Lethal mycotic pseudoaneurysm presenting as isolated sixth nerve palsy.

Pseudoaneurysm of the internal carotid artery caused by skull base osteomyelitis (SBO) is a lethal condition seen in immunocompromised patients, predominantly those with diabetes mellitus. Cranial nerve involvement is a common complication and generally indicates a poor prognosis. We report the case of a 62-year-old diabetic patient who presented with isolated sixth cranial nerve palsy. She had uncontrolled blood sugar levels and high erythrocyte sedimentation rate, and she suffered from pyelonephritis. Neuroimaging detected SBO with multiple secondary mycotic pseudoaneurysms prominent at the petrocavernous junction. Ischemia is the most common etiology for an isolated abducens nerve palsy, but in certain cases neuroimaging is warranted to prevent life-threatening complications. This case highlights the importance and urgency of identifying and managing such conditions.

Blood-based biomarkers of cerebral small vessel disease.

Age-associated cerebral small vessel disease (CSVD) represents a clinically heterogenous condition, arising from diverse microvascular mechanisms. These lead to chronic cerebrovascular dysfunction and carry a substantial risk of subsequent stroke and vascular cognitive impairment in aging populations. Owing to advances in neuroimaging, in vivo visualization of cerebral vasculature abnormities and detection of CSVD, including lacunes, microinfarcts, microbleeds and white matter lesions, is now possible, but remains a resource-, skills- and time-intensive approach. As a result, there has been a recent proliferation of blood-based biomarker studies for CSVD aimed at developing accessible screening tools for early detection and risk stratification. However, a good understanding of the pathophysiological processes underpinning CSVD is needed to identify and assess clinically useful biomarkers. Here, we provide an overview of processes associated with CSVD pathogenesis, including endothelial injury and dysfunction, neuroinflammation, oxidative stress, perivascular neuronal damage as well as cardiovascular dysfunction. Then, we review clinical studies of the key biomolecules involved in the aforementioned processes. Lastly, we outline future trends and directions for CSVD biomarker discovery and clinical validation.

Headache Disorders: Differentiating Primary and Secondary Etiologies.

In the initial assessment of a headache patient, several dangerous secondary etiologies must be considered. A thorough history and physical examination, along with a comprehensive differential diagnosis may alert a physician to the diagnosis of a secondary headache particularly when it is accompanied by certain clinical features. Evaluation and workup include a complete neurological examination, consideration of neuroimaging, and serum/spinal fluid analysis if indicated. Careful attention to the patients' history and physical examination will guide the diagnostic work-up and management. In this review, we summarize the diagnostic workup of various primary and secondary headache etiologies. Although most headaches are primary in nature, it is essential to screen for headache "red flags", as they can suggest life threatening secondary etiologies. When secondary causes are suspected, appropriate neuroimaging can further differentiate the underlying cause. The appropriate imaging is dependent on the most likely secondary etiology, which is deduced from history and physical examination. When no red flags are present, primary headaches are more likely. These can be differentiated by frequency, location, duration, triggers, and presence of aura. The different clinical presentations for secondary headaches, as well as the distinguishing features for primary headaches are outlined in this review.

Genomic analysis of presumed perinatal stroke in Saudi Arabia reveals a strong monogenic contribution.

Perinatal stroke is associated with significant short- and long-term morbidity and has been recognized as the most common cause of cerebral palsy in term infants. The diagnosis of presumed perinatal stroke (PPS) is made in children who present with neurological deficit and/or seizures attributable to focal chronic infarction on neuroimaging and have uneventful neonatal history. The underlying mechanism of presumed perinatal stroke remains unknown and thorough investigation of potential monogenic causes has not been conducted to date. Here, we describe the use of untargeted exome sequencing to investigate a cohort of eight patients from six families with PPS. A likely deleterious variant was identified in four families. These include the well-established risk genes COL4A2 and JAM3. In addition, we report the first independent confirmation of the recently described link between ESAM and perinatal stroke. Our data also highlight NID1 as a candidate gene for the condition. This study suggests that monogenic disorders are important contributors to the pathogenesis of PPS and should be investigated by untargeted sequencing especially when traditional risk factors are excluded.

