Journal of Neurology

https://doi.org/10.1007/s00415-019-09489-5

REVIEW

A focus on secondary progressive multiple sclerosis (SPMS): challenges

in diagnosis and definition
Hernan Inojosa1 · Undine Proschmann1 · Katja Akgün1 · Tjalf Ziemssen1 

Received: 2 July 2019 / Revised: 24 July 2019 / Accepted: 26 July 2019

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Abstract
Secondary progressive multiple sclerosis (SPMS) is the second most common form of multiple sclerosis (MS). One in two
relapse remitting multiple sclerosis (RRMS) patients will develop SPMS within 15 years and up to two-thirds after 30 years,
leading to a progressive decrease of neurological function and limitation of daily activities. Nevertheless, the SPMS diagnosis
is often established retrospectively and delayed up to 3 years due to several patient- and clinician-related factors. Definitive
clinical diagnostic criteria are lacking and research is currently ongoing to identify imaging and biochemical biomarkers.
As new therapies are introduced, early SPMS diagnosis may represent a window of opportunity for intervention. New
approaches, endpoints or technologies could help physicians establishing a diagnosis. Here, we review SPMS in relation to
its diagnostic and definition challenges and current screening techniques and tools.

Keywords  SPMS · Diagnosis · Definition · Screening · Endpoints

Introduction of MS with a prevalence that varies geographically with up

Multiple sclerosis (MS) is a chronic inflammatory disease
of the central nervous system (CNS). The affected areas in
the CNS are multifocal and variable, so are natural history
and individual clinical manifestation. Most of the patients
begin with a relapsing remitting phenotype of MS (RRMS)
characterized by episodic symptoms and signs (attacks or
relapses) with full or partial recovery and no disease pro-
gression between relapses.
After some years, many of these patients present a grad-
ual decline of the neurological function with and without
relapses, which is characteristic for the evolution of sec-
ondary progressive disease (SPMS). SPMS is distinguished
from primary progressive MS (PPMS) by its distinct course,
which necessarily includes and follows an initial course of
RRMS [1]. It has been reported that 85–90% of patients
have RRMS at the time of diagnosis and up to eight in
every ten of them may advance to SPMS within 20 years
[2]. Worldwide, SPMS is the second most common form
* Tjalf Ziemssen
Tjalf.Ziemssen@uniklinikum‑dresden.de
1
Department of Neurology, Center of Clinical Neuroscience,
Carl Gustav Carus University Clinic, University Hospital
of Dresden, Fetscherstr. 74, 01307 Dresden, Germany
to 57.8/100.000 in the UK, 37.1/100.000 in the USA and
33.3/100.000 in Germany [1].
Even though in the last decades, several disease-mod-
ifying therapies (DMT) have been developed for RRMS,
for SPMS there are still few therapeutic approaches. Not
until March 2019, Siponimod was approved in the US as
first treatment for SPMS [3]. Although the early diagnosis
of SPMS or transition from RRMS can be difficult for the
physician and confusing for the patients, it could open a win-
dow of opportunities for disease treatment. We review these
challenges on SPMS and the current status on diagnosis and
prognosis of this disease subtype.
From RRMS to SPMS
As commented above, up to 80% of patients could go from
RRMS to SPMS within 20 years [2]. However, epidemio-
logical data concerning secondary progression should be
carefully depicted considering the use of DMT, as it could
modify the natural history of the disease. Data based on
cohort of patients who have not received DMTs suggest that
this conversion occurred in more than one-third of patients
within 8 years, one in two after 15 years and two in three
after 30 years [4, 5]. Nevertheless, thanks to newer treatment

