Astrocytic phagocytosis of myelin debris and reactive characteristics in vivo and in vitro.

BACKGROUND INFORMATION: Persistent myelin debris can inhibit axonal regeneration, thereby hindering remyelination. Effective removal of myelin debris is essential to eliminate the interference of myelin debris in oligodendrocyte progenitor cell (OPC) activation, recruitment to demyelinating sites and/or differentiation into mature oligodendrocytes (OLs). In addition to microglia, it has been reported that astrocytic phagocytosis of myelin debris is a feature of early demyelination. RESULTS: In the present study, astrocytes effectively phagocytized myelin debris in vitro and in vivo. On the 5th day after injecting myelin debris into the brain, astrocytes were enriched in the area injected with myelin debris compared with microglia, and their ability to engulf myelin debris was stronger than that of microglia. When exposed to myelin debris, astrocytes phagocytizing myelin debris triggered self-apoptosis, accompanied by the activation of NF-κB, down-regulation of Nrf2, and the increase of ciliary neurotrophic factor (CNTF) and basic fibroblast growth factor (bFGF). However, the activation of astrocytic NF-κB did not influence the inflammatory cytokines IL-1ß, IL-6, and TNF-α, and the anti-inflammatory factor IL-10. The proliferation of astrocytes and mobilization of OPCs in the subventricular zone were elevated on the 5th day after intracerebral injection of myelin debris. CONCLUSIONS: The results suggested that myelin phagocytosis of astrocytes should help improve the microenvironment and promote myelin regeneration by increasing CNTF and bFGF within the central nervous system. SIGNIFICANCE: However, the molecular interaction of astrocytes acting as phagocytes remains to be further explored. Therefore, an improvement of astrocytes to phagocytize myelin debris may be a promising treatment measure to prevent demyelination and promote remyelination in MS and other diseases with prominent myelin injury.

Tocilizumab treatment in MOGAD: a case report and literature review.

Myelin oligodendrocyte glycoprotein-immunoglobulin G associated disease (MOGAD) is an autoimmune demyelinating disorder of the central nervous system (CNS) which usually occurs with recurrent optic neuritis, transverse myelitis, acute disseminating encephalomyelitis, or brainstem encephalitis. To date, the anti-CD 20 drug rituximab (RTX) is employed in MOGAD although some authors reported the efficacy of Tocilizumab (TCZ) in refractory patients. We present the case of a woman affected by refractory MOGAD who was treated with TCZ after therapy with RTX had failed to prevent relapses. We also conducted a current literature review on TCZ use in MOGAD. A 57-year-old Caucasian woman affected by MOGAD with severe motor impairment and cognitive dysfunction was treated from 2020 to February 2022 with RTX. However, she experienced progressive clinical and cognitive worsening associated with white matter lesions mimicking leukodystrophy. In February 2022, the patient started therapy with TCZ administered with improvement of cognitive performance, walking ability, and brainstem functions. During TCZ, our patient reached the condition of NEDA-3 (no relapse, no increase in disability, no MRI activity on neuroimaging follow-up performed in September 2023). Moreover, the patient experienced paucisymptomatic SARS-CoV-2 infection that did not modify TCZ schedule. To date, there are few evidence on the efficacy and safety of TCZ in MOGAD. However, all the reviewed cases showed that TCZ represents an effective therapy in drug-resistant MOGAD. Our case highlights the efficacy of TCZ in drug resistant MOGAD and strengthens previous reports of TCZ safety and efficacy in MOGAD.

Monocentric study of 28 cases of chronic inflammatory demyelinating polyneuropathy: first Tunisian study.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare affection of the peripheral nervous system. Its diagnostic criteria have evolved since 1975. The aim of our work is to study the epidemiological, clinical, and paraclinical aspects of CIDP. METHODS: We conducted a retrospective study of 28 CIDP patients of the neurology department of the military hospital of Tunis between January 2000 and December 2017. All these patients met the European Federation of Neurological Societies/Peripheral Nerve Society(EFNS/PNS)2010 diagnostic criteria for definite CIDP. RESULTS: The average age was 50 years with a gender ratio of 1.57. We found sensitivomotor symptoms in 66% of patients. Neurological assessment showed a proximal and distal motor weakness in 50% of cases, the involvement of superficial and deep sensory systems in 44% of patients with a generalized areflexia in all patients. Median Inflammatory Neuropthy Cause and Treatment (INCAT) score was 7. Concerning electrophysiology, all our patients met the EFNS/EPS 2010 diagnostic criteria for a definite CIDP. Screening for concurrent pathologies was positive in 11 patients. On the therapeutic side, there was no superiority of intravenous immunoglobin compared with pulsed methylprednisolone. Oral steroids were used as backup in about 50% of patients. There were good outcomes in 72% of patients who improved very well after treatment. CONCLUSION: CIDP is a rare and polymorphic disorder with a variety of concurrent pathologies. Our study is the first study in Tunisia and in Maghreb countries which included the most big series of patients. Our results were similar to literature. A multicentral study would be better profitable.

