Clinical Approach to Myelopathy Diagnosis.

OBJECTIVE: This article describes an integrative strategy to evaluate patients with suspected myelopathy, provides advice on diagnostic approach, and outlines the framework for the etiologic diagnosis of myelopathies. LATEST DEVELOPMENTS: Advances in diagnostic neuroimaging techniques of the spinal cord and improved understanding of the immune pathogenic mechanisms associated with spinal cord disorders have expanded the knowledge of inflammatory and noninflammatory myelopathies. The discovery of biomarkers of disease, such as anti-aquaporin 4 and anti-myelin oligodendrocyte glycoprotein antibodies involved in myelitis and other immune-related mechanisms, the emergence and identification of infectious disorders that target the spinal cord, and better recognition of myelopathies associated with vascular pathologies have expanded our knowledge about the broad clinical spectrum of myelopathies. ESSENTIAL POINTS: Myelopathies include a group of inflammatory and noninflammatory disorders of the spinal cord that exhibit a wide variety of motor, sensory, gait, and sensory disturbances and produce major neurologic disability. Both inflammatory and noninflammatory myelopathies comprise a broad spectrum of pathophysiologic mechanisms and etiologic factors that lead to specific clinical features and presentations. Knowledge of the clinical variety of myelopathies and understanding of strategies for the precise diagnosis, identification of etiologic factors, and implementation of therapies can help improve outcomes.

Vascular Myelopathies.

OBJECTIVE: Vascular injuries of the spinal cord are less common than those involving the brain; however, they can be equally devastating. This article discusses the diagnosis and management of ischemic and hemorrhagic vascular disorders of the spinal cord. LATEST DEVELOPMENTS: Clinical suspicion remains the mainstay for recognizing vascular myelopathies, yet diagnoses are often delayed and challenging in part because of their rarity and atypical manifestations. Noninvasive imaging such as CT and MRI continues to improve in spatial resolution and diagnostic precision; however, catheter-based spinal angiography remains the gold standard for defining the spinal angioarchitecture. In addition to hemorrhagic and ischemic disease, the contribution of venous dysfunction is increasingly appreciated and informs treatment strategies in conditions such as intracranial hypotension. ESSENTIAL POINTS: Vascular disorders of the spine manifest in variable and often atypical ways, which may lead to delayed diagnosis. Increased awareness of these conditions is critical for early recognition and treatment. The goal of treatment is to minimize long-term morbidity and mortality.

Metabolic and Toxic Myelopathies.

OBJECTIVE: This article reviews the clinical presentation, diagnostic evaluation, and treatment of metabolic and toxic myelopathies resulting from nutritional deficiencies, environmental and dietary toxins, drugs of abuse, systemic medical illnesses, and oncologic treatments. LATEST DEVELOPMENTS: Increased use of bariatric surgery for obesity has led to higher incidences of deficiencies in nutrients such as vitamin B12 and copper, which can cause subacute combined degeneration. Myelopathies secondary to dietary toxins including konzo and lathyrism are likely to become more prevalent in the setting of climate change leading to drought and flooding. Although modern advances in radiation therapy techniques have reduced the incidence of radiation myelopathy, patients with cancer are living longer due to improved treatments and may require reirradiation that can increase the risk of this condition. Immune checkpoint inhibitors are increasingly used for the treatment of cancer and are associated with a wide variety of immune-mediated neurologic syndromes including myelitis. ESSENTIAL POINTS: Metabolic and toxic causes should be considered in the diagnosis of myelopathy in patients with particular clinical syndromes, risk factors, and neuroimaging findings. Some of these conditions may be reversible if identified and treated early, requiring careful history, examination, and laboratory and radiologic evaluation for prompt diagnosis.

Immune-Mediated Myelopathies.

