Incomplete Transverse Myelitis Research Articles

Anti-Neurofascin Antibodies Associated with White Matter Diseases of the Central Nervous System: A Red Flag or a Red Herring?

Autoantibodies against nodal and paranodal proteins, specifically anti-neurofascin antibodies (ANFAs), have been recently described in central and peripheral nervous system demyelinating disorders. We retrospectively reviewed the charts of six individuals evaluated at our Multiple Sclerosis Program who tested positive for serum ANFAs on Western blot. We describe these patients’ clinical and diagnostic findings and attempt to identify features that might guide clinicians in checking for ANFAs. In our series, the women-to-men ratio was 2:1. At presentation, the median age was 60 years (range 30–70). The clinical presentation was pleiotropic and included incomplete transverse myelitis (n = 3), progressive myelopathy (n = 1), recurrent symmetric polyneuropathy (n = 1), and nonspecific neurological symptoms (n = 1). Atypical features prompting further workup included coexisting upper and lower motor neuron features, older age at presentation with active disease, atypical spinal cord MRI features, and unusual cerebrospinal fluid findings. The serum ANFAs panel was positive for the NF-155 isoform in five patients (IgM n = 2; IgG n = 2; both n = 1) and the NF-140 isoform in two (IgG n = 2). Larger studies are needed to assess the relevance of ANFAs in demyelinating nervous system diseases, their impact on long-term clinical outcomes, and associated therapeutic implications.

Transverse myelitis associated with primary biliary cirrhosis: clinical, laboratory, and neuroradiological features

Purpose Only five patients diagnosed with transverse myelitis (TM) associated with primary biliary cirrhosis (PBC) have been reported in the literature to date. We report two additional patients with TM associated with PBC at our hospital and review all seven cases. Materials and methods An association between neuromyelitis optic spectrum disease (NMOSD) and PBC is reported for the first time in one of our patients. The second patient was diagnosed with TM associated with PBC without Sjögren's syndrome (SS). A literature review was performed using the PubMed database. Results All patients diagnosed with TM associated with PBC were female with a median age of 53 years. TM was associated with SS in 71.4% of the patients. Complete TM and incomplete TM were diagnosed in 71.4% and 28.6% of the patients. The erythrocyte sedimentation rate was increased in 83.3% of patients. All patients were positive for anti-mitochondrial antibodies. Other autoantibodies, including anti-nuclear antibodies, rheumatoid factor, anti-SSA antibody, were detected in some patients. Cerebrospinal fluid analysis was abnormal in 83.3% of patients. The spinal cord lesions involved more than three vertebral segments in 85.7% of patients. Glucocorticoids were administered in 85.7% of patients, and good responses were observed. Conclusions The association between TM and PBC may be missed by neurologists. More attention should be paid to the association between NMOSD and PBC. Most patients show SS and may experience relapse, and there is a good rationale for early commencement of immunosuppressive therapy.

Protocolo diagnóstico del paciente con sospecha de enfermedad desmielinizante

Multiple sclerosis (MS) is the most common autoimmune inflammatory disease of the central nervous system and is pathologically characterized by multifocal areas of demyelination with loss of oligodendrocytes, glial scarring and axonal damage in more advanced stages. MS is a very common cause of disability in young people. Although there are atypical presentations, the clinical diagnosis is relatively simple in young patients with typical onset symptoms (such as optic neuritis, brainstem syndrome and incomplete transverse myelitis) and demyelinating lesions observed in the magnetic resonance imaging that meet the dissemination criteria in time and space. The diagnosis of MS can be reached with the first clinical flare-up according to the revised 2017 McDonald criteria, in the absence of another more plausible aetiology. A cerebrospinal fluid study can help determine this disease's inflammatory nature by demonstrating intrathecal synthesis and the presence of oligoclonal bands of IgG, considered a diagnostic criterion in the primary progressive forms of MS and a dissemination criterion in time in a first clinical flare-up.

Status migrainosus as an initial presentation of multiple sclerosis.

BackgroundDemyelinating plaques may induce headache through disruption of the pathways, which are implicated in the pathogeneses of migraine. We report a case of 25-year-old female patient, who presented with status migrainosus fulfilling the criteria of international classification of headache disorder. She was eventually diagnosed with multiple sclerosis (MS) after an extensive work-up and long-term clinical and radiological follow-up.FindingsAt the onset of status migrainosus, magnetic resonance imaging (MRI) revealed the presence of several demyelinating lesions fulfilling Swanton criteria. She was started on migraine prophylactic treatment but there was no subsequent response. One year later, she presented with recurrent status migrainosus and a follow-up MRI revealed multiple gadolinium-enhancing lesions in the brain. She was treated with abortive migraine medications. Within the following 2 year, she developed ascending parasthesia and weakness of both lower limbs indicative of incomplete transverse myelitis in association with recurrent status migrainosus. A diagnosis of MS was established based on a follow-up MRI that satisfied the revised 2010 McDonald criteria. Both the headache and neurological signs improved with IV methylprednisolone therapy. Her headache entered remission after initiation of a disease modifying therapy.ConclusionStatus migrainosus can be the initial presentation of MS. Unresponsiveness to migraine prophylactic therapy in the presence of active demyelinating plaque in MRI brain may pose a diagnostic challenge and a diagnosis of MS might be considered.

