Stable Intracerebral Transplantation of Neural Stem Cells for the Treatment of Paralysis Due to Ischemic Stroke.

NSI-566 is a stable, primary adherent neural stem cell line derived from a single human fetal spinal cord and expanded epigenetically with no genetic modification. This cell line is being tested in clinical trials in the U.S. for treatment of amyotrophic lateral sclerosis and spinal cord injury. In a single-site, phase I study, we evaluated the feasibility and safety of NSI-566 transplantation for the treatment of hemiparesis due to chronic motor stroke and determined the maximum tolerated dose for future trials. Three cohorts (n = 3 per cohort) were transplanted with one-time intracerebral injections of 1.2 × 107 , 2.4 × 107 , or 7.2 × 107 cells. Immunosuppression therapy with tacrolimus was maintained for 28 days. All subjects had sustained chronic motor strokes, verified by magnetic resonance imaging (MRI), initiated between 5 and 24 months prior to surgery with modified Rankin Scores [MRSs] of 2, 3, or 4 and Fugl-Meyer Motor Scores of 55 or less. At the 12-month visit, the mean Fugl-Meyer Motor Score (FMMS, total score of 100) for the nine participants showed 16 points of improvement (p = .0078), the mean MRS showed 0.8 points of improvement (p = .031), and the mean National Institutes of Health Stroke Scale showed 3.1 points of improvement (p = .020). For six participants who were followed up for 24 months, these mean changes remained stable. The treatment was well tolerated at all doses. Longitudinal MRI studies showed evidence indicating cavity-filling by new neural tissue formation in all nine patients. Although this was a small, one-arm study of feasibility, the results are encouraging to warrant further studies. Stem Cells Translational Medicine 2019;8:999-1007.

Posttraumatic subgaleal herniation of an intracranial cerebral arterial segment.

A rare case of extracranial herniation of an intracranial arterial segment is described in an elderly patient presenting with loss of consciousness following mild head trauma. Cross-sectional imaging of the brain revealed a temporal skull fracture with associated intra-axial and extra-axial bleeding, and a computed tomography angiogram of the head and cerebral digital subtraction angiogram performed a few hours later displayed a rare finding. A small segment of a parietal branch of the right middle cerebral artery (M4 segment) herniated through the skull fracture, which coursed into the extracranial subgaleal space overlying the fracture site, before coursing back into the intracranial compartment. There was no evidence of cerebral ischemia or vascular compromise. The presence of a subgaleal artery on computed tomography angiogram may point to herniation of intracranial artery. In the absence of knowledge of this entity, even basic routine emergency care such as application of a scalp bandage or suturing of a scalp laceration could potentially result in devastating complications of vascular compromise and stroke.

Prevalence of Potentially Clinically Significant Magnetic Resonance Imaging Findings in Athletes with and without Sport-Related Concussion.

Previous studies have shown that mild traumatic brain injury (mTBI) can cause abnormalities in clinically relevant magnetic resonance imaging (MRI) sequences. No large-scale study, however, has prospectively assessed this in athletes with sport-related concussion (SRC). The aim of the current study was to characterize and compare the prevalence of acute, trauma-related MRI findings and clinically significant, non-specific MRI findings in athletes with and without SRC. College and high-school athletes were prospectively enrolled and participated in scanning sessions between January 2015 through August 2017. Concussed contact sport athletes (n = 138; 14 female [F]; 19.5 ± 1.6 years) completed up to four scanning sessions after SRC. Non-concussed contact (n = 135; 15 F; 19.7 ± 1.6) and non-contact athletes (n = 96; 15 F; 20.0 ± 1.7) completed similar scanning sessions and served as controls. Board-certified neuroradiologists, blinded to SRC status, reviewed T1-weighted and T2-weighted fluid-attenuated inversion recovery and T2*-weighted and T2-weighted images for acute (i.e., injury-related) or non-acute findings that prompted recommendation for clinical follow-up. Concussed athletes were more likely to have MRI findings relative to contact (30.4% vs. 15.6%; odds ratio [OR] = 2.32; p = 0.01) and non-contact control athletes (19.8%; OR = 2.11; p = 0.04). Female athletes were more likely to have MRI findings than males (43.2% vs. 19.4%; OR = 2.62; p = 0.01). One athlete with SRC had an acute, injury-related finding; group differences were largely driven by increased rate of non-specific white matter hyperintensities in concussed athletes. This prospective, large-scale study demonstrates that <1% of SRCs are associated with acute injury findings on qualitative structural MRI, providing empirical support for clinical guidelines that do not recommend use of MRI after SRC.

