Why are people with multiple sclerosis and autoimmune neurological diseases referred for a neuropsychological evaluation?

Cognitive deficits are common in people with MS and certain types of autoimmune neurological diseases (e.g., autoimmune encephalitis [AE], neuromyeltitis optica spectrum disorders [NMOSD], and neurosarcoidosis), with frequency up to 100% in some cohorts AE1, around 30-70% in people with MS2 or NMOSD3, and around 20% in cohorts of myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD)4. Additionally, around 50% of cohorts with neurosarcoidosis report cognitive difficulties5. Cognitive impairment can significantly impact daily functioning, occupational performance and quality of — and may be further exacerbated by — high rates of mood disorders, anxiety, sleep problems and fatigue found in these groups.

Early identification and management of cognitive impairment in people with MS and autoimmune neurological diseases is crucial. Research has shown that interventions like cognitive rehabilitation yield the best results for individuals with a mild degree of cognitive impairment6. However, detection of cognitive deficits in a typical clinical setting can be challenging for many reasons, including those related to space and time limitations. Additionally, self-reported cognitive deficits correlate only weakly with performance on objective cognitive measures. Cognitive screening, which involves the administration of brief, validated measures, such as the Symbol Digit Modalities Test (SDMT)7 or the recently developed Brief Assessment of Cognitive Health (BACH)8, can be helpful in this regard and is a recommended part of routine clinical care9. However, screening measures are limited in scope, often only assessing processing speed, and may be insensitive to more subtle cognitive deficits or changes over time. Additionally, the utility of screening measures in people with demyelinating and/or autoimmune neurological diseases other than MS is unclear.

Given the wide range of cognitive deficits often observed in people with MS and autoimmune neurological diseases1,2, a more comprehensive neuropsychological assessment may be appropriate. Neuropsychological assessment can provide detailed information about an individual’s cognitive strengths and weaknesses across multiple cognitive domains and can inform treatment (i.e., cognitive rehabilitation, change in disease-modifying therapy) or determine the impact of cognitive deficits on an individual’s occupational or academic functioning. Neuropsychological assessment can also be used to help detect and characterize cognitive changes in individuals who experience cognitive relapses and change associated with the progression of disease. In some cases, the pattern of cognitive strengths and weaknesses (also known as the cognitive profile) can help distinguish between the cognitive effects of MS versus other causes, including other neurodegenerative diseases like Alzheimer’s disease. However, caution is needed for the latter distinction; research examining the cognitive profiles of pwMS and people with Alzheimer’s disease has revealed that the profiles may not be as distinct as we once thought10,11. Neuropsychological assessment can also help to clarify the extent to which cognitive deficits may be associated with underlying neurologic disease versus the impact of psychological comorbidities (including functional or somatic disorders), fatigue and sleep problems, among other factors.

Lastly, cognitive deficits are one of the so-called “invisible symptoms” that people with MS and autoimmune neurological diseases frequently cite as an unmet need that is not discussed enough in the typical clinical setting12. Assessment of cognitive deficits can assist with disease monitoring, implementation of workplace or school accommodations and guide rehabilitative treatments. In some cases, a neuropsychological evaluation can also provide critical information to guide return-to-work decisions. Additionally, as early cognitive impairment is linked to the risk of disease progression, detection of such deficits may help to inform treatment and prognosis.

What is a neuropsychological assessment and what does it involve?

A neuropsychological assessment is a comprehensive, formal evaluation of cognitive abilities, emotional functioning and behavior. Information is gathered through a combination of a thorough clinical history and administration of standardized instruments, which are used to identify areas of cognitive strength and/or deficit in the context of known or suspected neurological disease. Factors that may exacerbate cognitive difficulty, such as mood disorders, anxiety, sleep problems and fatigue are also identified. The evaluation is tailored to the needs of the individual being assessed.

