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Issue 3 (2016) – Supplement 3


Special Issue on Inflammatory Demyelinating Diseases of the Central Nervous System

This special issue on Inflammatory Demyelinating Diseases of the Central Nervous System provides an overview of recent advances on diagnosis of idiopathic inflammatory demyelinating diseases of the CNS, illustrates real clinical practice in this setting through various case reports and presents an inflammatory perspective of depression in the context of chronic immune-mediated diseases.

Guest editor:
Joana Guimarães, MD, PhD

Issue Nr:

3

|    Issue date: 2016-10-20

Guest Editorial


Advances on the diagnosis of idiopathic inflammatory demyelinating diseases of the central nervous system - read full article

By: Joana Guimarães

Diagnosis of acquired demyelinating syndromes can sometimes be delayed due to lack of awareness for these group of pathologies among clinicians, consequently, treatment opportunities may be missed. Multiple sclerosis (MS) is the most frequent disease of this group of acquired demyelinating syndromes and diagnosis is usually based on proof of disease dissemination in space and time, after exclusion of other disorders. With the advent of new drug therapies and the evidence that early treatment has significant long term benefits, it is extremely important to make an early, accurate diagnosis of MS; additionally, several MS mimics may require alternative treatments for best long-term outcome. In this Special Issue we present an overview of the recent advances on diagnosis of idiopathic inflammatory demyelinating diseases of the CNS and also case reports that illustrate real clinical practice, hoping that these will be useful for clinicians caring for patients with demyelinating syndromes. In the last selected paper, the inflammatory perspective of depression in the context of chronic immune-mediated diseases, will be discussed.

Special Issue on Inflammatory Demyelinating Diseases of the Central Nervous System

International Journal of Clinical Neurosciences and Mental Health 2016; 3(Suppl. 3):S01
DOI: http://dx.doi.org/10.21035/ijcnmh.2016.3(Suppl.3).S01

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Review Article


Inflammatory demyelinating disease of central nervous system in clinical practice - read full article

By: Joana Guimarães and Carolina Garrett

The diagnosis and treatment of central nervous system (CNS) idiopathic inflammatory demyelinating diseases have been recurrently reviewed over the past two decades. In this group of diseases, Multiple Sclerosis (MS) is the most frequent CNS pathology. However, MS diagnosis requires a systematic exclusion of alternative diagnoses. Our objective with this review is to help standardize and optimize the use of actual diagnosis criteria of inflammatory demyelinating diseases of the CNS, in clinical practice. Its focus is on exclusion of potential MS mimics, differentiating between MS and non-MS idiopathic inflammatory demyelinating conditions, as well as in the diagnosis of common initial isolated clinical syndromes.

Keywords: Multiple sclerosis, Differential diagnosis, Red flags.

Special Issue on Inflammatory Demyelinating Diseases of the Central Nervous System

International Journal of Clinical Neurosciences and Mental Health 2016; 3(Suppl. 3):S02
DOI: http://dx.doi.org/10.21035/ijcnmh.2016.3(Suppl.3).S02

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Case Report


Optic neuritis as presenting manifestation of Behçet's Disease with multisystem involvement - read full article

By: Pedro Barros, Pedro Madureira, Sofia Pimenta, and Joana Guimarães

Introduction: Optic nerve damage unrelated to uveitis, retinal disease and intracranial hypertension are extremely rare in Behçet's Disease (BD) . We report a case of BD with systemic manifestations in which the initial neurological expression was an optic neuritis. 
Case Report: A 20-year-old woman, with recurrent oral aphthosis, presented with acutely right blurred vision and was diagnosed with an optic neuritis. One year later she complained of lack of strength in the left limbs and had a mild left hemiparesis. Two years later she presented with a pancreatitis, skin ulcers and rectal bleeding, and she was diagnosed with multisystemic BD. 
Discussion: We present a case where the clinical and laboratory features were very typical of inflammatory damage to the optic nerve in a patient with a later diagnosis of BD. Recognition of this clinical syndrome, although uncommon, might help clinicians to remember BD in the differential diagnosis of patients presenting with optic neuritis.

Keywords: Optic neuritis, Multisystemic, Behçet's Disease.