An atypical case of hypomagnesemia-induced cerebellar syndrome with literature review.

Cerebellar ataxia in adults is always a diagnostic challenge. One of the important causes of late-onset cerebellar ataxia is hypomagnesemia. Hypomagnesemia can have varied manifestations and is attributable to numerous causes. Identification of hypomagnesemia-induced cerebellar syndrome (HiCS) is important as it is reversible but often missed. HiCS has distinct clinical findings and characteristic magnetic resonance imaging (MRI) findings. HiCS presents with distinct clinical, biochemical, and neuroimaging findings, but it cannot be ruled out even in the absence of neuroimaging findings. This condition has to be treated promptly and meticulously to avoid precipitating any serious complications, and a strong suspicion is required for the diagnosis. The underlying cause should be evaluated and managed, as HiCS is a serious but potentially reversible disease with a good prognosis. We present a case of HiCS presenting with a characteristic history of recurrent ataxia, tremor, and vertigo that improved with treatment. Our patient was atypical, as there were no significant MRI findings attributable to hypomagnesemia. Only seven case reports are available throughout the world that show such disparity.

Neuroimaging Modalities Used for Ischemic Stroke Diagnosis and Monitoring.

Strokes are one of the global leading causes of physical or mental impairment and fatality, classified into hemorrhagic and ischemic strokes. Ischemic strokes happen when a thrombus blocks or plugs an artery and interrupts or reduces blood supply to the brain tissue. Deciding on the imaging modality which will be used for stroke detection depends on the expertise and availability of staff and the infrastructure of hospitals. Magnetic resonance imaging provides valuable information, and its sensitivity for smaller infarcts is greater, while computed tomography is more extensively used, since it can promptly exclude acute cerebral hemorrhages and is more favorable speed-wise. The aim of this article was to give information about the neuroimaging modalities used for the diagnosis and monitoring of ischemic strokes. We reviewed the available literature and presented the use of computed tomography, CT angiography, CT perfusion, magnetic resonance imaging, MR angiography and MR perfusion for the detection of ischemic strokes and their monitoring in different phases of stroke development.

Links between brain neuroimaging and blood inflammatory markers in urological chronic pelvic pain syndrome.

Urological chronic pelvic pain syndrome (UCPPS) is a debilitating painful condition with unclear etiology. Prior researchers have indicated that compared to healthy controls, patients with UCPPS demonstrated altered brain activity. Researchers have also shown that in UCPPS, several blood inflammatory markers relate to clinical variables of pain, fatigue, and pain widespreadness. However, how altered brain function in patients with UCPPS relates to blood inflammation remains unknown. To extend and connect prior findings of altered brain function and inflammatory factors in UCPPS, we conducted a secondary analysis of data from a cohort of UCPPS patients (N = 29) and healthy controls (N = 31) who provided both neuroimaging and blood data (National Institute of Health MAPP Research Network publicly available dataset). In our present study, we aimed to evaluate relationships between a priori-defined brain neuroimaging markers and inflammatory factors of interest and their relationships to pain-psychological variables. We hypothesized that two brain alterations of interest (i.e., PCC - left hippocampus functional connectivity and PCC - bilateral amygdala functional connectivity) would be correlated with four cytokine markers of interest: interleukin (IL) - 6, tumor necrosis factor-alpha (TNF-a), IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF). In the UCPPS cohort, we identified a significant PCC - left hippocampus functional connectivity relationship with IL-6 (p = 0.0044). Additionally, in the UCPPS cohort, we identified a PCC - amygdala functional connectivity relationship with GM-CSF which did not meet our model's threshold for statistical significance (p = 0.0665). While these data are preliminary and cross-sectional, our findings suggest connections between brain function and levels of low-grade systemic inflammation in UCPPS. Thus, while further study is needed, our data indicate the potential for advancing the understanding of how brain functional circuits may relate to clinical symptoms and systemic inflammation.

