Cognition, Cognitive Dysfunction, and Cognitive Rehabilitation in Multiple Sclero sis Mary Pepping, PhD, ABPP-CNa,*, Julie Brunings, Myron Goldberg, PhD, ABPP-CNa
MS-CCC, BC-ANCDS
b
,
KEYWORDS Cognition Cognitive rehabilitation Cognitive retraining Multiple sclerosis Cognitive dysfunction KEY POINTS Nature of cognitive dysfunction in MS: complex attention, memory acquisition and retrieval, speed of information processing, and both the neurocognitive and neurobehavioral features of executive functions can all be disrupted in the context of often wellpreserved basic intelligence. Importance of comprehensive evaluation: this should include at a minimum a thorough neuropsychological evaluation and clinical observations of the treating cognitive rehabilitation specialist. Pathophysiology of MS: implications for neurocognitive and neurobehavioral changes: subcortical lesions exert a clear adverse effect on complex attention, memory retrieval, and frontal-subcortical executive functions, with inflammatory and degenerative processes each playing a unique role in the background strengths and weaknesses of the individual with particular forms of MS. Cognitive rehabilitation: sophisticated cognitive rehabilitation approaches combine clinicians’ understanding of each person’s particular neurocognitive and neurobehavioral strengths and difficulties, along with training of specific strategies designed to reduce the negative functional effects of the problem areas.
INTRODUCTION
Cognitive functioning problems are common in multiple sclerosis (MS), occurring in at least half of all persons with the disorder.1,2 Although the patterns of neuropsychological disruption in people with MS are well known (ie, attention, memory acquisition and
a
Department of Rehabilitation Medicine, University of Washington School of Medicine, Box 356490, 1959 Northeast Pacific Street, Seattle, WA 98195, USA; b Rehabilitation Therapy Department, University of Washington Medical Center, Box 356154, 1959 Northeast Pacific Street, Seattle, WA 98195, USA * Corresponding author. E-mail address: [email protected]
Phys Med Rehabil Clin N Am 24 (2013) 663–672 http://dx.doi.org/10.1016/j.pmr.2013.06.009 1047-9651/13/$ – see front matter Ó 2013 Elsevier Inc. All rights reserved.
pmr.theclinics.com
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retrieval, speed of information processing, and features of executive functions can be adversely affected1–8), much variability exists. A comprehensive neuropsychological evaluation is critical to effectively identify the set of neurologic and reactive disruptions for each person with MS.9 The expert cognitive rehabilitation specialist also gathers pertinent formal test data and important interview information at the start of therapy to guide the plan of treatment. Observations by the treating clinician of the person’s cognitive retraining needs as well as clinical data regarding effectiveness of selected strategies and approaches are key components of on-going evaluation for maximal treatment effectiveness. All of these strategies also allow the clinician to provide feedback to the person with MS about their residual strengths and the various practical applications of those strengths to support improved function and hope. The literature on typically preserved versus disrupted neuropsychological functions in people with MS has been well established over the last 25 years or more of study.1,2,6 The time of onset, range of affected features, and degree of severity may vary with each person’s disease presentation and subtype (relapsing remitting MS, primary progressive MS, secondary progressive MS, and clinical isolated syndrome10,11) in the particular context of their long-standing premorbid skills and difficulties. However, for most people with MS,1,2,4,7,8,12 the subcortical changes associated with white matter disease produce predictable problems in thinking. Lesion extension into cortical gray matter can occur,13 as can some degree of atrophy over lengthy disease course,14 in some individuals with MS. As we learn more about the underlying neurophysiology of MS (eg, lesion load, gray matter involvement, atrophy, and brain regions particularly vulnerable to disruption), we are in a better position to anticipate, understand, and treat residual neurocognitive and neurobehavioral difficulties. Given what is known about the initial primarily subcortical nature of disruptions and relative sparing in most instances of cortical functions, likely strengths can also be anticipated. This knowledge of residual strengths and difficulties can give clinicians and the patient a template to develop pertinent strategies and procedures to support current function and help establish effective overlearned systems for maximal future function to the fullest extent possible. Clinicians appreciate that these changes induced by MS do not occur in the abstract. They occur each time in a specific person who is trying to find the best way to live fully and with meaning despite