Pediatric non-Hodgkin lymphoma as a rare cause of spinal cord injury: When lymphoma hides in the canal.

Key Clinical Message: Spinal cord compression from non-Hodgkin lymphoma (NHL) should be considered as a potential diagnosis in cases of acute signs of myelopathy in pediatric patients. Abstract: Spinal cord compression in pediatric non-Hodgkin lymphoma (NHL) is a rare presentation with potential diagnostic challenges. We report on two pediatric patients with NHL who exhibited myelopathy signs as initial presentation. Considering NHL as a differential diagnosis in pediatric patients presenting with spinal cord compression is crucial for optimizing the outcome of these patients.

Tropical spastic paraparesis.

A large number of causative agents can result in spinal cord disorders in the tropics including etiologies similar to those of temperate regions such as trauma, spinal bone and disc lesions, tumors, epidural abscess, and congenital malformations. Yet infectious and nutritional disorders differ in their higher prevalence in tropical regions including Pott's disease; brucellosis; neuroborreliosis; various parasitic diseases such as schistosomiasis, neurocysticercosis, and eosinophilic meningitis. Notably, the retrovirus HTLV-1 is the causeof tropical spastic paraparesis/paraplegia or TSP. Nutritional causes of TSP include vitamin B and folate deficiencies, while endemic clusters of konzo and tropical ataxic myeloneuropathy occur in Africa, along with malnutrition and excessive consumption of cyanide-containing bitter cassava. Other toxic etiologies of TSP include lathyrism and fluorosis. Nutritional forms of myelopathy are associated often with optic and sensory neuropathy, hence the name tropical myeloneuropathies. Acute transverse myelopathy, seen in association with vaccination, infections, and fibrocartilaginous embolism of the nucleus pulposus, can be ubiquitous. Multiple sclerosis and optic myelopathy occur in the tropics but with lesser prevalence than in temperate regions. The advent of modern imaging in the tropics, including computed tomography and magnetic resonance imaging, has allowed better diagnosis and treatment of these conditions that are a frequent cause of death and disability. This chapter provides an overview of TSP emphasizing the most common causes with clues to diagnosis and effective therapy.

Identifying specific myelopathy etiologies in the evaluation of suspected myelitis: A retrospective analysis.

BACKGROUND: Myelopathies require prompt etiologic diagnosis. We aimed to identify a specific myelopathy diagnosis in cases of suspected myelitis to highlight clinicoradiologic differences. METHODS: In this retrospective, single-centre cohort of subjects with suspected myelitis referred to London Multiple Sclerosis (MS) Clinic between 2006 and 2021, we identified those with MS and reviewed the remaining charts for etiologic diagnosis based on clinical, serologic, and imaging details. RESULTS: Of 333 included subjects, 318/333 (95.5%) received an etiologic diagnosis. Most (274/333, 82%) had MS or clinically isolated syndrome. Spinal cord infarction (n = 10) was the commonest non-inflammatory myelitis mimic characterized by hyperacute decline (n = 10/10, 100%), antecedent claudication (n = 2/10, 20%), axial owl/snake eye (n = 7/9, 77%) and sagittal pencillike (n = 8/9, 89%) MRI patterns, vertebral artery occlusion/stenosis (n = 4/10, 40%), and concurrent acute cerebral infarct (n = 3/9, 33%). Longitudinal lesions were frequent in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) (n = 7/7, 100%) and myelin oligodendrocyte glycoprotein-IgG-associated disorder (MOGAD) (n = 6/7, 86%), accompanied by bright spotty (n = 5/7, 71%) and central-grey-restricted (n = 4/7, 57%) T2-lesions on axial sequences, respectively. Leptomeningeal (n = 4/4, 100%), dorsal subpial (n = 4/4, 100%) enhancement, and positive body PET/CT (n = 4/4, 100%) aided the diagnosis of sarcoidosis. Spondylotic myelopathies had chronic sensorimotor presentations (n = 4/6, 67%) with relative bladder sparing (n = 5/6, 83%), localizable to sites of disc herniation (n = 6/6, 100%). Metabolic myelopathies showed dorsal column or inverted 'V' sign (n = 2/3, 67%) MRI T2-abnormality with B12 deficiency. CONCLUSIONS: Although no single feature reliably confirms or refutes a specific myelopathy diagnosis, this study highlights patterns that narrow the differential diagnosis of myelitis and facilitate early recognition of mimics.

