroke and Alzheimer's disease may be important causes of cognitive impairment in later life, and the concomitant occurrence of these disorders may synergize to increase the risk of poor cognition in later life. In this review we discuss the definition and clinical presentation, mechanisms, cardiovascular risk factors and possible prevention and treatment of VCI. VCI is a potentially treatable and preventable cause of cognitive impairment in later life, and familiarity with this condition will help the practitioner provide better care to patients.

Malpractice Lawsuits Relating to Mechanical Thrombectomy for Acute Ischemic Stroke: A Systematic Review.

Background and Purpose: Medical-legal claims for malpractice relating to the use of alteplase for acute ischemic stroke (AIS) are usually for failure to treat rather than for complications. The advent of mechanical thrombectomy (MT) as a standard of AIS treatment has added a new dimension to the medical-legal landscape as there is a need for the delivery of a higher level of care creating the potential for delays and errors associated with such treatment. Information on causes of malpractice related to mechanical thrombectomy (MT) is currently lacking. Methods: We conducted a systematic review of legal databases (Westlaw, LexisNexis, Google Scholar Case Law, and VerdictSearch) to identify medical malpractice cases with and without verdicts filed in the United States up to March 31, 2021 which pertained to performance or non-performance of MT for AIS. We collected various case characteristics, case outcomes, and root causes for malpractice claims. Results: We found 25 cases, 16 of which alleged failure to treat with MT, 8 for harm due to delay in treatment and 1 case that alleged complications. Root causes included delay in vascular imaging, communication breakdowns, and transportation delays. Eight cases had an outcome in favor of the defendant, 9 in favor of the plaintiff, and 8 remained to be determined. Conclusions: As with alteplase, malpractice allegations regarding MT for AIS are largely for failure to treat or delay in treatment as opposed to complications. Addressing root causes of diagnostic delay, communication breakdowns, and transportation delays may reduce subsequent malpractice risk.

Genotype-guided dual antiplatelet therapy in cerebrovascular disease: assessing the risk and benefits for ethnic populations.

INTRODUCTION: Cerebrovascular disease is a leading cause of morbidity and mortality in the world and antiplatelet therapy is a main pharmacologic means of secondary prevention. Clinical information has accumulated about benefit of dual antiplatelet therapy in certain clinical scenarios, genetic causes of antiplatelet resistance and its effect on clinical outcomes, and ethnic and geographic distributions of genetic polymorphisms. AREAS COVERED: This review covers literature related to the pharmacogenomics of antiplatelet agents with a focus on ethnic variability, antiplatelet resistance, and dual antiplatelet therapy in cerebrovascular disease. EXPERT OPINION: Selecting patients for dual antiplatelet therapy and specific agents require consideration of multiple factors. Ethnic factors should be considered in certain circumstances, but additional research is needed to determine the generalizability of the findings.

Exophiala dermatitidis fungal infective endocarditis on prosthetic mitral valve.

Fungal infective endocarditis, although rare, carries a high mortality risk. We present a case of successful multidisciplinary management of Exophiala dermatitidis infective endocarditis in an immunocompetent male with a bio-prosthetic mitral valve. This case highlights the clinical presentation and provides valuable treatment insights into this rare fungal entity. Prompt consideration of fungal pathogens in predisposed patients, expedited detection through non-culture-based tests, and a combined surgical and prolonged antifungal approach are pivotal.

Subarachnoid Hemorrhage due to Cerebral Cavernous Malformation in a Young Female.

