Predicting progression in primary progressive multiple sclerosis: A 10‐year multicenter study

Khaleeli, Zhaleh; Ciccarelli, Olga; Manfredonia, Francesco; Barkhof, Frederik; Brochet, Bruno; Cercignani, Mara; Dousset, V.; Filippi, Massimo; Montalbán, Xavier; Polman, Chris H.; Rovaris, Marco; Rovira, Àlex; Sastre‐Garriga, Jaume; Vellinga, M.M.; Miller, David H.; Thompson, Alan J.

doi:10.1002/ana.21375

Cited by 99 publications

(97 citation statements)

References 19 publications

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“…4, significant increases and decreases in magnetization transfer across time can be used to assess remyelination and demyelination [18,19]. As in other MS subtypes, cerebral MTR values are decreased in PPMS patients relative to controls [22,41,42,69]. Comparisons of MTR values between groups of PPMS and RRMS patients have not found significant differences [23].…”

Section: Imaging Findings In Ppmsmentioning

confidence: 99%

Primary progressive multiple sclerosis: part of the MS disease spectrum or separate disease entity?

et al. 2012

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Multiple sclerosis (MS), the most frequent demyelinating disease, is characterized by a variable disease course. The majority of patients starts with relapsing remitting (RR) disease; approximately 50-60% of these patients progress to secondary progressive (SP) disease. Only about 15% of the patients develop a progressive disease course from onset, termed primary progressive multiple sclerosis (PPMS); the underlying pathogenic mechanisms responsible for onset of the disease with either PPMS or relapsing remitting multiple sclerosis (RRMS) are unknown. Patients with PPMS do not show a female predominance and usually have a later onset of disease compared to patients with RRMS. Monozygous twins can be concordant or discordant for disease courses indicating that the disease course is not only genetically determined. Primary progressive multiple sclerosis and secondary progressive multiple sclerosis (SPMS) share many similarities in imaging and pathological findings. Differences observed among the different disease courses are more of a quantitative than qualitative nature suggesting that the different phenotypes are part of a disease spectrum modulated by individual genetic predisposition and environmental influences. In this review, we summarize the knowledge regarding the clinical, epidemiological, imaging, and pathological characteristics of PPMS and compare those characteristics with RRMS and SPMS.

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Section: Imaging Findings In Ppmsmentioning

confidence: 99%

Primary progressive multiple sclerosis: part of the MS disease spectrum or separate disease entity?

et al. 2012

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“…Measures provided by diffusion tensor imaging and 1 H-magnetic resonance spectroscopy ( 1 H-MRS), have been shown to correlate with disability (SastreGarriga et al, 2005;Ramio-Torrenta et al, 2006;Bodini et al, 2013) and predict progression (Khaleeli et al, 2007(Khaleeli et al, , 2008. Applying similar techniques to the spinal cord has been technically challenging .…”

Section: Introductionmentioning

confidence: 99%

Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis

Abdel-Aziz¹,

Schneider²,

Solanky³

et al. 2015

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Spinal neurodegeneration is an important determinant of disability progression in patients with primary progressive multiple sclerosis. Advanced imaging techniques, such as single-voxel 1 H-magnetic resonance spectroscopy and q-space imaging, have increased pathological specificity for neurodegeneration, but are challenging to implement in the spinal cord and have yet to be applied in early primary progressive multiple sclerosis. By combining these imaging techniques with new clinical measures, which reflect spinal cord pathology more closely than conventional clinical tests, we explored the potential for spinal magnetic resonance spectroscopy and q-space imaging to detect early spinal neurodegeneration that may be responsible for clinical disability. Data from 21 patients with primary progressive multiple sclerosis within 6 years of disease onset, and 24 control subjects were analysed. Patients were clinically assessed on grip strength, vibration perception thresholds and postural stability, in addition to the Expanded Disability Status Scale, Nine Hole Peg Test, Timed 25-Foot Walk Test, Multiple Sclerosis Walking Scale-12, and Modified Ashworth Scale. All subjects underwent magnetic resonance spectroscopy and q-space imaging of the cervical cord and conventional brain and spinal magnetic resonance imaging at 3 T. Multivariate analyses and multiple regression models were used to assess the differences in imaging measures between groups and the relationship between magnetic resonance imaging measures and clinical scores, correcting for age, gender, spinal cord cross-sectional area, brain T 2 lesion volume, and brain white matter and grey matter volume fractions. Although patients did not show significant cord atrophy when compared with healthy controls, they had significantly lower total N-acetyl-aspartate (mean 4.01 versus 5.31 mmol/l, P = 0.020) and glutamate-glutamine (mean 4.65 versus 5.93 mmol/l, P = 0.043) than controls. Patients showed an increase in q-space imaging-derived indices of perpendicular diffusivity in both the whole cord and major columns compared with controls (P 5 0.05 for all indices). Lower total N-acetyl-aspartate was associated with higher disability, as assessed by the Expanded Disability Status Scale (coefficient = À 0.41, 0.01 5 P 5 0.05), Modified Ashworth Scale (coefficient = À 3.78, 0.01 5 P 5 0.05), vibration perception thresholds (coefficient = À 4.37, P = 0.021) and postural sway (P 5 0.001). Lower glutamate-glutamine predicted increased postural sway (P = 0.017). Increased perpendicular diffusivity in the whole cord and columns was associated with increased scores on the Modified Ashworth Scale, vibration perception thresholds and postural sway (P 5 0.05 in all cases). These imaging findings indicate reduced structural integrity of neurons, demyelination, and abnormalities in the glutamatergic pathways in the cervical cord of early primary progressive multiple sclerosis, in the absence of extensive spinal cord atrophy. The observed relationship between imaging measures and disa...

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“…[1][2][3] Although sex has a less dramatic effect on disease progression and clinical outcomes, several studies have reported more severe symptoms and faster progression in men. [4][5][6][7] The underlying processes thought to be involved in the development and progression of MS demonstrate significant sex differences. For example, male and female patients with MS have shown differences in the markers of autoimmune function, [8][9][10] and there has been extensive research on the effects of sex hormones on disease progression, particularly during and after pregnancy.…”

mentioning

confidence: 99%

Sex Differences in Resting-State Functional Connectivity in Multiple Sclerosis

Koenig

Lowe

Lin

et al. 2013

AJNR Am J Neuroradiol

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Predicting progression in primary progressive multiple sclerosis: A 10‐year multicenter study

Cited by 99 publications

References 19 publications

Primary progressive multiple sclerosis: part of the MS disease spectrum or separate disease entity?

Primary progressive multiple sclerosis: part of the MS disease spectrum or separate disease entity?

Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis

Sex Differences in Resting-State Functional Connectivity in Multiple Sclerosis

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