Serial MRI findings of acute flaccid myelitis during an outbreak of enterovirus D68 infection in Japan

Objecive

To clarify the neuroimaging findings of children with acute flaccid myelitis during an outbreak of EV-D68 infection.

Etiologic spectrum and functional outcome of the acute inflammatory myelitis

Clinical, neuroimaging, and laboratory features are not specific enough to establish the etiological diagnosis of the acute inflammatory myelitis (AIM). Longitudinally extensive transverse myelitis (LETM) seen on magnetic resonance imaging (MRI) has been associated with a poor functional prognosis. The aim of this study was to assess the functional outcomes of a first AIM event comparing patients with LETM vs. no LETM on MRI and to report the differential diagnosis. Clinical, radiological, biochemical aspects were collected, and Winner–Hughes Functional Disability Scale (WHFDS) was performed after 3 and 6 months. Centromedullary lesions were associated with LETM, lateral lesions with partial lesion (PL), and brain MRI lesions with multiple sclerosis and acute encephalomyelitis disseminated. LETM patients were associated with a worse functional outcome as the need of a wheelchair after 3 and 6 months (OR = 7.61 p = 0.01; OR 4.8 p = 0.04, respectively), a walker or cane (OR = 11.0 p = 0.002, OR = 4.3 p = 0.03, respectively). In addition, we found a correlation between LETM and acute complete transverse myelitis and PL with acute partial transverse myelitis (83.3 and 90.9%, respectively; p < 0.0001). In conclusion, AIM is a heterogeneous syndrome from an etiological point of view and LETM patients had worse functional prognosis compared with PL after 3 and 6 months.     

Atypical transverse myelitis due to cytomegalovirus in an immunocompetent patient

Abstract Cytomegalovirus (CMV)-associated transverse myelitis is rare in immunocompetent patients. We report a 73-year-old man with no evidence of immune compromise, who developed acute transverse myelitis. Cerebrospinal fluid pleocytosis indicated central nervous system inflammation, and spinal MRI showed weak signal hypointensity in T1, hyperintensity in T2 and DP between C7 and T2, but no contrast enhancement. High CSF anti- CMV IgG index with normal CSF IgG index indicated intact blood-brain barrier, and supported the diagnosis of CMV-induced myelitis in an immunocompetent patient.     

Comparison of acute flaccid myelitis and transverse myelitis in children and evaluation of diagnostic criteria

Background and purpose

Acute flaccid myelitis (AFM) and transverse myelitis (TM) are serious conditions that may be difficult to differentiate, especially at onset of disease. In this study, we compared clinical features of pediatric AFM and TM and evaluated current diagnostic criteria, aiming to improve early and accurate diagnosis.

Methods

Two cohorts of children with enterovirus D68-associated AFM and clinically diagnosed TM were compared regarding presenting clinical features, additional investigations, and outcome. Current diagnostic criteria for AFM and TM were applied to evaluate their specificity.

Results

Children with AFM (n = 21) compared to those with TM (n = 36) were younger (median 3 vs. 10 years), more often had a prodromal illness (100% vs. 39%), predominant proximal weakness (69% vs. 17%), and hyporeflexia (100% vs. 44%), and less often had sensory deficits (0% vs. 81%), bowel and/or bladder dysfunction (12% vs. 69%), and hyperreflexia (0% vs. 44%). On magnetic resonance imaging, brainstem involvement was more common in AFM (74% vs. 21%), whereas supratentorial abnormalities were only seen in TM (0% vs. 40%). When omitting the criterion of a sensory level, 11 of 15 (73%) children with AFM fulfilled the diagnostic criteria for TM. Of children with TM, four of 33 (12%) fulfilled the diagnostic criteria for probable/definite AFM.

Conclusions

Although there is considerable overlap between AFM and TM in children, we found important early differentiating clinical and diagnostic features. Meeting diagnostic criteria for AFM in children with TM and vice versa underlines the importance of thorough clinical examination and early and accurate diagnostic studies.     

