Virgen de la Arrixaca University Hospital
Neurology

Author Of 3 Presentations

Disease Modifying Therapies – Risk Management Poster Presentation

P0353 - Lymphopenia in patients treated with dimethyl fumarate. Risk factors and clinical significance. Experience in daily clinical practice (ID 1420)

Speakers
Presentation Number
P0353
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Dimethyl fumarate (DMF) treatment can cause sustained severe lymphopenia, which may be associated with an increased risk of developing infections, leading to discontinuation of treatment.

Objectives

The objective of the study is to identify the frequency and severity of lymphopenia and analyze risk factors for its development in our sample of patients with remitting recurrent multiple sclerosis (RRMS) treated with DMF. Another objective is to analyze whether the appearance of lymphopenia influences the evolution of the disease.

Methods

We carried out a retrospective, descriptive and analytical study of 50 RRMS patients treated with DMF between October 2014 and June 2020, followed for an average of 36.94 months.

Results

A total of 22 patients (44%) developed lymphopenia. Eleven patients developed grade 2 and 7 patients grade 3 lymphopenia. Eighty-two percent of patients developed lymphopenia in the first year. Only in 4 patients did lymphopenia resolve, 3 cases of grade II and 1 case of grade I lymphopenia.

Those patients who developed lymphopenia had a lower absolute lymphocyte count (ALC) before the start of DMF (p 0.013). Although with a trend towards statistical significance (OR 3.88, CI 0.87-17.3. p 0.068) an age at the start of DMF greater than 55 years was not correlated with an increased risk of lymphopenia. Seventy-six percent of the patients had received previous treatments for RRMS, including glatiramer acetate(22.5%), interferon (32.5%), teriflunomide (15.5%) and fingolimod (2.5%), without posing a risk of developing grade II-III lymphopenia.

In our population, the development of lymphopenia was not correlated with a greater probability of reaching NEDA3 at 2 years. Neither was it found to be associated with an increased risk of clinical or radiological activity or discontinuation due to ineffectiveness.

In our sample, lymphopenia was associated with a four times greater risk of developing infections (OR 4.1, CI 1.07-16.1. P 0.033), although all cases were mild. Six patients (12%) discontinued DMF due to sustained grade III lymphopenia. Three of them maintained an ALC of less than 800 at least 6 months after the end of DMF.

Conclusions

In our series, lymphopenia is a frequent adverse effect, it appears especially in the first year and in most cases it remains, even months after stopping DMF. Therefore, surveillance should be increased and control of ALC should be maintained given the increased risk of infection if lymphopenia develops, especially in those patients with lower ACL at baseline.

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Disease Modifying Therapies – Mechanism of Action Poster Presentation

P0358 - Multiple Sclerosis with anti-N-methyl-D-aspartate receptor immunoglobulin G antibodies. An unusual relationship. (ID 1790)

Abstract

Background

The association between demyelinating diseases and the presence of anti-N-methyl-D-Aspartate receptor antibodies (anti-NMDAR-ab) has been analyzed in recent years. This infrequent coexistence has been seen above all with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein associated disorders (MOGAD). The overlap with multiple sclerosis (MS) has been poorly described. In most of the published cases, patients presented symptoms consistent with NMDAR encephalitis, before, after, or concomitantly with demyelinating disease.

Objectives

We present the case of a patient with newly diagnosed Relapsing Remitting Multiple Sclerosis (RRMS) and with detection of anti-NMDAR-ab, without symptoms suggestive of encephalitis.

Methods

27-year-old woman, with gender identity disorder who was admitted for distal paresthesias in her lower limbs and in her hands which had developed in the last week. The examination revealed hypoesthesia and moderate hypopalestesia in these areas, with hyperreflexia in her lower limbs, suspecting myelitis as a diagnostic possibility.

Results

We performed a lumbar puncture that showed mild pleocytosis with normal proteins, increased Ig G and the presence of oligoclonal bands Ig G in cerebrospinal fluid (CSF).

Brain and spinal cord magnetic resonance showed twelve brain lesions, as well as several lesions in the cervical and dorsal spinal cord with a typical demyelinating appearance of MS and some of them with gadolinium enhancing.

In an autoimmunity study, anti-NMDAR-ab were detected at high titers in CSF and serum, with negative anti-aquoporin 4 (AQP4) and anti-MOG Ig G antibodies (performed in two centers using cell-based assay).

Given the presence of anti-NMDAR-ab, it was decided to extend the study by conducting a screening test for occult neoplasia that was negative, as well as an electroencephalogram and a neuropsychological study that did not show data suggestive of anti-NMDAR-ab clinical expression.

In the presence of a typical clinical syndrome together with characteristic findings in the complementary tests of RRMS, we treated the sensitive spinal cord outbreak with megadoses of corticosteroids with full resolution. The review of the little published evidence shows cases similar to ours that months or years later can develop NMDAR encephalitis. Given this risk, we believed that the use of anti-CD20 therapy of proven efficacy in RRMS was justified, which in turn presents a mechanism of action similar to Rituximab, widely used in pathology secondary to anti-NMDAr-ab. Finally, after a few weeks of stability, Ocrelizumab treatment was started, with a good response.

