Severe Acute Respiratory Syndrome Coronavirus 2 Third Vaccine Immune Response in Multiple Sclerosis Patients Treated with Ocrelizumab.

The introduction of a third-dose vaccination along with new variants of concern raises questions regarding serology and T-cell responses in patients with multiple sclerosis (pwMS) treated with B-cell depletion who develop attenuated humoral response to vaccines. The aim of this study was to longitudinally evaluate humoral and cellular response to SARS-CoV-2 mRNA vaccine in ocrelizumab-treated pwMS before and following a third vaccine dose. Following the third vaccine dose, patients who are low or nonresponders following initial vaccination did not increase antibody titers. In healthy controls and ocrelizumab-treated pwMS, cellular response decreased 6 months after initial vaccination and increased significantly after the third dose. ANN NEUROL 2022;91:796-800.

Brain MRI activity during the year before pregnancy can predict long-term clinical worsening in patients with Multiple Sclerosis.

BACKGROUND: Pregnancy has been observed to reduce the frequency of relapses in Multiple Sclerosis (MS) patients, but the relapse risk tends to increase during the early post-partum period. Increased pre- and post-partum disease activity may predict a poor long-term prognosis. This study aimed to evaluate the correlation between magnetic resonance imaging (MRI) activity during the year before pregnancy and long-term clinically meaningful worsening in Expanded Disability Status Scale (EDSS). METHODS: This observational, retrospective, case-control study included 141 pregnancies in 99 females with MS. Statistical analyses were used to evaluate the correlation between MRI activity during the year pre-pregnancy and post-partum clinical worsening during a 5-year follow-up. Clustered logistic regression was used to investigate the predictors of 5-year clinically meaningful worsening in EDSS (lt-EDSS). RESULTS: We found a significant correlation between an active MRI pre-pregnancy and lt-EDSS (p = 0.0006). EDSS pre-pregnancy and lt-EDSS were also significantly correlated (p = 0.043). Using a multivariate model, we predicted which females would not experience long-term clinical deterioration by a stable MRI pre-pregnancy (92.7% specificity; p = 0.004). CONCLUSIONS: An active MRI pre-conception is a strong predictor of lt-EDSS and a higher annual relapse rate during the follow-up period, regardless of whether the female had clinical evidence of disease activity prior to conception and delivery. Optimizing disease control and achieving imaging stability prior to conception may reduce the risk of long-term clinical deterioration.

Cortical Visual Mapping following Ocular Gene Augmentation Therapy for Achromatopsia.

The ability of the adult human brain to develop function following correction of congenital deafferentation is controversial. Specifically, cases of recovery from congenital visual deficits are rare. CNGA3-achromatopsia is a congenital hereditary disease caused by cone-photoreceptor dysfunction, leading to impaired acuity, photoaversion, and complete color blindness. Essentially, these patients have rod-driven vision only, seeing the world in blurry shades of gray. We use the uniqueness of this rare disease, in which the cone-photoreceptors and afferent fibers are preserved but do not function, as a model to study cortical visual plasticity. We had the opportunity to study two CNGA3-achromatopsia adults (one female) before and after ocular gene augmentation therapy. Alongside behavioral visual tests, we used novel fMRI-based measurements to assess participants' early visual population receptive-field sizes and color regions. Behaviorally, minor improvements were observed, including reduction in photoaversion, marginal improvement in acuity, and a new ability to detect red color. No improvement was observed in color arrangement tests. Cortically, pretreatment, patients' population-receptive field sizes of early visual areas were untypically large, but were decreased following treatment specifically in the treated eye. We suggest that this demonstrates cortical ability to encode new input, even at adulthood. On the other hand, no activation of color-specific cortical regions was demonstrated in these patients either before or up to 1 year post-treatment. The source of this deficiency might be attributed either to insufficient recovery of cone function at the retinal level or to challenges that the adult cortex faces when computing new cone-derived input to achieve color perception.SIGNIFICANCE STATEMENT The possibility that the adult human brain may regain or develop function following correction of congenital deafferentation has fired the imagination of scientists over the years. In the visual domain, cases of recovery from congenital deficits are rare. Gene therapy visual restoration for congenital CNGA3-achromatopsia, a disease caused by cone photoreceptor dysfunction, gave us the opportunity to examine cortical function, to the best of our knowledge for the first time, both before and after restorative treatment. While behaviorally only minor improvements were observed post-treatment, fMRI analysis, including size algorithms of population-receptive fields, revealed cortical changes, specifically receptive field size decrease in the treated eyes. This suggests that, at least to some degree, the adult cortex is able to encode new input.