the challenging constellation of symptoms caused by MS. It is the thesis of this article that the cognitive problems that result from MS can be anticipated, understood via appropriate examination, and then treated to support improved performance. We would also like the reader to expand their notion of cognitive changes to include both the neurocognitive (eg, memory retrieval problems) and neurobehavioral (eg, reduced awareness, impulsivity adversely affecting problem solving) dysfunction, which is important to address when designing treatment interventions. It is also important to appreciate premorbid personality strengths and vulnerabilities as well as reactive emotional concerns and physical symptoms that can adversely affect thinking performance. First, an overview is presented of the neuroanatomy, neuropathology, and neurophysiology relevant to MS and the particular brain structures and processes that underlie areas of disrupted versus preserved cognitive function. PATHOPHYSIOLOGY OF MS
MS is considered to be an autoimmune-related disorder of the central nervous system, affecting initially the myelin sheath of axons. The cause of this autoimmune
Cognitive Rehabilitation in MS
variant is unknown but is believed to involve an interaction of genetic and environmental factors. Brain and spinal cord regions are vulnerable. An inflammatory process at the myelin sheath site is considered to be a hallmark initial change in MS. As this process evolves, axonal damage and scarring have been shown.15,16 Axonal damage has been associated with loss of axonal integrity and degeneration, which can give rise to cerebral atrophy.17 MS-related disability is considered to stem from 2 processes: acute inflammatory demyelination and axonal degeneration.18 Although MS is often considered a disorder affecting only subcortical white matter, there is considerable evidence that cortical demyelination can also occur, even at the early stages of the disease.13 That both subcortical and cortical brain regions can be affected in MS indicates the diffuse nature of the disease and, in turn, the risk for a widespread set of cognitive functioning problems. However, despite the potential for diffuse brain involvement, MS lesions do tend to locate in the periventricular white matter, cerebellum, and brainstem.19,20 Through structural neuroimaging, several MS-related pathophysiologic changes have been examined in the literature as risks for cognitive functioning difficulties.21 Among these visualized changes, lesion load (also referred to as lesion burden), lesion location, and global or regional atrophy have received the most attention. Lesion load refers to the number of lesions identified on brain imaging within a given area and has been shown in numerous studies to be correlated positively with greater cognitive impairment.22,23 For example, Moriarty and colleagues24 reported a positive correlation between juxtacortical lesion load and memory dysfunction in persons with MS. Bermel and colleagues25 noted the role of frontal lobe disease in executive dysfunction in MS. Global atrophy and regional brain atrophy have also been found to be especially associated with cognitive dysfunction.14,25 Neocortical volume loss has been shown to differentiate cognitively impaired and cognitively intact individuals with MS.26 Moreover, in 2 studies by Benedict and colleagues,26,27 the relative contribution of brain atrophy to cognitive impairment was greater than lesion burden, whereas width of the third ventricle was more highly associated with cognitive dysfunction than was whole brain atrophy. More specifically, in some studies,28 cognitive impairment and thalamic atrophy were linked in people with MS, particularly men.29 The reason for the sex difference is not clear, but the central role of the thalamus as a relay station for transmission of information among and between frontal cortex, basal ganglia, and other cortical regions could explain why atrophy there would have such an important deleterious effect on key frontal-subcortical functions. COMPREHENSIVE ASSESSMENT
In the neurorehabilitation setting, effectively evaluating and treating patients with acquired brain dysfunction requires a thorough understanding of the person’s abilities, difficulties, reactions, and preferences. This understanding is essential to designing and delivering effective treatment. Although there is a role for briefer examinations in some circumstances to identify and document possible cognitive changes in MS,30 a brief examination alone is not typically sufficient to fully elucidate the nature of the person’s skills and deficits for optimal treatment planning purposes. It also does not obtain much information about personality style or features, which can augment or impede ability to participate and benefit from treatment, as natural premorbid factors or personality changes that may be developing with cortical atrophy.31 Hence, we typically use comprehensive standardized evaluations at the start of care.
