Dystypia Associated with Diaschisis of the Middle Frontal Gyri after Left Angular Infarction.

Dystypia without aphasia, agraphia, or apraxia is a rare symptom and has been suggested to result from a lesion in the left middle frontal cortex. We herein describe a man with dystypia with agraphia due to infarction of the left angular gyrus. His dystypia seemed to result from the convergence failure of the kana into the alphabetical spellings. During dystypia, hypoperfusion of the bilateral middle frontal cortices was discovered. However, after his symptoms improved, blood flow in the middle frontal cortices returned to normal. This case suggests that the middle frontal cortex is downstream of the angular gyrus in the dictating pathway and a lesion in the left middle frontal cortex could cause pure dystypia.

Regional hyperperfusion in older adults with objectively-defined subtle cognitive decline.

Although cerebral blood flow (CBF) alterations are associated with Alzheimer's disease (AD), CBF patterns across prodromal stages of AD remain unclear. Therefore, we investigated patterns of regional CBF in 162 Alzheimer's Disease Neuroimaging Initiative participants characterized as cognitively unimpaired (CU; n = 80), objectively-defined subtle cognitive decline (Obj-SCD; n = 31), or mild cognitive impairment (MCI; n = 51). Arterial spin labeling MRI quantified regional CBF in a priori regions of interest: hippocampus, inferior temporal gyrus, inferior parietal lobe, medial orbitofrontal cortex, and rostral middle frontal gyrus. Obj-SCD participants had increased hippocampal and inferior parietal CBF relative to CU and MCI participants and increased inferior temporal CBF relative to MCI participants. CU and MCI groups did not differ in hippocampal or inferior parietal CBF, but CU participants had increased inferior temporal CBF relative to MCI participants. There were no CBF group differences in the two frontal regions. Thus, we found an inverted-U pattern of CBF signal across prodromal AD stages in regions susceptible to early AD pathology. Hippocampal and inferior parietal hyperperfusion in Obj-SCD may reflect early neurovascular dysregulation, whereby higher CBF is needed to maintain cognitive functioning relative to MCI participants, yet is also reflective of early cognitive inefficiencies that distinguish Obj-SCD from CU participants.

The Neuropsychological Correlates of Brain Perfusion and Gray Matter Volume in Alzheimer's Disease.

BACKGROUND: Neuropsychological tests, structural neuroimaging, and functional neuroimaging are employed as diagnostic and monitoring biomarkers of patients with Alzheimer's disease (AD)Objective:We aimed to elucidate the similarities and differences in neuropsychological tests and neuroimaging with the use of the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog), structural magnetic resonance image (MRI), and perfusion single photon emission computed tomography (SPECT), and parametric image analyses to understand its role in AD. METHODS: Clinically-diagnosed AD patients (n = 155) were scanned with three-dimensional T1-weighted MRI and N-isopropyl-p-[123I] iodoamphetamine SPECT. Statistical parametric mapping 12 was used for preprocessing images, statistical analyses, and voxel-based morphometry for gray matter volume analyses. Group comparison (AD versus healthy controls), multiple regression analyses with MMSE, ADAS-cog total score, and ADAS-cog subscores as variables, were performed. RESULTS: The AD group showed bilateral hippocampal volume reduction and hypoperfusion in the bilateral temporo-parietal lobe and posterior midline structures. Worse MMSE and ADAS-cog total score were associated with bilateral temporo-parietal volume loss and hypoperfusion. MMSE, but not ADAS-cog, was associated with the posterior midline structures. The ADAS-cog subscores were associated with the temporal volume, while perfusion analyses were linked to the left temporo-parietal region with the language function and right analogous region with the constructional praxis subscore. CONCLUSION: MMSE and ADAS-cog are associated with temporo-parietal regions, both in volume and perfusion. The MMSE score is associated with posterior midline structures and linked to an abnormal diagnostic AD pattern. Perfusion image analyses better represents the cognitive function in AD patients.

A Rare Clinical Antity; Pure Gerstmann Syndrome.