Neuromyelitis optica and non organ-specific autoimmunity

BACKGROUND: Neuromyelitis optica (NMO) is often associated with other clinical or serological markers of non-organ-specific autoimmunity. OBJECTIVE: To evaluate the relationship between NMO spectrum disorders (NMOSDs), including NMO, longitudinally extensive transverse myelitis, and recurrent optic neuritis, and autoimmune disease. We concentrated on the association with systemic lupus erythematosus (SLE), Sj?gren syndrome (SS), or serological evidence of these disorders, which commonly is a source of diagnostic confusion. DESIGN: Retrospective blinded serological survey. SETTING: Mayo Clinic College of Medicine, Rochester, and Centre Hospitalier Régional Universitaire de Lille. METHODS: Group 1 included 153 US patients with NMOSDs (78 with NMO and 75 with longitudinally extensive transverse myelitis) and 33 control subjects with SS/SLE. Group 2 included 30 French patients with SS/SLE, 14 with NMOSDs (6 with NMO, 6 with longitudinally extensive transverse myelitis, and 2 with recurrent optic neuritis), 16 without NMOSDs, and 4 with NMO without SS/SLE. RESULTS: For group 1, NMO-IgG was detected in 66.7%, antinuclear antibodies in 43.8%, and Sj?gren syndrome A (SSA) antibodies in 15.7% of patients with NMO and longitudinally extensive transverse myelitis. Five NMO-IgG-seropositive patients with NMOSDs had coexisting SLE, SS, or both. Antinuclear antibodies and SSA antibodies were more frequent in NMO-IgG-seropositive patients than in NMO-IgG-seronegative patients (P= .001). For group 2, NMO-IgG was detected in 5 of 14 patients (35.7%) with NMOSDs and SS/SLE and in 2 of 4 patients (50.0%) with NMO without SS/SLE (P= .59). We detected NMO-IgG only in patients with NMOSDs and not in 49 controls with SS/SLE but without optic neuritis or myelitis from the 2 cohorts (P= .01). CONCLUSION: Neuromyelitis optica spectrum disorders with seropositive findings for NMO-IgG occurring with SS/SLE or non-organ-specific autoantibodies is an indication of coexisting NMO rather than a vasculopathic or other complication of SS/SLE.     

Acute myelitis with hyperIgEaemia and mite antigen specific IgE: atopic myelitis

An occurrence of acute localised myelitis was recentlyseen in four adult patients with atopic dermatitis who hadhyperIgEaemia and mite antigen specific IgE. The total and mite antigenspecific IgE was therefore studied in serum samples from 19 consecutive patients with acute localised myelitis of unknown aetiology, 56patients with clinically definite multiple sclerosis, and 40 healthy controls. The total IgE concentration was significantly higher in acutelocalised myelitis (median=360 U/ml) than in multiple sclerosis(median=52 U/ml, p<0.0001) and the controls (median=85 U/ml,p=0.0002). The specific IgE to Dermatophagoidespteronyssinus was found more often in patients with acutelocalised myelitis (95%) than in patients with multiple sclerosis(34%, p<0.0001) and the controls (35%, p<0.0001) and the specificIgE to Dermatophagoides farinae was similar (acutelocalised myelitis 79%, multiple sclerosis 29% (p<0.0001), controls30%, (p=0.0003). Atopic dermatitis coexisted more commonly in patientswith acute localised myelitis (37%) than in patients with multiplesclerosis (0%, p<0.0001) and the controls (7.5%, p=0.0089).Therefore, acute localised myelitis with hyperIgEaemia, in which atopyto mite antigens seems to exist, may be a distinct subtype of allergicmyelitis—that is, atopic myelitis.

     

Acute transverse myelitis in Buenos Aires, Argentina. A retrospective cohort study of 8 years follow up

Introduction

Epidemiological studies on acute transverse myelitis (ATM) in South America are scarce. The aim of our study was to describe demographic, clinical and para-clinical features of patients with ATM in a health care organisation in Buenos Aires. A further objective was to determine the aetiologies of ATM.

Methods

All patients diagnosed with ATM between June 1, 2002 and June 30, 2010 were retrospectively identified, using the Transverse Myelitis Consortium Working Group criteria.

Results

A total of 40 patients diagnosed with ATM, (24 females, 60%) were included. The mean follow-up was 57 ± 8 months. The principal cause of myelitis found was ATM secondary to demyelinating disease (55%). Idiopathic ATM was diagnosed in 15 (37.5%) cases in the sample. The majority of patients had an extensive cord lesion (50%) detectable with spinal MRI.

Conclusion

There are few epidemiological studies concerning ATM in Argentina, and we believe that it is important to be aware of the manner in which this condition manifests itself in this region. We would therefore be able to compare them with studies previously published in other countries.     

An evidence of brain-heart disorder: mental stress-induced myocardial ischemia regulated by inflammatory cytokines

ABSTRACT

Objective

Underlying Coronary Artery Disease (CAD) complicated by Mental Stress-Induced Myocardial Ischemia (MSIMI) has been linked with an increased risk for adverse cardiovascular events and even sudden death. However, the underlying mechanisms of MSIMI remain unknown. In this study, we investigated cytokine levels at baseline inflammation status and during acute inflammatory responses to mental stress in patients with known CAD who presented with MSIMI.     

