Virtual Planning and Augmented Reality-Guided Microsurgical Resection of a Frontal Arteriovenous Malformation.

Arteriovenous malformations (AVMs) are complex vascular lesions that can pose significant risk for spontaneous hemorrhage, seizures, and symptoms related to ischemia and venous hypertension.1 Microsurgical management of AVMs requires a deep understanding of the surrounding anatomy and precise identification of the lesion characteristics. We demonstrate the use of augmented reality in the localization of arterial feeders and draining veins in relation to bordering normal structures (Video 1). A 66-year-old man presented with several episodes of severe right frontal headaches. Magnetic resonance imaging revealed an AVM along the right frontal pole. Subsequent computed tomography angiography demonstrated arterial supply from the right anterior cerebral artery with venous drainage to the superior sagittal sinus. Due to the size, noneloquent location, and superficial pattern of venous drainage, the patient elected to proceed with microsurgery. A virtual planning platform was used in preparation for surgery. Augmented reality integrated with neuronavigation was used during microsurgical resection. Postoperative angiography showed complete resection of the AVM. The patient was discharged home on postoperative day 3 with no complications. He remains neurologically well at 4 months of follow-up.

Cerebral Blood Flow of the Frontal Lobe in Untreated Children with Trigonocephaly versus Healthy Controls: An Arterial Spin Labeling Study.

BACKGROUND: Craniofacial surgery is the standard treatment for children with moderate to severe trigonocephaly. The added value of surgery to release restriction of the frontal lobes is unproven, however. In this study, the authors aim to address the hypothesis that the frontal lobe perfusion is not restricted in trigonocephaly patients by investigating cerebral blood flow. METHODS: Between 2018 and 2020, trigonocephaly patients for whom a surgical correction was considered underwent magnetic resonance imaging brain studies with arterial spin labeling to measure cerebral perfusion. The mean value of cerebral blood flow in the frontal lobe was calculated for each subject and compared to that of healthy controls. RESULTS: Magnetic resonance imaging scans of 36 trigonocephaly patients (median age, 0.5 years; interquartile range, 0.3; 11 female patients) were included and compared to those of 16 controls (median age, 0.83 years; interquartile range, 0.56; 10 female patients). The mean cerebral blood flow values in the frontal lobe of the trigonocephaly patients (73.0 ml/100 g/min; SE, 2.97 ml/100 g/min) were not significantly different in comparison to control values (70.5 ml/100 g/min; SE, 4.45 ml/100 g/min; p = 0.65). The superior, middle, and inferior gyri of the frontal lobe showed no significant differences either. CONCLUSIONS: The authors' findings suggest that the frontal lobes of trigonocephaly patients aged less than 18 months have a normal cerebral blood flow before surgery. In addition to the very low prevalence of papilledema or impaired skull growth previously reported, this finding further supports the authors' hypothesis that craniofacial surgery for trigonocephaly is rarely indicated for signs of raised intracranial pressure or restricted perfusion for patients younger than 18 months. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Microsurgical Treatment for Posthemorrhagic Cavernoma of Frontal Lobe Coexisting with Unruptured Ipsilateral Middle Cerebral Artery Aneurysm.

Cerebral cavernous malformations, also known as cavernomas, are vascular abnormalities of the brain that are clinically associated with a variety of neurologic symptoms that may include hemorrhagic strokes. They are the most common vascular abnormality, representing 10%-25% of all vascular malformations.1 Lesions associated with cavernomas include developmental venous anomalies, capillary telangiectasias, and other vascular malformations2 but not intracranial aneurysms. The latter association is extremely rare; in fact, there is only 1 case reported in the literature, in which the cavernoma was obscured by the presence of a cerebral hemorrhage and an unruptured aneurysm, which was presumed to be the primary cause of the bleeding, thereby misleading the surgeons to treat only the aneurysm.2 There are different alternatives for the management of different types of lesions.3-5 In this 3-dimensional operative video (Video 1), we present a case of a cavernoma associated with hemorrhage coexisting with an unruptured aneurysm in which we achieved complete resolution of both with microsurgical treatment through a pterional approach.6 The patient consented to publication of images.

Loss with ageing but preservation of frontal cortical capillary pericytes in post-stroke dementia, vascular dementia and Alzheimer's disease.

