Transient Mumps-associated Vasculopathy Presenting as Ischemic Stroke in an Infant

Deoxyribonucleic acid (DNA) integrity plays a significant role in cell function. There are limited studies with regard to the role of DNA damage in bipolar affective disorder (BP). In the present study, we have assessed DNA integrity, conformation, and stability in the brain region of bipolar depression (BD) patients (n=10) compared to age-matched controls (n=8). Genomic DNA was isolated from 10 postmortem BD patients’ brain regions (frontal cortex, Pons, medulla, thalamus, cerebellum, hypothalamus, Parietal, temporal, occipital lobe, and hippocampus) and from the age-matched control subjects. DNA from the frontal cortex, pons, medulla, and thalamus showed significantly higher number of strand breaks in BD (P<0.01) compared to the age-matched controls. However, DNA from the hippocampus region was intact and did not show any strand breaks. The stability studies also indicated that the melting temperature and ethidium bromide binding pattern were altered in the DNA of BD patients’ brain regions, except in the hippocampus. The conformation studies showed B-A or secondary B-DNA conformation (instead of the normal B-DNA) in BD patients’ brain regions, with the exception of the hippocampus. The levels of redox metals such as Copper (Cu) and Iron (Fe) were significantly elevated in the brain regions of the sufferers of BD, while the Zinc (Zn) level was decreased. In the hippocampus, there was no change in the Fe or Cu levels, whereas, the Zn level was elevated. There was a clear correlation between Cu and Fe levels versus strand breaks in the brain regions of the BD. To date, as far as we are aware, this is a new comprehensive database on stability and conformations of DNA in different brain regions of patients affected with BD. The biological significance of these findings is discussed here.

HomeStrokeVol. 52, No. 12Updated Perspective on Severe Acute Respiratory Syndrome Coronavirus-2 Infection and Ischemic Stroke Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBUpdated Perspective on Severe Acute Respiratory Syndrome Coronavirus-2 Infection and Ischemic Stroke Adnan I. Qureshi Adnan I. QureshiAdnan I. Qureshi Correspondence to: Adnan I. Qureshi, MD, Zeenat Qureshi Institute and Department of Neurology in the University of Missouri, One Hospital Dr, CE507, Columbia, MO 65212. Email E-mail Address: [email protected] https://orcid.org/0000-0003-4962-540X Zeenat Qureshi Institute and Department of Neurology in the University of Missouri, Columbia. Originally published4 Nov 2021https://doi.org/10.1161/STROKEAHA.121.037010Stroke. 2021;52:3987–3988This article is a commentary on the followingRisk, Clinical Course, and Outcome of Ischemic Stroke in Patients Hospitalized With COVID-19: A Multicenter Cohort StudyOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: November 4, 2021: Ahead of Print See related article, p 3978The occurrence of ischemic stroke in patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, especially in those with multiple organ dysfunctions, was initially documented in the early period of the pandemic.1 The occurrence rate of ischemic stroke was initially estimated to be around 5% based on data from critically ill patients with SARS-CoV-2 infection but later studies identified the rate to be between 1% and 2% when patients with mild illness were included.2,3 There continues to be a controversy whether the risk of ischemic stroke is higher with SARS-CoV-2 infection compared with other respiratory illnesses.2,3Sluis et al4 report data from 16 Dutch hospitals participating in the international CAPACITY-COVID registry (registry of patients with SARS-CoV-2 including cardiovascular risk and complications) between March 1 and August 1, 2020. The occurrence rate of ischemic stroke was 1.8% among 2147 patients admitted with SARS-CoV-2 infection with a higher rate of 2.7% among patients admitted to the intensive care units. There are 3 important findings in this study. First, the median time between onset of SARS-CoV-2 infection symptoms and stroke diagnosis was 14 days suggesting that ischemic stroke was not the first manifestation but rather an occurrence after the SARS-CoV-2 infection had already been diagnosed. This observation suggests that the possibility of acute stroke patients presenting with undiagnosed SARS-CoV-2 infection5 is small which is reassuring for medical professionals involved in the evaluation of acute stroke patients. Second, pulmonary embolism was more common in patients with ischemic stroke than in those without stroke (21.1% versus 7.6%). The concurrent existence may support the occurrence of hyper coagulopathy in SARS-CoV-2 infection secondary to immune activation leading to both venous and arterial thrombosis.6 Third, a total of 27 of 38 patients with ischemic stroke had moderate to severe disability at discharge or had died during hospitalization. The high rate of death or disability in SARS-CoV-2 infected patients is probably related to multiple organ dysfunction/failure,1 such as pneumonia, respiratory failure, acute kidney injury, septic shock, cardiac arrest, and requirement for intubation/mechanical ventilation, and is unlikely to be influenced from acute revascularization treatments (thrombolysis and thrombectomy). An assessment of the magnitude of organ dysfunction may be helpful in delineating the overall care paradigm in acute stroke patients in accord with the expected prognosis in addition to stroke-related factors. The question whether the benefit of acute revascularization treatment is obscured by multiple organ dysfunction/failure1 and use be restricted in contrast to general population of patients with ischemic stroke requires additional data.7 One of the surprising findings was the lack of difference in proportions of patient with preexisting cardiovascular risk factors among SARS-CoV-2 infected patients with and without ischemic stroke. In a previous analysis,2 the proportion of patients with hypertension, diabetes, hyperlipidemia, atrial fibrillation, and congestive heart failure was significantly higher among SARS-CoV-2 infected patients who developed ischemic stroke compared with those who did not. The investigators recognize the difference between their studies and previous data and attribute this finding to the possibility be that older patients with more cardiovascular risk factors may not have been hospitalized or admitted to an intensive care units, because of treatment restrictions or patient preferences. However, the finding does raise the question that SARS-CoV-2 may trigger ischemic stroke in absence of preexisting cardiovascular risk factors. This observation in addition to the higher occurrence of pulmonary embolism in ischemic stroke patients suggests that generalized de novo hyper coagulopathy may be a contributing factor to occurrence of ischemic stroke seen in patients with SARS-CoV-2 infection.5Article InformationDisclosuresDr Qureshi has received consultation fees from AstraZeneca.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.This manuscript was sent to Marc Fisher, Senior Guest Editor, for review by expert referees, editorial decision, and final disposition.For Disclosures, see page 3988.Correspondence to: Adnan I. Qureshi, MD, Zeenat Qureshi Institute and Department of Neurology in the University of Missouri, One Hospital Dr, CE507, Columbia, MO 65212. Email qureshai@gmail.com

