A central nervous system metastasis of melanoma with stroke-like onset of left-lower quadrantanopsia.
ABSTRACT: "Stroke mimics" mean diseases presenting with acute neurological impairments that are taken for stroke. Discriminating them is crucial to avoid improper treatment or delayed correct treatment. We describe a 48-year-old woman presenting with a sudden onset of scintillating scotoma and left-lower quadrantanopsia. Hyperacute cerebral infarction was suspected. However, brain magnetic resonance imaging (MRI) revealed a mass at the cortico-medullary junction in the right occipital lobe. We diagnosed her as metastatic melanoma. We suspected that neurological deficits can be attributed to seizure, and therefore introduced levetiracetam. She showed neurological improvement immediately. Our case demonstrated the importance of considering brain tumor as a differential diagnosis in patients presenting with acute-onset neurological deficits. In addition to appropriate treatment of tumor, the use of newer antiepileptic drugs resulted in good neurological prognosis in metastatic brain tumors.
Project description:To identify susceptibility loci for visual migraine aura in migraine families primarily affected with scintillating scotoma type of aura.We included Finnish migraine families with at least 2 affected family members with scintillating scotoma as defined by the International Criteria for Headache Disorders-II. A total of 36 multigenerational families containing 351 individuals were included, 185 of whom have visual aura and 159 have scintillating scotoma. Parametric and nonparametric linkage analyses were performed with 378 microsatellite markers. The most promising linkage loci found were fine-mapped with additional microsatellite markers.A novel locus on chromosome 9q22-q31 for migraine aura was identified (HLOD = 4.7 at 104 cM). Fine-mapping identified a shared haplotype segment of 12 cM (9.8 Mb) on 9q21-q22 among the aura affected. Four other loci showed linkage to aura: a locus on 12p13 showed significant evidence of linkage, and suggestive evidence of linkage was detected to loci on chromosomes 5q13, 6q25, and 13q14.A novel visual migraine aura locus has been mapped to chromosome 9q21-q22. Interestingly, this region has previously been linked to occipitotemporal lobe epilepsy with prominent visual symptoms. Our finding further supports a shared genetic background in migraine and epilepsy and suggests that susceptibility variant(s) to visual aura for both of these traits are located in the 9q21-q22 locus.
Project description:Ischemic injury can be alleviated by the judicious use of hypothermia. However, the optimal regimens and the temporal kinetics of post-stroke neurovascular responses to hypothermic intervention have not been systematically studied. These gaps slow the clinical translation of hypothermia as an anti-stroke therapy. Here, we characterized the effects of transient selective brain hypothermia (TSBH) from the hyperacute to chronic stages of focal ischemia/reperfusion brain injury induced by transient middle cerebral artery occlusion in mice. A simple cooling device was used to induce TSBH during cerebral ischemia. This treatment reduced mortality from 31.8% to 0% and improved neurological outcomes for at least 35 days post-injury. TSBH mitigated blood-brain barrier leakage during the hyperacute and acute injury stages (1-23?h post-reperfusion). This early protection of the blood-brain barrier was associated with anti-inflammatory phenotypic polarization of microglia/macrophages, reduced production of pro-inflammatory cytokines, and less brain infiltration of neutrophils and macrophages during the subacute injury stage (three days post-reperfusion). TSBH elicited enduring protective effects on both grey and white matter for at least 35 days post-injury and preserved the long-term electrophysiological function of fiber tracts. In conclusion, TSBH ameliorates ischemia/reperfusion injury in the neurovascular unit from hyperacute to chronic injury stages after experimental stroke.
Project description:A migraine is a recurring neurological disorder characterized by unilateral, intense, and pulsatile headaches. In one-third of migraine patients, the attacks are preceded by a visual aura, such as a slowly-propagating scintillating scotoma. Migraine aura is thought to be a result of the neurovascular phenomenon of cortical spreading depression (SD), a self-propagating wave of depolarization that spreads across the cerebral cortex. Several animal experiments have demonstrated that cortical SD causes intracranial neurogenic inflammation around the meningeal blood vessels, such as plasma protein extravasation and pro-inflammatory peptide release. Cortical SD has also been reported to activate both peripheral and central trigeminal nociceptive pathways. Although several issues remain to be resolved, recent evidence suggests that cortical SD could be the initial trigger of intracranial neurogenic inflammation, which then contributes to migraine headaches via subsequent activation of trigeminal afferents.