Gerstmann syndrome is defined as a tetrad including agraphia, acalculia, finger agnosia, and right-left disorientation. In the case studies presented in the literature, it has been reported that Gerstmann syndrome usually appears as an incomplete tetrad of symptoms or accompanied by cognitive deficits including aphasia, alexia, apraxia and some perceptual disorders. Here, we present of the patient with left angular and supramarginal gyrus infarction affecting the parietal lobe. In addition to the symptoms mentioned above, the patient had alexia and anomic aphasia as well. We discussed the clinic appearance and reviewed the current literature.

Hemichorea as Presentation of Acute Cortical Ischemic Stroke. Case Series and Review of the Literature.

Hemichorea and other hyperkinetic movement disorders are a rare presentation of stroke, usually secondary to deep infarctions affecting the basal ganglia and the thalamus. Chorea can also result from lesions limited to the cortex, as shown in recent reports. Still, the pathophysiology of this form of cortical stroke-related chorea remains unknown. We report 4 cases of acute ischemic cortical strokes presenting as hemichorea, with the infarction being limited to the parietal and insular cortex in perfusion computed tomography scans and magnetic resonance imaging. These cases suggest potential dysfunction of pathways connecting these cortical regions with the basal ganglia.

Bladder Autonomic Dysfunction after a Parietal Stroke.

We describe a case of a 57-year-old man who, immediately after a right parietal ischemic stroke, showed urodynamically determined bladder sensory decrement during filling and an underactive detrusor during voiding, both of which were ameliorated during the course of his treatment. The lower urinary tract symptom (LUTS) occurs in stroke in up to 60% of patients, when it involves the frontal and insular cortices. In addition, LUTS does occur in parietal stroke as seen in our patient, presumably by sensory deafferentiation within the brain that is relevant to the central regulation of the micturition reflex.

Slowed Temporal and Parietal Cerebrovascular Response in Patients with Alzheimer's Disease.

BACKGROUND: Recent investigations now suggest that cerebrovascular reactivity (CVR) is impaired in Alzheimer's disease (AD) and may underpin part of the disease's neurovascular component. However, our understanding of the relationship between the magnitude of CVR, the speed of cerebrovascular response, and the progression of AD is still limited. This is especially true in patients with mild cognitive impairment (MCI), which is recognized as an intermediate stage between normal aging and dementia. The purpose of this study was to investigate AD and MCI patients by mapping repeatable and accurate measures of cerebrovascular function, namely the magnitude and speed of cerebrovascular response (τ) to a vasoactive stimulus in key predilection sites for vascular dysfunction in AD. METHODS: Thirty-three subjects (age range: 52-83 years, 20 males) were prospectively recruited. CVR and τ were assessed using blood oxygen level-dependent MRI during a standardized carbon dioxide stimulus. Temporal and parietal cortical regions of interest (ROIs) were generated from anatomical images using the FreeSurfer image analysis suite. RESULTS: Of 33 subjects recruited, 3 individuals were excluded, leaving 30 subjects for analysis, consisting of 6 individuals with early AD, 11 individuals with MCI, and 13 older healthy controls (HCs). τ was found to be significantly higher in the AD group compared to the HC group in both the temporal (p = 0.03) and parietal cortex (p = 0.01) following a one-way ANCOVA correcting for age and microangiopathy scoring and a Bonferroni post-hoc correction. CONCLUSION: The study findings suggest that AD is associated with a slowing of the cerebrovascular response in the temporal and parietal cortices.

Hemiballism: Unusual clinical manifestation in three patients with frontoparietal infarct.

The term hemiballism-hemichorea refers to a movement disorder characterized by involuntary movements, often violent, described as uncontrollable jerking, flinging, flailing or kicking, involving proximal muscles of a limb and it is often associated with lesions in the subthalamic nucleus. In this report, we described three cases of hemiballism-hemichorea as the first manifestation of acute ischemic stroke with lesion in the frontoparietal region on brain MRI and no involvement of the subthalamic nucleus. One patient was treated with thrombolysis and recovered within one hour. The other patients recovered within 48 h from symptoms onset. The impairment of the recently described "hyperdirect way", in which the cortical signal reach directly the subthalamic nucleus, may underlie the symptoms. We support, with a clinical point of view, the role of the frontoparietal region in the genesis of the hemiballism-hemichorea. An acute onset of this symptom should lead to think to an acute stroke.