Anatomical and functional visual network patterns in progressive multiple sclerosis.

The gradual accrual of disability over time in progressive multiple sclerosis is believed to be driven by widespread degeneration. Yet another facet of the problem may reside in the loss of the brain's ability to adapt to the damage incurred as the disease progresses. In this study, we attempted to examine whether changes associated with optic neuritis in the structural and functional visual networks can still be discerned in progressive patients even years after the acute insult. Forty-eight progressive multiple sclerosis patients, 21 with and 27 without prior optic neuritis, underwent structural and functional MRI, including DTI and resting state fMRI. Anatomical and functional visual networks were analyzed using graph theory-based methods. While no functional metrics were significantly different between the two groups, anatomical global efficiency and density were significantly lower in the optic neuritis group, despite no significant difference in lesion load between the groups. We conclude that long-standing distal damage to the optic nerve causes trans-synaptic effects and the early ability of the cortex to adapt may be altered, or possibly nullified. We suggest that this limited ability of the brain to compensate should be considered when attempting to explain the accumulation of disability in progressive multiple sclerosis patients.

The imprint of childhood adversity on emotional processing in high functioning young adults.

Adverse childhood experiences (ACEs) have been acknowledged as risk factors for increased mental health complications in adulthood, specifically increasing susceptibility to developing psychopathology upon exposure to trauma. Yet, little is known regarding the impact of mild ACEs on highly functioning population. In this study forty participants were selected from a group of 366 highly selected military parachute trainees using the self-report "childhood trauma questionnaire," and classified into two groups of 20 each, with and without ACEs. Behavioral measurements were obtained before and at the peak of an intensive combat training period, including anxiety, depression and executive function assessment. Functional MRI including a negative emotional face perception task was conducted at the first time point. Psychometric and cognitive measurements revealed higher levels of anxiety and depressive symptoms, and more difficulties in executive functioning in the ACE group at baseline. Slower reaction time to emotional faces presentation was found in the ACE group. Lower activation in response to negative emotional faces stimuli was found in this group in bilateral secondary visual areas, left anterior insula, left parietal cortex and left primary motor and sensory regions. In contrast, higher activation in the ACE group was found in the right ventral lateral prefrontal cortex (Vlpfc). No significant differences between groups were detected in the amygdala. To conclude, mild adverse childhood experiences produce long-term sequela on psychological wellbeing and neurocircuitry even in high functioning population. Brain regions modulated by childhood trauma may instigate avoidance mechanisms dampening the emotional and cognitive effects of intensive stress.

Brain MRI activity during the year before pregnancy can predict post-partum clinical relapses.

BACKGROUND: There are fewer multiple sclerosis (MS) relapses during pregnancy, although relapse risk increases in the early post-partum period, as has been predicted by pre-pregnancy or pregnancy disease activity in some studies. OBJECTIVE: The aim of this study was to evaluate the correlation between magnetic resonance imaging (MRI) changes in the year before pregnancy and the relapse rate in the year post-partum. METHODS: An observational retrospective case-control study included 172 pregnancies in 118 females with MS. Statistical analyses were used to evaluate the correlation between MRI and post-partum relapses. Clustered logistic regression was used to investigate the predictors of early post-partum relapses. RESULTS: We found a significant correlation for an active-MRI pre-pregnancy and relapses in the first 3 months post-partum (p < 0.001). Expanded Disability Status Scale (EDSS) pre-pregnancy and relapses in the first 3 months post-partum were also significantly correlated (p = 0.009). Using a multivariate model, we predicted which women will not experience post-partum relapse by EDSS and by an active-MRI pre-pregnancy (96.7% specificity; p < 0.001). CONCLUSION: An active-MRI pre-pregnancy is a strong and sensitive predictor of early post-partum relapse, regardless of whether the woman had clinical evidence of disease activity prior to conception and delivery. This finding could provide clinicians with a strategy to minimize post-partum relapse risk in women with MS planning pregnancy.

Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis.

In this study (trial registration: NCT02166021), we aimed to evaluate the optimal way of administration, the safety and the clinical efficacy of mesenchymal stem cell (MSC) transplantation in patients with active and progressive multiple sclerosis. Forty-eight patients (28 males and 20 females) with progressive multiple sclerosis (Expanded Disability Status Scale: 3.0-6.5, mean : 5.6 ± 0.8, mean age: 47.5 ± 12.3) and evidence of either clinical worsening or activity during the previous year, were enrolled (between 2015 and 2018). Patients were randomized into three groups and treated intrathecally (IT) or intravenously (IV) with autologous MSCs (1 × 106/kg) or sham injections. After 6 months, half of the patients from the MSC-IT and MSC-IV groups were retreated with MSCs, and the other half with sham injections. Patients initially assigned to sham treatment were divided into two subgroups and treated with either MSC-IT or MSC-IV. The study duration was 14 months. No serious treatment-related safety issues were detected. Significantly fewer patients experienced treatment failure in the MSC-IT and MSC-IV groups compared with those in the sham-treated group (6.7%, 9.7%, and 41.9%, respectively, P = 0.0003 and P = 0.0008). During the 1-year follow-up, 58.6% and 40.6% of patients treated with MSC-IT and MSC-IV, respectively, exhibited no evidence of disease activity compared with 9.7% in the sham-treated group (P < 0.0001 and P < 0.0048, respectively). MSC-IT transplantation induced additional benefits on the relapse rate, on the monthly changes of the T2 lesion load on MRI, and on the timed 25-foot walking test, 9-hole peg test, optical coherence tomography, functional MRI and cognitive tests. Treatment with MSCs was well-tolerated in progressive multiple sclerosis and induced short-term beneficial effects regarding the primary end points, especially in the patients with active disease. The intrathecal administration was more efficacious than the intravenous in several parameters of the disease. A phase III trial is warranted to confirm these findings.

Conduction delays in the visual pathways of progressive multiple sclerosis patients covary with brain structure.

In developed countries, multiple sclerosis (MS) is the leading cause of non-traumatic neurological disability in young adults. MS is a chronic demyelinating disease of the central nervous system, in which myelin is attacked, changing white matter structure and leaving lesions. The demyelination has a direct effect on white matter conductivity. This effect can be examined in the visual system, where damage is highly prevalent in MS, leading to substantial delays in conduction, commonly measured with visual evoked potentials (VEPs). The structural damage to the visual system in MS is often estimated with MRI measurements in the white matter. Recent developments in quantitative MRI (qMRI) provide improved sensitivity to myelin content and new structural methods allow better modeling of the axonal structure, leading researchers to link white matter microstructure to conduction properties of action potentials along fiber tracts. This study attempts to explain the variance in conduction latencies down the visual pathway using structural measurements of both the retina and the optic radiation (OR). Forty-eight progressive MS patients, participants in a longitudinal stem-cell therapy clinical trial, were included in this study, three and six months post final treatment. Twenty-seven patients had no history of optic neuritis, and were the main focus of this study. All participants underwent conventional MRI scans, as well as diffusion MRI and qMRI sequences to account for white matter microstructure. Optical coherence tomography scans were also obtained, and peripapillary retinal nerve fiber layer (pRNFL) thickness and macular volume measurements were extracted. Finally, latencies of recorded VEPs were estimated. Our results show that in non-optic neuritis progressive MS patients there is a relationship between the VEP latency and both retinal damage and OR lesion load. In addition, we find that qMRI values, sampled along the OR, are also correlated with VEP latency. Finally, we show that combining these parameters using PCA we can explain more than 40% of the inter-subject variance in VEP latency. In conclusion, this study contributes to understanding the relationship between the structural properties and conduction in the visual system in disease. We focus on the visual system, where the conduction latencies can be estimated, but the conclusions could be generalized to other brain systems where the white matter structure can be measured. It also highlights the importance of having multiple parameters when assessing the clinical stages of MS patients, which could have major implications for future studies of other white matter diseases.