Late changes in blood–brain barrier permeability in a rat tMCAO model of stroke detected by gadolinium-enhanced MRI

ABSTRACT

Objectives

After cerebral ischaemia the blood–brain barrier (BBB) may be compromised and this has been observed in both clinical and preclinical studies. The timing of BBB disruption after ischaemia has long been considered to be biphasic, however some groups contest this view. Therefore, the purpose of this study was to characterize the BBB permeability timecourse in a rat model at both acute and chronic time points     

Immunopathogenesis of acute transverse myelitis

Acute transverse myelitis is a group of disorders characterized by focal inflammation of the spinal cord and resultant neural injury. Acute transverse myelitis may be an isolated entity or may occur in the context of multifocal or even multisystemic disease. It is clear that the pathological substrate--injury and dysfunction of neural cells within the spinal cord--may be caused by a variety of immunological mechanisms. For example, in acute transverse myelitis associated with systemic disease (i.e. systemic lupus erythematosus or sarcoidosis), a vasculitic or granulomatous process can often be identified. In idiopathic acute transverse myelitis, there is an intraparenchymal or perivascular cellular influx into the spinal cord, resulting in the breakdown of the blood-brain barrier and variable demyelination and neuronal injury. There are several critical questions that must be answered before we truly understand acute transverse myelitis: (1) What are the various triggers for the inflammatory process that induces neural injury in the spinal cord? (2) What are the cellular and humoral factors that induce this neural injury? and (3) Is there a way to modulate the inflammatory response in order to improve patient outcome? Although much remains to be elucidated about the causes of acute transverse myelitis, tantalizing clues as to the potential immunopathogenic mechanisms in acute transverse myelitis and related inflammatory disorders of the spinal cord have recently emerged. It is the purpose of this review to illustrate recent discoveries that shed light on this topic, relying when necessary on data from related diseases such as acute disseminated encephalomyelitis, Guillain-Barré syndrome and neuromyelitis optica. Developing a further understanding of how the immune system induces neural injury will depend upon confirmation and extension of these findings and will require multicenter collaborative efforts.     

Acute lumbosacral transverse myelitis

We report two patients with idiopathic acute lumbosacral myelitis, a rare form of acute transverse myelitis. Both patients developed urinary retention, moderate motor and sensory paresis of the lower extremities, severe sensory deficit in the anogenital region and reduced deep tendon reflexes. Steroid pulse therapy was initiated within 2 days after onset, and progress of the symptoms stopped immediately after administration in both of our patients. The sequelae of the sensory deficits in the sacral dermatome distribution and urinary retention impaired daily functioning. Immediate immunosuppressive therapy, including high-dose steroid treatment, is important to improve the prognosis of acute lumbosacral transverse myelitis.     

Inflammatory demyelinating diseases of the central nervous system in Niger

Background

In sub-Saharan Africa (SSA), few studies have been reported on inflammatory demyelinating diseases of the central nervous system (CNS). Neuromyelitis optica spectrum disorders (NMOSD) seems to be the most frequent inflammatory demyelinating disease of CNS in sub-Saharan Africans or people of sub-Saharan African descent.

Acute transverse myelitis: demyelinating, inflammatory, and infectious myelopathies

Acute transverse myelitis is a rare neurologic condition that has an estimated incidence of up to 3 per 100,000 patient years (0.003%). Although rare, acute transverse myelitis can have devastating neurologic effects with up to two-thirds of patients having a moderate to severe degree of residual disability. The term acute transverse myelitis was previously reserved for idiopathic cases, but currently is used to encompass the general clinical syndrome, whether or not the cause is known. Once adequate neuroimaging has ruled out a compressive etiology, and a lumbar puncture has demonstrated signs of inflammation within the cerebrospinal fluid, a workup of causes for an acute transverse myelitis must be undertaken. Determining the etiology of transverse myelitis can be challenging because there are autoimmune, inflammatory, and infectious diseases associated with acute transverse myelitis. The authors discuss an approach to acute transverse myelitis including clinical symptoms, neuroimaging, and biomarkers that may aid the clinician in diagnosis.     