Regional Cerebral Blood Flow in the Posterior Cingulate and Precuneus and the Entorhinal Cortical Atrophy Score Differentiate Mild Cognitive Impairment and Dementia Due to Alzheimer Disease.

BACKGROUND AND PURPOSE: Alzheimer disease is the most common degenerative dementia affecting humans and mild cognitive impairment is considered the forerunner of this devastating illness with variable progression. Differentiating between them has become all the more essential with the advent of disease-modifying medications. The aim of this study was to test the utility of the entorhinal cortical atrophy score in combination with quantitative CBF in the posterior cingulate and precuneus using arterial spin-labeling to differentiate mild cognitive impairment and early Alzheimer disease. MATERIALS AND METHODS: We analyzed MR imaging from a prospective data base of 3 age-matched groups: 21 cognitively healthy controls, 20 patients with mild cognitive impairment, and 19 patients with early Alzheimer disease. The highest entorhinal cortical atrophy score and an atlas-based measurement of CBF in the posterior cingulate and precuneus were estimated in these groups. Statistical comparison was performed among the groups for disease-prediction probability with these parameters independently and in combination using a binary logistic regression model. RESULTS: The entorhinal cortical atrophy score performed well in distinguishing AD from HC, with a predicted probability of .887 (area under the curve, P < .001). The mean CBF of the posterior cingulate and precuneus was also found to be a useful discriminator (area under the curve, 0.810, P = < .001). Combining the entorhinal cortical atrophy score and CBF was the best predictor (area under the curve, 0.957, P < .001). In distinguishing mild cognitive impairment and Alzheimer disease, entorhinal cortical atrophy also did well with an area under the curve of 0.838 (P < .001). However regional CBF was not useful in differentiating them (area under the curve = 0.589, P = .339). Entorhinal cortical atrophy scored poorly in distinguishing mild cognitive impairment from healthy controls (AUC = 0.571, P = .493), but CBF fared well, with an area under the curve of 0.776 (P = .002). CONCLUSIONS: Combining entorhinal cortical atrophy and regional CBF could be a potential imaging biomarker in distinguishing mild cognitive impairment and Alzheimer disease.

Targeted genetic analysis of cerebral blood flow imaging phenotypes implicates the INPP5D gene.

The vascular hypothesis of Alzheimer's disease (AD) has proposed the involvement of brain hypoperfusion in AD pathogenesis, where cognitive decline and dysfunction result from dwindling cerebral blood flow (CBF). Based on the vascular hypothesis of Alzheimer's disease, we focused on exploring how genetic factors influence AD pathogenesis via the cerebrovascular system. To investigate the role of CBF endophenotypes in AD pathogenesis, we performed a targeted genetic analysis of 258 subjects from the Alzheimer's Disease Neuroimaging Initiative cohort to examine associations between 4033 single-nucleotide polymorphisms of 24 AD genes and CBF measures in 4 brain regions. A novel association with CBF measure in the left angular gyrus was identified in an INPP5D single-nucleotide polymorphism (i.e., rs61068452; p = 1.48E-7; corrected p = 2.39E-3). The gene-based analysis discovered both INPP5D and CD2AP associated with the left angular gyrus CBF. Further analyses on nonoverlapping samples revealed that rs61068452-G was associated with lower CSF t-tau/Aß1-42 ratio. Our findings suggest a protective role of rs61068452-G in an AD-relevant cerebrovascular endophenotype, which has the potential to provide novel insights for better mechanistic understanding of AD.

A Case of Cerebral Venous Sinus Thrombosis Presenting During Relapse of Ulcerative Colitis.

BACKGROUND Extra-intestinal manifestations of inflammatory bowel disease (IBD) include thromboembolic events that can present as deep vein thrombosis, pulmonary embolism, and cerebral venous sinus thrombosis. Cerebral venous sinus thrombosis is a rare complication of IBD that can be associated with high morbidity and mortality. This report is of a case of cerebral venous sinus thrombosis presenting in a young man during a relapse of ulcerative colitis (UC). CASE REPORT A 27-year-old man presented with seizures and focal neurological deficit during a relapse of chronic UC. He was found to have left cerebral venous sinus thrombosis complicated by left frontotemporal infarction that was treated with anticoagulation therapy. CONCLUSIONS Thromboembolic events are well documented extra-intestinal manifestation of IBD. Cerebral venous sinus thrombosis is a rare but serious complication that can be fatal. The correct diagnosis and timely management require a high degree of suspicion in patients with IBD who present with a new-onset headache, focal neurological symptoms, seizure, or altered mental status.