Global Brain Involvement in Posterior Cortical Atrophy: Multimodal MR Imaging Investigation.

Posterior cortical atrophy (PCA), considered a visual variant of Alzheimer's disease, has similar pathological characteristics yet shows a selective visual manifestation with relative preservation of other cortical areas, at least at early stages of disease. Using a gamut of imaging methods, we aim to evaluate the global aspect of this relatively local disease and describe the interplay of the involvement of the different brain components. Ten PCA patients and 14 age-matched controls underwent MRI scans. Cortical thickness was examined to identify areas of cortical thinning. Hippocampal volume was assessed using voxel-based morphometry. The integrity of 20 fiber tracts was assessed by Diffusion Tensor Imaging. Regions of difference in global functional connectivity were identified by resting-state fMRI, using multi-variant pattern analysis. Correlations were examined to evaluate the connection between grey matter atrophy, the network changes and the disease load. The patients presented bilateral cortical thinning, primarily in their brains' posterior segments. Impaired segments of white matter integrity were evident only within three fiber tracts in the left hemisphere. Four areas were identified as different in their global connectivity pattern. The visual network-related areas showed reduced connectivity and was correlated to atrophy. Right Broadman area 39 showed in addition increased connectivity to the frontal areas. Global structural and functional imaging pointed to the highly localized nature of PCA. Functional connectivity followed grey matter atrophy in visual regions. White matter involvement seemed less prominent, however damage is directly related to presence of disease and not mediated only by grey matter damage.

Evidence for Functional Networks within the Human Brain's White Matter.

Investigation of the functional macro-scale organization of the human cortex is fundamental in modern neuroscience. Although numerous studies have identified networks of interacting functional modules in the gray-matter, limited research was directed to the functional organization of the white-matter. Recent studies have demonstrated that the white-matter exhibits blood oxygen level-dependent signal fluctuations similar to those of the gray-matter. Here we used these signal fluctuations to investigate whether the white-matter is organized as functional networks by applying a clustering analysis on resting-state functional MRI (RSfMRI) data from white-matter voxels, in 176 subjects (of both sexes). This analysis indicated the existence of 12 symmetrical white-matter functional networks, corresponding to combinations of white-matter tracts identified by diffusion tensor imaging. Six of the networks included interhemispheric commissural bridges traversing the corpus callosum. Signals in white-matter networks correlated with signals from functional gray-matter networks, providing missing knowledge on how these distributed networks communicate across large distances. These findings were replicated in an independent subject group and were corroborated by seed-based analysis in small groups and individual subjects. The identified white-matter functional atlases and analysis codes are available at http://mind.huji.ac.il/white-matter.aspx Our results demonstrate that the white-matter manifests an intrinsic functional organization as interacting networks of functional modules, similarly to the gray-matter, which can be investigated using RSfMRI. The discovery of functional networks within the white-matter may open new avenues of research in cognitive neuroscience and clinical neuropsychiatry.SIGNIFICANCE STATEMENT In recent years, functional MRI (fMRI) has revolutionized all fields of neuroscience, enabling identifications of functional modules and networks in the human brain. However, most fMRI studies ignored a major part of the brain, the white-matter, discarding signals from it as arising from noise. Here we use resting-state fMRI data from 176 subjects to show that signals from the human white-matter contain meaningful information. We identify 12 functional networks composed of interacting long-distance white-matter tracts. Moreover, we show that these networks are highly correlated to resting-state gray-matter networks, highlighting their functional role. Our findings enable reinterpretation of many existing fMRI datasets, and suggest a new way to explore the white-matter role in cognition and its disturbances in neuropsychiatric disorders.

Keep Your Eyes Wide Open: On Visual- and Vision-Related Measurements to Better Understand Multiple Sclerosis Pathophysiology.