DIFFERENT PATHOLOGICAL DISTRIBUTION PATTERN OF PHOSPHORYLATED TAU AND MICROGLIA IN AMNESTIC AND NON-AMNESTIC ALZHEIMER’S DISEASE

See related article, pages 2425–2431. Stroke is the third leading cause of death.1,2 Fatal outcome has been primarily related to acute or chronic complications of stroke-induced executive deficits, such as muscle weakness, swallowing disorders, respiratory dysfunction with pneumonia, or cardiac complications.3,4 Only during the last 10 or 15 years has there been an increasing interest in and knowledge of associations between cerebral lesions and altered influences of the central autonomic nervous system on cardiovascular and respiratory function.5–7 Oppenheimer et al8–10 suggested a role of the insular cortex in the pathophysiology of sudden death. The group extensively assessed topographically distinct interactions of the left and the right insular cortex with heart rate and blood pressure control.11 There was agreement that insular cortex lesions essentially contribute to clinically relevant alterations of cardiovascular control.8 In this issue of Stroke , Rincon and coworkers present an analysis of associations between ischemic stroke location and fatal cardiac outcome, based on the epidemiological data of the Northern Manhattan Stroke study (NOMAS).12,13 Considering neurological syndromes and neuroimaging findings, the authors analyzed outcome during a 5-year follow-up period. Mortality rates or nonfatal myocardial infarctions, and particularly sudden unexpected or unwitnessed death, were associated with the location of brain infarctions. Apart from age, male gender, the National Institutes of Health Stroke Scale (NIHSS), and a history of coronary artery disease, the authors identified infarct locations in the frontal, parietal, temporal lobe, and …

A. Anatomic Classification 1. Idiotypic primary cortex (sensory or motor, e.g., primaryvisual cortex) a. Initial cortical processing of afferent sensory input orsource of primary motor efferents b. Modality-specific c. Directly connected with association cortices and subcor-tical modulating nuclei (e.g., basal ganglia, thalamus) 2. Homotypic unimodal association cortexa. Usually anatomically close to respective primary cortex; modulates the function of primary cortexb. Modality-specific c. Directly connected not only to respective primary cortexbut also with heteromodal association cortex (convergence of pathways) and subcortical modulating nuclei (e.g., basal ganglia, thalamus)3. Homotypic heteromodal (multimodal) association cortex a. Directly connected with each other and unimodal associ-ation cortices (including the limbic and paralimbic regions)b. Two major areas 1) Anterior heteromodal association area (prefrontal cor-tex): concerned with planning of movements and executive functions2) Posterior heteromodal association area (parietotemporalareas, junction between parietal, temporal, and occipital lobes): visuospatial perception and language4. Limbic and paralimbic cortex a. Corticoid areas: basal forebrain (primitive organizationwithout discernable lamination in some areas; least differentiated) 1) Amygdala complex 2) Septal nuclei 3) Substantia innominata (basal nucleus of Meynert)b. Allocortex 1) Hippocampal complex and piriform or primaryolfactory cortex (paleocortex) 2) One or two bands of neurons arranged in externaland internal pyramidal layers c. Mesocortex (paralimbic structures)1) Parahippocampal region 2) Orbitofrontal cortex 3) Temporal pole 4) Insula 5) Cingulate cortexB. Histology 1. Cell typesa. Pyramidal cells 1) Pyramidal-shaped cells with apical dendrites extendingtoward cortical surface 2) "Projection neurons" involved in transmitting signalsto other cortical, subcortical, or spinal areas 3) Located mainly in layers III, V, and VI 4) The neurotransmitter is glutamate (excitatory)b. Stellate cells 1) Star-shaped neurons with dendritic extensions in alldirections 2) Found in all layers, but most common in layer IV 3) Are local inhibitory interneurons; use γ-aminobutyricacid (GABA) c. Fusiform cells1) Found primarily in layer VIPrimary cortices do not communicate directly with each otherHeteromodal areas are responsible for integration of cortical processes and input from unimodal association areas, which in turn receive input from primary cortices2) Long dendritic processes extend toward cortical surface3) Axons project primarily to thalamus 2. Horizontal cortical organizationa. Neocortex (primary, unimodal, and heteromodal areas) is organized in six layers 1) Layers I to IV receive afferents 2) Layer V projects to spinal cord, brainstem, and basalganglia 3) Layer VI projects to thalamus 4) Corticocortical connections: mainly from layers IIand III of primary cortices to layers V and VI of association corticesb. Layer I-molecular (plexiform) layer: consists mainly of local interneurons and apical dendrites of pyramidal cells in deeper layerc. Layer II-external granular layer 1) Stellate cells: axons project to deeper cortical layers 2) Pyramidal cells: axons project to contralateral cortexas commissural fibers d. Layer III-external pyramidal layer: pyramidal cellswith projections to ipsilateral cortices (association fibers) or contralateral hemisphere (commissural fibers)e. Layer IV-internal granular layer 1) Consists mainly of stellate cells 2) Receives afferent glutaminergic input from thalamus 3) Prominent layer in primary sensory corticesf. Layer V-internal pyramidal layer 1) Pyramidal cells: axons project to basal ganglia, brain-stem, spinal cord, and contralateral cortex (commissural fibers)2) Prominent layer in primary motor cortex, which contains giant pyramidal cells of Betzg. Layer VI-multiform layer: pyramidal cells with projections to thalamus and layer IV3. Vertical (columnar) cortical organization a. Each column is a functional unit of cortex b. Specificity of connection with target cells is maintainedand afferent feedback from the same target is received c. Layer IV is the main input layer in