Cerebral pericytes are an integral component of the neurovascular unit, which governs the blood-brain barrier. There is paucity of knowledge on cortical pericytes across different dementias. We quantified cortical pericytes in capillaries in 124 post-mortem brains from subjects with post-stroke dementia (PSD), vascular dementia (VaD), Alzheimer's disease (AD) and AD-VaD (Mixed) and, post-stroke non-demented (PSND) stroke survivors as well as normal ageing controls. Collagen 4 (COL4)-positive nucleated pericyte soma were identified as protrusions on capillaries of the frontal cortex. The COL4-positive somata or nodule-like cell bodies were also verified by platelet derived growth factor receptor-ß (PDGFR-ß) immunohistochemistry. The mean (± SEM) pericyte somata in frontal cortical capillaries in normal young controls (46-65 years of age) was estimated as 5.2 ± 0.2 per mm capillary length. This number was reduced by 45% in older controls (> 78 years) to 2.9 ± 0.1 per mm capillary length (P < 0.001). We further found that the numbers of pericyte cell bodies per COL4 mm2 area or per mm capillary length were not decreased but rather preserved or increased in PSD, AD and Mixed dementia groups compared to similar age older controls (P < 0.01). Consistent with this, we noted that capillary length densities identified by the endothelial marker glucose transporter 1 or COL4 were not different across the dementias compared to older controls. There was a negative correlation with age (P < 0.001) suggesting fewer pericyte somata in older age, although the % COL4 immunoreactive capillary area was increased in older controls compared to young controls. Using a proven reliable method to quantify COL4-positive nucleated pericytes, our observations demonstrate ageing related loss but mostly preserved pericytes in the frontal cortex of vascular and AD dementias. We suggest there is differential regulation of capillary pericytes in the frontal lobe between the cortex and white matter in ageing-related dementias.

Ischemic Lesions in the Brain of a Neonate With SARS-CoV-2 Infection.

AIM: To describe a term newborn with acquired severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and multisystem involvement including seizures associated to ischemic lesions in the brain. BACKGROUND: Coronavirus disease 2019 (COVID-19) is predominantly a respiratory infection, but it may affect many other systems. Most pediatric COVID-19 cases range from asymptomatic to mild-moderate disease. There are no specific clinical signs described for neonatal COVID-19 infections. In children, severe central nervous system compromise has been rarely reported. CASE DESCRIPTION: We describe a 17-day-old newborn who acquired a SARS-CoV-2 infection in a family meeting that was admitted for fever, seizures and lethargy and in whom consumption coagulopathy, ischemic lesions in the brain and cardiac involvement were documented. CONCLUSIONS: SARS-CoV-2 neonatal infection can be associated with multi-organic involvement. In our patient, significant central nervous system compromise associated to ischemic lesions and laboratory findings of consumption coagulopathy were found. CLINICAL SIGNIFICANCE: Although neonatal SARS-CoV-2 infections are infrequent, they can be associated with multi-organic involvement. Neonatologists and pediatricians should be aware of this unusual way of presentation of COVID-19 in newborn infants.

Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With Gliosis.

Background Patients with restless legs syndrome (RLS) have increased silent microvascular disease by magnetic resonance imaging. However, there has been no previous autopsy confirmation of these magnetic resonance imaging findings. RLS is also frequently associated with inflammatory and immunologically mediated medical disorders. The postmortem cortex in patients with RLS was therefore evaluated for evidence of microvascular and immunological changes. Methods and Results Ten microvascular injury samples of precentral gyrus in 5 patients with RLS (3 men, 2 women; mean age, 81 years) and 9 controls (2 men, 7 women; mean age, 90 years) were studied by hematoxylin and eosin stains in a blinded fashion. None of the subjects had a history of stroke or neurologic insults. In a similar manner, the following immunohistochemistry stains were performed: (1) glial fibrillary acidic protein (representing gliosis, reactive change of glial cells in response to damage); (2) CD3 (a T-cell marker); (3) CD19 (a B-cell marker); (4) CD68 (a macrophage marker); and (5) CD117 (a mast cell marker). Patients with RLS had significantly greater silent microvascular disease (P=0.015) and gliosis (P=0.003). T cells were increased in RLS compared with controls (P=0.009) and tended to colocalize with microvascular disease (P=0.003). Other markers did not differ. There was no correlation between microvascular lesion load and RLS severity or duration. Conclusions Patients with RLS had statistically significantly more silent cerebral microvascular disease and gliosis than controls compatible with previous magnetic resonance imaging studies and with studies showing a link between RLS and hypertension, clinical stroke, and cardiovascular disease. T-cell invasion may be a secondary phenomenon.

