Recurrence and Prognostic Value of Asymptomatic Spinal Cord Lesions in Multiple Sclerosis

Spinal magnetic resonance imaging (MRI) is currently not recommended for the routine monitoring of clinically stable multiple sclerosis (MS) patients. We aimed to investigate the occurrence of asymptomatic spinal lesions (a-SL) in clinically stable MS patients, and their association with clinical and radiological outcomes, including the recurrence of spinal lesions. The hospital MS registry was searched for clinically stable MS patients (no relapses, no disability progression) with spinal MRIs performed at T1 (baseline) and T2 (9–36 months after T1). Information on relapses, disability and new brain/spinal MRI lesions at T3 (≥6 months after T2) was collected and analyzed. Out of 300 MS patients, 45 showed a-SL between T1 and T2. The presence of a-SL was not associated with the subsequent occurrence of relapses or disability progression at T3, but did correlate with the risk of new brain (rate ratio (RR) = 1.63, 95% CI = 1.16−2.25, p = 0.003) and recurrent spinal lesions (RR = 7.28, 95% CI = 4.02–13.22, p < 0.0001). Accounting for asymptomatic brain lesions (a-BL), the presence of either a-BL or a-SL was associated with subsequent risk for new brain (OR = 1.81, 95% CI = 1.25–2.60, p = 0.001) or spinal (RR = 2.63, 95% CI = 1.27–5.45, p = 0.009) lesions. Asymptomatic spinal demyelinating lesions occurred in 15% of clinically stable MS patients within a median period of 14 months and conferred an increased risk of future radiological activity at the brain and spinal level.

Download Full-text

827 Central Sleep Apnea in a patient with Multiple Sclerosis

SLEEP ◽

10.1093/sleep/zsab072.824 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A322-A323

Author(s):

Rahul Dasgupta ◽

Sonja Schütz ◽

Tiffany Braley

Keyword(s):

Multiple Sclerosis ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Sleep Disordered Breathing ◽

Central Sleep Apnea ◽

Progressive Multiple Sclerosis ◽

Obstructive Sleep ◽

Increased Risk ◽

Demyelinating Lesions ◽

The Brain

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.

Download Full-text

Leber’s hereditary optic neuropathy associated with a multiple-sclerosis-like picture in a man

Multiple Sclerosis Journal ◽

10.1177/1352458511404033 ◽

2011 ◽

Vol 17 (6) ◽

pp. 763-766 ◽

Cited By ~ 10

Author(s):

Antonella La Russa ◽

Rita Cittadella ◽

Virginia Andreoli ◽

Paola Valentino ◽

Francesca Trecroci ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Optic Neuropathy ◽

Brain Mri ◽

Resonance Imaging ◽

Gadolinium Enhancement ◽

Demyelinating Lesions ◽

Male Patients ◽

Magnetic Resonance Imaging Mri ◽

Symptoms And Signs

A 35-year-old young man displayed Leber’s optic neuropathy (LHON) due to T14484C and multiple sclerosis (MS) phenotype that was dominated by symptoms and signs of spinal cord impairment. Magnetic resonance imaging (MRI) revealed demyelinating lesions extending from D6 to D11 in the spinal cord with gadolinium enhancement, while only three linear demyelinating lesions were seen on brain MRI. In the literature, a major involvement of the spinal cord was already reported in three of four male patients with the 14484 LHON mutation who developed MS, but the reasons of this peculiar association remain unknown, and further research in this area is needed.

