Advances in Management of the Stroke Etiology One-Percenters.

PURPOSE OF REVIEW: Uncommon causes of stroke merit specific attention; when clinicians have less common etiologies of stoke in mind, the diagnosis may come more easily. This is key, as optimal management will in many cases differs significantly from "standard" care. RECENT FINDINGS: Randomized controlled trials (RCT) on the best medical therapy in the treatment of cervical artery dissection (CeAD) have demonstrated low rates of ischemia with both antiplatelet and vitamin K antagonism. RCT evidence supports the use of anticoagulation with vitamin K antagonism in "high-risk" patients with antiphospholipid antibody syndrome (APLAS), and there is new evidence supporting the utilization of direct oral anticoagulation in malignancy-associated thrombosis. Migraine with aura has been more conclusively linked not only with increased risk of ischemic and hemorrhagic stroke, but also with cardiovascular mortality. Recent literature has surprisingly not provided support the utilization of L-arginine in the treatment of patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS); however, there is evidence at this time that support use of enzyme replacement in patients with Fabry disease. Additional triggers for reversible cerebral vasoconstriction syndrome (RCVS) have been identified, such as capsaicin. Imaging of cerebral blood vessel walls utilizing contrast-enhanced MRA is an emerging modality that may ultimately prove to be very useful in the evaluation of patients with uncommon causes of stroke. A plethora of associations between cerebrovascular disease and COVID-19 have been described. Where pertinent, authors provide additional tips and guidance. Less commonly encountered conditions with updates in diagnosis, and management along with clinical tips are reviewed.

Leptomeningeal Carcinomatosis Mimicking Reversible Cerebral Vasoconstriction Syndrome.

Leptomeningeal carcinomatosis is the result of metastatic infiltration of the leptomeninges by malignant cells originating from an extra-meningeal primary tumor site. We describe a patient with active breast cancer who presented with thunderclap headaches (THs) and imaging showing multi-segment irregular arterial narrowing of intracranial vasculature. A 58-year-old Caucasian woman with active stage IV estrogen receptor-positive breast adenocarcinoma and migraine presented with THs. Computed tomography and brain magnetic resonance imaging (MRI) without contrast were unremarkable. Over a period of one week, she had recurrent THs. Interval vessel imaging showed multi-segment irregular arterial narrowing. Treatment with verapamil was initiated for suspected reversible cerebral vasoconstriction syndrome (RCVS). She subsequently had two discrete episodes of confusion with aphasia and left upper extremity numbness. Repeat gadolinium-enhanced MRI showed nodular leptomeningeal enhancement. Lumbar puncture revealed malignant cells in the cerebrospinal fluid consistent with leptomeningeal carcinomatosis. She subsequently underwent whole brain radiation treatment and intrathecal chemotherapy and had no further episodes of TH. Our case emphasizes the importance of considering leptomeningeal carcinomatosis in the differential diagnosis of THs and reversible cerebral vasculopathy, especially in patients with known underlying active cancer. The illustration also proves the importance of a complete work-up in patients with known malignancy in the setting of suspected RCVS.

Neurologic complications of nonbacterial thrombotic endocarditis.

Endocarditis is an inflammatory or infective condition affecting the cardiac valves or endocardium, often associated with serious neurological sequelae. Nonbacterial thrombotic endocarditis (NBTE)-referred to as degenerative, Libman-Sachs, marantic, verrucous, or terminal endocarditis-is a serious but rare cause of valvular heart disease characterized by deposition of sterile vegetations of fibrin and platelet aggregates on the cardiac valves, eventually resulting in life-threatening embolization of these thrombi to the brain, limbs, or visceral organs. NBTE may complicate a heterogeneous group of chronic conditions, predominantly connective tissue and autoimmune disorders, malignancies, and diseases associated with hypercoagulability states. NBTE usually affects the native rather than prosthetic valves, and unlike infective endocarditis (IE), sparing the involved valve function without its destruction. Compared to those seen in IE, vegetations in NBTE are small and friable, thus may easily be dislodged leading to systemic thromboembolism with devastating morbidities and mortality. There are no diagnostic criteria for NBTE, and antemortem diagnosis is challenging. The condition should be suspected in patients with thromboembolic events and vegetations on the cardiac valves on echocardiographic or cardiac imaging studies, in the absence of underlying infection, especially in disorders predisposing to coagulopathy. Early recognition and prompt treatment of the primary underlying disorder is essential. Anticoagulation with heparin or heparinoid products is recommended to prevent recurrent embolism. Surgical intervention is not indicated except in selected patients with life-threatening recurrent embolism.

Acute Stroke Care in the Coronavirus Disease 2019 Pandemic.