A neuropsychological assessment is conducted by a clinical neuropsychologist and involves medical record review, a clinical interview of the individual, and the administration of neuropsychological tests and questionnaires assessing various cognitive domains, mood, personality, behavior and other symptoms (e.g., fatigue or pain). These tests are administered by a trained examiner in either a paper-and-pencil or digital format. The evaluation typically takes two to four hours, though, in some cases, they may last longer. The assessment is sometimes conducted in two appointments to accommodate fatigue; this is determined on a case-by-case basis. Table 1 provides a list of commonly used neuropsychological test and the domains they assess.

Domain Test
Verbal Memory California Verbal Learning Test (CVLT), Rey Auditory Verbal Learning Test (RAVLT)
Visual Memory Brief Visuospatial Memory Test-Revised (BVMT-R)
Language Controlled Oral Word Association Test (COWAT), Boston Naming Test (BNT)
Visuospatial Skills Judgment of Line Orientation (JOLO), Rey-Osterrieth Complex Figure Test
Processing Speed Trail Making Test (A), Symbol Digit Modalities Test (SDMT), Paced Serial Addition Test (PASAT)
Executive Functions Trail Making Test (B), Wisconsin Card Sorting Test, DKEFS Sorting Test
Psychological Functioning Beck Depression and Anxiety Inventories, Personality Assessment Inventory, Minnesota Multiphasic Personality Assessment (MMPI)

Following completion of the assessment, the tests are scored and standardized according to normative data that considers factors such as the person’s age, sex, education level and race/ethnicity. The neuropsychologist then integrates the information obtained through the record review, clinical interview and test results into conclusions, which are summarized in the neuropsychological evaluation report. This report outlines cognitive test performance, including strengths and weaknesses and/or areas of deficit and potential etiological and contributing factors. The report also often provides recommendations for follow-up, strategies to optimize cognitive and day-to-day function and targets for treatment.

When should a person with MS be referred for neuropsychological assessment?

For people with MS, practice guidelines9 recommend baseline and annual cognitive screening with a validated screening tool, such as the SDMT, for: 1) all people, 8 years or older, who have been diagnosed with MS, 2) adults who have experienced their first clinical event and 3) adults who have MRI evidence consistent with MS (Radiologically Isolated Syndrome). Cognitive screening is also recommended for any person with MS who reports a change in their cognitive functioning.

A more comprehensive neuropsychological evaluation is recommended for: 1) any adult with a positive screen, 2) any adult whose yearly screening demonstrates a clinically significant drop in functioning from a previous assessment, and 3) for individuals who, regardless of their cognitive screening results, report problems at work/poor performance reviews or who are applying for disability benefits. The results from a comprehensive evaluation can also be helpful to confirm or refute suspected progression of disease. Neuropsychological evaluation is also recommended for any child with MS who experiences a decline in academic or behavioral functioning for unexplained reasons. Evaluations should not take place during a known or suspected exacerbation, as cognitive symptoms can acutely (and to some extent, temporarily) worsen during this time.

At the Mellen Center, we screen cognitive abilities using the Processing Speed Test13, an iPad-based analog to the SDMT at all Neurology visits. We recommend referral for neuropsychological evaluation for any individual if their PST score falls at least one standard deviation below the normative mean (z score ≤ -1) or if they demonstrate a decline of at least 1 standard deviation when compared to their own standardized PST scores across serial assessments. In addition, if resources allow, we recommend that early comprehensive assessment be considered to establish a cognitive baseline, regardless of the presence of subjective cognitive complaints. Establishing a comprehensive baseline can lead to earlier identification of future cognitive changes, allowing for earlier intervention if/when needed. Individuals without cognitive complaints can be assessed with an abbreviated cognitive test battery. We also recommend that individuals be referred for comprehensive neuropsychological assessment if they report concerns regarding cognitive decline or cognitive changes that impact their ability to complete daily tasks or interfere with their occupational or academic functioning. Neuropsychological evaluations can provide evidence to support reasonable accommodations in the workplace or in academic pursuits for people with MS and other autoimmune neurological diseases.

When should a person with an autoimmune neurological disease be referred for neuropsychological assessment?

There are no formal guidelines for neuropsychological testing in people with other autoimmune neurological diseases. Therefore, our recommendations are similar to those for people with MS. Specifically, for people with NMOSD, MOGAD or neurosarcoidosis, we recommend baseline and annual cognitive screening, with more comprehensive testing for those who screen positive, endorse cognitive concerns or show a decline in their cognitive screening performance over time. Re-evaluation may occur as needed, to monitor progression of disease, treatment effects, or assess for cognitive decline or to update recommendations for cognitive rehabilitation, occupational or academic accommodations.

For people with AE, we recommend early assessment, when a patient is able to tolerate testing, and annual follow-ups (as needed) to track recovery and/or treatment effects and may help to guide rehabilitative strategies and make recommendations for return to work.

How can neuropsychological assessment benefit people with MS or an autoimmune neurological disease?

The information derived from neuropsychological assessments has numerous benefits. Results can guide cognitive rehabilitation, identify factors that are contributing to cognitive difficulties and, if treated, can result in cognitive improvements. In some cases, the results can differentiate between neurologic, psychiatric, and other causes of cognitive symptoms. The evaluation can help identify potential safety concerns (such as driving, managing medications and making healthcare decisions). Results can also support a person’s pursuit of workplace or school accommodations or in the application for disability benefits. For people with autoimmune encephalitis, results of a neuropsychological evaluation can help monitor treatment effects and track recovery.

Re-evaluation may be useful to track for cognitive decline, either due to MS/an autoimmune neurological disease or the presence of a concomitant neurodegenerative disease, such as Alzheimer’s disease, and can be used to update recommendations as needed. However, it is recommended that repeated exposure to neuropsychological tests be managed cautiously, as scores can become artificially inflated due to previous and/or recent exposure to test stimuli (also known as practice effect). This limits the utility of the repeated exam to answer important clinical questions, and the validity of the test findings should be questioned. Repeating an evaluation less than one year before the prior exam is not recommended unless there is a strong clinical reason to do so (such as rapid decline in cognitive status, monitoring response to treatment). There is currently no recommended time frame for re-evaluation in MS or autoimmune neurological diseases.

While a thorough discussion about treatments is beyond the scope of this review, we did want to provide a brief note about it here. Currently, there are no gold standard treatments for cognitive impairment in MS.14 Cognitive rehabilitation is one commonly used approach; it aims to strengthen and improve cognitive skills using structured interventions that are tailored to the individual’s needs. This type of treatment is done by a variety of different professionals, depending on their training and experience. At the Mellen Center, it is done by clinical neuropsychologists and speech-language pathologists. Like more traditional PT and OT approaches, this treatment focuses on practice and rehearsal of weaker skills, often by using identified strengths to assist in this process. Cognitive rehabilitation also focuses on teaching practical strategies and workarounds that support weaker skills and help address day-to-day frustrations the individual encounters. The neuropsychological evaluation directly informs rehabilitation strategies and treatment planning by identifying both areas of weakness and strengths, the latter of which can be leveraged to address weaknesses. Research on cognitive rehabilitation has thus far revealed evidence supporting its use, but refining and standardizing these approaches has also been recommended15,16. Pharmacological interventions have limited or mixed evidence to support their use and could cause undesired side effects or be medically contraindicated. To date, the direct impact of disease-modifying therapies on cognitive impairment has not been extensively investigated. One recent systematic review and meta-analysis found modest positive effects of these drugs on cognitive skills in pwMS17, but a recent paper re-analyzed pharmaceutical study data and found that the positive effect may be nothing more than observed practice effect due to repeated exposure to the tests/test stimuli18. Therefore, cognitive rehabilitation remains our best option to address these symptoms.

*A note regarding disability applications: While the recommended guidelines indicate that people with MS who are applying for disability should be seen for a neuropsychological assessment, neuropsychologists at the Mellen Center are not contracted as examiners for the Social Security Administration. All neuropsychological assessments conducted through the Mellen Center are clinical in nature and are billed through insurance. Therefore, there should be a clinical indication for the evaluation.

References

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