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These evaluations include at a minimum in-depth neuropsychological evaluation and may include formal speech and language evaluation and occupational therapy evaluation of higher-level activities of daily living. We would like to broaden readers’ view of cognitive evaluation in MS to include the kind of on-going evaluative observation that is an integral part of the treating clinician’s role as they actively modify or refine treatment strategies and advice to fit the problems observed in the person’s performance. This performance can include the quality of the person’s in-session work, completed homework assignments, or other functional behavior (eg, observations of relevant behavior in the waiting room). For example, is the person rifling through a large messy backpack full of papers trying to find a homework assignment despite all attempts to impose some organizational structure? Perhaps it is time to rethink the strategies or approaches being used. A clinic-based therapist can also make note of the person’s ability to keep appointments, to show up on time for those appointments, to bring with them requested materials, and to complete other scheduled activities for the week. It is easy to check if the person has important items with them every session (eg, wallet or purse, keys, phone, schedule, note-taking device or materials). Feedback in the form of test or course grades for those in college or work performance evaluations for employed people also provides objective information regarding improvements in function. Including the person’s family member periodically allows the clinician to obtain observer updates on accomplishments in the home and community setting (eg, taking medications independently, better follow-through with completion of chores, improved efficiency of verbal communication, jotting down notes to aid memory performance). COGNITIVE REHABILITATION (COGNITIVE RETRAINING)
Cognitive rehabilitation is indebted to the early pioneers of these techniques32 in the traumatic brain injury (TBI) population and evidence-based reviews of cognitive rehabilitation efficacy33 for people with TBI and other acquired neurologic dysfunction. Cognitive retraining focuses on reducing cognitive impairment, developing compensatory strategies to minimize the impact of the deficits, and increasing awareness of impact of those deficits in daily activities. Impaired learning and memory (ie, efficient acquisition and retrieval) as well as slowed information processing and impaired working memory, which can adversely affect complex attention and other cognitive abilities (eg, verbal fluency, executive functions), have all been identified as primary cognitive difficulties associated with MS.34,35 In addition to the known disruptions that can occur in attention, memory and new learning, speed of information processing, and features of executive function,36 people with MS have unique additional vulnerabilities. These vulnerabilities can include variability in day-to-day performance secondary to waxing and waning of MS symptoms as well as additional problems with fatigue, paresthesia, or heat sensitivity. This variability must be taken into account when designing and delivering strategies for effective cognitive retraining. Periodic review and updated modification of cognitive rehabilitation needs and strategies over time is also recommended for people with MS and their families to help maximize maintenance of adaptive functions. Even although research evaluating cognitive retraining for MS is in its infancy, it points toward neurorehabilitation being beneficial for people with various types of cognitive problems caused by MS.37 Research specifically related to MS supports cognitive rehabilitation of impairments in the area of executive functioning,37 as do expert opinion articles.38 The TBI literature shows evidence to support a practice standard of metacognitive approaches for treating deficits in planning and problem
Cognitive Rehabilitation in MS
solving.39 Both the MS and TBI literature identify training in the use of compensatory techniques for memory as a practice guideline.37,40–42 The TBI literature has long supported the use of cognitive rehabilitation for improved attention.33,43 Although additional evidence is still being gathered for specific MS populations,37 it is reasonable to consider that people with MS, for whom the ability to sustain attention on relevant targets or topics and to filter competing stimuli is a main concern of treatment, can benefit from established approaches. As further research is conducted, many of the treatment approaches in use based on clinical usefulness and observed improvements in function for people with MS seem likely to achieve practice standard or practice guideline status. Treatment Planning Interview with Patient and Family
Developing a treatment plan for cognitive retraining must begin, as noted earlier, with effective evaluation. One of the most critical yet sometimes neglected elements of evaluation for treatment planning is a systematic interview with the patient and family member or significant other by the treating clinician at the outset of treatment. It is important to understand the functional impact of impairment in order to tailor the treatment plan and compensatory strategies to meet an individual’s needs. Interview questions can probe for specific examples of how deficits affect daily life. The answers to these questions are used in conjunction with test results to develop compensatory strategies for these situations as well as strategies that can be generalized to all aspects of daily life. The treatment plan includes education of the patient and family about the nature of the deficits and why it adversely affects them and development of compensatory strategies and therapeutic activities to target specific difficulties. Memory and New Learning
Memory and new learning are especially problematic when it is difficult to quickly determine main ideas and filter distracting versus relevant details. As a result, memory acquisition, storage, and retrieval become inefficient. Treatment targets memory deficits via extensive practice in synthesizing main elements and filtering out extraneous details with increasingly complex material. This skill is also effective for learning to take effective notes. The person’s ability and willingness to take structured and consistent notes during treatment and at home have been observed in clinical practice as one of the best strategies for improved spontaneous recall and follow-through. It is vital to develop a consistent system that uses a single location for notes and includes prompts to write and review the notes. A commercial day planner is a simple, inexpensive, and effective strategy for this system. It is also important to break new information into smaller units to be rehearsed and practiced, then summarized and noted. This strategy maximizes the chance that it will be stored and ready for later retrieval, before moving on to new material. Speed of Information Processing
Reduced speed of information processing can also adversely affect daily activities on many levels, including in conversation, when following directions, and mentally juggling ideas. Strategies are taught to slow the speed of incoming information by taking notes and asking clarifying questions in conversations or lectures. Receiving the same information in multiple complementary modalities (visual, auditory, written) seems to be beneficial to maximizing accuracy of input and retention. For example, a person may request an e-mail follow-up of quickly presented verbal auditory instructions to reinforce memory and understanding and maximize the chances for successful follow-through. It is also not an incidental factor for the person facing new