Coronavirus disease 2019 (COVID-19) is a pandemic respiratory disease with serious public health risk and has taken the world off-guard with its rapid spread. As the COVID-19 pandemic intensifies, overwhelming the healthcare system and the medical community, current practice for the management of acute ischemic stroke (AIS) will require modification, and guidelines should be relaxed while maintaining high standard quality of care. The aim of these suggestions is to avoid contributing to the rapid spread of COVID-19 as well as to conserve what are likely to be very limited resources (including personnel, intensive care/hospital beds as well as physicians) while maintaining high quality care for patients with AIS. We present our recommendations for the management of acute stroke during the COVID-19 pandemics.

Intravascular Lymphomatosis Presenting with Spinal Cord Infarction and Recurrent Ischemic Strokes.

Intravascular lymphomatosis (IVL) is a rare subtype of large B-cell lymphoma that follows an aggressive course with rapidly progressive neurological involvement and potentially fatal outcome.1 We report on a 64-year-old man with progressive myelopathy at T6-T7 and recurrent cerebral infarctions. This case is illustrative of the clinical course that is seen in IVL. It aims to present a timeline of imaging findings that demonstrate the progression of disease and characteristic pathology findings. We emphasize the importance of IVL on the differential diagnosis of spinal cord infarction.

Spinal Cord Infarction due to Fibrocartilaginous Embolism: A Report of 3 Cases.

Fibrocartilaginous embolism (FCE) is an uncommon cause of spinal cord infarction often misdiagnosed as transverse myelitis. The mechanism of ischemia is suspected to be due to retrograde embolization of nucleus pulposus material originating from Schmorl's nodes to the spinal vessels following acute disk herniation. We describe the clinical and imaging findings of FCE in 3 healthy young women with history of trivial spinal cord trauma, and recommend that FCE should be considered in the differential diagnosis of acute myelopathy.

Cerebral Infarctions Following Palliative Transarterial Chemoembolization with Embozene of a Vertebral Body Metastatic Tumor.

Preoperative transarterial chemoembolization has been widely used as an adjunct therapy for hypervascular metastatic spinal tumors. Several therapeutic iodized oil-based agents have been used in combination with anticancer drugs for injection into a feeding artery. Novel spherical agents with narrow-range particles and lower tendency to clump are preferred for the embolization of vascular malformations and hypervascular tumors. We describe the first case of cerebral embolization resulting in posterior circulation infarctions following transarterial embolization of a vascular vertebral body metastatic tumor with Embozene microspheres.

Intravenous thrombolysis for ischemic stroke in recurrent oligodendroglioma: a case report.

Data on efficacy and safety of intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rtPA) in patients with acute ischemic stroke (AIS) and intracranial neoplasm are lacking. To date, only a handful of case reports have been published in the literature addressing the administration of IV rtPA to patients with AIS and coexisting brain neoplasms. We present the case of successful IV thrombolysis with rtPA for AIS in a patient with oligodendroglioma on bevacizumab without hemorrhagic complications. We summarize the published cases of thrombolysis in AIS in patients with intracranial neoplasms.

Motor cortex stimulation: functional magnetic resonance imaging-localized treatment for three sources of intractable facial pain.

Neuropathic facial pain can be a debilitating condition characterized by stabbing, burning, dysesthetic sensation. With a large range of causes and types, including deafferentation, postherpetic, atypical, and idiopathic, both medicine and neurosurgery have struggled to find effective treatments that address this broad spectrum of facial pain. The authors report the use of motor cortex stimulation to alleviate 3 distinct conditions associated with intractable facial pain: trigeminal deafferentation pain following rhizotomy, deafferentation pain secondary to meningioma, and postherpetic neuralgia. Functional MR imaging was used to localize facial areas on the precentral gyrus prior to surgery. All 3 patients experienced long-lasting complete or near-complete resolution of pain following electrode implantation. Efficacy in pain reduction was achieved through variation of stimulation settings over the course of treatment, and it was assessed using the visual analog scale and narrative report. Surgical complications included moderate postsurgical incisional pain, transient cerebral edema, and intraoperative seizure. The authors' results affirm the efficacy and broaden the application of motor cortex stimulation to several forms of intractable facial pain.

Atypical Chronic Headache and Recurrent Facial Ecchymosis: A Case Report.

We present the case of a 57-year-old woman with chronic paroxysmal headache and recurrent facial ecchymosis. The headaches are chronic, unilateral, sharp, electric shock-like, of short duration, without nausea nor vomiting, ptosis, miosis, conjunctival injection nor tearing. The facial ecchymoses have been mainly located in the periorbital and epicanthal areas. General, neurological and ophthalmological examinations were unremarkable. Work-up was unremarkable, including negative skin biopsy. The headache was difficult to include in any particular category given the atypical features, but the characteristics were suggestive of a variant of trigeminal autonomic cephalalgia with lack of responsiveness to indomethacin. We discuss the possible pathogenetic mechanism of the occurrence of facial ecchymosis in primary headache disorders.