Download Full-text

Central hyperacusis with phonophobia in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1191/1352458502ms814oa ◽

2002 ◽

Vol 8 (6) ◽

pp. 505-509 ◽

Cited By ~ 19

Author(s):

H Weber ◽

K Pfadenhauer ◽

M Stöhr ◽

A Rösler

Keyword(s):

Multiple Sclerosis ◽

Auditory Evoked Potentials ◽

Auditory Pathway ◽

Directional Hearing ◽

Hearing Disorders ◽

Brainstem Lesion ◽

Acoustic Stimuli ◽

Demyelinating Lesions ◽

Magnetic Resonance Imaging Mri ◽

Central Auditory Pathway

Hearing disorders are a well-described symptom in patients with multiple sclerosis (MS). Unilateral or bilateral hyperacusis or deafness in patients with normal sound audiometry is often attributed to demyelinating lesions in the central auditory pathway. Less known in MS is a central phonophobia, whereby acoustic stimuli provoke unpleasant and painful paresthesia and lead to the corresponding avoidance behaviour. In our comparison collective, patient 1 described acute shooting pain attacks in his right cheek, each time set off by the ringing of the telephone. Patient 2 complained of intensified, unbearable noise sensations when hearing nonlanguage acoustic stimuli. Patient 3 noticed hearing unpleasant echoes and disorders of the directional hearing. All patients had a clinical brainstem syndrome. ENT inspection, sound audiometry and stapedius reflex were normal. All three patients had pathologically changed auditory evoked potentials (AEPs) with indications of a brainstem lesion, and in magnetic resonance imaging (MRI) demyelinating lesions in the ipsilateral pons and in the central auditory pathway. The origin we presume in case 1 is an abnormal impulse conduction from the leminiscus lateralis to the central trigeminus pathway and, in the other cases, a disturbance in the central sensory modulation. All patients developed in the further course a clinically definite MS. Having excluded peripheral causes for a hyperacusis, such as, e.g., an idiopathic facial nerve palsy or myasthenia gravis, one should always consider the possibility of MS in a case of central phonophobia. Therapeutic possibilities include the giving of serotonin reuptake inhibitors or acoustic lenses for clearly definable disturbing frequencies.

Download Full-text

Interferon beta failure predicted by EMA criteria or isolated MRI activity in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458513502399 ◽

2013 ◽

Vol 20 (5) ◽

pp. 566-576 ◽

Cited By ~ 36

Author(s):

Luca Prosperini ◽

Chiara Rosa Mancinelli ◽

Laura De Giglio ◽

Floriana De Angelis ◽

Valeria Barletta ◽

...

Keyword(s):

Multiple Sclerosis ◽

Interferon Beta ◽

European Medicines Agency ◽

First Year ◽

Resonance Imaging ◽

T2 Lesions ◽

Increased Risk ◽

Magnetic Resonance Imaging Mri ◽

One Year

Objective: The objective of this paper is to investigate four-year outcomes of interferon beta (IFNB)-treated patients with multiple sclerosis (MS) according to their clinical or magnetic resonance imaging (MRI) activity status at first year of treatment. Methods: A total of 370 patients with MS duration ≤5 years before IFNB start were followed-up for four years. The optimal threshold for one-year MRI activity that more accurately predicted subsequent relapses or disability worsening was identified. The risk of relapses and disability worsening after the first year was then estimated by propensity score (PS)-adjusted analyses in patients fulfilling European Medicines Agency (EMA) criteria for second-line escalation and in those with isolated MRI activity. Results: A total of 192 (51.9%) patients relapsed, and 66 (17.8%) worsened in disability from year 1 to 4 of follow-up. The more accurate threshold for one-year MRI activity was the occurrence of ≥1 enhancing or ≥2 new T2-lesions. An increased risk of relapses and disability worsening was found in either patients fulfilling EMA criteria (hazard ratio (HR) = 3.69, and HR = 6.02) and in those experiencing isolated MRI activity (HR = 3.15, and HR = 5.31) at first year of treatment, when compared with stable patients (all p values <0.001). Conclusion: The four-year outcomes of patients with isolated MRI activity did not differ from those fulfilling EMA criteria at first year of IFNB treatment.