Lower Body Mass Index at Baseline Is Related to Steeper Cognitive Decline in the Alzheimer's Disease Neuroimaging Initiative Cohort.

OBJECTIVE: Midlife obesity is a risk factor for dementia, whereas obesity in older age may be protective of cognition, a phenomenon known as the "obesity paradox." The mechanisms underlying this phenomenon and the relationship between body mass index (BMI) and cognitive function over time remain unclear. METHODS: In 1399 adults with and without mild cognitive impairment (median age 73.6 years) from the Alzheimer's Disease Neuroimaging Initiative, we modeled the effects of baseline BMI on within-person trajectories of cognitive decline using Latent Growth Curve Modeling. We also tested if the effects of BMI on cognitive decline are global or specific to memory, executive function, or language. RESULTS: Higher baseline BMI was associated with better memory ( ßBMI = 0.06, p < .05) and worse executive function ( ßBMI = -0.05, p < .05) and not associated with language. Independent of baseline diagnosis, higher baseline BMI was associated with slower rate of decline in executive function, memory, and language ( ßBMI = 0.13, 0.12, and 0.12, respectively; p < .01). Higher BMI was not associated with the intercept ( ßBMI = 0.04, p = .059) or change ( ßBMI = 0.04, p = .415) in a global cognitive factor. CONCLUSIONS: We found that higher baseline BMI was associated with slower cognitive decline in participants with and without mild cognitive impairment diagnosis. Higher BMI in this context seems to be protective of cognitive function for people at risk for dementia. Our findings also support domain-specific effects of obesity on various cognitive functions rather than a final common pathway.

Emotional Regulation and Adolescent Concussion: Overview and Role of Neuroimaging.

Emotional dysregulation symptoms following a concussion are associated with an increased risk for emotional dysregulation disorders (e.g., depression and anxiety), especially in adolescents. However, predicting the emergence or worsening of emotional dysregulation symptoms after concussion and the extent to which this predates the onset of subsequent psychiatric morbidity after injury remains challenging. Although advanced neuroimaging techniques, such as functional magnetic resonance imaging and diffusion magnetic resonance imaging, have been used to detect and monitor concussion-related brain abnormalities in research settings, their clinical utility remains limited. In this narrative review, we have performed a comprehensive search of the available literature regarding emotional regulation, adolescent concussion, and advanced neuroimaging techniques in electronic databases (PubMed, Scopus, and Google Scholar). We highlight clinical evidence showing the heightened susceptibility of adolescents to experiencing emotional dysregulation symptoms following a concussion. Furthermore, we describe and provide empirical support for widely used magnetic resonance imaging modalities (i.e., functional and diffusion imaging), which are utilized to detect abnormalities in circuits responsible for emotional regulation. Additionally, we assess how these abnormalities relate to the emotional dysregulation symptoms often reported by adolescents post-injury. Yet, it remains to be determined if a progression of concussion-related abnormalities exists, especially in brain regions that undergo significant developmental changes during adolescence. We conclude that neuroimaging techniques hold potential as clinically useful tools for predicting and, ultimately, monitoring the treatment response to emotional dysregulation in adolescents following a concussion.

Glymphatic pathway in sporadic cerebral small vessel diseases: From bench to bedside.

Cerebral small vessel diseases (CSVD) consist of a group of diseases with high heterogeneity induced by pathologies of intracranial small blood vessels. Endothelium dysfunction, bloodbrain barrier leakage and the inflammatory response are traditionally considered to participate in the pathogenesis of CSVD. However, these features cannot fully explain the complex syndrome and related neuroimaging characteristics. In recent years, the glymphatic pathway has been discovered to play a pivotal role in clearing perivascular fluid and metabolic solutes, which has provided novel insights into neurological disorders. Researchers have also explored the potential role of perivascular clearance dysfunction in CSVD. In this review, we presented a brief overview of CSVD and the glymphatic pathway. In addition, we elucidated CSVD pathogenesis from the perspective of glymphatic failure, including basic animal models and clinical neuroimaging markers. Finally, we proposed forthcoming clinical applications targeting the glymphatic pathway, hoping to provide novel ideas on promising therapies and preventions of CSVD.