Association of venous varix and developmental venous anomaly: report of a case and review of literature.

Cerebral developmental venous anomalies (DVAs) are the most frequently encountered cerebral vascular malformation. Most are asymptomatic and incidentally detected. Here we present a case of DVA associated with venous varix presented with chronic headache. A 50-year-old woman presented with right hemicranial headache since 6 months. There was no neurological deficit. MRI showed a well-defined oval T2 hyperintense, T1 isointense extra-axial lesion in the right parietal region showing intense homogeneous enhancement. Prominent vascular flow void was extending from the lesion up to the deep parietal white matter. Subtle thin linear areas of blooming noted in the parietal white matter converging towards the vascular flow void. The venous sac is in communication with the cortical vein draining to the superior sagittal sinus. These MRI findings favoured a diagnosis of DVA in the right parietal lobe with prominent draining vein forming a cortical venous varix. The patient was managed conservatively with symptomatic treatment for headache.

Beta-amyloid pathology in human brain microvessel extracts from the parietal cortex: relation with cerebral amyloid angiopathy and Alzheimer's disease.

Several pieces of evidence suggest that blood-brain barrier (BBB) dysfunction is implicated in the pathophysiology of Alzheimer's disease (AD), exemplified by the frequent occurrence of cerebral amyloid angiopathy (CAA) and the defective clearance of Aß peptides. However, the specific role of brain microvascular cells in these anomalies remains elusive. In this study, we validated by Western, ELISA and immunofluorescence analyses a procedure to generate microvasculature-enriched fractions from frozen samples of human cerebral cortex. We then investigated Aß and proteins involved in its clearance or production in microvessel extracts generated from the parietal cortex of 60 volunteers in the Religious Orders Study. Volunteers were categorized as AD (n = 38) or controls (n = 22) based on the ABC scoring method presented in the revised guidelines for the neuropathological diagnosis of AD. Higher ELISA-determined concentrations of vascular Aß40 and Aß42 were found in persons with a neuropathological diagnosis of AD, in apoE4 carriers and in participants with advanced parenchymal CAA, compared to respective age-matched controls. Vascular levels of two proteins involved in Aß clearance, ABCB1 and neprilysin, were lower in persons with AD and positively correlated with cognitive function, while being inversely correlated to vascular Aß40. In contrast, BACE1, a protein necessary for Aß production, was increased in individuals with AD and in apoE4 carriers, negatively correlated to cognitive function and positively correlated to Aß40 in microvessel extracts. The present report indicates that concentrating microvessels from frozen human brain samples facilitates the quantitative biochemical analysis of cerebrovascular dysfunction in CNS disorders. Data generated overall show that microvessels extracted from individuals with parenchymal CAA-AD contained more Aß and BACE1 and less ABCB1 and neprilysin, evidencing a pattern of dysfunction in brain microvascular cells contributing to CAA and AD pathology and symptoms.

Effect of mild hypothermia on cerebral microcirculation in a murine cardiopulmonary resuscitation model.

