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.

Case Report: Post-Chikungunya-Associated Myeloneuropathy.

Chikungunya virus (CHIKV) is an arbovirus endemic to South Asia with frequent outbreaks. A wide spectrum of neurological complications has been described in Chikungunya infections. Myeloneuropathy is a rare complication seen in Chikungunya and is proposed to have an underlying immune mediated pathogenesis. We report a case of a 45-year-old man presenting to the emergency services with acute onset of quadriparesis, breathlessness, urinary retention, profound pain, and sensory disturbances 6 weeks after the onset of high-grade fever and arthralgia. On examination, the patient had Medical Research Council grade 1 flaccid quadriparesis with prominent wasting and areflexia with distinct sensory level at T4. Immunoglobulin M CHIKV antibodies were positive, tested twice at a 1-week interval. He had notable magnetic resonance imaging (MRI) findings in the form of patchy T2 hyperintensities involving the entire length of the cervical and thoracic cord with normal brain imaging and extensive short tau inversion recovery hyperintense signal changes on muscle MRI. He was treated with five cycles of plasmapheresis and intravenous methylprednisolone followed by oral steroids for 8 weeks. At 20-week follow-up, the patient had improvement in upper limb weakness, but paraparesis persisted. The case highlights the presence of unusual MRI findings and also the importance of early recognition of after infective neurological complications, and prompt treatment with immunomodulation may be beneficial.

Clinical Features, Laboratory, and Radiological Findings of Patients With Acute Inflammatory Myelopathy After COVID-19 Infection: A Narrative Review.

ABSTRACT: The objective of this review was to analyze the existing data on acute inflammatory myelopathies associated with coronavirus disease 2019 infection, which were reported globally in 2020. PubMed, CENTRAL, MEDLINE, and online publication databases were searched. Thirty-three acute inflammatory myelopathy cases (among them, seven cases had associated brain lesions) associated with coronavirus disease 2019 infection were reported. Demyelinating change was seen in cervical and thoracic regions (27.3% each, separately). Simultaneous involvement of both regions, cervical and thoracic, was seen in 45.4% of the patients. Most acute inflammatory myelopathy disorders reported sensory motor and bowel bladder dysfunctions. On cerebrospinal fluid analysis, pleocytosis and increased protein were reported in 56.7% and 76.7% of the patients, respectively. Cerebrospinal fluid severe acute respiratory syndrome coronavirus 2 reverse transcriptase-polymerase chain reaction was positive in five patients. On T2-weighted imaging, longitudinally extensive transverse myelitis and short-segment demyelinating lesions were reported in 76% and 21%, respectively. Among the patients with longitudinally extensive transverse myelitis, 61% reported "moderate to significant" improvement and 26% demonstrated "no improvement" in the motor function of lower limbs. Demyelinating changes in the entire spinal cord were observed in three patients. Most of the patients with acute inflammatory myelopathy (including brain lesions) were treated with methylprednisolone (81.8%) and plasma-exchange therapy (42.4%). An early treatment, especially with intravenous methylprednisolone with or without immunoglobulin and plasma-exchange therapy, helped improve motor recovery in the patients with acute inflammatory myelopathy associated with coronavirus disease 2019.

Myelopathy associated with SARS-COV-2 infection. A systematic review.

Background׃COVID-19 (CoranaVirus disease 2019) is an ongoing infectious disease caused by the RNA SARS-CoV-2 virus (Severe Acute Respiratory Syndrome CoronaVirus-2). More than one-third of COVID-19 patients report neurological symptoms and cases of neurological diseases are increasingly accumulating. The aim of this systematic review was to characterize all - to date - reported cases with COVID-19 related myelopathy. Methods׃Eighteen papers were included in this review. Patients of all ages could be affected, although there is a predilection for middle-aged people. Results׃There were no significant co-morbidities or immunodeficiencies in the affected patients. COVID-19 related myelopathy started roughly within the first month after COVID-19 onset, either concomitantly with COVID-19 symptoms or within 10 days after their remission. The vast majority of cases fulfilled our criteria for postinfectious transverse myelitis. However, some cases were considered to have had parainfectious or infectious myelitis or, in one case, vascular myelopathy. Motor, sensory and bowel and/or bladder symptoms predominated the clinical presentation of myelopathies, explained mainly by centrally localized and longitudinally extensive lesions within the cervical and/or thoracic segments of the spinal cord. Occasionally lesions were complicated by necrosis and hemorrhages. Treatment with corticosteroids, intravenous immunoglobulin or plasma exchange was offered mostly a mild to marked improvement within a period of some weeks. Conclusions׃ Considering the imminent arrival of new vaccines against COVID-19 pandemic, and their potential risk for postvaccination transverse myelitis, this characterization of COVID-19 related myelopathy is of utmost importance.