BACKGROUND: Multiple sclerosis (MS), a demyelinating disease of the central nervous system, is multifaceted. It manifests as acute episodes as well as an accumulative chronic disability; myelin involvement as well as axonal damage; local as well as global effects; and disease load elements as well as compensatory mechanisms. The visual system, with its clear structural organization and relatively direct reflection of damage, may serve as an appropriate model to study MS. METHODS: In recent years, we have witnessed a blossoming in the field of visual measures in MS. Because it is impossible to cover all different aspects of these measures, we chose to focus on several hot topics in MS literature and shed light on them through studies conducted in the visual system. RESULTS: We argue that numerous methods can be used to study axonal and demyelinating aspects of the disease. Although optical coherence tomography and static visual functions better reflect the axonal aspects of the disease, conduction velocity as measured by visual-evoked potential latencies and dynamic visual function mirrors myelin levels. We also posit that the classic disease load parameters cannot be the only means by which we assess a patient's condition. Novel imaging methods such as diffusion tensor imaging and functional magnetic resonance imaging can be used to assess the global effects of local damage on neighboring white matter and compensatory abilities of the brain. CONCLUSIONS: There have been great advances in therapeutic research in MS. However, the stratification of patients according to their prognosis and predictive outcomes in response to treatment is still in its infancy. The many facets of MS make it difficult to piece all the data together into one cohesive conclusion for the individual patient. The visual system, with our ability to assess both structure and function, offers a promising opportunity to study both pathophysiologic mechanisms and novel therapies.

Cortical functional modifications following optic neuritis.

BACKGROUND: We have recently suggested that delayed visual evoked potential (VEP) latencies in the fellow eye (FE) of optic neuritis patients reflect a cortical adaptive process, to compensate for the delayed arrival of visual information via the affected eye (AE). OBJECTIVE: To define the cortical mechanism that underlies this adaptive process. METHODS: Cortical activations to moving stimuli and connectivity patterns within the visual network were tested using functional magnetic resonance imaging (MRI) in 11 recovered optic neuritis patients and in 11 matched controls. RESULTS: Reduced cortical activation in early but not in higher visual areas was seen in both eyes, compared to controls. VEP latencies in the AEs inversely correlated with activation in motion-related visual cortices. Inter-eye differences in VEP latencies inversely correlated with cortical activation following FE stimulation, throughout the visual hierarchy. Functional correlation between visual regions was more pronounced in the FE compared with the AE. CONCLUSION: The different correlation patterns between VEP latencies and cortical activation in the AE and FE support different pathophysiology of VEP prolongation in each eye. Similar cortical activation patterns in both eyes and the fact that stronger links between early and higher visual areas were found following FE stimulation suggest a cortical modulatory process in the FE.

Anatomical and functional connectivity in the default mode network of post-traumatic stress disorder patients after civilian and military-related trauma.

Posttraumatic stress disorder (PTSD) is characterized by unwanted intrusive thoughts and hyperarousal at rest. As these core symptoms reflect disturbance in resting-state mechanisms, we investigated the functional and anatomical involvement of the default mode network (DMN) in this disorder. The relation between symptomatology and trauma characteristics was considered. Twenty PTSD patients and 20 matched trauma-exposed controls that were exposed to a similar traumatic event were recruited for this study. In each group, 10 patients were exposed to military trauma, and 10 to civilian trauma. PTSD, anxiety, and depression symptom severity were assessed. DMN maps were identified in resting-state scans using independent component analysis. Regions of interest (medial prefrontal, precuneus, and bilateral inferior parietal) were defined and average z-scores were extracted for use in the statistical analysis. The medial prefrontal and the precuneus regions were used for cingulum tractography whose integrity was measured and compared between groups. Similar functional and anatomical connectivity patterns were identified in the DMN of PTSD patients and trauma-exposed controls. In the PTSD group, functional and anatomical connectivity parameters were strongly correlated with clinical measures, and there was evidence of coupling between the anatomical and functional properties. Type of trauma and time from trauma were found to modulate connectivity patterns. To conclude, anatomical and functional connectivity patterns are related to PTSD symptoms and trauma characteristics influence connectivity beyond clinical symptoms. Hum Brain Mapp 37:589-599, 2016. © 2015 Wiley Periodicals, Inc.

Using Advanced Imaging Methods to Study Neurolathyrism.