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Fig. 1  Illustration of the transition phase on the natural history of
MS. While patients are on the transition phase from RRMS to SPMS,
the brain reserve, cognitive reserve and other compensatory mecha-
nisms may cover early clinical manifestations of the progressive dis-
options the conversion rates may be much lower in future.
A study showed that after more than 16 years of follow-up,
11.3% of a treated cohort transitioned to SPMS, numbers
much lower than the 36–50% expected considering previ-
ous reports from the pre-treatment era [6]. Another study
reported a longer time to progression in patients treated with
first-generation DMTs compared with historical data from
patients of the same registry and after carefully adjusting to
different variables [7].
Pathophysiologically, the underlying neurodegenerative
processes at the CNS are already present in the asympto-
matic phase of MS. The main reason why people with MS do
not notice they have SPMS in early stages of their disease is
that the brain has the ability to compensate for neuronal loss
[8]. The exact nature of these compensating mechanisms
remains unknown, but some authors have postulated a larger
extra-region neuronal recruitment, increased homologous
area activation of additional brain areas and neuronal plas-
ticity in form of local expansion (specially around lesions),
which have been proven by neurophysiological and neuro-
imaging studies [9–12].
The brain reserve (seen as maximal lifetime brain vol-
ume), respectively, cognitive reserve could also have a pro-
tective effect against progression and may play a supportive
13
Journal of Neurology
ease. As these mechanisms are exhausted, patients are more easily
aware of newer and more progressive symptoms. Similarly, approved
treatment options decrease as the disease progresses
role to these mechanisms [13, 14]. The patients may only
become aware of worsening when these compensatory
mechanisms are exhausted later after a transition phase to
SPMS [15, 16]. These compensatory mechanisms can also
be an obstacle on the SPMS diagnosis in clinical practice
[17] (Fig. 1).
Recently, the concept of “silent progression” has been
proposed by Cree et al. as an interesting term in the con-
text of the subtle emergence of a neurodegenerative process
that cannot be early recognized on the evaluation of RRMS
patients [18]. On the same study, it was determined that
relapse activity was not associated with long-term disabil-
ity progression after 10-year follow-up even though it may
contribute to relative brain volume loss. On the other hand,
development of new lesions could increase the risk of long-
term disability progression and further SPMS [18].
Women who have had a multifocal syndrome or were
older than 34 years at disease onset and/or have had treat-
ment failure were at increased risk of conversion to SPMS
[4, 19]. The presence of motor symptoms at onset and male
gender was strongly associated with shorter time to SPMS
development in untreated patients, likewise younger age at
onset was associated with longer time to SPMS conversion
but also with younger age at progression [20].
Journal of Neurology
The effect of DMTs on conversion is still not universally
accepted. Although the use of DMTs in RRMS patients has
shown to reduce the proportion of patients progressing to
SPMS [6, 21–23], a long-term follow-up study reported sim-
ilar time to progression onset and clinical course in treated
patients compared to natural history studies [4]. The use of
DMT may also slow brain volume loss preserving the brain
reserve, which may have an impact on the onset of SPMS
[13, 18].
The diagnostic challenge of SPMS—patients’
perspective
A key characteristic of MS has been the presence of multiple
lesions affecting diverse anatomical locations at different
time points. This phenomenon has been considered since
its first formal description 150 years ago by Jean Martin
Charcot until nowadays, being an important factor of the
current diagnostic criteria [24, 25].
There is a great heterogeneity of clinical course, symp-
toms and response to therapy associated with different
immunopathological patterns [14]. They can evolve differ-
ently between patients over time and involve all body sub-
systems [16, 26, 27]. In addition, the progression of disease
can be differently modulated by genetic und epigenetic fac-
tors varying from one patient to the other.
Therefore, patients may notice subtle and different
changes that cause functional deficits and place further
burden on their daily living [28]. They may be aware of
an increase in the severity or intensity of their symptoms
and the appearance or worsening of some of MS-related
symptoms, such as spasticity and bladder or bowel prob-
lems [29–32]. Specific tasks such as sports activities or puz-
zle solving may become more difficult in this early stage
of SPMS [30]. In RRMS patients who already experienced
these symptoms for a while, these subtle changes may be
difficult to detect and communicate. With the time, patients
accustom to their situation with impairments and disabili-
ties, reassessing their perceived limitations of everyday life
[33, 34].
Compensatory processes at the CNS may delay the mani-
festation of a progressive disease (Fig. 1). Every patient is
different and can have a different heritable neurological or
brain reserve, modifiable cognitive reserve, or neuroplasti-
city capacity [13].
The psychosocial adjustment or adaptation to the