Peak Width of Skeletonized Mean Diffusivity: A Neuroimaging Marker for White Matter Injury.

A leading cause of white matter (WM) injury in older individuals is cerebral small vessel disease (SVD). Cerebral SVD is the most prevalent vascular contributor to cognitive impairment and dementia. Therapeutic progress for cerebral SVD and other WM disorders depends on the development and validation of neuroimaging markers suitable as outcome measures in future interventional trials. Diffusion-tensor imaging (DTI) is one of the best-suited MRI techniques for assessing the extent of WM damage in the brain. But the optimal method to analyze individual DTI data remains hindered by labor-intensive and time-consuming processes. Peak width of skeletonized mean diffusivity (PSMD), a recently developed fast, fully automated DTI marker, was designed to quantify the WM damage secondary to cerebral SVD and reflect related cognitive impairment. Despite its promising results, knowledge about PSMD is still limited in the radiologic community. This focused review provides an overview of the technical details of PSMD while synthesizing the available data on its clinical and neuroimaging associations. From a critical expert viewpoint, the authors discuss the limitations of PSMD and its current validation status as a neuroimaging marker for vascular cognitive impairment. Finally, they point out the gaps to be addressed to further advance the field.

Strengths and Weaknesses of the Vascular Apathy Hypothesis: A Narrative Review.

The vascular apathy hypothesis states that cerebral small vessel disease (CSVD) can cause apathy, even when no other symptoms of CSVD are present. In order to examine this hypothesis, the objectives of this narrative review are to evaluate the evidence for a pathophysiological mechanism linking CSVD to apathy and to examine whether CSVD can be a sole cause of apathy. The nature of the CSVD-apathy relationship was evaluated using the Bradford Hill criteria as a method for research on the distinction between association and causation. Pathological, neuroimaging, and behavioral studies show that CSVD can cause lesions in the reward network, which causes an apathy syndrome. Studies in healthy older individuals, stroke patients and cognitively impaired persons consistently show an association between CSVD markers and apathy, although studies in older persons suffering from depression are inconclusive. A biological gradient is confirmed, as well as a temporal relationship, although the evidence for the latter is still weak. The specificity of this causal relationship is low given there often are other contributing factors in CSVD patients with apathy, particularly depression and cognitive deterioration. Differentiating between vascular apathy and other apathy syndromes on the basis of clinical features is not yet possible, while in-depth knowledge about differences in the prognosis and efficacy of treatment options for apathy caused by CSVD and other apathy syndromes is lacking. Since we cannot differentiate between etiologically different apathy syndromes as yet, it is premature to use the term vascular apathy which would suggest a distinct clinical apathy syndrome.

Advantages of current fetal neuroimaging and genomic technologies in prenatal diagnosis: A clinical case.

The diagnosis of prenatal microcephaly, as well as the possibility of underlining a genetic cause, is becoming more frequent thanks to advances in prenatal imaging and parallel massive sequencing. One case of primary microcephaly in three sibs demonstrates how complementary diagnostic exams can help to diagnose and establish the etiology.

Fetal heart rate evolution and brain imaging findings in preterm infants with severe cerebral palsy.

