Large focal tumor-like demyelinating lesions of the brain: Intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis? A study of 31 patients

Abstract Introduction Sleep-disordered breathing is common in persons with multiple sclerosis (PwMS), and may contribute to debilitating fatigue and other chronic MS symptoms. The majority of research to date on SDB in MS has focused on the prevalence and consequences of obstructive sleep apnea; however, PwMS may also be at increased risk for central sleep apnea (CSA), and the utility of methods to assess CSA in PwMS warrant further exploration. We present a patient with secondary progressive multiple sclerosis who was found to have severe central sleep apnea on WatchPAT testing. Report of case(s) A 61 year-old female with a past medical history of secondary progressive multiple sclerosis presented with complaints of fragmented sleep. MRI of the brain, cervical spine, and thoracic spine showed numerous demyelinating lesions in the brain, brainstem, cervical, and thoracic spinal cord. Upon presentation, the patient noted snoring, witnessed apneas, and daytime sleepiness. WatchPAT demonstrated severe sleep apnea, with a pAHI of 63.3, and a minimum oxygen saturation of 90%. The majority of the scored events were non-obstructive in nature (73.1% of all scored events), and occurred intermittently in a periodic fashion. Conclusion The differential diagnosis of fatigue in PwMS should include sleep-disordered breathing, including both obstructive and central forms of sleep apnea. Demyelinating lesions in the brainstem (which may contribute to impairment of motor and sensory networks that control airway patency and respiratory drive), and progressive forms of MS, have been linked to both OSA and CSA. The present data illustrate this relationship in a person with progressive MS, and offer support for the WatchPAT as a cost-effective means to evaluate for both OSA and CSA in PwMS, while reducing patient burden. PwMS may be at increased risk for CSA. Careful clinical consideration should be given to ordering appropriate sleep testing to differentiate central from obstructive sleep apnea in PwMS, particularly for patients with demyelinating lesions in the brainstem. Support (if any) 1. Braley TJ, Segal BM, Chervin RD. Obstructive sleep apnea and fatigue in patients with multiple sclerosis. J Clin Sleep Med. 2014 Feb 15;10(2):155–62. doi: 10.5664/jcsm.3442. PMID: 24532998; PMCID: PMC3899317.

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Serum from patients with multiple sclerosis downregulates occludin and VE-cadherin expression in cultured endothelial cells

Multiple Sclerosis Journal ◽

10.1191/1352458503ms916oa ◽

2003 ◽

Vol 9 (3) ◽

pp. 235-238 ◽

Cited By ~ 46

Author(s):

Alireza Minagar ◽

Dmitry Ostanin ◽

Ann C Long ◽

Merilyn Jennings ◽

Roger E Kelley ◽

...

Keyword(s):

Multiple Sclerosis ◽

Endothelial Cells ◽

Inflammatory Cells ◽

Vascular Endothelial ◽

Cultured Endothelial Cells ◽

Demyelinating Lesions ◽

Endothelial Integrity ◽

Brain Microvasculature ◽

The Brain ◽

Normal Controls

Disruption of the blood -brain barrier (BBB) and transendothelial migration of inflammatory cells are crucial steps in the development of demyelinating lesions in multiple sclerosis (MS). O ccludin and vascular endothelial-cadher in (VE-cadherin) are two major components of the tight junctions (TJs) in the brain microvasculature that help to create the BBB. In the present study, we investigated the effect of serum from MS patients on the expression of these two junctional markers and on the endothelial integrity. Serum from six MS patients in exacerbation, six in remission, and six normal controls (10% by volume) was incubated with cultured endothelial cells, and the expression of occludin and VE-cadherin was measured by immunoblotting. Serum from MS patients in exacerbation significantly reduced the expression of occludin and VE-cadherin compared with patients in remission and normal controls. This disintegrating effect was more pronounced for occludin than for VE-cadherin. We assume that the elevation in cytokines or other serum-soluble factors in MS patients in exacerbation likely provokes downregulation of occludin and VE-cadherin. This downregulation of TJs proteins may, therefore, contribute to the disruption of the BBB in this condition.

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Immunology and Oxidative Stress in Multiple Sclerosis: Clinical and Basic Approach

Clinical and Developmental Immunology ◽

10.1155/2013/708659 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 86

Author(s):

Genaro G. Ortiz ◽

Fermín P. Pacheco-Moisés ◽

Oscar K. Bitzer-Quintero ◽

Ana C. Ramírez-Anguiano ◽

Luis J. Flores-Alvarado ◽

...

Keyword(s):

Oxidative Stress ◽

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Tissue Injury ◽

Autoimmune Disorder ◽

Demyelinating Lesions ◽

The Central Nervous System ◽

The Brain ◽

And Oxidative Stress

Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle.

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A Case of Acute Encephalopathy Due to Autoimmune Overload

Journal of Clinical Review & Case Reports ◽

10.33140/jcrc.05.06.07 ◽

2020 ◽

Vol 5 (6) ◽

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Pediatric Population ◽

Autoimmune Disorder ◽

Acute Disseminated Encephalomyelitis ◽

Acute Encephalopathy ◽

Demyelinating Disorder ◽

Demyelinating Disorders ◽

Brain And Spinal Cord ◽

The Brain

Acute disseminated encephalomyelitis, also known as postinfectious encephalomyelitis, is considered an autoimmune disorder that causes inflammation of the brain and spinal cord. It was seen mainly in pediatric population possibly due to vaccination but there have been cases identified in adult [1-9]. Acute disseminated encephalomyelitis can be challenging to diagnose owing to fact that there have been many overlapping symptoms among other demyelinating disorder such multiple sclerosis and Neuromyelitis Optica. In this case report, we will discuss a case about a patient that presented due to acute encephalopathy and was noted to have an atypical MRI of the brain that was not consistent with results of the lumbar puncture [10-12]. Knowledge gained from this case will help bring awareness to the diagnose of acute disseminated encephalomyelitis and how imaging in context with the clinical picture can help us differentiate between the various demyelinating disorders; thereby, giving a better understanding of managing these patients as management can affect prognosis and outcomes.