Stimulatory effects of (-)-epicatechin and its enantiomer (+)-epicatechin on mouse frontal cortex neurogenesis markers and short-term memory: proof of concept.

Consumption of (-)-epicatechin (Epi), a cacao flavanol improves cognition. The aim was to compare the effects of (-)-Epi or its stereoisomer (+)-Epi on mouse frontal cortex-dependent short-term working memory and modulators of neurogenesis. Three-month-old male mice (n = 7 per group) were provided by gavage either water (vehicle; Veh), (-)-Epi, at 1 mg kg-1 or (+)-Epi at 0.1 mg per kg of body weight for 15 days. After treatment, spontaneous alternation was evaluated by Y-maze. Brain frontal cortex was isolated for nitrate/nitrite measurements, Western blotting for nerve growth factor (NGF), microtubule associated protein 2 (MAP2), endothelial and neuronal nitric oxide synthase (eNOS and nNOS) and immunohistochemistry for neuronal specific protein (NeuN), doublecortin (DCX), capillary (CD31) and neurofilaments (NF200). Results demonstrate the stimulatory capacity of (-)-Epi and (+)-Epi on markers of neuronal proliferation as per increases in immunoreactive cells for NeuN (74 and 120% respectively), DCX (70 and 124%) as well as in NGF (34.4, 63.6%) and MAP2 (41.8, 63.8%). Capillary density yielded significant increases with (-)-Epi (∼80%) vs. (+)-Epi (∼160%). CD31 protein levels increased with (-)-Epi (∼70%) and (+)-Epi (∼140%). Effects correlated with nitrate/nitrite stimulation by (-)-Epi and (+)-Epi (110.2, 246.5%) and enhanced eNOS phosphorylation (Ser1177) with (-)-Epi and (+)-Epi (21.4, 41.2%) while nNOS phosphorylation only increased with (+)-Epi (18%). Neurofilament staining was increased in (-)-Epi by 135.6 and 84% with (+)-Epi. NF200 increased with (-)-Epi (116%) vs. (+)-Epi (84.5%). Frontal cortex-dependent short-term spatial working improved with (-)-Epi and (+)-Epi (15, 13%). In conclusion, results suggest that both enantiomers, but more effectively (+)-Epi, upregulate neurogenesis markers likely through stimulation of capillary formation and NO triggering, improvements in memory.

Identification of autism spectrum disorder based on short-term spontaneous hemodynamic fluctuations using deep learning in a multi-layer neural network.

OBJECTIVE: To classify children with autism spectrum disorder (ASD) and typical development (TD) using short-term spontaneous hemodynamic fluctuations and to explore the abnormality of inferior frontal gyrus and temporal lobe in ASD. METHODS: 25 ASD children and 22 TD children were measured with functional near-infrared spectroscopy located on the inferior frontal gyrus and temporal lobe. To extract features used to classify ASD and TD, a multi-layer neural network was applied, combining with a three-layer convolutional neural network, a layer of long and short-term memory network (LSTM) and a layer of LSTM with Attention mechanism. In order to shorten the time of data collection and get more information from limited samples, a sliding window with 3.5 s width was utilized after comparisons, and numerous short (3.5 s) fNIRS time series were then obtained and used as the input of the multi-layer neural network. RESULTS: A good classification between ASD and TD was obtained with considerably high accuracy by using a multi-layer neural network in different brain regions, especially in the left temporal lobe, where sensitivity of 90.6% and specificity of 97.5% achieved. CONCLUSIONS: The "CLAttention" multi-layer neural network has the potential to excavate more meaningful features to distinguish between ASD and TD. Moreover, the temporal lobe may be worth further study. SIGNIFICANCE: The findings in this study may have implications for rapid diagnosis of children with ASD and provide a new perspective for future medical diagnosis.