Special Issue on Inflammatory Demyelinating Diseases of the Central Nervous System

International Journal of Clinical Neurosciences and Mental Health 2016; 3(Suppl. 3):S03
DOI: http://dx.doi.org/10.21035/ijcnmh.2016.3(Suppl.3).S03

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Case Report


Neuromyelitis Optica Spectrum Disorders: a definite case with Autoimmune Thyroiditis - read full article

By: Luís Braz and Joana Guimarães

Introduction: The concept of Neuromyelitis Optica (NMO) spectrum disorders (NMOSD) encompasses patients with or without NMO-Immunoglobulin G antibodies, fulfilling several clinical and imagiological criteria defined in the international consensus diagnostic criteria of 2015. The coexistence of other autoimmune disorders is common and considered supportive of NMOSD" diagnosis. 
Case Report: A 24 year-old female was admitted due to a sudden painful hypovision in the left eye. The etiological investigation was negative but brain MRI showed T2 hyperintensity of the left optic nerve with gadolinium enhancement, but no signal changes in the brain parenchyma. Eleven years before, she had been diagnosed with autoimmune thyroiditis based on hypothyroid goiter with biopsy-proven chronic lymphocytic inflammation and positive thyroid-related antibodies. Two years after optical neuritis, she developed sensory complaints below a thoracic defined level. MRI revealed a diffuse T2 hyperintense area from D2 to D5. She tested positive for antibody anti-NMO/Aquaporin-4. One month later she had a new episode of left optic neuritis. With two optic neuritis and one longitudinally extensive myelitis, with positive serum test for NMO antibody, she was diagnosed with NMOSD with hypothyroidism and started Azathioprine. 
Discussion: In up to 20-30% patients with NMOSD there is an association with autoimmune thyroiditis. In the literature the reference to “thyroid disease” and seroprevalence of thyroid-related antibodies in NMOSD patients, ranges between 5.6% and 20.5%, but case reports/series with definite clinical, analytical and histological characterization of the thyroiditis are scarce. We present a case of a patient with clear data consistent with autoimmune thyroiditis who, more than a decade later, was diagnosed with NMO

Keywords: Neuromyelitis Optica, Neuromyelitis Optica Spectrum Disorders, Autoimmune Thyroiditis.

Special Issue on Inflammatory Demyelinating Diseases of the Central Nervous System

International Journal of Clinical Neurosciences and Mental Health 2016; 3(Suppl. 3):S04
DOI: http://dx.doi.org/10.21035/ijcnmh.2016.3(Suppl.3).S04

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Case Report


Autoimmune polyglandular syndrome: coincidental or multiple sclerosis mimic? - read full article

By: Ricardo Soares-dos-Reis, Carlos Andrade, Joana Oliveira, Paula Freitas, and Joana Guimarães

Introduction: Multiple sclerosis (MS) is an autoimmune disorder (AD) that has been associated with other ADs, such as thyroiditis. However, association with autoimmune polyglandular syndromes (APS) has seldom been described and some reports documented central nervous system (CNS) involvement by APG. 
Case Report: A 32-year-old female presented with acute, painful, unilateral vision loss. She had past medical history of follicular thyroid adenoma and lymphocytic thyroiditis, having undergone partial thyroidectomy, and diabetes mellitus type 1 (anti-GAD+), fulfilling criteria for APG type III. Her neurological examination was remarkable only for a right afferent pupillary defect. Laboratory tests showed cobalamin deficiency and positivity for anti-thyroid, anti-parietal celland anti-intrinsic factor antibodies. Anti-gliadin and anti-tissue transglutaminase antibodies were negative. Thyroid function, cortisol and adrenocorticotropic hormone (ACTH) levels were normal. Neuraxis MRI showed periventricular, juxtacortical and infratentorial white matter lesions and two small spinal lesions, all with no gadolinium enhancement. Cerebrospinal fluid analysis, including oligoclonal bands was unremarkable. Visual evocated potentials had bilaterally increased latency values. A course of intravenous corticosteroids was started and cobalamin was supplemented. No long-term treatment was initiated. During 2-year follow-up, no other relapse has been recorded and neuraxis MRI remains stable. 
Discussion: Few cases of APG have been described with inflammatory CNS involvement and/or MS. It is unclear whether there is concomitant occurrence of two ADs, or if there is a shared pathophysiology. Moreover, cobalamin deficiency is common in this condition, providing a potential cause for CNS disease. In this case, a watchful waiting approach was adopted.

Keywords: Multiple sclerosis, Autoimmune polyglandular syndrome.

Special Issue on Inflammatory Demyelinating Diseases of the Central Nervous System

International Journal of Clinical Neurosciences and Mental Health 2016; 3(Suppl. 3):S05 

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Case Report


Recurrent Optical Neuritis and Systemic Lupus Erythematosus in a case of benign form of Neuromyelitis Optica Spectrum Disorder - read full article

By: Henrique Costa, Olinda Faria, and Joana Guimarães

Introduction: Neuromyelitis optica (NMO) can occur in the context of autoimmune diseases, particularly systemic lupus erythematosus, in what is now defined as NMO spectrum disorders (NMOSD). 
Case Report: We describe a case of a 32-year old woman with recurrent optic neuritis and a long-standing history of systemic lupus erythematosus (SLE). She was subsequently found to be seropositive for neuromyelitis optica immunoglobulin G (NMO-IgG) (anti-aquaporin-4 antibody) and was diagnosed with NMOSD. Five years after this diagnosis the patient remains clinical stable (no relapses) with low doses of oral prednisolone. 
Discussion: There are no specific recommendations for the treatment of NMO/SLE overlapping cases and few data exist on a possible benign form of NMO. We present a case illustrative of a good-outcome NMOSD.