Therapeutic potential of stem cells for treatment of neurodegenerative diseases.

Neurodegenerative diseases are caused by a loss of neurons within the peripheral or central nervous system. Inadequate repairability in the central nervous system and failure of treatments are the significant hurdles for several neurological diseases. The regenerative potential of stem cells drew the attention of researchers to cell-based therapy for treating neurodegenerative diseases. The clinical application of stem cells may help to substitute new cells and overcome the inability of the endogenous repairing system to repair the damaged brain. However, the clinical application induced pluripotent stem cells are restricted due to the risk of tumor formation by residual undifferentiated upon transplantation. In this focused review, we briefly discussed different stem cells currently being studied for therapeutic development. Moreover, we present supporting evidence for the utilization of stem cell therapy for the treatment of neurodegenerative diseases. Also, we described the key issues that should be considered to transplantation of stem cells for different neurodegenerative diseases. In our conclusion, stem cell therapy probably would be the only treatment strategy that offers a cure for neurodegenerative disease. Although, further study is required to identify ideal stem cells candidate, dosing and the ideal method of cell transplantation. We suggest that all grafted cells would be transgenically armed with a molecular kill-switch that could be activated by the event of adverse side effects.

The contribution of astrocytes to the neuroinflammatory response in multiple sclerosis and experimental autoimmune encephalomyelitis.

Neuroinflammation is the coordinated response of the central nervous system (CNS) to threats to its integrity posed by a variety of conditions, including autoimmunity, pathogens and trauma. Activated astrocytes, in concert with other cellular elements of the CNS and immune system, are important players in the modulation of the neuroinflammatory response. During neurological disease, they produce and respond to cellular signals that often lead to dichotomous processes, which can promote further damage or contribute to repair. This occurs also in multiple sclerosis (MS), where astrocytes are now recognized as key components of its immunopathology. Evidence supporting this role has emerged not only from studies in MS patients, but also from animal models, among which the experimental autoimmune encephalomyelitis (EAE) model has proved especially instrumental. Based on this premise, the purpose of the present review is to summarize the current knowledge of astrocyte behavior in MS and EAE. Following a brief description of the pathological characteristics of the two diseases and the main functional roles of astrocytes in CNS physiology, we will delve into the specific responses of this cell population, analyzing MS and EAE in parallel. We will define the temporal and anatomical profile of astroglial activation, then focus on key processes they participate in. These include: (1) production and response to soluble mediators (e.g., cytokines and chemokines), (2) regulation of oxidative stress, and (3) maintenance of BBB integrity and function. Finally, we will review the state of the art on the available methods to measure astroglial activation in vivo in MS patients, and how this could be exploited to optimize diagnosis, prognosis and treatment decisions. Ultimately, we believe that integrating the knowledge obtained from studies in MS and EAE may help not only better understand the pathophysiology of MS, but also uncover new signals to be targeted for therapeutic intervention.

Myelin oligodendrocyte glycoprotein antibody-associated demyelination: comparison between onset phenotypes.