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information to enter the situation prepared (eg, to heighten their awareness of the techniques that they need to succeed and when to use them, to put extra effort into focused attention, to try to make use of settings that minimize distractions and tools that maximize understanding). Attention
The ability to shift attention without succumbing to internal or external distractions is a significant challenge. Many people with MS describe this phenomenon as “going down the rabbit hole” and then losing track of what was important. The first line of defense is to assess the environment to see what kinds of distractions are present so that those can then be minimized. Distractions can be visual, auditory, or internal. Simple strategies include wearing headphones or earplugs to decrease nonrelevant auditory distractions. For visual distractions, an environment can be created with limited clutter and fewer people present. To manage internal distractions, a person can quickly jot down intrusive ideas as they come to mind if these are items that should not be forgotten, rather than shifting attention to the new thought. It is also helpful to have a written plan for the day to focus on completing a particular set of tasks, few in number and manageable in size. Cognitive rehabilitation treatment also helps the person identify those tasks that are performed routinely, either at home or at work, and to develop a plan that helps decrease the number of times when shifts in attention are required. An example of this strategy is to check e-mail only at scheduled times and only for a certain period, rather than having alerts sound throughout the day that require the person to shift attention at every announcement. Executive Functions: Use of Structure and Routines
Structure is a critical component to successfully maintaining attention and completing tasks in a day. Often, the person with MS is completely overwhelmed by the number and complexity of the tasks that they must complete. They may also believe they have no control over their schedule. However, by creating some structure, it is easier to stay on task. Because it is difficult for someone with MS to predict how their symptoms will affect them each day, the schedule has to have some flexibility. Helping the person develop daily and weekly anchors (eg, routine scheduled tasks such as the morning get-ready process or a regular exercise time with activities that can be modified if needed) and a time to plan each day is more effective than a rigid weekly schedule that was developed a priori to complete tasks. It is also helpful to schedule blocks of time to work without interruption. Using consistent routines facilitates increased attention and follow-through of tasks as well as providing effective structure to the day/week. These routines are more successful if they are sequence based rather than time based, because of the variability of physical symptoms (eg, fatigue). Executive Functions: Techniques for Project Completion
People with MS are frequently unable to complete projects because they do not know how best to start or become distracted in carrying out the project. In treatment, the clinician helps develop a system to plan the steps in the projects, put those steps in order, and then schedule a time to complete each of the steps. Additional strategies to prompt the person to initiate the task or to pause and assess how they are progressing may also need to be taught. Use of timers or posting and checking the plan are suggestions for additional prompts. Another component of difficulty with project completion is time management. People with MS sometimes report a diminished or absent sense of elapsed time, or that tasks take longer as a result of fatigue. Further, they may be calculating their estimates of how long a project will take based on
Cognitive Rehabilitation in MS
premorbid experience and speed of performance, without taking into consideration the effects of MS. In addition, physical limitations, heightened distractibility, and memory retrieval disruptions can all contribute to more time needed. We encourage patients to double or triple the amount of estimated time needed to complete each step in the project. If they finish more quickly than estimated, that is bonus time, rather than having the stress of approaching deadlines that are impossible to meet given inaccurate planning. Education and Awareness
The importance of the person’s awareness of deficits (as well as of residual strengths) was alluded to earlier. An important aspect of overall neurorehabilitation (of which cognitive retraining/cognitive rehabilitation is a fundamental component) revolves around on-going education. By helping the person understand the relationship between specific kinds of cognitive impairments and their functional difficulties, they are better able to implement appropriate strategies. This kind of education can also facilitate ability to generalize strategies to additional tasks. By understanding the cause of the problem, (ie, why the difficulty manifests in the ways that it does), the person is less likely to be overwhelmed by it and more likely to be empowered to take control of the problem and its negative repercussions. Unique Challenges for Cognitive Function in MS
There are particular challenges to providing treatment to people with MS, which are not typical of other forms of acquired brain injury. One of the most pressing issues for people with MS is the variability in functional deficits that they may experience day to day related to fatigue, pain, or other sensory, motor, and physical symptoms. The combination, intensity, and unpredictability of symptoms can also be demoralizing from a psychological stand-point, leading to reactive emotional distress, which can aggravate the negative impact of residual neurologic difficulties. As a function of these problems in day-to-day variability, people with MS need some degree of flexibility in their schedules as well as time for scheduled rest breaks to pace energy expenditure. Generalization and Follow-Through with Strategies at Home
Another challenge for people with compromise in executive functions is to achieve a level of basic organization in one’s home or work life to make most effective use of all strategies. Working together to identify a family member, friend, or professional organizer who can assist in creating a work or home environment where visual and auditory distractions are minimized and a truly sustainable functional organizational system is in place may be necessary for application and maintenance of strategies. Individuals with MS, especially given the progressive nature of the illness, also benefit from a return to treatment periodically to review relevant strategies, modify them further for current needs, and identify new compensatory techniques as appropriate. SUMMARY
It is our observation over a combined 70 years or more of experience in neurorehabilitation that the cognitive rehabilitation specialist is the instrument of change for improved function in people with cognitive deficits caused by neurologic injury or illness. Although computer-based tasks can be fun, or allow practice with word games or other academic skills, unless they translate into practical applications for improved day-to-day function, they are not the best use of the person’s time and resource to achieve specific real-world improvements in cognitive performance.