Neuroimaging features in inflammatory myelopathies: A review.

Spinal cord involvement can be observed in the course of immune-mediated disorders. Although multiple sclerosis (MS) represents the leading cause of inflammatory myelopathy, an increasing number of alternative etiologies must be now considered in the diagnostic work-up of patients presenting with myelitis. These include antibody-mediated disorders and cytotoxic T cell-mediated diseases targeting central nervous system (CNS) antigens, and systemic autoimmune conditions with secondary CNS involvement. Even though clinical features are helpful to orient the diagnostic suspicion (e.g., timing and severity of myelopathy symptoms), the differential diagnosis of inflammatory myelopathies is often challenging due to overlapping features. Moreover, noninflammatory etiologies can sometimes mimic an inflammatory process. In this setting, magnetic resonance imaging (MRI) is becoming a fundamental tool for the characterization of spinal cord damage, revealing a pictorial scenario which is wider than the clinical manifestations. The characterization of spinal cord lesions in terms of longitudinal extension, location on axial plane, involvement of the white matter and/or gray matter, and specific patterns of contrast enhancement, often allows a proper differentiation of these diseases. For instance, besides classical features, such as the presence of longitudinally extensive spinal cord lesions in patients with aquaporin-4-IgG positive neuromyelitis optica spectrum disorder (AQP4+NMOSD), novel radiological signs (e.g., H sign, trident sign) have been recently proposed and successfully applied for the differential diagnosis of inflammatory myelopathies. In this review article, we will discuss the radiological features of spinal cord involvement in autoimmune disorders such as MS, AQP4+NMOSD, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and other recently characterized immune-mediated diseases. The identification of imaging pitfalls and mimics that can lead to misdiagnosis will also be examined. Since spinal cord damage is a major cause of irreversible clinical disability, the recognition of these radiological aspects will help clinicians achieve a correct and prompt diagnosis, treat early with disease-specific treatment and improve patient outcomes.

Risk factors for idiopathic myelitis at admission and predictors for late diagnostic change.

Immune-mediated myelopathy (IMM) diagnosis is challenging, and its etiology may remain unclear despite extensive investigation. We evaluated diagnostic changes in IMM patients during follow-up. We included 80 patients, 61.3% female, with median follow-up time 62.5 months. Diagnoses at discharge were: 48.8% Multiple Sclerosis-IMM (MS-IMM), 32.5% I-IMM, 11.3% Neuromyelitis Optica Spectrum Disorders-IMM (NMOSD-IMM), 1.3% MOG encephalomyelitis (MOGAD), and 6.2% Others IMM (O-IMM). Twenty-two  patients (27.5%) changed diagnosis (median 15.5  months): 68.8% MS-IMM, 12.5%  NMOSD-IMM, 3.8% MOGAD, 10.0% I-IMM, and 5.0% O-IMM. Most patients that changed diagnosis were I-IMM. Predictive factors for diagnostic change in I-IMM were: autonomous gait (p = 0.029), lesions suggestive of MS (p = 0.039), higher number of lesions (p = 0.043), lesions length < 3 vertebral bodies (p = 0.033), cervical involvement (p = 0.038), and lower EDSS at admission (p = 0.013). Etiologic reclassifications in IMM are common, therefore patients require an appropriate follow-up time to increase diagnostic accuracy.

Spinal vascular lesions: anatomy, imaging techniques and treatment.