BACKGROUND: Cerebral palsy is more common among preterm infants than among full-term infants. Although there is still no clear evidence that fetal heart rate monitoring effectively reduces cerebral palsy incidence, it is helpful to estimate the timing of brain injury leading to cerebral palsy and the causal relationship with delivery based on the fetal heart rate evolution patterns. Understanding the relationship between the timing and the type of brain injury can help to identify preventive measures in obstetrical care. OBJECTIVE: This study aimed to examine the relationship between the timing of insults and the type of brain injury in preterm infants with severe cerebral palsy. STUDY DESIGN: This longitudinal study was based on a nationwide database for cerebral palsy. The data of infants with severe cerebral palsy (equivalent to levels 3-5 of the Gross Motor Function Classification System-Expanded and Revised), born between 2009 and 2014 at 28 to 33 weeks of gestation, were included. The intrapartum fetal heart rate evolution patterns were evaluated by 3 obstetricians blinded to clinical information other than gestational age at birth, and these were categorized after agreement by at least 2 of the 3 reviewers into (1) continuous bradycardia, (2) persistently nonreassuring (prenatal onset), (3) reassuring-prolonged deceleration, (4) Hon's pattern (intrapartum onset), (5) persistently reassuring (pre- or postnatal onset), and (6) unclassified. Infant brain magnetic resonance imaging findings at term-equivalent age were assessed by a pediatric neurologist blinded to the background details, except for gestational age at birth and corrected age at image acquisition, and these were categorized as (1) basal ganglia-thalamus, (2) white matter, (3) watershed cortex or subcortex, (4) stroke, (5) normal, and (6) unclassified based on the predominant site involved. The risk factors for the basal ganglia-thalamus group were compared with those of the combined white matter and watershed injuries group. RESULTS: Among 1593 infants with severe cerebral palsy, 231 were born at 28 to 33 weeks of gestation, and 140 met the eligibility criteria. Fetal heart rate evolution patterns were categorized as bradycardia (17% [24]); persistently nonreassuring (40% [56]); reassuring-prolonged deceleration (7% [10]); reassuring-Hon (6% [8]); persistently reassuring (7% [10]); and unclassified (23% [32]). Cerebral palsy was presumed to have an antenatal onset in 57% of infants and to have been caused by intrapartum insult in 13% of infants. Magnetic resonance imaging showed that 34% (n=48) of infants developed basal ganglia-thalamus-dominant brain injury. Of the remaining 92 infants, 43% (60) showed white matter injuries, 1% (1) showed watershed injuries, 4% (5) showed stroke, 1% (1) had normal findings, and 18% (25) had unclassified findings. Infants with continuous bradycardia (adjusted odds ratio, 1033.06; 95% confidence interval, 15.49-68,879.92) and persistently nonreassuring fetal heart rate patterns (61.20; 2.09-1793.12) had a significantly increased risk for basal ganglia-thalamus injury. CONCLUSION: Severe cerebral palsy was presumed to have an antenatal onset in 57% of infants and to have been caused by intrapartum insult in only 13% of infants born at 28 to 33 weeks of gestation. Although the white matter-watershed injury was predominant in the study populations, severe acute hypoxia-ischemia may be an important prenatal etiology of severe cerebral palsy in preterm infants.

Diagnostic accuracy of neuroimaging in emergency department patients with acute vertigo or dizziness: A systematic review and meta-analysis for the guidelines for reasonable and appropriate care in the emergency department.