symptoms and disabilities secondary to MS is an impor-
tant aspect of the therapeutic approach on patients with
MS, necessary to manage new disease demands [35]. This
was better in those in remission than in those with SPMS
[36]. On the other hand, this adaption on patients still with
RRMS could also delay the diagnosis of SPMS, as the
patients and physicians do not detect new symptoms and
limitations. The exact importance of this adjustment on the
SPMS diagnosis is still not well described.
On the progressive phase, those MS symptoms that
the patients had during the relapsing–remitting stage may
become more difficult to cope with, having to experience
additionally new complaints [16]. Patients with SPMS
describe many physical and mental manifestations that
can restrict their activity and worsen disability [16, 28].
Fatigue, as one of the most commonly reported symptoms
of MS (up to 75–90% at some point in time), plays an
important role, and, together with the reduced mobility,
can be one of the most difficult symptoms to deal with
[16, 37].
However, there is a day-to-day variation of neurological
symptoms. MS symptoms variate with no clear replicable
pattern and related to stress. This variation could be chal-
lenging to understand by the patients and also an obstacle
objectively detecting new symptoms or progression by the
physicians [38–40].
The transition from RRMS to SPMS can be critical for
the patient at a psychosocial point of view, with uncer-
tainty and the feeling of being diagnosed again with a
different disease, with fewer or no treatment options [41,
42]. Communication skills of the treating neurologist with
concrete strategies should target this aspect of the disease.
The diagnostic process should be transparent to help the
patients understand the meaning of this new phase [16].
Clinicians’ challenges
For the clinicians, the diagnosis of the conversion from
RRMS to SPMS is challenging (Fig.  2). There are no
clear clinical, imaging, immunological or pathological
criteria that define the beginning of SPMS or transition
to the progressive phase of the disease [17, 43]. Clini-
cians frequently diagnose SPMS retrospectively, what
means a delay of SPMS diagnosis by up to 3 years after a
period of diagnostic uncertainty [44]. This steadily pro-
gression of baseline symptoms is independent of relapses
or remission, which are much more easily perceived by
the physician and patient as an intermittent neurological
deterioration [45]. It has been seen that up to two-thirds
of patients with insidious worsening of disability are still
considered by clinicians to have RRMS [18]. Together
with this uncertainty recognizing the transition to SPMS
and lack of objective tests, the physicians tend to be more
conservative than the patients regarding disease progres-
sion to avoid the categorization on a final phase of the
disease, sometimes also with an emotional component and
limited treatment options [8, 46].
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Fig. 2  Challenges and future  approaches on the definition of SPMS.
The lack of standardization, diagnosis delay, difficult communication
by subtle symptomatic changes and low sensitivity of the EDSS as
single diagnostic measure hinder a prompt diagnosis of SPMS. The
Defining SPMS
Several definitions of progressive disease and SPMS have
been discussed, e.g. by G. Ebers on retrospective clinical
trial data or the Cambridge definition [45, 47]. Lublin et al.
defined progressive disease as a steadily increasing, objec-
tively documented neurologic dysfunction or disability
without unequivocal recovery, admitting fluctuations and
stability phases [17].
Tightening up these definitions may facilitate earlier
diagnosis and, as Lublin suggests, already existing datasets
might provide answers on this problem.
Some SPMS predictor tools have been developed with
different approaches, parameters and output [43, 48, 49]
(Table 1). On a large cohort study (MSBase) and based on
a retrospective analysis of data from 17.356 patients with
MS and after analysis of 576 possible SPMS definitions, a
‘best definition’ was developed that can be used in clinical
trials to enable comparability of future research studies [43].
13
Journal of Neurology
adoption of a “Best definition”, development of screening tools and
adoption of newer clinical endpoints and outcome measures may be a
support for the physicians on the clinical practice
It is based on frequent EDSS evaluations and sugges-
tive of SPMS with a worsening in the EDSS step (1.0-point
with EDSS ≤ 5.5 or 0.5-point with EDSS ≥ 6.0), with a
minimum score of 4.0 and a pyramidal functional system
score of ≥ 2. This worsening should be confirmed at least
for 3 months within the same functional system score (FS)
that leads to progression. This definition identified 18% of
patients converting to SPMS compared with 14% who had
physician-diagnosed SPMS not using the definition, with a
good sensitivity (89%) and specificity (86%). Importantly,
it also enabled a diagnosis 3 years earlier than physician-
diagnosed SPMS [43].
The required time to confirm symptomatic disability pro-
gression has also been deeply discussed on different studies
as one of the most important factors concerning the stabil-
ity of the detected progression. Lublin defines “confirmed
progression” as an increase in neurological dysfunction
throughout a defined time interval (for example, 3, 6 or
12 months) [17]. Similarly, Lorscheider et al. evaluated the
 Journal of Neurology