Atypical HIV-vacuolar myelopathy: a case report.

BACKGROUND: Here, we report an atypical HIV-vacuolar myelopathy and search the available medical literature about atypical presentations of human immunodeficiency virus associate vacuolar myelopathy (HIV-VM) and immunoglobulin therapy response. CASE: A 26-year-old lady who was 4 weeks postpartum presented to us with acute flaccid quadriparesis, with no sensory level. Extensive workup ruled out other causes of myelopathy. She developed a stage 3 acute kidney injury, and MRI showed diffuse cord atrophy involving the lower cervical and thoracic cord. The patient received IV-immunoglobulin, ARVs, and supportive therapy with inadequate response. Unfortunately, she developed nosocomial pneumonia and died. DISCUSSION: In HIV-VM, there is spinal cord atrophy, which mainly involves the thoracic cord. In our case, this pathological process also affected the spinal cord's cervical region, leading to flaccid tetraplegia, with high CD4 level, without response to the treatment, including intravenous immunoglobulin. KEYNOTES: Vacuolar myelopathy, HIV, Immunoglobulin therapy, flaccid tetraplegia, hypokalaemia. Renal failure.

Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia/lymphoma with HTLV-1-associated myelopathy.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be curative for adult T-cell leukemia/lymphoma (ATL), but comorbidities increase transplant-related mortality. Here we report the outcome of allo-HSCT in a patient with ATL with human T-cell leukemia virus type I (HTLV-1)-associated myelopathy-tropical spastic paraparesis (HAM/TSP). A 48-year-old man was diagnosed with HAM/TSP and started prednisolone therapy. Ten years later, he developed lymphoma-type ATL. At the diagnosis of ATL, Osame's Motor Disability Score (OMDS) was 4. When prednisolone was gradually tapered and stopped following chemotherapy for ATL, HAM/TSP symptoms recurred (OMDS 7). Bone marrow transplantation from a human leukocyte antigen allele 8/8 matched unrelated donor was performed while ATL was in partial remission. Neutrophil engraftment with complete donor chimerism was achieved on day 19 after allo-HSCT. Mild gait improvement (OMDS 5) was observed on day 30. Although ATL relapsed on day 275, progression of HAM/TSP symptoms was not observed. Furthermore, there was no clear progression of HAM/TSP symptoms after donor lymphocyte infusions. The outcome of this case suggests that ATL patients with HAM/TSP tolerate allo-HSCT and donor lymphocyte infusions.

An update on human T-cell leukemia virus type I (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) focusing on clinical and laboratory biomarkers.

Human T-cell leukemia virus type I (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare inflammatory disease causing unremitting and progressive neurological disorders, such as spastic paraparesis, neurogenic bladder, and sensory disturbance of the lower extremities. Although there is no cure, immune-modulating agents such as corticosteroids are most widely used to slow disease progression. Biomarkers for the clinical assessment of HAM/TSP should be identified because the prediction of functional prognosis and the assessment of treatment efficacy are challenging due to the slowly progressive nature of the disease. The lack of surrogate biomarkers also hampers clinical trials of new drugs. This review summarizes biomarker candidates for the clinical assessment of patients with HAM/TSP. Most of the reported biomarker candidates are associated with viral components or inflammatory mediators because immune dysregulation provoked by HTLV-1 infection is thought to cause chronic inflammation and damage the spinal cord of patients with HAM/TSP. Although information on the diagnostic accuracy of most of the reported biomarkers is insufficient, several molecules, including inflammatory mediators such as CXCL10 and neopterin in the cerebrospinal fluid, have been suggested as potential biomarkers of functional prognosis and treatment response. Several clinical trials for HAM/TSP are currently underway, and we expect that these studies will provide not only evidence pertaining to treatment, but also novel findings regarding the utility of biomarkers in this disease. The establishment of clinical biomarkers will improve patient care and promote the development of therapies for HAM/TSP.

Infectious Myelopathies.