TDP-43 Vasculopathy in the Spinal Cord in Sporadic Amyotrophic Lateral Sclerosis (sALS) and Frontal Cortex in sALS/FTLD-TDP.

Sporadic amyotrophic lateral sclerosis (sALS) and FTLD-TDP are neurodegenerative diseases within the spectrum of TDP-43 proteinopathies. Since abnormal blood vessels and altered blood-brain barrier have been described in sALS, we wanted to know whether TDP-43 pathology also occurs in blood vessels in sALS/FTLD-TDP. TDP-43 deposits were identified in association with small blood vessels of the spinal cord in 7 of 14 cases of sALS and in small blood vessels of frontal cortex area 8 in 6 of 11 FTLD-TDP and sALS cases, one of them carrying a GRN mutation. This was achieved using single and double-labeling immunohistochemistry, and double-labeling immunofluorescence and confocal microscopy. In the sALS spinal cord, P-TDP43 Ser403-404 deposits were elongated and parallel to the lumen, whereas others were granular, seldom forming clusters. In the frontal cortex, the inclusions were granular, or elongated and parallel to the lumen, or forming small globules within or in the external surface of the blood vessel wall. Other deposits were localized in the perivascular space. The present findings are in line with previous observations of TDP-43 vasculopathy in a subset of FTLD-TDP cases and identify this pathology in the spinal cord and frontal cortex in a subset of cases within the sALS/FTLD-TDP spectrum.

Effects of site, cerebral perfusion and degree of cerebral artery stenosis on cognitive function.

OBJECTIVE: To investigate the effects of site, cerebral perfusion and degree of cerebral artery stenosis (CAS) on cognitive function. METHODS: A total of 57 patients with CAS and 53 controls from January 2019 to December 2019 were included. The former group was further divided into different subgroups according to the site, cerebral perfusion and degree of CAS. A series of neuropsychological tests were performed to evaluate the cognitive domains (such as memory, executive function, psychomotor speed, etc.). Rank sum test, t test, Chi-square test and analysis of variance were used for data analysis. Spearman correlation analysis was used to examine the relationship between the site, cerebral perfusion and degree of CAS and all tests' scores. RESULTS: For patients with CAS who have decreased cerebral perfusion, their global cognitive function, memory, psychomotor speed, executive function and frontal lobe function were significantly impaired (all P < 0.05). There was a significant decrease in global cognitive function, psychomotor speed, memory, executive function and frontal lobe function in patients with anterior circulation stenosis (all P < 0.05). Moderate and severe CAS impaired subjects' global cognitive function, memory, psychomotor speed, executive function and frontal lobe function (all P < 0.05). There was a correlation between the site, cerebral perfusion, the degree of CAS and cognitive function. CONCLUSION: Global cognitive function, memory, psychomotor speed, frontal lobe function and executive function are impaired in patients with CAS, especially in those with anterior circulatory stenosis, moderate to severe stenosis and low cerebral perfusion.See Video Abstract, http://links.lww.com/WNR/A613.

A Rare Case of Capgras Syndrome in Moyamoya Disease.

Moyamoya disease is a rare cerebrovascular disorder with unknown etiology and psychiatric symptoms occasionally manifest initially. Capgras syndrome is a unique neuropsychiatric symptom that is a delusional misidentification of a familiar person replaced by an identical imposter. We report the case of a 51-year-old woman with frontal lobe ischemic stroke caused by moyamoya disease, presenting with Capgras syndrome. Dysfunction of frontal areas may be attributable to development of Capgras syndrome.

A biventricular takotsubo cardiomyopathy complication: large thrombus formation to stroke in 150 min.

A 67-year-old postmenopausal African American woman presented with biventricular takotsubo cardiomyopathy (TTC)-evidenced by transthoracic echocardiography (TTE) showing apical akinesis of both left and right ventricles in the absence of obstructive coronary artery disease on left heart catheterisation. On the 4th hospital day, she experienced acute left facial droop, dysarthria and dysphagia. CT of the head showed a wedge infarct of the right middle cerebral artery territory. Cardioembolism was presumed after intracranial and extracranial sources of thromboembolism were ruled out. Intravenous tissue plasminogen activator (tPA) was administered with resolution of symptoms. She was later discharged without neurological deficits. Crucially, repeat TTE after tPA infusion revealed a left ventricular mass concerning for thrombus. TTE 150 min prior to stroke onset was devoid of a mass. This case uniquely illustrates the potential for rapid thrombus formation and embolism in patients with TTC. As such, it emphasises the high index of suspicion required for management of these patients.