BACKGROUND: Neurolathyrism is a toxic nutritional disorder caused by consumption of the grass pea, Lathyrus sativus. The disease, which manifests as an acute or insidiously evolving spastic paraparesis, continues to occur throughout Africa and Asia. Research on this disease is limited, and to our knowledge no imaging studies of patients with neurolathyrism have been published. OBJECTIVES: To better localize the site of damage in neurolathyrism using advanced imaging methods. METHODS: Three male patients, immigrants from Ethiopia, were included in the study. All had a history of arrested spastic paraparesis that had evolved before their emigration from Ethiopia, and a past history of exposure to grass pea without any other cause. Functional magnetic resonance imaging (fMRI) included simple motor tasks to evaluate cortical motor areas. Anatomic scans included diffusion tensor imaging (DTI) to evaluate the corticospinal tracts. RESULTS: In all patients clear activation was found in motor regions, and the patients' activity pattern was qualitatively similar to that in control sublects. In one patient in whom clinical symptoms were asymmetric, an asymmetric activity pattern in Ml was identified. DTI analysis identified intact corticospinal tracts connecting the pons and the primary motor regions, similar to control subjects. CONCLUSIONS: Advanced neuroimaging clearly identified well-functioning motor regions and tracts in neurolathyrism patients, suggesting a spinal etiology.

Physiological Correlates and Predictors of Functional Recovery After Chiasmal Decompression.

BACKGROUND: The intrinsic abilities and limits of the nervous system to repair itself after damage may be assessed using a model of optic chiasmal compression, before and after a corrective surgical procedure. METHODS: Visual fields (VFs), multifocal visual evoked potentials (mfVEP), retinal nerve fiber layer (RNFL) thickness, and diffusion tensor imaging were used to evaluate a patient before and after removal of a meningioma compressing the chiasm. Normally sighted individuals served as controls. The advantage of each modality to document visual function and predict postoperative outcome (2-year follow-up) was evaluated. RESULTS: Postsurgery visual recovery was best explained by critical mass of normally conducting fibers and not associated with average conduction amplitudes. Recovered VF was observed in quadrants in which more than 50% of fibers were identified, characterized by intact mfVEP latencies, but severely reduced amplitudes. Recovery was evident despite additional reduction of RNFL thickness and abnormal optic tract diffusivity. The critical mass of normally conducting fibers was also the best prognostic indicator for functional outcome 2 years later. CONCLUSIONS: Our results highlight the ability of the remaining normally conductive axons to predict visual recovery after decompression of the optic chiasm. The redundancy in anterior visual pathways may be explained, neuroanatomically, by overlapping receptive fields.

Seeing in the dark: High-order visual functions under scotopic conditions.

It is unknown how and to what degree people function visually in almost complete darkness, where only rod photoreceptors are active (scotopic conditions). To explore this, we first tested scotopic acuity and crowding. We demonstrated the ∼1° foveal scotoma and found that crowding increases with eccentricity, resulting in optimal scotopic discrimination 2° into the periphery. We then investigated whether these limitations affect high-level foveal tasks. We recorded eye movements while testing reading and upright/inverted face matching under photopic and scotopic conditions. Under scotopic conditions, participants read accurately and showed a face inversion effect. Temporally, fixation durations were longer. Spatially, surprisingly, participants did not avert their gaze 2° into the periphery. Instead, they fixated on similar locations as under photopic conditions, locations that were shown to correlate with global perception. We propose that this result suggests global perception governs under scotopic conditions, and we discuss how receptive-field properties support this conclusion.

Demyelination affects temporal aspects of perception: an optic neuritis study.