BACKGROUND AND PURPOSE: The aim of this study was to analyse the clinical and prognostic features of myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination with different onset phenotypes. METHODS: A total of 52 MOG-IgG-seropositive patients were divided into four groups: (i) optic neuritis (ON) at onset (MOG-ON+ , n = 23), (ii) transverse myelitis (TM) at onset (MOG-TM+ , n = 12), (iii) pure brain symptoms at onset (MOG-ON- -TM- , n = 14) and (iv) both ON and TM at onset (n = 3). This final group was not included in further analyses. Data were collected through medical records and regular follow-up. RESULTS: Median age at presentation was 24 (range, 3-63) years in the whole cohort (50% female). MOG-ON- -TM- patients had the youngest age of onset across the three groups. Patients with MOG-TM+ tended to relapse more frequently and had a longer interval to first relapse than was observed in MOG-ON+ and MOG-ON- -TM- patients. High MOG-IgG titres were associated with increased cerebrospinal fluid leukocytes. The likelihood of harbouring transient, low MOG-IgG titres was higher in the MOG-TM+ group than in the other groups. After a median disease duration of 20 months, most but not all cases had a favourable outcome, with 8% developing severe visual deficit, 2% becoming wheelchair-dependent and 6% developing cognitive impairment. The onset phenotype appeared to be an important predictor of disability type. Having high MOG-IgG titres (odds ratio, 0.168, P = 0.027) or female gender (odds ratio, 0.270, P = 0.067) was associated with a lower likelihood of complete recovery. CONCLUSIONS: Onset phenotype may influence long-term presentation, MOG-IgG status as well as outcome. Further large and prospective studies are needed to better clarify the clinical implications of the first demyelinating event.

Metagenomic Analysis of Cerebrospinal Fluid from Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of central nervous system of unknown etiology. However, some infectious agents have been suggested to play a significant role in its pathogenesis. Next-generation sequencing (NGS) and metagenomics can be employed to characterize microbiome of MS patients and to identify potential causative pathogens. In this study, 12 patients with idiopathic inflammatory demyelinating disorders (IIDD) of the central nervous system were studied: one patient had clinically isolated syndrome, one patient had recurrent optic neuritis, and ten patients had multiple sclerosis (MS). In addition, there was one patient with other non-inflammatory neurological disease. Cerebrospinal fluid (CSF) was sampled from all patients. RNA was extracted from CSF and subjected to a single-primer isothermal amplification followed by NGS and comprehensive data analysis. Altogether 441,608,474 reads were obtained and mapped using blastn. In a CSF sample from the patient with clinically isolated syndrome, 11 varicella-zoster virus reads were found. Other than that similar bacterial, fungal, parasitic, and protozoan reads were identified in all samples, indicating a common presence of contamination in metagenomics. In conclusion, we identified varicella zoster virus sequences in one out of the 12 patients with IIDD, which suggests that this virus could be occasionally related to the MS pathogenesis. A widespread bacterial contamination seems inherent to NGS and complicates the interpretation of results.

Body fluid markers for multiple sclerosis and differential diagnosis from atypical demyelinating disorders.

INTRODUCTION: Body fluid markers could be helpful to predict the conversion into clinically definite multiple sclerosis (MS) in people with a first demyelinating event of the central nervous system (CNS). Consequently, biomarkers such as oligoclonal bands, which are integrated in the current MS diagnostic criteria, could assist early MS diagnosis. AREAS COVERED: This review examines existing knowledge on a broad spectrum of body fluid markers in people with a first CNS demyelinating event, explores their potential to predict conversion to MS, to assess MS disease activity, as well as their utility to differentiate MS from atypical demyelinating disorders such as neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein associated disease. EXPERT OPINION: This field of research has shown a dramatic increase of evidence, especially in the last decade. Some biomarkers are already established in clinical routine (e.g. oligoclonal bands) while others are currently implemented (e.g. kappa free light chains) or considered as breakthroughs (e.g. neurofilament light). Determination of biomarkers poses challenges for continuous monitoring, especially if exclusively detectable in cerebrospinal fluid. A handful of biomarkers are measurable in blood which holds a significant potential.

An Aberrant Case of Neuromyelitis Optica Spectrum Disorder With a Review of Literature.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, acquired demyelinating condition predominantly affecting middle-aged women and is characterized by spinal cord inflammation and optic neuritis. Anti-aquaporin 4 (AQP4) antibodies are typically seen in NMOSD. However, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) shares clinical and imaging similarities. In NMOSD, longitudinally extensive spinal cord lesions (LESCLs), optic neuritis predominantly affecting the posterior aspect of optic nerves, and optic radiations are seen on magnetic resonance imaging (MRI). The brain parenchymal lesions particularly involve the dorsal medulla (area postrema). The report presents a case of a 26-year-old female with recurrent episodes of weakness, pain, and sensory symptoms in both upper and lower limbs who was initially treated for multiple sclerosis. Upon experiencing new symptoms of blurred vision and ataxia, an MRI of the spine and brain was performed, which showed short-segment cervical cord involvement and a lesion in the conus medullaris, raising the suspicion of NMOSD. Subsequent antibody testing confirmed the presence of anti-AQP4 antibodies. While the involvement of the conus medullaris is classically associated with MOGAD, unusual findings in the present case highlight the importance of comprehensive imaging evaluation and raising awareness among clinicians and radiologists regarding the imaging spectrum of NMOSD, thus facilitating timely diagnosis and tailored treatment strategies.