Cerebral cavernous malformations (CCMs) are usually intraparenchymal lesions commonly associated with intraparenchymal hemorrhage. Extra-axial Lesions are uncommon and have rarely been reported as the cause of aneurysmal like subarachnoid hemorrhage (SAH). We present a 33-years-old female with a past medical history significant for hypertension who presented with acute onset head and neck pain after bending over. En route to the hospital, she had abnormal motor movements suggestive of seizures. Computed tomography (CT) of the head was significant for diffuse aneurysmal like SAH. Head CT angiography (CTA) and catheter digital subtraction angiography (DSA) were both negative for aneurysm. Magnetic resonance imaging (MRI) of the brain showed susceptibility artifact in the right parafalcine frontal lobe suspicious for underlying CCM. This lesion was in the area suspected of having an aneurysm on CT head. The patient was diagnosed with SAH secondary to cavernous malformation mimicking aneurysmal etiology. This case is important as it serves as a good reminder to consider cavernous malformations in the differential in patients presenting with angiogram negative SAH. Diagnosis of this entity has treatment implications including discontinuation of calcium channel blockers if initiated, discussion about duration of anti-seizure medication, in addition to consideration for surgical intervention in select populations.

Corkscrew Angiopathy of the Basilar Artery: A Case Report.

A vascular malformation is an abnormal development of blood vessels that can be found in arteries, veins, or the lymphatic system. While pathology such as aneurysms, arteriovenous malformations (AVMs), dissections, and dolichoectasia have been documented frequently and linked to an increased incidence of stroke, we present a rare finding of a 'corkscrew' appearance of the basilar artery causing recurrent posterior circulation symptoms. Imaging during 3 separate hospitalizations showed recurrent acute strokes within the basilar artery vascular territory. A conventional cerebral angiogram revealed a corkscrew appearance of the basilar artery with no dilatation, outpouching, or aneurysm.

Wallenberg's syndrome with extradural-extracranial origin of the posterior inferior cerebellar artery.

We report a case of lateral medullary syndrome (LMS) with extradural origin of the posterior inferior cerebellar artery (PICA). A 45-year-old construction worker presented with acute signs and symptoms of typical LMS. Prolonged work-related neck extension was reported just prior to the onset of symptoms. Cerebral angiography revealed a patent vertebrobasilar tree with an extradural origin of an otherwise normal appearing PICA ipsilaterally. Workup did not show evidence for cardioembolic or atheroembolic source. The presence of an extradural origin of PICA may be considered a predisposing factor for non-traumatic LMS associated with head and neck movement.

Peripheral neuropathy: differential diagnosis and management.

Peripheral neuropathy has a variety of systemic, metabolic, and toxic causes. The most common treatable causes include diabetes mellitus, hypothyroidism, and nutritional deficiencies. The diagnosis requires careful clinical assessment, judicious laboratory testing, and electrodiagnostic studies or nerve biopsy if the diagnosis remains unclear. A systematic approach begins with localization of the lesion to the peripheral nerves, identification of the underlying etiology, and exclusion of potentially treatable causes. Initial blood tests should include a complete blood count, comprehensive metabolic profile, and measurement of erythrocyte sedimentation rate and fasting blood glucose, vitamin B12, and thyroid-stimulating hormone levels; specialized tests should be ordered if clinically indicated. Lumbar puncture and cerebrospinal fluid analysis may be helpful in the diagnosis of Guillain-Barré syndrome and chronic inflammatory demyelinating neuropathy. Electrodiagnostic studies, including nerve conduction studies and electromyography, can help in the differentiation of axonal versus demyelinating or mixed neuropathy. Treatment should address the underlying disease process, correct any nutritional deficiencies, and provide symptomatic treatment.

3D Hierarchically Mesoporous Zinc-Nickel-Cobalt Ternary Oxide (Zn0.6Ni0.8Co1.6O4) Nanowires for High-Performance Asymmetric Supercapacitors.