Angiographic study of the transdural collaterals at the anterior cranial fossa in patients with Moyamoya disease.

Unlike its parietal, temporal, and occipital counterparts, the frontal lobe has a broad basal surface directly facing the anterior cranial fossa dura mater which could permit establishment of transdural collaterals (TDCs) with the frontal lobe. Studies on the TDCs from the anterior cranial fossa in moyamoya disease (MMD) are scarce and inadequately investigated. A retrospective study of 100 hemispheres in 50 patients who were diagnosed with MMD by catheter angiography between January 2015 and June 2019 was performed in our institution. TDCs through the anterior ethmoid artery (AEA) or posterior ethmoid artery (PEA) were divided into 3 types respectively based on their respective angioarchitecture. Furthermore, we also studied TDCs to the temporal, parietal, and occipital lobes and collaterals from the posterior circulation to the territory of the anterior cerebral artery. TDCs through the AEA and PEA were identified in 89 (89/100, 89%) and 73 (73/100, 73%) of the hemispheres. The vascularization state of the frontal lobe was good in 89 (89/100, 89%) hemispheres. Rete mirabile and TDCs through the PEA were statistically different among patients with different Suzuki stages. No statistical difference was noted in TDCs through the AEA, frontal TDCs from other sources, and the vascularization state of the frontal lobe with regard to different Suzuki stages. TDCs through the AEA and PEA at the anterior cranial fossa play a very important role in compensating the ischemic frontal lobe. The frontal lobe could be well compensated in most of the patients with TDCs at the anterior cranial fossa.

Association Between Mental Stress-Induced Inferior Frontal Cortex Activation and Angina in Coronary Artery Disease.

BACKGROUND: The inferior frontal lobe is an important area of the brain involved in the stress response, and higher activation with acute mental stress may indicate a more severe stress reaction. However, it is unclear if activation of this region with stress correlates with angina in individuals with coronary artery disease. METHODS: Individuals with stable coronary artery disease underwent acute mental stress testing using a series of standardized speech/arithmetic stressors in conjunction with high resolution positron emission tomography imaging of the brain. Blood flow to the inferior frontal lobe was evaluated as a ratio compared with whole brain flow for each scan. Angina was assessed with the Seattle Angina Questionnaire's angina frequency subscale at baseline and 2 years follow-up. RESULTS: We analyzed 148 individuals with coronary artery disease (mean age [SD] 62 [8] years; 69% male, and 35.8% Black). For every doubling in the inferior frontal lobe activation, angina frequency was increased by 13.7 units at baseline ([Formula: see text], 13.7 [95% CI, 6.3-21.7]; P=0.008) and 11.6 units during follow-up ([Formula: see text], 11.6 [95% CI, 4.1-19.2]; P=0.01) in a model adjusted for baseline demographics. Mental stress-induced ischemia and activation of other brain pain processing regions (thalamus, insula, and amygdala) accounted for 40.0% and 13.1% of the total effect of inferior frontal lobe activation on angina severity, respectively. CONCLUSIONS: Inferior frontal lobe activation with mental stress is independently associated with angina at baseline and during follow-up. Mental stress-induced ischemia and other pain processing brain regions may play a contributory role.

Posterior Internal Frontal Artery Vascularization of the Precentral Gyrus Responsible for Proximal Arm Movement: Insight from a Case of Coil Migration.

Our knowledge of the vascularization of the precentral gyrus by branches of the anterior cerebral artery (ACA) relies mainly on anatomical cadaveric dissection. A distal branch of the ACA known as the posterior internal frontal artery (PIFA) is thought to vascularize the precentral gyrus responsible for proximal arm movement; however, no clinical correlation has yet been reported to confirm this relation. In this manuscript, we report a case of coil migration in the PIFA, causing proximal arm weakness in a 58-year-old woman treated for aneurysmal subarachnoid hemorrhage. The occurrence of clinical signs immediately following coil migration into the PIFA, combined with evidence of stroke in the cortical territory related to arm movement as seen on imaging, indicates that the PIFA indeed can vascularize this lateral portion of the precentral gyrus. This case confirms our current understanding of the vascularization of the precentral gyrus by distal ACA branches, in particular the PIFA.