BACKGROUND: Vascular lesions of the spinal cord are rare but potentially devastating conditions whose accurate recognition critically determines the clinical outcome. Several conditions lead to myelopathy due to either arterial ischemia, venous congestion or bleeding within the cord. The clinical presentation varies, according with the different aetiology and mechanism of damage. PURPOSE: The aim is to provide a comprehensive review on the radiological features of the most common vascular myelopathies, passing through the knowledge of the vascular spinal anatomy and the clinical aspects of the different aetiologies, which is crucial to promptly address the diagnosis and the radiological assessment.

Myelopathies in patients older than 50: not to miss inflammatory etiologies.

BACKGROUND: Inflammatory myelopathies are primarily associated with younger age, and there are few studies in the elderly. Longitudinally extensive spinal cord lesions (LECL) are common in inflammatory myelopathies, but when the first event occurs in older age may have a broader differential diagnosis. OBJECTIVES: To identify all non-traumatic myelopathies' etiologies in patients older than 50 years in a tertiary care hospital and to evaluate characteristics that differentiate inflammatory from non-inflammatory etiologies, focusing on the late-onset (≥50 years old) longitudinally extensive spinal cord lesions (LO-LECL) group. METHODS: Retrospective study of patients admitted between 2008 to 2019. Demographic, clinical, laboratory, and magnetic resonance imaging (MRI) data of all patients were analyzed to identify predictors that could more easily identify inflammatory from non-inflammatory etiologies and further identify the etiologies of LO-LECL. RESULTS: One hundred and three patients 50 years or older diagnosed with non-traumatic myelopathy were included, despite the lesion extension. Five were vascular (5%), 10 spondylotic (10%), 16 other etiologies (16%), 22 inflammatory (21%) and 50 neoplastic myelopathies (49%). Among 23 LO-LECL, 3 were vascular (13%), 4 neoplastic (17%), 7 other etiologies (30%) and 9 inflammatory (39%). The inflammatory LO-LECL had the median time to nadir significantly different from the neoplastic and the other etiologies groups and had the median EDSS at last visit (3.5) significantly lower than the non-inflammatory LO-LECL (7.0-7.5). CONCLUSIONS: Inflammatory etiologies are not to be disregarded in older adults with non-traumatic myelopathies. The symptoms' temporal profile is critical to differentiate inflammatory LO-LECL from other etiologies and it has better functional recovery after adequate treatment.

Magnetic resonance imaging in immune-mediated myelopathies.

Immune-mediated myelopathies are a heterogeneous group of inflammatory spinal cord disorders including autoimmune disorders with known antibodies, e.g. aquaporin-4 IgG channelopathy or anti-myelin oligodendrocyte glycoprotein-associated myelitis, myelopathies in the context of multiple sclerosis and systemic autoimmune disorders with myelopathy, as well as post-infectious and paraneoplastic myelopathies. Although magnetic resonance imaging of the spinal cord is still challenging due to the small dimension of the cord cross-section and frequent movement and susceptibility artifacts, recent methodological advances have led to improved diagnostic evaluation and characterization of immune-mediated myelopathies. Topography, length and width of the lesion, gadolinium enhancement pattern, and changes in morphology over time help in narrowing the broad differential diagnosis. In this review, we give an overview of recent advances in magnetic resonance imaging of immune-mediated myelopathies and its role in the differential diagnosis and monitoring of this heterogeneous group of disorders.

Etiological profile of noncompressive myelopathies in a tertiary care hospital of Northeast India.

