Progressive motor impairment from a critically located lesion in highly restricted CNS-demyelinating disease

Abstract

Objective:

To report progressive motor impairment from a critically located central nervous system (CNS) demyelinating lesion in patients with restricted magnetic resonance imaging (MRI)-lesion burden.

Methods:

We identified 38 patients with progressive upper motor-neuron impairment for >1 year, 2–5 MRI CNS-demyelinating lesions, with one seemingly anatomically responsible for progressive motor impairment. Patients with any alternative etiology for progressive motor impairment were excluded. A neuroradiologist blinded to clinical evaluation reviewed multiple brain and spinal-cord MRI, selecting a candidate critically located demyelinating lesion. Lesion characteristics were determined and subsequently compared with clinical course.

Results:

Median onset age was 47.5 years (24–64); 23 (61%) women. Median follow-up was 94 months (18–442); median Expanded Disability Status Scale Score (EDSS) at last follow-up was 4.5 (2–10). Clinical presentations were progressive: hemiparesis/monoparesis 31; quadriparesis 5; and paraparesis 2; 27 patients had progression from onset; 11 progression post-relapse. Total MRI lesions were 2 (n = 8), 3 (n = 12), 4 (n = 12), and 5 (n = 6). Critical lesions were located on corticospinal tracts, chronically atrophic in 26/38 (68%) and involved cervical spinal cord in 27, cervicomedullary/brainstem region in 6, thoracic spinal cord in 4, and subcortical white matter in 1.

Conclusion:

Progressive motor impairment may ascribe to a critically located CNS-demyelinating lesion in patients with highly restricted MRI burden. Motor progression from a specific demyelinating lesion has implications for understanding multiple sclerosis (MS) progression.

Keywords

Progressive myelopathy demyelinating disease multiple sclerosis magnetic resonance imaging

Get full access to this article

View all access options for this article.

References

Mahad

Trapp

Lassmann

. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol 2015; 14: 183–193.

Barkhof

. The clinico-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol 2002; 15: 239–245.

Keegan

Kaufmann

Weinshenker

et al . Progressive solitary sclerosis: Gradual motor impairment from a single CNS demyelinating lesion. Neurology 2016; 87: 1713–1719.

Schmalstieg

Keegan

Weinshenker

. Solitary sclerosis: Progressive myelopathy from solitary demyelinating lesion. Neurology 2012; 78: 540–544.

Tutuncu

Tang

Zeid

et al . Onset of progressive phase is an age-dependent clinical milestone in multiple sclerosis. Mult Scler 2013; 19: 188–198.

Paz Soldan

Novotna

Abou Zeid

et al . Relapses and disability accumulation in progressive multiple sclerosis. Neurology 2015; 84: 81–88.

Polman

Reingold

Banwell

et al . Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69: 292–302.

Kurtzke

. Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology 1983; 33: 1444–1452.

Lublin

Reingold

Cohen

et al . Defining the clinical course of multiple sclerosis: The 2013 revisions. Neurology 2014; 83: 278–286.

10.

Wingerchuk

Banwell

Bennett

et al . International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015; 85: 177–189.

11.

Transverse Myelitis Consortium Working G. Proposed diagnostic criteria and nosology of acute transverse myelitis. Neurology 2002; 59: 499–505.

12.

Zajicek

Scolding

Foster

et al . Central nervous system sarcoidosis—Diagnosis and management. QJM 1999; 92: 103–117.

13.

Flanagan

Krecke

Marsh

et al . Specific pattern of gadolinium enhancement in spondylotic myelopathy. Ann Neurol 2014; 76: 54–65.

14.

Brex

Ciccarelli

O’Riordan

et al . A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med 2002; 346: 158–164.

15.

Lattanzi

Logullo

Di Bella

et al . Multiple sclerosis, solitary sclerosis or something else? Mult Scler 2014; 20: 1819–1824.

16.

Cohen

Lebrun

Ayrignac

et al . Solitary sclerosis: Experience from three French tertiary care centres. Mult Scler 2015; 21: 1216.

17.

Rathnasabapathi

Elsone

Krishnan

et al . Solitary sclerosis: Progressive neurological deficit from a spatially isolated demyelinating lesion: A further report. J Spinal Cord Med 2015; 38: 551–555.

18.

Rocca

Battaglini

Benedict

et al . Brain MRI atrophy quantification in MS: From methods to clinical application. Neurology 2017; 88: 403–413.

19.

Staff

Lucchinetti

Keegan

. Multiple sclerosis with predominant, severe cognitive impairment. Arch Neurol 2009; 66: 1139–1143.

20.

Tintore

Rovira

Arrambide

et al . Brainstem lesions in clinically isolated syndromes. Neurology 2010; 75: 1933–1938.

21.

Hickman

Brierley

Silver

et al . Infratentorial hypointense lesion volume on T1-weighted magnetic resonance imaging correlates with disability in patients with chronic cerebellar ataxia due to multiple sclerosis. J Neurol Sci 2001; 187: 35–39.

22.

Kearney

Altmann

Samson

et al . Cervical cord lesion load is associated with disability independently from atrophy in MS. Neurology 2015; 84: 367–373.

23.

Rocca

Horsfield

Sala

et al . A multicenter assessment of cervical cord atrophy among MS clinical phenotypes. Neurology 2011; 76: 2096–2102.

24.

Brownlee

Altmann

Alves Da Mota

et al . Association of asymptomatic spinal cord lesions and atrophy with disability 5 years after a clinically isolated syndrome. Mult Scler 2017; 23: 665–674.

25.

Kantarci

Lebrun

Siva

et al . Primary progressive multiple sclerosis evolving from radiologically isolated syndrome. Ann Neurol 2016; 79: 288–294.

26.

Krieger

Cook

De Nino

et al . The topographical model of multiple sclerosis: A dynamic visualization of disease course. Neurol Neuroimmunol Neuroinflamm 2016; 3: e279.

27.

Bot

Barkhof

Polman

et al . Spinal cord abnormalities in recently diagnosed MS patients: Added value of spinal MRI examination. Neurology 2004; 62: 226–233.

28.

Saidha

Chen

et al . Spinal cord quantitative MRI discriminates between disability levels in multiple sclerosis. Neurology 2013; 80: 540–547.

29.

Hollingsworth

Khouri

Imitola

. Endogenous repair and development inspired therapy of neurodegeneration in progressive multiple sclerosis. Expert Rev Neurother 2017; 17: 611–629.

30.

Marrie

. Comorbidity in multiple sclerosis: Implications for patient care. Nat Rev Neurol 2017; 13: 375–382.

31.

Filippi

Preziosa

Rocca

. Microstructural MR imaging techniques in multiple sclerosis. Neuroimaging Clin N Am 2017; 27: 313–333.

32.

Disanto

Barro

Benkert

et al . Serum neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Ann Neurol 2017; 81: 857–870.

33.

Saidha

Sotirchos

et al . Relationships between retinal axonal and neuronal measures and global central nervous system pathology in multiple sclerosis. JAMA Neurol 2013; 70: 34–43.

34.

Martinez-Lapiscina

Arnow

Wilson

et al . Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: A cohort study. Lancet Neurol 2016; 15: 574–584.