each column d. Afferents from a specific group of neurons in thalamusproject to a designated cortical column (layer IV): the organizational specificity of neuronal columns is mirrored in subcortical modulating nuclei (e.g., thalamus, basal ganglia)4. Intercortical connections a. Association fibers: connection between different corticesin same hemisphere 1) U-fibers (short association fibers) 2) Superior longitudinal fasciculus3) Cingulum (part of the Papez circuit) 4) Inferior longitudinal fasciculus 5) Uncinate fasciculusb. Commissural fibers: connection between the two cerebral hemispheres 1) Corpus callosum 2) Anterior commissure 3) Posterior commissure 4) Hippocampal commissurec. Projection fibers: corticosubcortical fibersC. Cortical Localization 1. Frontal lobea. Primary motor cortex (Brodmann area 4, M I) 1) Type: idiotypic primary cortex 2) Voluntary discrete movements involving direct projec-tions to spinal cord anterior horn cells and subsequent direct activation of a motor unit3) Lesion: contralateral pattern of upper motor neuron weakness a) Acute lesion: hypotonic and flaccid b) Chronic lesion: spastic, increased reflexes4) Stimulation or epileptic activity: partial motor seizures with spread (jacksonian march) reflect somatotopic organization of the areab. Premotor areas (area 6, M II) 1) Type: homotypic unimodal cortex 2) All areas project to primary motor cortex and spinalcord 3) All receive projections from parietal cortex: parieto-premotor pathways are important in goal-directed movements (reaching and grasping)4) Divisions a) Ventral and dorsolateral premotor cortexi) Located on lateral aspect of frontal lobe anterior to M Iii) Input from parietal lobe and medial premotor areasiii) Responsible for initiating motor plans in response to sensory stimuli (e.g., stopping at a red light)iv) Involved in learning to associate a particular sensory stimulus with a particular motor movement (associative learning)b) Supplementary motor cortex (medial premotor area, area 6, M II) i) Located on medial aspect of frontal lobe anteriorto M I ii) Input from ipsilateral parietal lobe and pre-frontal "presupplementary area" iii) Presupplementary area is responsible for learningsequences of a motor plan and supplementary motor cortex is responsible for producing the motor sequence already learned-does not initiate motor plans in response to sensory stimuli as the lateral premotor regions doiv) Blood flow to supplementary motor cortex increases when one is thinking about or planning a movementv) Contains complete bilateral somatotopic representation of the bodyvi) Responsible for coordinating and advance planning of movements on the two sides of the bodyvii) Stimulation/epileptic activity: tonic abduction and external rotation/elevation of the contralateral arm with forced head turn toward elevated arm (fencing posture)c. Frontal eye fields (homotypic unimodal cortex): voluntary conjugate horizontal eye movements (lesion: transient paralysis of contralateral gaze)d. Broca's area 1) Receives connections from Wernicke's area via arcuatefasciculus 2) Projects to premotor areas involved in motor programsrequired for speech production 3) Lesion: nonfluent aphasia, typically involving deficitsin both language production and motor speech outputs 2. Prefrontal lobea. Type: homotypic heteromodal cortex (all three regions discussed below)b. Dorsolateral prefrontal cortex 1) Located on convexity of the gyri anterior to areas 8and 45 2) Interconnects with other heteromodal regions, basalganglia, and dorsomedial thalamus 3) Important for executive functions, planning, judgment,problem-solving 4) Lesion: poor abstract thought, poor planning, poorjudgment and problem solving, psychomotor retardation, motor impersistance and perseveration, poor executive functioning, and dysexecutive syndromec. Orbitofrontal cortex 1) Located on inferior surface of frontal lobes andincludes the frontal poles 2) Widespread interconnection with limbic system andbasal ganglia 3) Responsible for emotional and visceral activities,social behavior, and inhibition of inappropriate behavior in a particular social context as well as judgment4) Responsible for conscious perception of smell:receives input from piriform cortex via thalamic relay 5) Impairment: disinhibited, impulsive behavior; poorjudgment and insight; emotional lability; euphoria and excessive and inappropriate laughter and jocular affect, especially with right hemispheric lesions; speech apraxia; environmental dependency syndrome with utilization; perseveration; hyperorality; hypersexuality6) Impairment also associated with obsessive-compulsive behavior7) Lesions of orbitofrontal cortex a) Meningioma: commonly involving the sphenoidwing or olfactory groove b) Closed head injury: usually affecting orbitofrontaland anterior temporal areas because of the irregular surface of the anterior and middle cranial fossae8) Stimulation/epileptic activity a) Motor and gestural automatisms that may be com-plex (bicycling, walking around the room) b) Olfactory hallucinations and forced thinking withanterior frontopolar focus d. Mesial frontal cortex and anterior cingulate cortex1) Interconnections with limbic system (especially amygdala)2) Important role in initiation, motivation, and goaloriented behavior3) Impairment: abulia, indifference, poor speech output, impaired initiation of a behavior or motor movement with reduced spontaneous movements; associated with urinary incontinence and gait disturbance4) With severe impairment: akinetic mutism (no spontaneous behavior)5) Anterior cerebral artery distribution strokes orruptured anterior communicating artery aneurysms can selectively involve mesial frontal structures6) Stimulation/epileptic activity: complex motor and gestural automatismse. Wisconsin Card Sorting Test 1) Sensitive measure of function of prefrontal cortex 2) The subject is asked to sort the cards according to acertain perceptual attribute of a visual stimulus (e.g., color, form, number) and, then, challenges the subject to shift cognitive sets without warning3) Patients with frontal lobe lesions have difficulty with this task because of poor cognitive flexibility and perseveration)3. Parietal lobe a. Primary somatosensory cortex (S I, postcentral gyrus):idiotypic primary cortex b. Secondary somatosensory cortex (S II) on the parietaloperculum (on superior lip of sylvian fissure): homotypic unimodal cortex 1) Direct input from thalamus and postcentral gyrus(S I) 2) Bilateral receptive fields (mostly contralateral),receives and integrates information from both sides of the body3) Provides somatosensory input to motor cortex 4) Projections to limbic system: important for tactilelearning c. Dorsal M pathway: occipitoparietal visuospatial pathwayresponsible for visuomotor tasks (see below) d. Impairment1) Lesion of primary somatosensory cortex (S I): primary somatosensory deficits (e.g., touch, vibration, joint position, stimulus localization), sparing pain and temperature sensations, which are projected to second somatosensory cortex (S II)2) Lesion of S II at parietal operculum: pseudothalamic syndrome a) Impairment of pain and temperature (may havecomplete loss of elementary sensory modalities) b) Syndrome of delayed pain and paresthesias, as mayoccur sometimes with thalamic infarcts 3) Parietal somatosensory association corticesa) Complex somatosensory functions b) Lesions produce "cortical sensory deficits" (e.g.,two-point discrimination, graphesthesia, stereognosis, and recognition of bilateral simultaneous stimulation)4) Impairment of nondominant hemisphere: anosognosia, dressing apraxia, geographic agnosia, constructional apraxia, hemispatial sensory neglectLesions of Prefrontal Cortex Dorsolateral: poor executive functions, planning, judgment, and problem solvingOrbitofrontal: disinhibition, impulsive behavior, poor judgment and insightMedial frontal and anterior cingulate Abulia, indifference, poor speech output, impaired initiation of a behavior or motor movement with reduced spontaneous movementsAssociated with urinary incontinence and gait disturbance5) Lesions of dominant hemisphere: finger agnosia, acalculia, agraphia, alexia, aphasia (primarily conduction aphasia and/or transcortical sensory aphasia), right-left disorientation, conduction apraxia a) Angular gyrus syndrome (lesion of angular gyrus,heteromodal cortex): anomia, alexia, constructional difficulties, acalculia, dysgraphia, finger anomia, right-left disorientation (aphasia may be present if lesion extends to superior temporal gyrus and Wernicke's area)b) Gerstmann's syndrome: acalculia, dysgraphia, finger anomia, right-left disorientation6) Lower homonymous quadrantanopia from damage to optic radiations (if lesion extends deep enough)7) Balint's syndrome: optic ataxia, ocular apraxia, simultanagnosia (bilateral lesions)8) Reduced slow phase of optokinetic nystagmus 4. Temporal lobea. Primary auditory cortex (idiotypic primary cortex) 1) Located on dorsomedial aspect of superior temporalgyrus 2) Has a well-defined tonotopic map reflecting cochlearorganization 3) Unilateral lesions do not cause hearing loss, butsubject may have difficulty localizing sound stimuli in space, especially from the opposite sideb. Auditory association cortex (homotypic unimodal cortex): no well-defined tonotopic mapc. Wernicke's area d. Middle and inferior temporal lobes: memory and learning e. Limbic area: inferior and medial temporal areas f. Uncus receives olfactory and gustatory input g. Subcortical occipitotemporal projections and opticradiations (Meyer's loop) h. Insular cortex: taste area II (taste area I is on dorsal aspectof lateral sulcus near insular cortex) i. Impairment1) Superior homonymous quadrantanopia 2) Cortical hearing loss with bilateral temporal (or sub-cortical) lesions 3) Auditory agnosia with lesions of bilateral, more thanunilateral, temporal cortex (and/or corresponding subcortical areas): difficulty recognizing different sounds (nonverbal auditory agnosias may also result from right-sided lesions)4) Dysacusis: perception of particular sounds as unpleasant5) Pure word deafness (often bilateral lesions) a) A verbal auditory agnosia (due to auditory-verbaldisconnection)b) Patients can hear and react to environmental auditory cues and can understand written language, but are unable to understand spoken language6) Wernicke's aphasia (dominant lesions) 7) Klüver-Bucy syndrome: bilateral anterior temporallobe lesions (see below) 8) Amnesiaa) Nondominant hemisphere: amnesia for nonverbal, visuospatial informationb) Dominant hemisphere: amnesia for verbal information)9) Amusia a) Example of nonverbal auditory agnosia b) Difficulty with recognition of songs, primarilybecause of disturbance of recognition of different characteristics of music composition (e.g., rhythm, pitch, tone) due to right temporal lobe lesionsc) Left temporal lobe lesions: not true amusia, patient has difficulty understanding lyricsd) Left temporal lobe lesions in musicians who analyze different aspects of music composition may produce some degree of amusia10) Ageusia (lack of taste): possibly occurs with bilateral lesions of insular cortex11) Semantic dementia: dominant anterior temporal lobe is site of word meaning (object-word associations)12) Prosopagnosia (defined below) a) Lesion in posteroinferior temporo-occipital region b) Usually bilateral lesions, but nondominant hemi-sphere lesion may be sufficient j. Stimulation/epileptic phenomena1) Complex visual hallucinations of people, animals, etc. from a posterior temporal lobe epileptic focus2) Auditory hallucinations 3) Olfactory hallucinations (especially unpleasant odor,"uncinate fits"), gustatory hallucinations, epigastric rising sensation, intense fear (or pleasure), usually associated with alteration of consciousness and associated with complex partial seizures arising from medial temporal lobe4) Alternation of memory a) Déjà vu: sensation of familiarity with a previouslyunfamiliar experience, place, or event b) Déjà entendu: sensation of familiarity with apreviously unfamiliar auditory experience (e.g., sound, music, speech, or narrative)c) Jamais vu: sensation of unfamiliarity with a previously familiar experience, place, or eventd) Jamais entendu: sensation of unfamiliarity with a previously familiar auditory experiencesymptoms such as amaurosis, scotoma, or visual field defects)b) Eye deviation, nystagmoid eye movements5) Palinopsia a) Recurrence of an image no longer present in visualfield b) May occur with posterior temporo-occipitalepileptic focus 6) Automatisms are associated with the complex partialseizures arising from, or spreading to, mesial temporal lobe7) Postictal cough 5. Occipital lobea. Primary visual (striate) cortex (V1) 1) Type: idiotypic primary cortex (area 17) 2) Located along the banks of calcarine fissure 3) Layer IVa) Receives the majority of input from lateral geniculate nucleusb) Projects primarily to layers II and III, which then project to association cortices4) Projections to superficial layer of superior colliculus and pulvinar: responsible for production of saccades and rapid shifting of gaze to another point in the visual field in response to a novel stimulus a) Other sensory cortices project to deep layers ofsuperior colliculus b) Superior colliculus acts as a sensory integration center c) Novel visual stimulii) Retinal ganglion cells and primary visual cortex project to superior colliculus (e.g., moving vehicle entering the far right visual field)ii) Other sensory input (e.g., auditory-projections from corresponding primary sensory [auditory] cortex) to deep layers of superior colliculusiii) Superior colliculus: integrated sensory response to direct gaze toward novel stimuli5) Occipital pole: central (macular) vision 6) More anterior portions of calcarine cortex: peripheralvision 7) Impairmenta) Homonymous hemianopsia: may or may not spare macular area (vascular lesions often spare the macula because of dual blood supply)b) Anton's syndrome: bilateral lesions of medial occipital lobe (usually acute onset) cause cortical blindness associated with denial of the deficit, of which the patient is unaware, and confabulation8) Stimulation/epileptic phenomena a) Simple elementary visual hallucinations, primarilygeometric shapes and (usually but may be Cortical Angular gyrus angular gyrus lesion alexia, constructional difficulties, acalculia, dysgraphia, finger anomia, right-left disorientation syndrome Dominant angular gyrus lesion dysgraphia, finger anomia, right-left syndrome Bilateral medial occipital lobe lesion Cortical blindness associated with denial of the deficit, for which the patient is unaware, and syndrome Lesion occipitotemporal pathways often with ataxia, ocular apraxia, simultanagnosia Klüver-Bucy anterior temporal lobe lesion and behavior, emotional of response to fear and and activity syndrome that the are the patient as in context of that a is an Usually associated with in the context of syndrome of are but not in context of and but may also be in syndrome to produce an internal image of a the to inferior temporal primarily with perception of and important in recognition of and and pattern cells do to in Impairment of can cause i) visual visual or the the lesions usually involve occipital or bilateral occipitotemporal this is in to visual agnosia in which perception is and patient can the but is unable to the disturbance may be in lesions involving the posterior parietal area, sparing the cortices responsible for cortical blindness with lesions of inferior association areas 1) Type: homotypic unimodal cortex 2) Located in the occipital areas and middle and inferior temporal gyri of visual input perception of different aspects of visual input as well as perception of and integration with other sensory projections to parietal and temporal Dorsal M a) in M cells of that project to of lateral geniculate nucleus b) dorsal to middle temporal medial superior temporal areas to the posterior parietal area i) and in the in is primarily the junction of parietal, and temporal Bilateral lesions of can cause agnosia to M cells do not to in but neurons are to primarily in the M information on perception of of and of a particular visual Important for and information about the of an in optic and Important role in shifting of gaze in response to visual ocular Important for understanding the meaning of an image as a in simultanagnosia perception of different of the Balint's syndrome: the of optic ataxia, ocular apraxia, and simultanagnosia (usually occurs with bilateral Other of impairment: or bilateral inferior slow of optokinetic Ventral a) in cells in that project to of lateral geniculate in the hemisphere or and a superior quadrantanopia because the lesion inferior cortex to the calcarine or inferior temporal patient can but of (e.g., patient that the of is difficulty recognizing familiar and lesion occipitotemporal areas or affecting Difficulty the characteristics and of and Unilateral or bilateral superior and of and the of 1. complex of most organization is in and have dendrites to Receives input from major and sensory cerebral cortex, for of Projects to cerebral cortex directly or via thalamic relay to cortical Interconnections between thalamus and cerebral are important for coordinating cortical activity and processing sensory most important for 1) Projections to basal forebrain and for 2) Lesion may cause functional 1) to thalamic nucleus inhibitory projections to other thalamic 2) to and basal forebrain 3) cortical mainly from and h. 2) receives afferent 3) responsible for 1) forebrain important in of behavior, projections to thalamus and important in of and neurons a) Located in nuclei of b) Reduced with from to 3) Located in and b) group is in c) Responsible for of Cortical of the occipital lobe inferior to the calcarine involving the inferior occipitotemporal produce a superior visual field and loss of vision in the inferior visual field perception of both the superior and inferior visual fields are but the superior visual field the of the superior Patients to and is more when are in a particular of a (e.g., is of and familiar to the patient is and may use other such as or a to the difficulty and emotional to the right gyrus more to gyri Responsible for of which modulates and of in response to of stimuli i) activation for ii) activation associated and increased emotional 4) a. connections with b. local inhibitory projections to thalamic nuclei nucleus and nuclei b. neurons project to cerebral cortex: of 1. Inferior posterior parietal cortex and the primary sensory cortices are important for perception of a novel stimulus and initiation of a response to the stimulus a. Superior and parietal lobe connections with the frontal eye all important for perception of a novel visual cortices selectively the thalamic nucleus and the inhibitory of this nucleus on other thalamic thalamic relay of sensory Prefrontal cortex (especially mesial frontal frontal eye and anterior cingulate cortex are responsible for and selectively on the novel stimulus to the important stimuli in the as well as a. Lesion can cause motor perseveration, and akinetic mutism with severe of the mesial frontal lobes or a cortical (especially a. Projects to prefrontal areas and is an important prefrontal function b. Lesion of or or 4. Primary and association sensory cortices 5. and and are important in of of 1. Acute b. Chronic of and memory as a (e.g., c. or other d. Subcortical associated and possibly other frontal lobe may be of projections and other subcortical pathways as in or dominant with subcortical infarcts and Unilateral a. Unilateral sensory is with bilateral simultaneous of the of the of the is as of the May be to when is severe of the primary sensory 1) may be to has a 2) the patient the to hemispatial from of the of hemispheric lesions usually cause contralateral usually with hemispheric lesions) 1) hemisphere the inferior parietal for for both sides of the and hemisphere only for the right of the patient is of the deficits (e.g., and perceptual and cognitive most commonly with right hemisphere patient is to the recognition of or often