BACKGROUND: The discovery of antibodies against aquaporin-4 and evolving concepts of noncompressive myelopathies in the 21st century have made a major impact on the etiological profile of these diseases, with few cases turning out to be idiopathic. OBJECTIVE: To find causes of noncompressive myelopathy in a tertiary care hospital of Northeast India. MATERIALS AND METHODS: An observational study was carried out in the Neurology Department of Gauhati Medical College, Guwahati, from September 2013 to February 2016. Patients of noncompressive myelopathies who underwent magnetic resonance imaging (MRI) of the spine were segregated into two categories: acute-to-subacute myelopathy (ASM) and chronic myelopathy (CM). In addition to routine blood tests, chest X-ray, urinalysis, and visual evoked potentials, investigations included MRI of the brain, cerebrospinal fluid analysis, and immunological, infectious, and metabolic profile based on the pattern of involvement. RESULTS: The study had 151 patients (96 ASM and 55 CM) with a median age of 35 years and male: female ratio 1.4:1. The causes of ASM were neuromyelitis optica spectrum disorder (23), multiple sclerosis (MS) (8), systemic lupus erythematosus (1), Hashimoto's disease (1), postinfectious acute disseminated encephalomyelitis (6), postinfectious myelitis (8), infections (9), spinal cord infarct (5), and electrocution (1). The causes of CM were MS (1), probable or possible sarcoidosis (7), mixed connective tissue disease (1), Hashimoto's disease (2), infections (9), Vitamin B12 deficiency (4), folate deficiency (2), hepatic myelopathy (2), radiation (11), and paraneoplastic (1). No etiology could be found in 48 (31.8%) patients (34 ASM and 14 CM). In 21/96 (21.9%) patients of ASM, acute transverse myelitis was idiopathic based on current diagnostic criteria. CONCLUSION: Underlying etiology (demyelinating, autoimmune, infectious, vascular, metabolic disorder, or physical agent) was found in 68% patients of noncompressive myelopathy.

Redescription and first molecular characterization of the little known feline neurotropic nematode Gurltia paralysans (Nematoda: Metastrongyloidea).

Gurltia paralysans is a poorly documented metastrongyloid nematode of cats, which mainly parasitizes the veins in the spinal cord subarachnoid space and parenchyma. Parasitic paraparesis caused by G. paralysans is a lesser-known spinal cord disease affecting domestic and wild felids of South America. Regions where feline gurltiosis is endemic include the southern parts of Chile and Argentina. Intra vitam diagnosis of feline gurltiosis remains challenging and is based primarily on neurological signs and the exclusion of other ethiologies for feline myelopathies. In view of the lack of information in the literature for this neglected feline neurological parasitosis, we have undertaken a detailed redescription and molecular characterization to expand on the previously available details in the original descriptions by Wolffhügel in 1993. The specimens used in this study were collected from spinal cord lesions of gurltiosis-affected domestic cats. Female and male specimens were morphologically and morphometrically examined using light and scanning electron microscopy. Molecular characterization was performed by sequencing a partial region of the nuclear ribosomal DNA and cytochrome oxidase gene of this parasite, and phylogenetic trees were constructed from the 28S D2-D3 and ITS2 regions using the Maximum Likelihood method. Sequence matching and phylogenetic analysis with these new sequences were consistent with the morphological classification of G. paralysans being within the Metastrongyloidea superfamily, but no consistent relation to a specific metastrongyloid family. The newly developed G. paralysans-specific PCR described here not only provides a useful diagnostic tool for feline gurltiosis in domestic cats living in endemic areas, but could also be used in large-scale epidemiological surveys on the intermediate mollusk host and the final host. By combining the morphology, molecular, and phylogenetic data we have reliably identified G. paralysans and confirmed its taxonomic status within the Metastrongyloidea.

Acute parasitic and other infectious myelopathies in the tropics: 26 cases at the University Hospital in Conakry.

In tropical countries, laboratory-confirmed diagnostic certainty of parasitic and other infectious causes of acute myelopathy is difficult because of a shortage of medical professionals and consulting delays. We performed a retrospective study of 168 patients hospitalized for spinal disorders between 2007 and 2013 and identified 26 diagnosed with acute non-compressive myelopathy of presumed sudden onset. An parasitic or other infectious cause was established for all. A preliminary clinical infection preceding the development of neurologic signs was reported for 22 patients (84.6 %). Neurological signs were limited to the existence of a progressive sensorimotor symptomatology with sphincter disorders.