Differences in oligoclonal bands and visual evoked potentials in patients with radiologically and clinically isolated syndrome

The aim of this study was to determine the prevalence of cerebrospinal fluid (CSF) and visual evoked potentials (VEP) abnormalities, and ANA titers in patients with either clinically or radiologically isolated syndrome (CIS and RIS). We gathered records from 330 hospitalized patients diagnosed with CIS/RIS within a 3-year period. Symptoms, CSF findings, VEP and ANA titers were analyzed. Incomplete transverse myelitis was the presenting symptom in 32.7%, optic neuritis in 22.7%, brainstem/cerebellar symptoms in 19.4%, hemispheral symptoms in 2.7% and multifocal symptoms in 15.2% of patients in the CIS cohort. We identified 24 (7.3%) patients with atypical or no symptoms-RIS cohort. Positive oligoclonal bands (OCB) were found in 75.5% patients. When we divided the patients into CIS and RIS groups, the presence of OCB was 82.4 and 44%, respectively. VEP were performed in 87.3% patients and prolonged latencies were found in 39.6% of them (43.8 and 14.3% in the CIS and RIS cohort, respectively). ANA were positive in 15.2% (14.7 and 16% in the CIS and RIS cohort, respectively) of patients. RIS patients had statistically significant lower percentages of positive OCB and positive VEP (P=0.002 and 0.001, respectively). Detection of OCB and VEP still has an important role for satisfying the "no better explanation for the clinical presentation" criteria when presented with a patient with a first "radiological" demyelinating episode.

Neuromyelitis Optica Antibodies in Patients With Severe Optic Neuritis in China

Severe visual loss is seen in both multiple sclerosis-associated optic neuritis (ON) and neuromyelitis optica (NMO)-associated ON. NMO (aquaporin 4) antibodies have been reported to have diagnostic and prognostic value for visual and neurological outcomes of recurrent ON. We performed this study to investigate the frequency of NMO antibodies and its prognostic value for visual and neurological outcomes in Chinese patients with severe ON. Single-center prospective cohort study. Detection of NMO antibodies was by indirect immunofluorescence method using human aquaporin 4-transfected cells. Severe ON was defined as visual acuity of 20/200 or worse in at least 1 eye at the nadir of the patients' course. Clinical features at baseline, visual outcome, and sequential neurological events were compared between seropositive and seronegative groups. NMO antibodies were detected in 11 of 34 patients (32.4%) with severe ON. Five seropositive patients with recurrent ON had significantly higher titers (range: 1:512 to 1:65,536; median: 1:512) than those of 6 seropositive patients with only 1 episode (range: 1:16 to 1:512; median: 1:32) (P=0.021). Female to male ratio (10:1) and antinuclear autoantibody positivity in seropositive patients (3 of 9, 33.3%) were statistically higher than those of the seronegative group (12:11; 0 of 19; P=0.026). The seropositive patients had significantly poorer visual outcomes than seronegative patients (P=0.025). During the averaged 32-month follow-up, 2 of 11 seropositive patients (18.2%) developed clinically incomplete transverse myelitis, while no similar symptoms were reported in the seronegative group. NMO antibody positivity is relatively high in Chinese patients with severe ON and suggests a poorer visual outcome, probably higher risk of developing spinal cord lesions and a closer association with systemic autoimmune disorders.

Mycobacteria Infection in Incomplete Transverse Myelitis Is Refractory to Steroids: A Pilot Study

Incomplete transverse myelitis (ITM) of unknown origin is associated with high rates of morbidity and mortality. This prospective, open-label study was undertaken to determine whether antituberculous treatment (ATT) might help patients with ITM whose condition continues to deteriorate despite receiving IV methylprednisolone treatment. The study consisted of 67 patients with steroid-refractory ITM in whom Mycobacterium tuberculosis (MTB) was suspected clinically and in whom other known causes of myelopathy were excluded. The study occurred from January 2003 to June 2010. Patients underwent trial chemotherapy with ATT. Efficacy was assessed by the American Spinal Injury Association (ASIA) scoring system, the Barthel Index (BI) and the Hauser Ambulation Index (AI) at baseline, 12 months, and 24 months, using magnetic resonance imaging (MRI). Of the 67 patients enrolled, 51 were assessed and 16 withdrew. At 24 months, 49 patients experienced benefits as indicated by significantly increased ASIA and BI scores. The Hauser AI index also improved with markedly decreased abnormal signals in spinal cord MRI over time. The results from this prospective study provide beneficial clinical and MRI data on the efficacy of ATT in ITM patients and suggests mycobacteria may be an important and neglected cause of myelitis.

A pilot study of mycobacteria infection in incomplete transverse myelitis refractory to steroids

Objective Incomplete transverse myelitis (ITM) of unknown origin is associated with high rates of morbidity and mortality，and treatment options for these patients are few. This pilot study was undertaken to determine whether antituberculous treatment(ATT)might help in patients with ITM whose condition continued to worsen despite receiving IV methylprednisolone treatment. Methods This is a prospective，open-label study. A group of 67 patients with steroid-refractory ITM were included from Jan 2003 to Jun 2009，and known causes of myelopathy were excluded.They underwent trial chemotherapy of ATT. All patients were followed up for at least 1 year after treatment.Efficacy was assessed by the ASIA scoring system，Barthel Index(BI)and Hauser Ambulation Index(AI)at baseline and at 12 months，and magnetic resonance imaging(MRI)changes were also assessed. Results Of 67 patients enrolled，16 withdrew. 51 patients completed the entire course of treatment;and were able to be assessed. At 12 months，49 patients experienced benefits. ASIA rating，BI significantly increased，Hauser AI improved validity，concomitantly with markedly decreased abnormal signals in spinal cord on MRI over time. Conclusions The results from this perspective study provide beneficial clinical and MRI data on the efficacy of ATT in ITM patients，and suggests mycobacteria may be an important and being neglected infection of myelitis.

The challenge of acute non-compressive transverse myelopathies

The challenge of acute non-compressive transverse myelopathies

Multiple sclerosis presented as clinically isolated syndrome: the need for early diagnosis and treatment

To aid in the timely diagnosis of patients who present with clinically isolated syndrome (CIS). We studied 25 patients (18 women, 7 men), originally presented in our clinic with a CIS suggestive of multiple sclerosis (MS). All patients underwent the full investigation procedure including routine tests, serology, cerebrospinal fluid (CSF) examinations, evoked potentials (EPs), and magnetic resonance imaging (MRI) of brain and cervical spinal cord. Patients were imaged at baseline, and every three months thereafter up to a year. The CIS was consisted of optic neuritis in 12 cases, incomplete transverse myelitis (ITM) in 7 cases, Lhermitte sign in 2 cases, internuclear ophthalmoplegia (INO) in 2 cases, mild brainstem syndrome in 1 case, and tonic-clonic seizures in 1 case. Using the baseline and three-month scans 18/25 (72%) patients developed definite MS in one year of follow up while 7 (28%) had no further findings during this observation period. Immunomodulatory treatments were applied to all definite MS patients. In light of new treatments available, MRIs at 3 month intervals are helpful to obtain the definite diagnosis of MS as early as possible.

Acute demyelinating optic neuritis.

Acute demyelinating optic neuritis associated with multiple sclerosis (MS) is the most common cause of inflammation of the optic nerve. The Optic Neuritis Treatment Trial (ONTT) has provided important clinical data on the use of corticosteroids, and demonstrated that patients with characteristic inflammatory lesions within the brain on magnetic resonance imaging had a greater chance of developing clinically definite MS (CDMS). The current approach to patients with optic neuritis has been modified by the results of the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS). Patients with an initial clinical episode of demyelination (optic neuritis, incomplete transverse myelitis, or brain-stem/cerebellar syndrome) and at least two characteristic demyelinating lesions within the brain were randomized to receive interferon beta-1a or placebo after initial treatment with intravenous corticosteroids. At the 3-year point patients treated with interferon beta-1a showed a 50% less risk of CDMS. The results of this study have set the standard for patients with a first bout of demyelinating optic neuritis.

Myelitis associated with atopic disorders in Japan: a retrospective clinical study of the past 20 years.

To clarify the clinical features of myelitis associated with atopic disorders in Japanese patients. We retrospectively studied the clinical, immunological and electrophysiological features of 68 consecutive patients with myelitis of acute or subacute onset diagnosed at Kyushu University Hospital during the past 20 years. While only 2 of 28 (7%) patients with myelitis diagnosed between 1979 and 1993 had either atopic dermatitis (AD) or bronchial asthma (BA), 19 of 40 (48%) patients with myelitis diagnosed between 1994 and 1998 did. Among the 40 patients with myelitis diagnosed between 1994 and 1998, 19 patients with either AD or BA as well as 21 patients without either disease showed a significantly higher level of serum total IgE, higher frequency of hyperIgEaemia and higher frequency of mite antigen-specific IgE than 82 healthy controls. Myelitis patients with AD presenting as persistent paresthesia/dysesthesia in all four limbs showed cervical cord lesions on MRI and abnormalities in upper limb motor evoked potentials but no abnormalities in the cerebrospinal fluid (CSF), while myelitis patients with BA showed preferential involvement of the lower motor neurons clinically and electromyographically. In addition, 12 patients with myelitis who had hyperIgEaemia and mite antigen-specific IgE but neither AD nor BA showed incomplete transverse myelitis with mild motor disability and few CSF abnormalities. The clinical features of myelitis associated with atopic disorders were in part distinguished by the type of preceding atopic disorder, and also were different from those of hyperIgEaemic myelitis with no preceding atopic disorders.