Table 1  Overview of published SPMS predictor tools

msprediction.com SPMS nomogram Definitions of SPMS
MSARD (2014) [48] MSJ (2019) [49] Brain 2016 Lorscheider [43]

Study centre Gothenburg Karolinska MSBase

Source of data Of 306 untreated MS patients, 157 were diagnosed with Derivation cohort Swedish national registry SMSreg Analyzed 576 definitions of SPMS (based on EDSS, FS,
RRMS; 118/157 converted to SPMS; median observa- n = 8825 (of which 1488 converted to SPMS); patients confirmed progression and relapses)
tion time 11.5 years; Gothenburg Incidence Cohort included during 1940–2000, follow-up till 2016 N = 17,356 patients (June 2015) of which n = 2360 SPMS,
3 validation cohorts min follow-up 1 year
  British Columbia, n = 3967 (1980–2004), follow-up till
2008
  ACROSS and FREEDOMS
Approach used Onset of SPMS determined retrospectively based on Survival model containing selected variables based Comparing the different definitions to consensus diagno-
Lublin et al. [17]; continuous hazard functions/Poisson on literature with final selection based on backward sis of 3 neurologists
regression model selection model, Bayesian information criterion, and Sample of n = 200 pts of which n = 57 SPMS
prediction accuracy; SPMS based on Lublin et al. [17] Evaluation of long-term outcome—5 years
(retrospective in FREEDOMS)
Parameters Significant independent predictors: age, time since last Gender, age (year of birth), first recorded EDSS, age at Best definition: EDSS progression confirmed for
relapse; symptoms of last relapse and recovery disease onset (relapses and MRI not predictive) ≥ 3 months (1 point if EDSS < 6.0 or 0.5 if EDSS ≥ 6)
Not significant: gender, age at onset, number of relapses in the absence of a relapse, with minimum EDSS 4, and
and nature of first relapse pyramidal FS score 2
Output Estimates current risk of SPMS; expressed as a percent- Estimates risk of conversion to SPMS at 10, 15 and The data-derived algorithm was primarily designed for
age 20 years application to clinical trial data and to enable compara-
bility of future research studies

SPMS secondary progressive multiple sclerosis, EDSS expanded disease disability scale, FS functional system