Keywords: Systemic lupus erythematosus, Neuromyelitis optica, NMO-IgG aquaporin-4 antibody.

Special Issue on Inflammatory Demyelinating Diseases of the Central Nervous System

International Journal of Clinical Neurosciences and Mental Health 2016; 3(Suppl. 3):S06
DOI: http://dx.doi.org/10.21035/ijcnmh.2016.3(Suppl.3).S06

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Case Report


Multiple sclerosis and inflammatory bowel disease: what implications in therapeutic decisions? - read full article

By: Ana Aires and Pedro Abreu

Introduction: Recent observations suggest an association between Multiple sclerosis (MS) and Inflammatory Bowel Disease (IBD). The anti-TNF-alpha antagonists such as infliximab are an effective therapeutic option in IBD, but may induce worsening of demyelinating diseases. 
Case Report: A 33-year-old Caucasian male with a diagnosis of ulcerative colitis (UC) since 2007 and of relapse-remitting MS since 2004. After MS diagnosis, he started subcutaneous interferon beta-1a thrice a week. No relapses were observed. Six years after diagnosis, the patient developed injection-site reaction and had ulcerative colitis exacerbation. In spite of testing positive for anti-JC virus antibodies, he was medicated with natalizumab (Tysabri®) for two years. After this treatment, in the subsequent three years, by reason of UC worsening, he began azathioprine 150 mg daily. Patient persisted asymptomatic until 2013, when a significant aggravation of UC was detected. Consequently, he started anti-TNF-alpha agent (infliximab), maintaining azathioprine. He had no relapses until the one registered in May 2015. At that time high dose metilprednisolone pulse was initiated and anti-TNF-alpha was interrupted, azathioprine was augmented (200 mg/day) and, later on, the patient started daily subcutaneous glatiramer acetate (Copaxone®). 
Discussion: Our report emphasizes the complexity of treating patients with MS and other autoimmune diseases such as IBD. Despite being very effective in controlling ulcerative colitis, infliximab may worsen MS. The authors discuss what should be the best treatment to control both conditions.

Keywords: Multiple sclerosis, Inflammatory bowel disease, Infliximab.

Special Issue on Inflammatory Demyelinating Diseases of the Central Nervous System

International Journal of Clinical Neurosciences and Mental Health 2016; 3(Suppl. 3):S07

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Case Report


Multiphasic ADEM reclassified in Multiple Sclerosis: a case with therapeutic implications - read full article

By: Luís Braz, Mafalda Sampaio, Joana Guimarães, and Miguel Leão

Introduction: Acute disseminated encephalomyelitis (ADEM) is classically defined as a multifocal encephalopathic and typically monophasic demyelinating inflammatory clinical event. A multiphasic form of ADEM has been recognized; differentiating multiphasic ADEM from Multiple Sclerosis (MS) may represent a diagnosis challenge. 
Case Report: We present the case of a patient with a five episodes of subacute encephalopathy together with various focal neurological deficits, suggestive of multiphasic ADEM. Lastly, a sixth event presented as a non-encephalopathic relapse. According to the new criteria for diagnosis of pediatric acquired demyelinating syndromes, the patient actually displays a chronic relapsing disease like. However, 5 years after onset of illness, the patient is being treated with Azathioprine 150 mg/day and remains clinical and imagiologically stable. 
Discussion: Progression to MS occurs in pediatric patients in which the initial presentation is ADEM; however, in this patient, the current stability raises questions about the need for changing the current therapeutic regimen.

Keywords: Acute disseminated encephalomyelitis, Multiphasic Acute disseminated encephalomyelitis, Multiple Sclerosis.