Neuromyelitis optica IgG status in acute partial transverse myelitis

BACKGROUND: Neuromyelitis optica (NMO) IgG is a specific marker for NMO. Furthermore, a high proportion of patients with longitudinally extensive transverse myelitis (characterized by spinal cord lesions extending 3 vertebral segments or more on magnetic resonance imaging) are seropositive for NMO-IgG and are considered to have a limited form of NMO. The NMO-IgG status in mild cases of acute partial transverse myelitis asociated with minimal magnetic resonance imaging abnormalities (spinal cord lesions <2 vertebral segments on magnetic resonance imaging) is unknown. OBJECTIVE: To investigate the NMO-IgG status of patients with acute partial transverse myelitis and a normal cerebral magnetic resonance image. DESIGN: Observational, retrospective consecutive case series with longitudinal follow-up. SETTING: Allegheny Multiple Sclerosis Treatment Center. PATIENTS: Three groups of patients were tested for NMO-IgG. Group 1 consisted of 22 patients with acute partial transverse myelitis, group 2 consisted of 4 patients with definite NMO (by 1999 criteria of Wingerchuk et al), and group 3 consisted of 6 patients with definite multiple sclerosis. MAIN OUTCOME MEASURE: NMO-IgG status. A commercially available assay for NMO antibodies was performed at the Mayo Clinic. Testing was performed during the convalescent stage of the illness. RESULTS: Of the 22 patients with acute partial transverse myelitis, only 1 was seropositive for NMO-IgG at presentation. This patient subsequently developed recurrent episodes of longitudinally extensive transverse myelitis that are typicaly seen in association with NMO-IgG. Three of the 4 patients meeting criteria for NMO were seropositive. None of the patients with multiple sclerosis had NMO-IgG detected. CONCLUSION: NMO-IgG is rarely encountered in patients with acute partial transverse myelitis, which is in sharp contrast to the high frequency of this antibody in patients with NMO and longitudinally extensive transverse myelitis.     

Inflammatory transverse myelitis: evolving concepts

PURPOSE OF REVIEW: Acute transverse myelitis is a pathogenetically heterogeneous inflammatory disorder of the spinal cord. Here we describe recent advances in inflammatory non-infectious transverse myelitis. Particular attention will be paid to the serum autoantibody marker NMO-IgG and its application to acute transverse myelitis. RECENT FINDINGS: The recent identification of neuromyelitis optica-IgG, a novel marker of neuromyelitis optica spectrum disorders (including longitudinally extensive transverse myelitis), contributes to an evolving understanding of acute transverse myelitis. Other serological markers, such as collapsin response-mediator protein-5 -IgG and amphiphysin-IgG, predict specific cancers in the setting of a paraneoplastic acute transverse myelitis. Furthermore, novel inflammatory markers such as interleukin-6 or other proteins in their signaling pathways may represent markers of disease severity and potential therapeutic targets. Additional cerebrospinal fluid biomarkers, such as protein 14-3-3 and neuron-specific enolase, may be useful prognostic indicators in transverse myelitis. Acute transverse myelitis in children, in contrast to adults, is more likely to be longitudinally extensive, and has a better prognosis and lower likelihood of recurrence. Prognostic factors in pediatric transverse myelitis are reviewed. SUMMARY: The recent identification of novel biomarkers associated with acute transverse myelitis has led to a better understanding of the spectrum of disorders associated with inflammatory transverse myelitis, as well as a greater appreciation of its diverse and complex pathogenetic basis.     

The Etiological Spectrum of Acute Sensory Myelitis

Background and Purpose

Acute myelitis patients exhibiting only sensory deficits upon initial presentation are not commonly encountered in clinical practice, but they definitely exist. Since acute sensory myelitis has not been investigated previously, this study evaluated the etiological spectrum of the condition with the aim of describing the clinical characteristics thereof.

Methods

Patients with acute myelitis who presented at the Ewha Womans University Medical Center (during 1999-2012) and the National Cancer Center (during 2005-2014) with only sensory symptoms as first clinical features were enrolled in this study. Their medical records, electrophysiological and laboratory data, and MRI findings were analyzed retrospectively.

Results

Of a total of 341 acute myelitis patients, 52 (15%) were identified as having acute sensory myelitis. The male-to-female ratio of these patients was 35:17, and their age at the onset of the condition was 41.7±10.5 years (mean±SD; range, 24-72 years). Acute sensory myelitis developed in patients with multiple sclerosis (MS; 14%), neuromyelitis optica spectrum disorder (NMOSD; 17%), and acute myelitis associated with concurrent systemic diseases including Behçet''s disease and cancer (6%). Despite detailed evaluation, the etiology of 33 patients with acute myelitis could not be determined. Longitudinally extensive transverse myelitis on spinal MRI and progression of the sensory level were observed most commonly in NMOSD patients (89% and 78%, respectively); however, these patients did not exhibit sensory dissociation. Residual negative sensory symptoms were observed more frequently in NMOSD patients (33%) than in those with acute myelitis of unknown cause (24%) or MS (14%). During the long-term follow-up (4.7±2.7 years) of patients who did not undergo maintenance immunotherapy, a monophasic clinical course was common in those with acute myelitis of unknown cause (76%), but not in NMOSD or MS patients.