OBJECTIVE: Visual Evoked Potentials (VEPs) following optic neuritis (ON) remain chronically prolonged, although standard visual tests indicate full recovery. We hypothesized that dynamic visual processes, such as motion perception, may be more vulnerable to slowed conduction in the optic nerve, and consequently be better associated with projection rates. METHODS: Twenty-one patients with acute unilateral, first-ever ON were studied during 1 year. Static visual functions (visual acuity, color perception, visual field, and contrast sensitivity), dynamic visual functions (motion perception), and VEPs were assessed repeatedly. RESULTS: Visual and electrophysiological measurements reached maximal performance 4 months following the acute phase, with no subsequent improvement. Whereas VEP amplitude and static visual functions recovered, VEP latency remained significantly prolonged, and motion perception remained impaired throughout the 12-month period. A strong correlation was found between VEP latencies and motion perception. Visual performance at 1 month was strongly predictive of visual outcome. For static functions, patients who showed partial recovery at 1 month subsequently achieved full recovery. For dynamic functions, the rate of improvement was constant across patients, independent of the initial deficit level. INTERPRETATION: Conduction velocity in the visual pathways correlated closely with dynamic visual functions, implicating the need for rapid transmission of visual input to perceive motion. Motion perception level may serve as a tool to assess the magnitude of myelination in the visual pathways. The constancy across patients may serve as a baseline to assess the efficacy of currently developing neuroprotective and regenerative therapeutic strategies, targeting myelination in the central nervous system.

An FMRI investigation of the cortical network underlying detection and categorization abilities in hemianopic patients.

The current study aims to investigate visual scene perception and its neuro-anatomical correlates for stimuli presented in the central visual field of patients with homonymous hemianopia, and thereby to assess the effect of a right or a left occipital lesion on brain reorganization. Fourteen healthy participants, three left brain damaged (LBD) patients with right homonymous hemianopia and five right brain damaged (RBD) patients with left homonymous hemianopia performed a visual detection task (i.e. "Is there an image on the screen?") and a categorization task (i.e. "Is it an image of a highway or a city?") during a block-designed functional magnetic resonance imaging recording session. Cerebral activity analyses of the posterior areas-the occipital lobe in particular-highlighted bi-hemispheric activation during the detection task but more lateralized, left occipital lobe activation during the categorization task in healthy participants. Conversely, in patients, the same network of activity was observed in both tasks. However, LBD patients showed a predominant activation in their right hemisphere (occipital lobe and posterior temporal areas) whereas RBD patients showed a more bilateral activation (in the occipital lobes). Overall, our preliminary findings suggest a specific pattern of cerebral activation depending on the task instruction in healthy participants and cerebral reorganization of the posterior areas following brain injury in hemianopic patients which could depend upon the side of the occipital lesion.

[Inflammation of the optic nerve: when it should be considered as neuromyelitis optica--the experience of the Department of Neurology at Hadassah Hospital].

INTRODUCTION: Inflammatory demyelinative diseases of the central nervous system are mostly idiopathic and represent the major cause of neurological disability in young adults. These diseases differ in terms of clinical symptoms, severity, pathological characteristics and epidemiology. However, there are also significant similarities between these diseases, which sometimes bring to a misleading diagnosis. Neuromyelitis optica (NMO) is a demyelinative disease in which the optic nerve and the spinal cord are predominantly affected. The detection of specific antibodies to aquaporin-4 (NMO-IgG) led to a modification of the diagnostic criteria for NMO. METHODS: We performed a retrospective study on NMO-IgG positive patients referred to the Department of Neurology MS Center (2006-2011) with suspected NMO. Based on the presenting symptomatology of the patients, we identified the cases with optic neuritis and various parameters that may differentiate between NMO and MS. NMO-IgG were evaluated by ELISA. RESULTS: A total of 50% of the 107 patients with NMO-IgG fulfilled the revised criteria of NMO; 38 patients had a single attack of optic neuritis or long lesion in the spinal cord and 15 patients presented with an opticospinal type of MS. The visual acuity following a single attack of optic neuritis remained significantly lower in NMO patients as compared to MS patients. Most of the NMO patients with NMO-IgG had additional attacks of optic neuritis within a short time from the initial event. CONCLUSIONS: The finding of NMO-IgG in patients with optic neuritis foreshadows a bad prognosis and relapses. These patients are at high risk of experiencing a second event in the central nervous system and fulfilling the clinical criteria for NMO. Due to the difference in the severity of inflammation of the optic nerve between NMO and MS, it is highly recommended to seek a laboratory check-up for NMO-IgG in serum, immediately after the first event, in order to determine the necessity and the kind of treatment for the patient.