13

sensitivity and specificity of definitions considering 3, 6,
12 and 24 months as confirmation period. The definitions
that led to the earliest diagnosis of SPMS were those with
confirmation period of 6 months combined with a minimum
EDSS score of 3.0 or a confirmation period of 3 months with
a minimum EDSS score of 4.0. The definition with 3 months
as required confirmation was considered as the ideal with
good accuracy and sensitivity despite lower specificity com-
pared to longer periods [43].
However, it has been reported that a short-term con-
firmation period of just 3 or 6 months could overestimate
the accumulation of disability by 30%, respectively, 26%
with low long-term progression stability and great risk of
disability regression [50]. This was also considered on the
MSBase definition: the psychometric characteristics of the
EDSS (with lower variability at higher scores) and lower
fluctuation after reaching certain level of disability allowed
a shorter confirmation period as long as a minimum disabil-
ity step and pyramidal FS where established. Added-on, the
exclusion of progression events related to relapse activity
had great influence on progression stability [43]. Therefore,
using the EDSS as clinical outcome and with the definition
limits proposed, a 3-month confirmation period could be
enough at the definition of SPMS.
On the setting of clinical trials, the evaluation of events
unrelated to relapses is usually realized using the baseline
EDSS as a reference. A recent study by Kappos et al. has
shown that a roving EDSS reference, whereas the obtained
EDSS Step is compared with the last visit instead of the
baseline, could be more sensitive on this goal. With this sub-
tle change, 50% more overall worsening events and approxi-
mately 70% more progression events were detected than the
regular methods [51]. This could change the way clinical
trials are designed and have a more realistic relationship
with the daily medical practice, where the EDSS is often
compared with the last visit instead of the baseline.
In clinical practice, a detailed neurological examination
leading to the Neurostatus-EDSS is not standard of care.
That is why, instead of neurological examination and EDSS,
a careful standardized neurological history and additional
functional testing including specific functional systems
as, e.g. cognition and vision can further help to assist with
an earlier diagnosis of SPMS. In addition, the EDSS as an
assessment tool has been widely criticized due to its lack
of linearity, low responsiveness, sensitivity and inter-rater
reliability [52, 53]. A silent progression during RRMS phase
could not be detected due to EDSS limitations [18]. There-
fore, different outcome measures could be included on the
diagnosis such as the Timed 25-Foot Walk (T25FW), the
9-Hole Peg Test (9HPT), low contrast letter acuity test and
cognitive function testing [34, 54–57].
A modified version of the conventional EDSS called
EDSS-Plus has been proposed as an interesting evaluation
13
Journal of Neurology
tool, adding the T25FW and 9HPT to the regular neurologi-
cal examination [55]. A change of ≥ 20% for T25FW and
9HPT, both parts of the Multiple Sclerosis Functional Com-
posite Measure (MSFC), may be more sensitive on detecting
disease impact and progression and has been even demon-
strated in cohorts of exclusively SPMS patients [54, 58–61].
New outcome measures could be used as endpoints for
patients with RRMS, such as the confirmed disability pro-
gression (CDP), that uses the parameter described also on
the EDSS-Plus; the progression independent of relapse
activity (PIRA), helping to distinguish the progression of
disability; or the “no evidence of disease activity” (NEDA)
outcome [43, 62, 63]. On a similar order of ideas, the use
of a cognition markers such as the Symbol Digit Modali-
ties Test (SDMT) combined with the EDSS could probably
detect more progression events measuring different aspects
of disability [64].
These measures should be defined as a complement to
clinical history. An integration of new and old methods with
the classical clinical history, in combination with several
patient outcome measures, could be key for the detection
of early progressive disease.
Screening tools for SPMS
The relationship between physicians and patients is a chal-
lenging aspect. The physicians need excellent communica-
tive practices to detect subtle disease changes [65]. In addi-
tion, physicians tend to avoid discussion of the emotional
and social aspects of disease changes, wishing to avoid
alarming patients with news that they are entering the final
phase of MS disease [28, 44, 65]. Similarly, the lack of evi-
dence-based treatments may obstruct the application of a
“progressive” label.
To help surmount such factors that contribute to diag-
nostic delay and under-diagnosis, screening tools, such as
the MS Progression Discussion Tool [66, 67], the MS pre-
diction score [48] or the SPMS nomogram [49], have been
developed and are on their way into clinical practice. This
could help clinicians quickly and more accurately to detect
the early, and often subtle, signs of progression of SPMS in
a standardized manner.
The MS Progression Discussion Tool, in example, inte-
grates computer technologies in a digital tool based on a
set of weighted questions regarding relapses, symptoms
and impacts experienced by the patient in the last 6 months
(Fig.  3). It uses quantitative and qualitative methods as
approach to evaluate subtle signs suggestive of progres-
sion to differentiate RRMS from early SPMS. The variables
associated to the nature of the symptoms (e.g. intermittent
vs. persistent, stable vs. worsening) and the presence of
ambulatory, mobility and cognitive symptoms where most
Journal of Neurology
Fig. 3  MS Progression Discussion Tool [67]. Screening questions are
addressed in three main areas considering the last 6 months: disease
activity (also relapse and recovery, MRI), symptoms experienced and
significantly associated to early SPMS [66]. This tool could
differentiate between RRMS and SPMS with high sensitivity
and specificity without need of an EDSS assessment.
Similarly, the SPMS nomogram emerges as the first vali-
dated graphical tool for representation of the patient’s risk
of developing SPMS within 10, 15 and 20 years. It uses data
available on routine clinical setting, such as year of birth,
sex, onset age, and first recorded EDSS to accurate predict
evolution [49].
Biomarkers in SPMS
Different contemporary biomarkers could have a clinical
utility to distinguish SPMS from RRMS, such as magnetic
resonance imaging (MRI) data or protein and metabo-
lite measurement of cerebrospinal fluid (CSF) or blood.
Research is still ongoing to identify those that can be used
for early identification of the transition to SPMS reflecting
its immunopathological characteristics [68]. A combined
approach with different biomarkers has also been discussed
that could aid the diagnosis and track disease progression,
such as MRI variables, proteins and metabolites [69]. A
composite marker that included cognitive evaluation and
MRI measures was also accurate in discriminating between
RRMS and SPMS [70].
Notwithstanding, there are still no defined biomark-
ers that allow to anticipate the conversion to SPMS. Here,
impact of these symptoms. Symptoms evaluated involve following
domains: visual, sensory, ambulatory, bladder and bowl, coordination
and balance, cognition, fatigue, speech and pain
we summarize the current progress on the most important
parameters and their possible future uses.
Imaging
Imaging measures of progression are not established or
standardized as phenotype descriptors for individual patients
although many markers are under consideration [71]. Newer
non-conventional MRI technologies have been developed
improving the quality of the obtained data, with more tissue-
specific imaging tools and more sensitive measurements to
detect grey matter lesions in vivo and progression in MS.
Some of the most used markers are the brain T2 hyperin-
tense lesion volume, brain T1 hypointense volume, new and
enlarging active T1 and T2 lesion number and global and
global/regional brain atrophy, the magnetization transfer
ratio in brain lesions or the spinal cord cross-sectional area
[72–75]. Between them, the brain atrophy and spinal cord
area may be the most promising biomarkers for monitoring
neurodegeneration, particularly in patients with SPMS who
are characterized by less inflammation. They could be a very
promising tool for distinguishing disease- and treatment-
related brain volume changes and also the transition from
RRMS to SPMS [18, 71, 76–78].
Advanced MRI techniques are also on investigation and
may provide higher pathological specificity and be more
closely associated with clinical correlates, such as the
magnetization transfer ratio, diffusion tensor imaging and
13