Conclusions

Accurate identification of the diverse nature of acute sensory myelitis may assist in patient care.     

Acute transverse myelitis in demyelinating diseases among the Chinese

The aim of the study was to characterize the demographic, clinical, and prognostic features of Chinese patients with acute transverse myelitis (ATM). The clinical data from ATM patients in a demyelinating disease database were analyzed retrospectively. Sixty-seven ATM patients with a follow-up duration longer than 2 years were identified. The frequency of neuromyelitis optica-related ATM (NMO-ATM) was high in our cohort (40.3%). Recurrent ATM (R-ATM), with a female predominance, was common in total idiopathic ATM (69.0%, 20/29). In R-ATM with longitudinally extensive spinal cord lesions (LESCLs), the high seropositivity of NMO-IgG, spinal cord lesions mostly involved the central gray matter and severer long-term disability were similar to NMO-ATM. In RTM without LESCLs, low seropositivity of NMO-IgG, preferentially involvement of the peripheral white matter and relative better neurological recovery were consistent with multiple sclerosis-related ATM (MS-ATM). The transition rates to MS in patients with acute partial transverse myelitis (APTM) and acute complete transverse myelitis (ACTM) were not significant (16.7 vs. 6.3%, P = 0.753), while LESCLs (OR = 11.4, P = 0.028) were significantly correlated with transition to NMO. The presence of LESCLs was the only variable showing a higher risk for reaching Rankin 3 (hazard ratio: 2.5, 95% CI: 1.0–6.1). Chinese patients with ATM had demographic, clinical, and prognostic features different from those in Western populations. Idiopathic R-ATM, common in Chinese, is a heterogeneous entity that shares partial clinical, spinal MRI and prognostic features with MS-ATM and NMO-ATM. The length of spinal cord lesion, rather than APTM/ACTM, may be a prognostic factor associated with clinical outcome and long-term disability in our population.     

A score that predicts aquaporin-4 IgG positivity in patients with longitudinally extensive transverse myelitis

Background and purpose

Longitudinally extensive transverse myelitis (LETM) associated with aquaporin-4 autoantibodies (AQP4-IgG) can cause severe disability. Early diagnosis and prompt treatment are critical to prevent relapses. A novel score is described based on clinical and neuroimaging characteristics that predicts AQP4-IgG positivity in patients with LETM.

Methods

Patients were enrolled both retrospectively and prospectively from multiple Italian centers. Clinical and neuroimaging characteristics of AQP4-IgG positive and negative patients were compared through univariate and multivariate analysis.

Results

Sixty-six patients were included. Twenty-seven (41%) were AQP4-IgG positive and median age at onset was 45.5 years (range 19–81, interquartile range 24). Female sex (odds ratio [OR] 17.9, 95% confidence interval [CI] 2.6–381.9; p = 0.014), tonic spasms (OR 45.6, 95% CI 3.1–2197; p = 0.017) and lesion hypointensity on T1-weighted images (OR 52.9, 95% CI 6.8–1375; p = 0.002) were independently associated with AQP4-IgG positivity. The AQP4-IgG positivity in myelitis (AIM) score predicted AQP4-IgG positivity with 85% sensitivity and 95% specificity. Positive and negative likelihood ratios were 16.6 and 0.2 respectively. The inter-rater and intra-rater agreement in the score application were both excellent.

Conclusions

The AIM score predicts AQP4-IgG positivity with good sensitivity and specificity in patients with a first episode of LETM. The score may assist clinicians in early diagnosis and treatment of AQP4-IgG positive LETM.     

Relationship between ischemic stroke locations,etiology subtypes,neurological outcomes,and autonomic cardiac function

ABSTRACT

Background

Post-stroke autonomic nervous dysfunction measured with heart rate variability (HRV) is correlated with the traditional risk factors and poor outcome. This study aimed to investigate the association between HRV and infarct locations, etiology subtypes, and neurological functional outcomes in patients with acute ischemic stroke (AIS).     

Pycnogenol achieves neuroprotective effects in rats with spinal cord injury by stabilizing the mitochondrial membrane potential

ABSTRACT

Objectives

In this study, we aimed to verify the neuroprotective effects of pycnogenol (PYC) on spinal cord injury (SCI) and to determine the underlying mechanisms.