Shedding light on the frontal hemodynamics of spatial working memory using functional near-infrared spectroscopy.

The dorsolateral prefrontal cortex has been shown to be a key functional network within the middle frontal gyrus in regards to working memory processing. A commonly used paradigm in this line of research is the n-back task. The standard variant of the task requires participants to state whether the current item has been presented n trials prior (or not). Two possible strategies could be used to complete the task. Participants may either actively uphold the last n items in working memory or they may use item familiarity as basis for a decision. Previous functional near infrared spectroscopy studies using this paradigm have reported differing load dependent patterns of middle frontal gyrus activation which might at least in part be attributed to these different strategies. We used a spatial variant of the n-back task in which participants had to reproduce a pattern of locations n trials after presentation. We could thus eliminate the possibility of relying on familiarity for successful task completion. In line with previous functional magnetic resonance imaging studies we found a rise in middle frontal gyrus activity with rising working memory load. This was mainly reflected by a decrease in concentration of deoxygenated blood in this area. In line with previous research utilizing spatial paradigms, we found a lateralization of activity to the right hemisphere. We propose that the forced recall version of the n-back task is a valid alternative to the standard paradigm and can eliminate unwanted variance due to differing strategies, especially in high load conditions.

The regional pattern of abnormal cerebrovascular reactivity in HIV-infected, virally suppressed women.

The purpose of this study was to assess whole brain and regional patterns of cerebrovascular reactivity (CVR) abnormalities in HIV-infected women using quantitative whole brain arterial spin labeling (ASL). We hypothesized that HIV-infected women would demonstrate decreased regional brain CVR despite viral suppression. This cross-sectional study recruited subjects from the Bay Area Women's Interagency Health Study (WIHS)-a cohort study designed to investigate the progression of HIV disease in women. In addition to conventional noncontrast cerebral MRI sequences, perfusion imaging was performed before and after the administration of intravenous acetazolamide. CVR was measured by comparing quantitative ASL brain perfusion before and after administration of intravenous acetazolamide. In order to validate and corroborate ASL-based whole brain and regional perfusion, phase-contrast (PC) imaging was also performed through the major neck vessels. FLAIR and susceptibility weighted sequences were performed to assess for white matter injury and microbleeds, respectively. Ten HIV-infected women and seven uninfected, age-matched controls were evaluated. Significant group differences were present in whole brain and regional CVR between HIV-infected and uninfected women. These regional differences were significant in the frontal lobe and basal ganglia. CVR measurements were not significantly impacted by the degree of white matter signal abnormality or presence of microbleeds. Despite complete viral suppression, dysfunction of the neurovascular unit persists in the HIV population. Given the lack of association between CVR and traditional imaging markers of small vessel disease, CVR quantification may provide an early biomarker of pre-morbid vascular disease.

[A case of cerebral venous sinus thrombosis mimicking transient ischemic attack].

A 48-year-old woman with a right-sided headache beginning a month prior to admission presented with sudden-onset right hemiparesis. On admission, she had weakness of the right lower extremity, which disappeared 3 hours after onset. Contrast enhanced brain MRI revealed no parenchymal lesion, while indicated thrombi in the superior sagittal sinus and the right side of the transverse sinus, sigmoid sinus, and internal jugular vein, leading to the diagnosis of cerebral venous sinus thrombosis. Brain perfusion single photon emission computed tomography presented slightly decreased blood flow in the bilateral frontal lobes (left-sided dominant) and the right occipitotemporal lobe. Electroencephalogram showed no abnormal finding. After anticoagulant therapy, thrombi in the venous sinuses decreased and brain blood flow improved. We should consider cerebral venous sinus thrombosis in the case of a patient presenting with symptoms of a transient ischemic attack accompanied with headache. Moreover, the etiology of transient neurological deficits remains controversial.