Why Is This Auntminnie a Diagnostic Conundrum?: A Knowledge-Based Approach to Balo's Concentric Sclerosis From Reports of 3 Cases and Pooled Data From 68 Other Patients in the Literature.

INTRODUCTION: We came across 3 cases of Balo's concentric sclerosis (BCS). The first of these patients presented to an outside hospital and was transferred to our institution due to complications resulting from a biopsy. The other 2 patients, despite having a characteristic imaging appearance and despite insistence on our part on the diagnosis of BCS, underwent a surgical procedure, which could have been prevented. This led us to review the available literature on BCS. MATERIAL AND METHODS: A total of 68 patients diagnosed with BCS between 1995 and 2015 were studied and the data collected for the clinical presentation and course, imaging, spinal fluid analysis, treatment, and clinical and imaging outcome. CONCLUSIONS: A 25% surgery rate (biopsy or resection) was found in the study. We concluded that this relatively high surgery rate in this auntminnie nonsurgical disease is multifactorial; and includes factors like nonfamiliarity with the disease, anxiety on the part of patients and physicians, due to a sometimes rapidly deteriorating clinical picture; and resemblance of the disease with other entities such as tumor and infection. However, characteristic imaging appearance combined with acute or subacute presentation and dramatic improvement in clinical status after high-dose steroid chemotherapy; are highly suggestive of the disease, and can prevent unnecessary surgery.

Multimodality imaging in cranial blastomycosis, a great mimicker: Case-based illustration with review of clinical and imaging findings.

We describe the clinical, laboratory, and imaging data of three patients who are proven cases of blastomycosis with cranial involvement. In this review, we discuss the imaging features of cranial blastomycosis with relevant clinical case examples including computed tomography (CT), magnetic resonance imaging (MRI), and advanced MR imaging techniques like magnetic resonance spectroscopy (MRS) and MR perfusion. Literature is reviewed for modern-day diagnosis and treatment of this fatal intracranial infection, if not diagnosed promptly and managed effectively.

Imaging of Cerebrovascular Disease in Pregnancy and the Puerperium.

OBJECTIVE: The purpose of this article is to review the unique physiologic changes that characterize pregnancy and the puerperium, some that substantially affect the cerebrovascular system. Conditions that can cause neurologic deterioration and share features with preeclampsia-eclampsia include postpartum angiopathy, reversible cerebral vasoconstriction syndrome, posterior reversible encephalopathy syndrome, and amniotic fluid embolism. Other conditions not specific to this patient group include cerebral venous thrombosis, cervicocephalic arterial dissection, ischemic stroke, and hemorrhagic stroke, which can pose specific diagnostic and therapeutic challenges. CONCLUSION: Radiologists must be familiar with the imaging findings of cerebrovascular complications and pathologic entities encountered during pregnancy and the puerperium. Ongoing improvements in understanding of molecular changes during pregnancy and the puerperium and advances in diagnostic tests should allow radiologists to continue to make important contributions to the care of this patient population.

Imaging correlates of neural control of ocular movements.

The purpose of oculomotor movements is maintenance of clear images on the retina. Beyond this oversimplification, it requires several different types of ocular movements and reflexes to focus objects of interest to the fovea-the only portion of retina capable of sharp and clear vision. The different movements and reflexes that execute this task are the saccades, smooth pursuit movements, fixation, accommodation, and the optokinetic and vestibulo-ocular reflexes. Many different centres in the cerebrum, cerebellum, brainstem and thalami, control these movements via different pathways. At the outset, these mechanisms appear dauntingly complex to a radiologist. However, only a little effort could make it possible to understand these neural controls and empower the reading session. The following review on ocular movements and their neural control will enable radiologists and clinicians to correlate lesions with clinical deficits effectively without being swamped by exhaustive detail. Key Points • Knowledge of cortical and subcortical areas controlling ocular movements is important. • Understanding of neural control of ocular movements makes a good foundation. • Awareness of anatomic areas controlling ocular movements helps in clinico-radiologic correlation.

Rise of Functional Neuroradiologists in Clinical Care.