BACKGROUND: Patients presenting to the emergency department (ED) with acute vertigo or dizziness represent a diagnostic challenge. Neuroimaging has variable indications and yield. We aimed to conduct a systematic review and meta-analysis of the diagnostic test accuracy of neuroimaging for patients presenting with acute vertigo or dizziness. METHODS: An electronic search was designed following patient-intervention-control-outcome (PICO) question-(P) adult patients with acute vertigo or dizziness presenting to the ED; (I) neuroimaging including computed tomography (CT), CT angiography (CTA), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and ultrasound (US); (C) MRI/clinical criterion standard; and (O) central causes (stroke, hemorrhage, tumor, others) versus peripheral causes of symptoms. Articles were assessed in duplicate. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was used to assess certainty of evidence in pooled estimates. RESULTS: We included studies that reported diagnostic test accuracy. From 6309 titles, 460 articles were retrieved, and 12 were included: noncontrast CT scan-six studies, 771 patients, pooled sensitivity 28.5% (95% confidence interval [CI] 14.4%-48.5%, moderate certainty) and specificity 98.9% (95% CI 93.4%-99.8%, moderate certainty); MRI-five studies, 943 patients, sensitivity 79.8% (95% CI 71.4%-86.2%, high certainty) and specificity 98.8% (95% CI 96.2%-100%, high certainty); CTA-one study, 153 patients, sensitivity 14.3% (95% CI 1.8%-42.8%) and specificity 97.7% (95% CI 93.8%-99.6%), CT had higher sensitivity than CTA (21.4% and 14.3%) for central etiology; MRA-one study, 24 patients, sensitivity 60.0% (95% CI 26.2%-87.8%) and specificity 92.9% (95% CI 66.1%-99.8%); US-three studies, 258 patients, sensitivity ranged from 30% to 53.6%, specificity from 94.9% to 100%. CONCLUSIONS: Noncontrast CT has very low sensitivity and MRI will miss approximately one in five patients with stroke if imaging is obtained early after symptom onset. The evidence does not support neuroimaging as the only tool for ruling out stroke and other central causes in patients with acute dizziness or vertigo presenting to the ED.

Challenging Myelopathy Cases.

Misdiagnosis of myelopathies is common and can lead to irreversible disability when diagnosis- and disease-specific treatments are delayed. Therefore, quickly determining the etiology of myelopathy is crucial. Clinical evaluation and MRI spine are paramount in establishing the correct diagnosis and subsequently an appropriate treatment plan. Herein, we review an approach to myelopathy diagnosis focused on the time course of neurologic symptom progression and neuroimaging pearls, and apply them to a variety of inflammatory, structural, and vascular myelopathy cases.

[CASE SERIES OF EARLY NEUROIMAGING IN PATIENTS WITH VASCULAR RISK FACTORS AND ISOLATED SIX CRANIAL NERVE PALSY, DEMONSTRATING THE DILEMMA OF EARLY IMAGING].

INTRODUCTION: There are various etiologies for isolated third, fourth and sixth cranial nerve palsies. The most common etiology in adults aged 50 years and older with vascular risk factors such as diabetes, hyperlipidemia, and hyperlipidemia, is microvascular ischemia. The role of early neuroimaging in older patients with vascular risk factors presenting with acute isolated ocular motor nerve palsy is controversial. AIMS: We present six cases of patients aged 50 years and older, with vascular risk factors, who suffered from acute isolated paralysis of the sixth nerve. All cases were diagnosed with a non-microvascular ischemia etiology. RESULTS: The identified etiologies included petroclival meningioma with involvement of the cavernous sinus, metastatic hepatoma, plasmacytoma, venous thrombosis, arterial-venous malformation and aneurysm. CONCLUSIONS: Despite the high cost and presumed low yield, early neuroimaging can change the clinical management in certain cases. DISCUSSION: Previous studies have found the yield of early neuroimaging in older vasculopathic patients with acute 4th or 6th cranial nerve palsies to be 1-15%. In spite of these reports, our cases demonstrate the need for early onset imaging in these cases.

Identifying encephalopathies from acute metabolic derangements.

Metabolic derangements, when acute and severe, affect brain function. This presents mostly with a marked decline in the level of consciousness, resulting in impaired responsiveness, abnormal receptivity, impaired content, and loss of memory retention. The term metabolic encephalopathy has been used but is conjecture that can be challenged in the age of modern neuroimaging. We now recognize that many metabolic encephalopathies may involve structural lesions and at an early stage. Common clinical conundrums are the evaluation of the degree of brain injury and its recoverability. This review discusses the appropriate terminology for these conditions, the diagnostic approach, therapy recommendations, and prediction of recovery potential. In evaluating a presumed metabolic cause for encephalopathy, we must (1) search for and rule out structural injury to the brain despite an obvious explanatory metabolic derangement, (2) recognize that several confounding conditions often co-exist, and (3) acknowledge that resolution of brain dysfunction may be protracted despite normalization of laboratory values.