PURPOSE OF REVIEW: This article reviews bacterial, viral, fungal, and parasitic pathogens associated with myelopathy. Infectious myelopathies may be due to direct infection or parainfectious autoimmune-mediated mechanisms; this article focuses primarily on the former. RECENT FINDINGS: Some microorganisms exhibit neurotropism for the spinal cord (eg, enteroviruses such as poliovirus and flaviviruses such as West Nile virus), while others are more protean in neurologic manifestations (eg, herpesviruses such as varicella-zoster virus), and others are only rarely reported to cause myelopathy (eg, certain fungal and parasitic infections). Individuals who are immunocompromised are at increased risk of disseminated infection to the central nervous system. Within the last few years, an enterovirus D68 outbreak has been associated with cases of acute flaccid paralysis in children, and emerging Zika virus infection has been concurrent with cases of acute flaccid paralysis due to Guillain-Barré syndrome, although cases of myelitis have also been reported. Associated pathogens differ by geographic distribution, with myelopathies related to Borrelia burgdorferi (Lyme disease) and West Nile virus more commonly seen in the United States and parasitic infections encountered more often in Latin America, Southeast Asia, and Africa. Characteristic CSF and MRI patterns have been identified with many of these infections. SUMMARY: A myriad of pathogens are associated with infectious myelopathies. Host factors, geographic distribution, clinical features, CSF profiles, and MRI findings can assist in formulating the differential diagnosis and ultimately guide management.

Temporal trends in Human T-Lymphotropic virus 1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/TSP) incidence in Martinique over 25 years (1986-2010).

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) has been discovered in 1980 and has been linked to tropical spastic paraparesis (HAM/TSP) in 1985 in Martinique. There is no data on HAM/TSP incidence trends. We report, in the present work, the temporal trends incidence of HAM/TSP in Martinique over 25 years. METHODS: Martinique is a Caribbean French West Indies island deserved by a unique Neurology Department involved in HAM/TSP diagnosis and management. A registry has been set up since 1986 and patients diagnosed for a HAM/TSP were prospectively registered. Only patients with a definite HAM/TSP onset between 1986 and 2010 were included in the present study. The 25-year study time was stratified in five-year periods. Crude incidence rates with 95% confidence interval (95%CI) were calculated using Poisson distribution for each period. Age-standardized rates were calculated using the direct method and the Martinique population census of 1990 as reference. Standardized incidence rate ratios with 95% CIs and P trends were assessed from simple Poisson regression models. Number of HTLV-1 infection among first-time blood donors was retrospectively collected from the central computer data system of the Martinique blood bank. The HTLV-1 seroprevalence into this population has been calculated for four 5-year periods between 1996 and 2015. RESULTS: Overall, 153 patients were identified (mean age at onset, 53+/-13.1 years; female:male ratio, 4:1). Crude HAM/TSP incidence rates per 100,000 per 5 years (95%CI) in 1986-1990, 1991-1995, 1996-2000, 2001-2005 and 2006-2010 periods were 10.01 (6.78-13.28), 13.02 (9.34-16.70), 11.54 (8.13-14.95), 4.27 (2.24-6.28) and 2.03 (0.62-3.43). Age-standardized 5-year incidence rates significantly decreased by 69% and 87% in 2001-2005 and 2006-2010 study periods. Patients characteristics did not differ regarding 1986-2000 and 2001-2010 onset periods. Between 1996-2000 and 2011-2015 study periods, the HTLV-1 seroprevalence significantly decreased by 63%. CONCLUSION: Martinique faces a sudden and rapid decline of HAM/TSP incidence from 2001 in comparison to 1986-2000 periods. Reduction of HTLV-1 seroprevalence, that may result from transmission prevention strategy, could account for HAM/TSP incidence decrease.

The Risks of Hepatitis C in Association With Cervical Spinal Surgery: Analysis of Radiculopathy and Myelopathy Patients.