Special Issue on Inflammatory Demyelinating Diseases of the Central Nervous System

International Journal of Clinical Neurosciences and Mental Health 2016; 3(Suppl. 3):S08
DOI: http://dx.doi.org/10.21035/ijcnmh.2016.3(Suppl.3).S08

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Case Report


Tumour-like lesion of the central nervous system: an elusive cause - read full article

By: Ana Monteiro, Bruno Carvalho, Cátia Caldas, António Sarmento, Rui Vaz, and Joana Guimarães

Introduction: Several central nervous system (CNS) disorders may present with a tumour-like mass mimicking brain tumour, including infections and vasculitis of the CNS. 
Case Report: We report the case of a previously healthy 61-year-old woman presenting with paraphasia. MRI showed a large left temporal, ill-defined lesion with heterogeneous signal intensity on both T1W and T2W images, and heterogeneous contrast enhancement, surrounded by oedema, suggestive of a high-grade glioma. Surgery was performed, but the pathology of the tissue was negative for neoplastic tissue and suggested chronic inflammation. Two months later she presented with progressively worsening neurological signs, and a repeat MRI revealed extensive re-growth of the lesion. In the absence of a definitive diagnosis, a second surgical approach was undertaken. Pathological examination now suggested, additionally, chronic non-granulomatous vasculitis. Pseudotumor form of primary angiitis of the CNS was considered. However, after specific DNA probing, Aspergillus fumigatus was found present in both the biopsy tissue and peripheral blood samples. 
Discussion: Aspergillus fumigatus is a common fungus that rarely infects the CNS. Immunocompromised patients are more commonly infected, although there have been several reports in immunocompetent patients, usually presenting as a mass lesion. Due to the unspecific imaging appearance pseudotumor masses pose a real diagnostic challenge.

Keywords: Pseudotumor, Vasculitis, Aspergillus fumigatus.

Special Issue on Inflammatory Demyelinating Diseases of the Central Nervous System

International Journal of Clinical Neurosciences and Mental Health 2016; 3(Suppl. 3):S09
DOI: http://dx.doi.org/10.21035/ijcnmh.2016.3(Suppl.3).S09

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Case Report


White matter lesions mimic multiple sclerosis in a minimally symptomatic CADASIL - read full article

By: Miguel Grilo and Joana Guimarães

Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a heritable small-vessel disease of the brain characterized by subcortical ischaemic events, cognitive impairment and leukoencephalopathy. The clinical presentation of the disease varies substantially between and within families and might be modulated by gender and common vascular risk factors. 
Case Report: We present the clinical case of a 57-year-old patient initially misdiagnosed with multiple sclerosis. The case illustrates how important it is to re-evaluate family history and imaging features in clinically non-progressive patients and demonstrates the substantial diversity of CADASIL within family members. In this setting, the approach of minimally symptomatic patients with white matter changes can present some diagnostic challenges.
Discussion: This case illustrates the diagnostic challenge of minimally symptomatic CADASIL. The need to reassess the diagnosis in such patients is of uttermost importance, since it has implications for disease management and genetic counseling.

Keywords: CADASIL, Multiple sclerosis, White matter lesions.

Special Issue on Inflammatory Demyelinating Diseases of the Central Nervous System

International Journal of Clinical Neurosciences and Mental Health 2016; 3(Suppl. 3):S10 

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Review Article


The inflammatory perspective of depression in the context of chronic medical conditions - read full article

By: Sara Azevedo-Pinto, Susana Santos, Orlando von Doellinger, Mário Barbosa, and Rui Coelho

Background: The inflammatory hypothesis of depression implies that an unbalance of the immune system may trigger abnormal responses, affecting neural signalling mediators and the hypothalamic-pituitary-adrenal axis. This theory underlies a bidirectional hypothesis on the influence of depressive symptoms in the clinical course of chronic inflammatory disorders (CID), as well as in the genesis of mood disturbances. We aim to review current knowledge on depressive disorders and chronic inflammatory diseases as comorbidities and the underlying pathophysiologic mechanisms. 
Methods: We performed a bibliographic search in PubMed, including publications released in the last 5 years, written in English, Portuguese and Spanish, containing the key words: depression, chronic inflammatory disorders, psoriasis, arthritis, inflammatory bowel disease and multiple sclerosis. 
Results: According to the literature, the incidence of depressive disorders is significantly higher in patients with CID. The medical conditions also present a worse clinical progression, with more frequent flares and decreased response to treatment. At the cellular and biochemical level, there is a deregulation of innate and adaptive immune responses, common to both medical and psychiatric pathologies, as well as an increase of the pro-inflammatory and acute phase reactants, with a inhibition of anti-inflammatory mechanisms. CID exert a major impact on the patients, at social, relational, functional and working levels, leading to decreased global performance, and enhancing several risk factors for depressive disorders. 
Conclusion: Besides the life stressing factors associated to CID, there are cellular and biochemical alterations triggering the dysfunction of the immune system, establishing a bridge with the pathophysiology of depressive disorders.

Keywords: Depression, Chronic inflammatory disorders, Psoriasis, Arthritis, Inflammatory bowel disease, Multiple sclerosis.

Special Issue on Inflammatory Demyelinating Diseases of the Central Nervous System

International Journal of Clinical Neurosciences and Mental Health 2016; 3(Suppl. 3):S11 

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