Increased efforts have been devoted recently to develop high-energy-density supercapacitors (SC) without renouncing their power efficiency. Herein, a hierarchically mesoporous nanostructure of zinc-nickel-cobalt oxide (ZNCO) nanowires (NWs) is constructed by hierarchical aggregation of ZNCO nanoparticles. It is worth noting that cobalt and nickel rich lattice imparts higher charge storage capability by enhanced reversible Faradaic reaction while zinc provides structural stability and higher conductivity. Moreover, particulate nature of ZNCO NWs allows deep diffusion of electrolyte thus enabling reversible charge storage under higher current densities. The as-prepared ZNCO NWs exhibited excellent specific capacitance of 2082.21 F g-1 at the current density of 1 A g-1 with high stability up to 5,000 charge-discharge cycles. Further, the asymmetric SC device was assembled using ZNCO NWs (ZNCO NWs//MWCNTs) which exhibited high energy density of 37.89 Wh kg-1 and excellent capacitance retention up to 88.5% over 1,000 cycles. This work presents ways to construct multi-component high-energy-density materials for next-generation energy storage devices.

Cardiac dysfunction after left permanent cerebral focal ischemia: the brain and heart connection.

BACKGROUND AND PURPOSE: Stroke can lead to cerebrogenic cardiac arrhythmias. We sought to investigate the effect of ischemic stroke on cardiac function in a mouse model of permanent middle cerebral artery occlusion (pMCAO). METHODS: Twenty-four hours after the induction of focal ischemia, cardiac function was measured in mice by endovascular catheterization of the heart. Immediately after hemodynamic measurements, mice were euthanized and brains were excised and sectioned to measure infarct volume and the severity of insular cortex injury. Myocardial damage was evaluated by hematoxylin-eosin staining. Serum and heart levels of norepinephrine (NE) were also determined. RESULTS: Cardiac dysfunction occurred in 9 out of 14 mice that underwent left pMCAO. In these 9 mice, the severity of left insular cortex lesion was greater than the mice with normal heart function. The serum and heart levels of NE were significantly higher in left pMCAO mice with heart dysfunction. Liner regression analysis indicates significant inverse correlation between the severity of left insular cortex damage and heart dysfunction. Mice that underwent right pMCAO did not exhibit cardiac dysfunction. CONCLUSIONS: This study shows that left focal cerebral ischemia can produce cardiac dysfunction, which is associated with the extent of left insular cortex damage. Furthermore, mice exhibiting cardiac dysfunction had elevated levels of NE in the serum and heart.

Extent of intra-arterial calcification on head CT is predictive of the degree of intracranial atherosclerosis on digital subtraction angiography.

BACKGROUND: Intracranial intra-arterial calcifications (ICAC) are a common finding on head CT examinations, but their significance is not known. The aim of this study is to determine if a relationship exists between ICAC on head CT and the presence of a high-grade atherosclerotic stenosis on cerebral angiography. METHODS: This was a retrospective study of 108 consecutive patients admitted to the stroke service at Parkland Hospital in Dallas, Tex., USA. Each patient had undergone a head CT and catheter-based angiographic study to meet the inclusion criteria. Demographic information was recorded along with CT imaging data in regards to the amount of calcification. Angiographic images were reviewed independently, and a comparison was made to determine if calcification was predictive of finding a high-grade stenosis on angiography. RESULTS: A total of 108 consecutive patients with a mean age of 56 +/- 12 years were studied. Of the 540 vessels studied, 65 (12%) were found to have a stenosis of >or=50% on angiography, and 71 (13.1%) were found to have a calcium grade of 3 or 4 on head CT. ICAC appeared to be more common in the anterior circulation compared to the posterior circulation. Patients with grade 3 or 4 calcification of an intracranial vessel on head CT were more likely to have a stenosis of >or=50% on cerebral angiography. CONCLUSIONS: The presence of ICAC on head CT appears to correlate with the presence of an underlying intracranial stenosis on angiography. Further study is required to validate these preliminary findings.

Chemotherapy-related posterior reversible leukoencephalopathy syndrome.