HAM/TSP and major depression: the role of age.

OBJECTIVE: To investigate the role of demographic variables in the relationship between the presence of HAM/TSP and current major depression. METHODS: It is a cross-sectional study of 108 HTLV-1 infected patients (47 with TSP/HAM) resident of Salvador, Brazil. The Mini International Neuropsychiatric Interview, Brazilian Version 5 was used to evaluate the presence of depression. Prevalence ratios were used to describe relationship between HAM/TSP and depression. The HAM/TSP classification was carried out according to the criteria proposed by Castro-Costa et al. RESULTS: Prevalence of depression was 37.96%. No association was observed between presence of HAM/TSP and diagnosis of current major depression in the global analysis of patients (PR: 0.94; CI 95%: 0.57-1.55). In the stratified analysis, however, greater prevalence of depression was observed amongst individuals with HAM/TSP in the 18-39 age group (PR: 2.59; CI 95%: 1.36-4.95). CONCLUSION: Our findings suggest that age is an effect modifier in the relationship between HAM/TSP and depression, and this aspect should be considered in future studies on the topic.

Neurogenic bladder following myelopathies: Has it any correlation with neurological and functional recovery?

OBJECTIVES: To observe neurogenic bladder pattern in patients with myelopathy by performing urodynamic study (UDS) and to observe whether it has any correlation with functional and neurological recovery. PATIENTS AND METHODS: This prospective study was conducted with 90 patients with myelopathy, both traumatic and non-traumatic (males = 65) in a university tertiary research hospital in India between January 2011 and December 2013. Mean age was 33.5 ± 13.2 years (range 15-65 years), mean duration of injury was 82.63 ± 88.3 days (range 14-365 days) and mean length of stay (LOS) in the rehabilitation unit 42.5 ± 23.3 days (range 14-130 days). The urodynamic study was performed in all the patients to assess the neurogenic bladder pattern. Management was based on the UDS findings. Functional recovery was assessed using Barthel index (BI) scores and spinal cord independence measures (SCIM) scores. Neurological recovery was assessed using ASIA impairment scale (AIS). We tried to correlate neurogenic bladder patterns with recovery. RESULTS: Fifty patients (55.6%) had overactive detrusor with 25 each had detrusor sphincter dyssynergia (DSD) and synergic sphincter. Thirty-eight patients had hypoactive/acontractile detrusor and two had normal studies. No significant correlation observed between neurogenic bladder pattern and change in BI scores (P = 0.696), SCIM scores (P = 0.135) or change in ASIA status (P = 0.841) in the study. CONCLUSIONS: More than half of the patients with myelopathies had overactive detrusor with or without dyssynergic sphincter according to the urodynamic study. Neurogenic bladder patterns had no significant correlation with functional and neurological recovery in these patients.

Tropical myelopathies.

A large number of causal agents produce spinal cord lesions in the tropics. Most etiologies found in temperate regions also occur in the tropics including trauma, herniated discs, tumors, epidural abscess, and congenital malformations. However, infectious and nutritional disorders occur with higher prevalence in tropical regions. Among the most common infectious etiologies are tuberculous Pott's disease, brucellosis, and neuroborreliosis. Parasitic diseases such as schistosomiasis, neurocysticercosis, and eosinophilic meningitis are frequent causes of nontraumatic paraplegia. The retrovirus HTLV-1 is a cause of tropical spastic paraparesis. Nutritional causes of paraparesis include deficiencies of vitamin B12 and folate; endemic clusters of konzo and tropical ataxic myeloneuropathy are associated in Africa with malnutrition and excessive consumption of cyanide-containing bitter cassava. Other toxic etiologies of tropical paraplegia include lathyrism and fluorosis. Nutritional forms of myelopathy are associated often with optic and sensory neuropathy, hence the name tropical myeloneuropathies. Acute transverse myelopathy is seen in association with vaccination, infections, and fibrocartilaginous embolism of the nucleus pulposus. Multiple sclerosis and optic myelopathy occur in the tropics but with lesser prevalence than in temperate regions. The advent of modern imaging in the tropics, including computed tomography and magnetic resonance imaging, has allowed better diagnosis and treatment of these conditions that are a frequent cause of death and disability.