STUDY DESIGN: Retrospective review. OBJECTIVE: To investigate rates of in-hospital postsurgical complications among hepatitis C-infected patients after cervical spinal surgery in comparison with uninfected patients and determine independent risk factors. SUMMARY OF BACKGROUND DATA: Studying hepatitis C virus (HCV) as a possible risk factor for cervical spine postoperative complications is prudent, given the high prevalence of cervical spondylosis and HCV in older patients. Spine literature is limited with respect to the impact of chronic HCV upon complications after surgery. MATERIALS AND METHODS: Patients who underwent cervical spine surgery for cervical radiculopathy (CR) or cervical myelopathy (CM) from 2005 to 2013 were retrospectively reviewed using the Nationwide Inpatient Sample database. Patients were divided into CR and CM groups, with comparative subgroup analysis of HCV and no-HCV patients. Univariate analysis compared demographics and complications. Binary logistic stepwise regression modeling identified any independent outcome predictors (covariates: age, sex, Deyo score, and surgical approach). RESULTS: In total, 227,310 patients (HCV: n=2542; no-HCV: n=224,764) were included. From 2005 to 2013, HCV infection prevalence among all cervical spinal fusion cases increased from 0.8% to 1.2%. HCV patients were more likely to be African American or Hispanic and have Medicare and/or Medicaid (all P<0.001). Overall complication rates among HCV patients with CR or CM increased, specifically related to device (CR: 3.1% vs. 1.9%; CM: 2.9% vs. 1.3%), hematoma/seroma (CR: 1.1% vs. 0.4%; CM: 1.8% vs. 0.8%), and sepsis (CR: 0.4% vs. 0.1%; CM: 1.1% vs. 0.5%) (all P≤0.001). Among CR and CM patients, HCV significantly predicted increased complication rates [odds ratio (OR): 1.268; OR: 1.194], hospital stay (OR: 1.738; OR: 1.861), and hospital charges (OR: 1.516; OR: 1.732; all P≤0.044). CONCLUSIONS: HCV patients undergoing cervical spinal surgery were found to have increased risks of postoperative complications and increased risk associated with surgical approach. These findings should augment preoperative risk stratification and counseling for HCV patients and their spine surgeons. LEVEL OF EVIDENCE: Level III.

Congenital Zika Virus Infection Induces Severe Spinal Cord Injury.

We report 2 fatal cases of congenital Zika virus (ZIKV) infection. Brain anomalies, including atrophy of the cerebral cortex and brainstem, and cerebellar aplasia were observed. The spinal cord showed architectural distortion, severe neuronal loss, and microcalcifications. The ZIKV proteins and flavivirus-like particles were detected in cytoplasm of spinal neurons, and spinal cord samples were positive for ZIKV RNA.

Reducing the global burden of HTLV-1 infection: An agenda for research and action.

Even though an estimated 10-20 million people worldwide are infected with the oncogenic retrovirus, human T-lymphotropic virus type 1 (HTLV-1), its epidemiology is poorly understood, and little effort has been made to reduce its prevalence. In response to this situation, the Global Virus Network launched a taskforce in 2014 to develop new methods of prevention and treatment of HTLV-1 infection and promote basic research. HTLV-1 is the etiological agent of two life-threatening diseases, adult T-cell leukemia and HTLV-associated myelopathy/tropical spastic paraparesis, for which no effective therapy is currently available. Although the modes of transmission of HTLV-1 resemble those of the more familiar HIV-1, routine diagnostic methods are generally unavailable to support the prevention of new infections. In the present article, the Taskforce proposes a series of actions to expand epidemiological studies; increase research on mechanisms of HTLV-1 persistence, replication and pathogenesis; discover effective treatments; and develop prophylactic and therapeutic vaccines.

HLA-G 3'-untranslated region polymorphisms are associated with HTLV-1 infection, proviral load and HTLV-associated myelopathy/tropical spastic paraparesis development.

Most human T-lymphotropic virus type 1 (HTLV-1)-infected patients remain asymptomatic throughout life. The factors associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development have not been fully elucidated; immunological and genetic factors may be involved. The association of 14 bp INS/DEL HLA-G polymorphism with HTLV-1 infection susceptibility has been reported previously. Here, other polymorphic sites at the HLA-G 3'-UTR (14-bp D/I, +3003C/T, +3010C/G, +3027A/C, +3035C/T, +3142C/G, +3187A/G and +3196C/G) were evaluated in 37 HTLV-1-infected individuals exhibiting HAM/TSP, 45 HTLV-1 asymptomatic carriers (HAC) and 153 uninfected individuals, followed up at University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil. It was observed that: (i) 14bpDI genotype is a risk factor for HTLV-1 infection, while the 14bpDD and +3142CC genotypes were associated with protection against infection; (ii) the +3142C allele and the +3003CT and +3142CC genotypes were associated with susceptibility, while 14bpII and +3003TT genotypes were associated with protection against HAM/TSP development; and (iii) the 14bpII, +3010CC, +3142GG and +3187AA genotypes were associated with lower HTLV-1 proviral load compared to respective counterpart genotypes. Findings that HLA-G has a well-recognized immunomodulatory role and that the genetic variability at HLA-G 3'-UTR may post-transcriptionally modify HLA-G production indicate a differential genetic susceptibility to: (i) the development of HTLV-1 infection, (ii) the magnitude of HTLV-1 proviral load and (iii) HAM/TSP development.