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REFERENCES
1. Rao SM, Leo GJ, Bernardin L, et al. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 1991;41(5):685–91. 2. Rao SM, Leo GJ, Ellington L, et al. Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning. Neurology 1991;41(5):692–6. 3. Arnett PA, Rao SM, Grafman J, et al. Executive functions in multiple sclerosis: an analysis of temporal ordering, semantic encoding, and planning abilities. Neuropsychology 1997;11(4):535–44. 4. Fischer JS. Cognitive impairment in multiple sclerosis. In: Cook SD, editor. Handbook of multiple sclerosis. 3rd edition. New York: Marcel Dekker; 2001. p. 233–55. 5. D’Esposito M, Ohishi K, Thompson H, et al. Working memory impairments in multiple sclerosis: evidence from a dual task paradigm. Neuropsychology 1996;10: 51–6. 6. Beatty WW, Goodkin DE, Monson N, et al. Cognitive disturbances in patients with relapsing remitting multiple sclerosis. Arch Neurol 1989;46:1113–9. 7. Beatty WW. Multiple sclerosis. In: Adams RL, Parsons OA, Gulbertson JL, et al, editors. Neuropsychology for clinical practice: etiology, assessment, and treatment of common neurological disorders. Washington, DC: American Psychological Association; 1996. p. 225–42. 8. DeLuca J, Gaudino EA, Diamond BJ, et al. Acquisition and storage deficits in multiple sclerosis. J Clin Exp Neuropsychol 1998;20:376–90. 9. Pepping M, Ehde D. Neuropsychological evaluation and treatment of multiple sclerosis: the importance of a neuro-rehabilitation focus. Phys Med Rehabil Clin N Am 2005;16(2):411–36. 10. Huijbregts SC, Kalkers NF, de Sonneville LM, et al. Cognitive impairment and decline in different MS subtypes. J Neurol Sci 2006;245:187–94. 11. Potogas C, Giogkaraki E, Koutsis G, et al. Cognitive impairment in different MS subtypes and clinically isolated syndromes. J Neurol Sci 2008;267(1–2):100–6. 12. DeLuca J, Chelune GJ, Tulsky DS, et al. Is speed of processing or working memory the primary information-processing deficit in multiple sclerosis? J Clin Exp Neuropsychol 2004;26(4):550–62. 13. Trapp B, Nave KA. Multiple sclerosis: an immune or neurodegenerative disorder. Annu Rev Neurosci 2008;31:247–69. 14. Hohol MJ, Guttmann CR, Oray J, et al. Serial neuropsychological assessment and magnetic resonance imaging analysis in multiple sclerosis. Arch Neurol 1997;54:1018–25. 15. O’Connor P. Key issues in the diagnosis and treatment of multiple sclerosis: an overview. Neurology 2002;59(Suppl 3):S1–3. 16. Vigeveno RM, Wiebenga OT, Wattjes MP, et al. Shifting imaging targets in multiple sclerosis: from inflammation to neurodegeneration. J Magn Reson Imaging 2012; 36:1–19. 17. Rudick R, Fisher E, Lee JC, et al. Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing remitting MS. Neurology 1999;53:1698–704. 18. Chelune GJ, Stott H, Pinkston JB. Multiple sclerosis. In: Morgan J, Ricker J, editors. Textbook of clinical neuropsychology. New York: Taylor & Francis; 2008. p. 599–615. 19. Fazekas F, Barkhof F, Filippi M, et al. The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis. Neurology 1999;53:448–56. 20. Foong J, Rozewicz L, Quaghebeur G, et al. Executive function in multiple sclerosis: the role of frontal lobe pathology. Brain 1997;120(Pt 1):15–26.