Resolution of paroxysmal hemicrania after resection of intracranial meningioma.

Paroxysmal hemicrania is a trigeminal autonomic cephalalgia first described in 1976, characterized by episodic attacks of excruciating unilateral periorbital and temporal stabbing, pulsatile, craw-like, or boring headaches lasting 2 - 30 minutes, accompanied by autonomic features, and alleviated by indomethacin. Paroxysmal hemicrania is divided into an episodic or chronic form, depending on the duration and frequency of the attacks. We describe a case of paroxysmal hemicrania in a patient with a contralateral anterior clinoid meningioma, which resolved after tumor resection. Most cases of autonomic cephalgias are primary headaches and not caused by underlying intracranial structural lesions. Based on our patient and a literature review of secondary causes of trigeminal autonomic cephalalgias, we recommend that all patients with trigeminal autonomic cephalalgias including paroxysmal hemicrania undergo neuroimaging studies. The preferred neuro-radiologic procedure should be a cranial MRI to exclude underlying structural intracranial lesions, particularly in the sellar and parasellar regions.

Childhood maltreatment and migraine (part III). Association with comorbid pain conditions.

OBJECTIVE: To evaluate in a headache clinic population the relationship of childhood maltreatment on the prevalence of pain conditions comorbid with migraine. BACKGROUND: Childhood maltreatment is highly prevalent and has been frequently associated with recurrent headache. The relationship of maltreatment and pain has, however, been a subject of some debate. METHODS: Cross-sectional data on self-reported physician-diagnosed pain conditions were electronically collected from persons with migraine (diagnosed according to International Classification of Headache Disorders-2), seeking treatment in headache clinics at 11 centers across the US and Canada. These included irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), fibromyalgia (FM), interstitial cystitis (IC), arthritis, endometriosis, and uterine fibroids. Other information included demographics, migraine characteristics (frequency, headache-related disability), remote and current depression (The Patient Health Questionnaire-9), and remote and current anxiety (The Beck Anxiety Inventory). Patients also completed the Childhood Trauma Questionnaire regarding sexual, emotional, and physical abuse, and emotional and physical neglect under the age of 18 years old. Statistical analyses accounted for the survey design and appropriate procedures in SAS such as surveymeans, surveyfreq, and surveylogistic were applied to the weighted data. RESULTS: A total of 1348 migraineurs (88% women) were included in this study (mean age 41 years). Based on physician diagnosis or validated criteria, 31% had IBS, 16% had CFS, and 10% had FM. Diagnosis of IC was reported by 6.5%, arthritis by 25%, and in women, endometriosis was reported by 15% and uterine fibroids by 14%. At least 1 comorbid pain condition was reported by 61%, 2 conditions by 18%, and 3 or more by 13%. Childhood maltreatment was reported by 58% of the patients. Emotional abuse was associated with increased prevalence of IBS, CFS, arthritis, and physical neglect with arthritis. In women, physical abuse was associated with endometriosis and physical neglect with uterine fibroids. Emotional abuse, and physical abuse and neglect (P < .0001 for all) were also associated with increased total number of comorbid conditions. In ordinal logistic regression models, adjusted for sociodemographics and current depression (prevalence 28%) and anxiety (prevalence 56%), emotional abuse (odds ratios [OR] = 1.69, 95% confidence intervals [CI]: 1.224-2.33) and physical neglect (OR = 1.73, 95% CI: 1.22-2.46) were independently associated with an increased number of pain conditions. The cohort of women, similarly, had associations of emotional abuse (OR = 1.94, 95% CI: 1.40-2.72) and physical neglect (OR = 1.90, 95% CI: 1.34-2.68) with an increased number of pain comorbidities. CONCLUSION: The association of childhood maltreatment and pain was stronger in those reporting multiple pain conditions and multiple maltreatment types. This finding suggests that in migraineurs childhood maltreatment may be a risk factor for development of comorbid pain disorders.

Allodynia in migraine: association with comorbid pain conditions.