Recent translational advances in neuroimaging herald a fundamental shift in the practice of Neuroradiology. Biological, physiological, microstructural, metabolic, and functional imaging techniques have bridged the gaps between clinical imaging and the clinical neurosciences. These advancements are guiding the transition of neuroradiology from traditional pattern-based, image-centric toward knowledge-based, patient-centric practice strategies. The willingness of the neuroradiologist to embrace this shift is critical to the process. The chapter highlights the expanding role and importance of the functional neuroradiologist in clinical care.

Functional and Dysfunctional Sensorimotor Anatomy and Imaging.

The sensorimotor system of the human brain and body is fundamental only in its central role in our daily lives. On further examination, it is a system with intricate and complex anatomical, physiological, and functional relationships. Sensorimotor areas including primary sensorimotor, premotor, supplementary motor, and higher order somatosensory cortices are critical for function and can be localized at routine neuroimaging with a familiarity of sulcal and gyral landmarks. Likewise, a thorough understanding of the functions and dysfunctions of these areas can empower the neuroradiologist and lead to superior imaging search patterns, diagnostic considerations, and patient care recommendations in daily clinical practice. Presurgical functional brain mapping of the sensorimotor system may be necessary in scenarios with distortion of anatomical landmarks, multiplanar localization, homunculus localization, congenital brain anomalies, informing diffusion tensor imaging interpretations, and localizing nonvisible targets.

Imaging of Cortical and White Matter Language Processing.

Although investigations into the functional and anatomical organization of language within the human brain began centuries ago, it is recent advanced imaging techniques including functional magnetic resonance imaging and diffusion tensor imaging that have helped propel our understanding forward at an unprecedented rate. Important cortical brain regions and white matter tracts in language processing subsystems including semantic, phonological, and orthographic functions have been identified. An understanding of functional and dysfunctional language anatomy is critical for practicing radiologists. This knowledge can be applied to routine neuroimaging examinations as well as to more advanced examinations such as presurgical brain mapping.

Imaging of the Functional and Dysfunctional Visual System.

Functional magnetic resonance imaging (fMRI) is used clinically to map the visual cortex before brain surgery or other invasive treatments to achieve an optimal balance between therapeutic effect and the avoidance of postoperative vision deficits. Clinically optimized stimuli, analyses, and displays permit identification of cortical subregions supporting high-acuity central vision that is critical for reading and other essential visual functions. A novel data display permits instant appreciation of the functional relationship between the pattern of fMRI brain activation and the pattern of vision loss and preservation within the patient׳s field of view. Neurovascular uncoupling and its detection in the visual cortex are key issues for the interpretation of fMRI results in patients with existing brain pathology.

Imaging of Functional and Dysfunctional Episodic Memory.

A foundational framework for understanding functional and dysfunctional imaging of episodic memory emerges from the last 3 decades of human and animal research. This comprehensive review is presented from the vantage point of the fornix, a white matter bridge that occupies a central position in this functional network. Salient insights are identified, spanning topics such as hippocampal efferent and afferent networks, input and processing streams, hemispheric specialization, dysfunctional effects of pathologic and surgical injury, optimization of functional magnetic resonance imaging design and neuropsychological tests, and rehabilitation strategies. Far-reaching implications are considered for radiologists, whose clinical effect stretches beyond imaging and interfaces with neurosurgeons, neuropsychologists, and other neurospecialists.

Cortical and Subcortical Substrates of Cranial Nerve Function.

The pivotal role of cranial nerves in a wholesome life experience cannot be overemphasized. Research has opened new avenues to understand cranial nerve function. Classical concept of strict bilateral cortical control of cranial nerves has given way to concepts of hemispheric dominance and hemispheric lateralization. An astute Neuroradiologist should keep abreast of these concepts and help patients and referring physicians by applying this knowledge in reading images. This chapter provides an overview of cranial nerve function and latest concepts pertaining to their cortical and subcortical control.

Preoperative diffusion tensor imaging: improving neurosurgical outcomes in brain tumor patients.

Preoperative mapping has revolutionized neurosurgical care for brain tumor patients. Maximizing resections has improved diagnosis, optimized treatment algorithms, and decreased potentially devastating postoperative deficits. Although mapping has multiple steps and complimentary localization sources, diffusion tensor imaging (DTI) excels in its essential role in depicting white matter tracts. A thorough understanding of DTI, data visualization methods, and limitations with mastery of functional and dysfunctional white matter anatomy is necessary to realize the potential of DTI. By establishing spatial relationships between lesion borders and functional networks preoperatively and intraoperatively, DTI is central to high-risk neurosurgical resections and becoming the standard of care.