BACKGROUND: A 45-year-old woman with small-cell lung cancer presented to a hospital emergency department in an acute confusional state, with blurred vision and mild headache. Following progressively increasing lethargy, she subsequently became unresponsive to tactile and verbal stimuli. She had recently been started on chemotherapy with carboplatin and gemcitabine. INVESTIGATIONS: Physical examination, imaging studies including brain MRI, noncontrast brain CT scans and magnetic resonance angiography, continuous EEG monitoring, and cerebrospinal fluid analysis. DIAGNOSIS: Posterior reversible leukoencephalopathy syndrome (PRES) related to chemotherapy, and nonconvulsive status epilepticus related to PRES. MANAGEMENT: Withholding of chemotherapeutic agents, and antiseizure therapy for the status epilepticus.

Hereditary neuropathy with liability to pressure palsies and amyotrophic lateral sclerosis.

A 56-year-old male with recurrent painless focal neuropathies and a family history of peripheral neuropathy of unknown etiology presented with progressively worsening of impaired sensations and weakness in his lower extremities. His initial electrodiagnostic evaluation was suggestive of severe sensory and motor peripheral polyneuropathy. The genetic testing was performed for familial causes of peripheral neuropathy as there was a family history of peripheral neuropathy of unknown etiology. The patient was found to have 1.5-Mb deletion in the PMP22 gene which was confirmatory of hereditary neuropathy with liability to pressure palsies (HNPP). He developed progressive upper and lower extremity weakness, bulbar dysfunction and widespread fasciculations during the course of his illness. He was subsequently diagnosed with amyotrophic lateral sclerosis (ALS). This is the second reported case of HNPP associated with ALS. We discuss significant clinical and electrodiagnostic findings of this interesting case.

Diffusion-weighted imaging: not all that glitters is gold.

Diffusion-weighted imaging (DWI) is a sophisticated magnetic resonance imaging (MRI) technique with rapid acquisition time and high sensitivity for depicting acute cerebral ischemia. It is currently part of the routine workup in most medical centers when ischemic stroke is in the differential diagnosis. DWI helps establish a diagnosis of acute ischemic infarct even in cases where the clinical presentation is not typical for ischemic stroke. However, contrary to popular belief, not every hyperintensity on DWI is an ischemic stroke. Consequently, DWI with high intensity signals, commonly called "positive" DWI, is sometimes misinterpreted and leads to incorrect medical management. In this report, we briefly discuss some of the essential, technical aspects of DWI and report various clinical scenarios, which may lead to "positive" DWI findings but are not ischemic strokes. Although the sensitivity of DWI for ischemic stroke is very high, the specificity is not as high, and a "positive" DWI does not exclude other diagnoses that should be considered based on each patient's clinical history and examination, and the appearance of other sequences of MRI scans.

Decompressive hemicraniectomy in a 19-month-old female after malignant cerebral infarction.

Malignant cerebral infarction is a life-threatening condition with case fatality rates of approximately 80% in adults with malignant infarction of the middle cerebral artery. No medical treatment has been proven effective for this condition. Decompressive hemicraniectomy within 48 h of massive cerebral infarction significantly reduces mortality and improves outcome in adults 18-60 years of age. However, there is very limited data available about the role of decompressive hemicraniectomy in children with acute malignant cerebral infarction. We present the case of a 19-month-old female who presented with progressive encephalopathy and right hemiparesis. Computed tomography and magnetic resonance imaging of the brain showed massive cerebral infarction in the distribution of the left carotid artery with midline shift and impeding brain stem herniation. She underwent emergent decompressive hemicraniectomy with duraplasty and placement of an intracranial pressure monitor. Intracranial pressure was controlled with sedation and the patient was extubated on postoperative day 4. Extensive stroke workup was negative. Cranioplasty was performed at 3 months post-op. At the 6-month follow-up, she had an excellent recovery (modified Rankin scale of 1). Decompressive hemicraniectomy should be considered for the treatment of cerebral edema in children with malignant cerebral infarction. This may improve mortality and functional outcome compared to medical therapy alone. Due to the rare occurrence of stroke in children, more reports of decompressive hemicraniectomy are encouraged.