Clinically Isolated Syndrome and Frontal Lobe Arteriovenous Malformation Presenting With Behavior Issues.

Prevalence of brain arteriovenous malformation ranges from 0.14% to 0.6% according to various estimates. A large number of these patients remain asymptomatic. The most common presentation is due to brain hemorrhage. A 14-year-old girl presented to the pediatrician with erratic behavior issues and hallucinations. She was diagnosed by the pediatrician and mental health facility as having schizophrenia and bipolar disorder. Once she was transferred to our children's hospital, evaluation by a pediatric neurologist, computed tomography scan, magnetic resonance imaging, and laboratory workup including lumbar puncture confirmed a clinically isolated syndrome and frontal lobe arteriovenous malformation. Frontal lobe lesions including arteriovenous malformation in the frontal lobe can cause psychological symptoms and behavioral issues. We also discuss the differential diagnosis of acute demyelinating syndromes.

Inpatient Burden of Neurological Disorders: A Route Map for Allocation of Resources and Postgraduate Training.

Introduction There are limited data regarding the profile of inpatient neurological disorders in India. Understanding the spectrum of diseases and the profile of patients admitted in an inpatient setting will help to streamline services, allocate resources, develop management protocols, design curricula, and improve training programs of postgraduate students in neurology training. Objective The objective of this study is to study the profile of inpatient neurological disorders in 1000 consecutive patients admitted to a tertiary care neurological center. Methods Data from 1000 consecutive inpatients admitted to the Neurology Department at St. John's Medical College Hospital, Bengaluru from January 2018 to October 2018 were collected from the medical records. The data obtained from the case records were entered into a Microsoft Excel spreadsheet for descriptive analysis. Results The average age of the patients was 48 years (±18.18) and 606 of the 1000 patients were males. Strokes, including arterial and venous strokes, formed the major inpatient caseload, accounting for 48.7% of cases. Of these, 84% had ischemic arterial strokes, 7.4% had intracranial hemorrhage, and 8.4 % had cerebral sinus venous strokes; 19.3% of patients were admitted for seizures while 8.2% of patients were admitted for headache. Meningitis was diagnosed in 5.2% of patients; 4.8% of patients had central nervous system demyelinating and autoimmune diseases. A number of other diagnoses comprised less than 2.5% each and included movement disorders, peripheral nerve, spine and nerve roots disorders, neuromuscular diseases, neurodegenerative diseases, and medical and functional illness. Conclusion The most common disorders in the inpatient setting are stroke, seizure, headache, meningitis, and autoimmune/demyelinating disorders. These disorders should receive priority while planning the allocation of resources, educational curriculum, training, and teaching programs.

Chronic Inflammatory Demyelinating Polyneuropathy Post-mRNA-1273 Vaccination.

Massive efforts are being made to develop coronavirus disease 2019 (COVID-19) vaccines at an unprecedented rate. The vaccinations' adverse impact profile, on the other hand, has not been well established. Neurological complications are increasingly reported as a result of these vaccines. One such complication identified is immune-mediated inflammatory polyneuropathy, which affects peripheral nerves and neurons. We report a case of chronic inflammatory demyelinating polyneuropathy (CIDP) post-mRNA-1273 (Moderna) COVID-19 vaccine. Recognizing this complication and distinguishing it from Guillain-Barré syndrome enables timely initiation of treatment. Additionally, our report highlights a possible link between vaccination and subsequent development of CIDP, but conclusive evidence of a causal relationship requires more extensive studies.

Serum Peptide Immunoglobulin G Autoantibody Response in Patients with Different Central Nervous System Inflammatory Demyelinating Disorders.