BACKGROUND: We hypothesized that mild hypothermia may improve brain microcirculation by reducing cerebral microvascular endothelial cells apoptosis, and this effect may be maximized by moving up the initiation of mild hypothermia from after return of spontaneous circulation (ROSC) to the start of cardiopulmonary resuscitation (CPR). METHODS: A total of 35 rats were randomized into the intra-arrest hypothermia group (IAH), post-resuscitation hypothermia group (PRH), normothermia group (NT), or the sham control group. A craniotomy exposed the parietal cortex for visualization of microcirculation. Ventricular fibrillation was electrically induced and untreated for 8 minutes, followed by 8 minutes of precordial compression and mechanical ventilation. Hypothermia (33 ± 0.5°C) in the IAH and PRH group was induced and maintained for 6 hours at the beginning of CPR or after ROSC, respectively. At baseline, 1, 3, and 6 hours, hemodynamic parameters were measured and the pial microcirculations were visualized with a sidestream dark field imaging video microscope. Microvascular flow index and perfused microvessel density (PMD) were calculated. Rats were euthanized, and brain tissues were removed at 3 and 6 hours separately. Expression of Bax, Bcl-2, and Caspase 3 in brain microvascular endothelial cells was examined by Western blot. RESULTS: Microvascular flow index and PMD were significantly reduced after cardiac arrest and resuscitation (all P < 0.05), and the former was largely preserved by hypothermia regardless when the hypothermia treatment was induced (P < 0.05). Bax and Caspase 3 increased and Bcl-2 decreased significantly after resuscitation, and hypothermia treatment reversed the trend partly (all P < 0.05). A moderate correlation was observed between MFI and those proteins (Bcl-2/BAX: 3 hours: r = 0.730, P = 0.002; 6 hours: r = 0.743, P = 0.002). CONCLUSION: Mild hypothermia improves cerebral microcirculatory blood supply, partly by inhibiting endothelial cell apoptosis. Mild hypothermia induced simultaneously with CPR has shown no additional benefit in microcirculation or endothelial cell apoptosis.

[A case of body lateropulsion to the left in acute cerebral infarction of the right medial parietal lesion].

A 68-year-old right-handed woman with acute-onset inability to stand was admitted to our department. Although left hemiparesis was minor, the neurological examination on admission showed marked body lateropulsion (BL) to the left when she stood or stepped with eyes open and feet closed. Neither ataxia nor sensory disturbance was present. Brain MRI and 3D-CT angiography revealed infarction of the right posterior cingulate and the precuneus due to dissection of the right anterior cerebral artery. BL improved on day 10 and she was discharged without sequelae on day 26. BL caused by cerebral lesions is rare, and we should recognize that infarction of the posterior cingulate and/or the precuneus can cause BL.

Recognition of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) in Two Oligosymptomatic Sisters with Low CADASIL Scale Scores and a Venous Dysplasia: Report of a Novel Greek Family.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) due to mutations of the NOTCH3 gene is the most common cause of inherited cerebral small-vessel disease and one of the genetic causes of migraine with aura. The so-called CADASIL scale has been proposed as a clinical screening tool, and a score of 15 or higher seems useful in identifying patients with high probability of carrying NOTCH3 mutations. We studied a novel Greek family with clinical features compatible with CADASIL. Genetic analysis of NOTCH3 in the 2 living patients revealed the R182C mutation. Both patients had low scores (12 and 14) in the CADASIL scale, probably due to their relatively young age (38 and 37 years, respectively) at which cognitive decline and external capsule involvement have not developed yet. Another unusual feature in the second patient was a venous dysplasia in the parietal lobe. Observations presented here add to the notion that the CADASIL scale, although useful, probably needs a revision, taking into account the patient's age at which the score is calculated.

Pulsed Electromagnetic Field (PEMF) Mitigates High Intracranial Pressure (ICP) Induced Microvascular Shunting (MVS) in Rats.

OBJECTIVE: High-frequency pulsed electromagnetic field (PEMF) stimulation is an emerging noninvasive therapy that we have shown increases cerebral blood flow (CBF) and tissue oxygenation in the healthy rat brain. In this work, we tested the effect of PEMF on the brain at high intracranial pressure (ICP). We previously showed that high ICP in rats caused a transition from capillary (CAP) to non-nutritive microvascular shunt (MVS) flow, tissue hypoxia and increased blood brain barrier (BBB) permeability. METHODS: Using in vivo two-photon laser scanning microscopy (2PLSM) over the rat parietal cortex, and studied the effects of PEMF on microvascular blood flow velocity, tissue oxygenation (NADH autofluorescence), BBB permeability and neuronal necrosis during 4 h of elevated ICP to 30 mmHg. RESULTS: PEMF significantly dilated arterioles, increased capillary blood flow velocity and reduced MVS/capillary ratio compared to sham-treated animals. These effects led to a significant decrease in tissue hypoxia, BBB degradation and neuronal necrosis. CONCLUSIONS: PEMF attenuates high ICP-induced pathological microcirculatory changes, tissue hypoxia, BBB degradation and neuronal necrosis.

Dynamics of Distribution of Capillaries with Matrix Metalloproteinase-2 and Its Tissue Inhibitor in Rat Brain during Development of Experimental Hypertension.