BACKGROUND: Cutaneous allodynia (CA) in migraine is a clinical manifestation of central nervous system sensitization. Several chronic pain syndromes and mood disorders are comorbid with migraine. In this study we examine the relationship of migraine-associated CA with these comorbid conditions. We also evaluate the association of CA with factors such as demographic profiles, migraine characteristics, and smoking status that may have an influence on the relationships of CA to pain and mood. METHODS: Data are from a cross-sectional multicenter study of comorbid conditions in persons seeking treatment in headache clinics. Diagnosis of migraine was determined by a physician based on the International Classification of Headache Disorders-II criteria. Participants completed a self-administered questionnaire ascertaining sociodemographics, migraine-associated allodynia, physician-diagnosed comorbid medical and psychiatric disorders, headache-related disability, current depression, and anxiety. RESULTS: A total of 1413 migraineurs (mean age = 42 years, 89% women) from 11 different headache treatment centers completed a survey on the prevalence of comorbid conditions. Aura was reported by 38% and chronic headache by 35% of the participants. Sixty percent of the study population reported at least one migraine-related allodynic symptom, 10% reported > or =4 symptoms. Symptoms of CA were associated with female gender, body mass index, current smoking, presence of aura, chronic headaches, transformed headaches, severe headache-related disability, and duration of migraine illness from onset. The prevalence of self-reported physician diagnosis of comorbid pain conditions (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia) and psychiatric conditions (current depression and anxiety) was also associated with symptoms of CA. Adjusted ordinal regression indicated a significant association between number of pain conditions and severity of CA (based on symptom count). Adjusting for sociodemographics, migraine characteristics, and current depression and anxiety, the likelihood of reporting symptoms of severe allodynia was much higher in those with 3 or more pain conditions (odds ratio = 3.03, 95% confidence interval: 1.78-5.17), and 2 pain conditions (odds ratio = 2.67, 95% confidence interval: 1.78-4.01) when compared with those with no comorbid pain condition. CONCLUSION: Symptoms of CA in migraine were associated with current anxiety, depression, and several chronic pain conditions. A graded relationship was observed between number of allodynic symptoms and the number of pain conditions, even after adjusting for confounding factors. This study also presents the novel association of CA symptoms with younger age of migraine onset, and with cigarette smoking, in addition to confirming several previously reported findings.

Acute methotrexate neurotoxicity with choreiform movements and focal neurological deficits: a case report.

Methotrexate (MTX) is an effective antimetabolite treatment for various oncological disorders including the central nervous system involvement (CNS) in widespread leukemia and CNS lymphoma. This form of treatment has a notable toxic effect on the nervous system, and the pediatric population seems to be more vulnerable to the neurologic toxicity of this drug. Though chronic leukoencephalopathy from an MTX regimen, especially when administered in conjunction with whole brain radiation, is well described, the acute manifestations are rare and not well understood. The diagnosis of acute focal symptoms from MTX treatment is especially difficult in patients who receive chemotherapy for neoplastic disorders and who may have many reasons for CNS involvement in general and parenchymal involvement in particular. We report the unusual clinical and neuro-imaging findings in a teenager with acute focal symptoms after MTX treatment for acute lymphoblastic leukemia.

Successful delayed thrombolysis for cerebral venous and dural sinus thrombosis: a case report and review of the literature.

Cerebral venous and dural sinus thrombosis (CVDST) is a rare but not uncommon life-threatening disease accounting for less than 1% of stroke, affecting people of any age group, predominantly the extremes of age. CVDST carries a variable prognosis: although the majority of cases are associated with complete recovery, outcome may be fatal in less than 10% of patients. Thrombolysis has been widely used in CVDST in patients with rapidly deteriorating symptoms who fail to improve despite adequate anticoagulation, but the exact therapeutic time window remains unclear. We report a case of CVDST with rapid clinical deterioration despite therapeutic anticoagulation treated with direct endovascular thrombolysis with intravenous recombinant tissue plasminogen activator 1 week after presentation with complete recovery, and we present a review of the literature on the efficacy and safety of thrombolysis in CVDST.

Antiphospholipid syndrome: role of antiphospholipid antibodies in neurology.

Antiphospholipid antibodies (aPLs) are acquired antibodies against anionic phospholipid containing moieties in cell membranes. Their presence often is associated with the antiphospholipid syndrome (APS), an acquired autoimmune prothrombotic syndrome associated with thrombosis in the arterial and venous circulations, recurrent unexplained fetal loss, and thrombocytopenia. The association of aPLs with other nonthrombotic neurological disorders remains of unclear significance. This article reviews the definition of APS, its clinical presentations, and therapeutic approaches.

Risk estimates of stroke after coronary artery bypass graft and carotid endarterectomy.

Neurologic complications of cardiovascular surgeries are well documented in the literature. Neurologic deficits may be mild and reversible or may be associated with permanent neurologic deficit. The incidence and severity of such complications vary according to the type of surgical procedure and usually correlate with patients' preoperative general medical condition, duration of surgeries, and intraoperative complications.

Chordae tendinae tumor as the cause of cardioembolic stroke.

We describe the case of a chordae tendinae papillary fibroelastoma with patent foramen ovale and interatrial septal aneurysm in a healthy young woman who suffered from acute ischemic right middle cerebral artery infarction.