magnetic resonance spectroscopy or fractional anisotropy
[76, 79].
The study of the retina through the Optical Coherence
Tomography (OCT) is also promising in MS progression
detection and neuroprotective strategies. The measurement
of retinal nerve fibre layer (RNFL) thickness and macular
volume have been included in clinical trials on progressive
MS and data suggest that RNFL thinning may be greater in
SPMS and PPMS patients compared to those with RRMS,
especially within quadrants of peripapillary retina [80].
However, patients with progressive and non-progressive
forms of MS have thinner RNFL compared to controls
independent of history of optic neuritis [80, 81]. Thus,
further data are needed to demonstrate how these measures
could predict or detect disease progression.
Molecular markers
Alterations on selected biochemical markers on patients
with SPMS compared with RRMS have been reported but
there is no clear standardized use of them at the moment.
High levels of 14-3-3 protein, tau, neurofilaments, chi-
tinase 3-like 1 and cystatin C correlated with disability
progression in MS patients [76]. Up to 19 metabolites
from the tryptophan and phenylalanine metabolisms show
unique alterations to the SPMS phenotype and significant
correlations to EDSS, disease duration and MRI measures
[82].
Neuronal destruction markers
Current interesting biomarkers are the neurofilaments, espe-
cially neurofilaments light chain (NfL). Nowadays, they
can be even detectable at very low blood concentrations,
proportional to CSF levels. This is of great use in several
neurological diseases, as well as in MS, being a sensitive
(although non-specific) and clinically meaningful biomarker
to monitor tissue damage on MS [83–87]. Regular moni-
toring of serum NfL could demonstrate future or present
disease activity even when other clinical parameters seemed
to be stable [88]. Blood NfL levels show a good correlation
with brain atrophy detected by MRI measures and are sen-
sitive to detect disease activity on progressive forms of the
disease [89, 90]. NfL levels could even have a prognostic
value of disease worsening, with a direct correlation between
serum NfL percentile level and future brain and cervical
spinal volume loss [91, 92]. Even the risk of conversion from
RRMS to SPMS has been associated with CSF-NfL levels
[93]. However, the use of NfL is currently mostly restricted
to sub-specialized centres and further data must be generated
to support its use on the daily practice.
13
Journal of Neurology
Prognosis in patients with SPMS
MS is variable from person to person, so predicting
patients’ prognoses is challenging. Generally, patients
with SPMS have an unfavourable prognosis and can
expect a slow and unremitting worsening of their abil-
ity to function. Data concerning time to reach determined
disability scores are variable [94]. Based on data from a
cohort of more than 800 patients assessed over a period of
28 years, patients with SPMS progressed to EDSS of 6.0,
8.0 and 10.0 within about 5, 15 and 30 years, respectively,
of SPMS onset [5]. Greater frequency of early relapse,
brainstem and cerebellar presentation, and disease onset
at age ≤ 20  years were associated with faster progres-
sion to EDSS 8.0 [5]. In another cohort of 212 patients
with RRMS followed up to 50 years, the median time to
EDSS 6.0 was 22 years and to EDSS 7.0 was 37 years
[95]. Fifty years after onset, 14% of patients remained
progressive, 22% were progressive but ambulatory, 16%
were non-ambulatory and 48% had died. It has also been
reported that 25% of patients will reach a EDSS of 8.0
within 16 years [19].
Most SPMS patients will find a continued accumulative
worsening of disability compared to the relapsing–remit-
ting phase of the disease [31, 43]. Physical functioning
will generally be significantly impaired [31], with a great
group no longer being able to walk 100 m unaided [43].
Those patients who are still able to work are more likely to
need time off work than those with RRMS [31].
Coping with a diagnosis of SPMS is emotionally dif-
ficult for patients, but the prognostic uncertainty and dif-
ficulties in communication can be equally challenging for
clinicians, particularly as patients’ views and opinions on
how much information they want varies widely [16, 96].
Some patients experience unsatisfactory discussions with
clinicians, particularly at the time of diagnosis, which can
have long-lasting effects and expectations on future dis-
cussions. Positive adjustment will help patients to cope
emotionally and psychologically with SPMS. This is often
realized through self-management and adapting strategies,
such as accepting the limitations placed on their daily liv-
ing by the progressive nature of the disease and staying
focused on the present and on positive aspects of their
lives in spite of such a debilitating disease [16, 96].
Patients with SPMS are likely to eventually require pal-
liative care. Support should be provided by a multidiscipli-
nary team considering their physical and emotional needs,
spiritual and social care [32, 97, 98]. A palliative approach
offers patients and their families help with symptoms and
support in anticipating and planning for decisions that are
likely to arise as the disease progresses, with the overall
goal of providing the best possible quality of life [97].
Journal of Neurology

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