Nation-wide epidemiological study of Japanese patients with rare viral myelopathy using novel registration system (HAM-net).

BACKGROUND: At least one million people are infected with human T-lymphotropic virus type 1 (HTLV-1) in Japan, a small percentage of whom develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T-cell leukemia/lymphoma (ATLL). Patients with HAM/TSP suffer from progressively worsening myelopathic symptoms, such as motor disability and bladder dysfunction, and may become wheelchair-bound or even bedridden. METHODS: To learn more about this rare, debilitating disease, we established the national registration system "HAM-net" in March 2012. We continuously obtain detailed data from enrolled patients using the registration forms and an annual telephone interview. In this retrospective study, we describe the demographics and clinical histories of 383 registered patients from all over Japan. RESULTS: Patients were diagnosed at a median of 53 years old, long after disease onset at 45. Most (55.3 %) were originally from the southernmost regions, Kyushu and Okinawa. The main initial symptoms were difficulty walking (81.9 %), urinary dysfunction (38.5 %), and lower limb sensory disturbances (13.9 %). Many patients reported frequent leg numbness and leg pain, and the vast majority required medical intervention for urinary symptoms and constipation. A median of 8 years elapsed from the onset of motor symptoms to Osame Motor Disability Score (OMDS) 5 (requiring unilateral support), 12.5 years to OMDS 6 (requiring bilateral support), and 18 years to OMDS 9 (unable to walk). Health Assessment Questionnaire - Disability Index (HAQ-DI) tasks related to mobility, as opposed to hand motions, were very difficult for HAM/TSP patients and well-correlated with OMDS. Scores on the MOS 36-Item Short-Form Health Survey (SF-36) indicated that physical functioning was severely impaired in HAM/TSP patients. Patients with a history of blood transfusion (19.1 %) were older and suffered from more severe disability as indicated by their high HAQ-DI scores. Patients with a family history of HAM/TSP (8.4 %) were younger and had relatively mild symptoms given their long disease durations; many (15.6 %) also had a relative with ATLL. CONCLUSIONS: The HAM-net national registration system has been an effective tool for gathering personal and clinical data from HAM/TSP patients scattered throughout Japan. We expect to conduct many retrospective and prospective epidemiological studies using HAM-net in the future.

Amyotrophic lateral sclerosis presentation of a human T-lymphotropic virus type-1 myelopathy--insight into pathogenesis.

A 41-year-old human T-lymphotropic virus type 1-positive woman developed a syndrome with upper and lower motor neuron signs sometime after bilateral vertebral artery dissections. Over 2 years, she developed a progressive myelopathy affecting predominantly the motor system. She had the picture of a 'person in a barrel' and died from complications. At autopsy, spinal cord revealed inflammatory infiltrates and extensive gliosis involving mainly the anterior horns. The vertebral arterial dissections may have permitted the entry of infected lymphocytes and macrophages, secreting cytokines and metalloproteinases, into the medulla progressing to the spinal cord. Few cases with pathological correlation have been reported.

Myelopathy associated with microorganisms.

PURPOSE OF REVIEW: This article reviews the common infectious etiologies of spinal cord dysfunction that span the globe epidemiologically and vary pathophysiologically. RECENT FINDINGS: Many microorganisms have the ability to directly or indirectly result in spinal cord dysfunction. These agents may have the ability to infect the spinal cord itself, but frequently cause indirect damage by parainfectious or postinfectious immune-mediated destruction or external compression of the spinal cord. SUMMARY: Infectious myelopathies can pose diagnostic difficulty but are potentially reversible causes of spinal cord dysfunction. The often complex relationship among the infectious agent, the immune system, and the neuraxis can create a difficult management conundrum whereby immune modulation may be the preferred approach.