In emergency departments, radiologists' access to EHRs may influence interpretations and medical management.

The adoption of electronic health records (EHRs) that meet federal meaningful-use standards is a major US national policy priority. Policy makers recognize the potential of electronic communication in delivering high-quality health care, particularly in an environment of expanding remote access to medical care and the ever-increasing need to transmit health care records across institutions. To demonstrate this principle, we sought to estimate the significance of EHR access in emergent neuroradiologic interpretations. Three neuroradiologists conducted a prospective expert-rater analysis of 2,000 consecutive head computed tomography (CT) exams ordered by emergency department (ED) physicians. For each head CT exam, the neuroradiologists compared medical information generated by ED physicians to information generated by the interpreting radiologists who had access to additional EHR-derived patient data. In 6.1 percent of the head CT exams, the neuroradiologists reached consensus--meaning two out of three agreed--that the additional clinical data derived from the EHR was "very likely" to influence radiological interpretations and that the lack of that data would have adversely affected medical management in those patients. Health care providers must recognize the value of implementing EHRs and foster their widespread adoption.

Diffusion tensor imaging of the spinal cord: insights from animal and human studies.

Diffusion tensor imaging (DTI) provides a measure of the directional diffusion of water molecules in tissues. The measurement of DTI indexes within the spinal cord provides a quantitative assessment of neural damage in various spinal cord pathologies. DTI studies in animal models of spinal cord injury indicate that DTI is a reliable imaging technique with important histological and functional correlates. These studies demonstrate that DTI is a noninvasive marker of microstructural change within the spinal cord. In human studies, spinal cord DTI shows definite changes in subjects with acute and chronic spinal cord injury, as well as cervical spondylotic myelopathy. Interestingly, changes in DTI indexes are visualized in regions of the cord, which appear normal on conventional magnetic resonance imaging and are remote from the site of cord compression. Spinal cord DTI provides data that can help us understand underlying microstructural changes within the cord and assist in prognostication and planning of therapies. In this article, we review the use of DTI to investigate spinal cord pathology in animals and humans and describe advances in this technique that establish DTI as a promising biomarker for spinal cord disorders.

Atypical retinotopic organization of visual cortex in patients with central brain damage: congenital and adult onset.

It remains unclear to what extent retinotopic maps can undergo large-scale plasticity following damage to human visual cortex. The literature has predominately focused on retinotopic changes in patients with retinal pathologies or congenital brain malformations. Yet, damage to the adult visual cortex itself is common in cases such as stroke, tumor, or trauma. To address this issue, we used a unique database of fMRI vision maps in patients with adult-onset (n=25) and congenital (n=2) pathology of the visual cortex. We identified atypical retinotopic organization in three patients (two with adult-onset, and one with congenital pathology) consisting of an expanded ipsilateral field representation that was on average 3.2 times greater than healthy controls. The expanded representations were located at the vertical meridian borders between visual areas such as V1/V2. Additionally, two of the three patients had apparently an ectopic (topographically inconsistent) representation of the ipsilateral field within lateral occipital cortex that is normally associated with visual areas V3/V3A (and possibly other areas). Both adult-onset cases had direct damage to early visual cortex itself (rather than to the afferent drive only), resulting in a mostly nonfunctional hemisphere. The congenital case had severe cortical malformation of the visual cortex and was acallosal. Our results are consistent with a competitive model in which unilateral damage to visual cortex or disruption of the transcallosal connections removes interhemispheric suppression from retino-geniculate afferents in intact visual cortex that represent the vertical meridian and ipsilateral visual field.

Characterization and limitations of diffusion tensor imaging metrics in the cervical spinal cord in neurologically intact subjects.

PURPOSE: To characterize diffusion tensor imaging (DTI) metrics across all levels of the cervical spinal cord (CSC) and to study the impact of age and signal quality on these metrics. MATERIALS AND METHODS: DTI metrics were calculated for gray matter (GM) and white matter (WM) funiculi throughout the CSC (C1-T1) in 25 healthy subjects (22-85 years old). Signal-to-noise ratios (SNRs) and mean DTI metrics were measured for the upper (C1-3), middle (C4-6) and lower (C7-T1) cervical segments. Age-related changes in DTI metrics were analyzed for the individual segment groups. RESULTS: Fractional anisotropy (FA), mean diffusivity (MD) and transverse apparent diffusion coefficient (tADC) showed significant differences between GM and WM funiculi. Significant age-related changes were observed in FA in upper and middle CSC segments but not in the lower CSC. The median SNR was significantly lower in the middle and lower segment groups as compared to the upper levels, contributing to poor spatial resolution in these regions. CONCLUSION: This study provides DTI data for GM and WM funiculi throughout the CSC. While DTI metrics may be used to define cord pathology, variations in metrics due to age and signal quality need to be accounted for before making definitive conclusions.