Download Full-text

Clinical and MRI characteristics of multiple sclerosis in patients of Middle Eastern and North African ancestry residing in Ontario, Canada

Multiple Sclerosis Journal ◽

10.1177/1352458520948212 ◽

2020 ◽

pp. 135245852094821

Author(s):

Estelle Seyman ◽

Ashley Jones ◽

Melanie Guenette ◽

Reza Vosoughi ◽

Daniel Selchen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Middle Eastern ◽

African Ancestry ◽

Genetic Determinants ◽

Disability Progression ◽

Disease Characteristics ◽

Magnetic Resonance Imaging Mri ◽

Mri Characteristics ◽

Age And Sex

Background: Multiple sclerosis (MS) incidence is rising in traditionally low-burden regions, including the Middle East and North Africa (MENA). Objectives: Our objective was to evaluate disease characteristics in MS patients of MENA descent (MENA-MS). Methods: MENA-MS patients and age- and sex-matched MS patients of European descent (EUR-MS) were identified through the MS Clinic Registry of St. Michael’s Hospital in Toronto, Canada. Disease activity and severity were evaluated by the annualized relapse rate (ARR), magnetic resonance imaging (MRI) activity, change in the Expanded Disability Status Scale (EDSS), progression index (PI), and MS Severity Score (MSSS). Results: All MS patients within the registry identified to be of MENA origin ( n = 192), and age- and sex-matched EUR-MS patients were included. Mean age was 42.9 years, 67% female. A total of 25% and 24% of EUR-MS and MENA-MS had progressive disease, with similar mean disease durations (11.5 and 11.4 years, respectively). Clinical and radiological disease activity (ARR, proportion with new/enlarging MRI lesions) was similar. MENA-MS showed greater disability progression over time (EDSS change = 0.24 vs. 0.06, p = 0.01), a higher MSSS (3.12 vs. 2.67, p = 0.04), and higher PI (0.34 vs. 0.27, p = 0.07). Conclusion: MENA-MS patients demonstrate higher disease severity compared to EUR-MS patients, despite having similar inflammatory measures of disease activity, with disability progression in the absence of relapses. These observations illustrate the importance of the intersections of environmental, socioeconomic, and genetic determinants in optimizing individualized MS care.

Download Full-text

Asymptomatic spinal cord lesions do not predict the time to disability in patients with early multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458517736147 ◽

2017 ◽

Vol 24 (4) ◽

pp. 481-490 ◽

Cited By ~ 11

Author(s):

Iris Dekker ◽

Madeleine H Sombekke ◽

Birgit I Witte ◽

Jeroen JG Geurts ◽

Frederik Barkhof ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Demographic Data ◽

Disability Progression ◽

Definite Multiple Sclerosis ◽

Relapsing Remitting ◽

Clinically Definite Multiple Sclerosis ◽

Magnetic Resonance Imaging Mri ◽

Relapsing Remitting Multiple Sclerosis ◽

In Cis

Background: The presence of asymptomatic spinal cord (SC) lesions in patients with clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS) predicts conversion to clinically definite multiple sclerosis (CDMS). The relation between asymptomatic SC abnormalities and disability progression warrants further investigation. Objective: To determine the prognostic value of asymptomatic SC lesions in CIS and early RRMS with respect to the time to disability development. Methods: Clinical and demographic data, brain and SC magnetic resonance imaging (MRI) were collected of CIS or early RRMS patients. Two main analyses were performed. For the first analysis, patients were divided into two groups: (1) patients with asymptomatic SC lesions and (2) patients without SC lesions and patients with symptomatic SC lesions. The second analysis excluded patients with symptomatic SC lesions. Incidence curves were used to analyse differences between these groups in time to the development of disability and time to a second relapse. Results: A total of 178 patients were included, and 42 patients (23.6%) had asymptomatic SC lesions. No significant differences were found on the time to disability development or the time to a second event. Conclusion: Asymptomatic SC lesions early in the disease course do not predict the time to disability development in patients diagnosed with CIS or early RRMS.