Urodynamic profile of patients with neurogenic bladder following non-traumatic myelopathies.

OBJECTIVE: To observe the urodynamic profile of the patients following non-traumatic myelopathies (NTMs) with neurogenic bladder. SETTING: Neurological rehabilitation department of university tertiary research hospital. MATERIALS AND METHODS: Seventy-nine patients (44 men) with monophasic NTM, with the age range 8-65 years (31.0 ± 16.0 years), were admitted for inpatients' rehabilitation. Length of stay in rehabilitation ranged from 6 to 120 days (32.0 ± 24.8 days). Fifty-six patients (70.9%) had spinal lesion above D10, 17 had lesion between D10 and L2 (21.5%), and 6 (7.6%) had cauda equina syndrome. All patients had neurogenic bladder with urinary complaints. Urodynamic study (UDS) was performed in all patients. RESULTS: UDS showed 71.4% patients (40/56) had neurogenic detrusor overactivity (NDO) with or without sphincter dyssynergy (DSD) with lesion above D10; only 52.9% patients (9/17) had NDO with or without DSD detrusor with lesion between D10 and L2; and majority (5/6 patients) had underactive detrusor in the cauda equina group. Bladder management was based on the UDS findings. No significant correlation was found (P > 0.05) between detrusor behavior and the level, severity (ASIA Impairment Scale) of spinal injury, or gender using chi-square test. CONCLUSIONS: Neurogenic bladder following NTM was observed in all patients. UDS suggested predominantly NDO in lesions above D10 and mixed pattern in between D10 and L2 lesions. No significant correlation was found between detrusor behavior and the level or severity of NTM in the study.

Severity score system for progressive myelopathy: development and validation of a new clinical scale

Progressive myelopathies can be secondary to inborn errors of metabolism (IEM) such as mucopolysaccharidosis, mucolipidosis, and adrenomyeloneuropathy. The available scale, Japanese Orthopaedic Association (JOA) score, was validated only for degenerative vertebral diseases. Our objective is to propose and validate a new scale addressing progressive myelopathies and to present validating data for JOA in these diseases. A new scale, Severity Score System for Progressive Myelopathy (SSPROM), covering motor disability, sphincter dysfunction, spasticity, and sensory losses. Inter- and intra-rater reliabilities were measured. External validation was tested by applying JOA, the Expanded Disability Status Scale (EDSS), the Barthel index, and the Osame Motor Disability Score. Thirty-eight patients, 17 with adrenomyeloneuropathy, 3 with mucopolysaccharidosis I, 3 with mucopolysaccharidosis IV, 2 with mucopolysaccharidosis VI, 2 with mucolipidosis, and 11 with human T-cell lymphotropic virus type-1 (HTLV-1)-associated myelopathy participated in the study. The mean ± SD SSPROM and JOA scores were 74.6 ± 11.4 and 12.4 ± 2.3, respectively. Construct validity for SSPROM (JOA: r = 0.84, P < 0.0001; EDSS: r = -0.83, P < 0.0001; Barthel: r = 0.56, P < 0.002; Osame: r = -0.94, P < 0.0001) and reliability (intra-rater: r = 0.83, P < 0.0001; inter-rater: r = 0.94, P < 0.0001) were demonstrated. The metric properties of JOA were similar to those found in SSPROM. Several clinimetric requirements were met for both SSPROM and JOA scales. Since SSPROM has a wider range, it should be useful for follow-up studies on IEM myelopathies.