Conclusions

The coexistence of MS and NMDAR encephalitis is an entity under study. In our case, the anti-NMDAR-ab is asymptomatic so far, but it forces us to dismiss neoplasia, to monitor symptoms in the following years, and it has also been decisive in the choice of the disease-modifying drug.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0724 - Isolated recurrent non longitudinally extensive myelitis in two MOG positive patients (ID 1399)

Abstract

Background

The presence of antibodies against the oligodendrocyte myelin glycoprotein (antiMOG-ab) is related to demyelinating disease of the central nervous system that especially affects the optic nerves (ON) and spinal cord (SC).

Objectives

Isolated and recurrent involvement of the SC without involvement of the ON is infrequent. More infrequently, this involvement occurs in the form of non-longitudinally extensive transverse myelitis (NLEMT).

Methods

We present two patients with the presence of antiMOG-ab and two episodes of NLEMT without ON involvement during the course of the disease.

Results

The first case is a 43-year-old man, with a history of pars planitis in childhood, who was admitted in March 2019 with lower limbs (LL) sensory symptoms and urinary sphincter disturbance of two weeks of evolution. Spinal magnetic resonance imaging (MRI) revealed an enhancing cord lesion at T4 level. The patient showed a positive determination of antiMOG-ab in serum. After treatment with methylprednisolone (MP) megadose, the patient recovered without sequelae. Chronic immunosuppression was not started after this first episode. In June 2020, symptoms compatible with a new transverse myelitis (TM) began. Complementary tests showed a new T9-T10 gadolinium (GD) enhancing lesion in MRI, and maintained antiMOG-ab positivity. It was treated with MP megadose with symptons resolution. Currently, the patient is receiving prednisone at a dose of 1mg/ kg and is pending the initiation of Rituximab.

The second case is a 48-year-old man, with no history of interest, who was admitted in November 2009 for symptoms of sensory disturbance and weakness in LL. The MRI study showed the presence of a GD enhancing lesion at C3 level and no additional alterations were observed by complementary tests. AntiMOG-ab was not determined. The patient improved after treatment with MP megadoses. Interpreted as idiopathic TM it remained asymptomatic until December 2019, when it started a clinical picture compatible with a Brown-Sequard syndrome. The spinal MRI revealed a new lesion at C6 level. On this occasion, a positive determination of antiMOG-ab was obtained in serum. It was treated with MP megadoses with almost complete resolution of the symptoms. Currently on Rituximab treatment with good response after six months.

In both patients, the first determination of anti MOG-ab was obtained using ELISA techniques in our hospital laboratory. These results were confirmed in an external laboratory using cell-based assay techniques.
In both cases, optical coherence tomography and evoked potentials were performed, which did not show alterations of ON.

Conclusions

In patients with recurrent NLEMT and no involvement of ON, a determination of antiMOG-ab should be performed as part of their evaluation.

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Presenter Of 1 Presentation

Disease Modifying Therapies – Mechanism of Action Poster Presentation

P0358 - Multiple Sclerosis with anti-N-methyl-D-aspartate receptor immunoglobulin G antibodies. An unusual relationship. (ID 1790)

Abstract

Background

The association between demyelinating diseases and the presence of anti-N-methyl-D-Aspartate receptor antibodies (anti-NMDAR-ab) has been analyzed in recent years. This infrequent coexistence has been seen above all with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein associated disorders (MOGAD). The overlap with multiple sclerosis (MS) has been poorly described. In most of the published cases, patients presented symptoms consistent with NMDAR encephalitis, before, after, or concomitantly with demyelinating disease.

Objectives

We present the case of a patient with newly diagnosed Relapsing Remitting Multiple Sclerosis (RRMS) and with detection of anti-NMDAR-ab, without symptoms suggestive of encephalitis.

Methods

27-year-old woman, with gender identity disorder who was admitted for distal paresthesias in her lower limbs and in her hands which had developed in the last week. The examination revealed hypoesthesia and moderate hypopalestesia in these areas, with hyperreflexia in her lower limbs, suspecting myelitis as a diagnostic possibility.

Results

We performed a lumbar puncture that showed mild pleocytosis with normal proteins, increased Ig G and the presence of oligoclonal bands Ig G in cerebrospinal fluid (CSF).

Brain and spinal cord magnetic resonance showed twelve brain lesions, as well as several lesions in the cervical and dorsal spinal cord with a typical demyelinating appearance of MS and some of them with gadolinium enhancing.

In an autoimmunity study, anti-NMDAR-ab were detected at high titers in CSF and serum, with negative anti-aquoporin 4 (AQP4) and anti-MOG Ig G antibodies (performed in two centers using cell-based assay).

Given the presence of anti-NMDAR-ab, it was decided to extend the study by conducting a screening test for occult neoplasia that was negative, as well as an electroencephalogram and a neuropsychological study that did not show data suggestive of anti-NMDAR-ab clinical expression.

In the presence of a typical clinical syndrome together with characteristic findings in the complementary tests of RRMS, we treated the sensitive spinal cord outbreak with megadoses of corticosteroids with full resolution. The review of the little published evidence shows cases similar to ours that months or years later can develop NMDAR encephalitis. Given this risk, we believed that the use of anti-CD20 therapy of proven efficacy in RRMS was justified, which in turn presents a mechanism of action similar to Rituximab, widely used in pathology secondary to anti-NMDAr-ab. Finally, after a few weeks of stability, Ocrelizumab treatment was started, with a good response.

Conclusions

The coexistence of MS and NMDAR encephalitis is an entity under study. In our case, the anti-NMDAR-ab is asymptomatic so far, but it forces us to dismiss neoplasia, to monitor symptoms in the following years, and it has also been decisive in the choice of the disease-modifying drug.

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