By Dr Tatjana Reynders

Introduction

Cognitive dysfunction is prevalent in 40-70% of patients with multiple sclerosis (MS) (1), more so in progressive than in relapsing-remitting phenotypes (2). It appears in up to 68% in early MS (disease duration ≤ 2y) and in up to 81% in late MS (disease duration ≥ 12y) (3). Cognitive impairment in MS preferentially occurs in the following domains: information processing speed (28-52%), episodic memory (30-55%), working memory, verbal and visual memory, verbal fluency and executive functions (4), and impacts on employment and socio-economic status, resulting in increased socio-economic burden, as well as on the patient’s social life, coping skills, quality of life and compliance for disease-modifying therapy (DMT) (5).

Method

We performed a retrospective review of case notes for MS patients (according to the 2017 McDonald criteria (6) treated in the outpatient MS clinic of a teaching academic hospital (Universitair Ziekenhuis Antwerpen, Edegem, Belgium) who visited the clinic between January 1st and 31st 2018. Patients were seen by either an MS specialist or one of the three assistant neurologists in training with an EDSS certificate. These patients were often also seen by the MS nurse or a social assistant, preceding or following the medical consultation.
In this internal audit, we aimed to 1) determine the report rate of cognitive impairment in MS patients, 2) to evaluate how cognitive symptoms are diagnosed and managed, and 3) to set up a plan of action to improve the management of cognitive symptoms in MS. For reference, we used the guidelines published by The National Institute for Health and Care Excellence (NICE), promoting 1) awareness of cognitive problems, including memory problems that the person may not immediately recognize or associate with their MS, 2) awareness that anxiety, depression, difficulty in sleeping and fatigue can impact on cognitive problems, for which to offer appropriate assessment and treatment, and 3) referral of people with MS and persisting memory or cognitive problems to both an occupational therapist and a neuropsychologist to assess and manage these symptoms (7).

Results

In total, 120 patient reports were reviewed. Median age, gender distribution, median EDSS values and DMT use are shown in Table 1.

  All MS

(n = 120)

RRMS

(n = 105)

SPMS

(n = 9)

PPMS

(n = 6)

Median age (SD) 43 (13.2) 41 (11.9) 60 (10.1) 66.5 (8.7)
Female (%) 75.8 78.1 44.4 83.3
Median EDSS (SD) 3.0 (2) 2.5 (2) 6.5 (2) 6.0 (1.5)
DMT (%) 70.8 80.0 11.1 0.0
Interferon (n) 17 16 1
Teriflunomide (n) 5 5
Fingolimod (n) 8 8
Dimethyl fumarate (n) 15 15
Natalizumab (n) 27 27
Ocrelizumab (n) 4 4
Alemtuzumab (n) 4 4
ASCLEPIOS study (n) 3 3
TolDC study (n) 2 2

 

Table 1:

Overview of demographics, EDSS scores and DMT use in the reviewed MS population. DMT: disease modifying therapie. EDSS: expanded disability status scale. MS: multiple sclerosis. PPMS: primary-progressive multiple sclerosis. RRMS: relapsing-remitting multiple sclerosis. SD: standard deviation. SPMS: secondary-progressive multiple sclerosis.
Cognitive impairment was reported in 7.5% (n = 9) of all MS patients (see Table 2), with a predominance for the RRMS phenotype (n = 5), followed by SPMS (n = 3) and PPMS (n = 1). Deficits in short-term memory and concentration were most reported by either patient, family member of the physician. Despite the low numbers, in only 1.7% of cases the report included a statement on the absence of cognitive symptoms.

 

  All MS

(n = 120)

RRMS

(n = 105)

SPMS

(n = 9)

PPMS

(n = 6)

Cognitive impairment (%) 7.5 4.8 33.3 16.7
Patient reported (n) 5 3 2 0
Partner reported (n) 1 0 0 1
Reported by MD (n) 3 2 1 0
Cognitive domain
Short-term memory (n) 4 3 0 1
Frontal behaviour (n) 1 1 0 0
Concentration (n) 4 3 1 0
Information processing speed (n) 1 1 0 0
Not specified (n) 2 0 2 0
Reported absence of CI (%) 1.7 1.9 0.0 0.0

 

Table 2:

Prevalence of reported cognitive impairment (CI) in the reviewed MS population and cognitive domains that were reported to be affected. MD: medical doctor. MS: multiple sclerosis. PPMS: primary-progressive multiple sclerosis. RRMS: relapsing-remitting multiple sclerosis. SD: standard deviation. SPMS: secondary-progressive multiple sclerosis.
In patients where cognitive symptoms were reported, only 22.2% received additional neurocognitive testing, while about half received some form of treatment (see Table 3). This treatment was equally distributed among coaching of behavioural changes (adapting the work-environment, sleep hygiene), the use of performance enhancing drugs (amphetamines), the cessation of medication that could have induced the reported cognitive symptoms (amitryptiline) and referral for cognitive rehabilitation with an occupational therapist and a speech therapist. Two patients refused further diagnostic or therapeutic actions, one showed spontaneous amelioration of symptoms and for two patients no reason was documented in the patient report (see Table 3).

 

  All MS

(n = 9)

RRMS

(n = 5)

SPMS

(n = 3)

PPMS

(n = 1)

Action taken (%) 22.2 20 33.3 0
Complete NPE (n) 1 1
BICAMS (n) 1 1
Treatment
Behavioural (n) 1 1
Performance enhancing drugs (n) 1 1
Stop causal drug (n) 1 1
Rehabilitation (n) 1 1
Reason if no action
Refused (n) 2 1 1
Evolution (n) 1 1
None given (n) 2 1 2

 

Table 3:

Summary of appraisal and management of cognitive symptoms in patients with suspicion of cognitive impairment. BICAMS: brief international cognitive assessment for multiple sclerosis. MS: multiple sclerosis. NPE: neuropsychological evaluation. PPMS: primary-progressive multiple sclerosis. RRMS: relapsing-remitting multiple sclerosis. SD: standard deviation. SPMS: secondary-progressive multiple sclerosis.
Discussion
Compared to prevalence reports in medical literature, cognitive impairment was under-reported in our sample. Often patients don’t spontaneously complain of cognitive symptoms or are not aware of them, while family members and/or caregivers are not always present during routine visits. In addition, even though physicians often inquire about cognitive symptoms, there is significant underreporting in case of absence of cognitive deficits.
Neuropsychological test batteries are infrequently used, which could be explained by the time-consuming nature of full neuropsychological evaluations and the fact that a consultation with the neuropsychologist and/or MS nurse is not reimbursed by the government in Belgium. Therefore, only selected cases, usually patients who are still employed, are referred for diagnostic tests and subsequently for cognitive rehabilitation.
One solution could be to use the Symbol Digit Modalities Test (SDMT) which takes little time to perform and was proven sensitive to detect early signs of cognitive impairment in MS patients as it screens for impaired information processing speed, which is most often first affected (8). The SDMT can be performed yearly as a screening tool (9) and additionally in case of cognitive symptoms. The threshold for diagnosis of impaired processing speed should be based on the patient’s age category, as increasing age also affects processing speed (10).
One patient who was referred for rehabilitation was adequately managed by a multidisciplinary team consisting of the neuropsychologist (intake), occupational therapist and speech therapist. While NICE only recommends the first two (7), speech therapists in Belgium are also trained to deal with cognitive deficits and could therefore provide additional support for the patient and/or their family members. However, at the time it is unclear whether this method is cost-effective.
One limitation of the audit is that consultation notes from the MS nurse were not included in the electronic record review. While this could have provided a better view on the prevalence of cognitive symptoms in the outpatient MS population, the current analysis provides clear clues on how to increase the quality on cognitive appraisal by the physician who is ultimately responsible for his/her patients.

Action plan

  • Set-up a standardized protocol to include cognitive appraisal in patient reports
  • Yearly cognitive screening with the SDMT by the MS nurse
  • Additional SDMT testing in case of cognitive symptoms
  • Interpretation of SDMT test result using age-adjusted normative values
  • Referral to neuropsychologist for NPE in case of abnormal age-adjusted SDMT results
  • Appraisal of cognitive dysfunction with BICAMS by the neuropsychologist (detailed if indicated)
  • Multidisciplinary rehabilitation: neuropsychologist, occupational therapist, speech therapist

References

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  2. Potagas C. et al. Cognitive impairment in different MS subtypes and clinically isolated syndromes. J Neurol Sci 2008;267(1-2):100-106.
  3. Fischer M. et al. How reliable is the classification of cognitive impairment across different criteria in early and late stages of multiple sclerosis? J Neurol Sci 2014;343(1-2):91-99.
  4. Sumowski JF. et al. Cognition in multiple sclerosis: State of the field and priorities for the future. Neurology 2018;90(6):278-288.
  5. Morrow SA. et al. Predicting loss of employment over three years in multiple sclerosis: clinically meaningful cognitive decline. Clin Neuropsychol 2010;24(7):1331-1145.
  6. Thompson AJ. et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurology 2018;17(2):162-173.
  7. Nice.org.uk. (2014). Multiple sclerosis in adults: management | Guidance and guidelines | NICE. [online] Available at: https://www.nice.org.uk/guidance/cg186 [Accessed 4 Jun. 2018].
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  9. López-Górongora M., Querol L., Escartín A. A one-year follow-up study of the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT) in relapsing-remitting multiple sclerosis: an appraisal of comparative longitudinal sensitivity. BMC Neurol 2015;15:40.
  10. Burggraaff J., Knol DL., Uitdehaag BMJ. Regression-based norms for the Symbol Digit Modalities Test n the Dutch population: improving detection of cognitive impairment in Multiple Sclerosis. Eur Neurol 2017;77(5-6):246-252.