Project description:Introduction: Neurological manifestations are emerging as relatively frequent complications of corona virus disease 2019 (COVID-19), including stroke and encephalopathy. Clinical characteristics of the latter are heterogeneous and not yet fully elucidated, while the pathogenesis appears related to neuroinflammation in a subset of patients. Case: A middle-aged man presented with acute language disturbance at the emergency department. Examination revealed expressive aphasia, mild ideomotor slowing, and severe hypocapnic hypoxemia. Multimodal CT assessment and electroencephalogram (EEG) did not reveal any abnormalities. COVID-19 was diagnosed based on chest CT findings and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription PCR (RT-PCR) on nasopharyngeal swab. The following day, neurological symptoms progressed to agitated delirium and respiratory status worsened, requiring admission to the ICU and mechanical ventilation. Brain MRI and cerebrospinal fluid (CSF) studies were unremarkable. RT-PCR for SARS-CoV-2 on CSF was negative. He received supportive treatment and intravenous low-dose steroids. His neurological and respiratory status resolved completely within 2 weeks. Conclusions: We report a patient with reversible COVID-19-related encephalopathy presenting as acute aphasia, mimicking stroke or status epilepticus, eventually evolving into delirium. Although large-vessel stroke is frequently encountered in COVID-19, our case suggests that focal neurological deficits may occur as the earliest feature of encephalopathy. Neurological status reversibility and the absence of abnormalities on brain MRI are consistent with a functional rather than a structural neuronal network impairment.
Project description:BACKGROUND AND PURPOSE:The purposes of this study were to describe features of children with intracerebral hemorrhage (ICH) and to determine predictors of short-term outcome in a single-center prospective cohort study. METHODS:A single-center prospective consecutive cohort study was conducted of spontaneous ICH in children aged 1 to 18 years from January 2006 to June 2008. Exclusion criteria were inciting trauma; intracranial tumor; isolated epidural, subdural, intraventricular, or subarachnoid hemorrhage; hemorrhagic transformation of ischemic stroke; and cerebral sinovenous thrombosis. Hospitalization records were abstracted. Follow-up assessments included outcome scores using the Pediatric Stroke Outcome Measure and King's Outcome Scale for Childhood Head Injury. ICH volumes and total brain volumes were measured by manual tracing. RESULTS:Twenty-two patients, median age 10.3 years (range, 4.2 to 16.6 years), had presenting symptoms of headache in 77%, focal deficits 50%, altered mental status 50%, and seizures 41%. Vascular malformations caused hemorrhage in 91%. Surgical treatment (hematoma evacuation, lesion embolization or excision) was performed during acute hospitalization in 50%. One patient died acutely. At a median follow-up of 3.5 months (range, 0.3 to 7.5 months), 71% of survivors had neurological deficits; 55% had clinically significant disability. Outcome based on Pediatric Stroke Outcome Measure and King's Outcome Scale for Childhood Head Injury scores was worse in patients with ICH volume >2% of total brain volume (P=0.023) and altered mental status at presentation (P=0.005). CONCLUSIONS:Spontaneous childhood ICH was due mostly to vascular malformations. Acute surgical intervention was commonly performed. Although death was rare, 71% of survivors had persisting neurological deficits. Larger ICH volume and altered mental status predicted clinically significant disability.
Project description:Crosstalk between the brain and systemic responses in blood is increasingly suspected of playing critical roles in stroke. However, how this communication takes place remains to be fully understood. Here, we show that reactive astrocytes can release a damage-associated molecular-pattern molecule called high-mobility-group-box-1 (HMGB1) that promotes endothelial progenitor cell (EPC)-mediated neurovascular remodeling during stroke recovery. Conditioned media from reactive astrocytes increase EPC proliferation in vitro. siRNA suppression of HMGB1 in astrocytes or blockade of the HMGB1 receptor for advanced glycation endproducts in EPCs prevents this effect. In a mouse model of focal cerebral ischemia, reactive astrocytes in the peri-infarct cortex up-regulate HMGB1 at 14 d poststroke, along with an accumulation of endogenous EPCs. In vivo siRNA suppression of HMGB1 blocks this EPC response, reduces peri-infact angiogenesis, and worsens neurological deficits. Taken together, these molecular and in vivo findings support a previously undescribed mechanism of crosstalk between reactive astrocytes and EPCs wherein HMGB1 promotes neurovascular remodeling and functional recovery after stroke and brain injury.
Project description:Stroke is a significant cause of death and disability in Singapore; in 2014, it was the fourth most common cause of death. Transient ischaemic attack (TIA) is defined as a transient episode of neurological dysfunction caused by focal brain, spinal cord or retinal ischaemia without evidence of acute infarction. The diagnosis of TIA/acute stroke needs to be considered in all patients who present with sudden focal neurological dysfunction. Prompt referral for assessment, neuroimaging and intervention provides the best chance for neurological recovery and/or minimising further neurological damage. Primary care physicians have a crucial role in TIA/stroke prevention and management. This includes referring patients with suspected acute TIA/stroke to hospitals with stroke treatment facilities immediately; managing the modifiable risk factors of cerebral ischaemia; continuing prescription of antiplatelet agents and/or anticoagulation where indicated; and teaching patients to recognise and respond to suspected cerebral ischaemia using the FAST (face, arm, speech, time) acronym.