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Pseudotumoral Demyelinating Lesions: A Presentation of Acute Disseminated Encephalomyelitis

Case Reports in Neurology ◽

10.1159/000515174 ◽

2021 ◽

pp. 289-296

Author(s):

Rachid Belfkih ◽

Omar Ghomari Khayat ◽

Hind H’daidane ◽

Fatima Zahra El Amrani

Keyword(s):

Multiple Sclerosis ◽

Brain Mri ◽

Brain Biopsy ◽

Acute Disseminated Encephalomyelitis ◽

Neurological Deficits ◽

High Dose ◽

Good Recovery ◽

Disease Diagnostics ◽

Demyelinating Lesions ◽

Demyelinating Disorders

Pseudotumoral forms of demyelination are related to central nervous system demyelinating disorders, usually considered to be an atypical presentation of multiple sclerosis including its different varieties such as Balo’s, Schilder’s, and Marburg diseases. These lesions could also be seen in myelin oligodendrocyte glycoprotein antibody-associated demyelination, acute disseminated encephalomyelitis (ADEM), and neuromyelitis optica spectrum disorder. The pseudotumoral aspect may be mistakenly considered as an abscess or a cancerous tumor, in which case, patients could endure unnecessary possibly harmful brain biopsy and have a delay in their disease diagnostics and management. Once latter differential diagnosis is discarded, pseudotumoral demyelination prompts uncertainties concerning the nature of the underlying demyelinating condition as prognosis and management differ from multiple sclerosis to other syndromes, especially whether a chronic treatment is needed or not. In this case report, we present a 35-year-old male patient hospitalized in the department of neurology for a rapidly progressive onset of encephalopathy and polyfocal neurological deficits, with pseudotumoral lesions shown on brain MRI. On further investigations, ADEM was the more likely diagnosis that could fit the patient’s clinical and radiological presentation. Thence, he was put on high dose of intravenous corticosteroids, with a followed good recovery within the first week of the treatment.

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Large focal tumor-like demyelinating lesions of the brain

Annals of Neurology ◽

10.1002/ana.410340619 ◽

1993 ◽

Vol 34 (6) ◽

pp. 871-871 ◽

Cited By ~ 1

Author(s):

Gordon Francis

Keyword(s):

Demyelinating Lesions ◽

The Brain ◽

Focal Tumor

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Is that a scolex? a case of clinically isolated syndrome

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20194757 ◽

2019 ◽

Vol 6 (6) ◽

pp. 2697

Author(s):

Van K. Ma ◽

Lourdemillard Bellevue ◽

Maria Espiritu Fuller

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Clinical Signs ◽

Signs And Symptoms ◽

Clinically Isolated Syndrome ◽

Mri Brain ◽

Demyelinating Lesions ◽

The Central Nervous System ◽

Clinical Signs And Symptoms ◽

The Brain

Clinically Isolated Syndrome is an initial demyelinating event of the central nervous system that has been associated with the future development of multiple sclerosis. Diagnostic studies include clinical and paraclinical studies. Patients with lesions on MRI of the brain at baseline will more likely develop multiple sclerosis compared to patients without findings. We report a case of a 10-year-old female of Colombian ancestry and origin, who presented with indiscernible neurological clinical signs and symptoms, with MRI brain with and without contrast showing demyelinating lesions with one lesion “suggesting” a scolex.

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039 Estimating the health and economic burden of investigating tumefactive demyelination compared to conventional multiple sclerosis

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-anzan.36 ◽

2019 ◽

Vol 90 (e7) ◽

pp. A13.3-A14

Author(s):

Matthew Silsby ◽

Pedro S Lopez ◽

Judy Spies ◽

Stephen Reddel ◽

Jane Frith ◽

...

Keyword(s):

Multiple Sclerosis ◽

Brain Biopsy ◽

Adverse Outcomes ◽

Diagnostic Challenge ◽

Mcdonald Criteria ◽

Relapsing Remitting ◽

Demyelinating Lesions ◽

The Cost ◽

The Brain ◽

Improve Health

IntroductionTumefactive demyelinating lesions, defined as demyelinating lesions > 2cm in diameter, occur most commonly in association with multiple sclerosis (MS), and can pose a diagnostic challenge. The aim of this study was to estimate the cost and morbidity associated with the diagnostic investigation of patients with tumefactive demyelination (TD) compared to patients with conventional relapsing-remitting MS.MethodsRetrospective review of patients seen between 2013–2018 in clinics at the Brain and Mind Centre, Sydney; a centre with tertiary referral expertise in MS. Records were searched for the terms ‘tumefactive’ and ‘pseudotumour’. All patients diagnosed with TD were included and paired with a patient of similar age diagnosed in the same year with MS according to 2010 McDonald criteria.ResultsThere were 31 patients with TD and 31 patients with conventional relapsing remitting MS. The estimated cost of investigating TD was more than 7.5 times higher per patient than in MS ($18,300 AUD vs $2,418 AUD, p<0.001). Brain biopsy was performed in 6/31 TD patients and 0/31 MS patients and was the cause of more adverse outcomes in the TD versus MS group. More patients in the TD group were admitted to hospital (22/31 vs 10/31) and ICU admissions only occurred in the TD group (10/22 vs 0/10).ConclusionThe cost and adverse outcomes associated with investigating TD are higher than in conventional MS. Improvements in the diagnosis of TD have the potential to improve health and economic outcomes.

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