Previous efforts to discover new surrogate markers for the central nervous system (CNS) inflammatory demyelinating disorders have shown inconsistent results; moreover, supporting evidence is scarce. The present study investigated the IgG autoantibody responses to various viral and autoantibodies-related peptides proposed to be related to CNS inflammatory demyelinating disorders using the peptide microarray method. We customized a peptide microarray containing more than 2440 immobilized peptides representing human and viral autoantigens. Using this, we tested the sera of patients with neuromyelitis optica spectrum disorders (NMOSD seropositive, n = 6; NMOSD seronegative, n = 5), multiple sclerosis (MS, n = 5), and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD, n = 6), as well as healthy controls (HC, n = 5) and compared various peptide immunoglobulin G (IgG) responses between the groups. Among the statistically significant peptides based on the pairwise comparisons of IgG responses in each disease group to HC, cytomegalovirus (CMV)-related peptides were most clearly distinguishable among the study groups. In particular, the most significant differences in IgG response were observed for HC vs. MS and HC vs. seronegative NMOSD (p = 0.064). Relatively higher IgG responses to CMV-related peptides were observed in patients with MS and NMOSD based on analysis of the customized peptide microarray.

Comparison of the Efficacy of Optogenetic Stimulation of Glia versus Neurons in Myelination.

Increasing evidence demonstrates that optogenetics contributes to the regulation of brain behavior, cognition, and physiology, particularly during myelination, potentially allowing for the bidirectional modulation of specific cell lines with spatiotemporal accuracy. However, the type of cell to be targeted, namely, glia vs neurons, and the degree to which optogenetically induced cell activity can regulate myelination during the development of the peripheral nervous system (PNS) are still underexplored. Herein, we report the comparison of optogenetic stimulation (OS) of Schwann cells (SCs) and motor neurons (MNs) for activation of myelination in the PNS. Capitalizing on these optogenetic tools, we confirmed that the formation of the myelin sheath was initially promoted more by OS of calcium translocating channelrhodopsin (CatCh)-transfected SCs than by OS of transfected MNs at 7 days in vitro (DIV). Additionally, the level of myelination was substantially enhanced even until 14 DIV. Surprisingly, after OS of SCs, > 91.1% ± 5.9% of cells expressed myelin basic protein, while that of MNs was 67.8% ± 6.1%. The potent effect of OS of SCs was revealed by the increased thickness of the myelin sheath at 14 DIV. Thus, the OS of SCs could highly accelerate myelination, while the OS of MNs only somewhat promoted myelination, indicating a clear direction for the optogenetic application of unique cell types for initiating and promoting myelination. Together, our findings support the importance of precise cell type selection for use in optogenetics, which in turn can be broadly applied to overcome the limitations of optogenetics after injury.

CLINICAL course of acute disseminated encephalomyelitis in adults from Rio de Janeiro: Retrospective study of 23 cases and literature review.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory demyelinating disorder. Most studies involve white children in developed countries in the northern hemisphere. The authors aimed to describe the clinical course and prognostic of a cohort of adult patients with ADEM from Rio de Janeiro city, where most of the population is Afro-descendant. METHODS: We performed a longitudinal study with retrospective data collection of patients with ADEM seen from 1999 to 2016 at a reference center for demyelinating diseases, identifying demographic, clinical, and laboratory data. Then we compared our findings with data from an extensive review of previously published reports. The literature review was carried out using Google Scholar, PubMed, and the reference lists of included studies. Searches were limited to English language original manuscripts published between 2000 and 2019. RESULTS: Among 1396 registers, we identified 23 cases of ADEM, mostly women (78.3%), Afro-descendant (52.4%) with a mean age of 30.8 ± 11.9 years at onset. One quarter had a previous viral infection and, 4.3% vaccination. The presentation was polyfocal, characterized by the association of pyramidal 82.6%, brainstem 69.6%, mental 65.2%, cerebellar 39.1%, sensory 39.1%, sphincter 43.5%, and visual 34.8% syndromes with severe disability in 86.6%. The breakdown of the blood-brain barrier occurred at 60%. MRI was suggestive of ADEM in 87%, with good radiological evolution. A majority had a significant recovery after treatment. CONCLUSIONS: ADEM in adults is a rare, severe, polyfocal disease with a favorable prognosis. The absence of encephalopathy does not exclude the diagnosis.

Cognitive Functioning in Patients with Pediatric-Onset Multiple Sclerosis, an Updated Review and Future Focus.