OBJECTIVE: Immune-mediated myelopathies are conditions in which the immune system attacks the spinal cord. This article describes the distinguishing characteristics of immune-mediated myelopathies and treatment strategies for patients affected by these disorders. LATEST DEVELOPMENTS: New biomarkers, such as aquaporin 4 and myelin oligodendrocyte glycoprotein antibodies, in the blood and spinal fluid have led to the identification of antigen-specific immune-mediated myelopathies and approved therapies to prevent disease progression. ESSENTIAL POINTS: The first step in the diagnosis of an immune-mediated myelopathy is confirming that the immune system is the cause of the attack by excluding non-immune-mediated causes. The second step is to narrow the differential diagnosis based on objective biomarkers such as serology and MRI patterns. The third step is to treat the specific immune-mediated myelopathy by using evidence-based medicine.

Infectious Myelopathies.

OBJECTIVE: Infectious myelopathy of any stage and etiology carries the potential for significant morbidity and mortality. This article details the clinical presentation, risk factors, and key diagnostic components of infectious myelopathies with the goal of improving the recognition of these disorders and guiding subsequent management. LATEST DEVELOPMENTS: Despite our era of advanced multimodal imaging and laboratory diagnostic technology, a causative organism often remains unidentified in suspected infectious and parainfectious myelopathy cases. To improve diagnostic capability, newer technologies such as metagenomics are being harnessed to develop diagnostic assays with a greater breadth of data from each specimen and improvements in infection identification. Conventional assays have been optimized for improved sensitivity and specificity. ESSENTIAL POINTS: Prompt recognition and treatment of infectious myelopathy decreases morbidity and mortality. The key diagnostic tools include serologies, CSF analysis, and imaging; however clinical presentation, epidemiologic risk factors, and history of recent illness are all vital to making the proper diagnosis because current laboratory and imaging modalities are often inconclusive. The cornerstone of recommended treatment is targeted antimicrobials with appropriate immune modulation, surgical intervention, supportive care, and interdisciplinary involvement, all of which further improve outcomes for patients with infectious myelopathy.

Genetic Myelopathies.

OBJECTIVE: This article provides an overview of genetic myelopathies, a diverse group of inherited, degenerative conditions that may be broadly categorized as motor neuron disorders, disorders of spinocerebellar degeneration, leukodystrophies, and hereditary spastic paraplegia. Clinical examples from each category are provided to illustrate the spectrum of genetic myelopathies and their distinguishing features that aid in differentiating genetic myelopathies from potentially treatable acquired causes of myelopathy. LATEST DEVELOPMENTS: Advances in genetic testing have vastly enhanced current knowledge of genetic myelopathies and the ability to diagnose and provide appropriate counseling to patients and their families. However, potential health care disparities in access to genetic testing is a topic that must be further explored. Although treatment for most of these conditions is typically supportive, there have been recent therapeutic breakthroughs in treatments for amyotrophic lateral sclerosis, spinal muscular atrophy, and Friedreich ataxia. ESSENTIAL POINTS: Genetic myelopathies may present with chronic and progressive symptoms, a family history of similar symptoms, and involvement of other structures outside of the spinal cord. Imaging often shows spinal cord atrophy, but cord signal change is rare. Exclusion of reversible causes of myelopathy is a key step in the diagnosis. There are many different causes of genetic myelopathies, and in some cases, symptoms may overlap, which underscores the utility of genetic testing in confirming the precise underlying neurologic condition.

SARS-CoV-2 infection and spontaneous spinal hemorrhage: a systematic review.

The neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including spontaneous spinal hemorrhage (SSH), are diverse. SSH is a detrimental neurosurgical event requiring immediate medical attention. We aimed to investigate the association between SARS-CoV-2 and SSH and delineate a rational clinical approach. The authors searched PubMed, Scopus, Web of Science, and Google Scholar for studies published up to January 25, 2023, on SSH and SARS-CoV-2 infection. For each dataset, the authors performed pooled estimates examining three outcomes of interest: (1) early post-intervention neurological status, (2) mortality, and (3) post-intervention neurological rehabilitation outcomes. After reviewing 1341 results, seven datasets were identified for the final analysis. Fifty-seven percent of patients were females. Twenty-eight percent of the patients experienced severe systemic infection. The mean interval between the SARS-CoV-2 infection and neurological presentation was 18 days. Pain and sensorimotor deficits were the most common (57%). Spinal epidural hematoma (EDH) was the most common presentation (71.4%). Three patients were treated conservatively, while 4 received neurosurgical intervention. Pain and sensorimotor deficits had the best treatment response (100%), while the sphincter had the worst response (0%). Long-term follow-up showed that 71% of patients had good recovery. SARS-CoV-2-associated SSH is a rare complication of infection, with an often insidious presentation that requires high clinical suspicion. Patients with SARS-CoV-2 infection and new neurological symptoms or disproportionate neck or back pain require a neuroaxis evaluation. Neurosurgical intervention and conservative management are both viable options to treat SSH following COVID-19. Still, a homogenous approach to the treatment paradigm of SSH cannot be obtained, but lesions with space-occupying effects are suitable for neurosurgical evacuation-decompression while more indolent lesions could be treated conservatively. These options should be tailored individually until larger studies provide a consensus.

Spinal cord motor disorders.

Spinal cord diseases are frequently devastating due to the precipitous and often permanently debilitating nature of the deficits. Spastic or flaccid paraparesis accompanied by dermatomal and myotomal signatures complementary to the incurred deficits facilitates localization of the insult within the cord. However, laboratory studies often employing disease-specific serology, neuroradiology, neurophysiology, and cerebrospinal fluid analysis aid in the etiologic diagnosis. While many spinal cord diseases are reversible and treatable, especially when recognized early, more than ever, neuroscientists are being called to investigate endogenous mechanisms of neural plasticity. This chapter is a review of the embryology, neuroanatomy, clinical localization, evaluation, and management of adult and childhood spinal cord motor disorders.

Diagnosis and management of dogs with degenerative myelopathy: A survey of neurologists and rehabilitation professionals.

BACKGROUND: Antemortem diagnosis of degenerative myelopathy (DM) in dogs is presumptive and there are no accepted guidelines for the management of this condition. HYPOTHESIS/OBJECTIVES: Describe current practices of neurology clinicians and physical rehabilitation professionals in the diagnosis and management of DM. ANIMALS: None. METHODS: Online surveys examining diagnosis and management of DM were constructed and distributed via neurology and rehabilitation listservs. RESULTS: One hundred ninety neurology and 79 rehabilitation professionals from 20 countries participated. Most neurology (142/189) and rehabilitation (23/39) respondents required genetic testing for the superoxide dismutase 1 (SOD1) mutation and 82/189 neurologists also required spinal magnetic resonance imaging (MRI) for presumptive DM diagnosis. Most neurology respondents recommended exercise (187/190) and physical rehabilitation (184/190). Over 50% (102/190) of neurology respondents perform rechecks on dogs diagnosed with DM. Rehabilitation respondents reported preservation or improvement of strength (78/79) and coordination (77/79) as therapeutic goals. At-home exercises (75/79), underwater treadmill (64/79), gait training (55/79), and strength building exercises (65/79) were used to maintain strength (58/79), coordination (56/79), muscle mass (56/79), and improve overall wellbeing (54/79). Neurology respondents reported that owners elect euthanasia when dogs become nonambulatory paraparetic whereas rehabilitation respondents report euthanasia when paraplegia and incontinence develop. CONCLUSION AND CLINICAL IMPORTANCE: The majority of dogs diagnosed with DM have not undergone advanced imaging, the combination of history, neurological findings, and genetic testing is heavily relied upon. Whereas the diagnosis of DM is frequently made by veterinary neurologists, continued care is often performed by rehabilitation professionals or primary veterinarians.

Secondary analysis of a James Lind Alliance priority setting partnership to facilitate knowledge translation in degenerative cervical myelopathy (DCM): insights from AO Spine RECODE-DCM.