Diffusion tensor imaging of the spinal cord: a review / Imagem da medula espinal por tensor de difusão / Imagen de difusión tensora de la médula espinal: una revisión

Diffusion tensor imaging (DTI) is a magnetic resonance technique capable of measuring the magnitude and direction of water molecule diffusion in various tissues. The use of DTI is being expanded to evaluate a variety of spinal cord disorders both for prognostication and to guide therapy. The purpose of this article is to review the literature on spinal cord DTI in both animal models and humans in different neurosurgical conditions. DTI of the spinal cord shows promise in traumatic spinal cord injury, cervical spondylotic myelopathy, and intramedullary tumors. However, scanning protocols and image processing need to be refined and standardized.

O exame por imagem de ressonância magnética utilizando a técnica de tensores de difusão (DTI, Diffusion tensor imaging) consegue medir a magnitude e direção da difusão de moléculas de água em vários tecidos. A DTI está começando a ser usada para avaliar uma série de patologias da medula espinal, tanto para prognósticos como para orientar o tratamento. O presente artigo revisa a literatura sobre DTI da medula espinhal, em modelos animais e humanos, em diferentes condições neurocirúrgicas. A DTI da medula espinal é promissora para lesões traumáticas da medula, mielopatia espondilótica cervical e tumores intramedulares. Contudo, os protocolos de escaneamento e processamento de imagens precisam ser refinados e padronizados.

La técnica de imagen por difusión tensora (DTI, Diffusion tensor imaging) es una técnica de resonancia magnética que mide la magnitud y dirección de la difusión de moléculas de agua en varios tejidos. El uso de DTI se ha expandido para evaluar una variedad de disturbios de la columna vertebral tanto para pronóstico como para orientación de la terapia. La finalidad de este artículo es revisar la literatura sobre DTI de la médula espinal tanto en modelos animales como en humanos en diferentes condiciones neuroquirúrgicas. La DTI de la médula espinal se muestra promisora en las lesiones traumáticas de la médula, en la mielopatía espondilótica cervical y en los tumores intramedulares. Sin embargo, los protocolos de barrido y el procesamiento de imágenes necesitan ser refinados y estandarizados.

Motor homunculus: passive mapping in healthy volunteers by using functional MR imaging--initial results.

PURPOSE: To determine the concurrence of activation in the primary motor cortex, induced by paradigms of active and passive movement of extremities, by using blood oxygen level-dependent functional magnetic resonance (MR) imaging. MATERIALS AND METHODS: The HIPAA-compliant study was approved by the institutional review board, and written informed consent was obtained from the participating volunteers. Functional MR imaging data were collected from 11 healthy volunteers (four women, seven men; age range, 24-42 years) during active and passive movements of hand, elbow, shoulder, ankle, knee, and hip. These data were then mapped onto three-dimensional anatomic images. Volumes of activation were determined by using cross-correlation analysis at a coefficient threshold of 0.4 (P < .01). Regions of interest were drawn in pre- and postcentral gyri based on anatomic criteria. The mean number of activated voxels in the pre- and postcentral gyri induced by active and passive movements was compared by using Wilcoxon analysis. Concurrence ratios and proportional ratios of activation between active and passive movements were calculated for each somatotopic location. RESULTS: Primary motor cortex activation tended to increase with active compared with passive movements, although in the precentral gyrus, hand, elbow, and shoulder movements showed no statistically significant difference in mean number of activated voxels. In the postcentral gyrus, only the shoulder revealed a significant difference (P < .05). Concurrence ratios (activation volume overlap of two tasks/combined activation area of both tasks) ranged from 0.44 to 0.57. Proportional ratios (activation volume overlap of passive task with active task/total activation volume of passive task) ranged from 0.64 to 0.82. CONCLUSION: Passive movement paradigms may be an alternative to or complement to active movement tasks in patient populations.