with right hemisphere hemisphere lesions may also be associated with the a) reduced of emotional in speech hemisphere especially right of or disorientation, impaired and in the of right posterior cortex of or right parietal or motor of motor behavior to the primarily a result of sensory and 1. of and experience and alteration of behavior as a result of the form, in response to to the same and for a. behavior can be with of neuronal pathways b. in neuronal and are of and are responsible for learning and or learning of information 5. of previously as memory of memory 1) that conscious and is which is and meaning of people, and and conscious (e.g., for of perception of sensory association cortices and e.g., visual association cortices are involved in and of specific aspects of a particular visual stimulus is of is mesial temporal lobe and and cortices the of of involving association cortices mesial temporal aspects of a particular experience are in different regions, and memory for a experience is in a of a particular region loss of previously in that region and loss of to in that of a) of and abstract to (e.g., Semantic memory association areas and other regions mesial temporal Semantic memory loss usually memory memory loss may be in a of and can also be in in with memory and other i) of that have and with in particular and of that conscious and and conscious memory that not conscious is memory nonverbal Long or more to and cerebral for that occur a event memory loss to to information a particular previously memory 1) that not conscious is slow 2) of memory i) for a motor task the same is slow and the is to Motor learning occurs with the of the and motor and cortical Cortical pathways important for motor motor cortex, premotor cortex, supplementary motor cortex, the parietal lobe (lesion of pathways may produce perceptual is to of memory on the of a. in hemisphere (dominant amnesia for verbal memory of verbal may be with temporal lobe 1) in right hemisphere 2) amnesia for visual memory may be right temporal lobe patient may have difficulty recognizing etc.

Circadian rhythms in noradrenergic (NE) and dopaminergic (DA) metabolites and in cyclic nucleotide production were measured in discrete regions of rat brain. A circadian rhythm was found in the concentration of the NE metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), in the hippocampus. No MHPG rhythm was found in frontal, cingulate, parietal, piriform, insular or temporal cortex, or in hypothalamus. Circadian rhythms in the concentration of the NE metabolite, 3,4-dihydroxyphenylglycol (DHPG), occurred in occipital and parietal cortex and hypothalamus, with no rhythm observable in temporal or insular cortex, hippocampus, pons-medulla or cerebellum. The 24-hr mean concentration of MHPG varied 3.5-fold, highest in cingulate and lowest in parietal, temporal and occipital cortex. The 24-hr mean concentration of DHPG varied 6-fold, highest in hypothalamus and lowest in parietal cortex. Circadian rhythms in the concentration of the DA metabolite, homovanillic acid (HVA), were found in olfactory tubercle, amygdala and caudate-putamen, but not in nucleus accumbens. A circadian rhythm in the concentration of the DA metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), occurred in nucleus accumbens, but not in olfactory tubercle or caudate-putamen. The mean 24-hr concentration of HVA was highest in caudate-putamen, intermediate in nucleus accumbens, and lowest in olfactory tubercle and amygdala. The mean 24-hr concentration of DOPAC was highest in nucleus accumbens and lower in olfactory tubercle and caudate-putamen. Circadian rhythms were found in the concentration of cyclic GMP (cGMP) in all regions measured except parietal cortex. The mean 24-hr concentration varied 128-fold, highest in nucleus accumbens, frontal poles, and hypothalamus and lowest in cingulate cortex. Circadian rhythms in cyclic AMP (cAMP) concentration were found in piriform, temporal, occipital, cingulate, and parietal cortex, amygdala and nucleus accumbens. No rhythms were found in frontal or insular cortex, hypothalamus, hippocampus, caudate-putamen or olfactory tubercle. The 24-hr mean cAMP concentration varied 4-fold, highest in parietal cortex and lowest in caudate-putamen and amygdala. Norepinephrine metabolites and dopamine metabolites were rhythmic in few regions. It is, therefore, unlikely that the rhythmicity measured in adrenergic receptors is, in general, a response to rhythmic changes in adrenergic transmitter release. The putative second messenger response systems, especially cGMP, were more often rhythmic. The rhythms in cGMP are parallel in form and region to those in the alpha 1-adrenergic receptor and may act as 2nd messenger for that receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Severe complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include arterial ischemic stroke (AIS) in adults and multisystem inflammatory syndrome in children. Whether stroke is a frequent complication of pediatric SARS-CoV-2 is unknown. This study aimed to determine the proportion of pediatric SARS-CoV-2 cases with ischemic stroke and the proportion of incident pediatric strokes with SARS-CoV-2 in the first 3 months of the pandemic in an international cohort. We surveyed 61 international sites with pediatric stroke expertise. Survey questions included: numbers of hospitalized pediatric (≤ 18 years) patients with SARS-CoV-2; numbers of incident neonatal and childhood ischemic strokes; frequency of SARS-CoV-2 testing for pediatric patients with stroke; and numbers of stroke cases positive for SARS-CoV-2 from March 1 to May 31, 2020. Of 42 centers with SARS-CoV-2 hospitalization numbers, 8 of 971 (0.82%) pediatric patients with SARS-CoV-2 had ischemic strokes. Proportions of stroke cases positive for SARS-CoV-2 from March to May 2020 were: 1 of 108 with neonatal AIS (0.9%), 0 of 33 with neonatal cerebral sinovenous thrombosis (CSVT; 0%), 6 of 166 with childhood AIS (3.6%), and 1 of 54 with childhood CSVT (1.9%). However, only 30.5% of neonates and 60% of children with strokes were tested for SARS-CoV-2. Therefore, these proportions represent 2.9, 0, 6.1, and 3.0% of stroke cases tested for SARS-CoV-2. Seven of 8 patients with SARS-CoV-2 had additional established stroke risk factors. As in adults, pediatric stroke is an infrequent complication of SARS-CoV-2, and SARS-CoV-2 was detected in only 4.6% of pediatric patients with ischemic stroke tested for the virus. However, < 50% of strokes were tested. To understand the role of SARS-CoV-2 in pediatric stroke better, SARS-CoV-2 testing should be considered in pediatric patients with stroke as the pandemic continues. ANN NEUROL 2021;89:657-665.