The capillaries containing MMP-2 and its tissue inhibitor TIMP-2 were examined in cerebral cortex and white matter obtained from intact Wistar rats (n=5) and the rats with progressing experimental renovascular hypertension (n=35). In hypertensive rats, the changes in intensity of the immunohistochemical reaction and in the density of capillaries expressing TIMP-2 significantly differed from the corresponding values in MMP-2-positive capillaries, which resulted in pronounced deviation of MMP-2/TIMP-2 index from the control level (especially in cerebral cortex) probably attesting to enhanced risk of complications in cases with arterial hypertension.

Contralateral posterior interhemispheric approach to deep medial parietooccipital vascular malformations: surgical technique and results.

OBJECTIVE Deep medial parietooccipital arteriovenous malformations (AVMs) and cerebral cavernous malformations (CCMs) are traditionally resected through an ipsilateral posterior interhemispheric approach (IPIA), which creates a deep, perpendicular perspective with limited access to the lateral margins of the lesion. The contralateral posterior interhemispheric approach (CPIA) flips the positioning, with the midline positioned horizontally for retraction due to gravity, but with the AVM on the upper side and the approach from the contralateral, lower side. The aim of this paper was to analyze whether the perpendicular angle of attack that is used in IPIA would convert to a parallel angle of attack with the CPIA, with less retraction, improved working angles, and no significant increase in risk. METHODS A retrospective review of pre- and postoperative clinical and radiographic data was performed in 8 patients who underwent a CPIA. RESULTS Three AVMs and 5 CCMs were resected using the CPIA, with an average nidus size of 2.3 cm and CCM diameter of 1.7 cm. All lesions were resected completely, as confirmed on postoperative catheter angiography or MRI. All patients had good neurological outcomes, with either stable or improved modified Rankin Scale scores at last follow-up. CONCLUSIONS The CPIA is a safe alternative approach to the IPIA for deep medial parietooccipital vascular malformations that extend 2 cm or more off the midline. Contralaterality and retraction due to gravity optimize the interhemispheric corridor, the surgical trajectory to the lesion, and the visualization of the lateral margin, without resection or retraction of adjacent normal cortex. Although the falx is a physical barrier to accessing the lesion, it stabilizes the ipsilateral hemisphere while gravity delivers the dissected lesion through the transfalcine window. Patient positioning, CSF drainage, venous preservation, and meticulous dissection of the deep margins are critical to the safety of this approach.

Corticosterone and exogenous glucose alter blood glucose levels, neurotoxicity, and vascular toxicity produced by methamphetamine.

Our previous studies have raised the possibility that altered blood glucose levels may influence and/or be predictive of methamphetamine (METH) neurotoxicity. This study evaluated the effects of exogenous glucose and corticosterone (CORT) pretreatment alone or in combination with METH on blood glucose levels and the neural and vascular toxicity produced. METH exposure consisted of four sequential injections of 5, 7.5, 10, and 10 mg/kg (2 h between injections) D-METH. The three groups given METH in combination with saline, glucose (METH+Glucose), or CORT (METH+CORT) had significantly higher glucose levels compared to the corresponding treatment groups without METH except at 3 h after the last injection. At this last time point, the METH and METH+Glucose groups had lower levels than the non-METH groups, while the METH+CORT group did not. CORT alone or glucose alone did not significantly increase blood glucose. Mortality rates for the METH+CORT (40%) and METH+Glucose (44%) groups were substantially higher than the METH (< 10%) group. Additionally, METH+CORT significantly increased neurodegeneration above the other three METH treatment groups (≈ 2.5-fold in the parietal cortex). Thus, maintaining elevated levels of glucose during METH exposure increases lethality and may exacerbate neurodegeneration. Neuroinflammation, specifically microglial activation, was associated with degenerating neurons in the parietal cortex and thalamus after METH exposure. The activated microglia in the parietal cortex were surrounding vasculature in most cases and the extent of microglial activation was exacerbated by CORT pretreatment. Our findings show that acute CORT exposure and elevated blood glucose levels can exacerbate METH-induced vascular damage, neuroinflammation, neurodegeneration and lethality. Cover Image for this issue: doi. 10.1111/jnc.13819.