OBJECTIVES: To explore whether a James Lind Alliance Priority Setting Partnership could provide insights on knowledge translation within the field of degenerative cervical myelopathy (DCM). DESIGN: Secondary analysis of a James Lind Alliance Priority Setting Partnership process for DCM. PARTICIPANTS AND SETTING: DCM stake holders, including spinal surgeons, people with myelopathy and other healthcare professionals, were surveyed internationally. Research suggestions submitted by stakeholders but considered answered were identified. Sampling characteristics of respondents were compared with the overall cohort to identify subgroups underserved by current knowledge translation. RESULTS: The survey was completed by 423 individuals from 68 different countries. A total of 22% of participants submitted research suggestions that were considered 'answered'. There was a significant difference between responses from different stakeholder groups (p<0.005). Spinal surgeons were the group which was most likely to submit an 'answered' research question. Respondents from South America were also most likely to submit 'answered' questions, when compared with other regions. However, there was no significant difference between responses from different stakeholder regions (p=0.4). CONCLUSIONS: Knowledge translation challenges exist within DCM. This practical approach to measuring knowledge translation may offer a more responsive assessment to guide interventions, complementing existing metrics.

Rehabilitation Therapy for the Degenerative Myelopathy Patient.

Degenerative myelopathy is an inherited, progressive, neurodegenerative disorder affecting the spinal cord of dogs. There is no treatment of the disease. Physical rehabilitation is the only intervention that slows progression and prolongs quality of life. Further studies are needed to develop advanced treatment options and to better characterize the use of complementary therapeutic modalities in palliative care for these patients.

Spinal Dorsal Intradural Arteriovenous Fistulas: Natural History, Imaging, and Management.

In this review, we describe the pathophysiology, diagnosis, and treatment of spinal dorsal intradural arteriovenous fistulas (DI-AVFs), focusing on novel research areas. DI-AVFs compose the most common subgroup of spinal arteriovenous lesions and most commonly involve the thoracic spine, followed by lumbar and sacral segments. The pathogenesis underlying DI-AVFs is an area of emerging understanding, thought to be attributable to venous congestion and hypertension that precipitate ascending myelopathy. Patients with DI-AVFs typically present with motor, sensory, or urinary dysfunction, although a wide swath of other less common symptoms has been reported. DI-AVFs can be subdivided by spinal region, which in turn is associated with 4 distinct clinical phenotypes: craniocervical junction (CCJ), subaxial cervical, thoracic, and lumbosacral. Patients with CCJ and lumbosacral DI-AVFs have particularly interesting presentations and treatment considerations. High-value diagnostic findings on MRI include flow voids, missing-piece sign, and T2-weighted intramedullary hyperintensity. However, digital subtraction angiography is the gold standard for diagnosis and localization of DI-AVFs and for definitive treatment planning. Surgical disconnection of DI-AVFs is almost universally curative and frontline treatment, especially for CCJ and lumbosacral DI-AVFs. Endovascular techniques evolve in promising ways, such as improved visualization, distal access, and liquid embolic techniques. The pathophysiology of DI-AVFs is better understood using newly identified radiologic diagnostic markers. Despite new techniques and devices introduced in the endovascular field, surgery remains the gold-standard treatment for DI-AVFs.

The information needs of people with degenerative cervical myelopathy: A qualitative study to inform patient education in clinical practice.

BACKGROUND: Individuals with lifelong illnesses need access to adequate information about their condition to make optimal health decisions. Degenerative Cervical Myelopathy (DCM) is the most common form of spinal cord dysfunction in adults worldwide. Its chronic and debilitating nature, varied impact, clinical trajectory, and management options necessitate appropriate informational support to sustain effective clinical and self-directed care strategies. However, before clinicians can meet patients' information needs, they must first have an understanding of their baseline requirements. This study explores the information needs of people with DCM (PwCM). In doing so, it provides a starting point for the development of patient education and knowledge management strategies in clinical practice. METHODS: Semi-structured interviews with PwCM were conducted using an interview guide. Interviews were audio-recorded and transcribed verbatim. Thematic analysis according to Braun and Clarke's six-phase approach was used to analyse the data. Findings were reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. RESULTS: Twenty PwCM (65% female, 35% male), with ages ranging from 39 to 74 years old participated in the interviews. The findings indicated that the provision of information to PwCM during clinical interactions varies. Accordingly, PwCM's information needs were broad-ranging, as was the nature of the information they found useful. Three main themes were identified (1) Variation in the provision of information to PwCM during clinical interactions, (2) Variations in the information needs of PwCM, and (3) Information that PwCM find useful. CONCLUSION: Efforts must turn to adequately educating patients at the time of the clinical encounter. A comprehensive and consistent patient-centered information exchange in DCM is necessary to achieve this.