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21. Wallin MT, Wilken JA, Kane R. Cognitive dysfunction in multiple sclerosis: assessment, imaging and risk factors. J Rehabil Res Dev 2006;43(1):63–72. 22. Rao SM, Leo GJ, Haughton VM, et al. Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis. Neurology 1989;39:161–6. 23. Rovaris M, Filippi M, Minicucci L, et al. Cortical/subcortical disease burden and cognitive impairment in patients with multiple sclerosis. AJNR Am J Neuroradiol 2000;21:402–8. 24. Moriarty DM, Blackshaw AJ, Talbot PR, et al. Memory dysfunction in multiple sclerosis corresponds to juxtacortical lesion load on fast fluid-attenuated inversion-recovery MR images. AJNR Am J Neuroradiol 1999;20(10):1956–62. 25. Bermel RA, Bakshi R, Tjoa C, et al. Bicaudate ratio as a magnetic resonance imaging marker of brain atrophy in multiple sclerosis. Arch Neurol 2002;59: 275–80. 26. Benedict RH, Bruce JM, Dwyer MG, et al. Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis. Arch Neurol 2006;63: 1301–6. 27. Benedict RH, Weinstock-Guttman B, Fishman I, et al. Prediction of neuropsychological impairment in multiple sclerosis: comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden. Arch Neurol 2004; 61:226–30. 28. Fischer E, Benedict RH. Correlation of cognitive impairment and thalamic atrophy in MS: for men only? Neurology 2012;79:1748–9. 29. Schoonheim MM, Popescu V, Rueda Lopes FC, et al. Subcortical atrophy and cognition: sex effects in multiple sclerosis. Neurology 2012;79:1754–61. 30. Benedict RH, Fischer JS, Archibald CJ, et al. Minimal neuropsychological assessment of MS patients: a consensus approach. Clin Neuropsychol 2002; 16(3):381–97. 31. Benedict RH, Hussein S, Englert J, et al. Cortical atrophy and personality in multiple sclerosis. Neuropsychology 2008;22(4):432–41. 32. Ben-Yishay Y, Diller L. Cognitive remediation in traumatic brain injury: update and issues. Arch Phys Med Rehabil 1993;74:204–13. 33. Cicerone KD, Dahlberg C, Malec JF, et al. Evidence-based cognitive rehabilitation: updated review of the literature from 1998 through 2002. Arch Phys Med Rehabil 2005;86(8):1681–92. 34. Mattioli FF, Stampatori CC, Bellomi FF, et al. Neuropsychological rehabilitation in adult multiple sclerosis. Neurol Sci 2010;31:271–4. 35. Rosti-Otaja¨rvi EM, Ha¨ma¨la¨inen PI. Neuropsychological rehabilitation for multiple sclerosis. Cochrane Database Syst Rev 2011;(11):CD009131. http://dx.doi.org/ 10.1002/14651858.CD009131.pub2. 36. Flavia M, Stampatori C, Zanotti D, et al. Efficacy and specificity of intensive cognitive rehabilitation of attention and executive functions in multiple sclerosis. J Neurol Sci 2010;288(1–2):101–5. 37. O’Brien AR, Chiaravalloti N, Goverover Y, et al. Evidenced-based cognitive rehabilitation for persons with multiple sclerosis: a review of the literature. Arch Phys Med Rehabil 2008;89(4):761–9. 38. National Multiple Sclerosis Society. Expert opinion paper: assessment and management of cognitive impairment in multiple sclerosis. New York: The Multiple Sclerosis Society; 2006. 39. Kennedy MR, Coelho C, Turkstra L, et al. Intervention for executive functions after traumatic brain injury: a systematic review, meta-analysis and clinical recommendations. Neuropsychol Rehabil 2008;18(3):257–99.
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40. Ehlardt L, Sohlberg MM, Kennedy MR, et al. Evidence-based practice guidelines for instructing individuals with acquired memory impairments: what have we learned in the past 20 years? Neuropsychol Rehabil 2008;18(3):300–42. 41. Sohlberg MM, Kennedy MR, