Treatment of MOG antibody associated disorders: results of an international survey.

INTRODUCTION: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD. METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019). RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.

The Brazilian database on pregnancy in multiple sclerosis.

OBJECTIVES: To report the results from the Brazilian database on multiple sclerosis (MS) and pregnancy. METHODS: Retrospective data from MS patients who became pregnant at any time of their disease were sent to a Brazilian database, using a specific file for this purpose. RESULTS: Data on 128 women (142 pregnancies) from 30 neurologists working in 21 cities in Brazil were collected. Patients' average age at pregnancy was 29.8 years (range 16-42). EDSS at start of pregnancy was 1.5±1.4; and the relapse rate in the year preceding pregnancy was 1.2±1.5. Exposure to medication at any time during pregnancy was high (69.7%): 48.6% to interferon beta; 14.1% to glatiramer acetate; and 7% to other immunomodulatory and immunosuppressive drugs. There was a significant decrease in relapse rate during pregnancy. The prevalence of complications was relatively low, with 4.9% of obstetric and 1.4% neonatal unfavorable outcomes. CONCLUSIONS: Our patients had low degrees of disability, short histories of disease, high drug exposure, and relatively high relapse rate in the year previous to pregnancy. Obstetric and neonatal outcomes were successful in over 90% of our patients.

Profile of the Brazilian scientific production in multiple sclerosis.

This paper analyzes the profile of the Brazilian output in the field of multiple sclerosis from 1981 to 2004. The search was conducted through the MEDLINE and LILACS databases, selecting papers in which the term "multiple sclerosis" was defined as the main topic and "Brazil" or "Brasil" as others. The data were analyzed regarding the themes, the state in Brazil and institution where the papers were produced, the journals where the papers were published, journal's impact factor, and language. The search disclosed 141 documents (91 from MEDLINE and LILACS, and 50 from LILACS only) published in 44 different journals (23 of them MEDLINE-indexed). A total of 111 documents were produced by 17 public universities, 29 by 3 private medical schools and 1 by a non-governmental organization. There were 65 original contributions, 37 case reports, 20 reviews, 6 PhD dissertations, 5 guidelines, 2 validation studies, 2 clinical trials, 2 chapters in textbooks, 1 Master of Science thesis, and 1 patient education handout. The journal impact factor ranged from 0.0217 to 6.039 (median 3.03). Of 91 papers from MEDLINE, 65 were published by Arquivos de Neuro-Psiquiatria. More than 90% of the papers were written in Portuguese. São Paulo was the most productive state in the country, followed by Rio de Janeiro, Minas Gerais and Paraná. Eighty-two percent of the Brazilian output came from the Southeastern region.

Profile of the Brazilian scientific production in multiple sclerosis

This paper analyzes the profile of the Brazilian output in the field of multiple sclerosis from 1981 to 2004. The search was conducted through the MEDLINE and LILACS databases, selecting papers in which the term "multiple sclerosis" was defined as the main topic and "Brazil" or "Brasil" as others. The data were analyzed regarding the themes, the state in Brazil and institution where the papers were produced, the journals where the papers were published, journal's impact factor, and language. The search disclosed 141 documents (91 from MEDLINE and LILACS, and 50 from LILACS only) published in 44 different journals (23 of them MEDLINE-indexed). A total of 111 documents were produced by 17 public universities, 29 by 3 private medical schools and 1 by a non-governmental organization. There were 65 original contributions, 37 case reports, 20 reviews, 6 PhD dissertations, 5 guidelines, 2 validation studies, 2 clinical trials, 2 chapters in textbooks, 1 Master of Science thesis, and 1 patient education handout. The journal impact factor ranged from 0.0217 to 6.039 (median 3.03). Of 91 papers from MEDLINE, 65 were published by Arquivos de Neuro-Psiquiatria. More than 90 percent of the papers were written in Portuguese. São Paulo was the most productive state in the country, followed by Rio de Janeiro, Minas Gerais and Paraná. Eighty-two percent of the Brazilian output came from the Southeastern region.

Chemokines in the cerebrospinal fluid of patients with active and stable relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the human central nervous system. Although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. Chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. They are divided into subfamilies on the basis of the location of conserved cysteine residues. We determined the levels of some CC and CXC chemokines in the cerebrospinal fluid (CSF) of 23 relapsing-remitting MS patients under interferon-ss-1a therapy and 16 control subjects using ELISA. MS patients were categorized as having active or stable disease. CXCL10 was significantly increased in the CSF of active MS patients (mean +/- SEM, 369.5 +/- 69.3 pg/mL) when compared with controls (178.5 +/- 29.1 pg/mL, P < 0.05). CSF levels of CCL2 were significantly lower in active MS (144.7 +/- 14.4 pg/mL) than in controls (237.1 +/- 16.4 pg/mL, P < 0.01). There was no difference in the concentration of CCL2 and CXCL10 between patients with stable MS and controls. CCL5 was not detectable in the CSF of most patients or controls. The qualitative and quantitative differences of chemokines in CSF during relapses of MS suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease.

Chemokines in the cerebrospinal fluid of patients with active and stable relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the human central nervous system. Although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. Chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. They are divided into subfamilies on the basis of the location of conserved cysteine residues. We determined the levels of some CC and CXC chemokines in the cerebrospinal fluid (CSF) of 23 relapsing-remitting MS patients under interferon-ß-1a therapy and 16 control subjects using ELISA. MS patients were categorized as having active or stable disease. CXCL10 was significantly increased in the CSF of active MS patients (mean ± SEM, 369.5 ± 69.3 pg/mL) when compared with controls (178.5 ± 29.1 pg/mL, P < 0.05). CSF levels of CCL2 were significantly lower in active MS (144.7 ± 14.4 pg/mL) than in controls (237.1 ± 16.4 pg/mL, P < 0.01). There was no difference in the concentration of CCL2 and CXCL10 between patients with stable MS and controls. CCL5 was not detectable in the CSF of most patients or controls. The qualitative and quantitative differences of chemokines in CSF during relapses of MS suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease.

Simple phonic tic in multiple sclerosis.

Movement disorders occurring in association with multiple sclerosis (MS) are rare. Among them paroxysmal dystonia is the most common, although chorea, ballism, palatal myoclonia, spasmodic torticollis, writer's cramp and generalized dystonia have been reported. We describe a 34-year old woman with MS who developed simple phonic tic characterized by throat-clearing sounds. Magnetic resonance imaging showed demyelinating lesions involving the thalamus and basal ganglia. This is the first report of tic disorder occurring as a manifestation of MS.

[Historical aspects of multiple sclerosis]. / Aspectos históricos de la esclerosis múltiple.

INTRODUCTION: Multiple sclerosis (MS) is one of the most common diseases of the central nervous system (CNS) in young adults. MS is the most common disorder of the central nervous system in young people living in temperate climate regions. Although a few references to possible cases of the disease come from the xiii century, its scientific observation and systematic study only started in the late xix century. DEVELOPMENT: Robert Carswell e Jean Cruveilhier were the first investigators to document the pathological lesions while the clinical picture was first studied by Charcot. In spite of a huge number of infectious agents has been proposed for the etiology of MS and a genetic susceptibility trait recently defined, the ultimate cause of the disease remains to be determined. The development of diagnostic criteria sets, clinical disability scales and image methods in the latter half of the last century has provided investigators with useful research tools allowing unprecedented advances. In the last 30 years ACTH and corticosteroids have been employed as treatment for MS relapses. Starting in 1993 a new class of drugs called disease modifying agents, such as interferon beta and more recently glatiramer acetate, was introduced with encouraging results. CONCLUSIONS: MS is postulated to be a cell mediated autoimmune disease directed against CNS myelin components and characterized by inflammation and chronic demyelination. This paper is a review of the principal most significant events in the search for knowledge of the disease in the world.

Schistosomal myeloradiculopathy due to Schistosoma mansoni: report on 23 cases.

Schistosoma mansoni infection is likely to be responsible for a significant proportion of cases of myelopathy occurring in areas where schistosomiasis is endemic. The aim of this study is to describe the clinical, laboratory and therapeutic data of 23 patients with schistosomal myeloradiculopathy. The medical records of 23 patients with schistosomal myelopathy admitted to two general hospitals of Belo Horizonte (MG), in Brazil, from 1995 to 1999, were reviewed retrospectively. Seventeen patients were male (74%). The mean age for the whole group was 27 years. Lower limb weakness and associated lumbar and/or lower limb pain were reported by 20 patients (87%), and 16 (70%) were unable to walk. All individuals presented urinary retention and 19 (83%) complained of intestinal dysfunction. The treatment was based on the association of antischistosomal drugs and corticosteroids. Five patients (22%) presented a full response to treatment, 13 (57%) partial response without functional limitations and 4 (17%) partial improvement with limitations or no response. Three out of the 4 patients who stopped steroids before 45 days of treatment developed recurrence of the symptoms and signs of myelopathy. Our cases demonstrate the severe presentation of the disease and the data disclosed here suggest that treatment with steroids should be kept for months after clinical improvement.

Schistosomal myeloradiculopathy due to Schistosoma mansoni: report on 23 cases

Schistosoma mansoni infection is likely to be responsible for a significant proportion of cases of myelopathy occurring in areas where schistosomiasis is endemic. The aim of this study is to describe the clinical, laboratory and therapeutic data of 23 patients with schistosomal myeloradiculopathy. The medical records of 23 patients with schistosomal myelopathy admitted to two general hospitals of Belo Horizonte (MG), in Brazil, from 1995 to 1999, were reviewed retrospectively. Seventeen patients were male (74 percent). The mean age for the whole group was 27 years. Lower limb weakness and associated lumbar and/or lower limb pain were reported by 20 patients (87 percent), and 16 (70 percent) were unable to walk. All individuals presented urinary retention and 19 (83 percent) complained of intestinal dysfunction. The treatment was based on the association of antischistosomal drugs and corticosteroids. Five patients (22 percent) presented a full response to treatment, 13 (57 percent) partial response without functional limitations and 4 (17 percent) partial improvement with limitations or no response. Three out of the 4 patients who stopped steroids before 45 days of treatment developed recurrence of the symptoms and signs of myelopathy. Our cases demonstrate the severe presentation of the disease and the data disclosed here suggest that treatment with steroids should be kept for months after clinical improvement

The clinical profile of childhood optic neuritis.

PURPOSE: To report the clinical features and outcome of a series of children with optic neuritis. METHODS: We reviewed the medical records of patients up to 16 years old with optic neuritis. Group 1 comprised children seen up to two weeks after the onset of visual loss; Group 2 comprised patients already harboring optic atrophy. RESULTS: There were 15 boys and 12 girls. The mean age was 10.9 years. Bilateral optic neuritis occurred in 10. Optic disc pallor was found in 35%, edema in 46%, and 19% had normal fundus. During follow-up visual acuity improved in all but one eye in Group 1, and in six of seven eyes in children in Group 2. Just one child converted to multiple sclerosis. CONCLUSIONS: This study shows that the clinical features of childhood optic neuritis differ from those observed in adults. In children it has a better visual outcome and a lower conversion rate to multiple sclerosis than in adults.

[Recommendations for the use of immunomodulatory drugs in multiple sclerosis: the BCTRIMS consensus] [Brazilian Committee for Treatment and Research in Multiple Sclerosis]. / Recomendações quanto ao uso de drogas imunomoduladoras na esclerose múltipla: o consenso do BCTRIMS.

After brief considerations about clinical course and diagnosis in multiple sclerosis, the members of the BCTRIMS present some recommendations for the use of the immunomodulatory drugs in the treatment of this disease.

[Etiological and clinical characteristics of infectious optic neuritis]. / Caracterização etiológica e clínica das neurites ópticas infecciosas.

Fifty-one patients with infectious optic neuritis (ION) with no associated choroidal or retinal involvement were studied in relation to the etiologic agents, and to the epidemiological and clinical features to look up features which could be used to distinct them from the demyelinating optic neuritis (DON) which have a well-known tendency to convert to multiple sclerosis. Bilateral involvement was found in 23 patients (45.1%), simultaneously in 18 cases. Sex distribution was 2M:1F. The ages ranged from 1 to 82 years (median 34.8); 1/3 of the patients were younger than 20 and 1/3 were 50 years of age or older. Syphilis was found in 19 patients being the single most common etiology, whereas viral infections were found in 41.2% of the cases. Visual acuity was severely damaged in most patients and was worse than 20/200 in 57.3% of the involved eyes. Color vision was affected in 91.8%. Visual field defects were found in 92.2%, with predominance of the central defects (40.7%). The optic disc was abnormal in 90.5% of the eyes. This study clearly demonstrates that ION and DON have distinct epidemiological and clinical features. The awareness of these differences may help clinicians to follow different paths for the correct diagnosis and appropriate treatment and prognostic orientation of their patients.

HTLV-I associated uveitis, myelopathy, rheumatoid arthritis and Sjögren's syndrome.

A 62 year-old white female presented with a 10-year-history of slowly progressive spastic paraparesis, pain and dysesthesia in the lower limbs and sphincter disturbance. A few years after the onset of the neurologic symptoms she developped migratory arthritis with swelling of the knees and pain on palpation of knees and fingers, dry eyes, mouth and skin. Two months before admission she presented bilateral nongranulomatous anterior uveitis. Examination revealed spastic paraparesis with bilateral Babinski sign, a decreased sensation level below L3, decreased vibration sense in the lower extremities, and a postural tremor of the upper limbs. Laboratory work-up disclosed HTLV-I positive tests in the blood and cerebrospinal fluid (CSF), and a mild pleocytosis in the CSF with a normal protein content. Nerve conduction velocity studies were normal. The present case shows the association of uveitis, arthritis and Sjögren's syndrome in a patient with tropical spastic paraparesis/human T-cell lymphotropic virus type I (HTLV-I) associated myelopathy (TSP/HAM), and illustrates the wide spectrum of clinical manifestations which may accompany this infection with this virus.

Multiple sclerosis and positive Lyme serology.

As Lyme neuroborreliosis (LNB) may clinically mimic multiple sclerosis (MS) the presence of antibodies to Borrelia burgdorferi in serum of patients with a MS-like disease in non-endemic areas for Lyme disease may be troublesome. We report the case of a 45-year-old white female with the diagnosis of relapsing/remitting form of MS due to a 15-year history of optic neuritis and recurrent episodes of motor and sensation disturbance in the upper right limb and in both lower extremities associated with bladder dysfunction. A magnetic resonance imaging of the brain revealed multiple high intensity periventricular white matter lesions. The patient had been exposed to ticks but did not recall the presence of erythema migrans. ELISA for Lyme disease was positive in two different laboratories and the positive serology was confirmed by Western blotting. No convincing response followed treatment with ceftriaxone. Although it is clear that the patient had been infect by Borrelia burgdorferi the relationship of this spirochetal infection with the neurological disease could not be ascertained.

[The arteritic type of anterior ischemic optic neuropathy. Study of 25 cases]. / A forma arterítica da neuropatia óptica isquêmica anterior. Estudo de 25 casos.

The clinical, laboratorial perimetric and fluorescein angiographic features of the arteritic type of the anterior ischemic optic neuropathy (A-AION) was studied in 25 patients (40 eyes) in order to characterize the profile of the disease and to allow the differential diagnosis with the non-arteritic anterior ischemic optic neuropathy (NA-AION) and other disorders of the optic nerve. The A-AION occurred in patients 60 to 88 years old (mean 74 years) and was highly predominant in females (64 per cent). Fifteen patients had both eyes involved, either simultaneously or usually within few days or weeks after the initial involvement. Headache and eye pain were the most commonly observed prodromic complaints whereas systemic symptoms of giant cell arteritis (GCA) were seen in all patients. The laboratorial abnormalities most commonly found were high values of reactive C protein, plasmatic fibrinogen and erythrocyte sedimentation rate. In the great majority of the patients visual acuity was severely affected. The optic disc was always abnormal, usually showing a pale edema. In addition to that retinal changes were commonly found. Goldmann perimetry disclosed a wide variety of visual fields abnormalities, the most common of them being inferior altitudinal defects. Fluorescein fundus angiography revealed delayed or absent disc fluorescence, or sectorial or diffuse hypofluorescence or hyperfluorescence of the optic disc. Choroidal filling delay was the most characteristic and frequent angiographic finding in the arteritc type of the disease.