Download Full-text

Escalation to natalizumab or switching among immunomodulators in relapsing multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458511417481 ◽

2011 ◽

Vol 18 (1) ◽

pp. 64-71 ◽

Cited By ~ 61

Author(s):

Luca Prosperini ◽

Costanza Giannì ◽

Laura Leonardi ◽

Laura De Giglio ◽

Giovanna Borriello ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cox Regression ◽

Line Treatment ◽

Disability Progression ◽

First Line ◽

Hazard Ratios ◽

Post Marketing ◽

Magnetic Resonance Imaging Mri ◽

Relapsing Remitting Multiple Sclerosis ◽

First Line Treatment

Objective: To evaluate whether an escalation approach was more effective in suppressing clinical and magnetic resonance imaging (MRI) activity than switching among immunomodulators in relapsing–remitting multiple sclerosis (RRMS) patients. Methods: In this post-marketing, prospective, observational study in two Italian multiple sclerosis (MS) centres, a total of 285 RRMS patients who failed a first-line treatment with interferon beta (IFNβ) or glatiramer acetate (GA) were considered. Patients were subdivided according to the strategy adopted after the failure (defined as the occurrence of ≥2 relapses or 1 relapse with residual disability): the switching (SWI) group, i.e. those switched among different IFNβ formulations, or from IFNβ to GA and vice versa; and the escalating (ESC) group, i.e. those escalated to natalizumab. Proportions of patients free from different types of disease activity (relapses, sustained disability progression, new active lesions on MRI, or a combination of them) were calculated at 12 and 24 months. Since patients were not randomized to treatment group, propensity score (PS)-adjusted Cox regression models were built to control for several potential confounders. Results: At 12 months there were no differences between the two groups in proportions of patients free from relapse, disability progression, MRI activity, and combined activity. After 24 months we observed greater proportions of patients in the ESC than SWI group free from relapse ( p < 0.0001), disability progression ( p = 0.0045), MRI activity ( p = 0.0003), and combined activity ( p < 0.0001). PS-adjusted models confirmed these findings, with hazard ratios ranging from 0.38 to 0.56 favours the ESC group. Conclusion: We suggest that an escalation to natalizumab is more effective than switching among immunomodulators in RRMS patients who failed a first-line treatment.

Download Full-text

Deep gray matter T2 hypointensity is present in patients with clinically isolated syndromes suggestive of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458509350310 ◽

2009 ◽

Vol 16 (1) ◽

pp. 39-44 ◽

Cited By ~ 44

Author(s):

Antonia Ceccarelli ◽

Maria A Rocca ◽

Mohit Neema ◽

Vittorio Martinelli ◽

Ashish Arora ◽

...

Keyword(s):

Multiple Sclerosis ◽

Caudate Nucleus ◽

Gray Matter ◽

Lesion Volume ◽

Clinically Isolated Syndromes ◽

Increased Risk ◽

Left Caudate ◽

Magnetic Resonance Imaging Mri ◽

Putative Marker ◽

In Cis

Gray matter (GM) magnetic resonance imaging (MRI) T2 hypointensity, a putative marker of iron deposition, is a frequent finding in patients with clinically definite (CD) multiple sclerosis (MS). The objective of this study was to assess: (a) how early deep GM T2 hypointensity occurs in MS, by studying patients with clinically isolated syndromes (CIS) suggestive of MS, and (b) whether they contribute to predict subsequent evolution to CDMS. Dual-echo scans using two different acquisition protocols were acquired from 47 CIS patients and 13 healthy controls (HC). Normalized T2-intensity of the basal ganglia and thalamus was quantified. Patients were assessed clinically at the time of MRI acquisition and after three years. During the observation period, 18 patients (38%) evolved to CDMS. At the baseline, only the GM T2-intensity of the left caudate nucleus was significantly reduced in CIS patients in comparison with the HC (p = 0.04). At the baseline, the T2 intensity of the left caudate nucleus was significantly lower (p = 0.01) in CIS patients with disease dissemination in space (DIS), but not in those without DIS, compared to the HC. The baseline T2 lesion volume, but not GM T2 hypointensity, was associated with evolution to CDMS (hazard ratio = 1.60, 95% confidence interval (CI) = 1.05—2.42; p = 0.02). In CIS patients, deep GM is not spared, suggesting that iron-related changes and neurodegeneration occurs early. The magnitude of such damage is only minor and not associated with an increased risk of evolution to CDMS.