Objective To investigate the value of PET/CT imaging of cerebral glucose metabolism (CGM) and cerebral blood flow (CBF) in evaluating chronic disorders of consciousness (CDC). Methods A total of 10 CDC patients (5 males, 5 females, age (50.9±17.2) years) and 10 healthy controls (5 males, 5 females, age (52.0±10.3) years) from January 2016 to March 2017 were recruited to perform brain PET/CT of CGM and CBF. The brain PET imaging using 13N-Ammonia was performed and followed by 18F-fluorodeoxyglucose (FDG) PET. The mean standardized uptake values (SUVmean) of frontal, parietal, temporal and occipital lobes as well as basal ganglia, thalamus were obtained. The SUVmean of cerebral regions/SUVmean of cerebellum ratios (SUVr) were acquired. The SUVr were compared between the patients and controls. The imaging characteristics of CGM and CBF were investigated, and their relationships with clinical scores were further analyzed. Two-sample t test and Pearson correlation analysis were used to analyze the data. Results The radioactive distribution in the brain of healthy controls was symmetrical. SUVr of cerebral regions in the affected side of patients were significantly lower than those of the controls both in CGM imaging and CBF imaging (t values: 2.90-5.19, all P<0.05). In 10 CDC patients, there were 9 with hypometabolism in basal ganglia and thalamus, 8 with hypometabolism in frontal and parietal lobes, and 7 with hypometabolism in temporal and occipital lobes. At the same time, there were 7 with parietal hypoperfusion and 6 with hypoperfusion in other cerebral regions in the CDC patients. In the frontal, parietal lobes and basal ganglia, the CGM and CBF were both correlated with the clinical scores (r values: 0.473-0.606, all P<0.05). Abnormal metabolism-perfusion patterns were divided into 3 types. Type Ⅰ included 2 patients and their hypometabolism and hypoperfusion were mismatched completely. Type Ⅱ included 3 patients and their hypometabolism and hypoperfusion were matched in frontal, parietal, occipital and temporal lobes, while mismatched in basal ganglia and thalamus. Type Ⅲ included 5 patients and their hypometabolism and hypoperfusion were matched completely. The clinical scores of typeⅠ, Ⅱand Ⅲ were 10.5, 8.3 and 5.6, respectively. Conclusion The PET/CT imaging of cerebral blood flow and metabolism is useful in evaluating the disorders of consciousness. Key words: Consciousness disorders; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose; Ammonia

This study was designed to estimate cerebral dysfunction in senile dementia of the Alzheimer's type (SDAT). Regional cerebral blood flow (rCBF), oxygen extraction fraction (rOEF) and cerebral oxygen consumption (rCMRO2) were studied in 16 patients with SDAT and 5 age-matched normal elderly people by positron emission tomography (PET), using the 15O labeled CO2 and O2 inhalation technique. This technique was also applied to the evaluation of PET in diagnosing the dementing illnesses. In this study, a total of 19 pairs of bilateral cerebral regions were analyzed and the reductions of rCBF and rCMRO2 in each region were compared with those of the primary sensorimotor cortex to demonstrate any significant localized difference between each clinical stage of the SDAT and normal controls. In the mild SDAT group, CMRO2 of the temporal cortex was significantly reduced, as compared with that of controls. In the moderate SDAT group, CBF of the temporal cortex and CMRO2 of the temporal and parietal cortices were significantly reduced. In the severe SDAT group, CBF and CMRO2 of the frontal cortex were also reduced and those of the occipital cortex were relatively unchanged. This suggested that mildly demented patients showed a metabolic reduction in the temporal cortex and as the dementia progressed, metabolic reductions were extended to the parietal and frontal cortices. Reductions in blood flow were followed by further metabolic reductions. More detailed investigation of the PET images of SDAT revealed that relative oxygen hypometabolism of the posterior temporal and posterior parietal association cortices occurred in the mildly demented patients earlier than that of the other association cortices. These findings are consistent with neuropathological studies of SDAT. The right/left ratio of rCMRO2 was also analyzed in each region. The right/left oxygen metabolic asymmetry in the temporal and parietal cortices was correlated with the difference between speech and visuospatial functions. Namely, the patients with a lower metabolism in the left hemisphere had more disturbances in speech than visuospatial functions. In addition, the PET images of SDAT were compared with those of multi-infarct dementia (MID) and Pick disease. In patients with MID, there were reductions of CBF and CMRO2 unhomogenously all over association cortices, but the reductions were most remarkable in the frontal cortex. Patients with Pick disease showed diffuse lobar reductions of CBF and CMRO2 in the frontal and temporal cortices.(ABSTRACT TRUNCATED AT 400 WORDS)

Technetium-99m HMPAO brain SPECT in autistic children and their families