Pediatric-onset multiple sclerosis (POMS) is relatively rare, but as technology and neuroimaging advance, an increasing number of cases are identified, and our understanding of how multiple sclerosis (MS) impacts the developing brain improves. There are consistent findings in the literature highlighting the impact of MS and other demyelinating diseases on cognitive functioning and cognitive development. We also have a better understanding of how POMS impacts psychosocial functioning and functional outcomes in daily living. This paper hopes to review findings associated with cognitive and psychosocial functioning in patients with POMS, as well as explore more recent advances in the field and how they relate to cognitive and psychosocial outcomes. We also discuss the ongoing need for future studies with a focus on better understanding deficits and disease correlates, but also preventative measures and potential rehabilitation.

Acute disseminated encephalomyelitis following Influenza A pneumonia.

Acute disseminated encephalomyelitis (ADEM) is an autoimmune demyelinating disorder of the central nervous system and can present following influenza A infections as multifocal neurological deficits. ADEM remains a challenging diagnosis, and high clinical suspicious coupled with laboratory investigations and neuroimaging is required to exclude other primary and secondary demyelinating disorders.

Demyelinating disorders secondary to TNF-inhibitor therapy for the treatment of psoriasis: A review.

BACKGROUND: Tumor necrosis factor-α inhibitors (TNFi) are the most widely used systemic treatments for patients with psoriasis and psoriatic arthritis. There currently exists a U.S. Food and Drug Administration issued warning label on all TNFi for "rare cases of new onset or exacerbation of central nervous system demyelinating disorders." The aim of this review was to update the incidence of TNFi-induced demyelinating diseases. METHODS: Pubmed database was searched for safety data regarding demyelinating disease secondary to TNFi therapy prescribed for psoriasis. RESULTS: In clinical trials: 6990 patients had received treatment with etanercept with one reported case of multiple sclerosis; 5204 patients were treated with adalimumab with no cases identified and 2322 patients were treated with infliximab with one case of demyelinating polyneuropathy. Outside of clinical trials: 19 individual cases of demyelinating disorders from TNFi treatment have been reported. CONCLUSION: Although there is potential for TNF blockade to lead to demyelination of the central and peripheral nervous systems, the results of the present review suggest that demyelinating diseases associated with TNFi are extremely rare. TNFi are not recommended for use in patients with a personal history of demyelinating disease. However, with clinical vigilance and individualized treatment regimen, TNFi may be safe for use in other patients.

Myelopathy.

Myelopathy is an inclusive term, referring to pathology leading to a neurologic deficit related to the spinal cord. The clinical diagnosis of myelopathy requires a detailed history and physical examination to define the clinical syndrome. Neuroimaging is indicated in most instances of new-onset myelopathy. It is indicated also when the worsening of a myelopathy is unexplained. Advances in neuroimaging have proved to play a vital role in diagnosis. Appropriate diagnosis and treatment are dependent upon an adequate imaging evaluation to establish the presence of mechanical stability, extrinsic spinal cord compression, or an intramedullary lesion. The most frequent etiology of myelopathy is related to degenerative disease of the spine from osteophyte or extruded disc material causing compression of the spinal cord in the cervical or thoracic spine. The next common etiologies are spinal cord compression due to extradural masses caused by metastatic disease to bone or blunt trauma. In these cases, emergency imaging should be performed to assess the nature of the lesion causing the myelopathy and plan the most appropriate treatment. Also urgent imaging should be performed when an abscess in the spinal canal is suspected. Less urgent is imaging of primary neoplasms of the meninges, roots, or spinal cord, as well as noninfectious inflammatory processes, such as multiple sclerosis, and neurodegenerative, vascular, nutritional, or idiopathic disorders leading to myelopathy. Although a survey of the entire spinal cord can be performed with imaging, it is more appropriate to define from the clinical findings what levels of the spine and spinal cord should be imaged. This approach helps limit the likelihood of false-positive imaging findings that may encourage needless attempts to fix what is not broken. Similarly, the most appropriate imaging study and protocol should be selected in order to provide a timely and accurate diagnosis. To do so requires detailed knowledge regarding the strengths and limitations of the multiple imaging modalities available. This chapter outlines an approach to proper study selection based on the likely etiology of myelopathy from the clinical findings. Chapters 33-39 cover these disorders in detail.