Download Full-text

Relevance of asymptomatic spinal MRI lesions in patients with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458515599246 ◽

2015 ◽

Vol 22 (6) ◽

pp. 782-791 ◽

Cited By ~ 20

Author(s):

C Zecca ◽

G Disanto ◽

MP Sormani ◽

GC Riccitelli ◽

A Cianfoni ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disability Progression ◽

Mri Brain ◽

Relapsing Remitting ◽

Spinal Mri ◽

The Impact ◽

Serial Mri ◽

Clinical Stability ◽

Median Interval

Background: The impact of new asymptomatic spinal cord lesions (a-SL) in multiple sclerosis (MS) course is poorly characterized. Objective: The objective of this research paper is to assess the prognostic value of a-SL in predicting MS course. Methods: Relapsing–remitting MS patients who received serial MRI (brain and spinal) at baseline (t1) and within 12 to 36 months (t2) during clinical stability, and had a follow-up (t2–t3) ⩾24 months were included. Relapses and disability progression were evaluated between t2 and t3. Results: Of 413 consecutive screened MS patients, 103 patients (65 females, median age 43 years) were included. After a median t1–t2 interval of 17 (IQR 13–26) months, 25.2% and 43.7% patients had ⩾1 new a-SL (a-SL+) and asymptomatic brain lesions (a-BL+), respectively. Relapse risk between t2 and t3 (median interval: 42 (IQR 32–57.5) months) was significantly increased in a-SL+ and/or a-BL+ vs a-BL– and a-SL– (HR = 2.31, 95% CI = 1.13–4.72, p = 0.02). No differences in the risk of disability progression were found in a-SL+ and/or a-BL+ vs a-SL- and a-BL–. Conclusion: a-SL occur in one-quarter of clinically stable RRMS, and combined with a-BL contribute significantly in predicting future disease course.

Download Full-text

Depression in Multiple Sclerosis: A Case Report

European Psychiatry ◽

10.1016/s0924-9338(09)70900-9 ◽

2009 ◽

Vol 24 (S1) ◽

pp. 1-1

Author(s):

L. Paixão ◽

M.J. Avelino

Keyword(s):

Multiple Sclerosis ◽

Side Effects ◽

Interferon Β ◽

Psychological Disturbance ◽

Disease Modifying Drugs ◽

Loss Of Self ◽

Duration Of Illness ◽

Increased Risk ◽

Demyelinating Lesions

Introduction:Depression is the predominant psychological disturbance in Multiple Sclerosis (MS) with lifetime prevalence around 50% and annual prevalence of 20%. Depression is commoner during relapses and may exacerbate fatigue and cognitive dysfunction. The aetiology of depression is multifactorial and likely associated with psychological stress, focal demyelinating lesions and immune dysfunction. There is no correlation between age, gender, duration of illness and sex. Unlike it was believed for the treatment with interferon β, recent side effects data from clinical trials have failed to confirm that this medication is associated with an increased risk of depression in patients with MS. Treating depression improves quality of life and improves adherence to disease-modifying drugs. Treatment with pharmacotherapy is particularly challenging given the somatic symptoms overlap between MS and depression and the increased burden of their side effects.Aims:To demonstrate the relationship between depression and MS.Methods:We report a case of depression in a 32 year old woman with MS, treated twice with bolus of metilprednisolone, taking interferon β at present. Her psychopathological symptoms have been sadness, terminal insomnia, anorexia, fatigue, social isolation, anhedonia, increased worry, pessimism, loss of self-esteem and suicidal ideation (not structured). The pharmacotherapy used to treat the depression was firstly fluoxetine and lately venlafaxine.Results:There has been an improvement on the patient's symptoms related both to the depression and to the MS.Conclusions:This case demonstrates once more, the complex relationship between those two clinical entities.

Download Full-text