To investigate the impact of traumatic injury on the developing prefrontal-temporal adolescent cortex, and correlated brain structural measures with neurocognitive functioning. Nineteen adolescents (12 males, 7 females, age range: 11-17y, mean 15y 8mo, standard deviation 1y 7mo, median 15y 11mo) with traumatic brain injury (TBI) were included. Cortical thickness of frontal and temporal lobes was assessed using magnetic resonance imaging. We correlated cortical thickness of prefrontal-temporal regions with age, time since injury, and neurocognitive functioning, and compared these results with a matched control cohort without TBI. We found thinner prefrontal (p=0.039) and temporal cortices (p=0.002) in adolescents with TBI compared to typically developing children. Furthermore, significant age effect was observed on the prefrontal (r=-0.75, p=0.003) and temporal (r=-0.66, p=0.013) cortical thickness in typically developing adolescents, but not in adolescents with TBI. Executive function (measured using the Behaviour Rating Inventory of Executive Function questionnaire, with lower scores meaning higher functioning) was correlated with prefrontal cortical thickness in typically developing adolescents (r=0.72, p=0.009). Opposite trends were found for correlations between cortical thickness and executive function in the TBI and control cohort. Structural maturation in typically developing adolescents correlates with functional development: the older the adolescent, the thinner the prefrontal cortex, the better executive function. In adolescents with TBI we observed an opposite trend, that appeared significantly different from the control group: the thinner the prefrontal and temporal cortex, the worse executive functioning. Cortical thickness is negatively correlated with age in typically developing adolescents. Prefrontal cortex thickness correlates negatively with executive function in typically developing adolescents. Correlations between cortical thickness and executive functioning rise for adolescents without traumatic brain injury (TBI). Correlations between cortical thickness and executive functioning fall for adolescents with TBI. Adolescents with TBI have a long-term impairment of adaptive functioning in daily living.

Imaging of Eating Disorders: Multiple Techniques to Demonstrate the Dynamic Brain

Circadian rhythms were measured in alpha 1-, alpha 2- and beta-adrenergic, acetylcholine muscarinic (ACh), and benzodiazepine (BDZ) receptor binding in small regions of rat brain. Rhythms in alpha 1-receptor binding were measured in olfactory bulb, frontal, cingulate, piriform, parietal, temporal and occipital cortex, hypothalamus, hippocampus, pons-medulla, caudate-putamen and thalamus-septum. No rhythm was found in cerebellum. Rhythms in alpha 2-receptor binding were measured in frontal, parietal and temporal cortex, and pons-medulla. No rhythm was found in cingulate, piriform or occipital cortex, or hypothalamus. Rhythms in binding to beta-receptors were measured in olfactory bulb, piriform, insular, parietal and temporal cortex, hypothalamus and cerebellum. No rhythms were found in frontal, entorhinal, cingulate, or occipital cortex, hippocampus, caudate-putamen, or pons-medulla. Rhythms in ACh receptor binding were measured in olfactory bulb, parietal cortex and caudate-putamen. No rhythms were found in frontal or occipital cortex, nucleus accumbens, hippocampus, thalamus-septum, pons-medulla or cerebellum. Rhythms in BDZ receptor binding were measured in olfactory bulb, olfactory and occipital cortex, olfactory tubercle, nucleus accumbens, amygdala, caudate-putamen, hippocampus and cerebellum. No rhythms were found in parietal cortex, pons-medulla or thalamus-septum. The 24-hr mean binding to receptors varied between 3- and 10-fold, the highest in cortex and the lowest, usually, in cerebellum. The piriform cortex was particularly high in alpha 1- and alpha 2-adrenergic receptors; the nucleus accumbens and caudate, in ACh receptors; and the amygdala, in BDZ receptors. Most adrenergic and ACh receptor rhythms peaked in subjective night (the period when lights were off under L:D conditions), whereas most BDZ receptor rhythms peaked in subjective day (the time lights were on in L:D). Perhaps in the rat, a nocturnal animal, the adrenergic and ACh receptors mediate activity and the functions that accompany it, and the BDZ receptors mediate rest, and with it, sleep.

Ischemic Stroke Epidemiology During the COVID-19 Pandemic: Navigating Uncharted Waters With Changing Tides.

Purpose: As of November 28, 2020, COVID-19 has been reported in 220 countries with 61,036,793 confirmed cases and 1,433,316 confirmed deaths; countries became vigilant around the world. In addition to SARS-CoV-2 causing pneumonia, many studies have reported ischemic stroke in patients with COVID-19. This article describes the effects and possible underlying mechanisms of SARS-CoV-2 on ischemic stroke. Materials and methods: A literature search was performed using PubMed, Web of Science, and other COVID-dedicated databases and the combination of the keywords ‘SARS-CoV-2’, ‘COVID-19’ and ‘ischemic stroke’ up to November 28, 2020. Results: SARS-CoV-2 invades the host through angiotensin converting enzyme 2 (ACE2). ACE2 is expressed not only in the lungs, but also in the brain and vascular endothelial cells. SARS-CoV-2 infection might cause direct vascular disease or enhance the immunogenic thrombosis environment through several mechanisms. SARS-CoV-2 infection can modulate the host immune response and can cause inflammation, coagulation disorders, renin angiotensin system disorders, hypoxia, and stress disorders, which may lead to the occurrence of ischemic stroke. Conclusions: Some patients with COVID-19 can develop ischemic stroke. Ischemic stroke has a high risk of causing disability and is associated with a high mortality rate. It is hoped that when medical staff treat patients with COVID-19, they would pay attention to the occurrence of ischemic stroke to improve the prognosis of patients with COVID-19.