Nelarabine-induced myelopathy in patients undergoing allogeneic hematopoietic cell transplantation: a report of three cases.

Nelarabine is an effective treatment for T-cell acute lymphoblastic leukemia/lymphoma. Myelopathy is a rare but serious adverse event associated with this drug. Three patients who received nelarabine at the National Cancer Center Hospital from December 2014 to March 2021 developed myelopathy 20 days before, 12 days after, and 29 days after allogeneic hematopoietic cell transplantation (allo-HCT), respectively. Magnetic resonance imaging showed that two of the patients had lesions in the dorsal column or medulla oblongata, and one had no abnormalities in the head or spine. Despite treatment with intravenous immunoglobulin and methylprednisolone, all patients became unable to walk. One patient died on day 101 after allo-HCT due to progressive neurotoxicity. The other two patients showed spontaneous improvement in neurological symptoms, but one died of mucormycosis on day 476. Autopsy revealed spongiosis in the posterior funiculus in both patients who died, and also in the medulla oblongata in one patient. In the surviving patient, positron emission tomography on day 84 showed abnormal accumulation, suggesting continued inflammation. These cases demonstrated pathophysiological features of nelarabine-induced myelopathy and indicate that allo-HCT may worsen the condition. It is necessary to elucidate the underlying mechanism and establish diagnostic methods and therapies.

Comparison of treatment recompression tables for neurologic decompression illness in swine model.

BACKGROUND: Significant reductions in ambient pressure subject an individual to risk of decompression illness (DCI); with incidence up to 35 per 10,000 dives. In severe cases, the central nervous system is often compromised (>80%), making DCI among the most morbid of diving related injuries. While hyperbaric specialists suggest initiating recompression therapy with either a Treatment Table 6 (TT6) or 6A (TT6A), the optimal initial recompression treatment for severe DCI is unknown. METHODS: Swine were exposed to an insult dive breathing air at 7.06 ATA (715.35 kPa) for 24 min followed by rapid decompression at a rate of 1.82 ATA/min (184.41 kPa/min). Swine that developed neurologic DCI within 1 hour of surfacing were block randomized to one of four United States Navy Treatment Tables (USN TT): TT6, TT6A-air (21% oxygen, 79% nitrogen), TT6A-nitrox (50% oxygen, 50% nitrogen), and TT6A-heliox (50% oxygen, 50% helium). The primary outcome was the mean number of spinal cord lesions, which was analyzed following cord harvest 24 hours after successful recompression treatment. Secondary outcomes included spinal cord lesion incidence and gross neurologic outcomes based on a pre- and post- modified Tarlov assessment. We compared outcomes among these four groups and between the two treatment profiles (i.e. TT6 and TT6A). RESULTS: One-hundred and forty-one swine underwent the insult dive, with 61 swine meeting inclusion criteria (43%). We found no differences in baseline characteristics among the groups. We found no significant differences in functional neurologic outcomes (p = 0.77 and 0.33), spinal cord lesion incidence (p = 0.09 and 0.07), or spinal cord lesion area (p = 0.51 and 0.17) among the four treatment groups or between the two treatment profiles, respectively. While the trends were not statistically significant, animals treated with TT6 had the lowest rates of functional deficits and the fewest spinal cord lesions. Moreover, across all animals, functional neurologic deficit had strong correlation with lesion area pathology (Logistic Regression, p < 0.01, Somers' D = 0.74). CONCLUSIONS: TT6 performed as well as the other treatment tables and is the least resource intensive. TT6 is the most appropriate initial treatment for neurologic DCI in swine, among the tables that we compared.

[Degenerative cervical myelopathy]. / Mielopatía cervical degenerativa: una patología cada vez más frecuente y que requiere diagnóstico y manejo precoz.

Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord dysfunction in adults. Its prevalence is increasing as a result of population aging. The diagnosis of DCM is often delayed or overlooked, resulting in secondary neurologic morbidity. The natural course of DCM typically presents as a gradual neurological deterioration, with symptoms ranging from muscle weakness to complete paralysis, with variable degrees of sensory deficits and sphincter dysfunction. Magnetic resonance imaging (MRI) and electrophysiological studies allow the assessment of spinal cord function and its structural damage to determine treatment and clinical outcomes. All patients with signs and symptoms consistent with DCM should be referred to a spine surgeon for assessment and tailored treatment. Those patients with mild DCM can be managed non-operatively but require close monitoring and education about potentially alarming signs and symptoms. Surgery is not currently recommended for asymptomatic patients with evidence of spinal cord compression or cervical spinal stenosis on MRI, but they require a structured follow-up. Patients with moderate or severe DCM require surgical decompression to avoid further progression. The objective of this review is to raise awareness of degenerative cervical myelopathy and its increasing prevalence as well as to aid non-surgical healthcare workers for a timely diagnosis and management of this disabling condition.

[Expert consensus for diagnosis and treatment of cervical spondylotic myelopathy with the integrated traditional Chinese and western medicine].

Cervical spondylotic myelopathy (CSM) is the most serious subtype, which is characterized by severe clinical symptoms, a high disability rate, and poor prognosis. Traditional Chinese medicine and Western medicine have their own advantages in the diagnosis and treatment of CSM at different stages. In order to further standardize the clinical diagnosis and treatment of CSM and improve the clinical efficacy, based on previous experience and evidence-based medicine, after repeated discussions by the national expert group, the expert consensus on the diagnosis and treatment of integrated traditional Chinese and Western medicine was compiled. This consensus comprehensively introduces the definition, etiology, pathogenesis, diagnosis treatment principles, integrated traditional Chinese and Western medicine treatment, postoperative rehabilitation and nursing care of cervical spondylotic myelopathy, so as to provide reference for clinicians.

Mielopatía cervical degenerativa: una patología cada vez más frecuente y que requiere diagnóstico y manejo precoz / Degenerative cervical myelopathy

Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord dysfunction in adults. Its prevalence is increasing as a result of population aging. The diagnosis of DCM is often delayed or overlooked, resulting in secondary neurologic morbidity. The natural course of DCM typically presents as a gradual neurological deterioration, with symptoms ranging from muscle weakness to complete paralysis, with variable degrees of sensory deficits and sphincter dysfunction. Magnetic resonance imaging (MRI) and electrophysiological studies allow the assessment of spinal cord function and its structural damage to determine treatment and clinical outcomes. All patients with signs and symptoms consistent with DCM should be referred to a spine surgeon for assessment and tailored treatment. Those patients with mild DCM can be managed non-operatively but require close monitoring and education about potentially alarming signs and symptoms. Surgery is not currently recommended for asymptomatic patients with evidence of spinal cord compression or cervical spinal stenosis on MRI, but they require a structured follow-up. Patients with moderate or severe DCM require surgical decompression to avoid further progression. The objective of this review is to raise awareness of degenerative cervical myelopathy and its increasing prevalence as well as to aid non-surgical healthcare workers for a timely diagnosis and management of this disabling condition.

[Cervical myelopathy due to nitrous oxide inhalation]. / Omfattande inhalationsbruk av lustgas gav ryggmärgsskada.

A 19 year old male presented to his GP with bilateral numbness and stiffness of hands and lower limbs, as well as muscle weakness and poor balance. The patient admitted recreational use of nitrous oxide (laughing gas) some days earlier. He was hospitalised and underwent a series of plasmapheresis treatments due to an initial suspicion of inflammatory myelitis. Further investigation gave evidence of cervical myelopathy which was deemed secondary to heavy use of nitrous oxide. Substitution therapy with hydroxycobalamine was initiated and the patient gradually recovered, although he was later found to have hyperhomocysteinaemia. The adverse effects of recreational nitrous oxide use are discussed, as well as potential pitfalls in diagnosis.