Project description:Microparticles (MPs, ~size between 0.1 and 1 mm) are lipid encased containers derived from intact cells which contain antigen from the parent cells. MPs are involved in intercellular communication and regulate inflammation. Stroke increases secretion of brain derived MP (BDMP) which activate macrophages/microglia and induce neuroinflammation. Lactadherin (Milk fat globule-EGF factor-8) binds to anionic phospholipids and extracellular matrices, promotes apoptotic cell clearance and limits pathogenic antigen cross presentation. In this study, we investigate whether BDMP affects stroke-induced neuroinflammation and whether Lactadherin treatment reduces stroke initiated BDMP-induced neuroinflammation, thereby improving functional outcome after stroke. Middle aged (8-9 months old) male C57BL/6J mice were subjected to distal middle cerebral artery occlusion (dMCAo) stroke, and BDMPs were extracted from ischemic brain 24 h after dMCAo by ultracentrifugation. Adult male C57BL/6J mice were subjected to dMCAo and treated via tail vein injection at 3 h after stroke with: (A) +PBS (n = 5/group); (B) +BDMPs (1.5 × 108, n = 6/group); (C) +Lactadherin (400 ?g/kg, n = 5/group); (D) +BDMP+Lactadherin (n = 6/group). A battery of neurological function tests were performed and mice sacrificed for immunostaining at 14 days after stroke. Blood plasma was used for Western blot assay. Our data indicate: (1) treatment of Stroke with BDMP significantly increases lesion volume, neurological deficits, blood brain barrier (BBB) leakage, microglial activation, inflammatory cell infiltration (CD45, microglia/macrophages, and neutrophils) into brain, inflammatory factor (TNF?, IL6, and IL1?) expression in brain, increases axon/white matter (WM) damage identified by decreased axon and myelin density, and increases inflammatory factor expression in the plasma when compared to PBS treated stroke mice; (2) when compared to PBS and BDMP treated stroke mice, Lactadherin and BDMP+Lactadherin treatment significantly improves neurological outcome, and decreases lesion volume, BBB leakage, axon/WM injury, inflammatory cell infiltration and inflammatory factor expression in the ischemic brain, respectively. Lactadherin treatment significantly increases anti-inflammatory factor (IL10) expression in ischemic brain and decreases IL1? expression in plasma compared to PBS and BDMP treated stroke mice, respectively. BDMP increases neuroinflammation and aggravates ischemic brain damage after stroke. Thus, Lactadherin exerts anti-inflammatory effects and improves the clearance of MPs to reduce stroke and BDMP induced neurological deficits.
Project description:Background and Purpose- The complexity and heterogeneity of stroke, as well as the associated comorbidities, may render neuroprotective drugs less efficacious in clinical practice. Therefore, the development of targeted therapies to specific patient subsets has become a high priority in translational stroke research. Ischemic stroke with type 2 diabetes mellitus has a nearly double mortality rate and worse neurological outcomes. In the present study, we tested our hypothesis that rFGF21 (recombinant human fibroblast growth factor 21) administration is beneficial for improving neurological outcomes of ischemic stroke with type 2 diabetes mellitus. Methods- Type 2 diabetes mellitus db/db and nondiabetic genetic control db/+ mice were subjected into permanent focal ischemia of distal middle cerebral artery occlusion, we examined the effects of poststroke administration with rFGF21 in systemic metabolic disorders, inflammatory gatekeeper PPAR? (peroxisome proliferator-activated receptor ?) activity at 3 days, mRNA expression of inflammatory cytokines and microglia/macrophage activation at 7 days in the perilesion cortex, and last neurological function deficits, ischemic brain infarction, and white matter integrity up to 14 days after stroke of db/db mice. Results- After permanent focal ischemia, diabetic db/db mice presented confounding pathological features, including metabolic dysregulation, more severe brain damage, and neurological impairment, especially aggravated proinflammatory response and white matter integrity loss. However, daily rFGF21 treatment initiated at 6 hours after stroke for 14 days significantly normalized systemic metabolic disorders, rescued PPAR? activity decline, inhibited proinflammatory cytokine mRNA expression, and M1-like microglia/macrophage activation in the brain. Importantly, rFGF21 also significantly reduced white matter integrity loss, ischemic brain infarction, and neurological function deficits up to 14 days after stroke. The potential mechanisms of rFGF21 may in part consist of potent systematic metabolic regulation and PPAR?-activation promotion-associated antiproinflammatory roles in the brain. Conclusions- Taken together, these results suggest rFGF21 might be a novel and potent candidate of the disease-modifying strategy for treating ischemic stroke with type 2 diabetes mellitus.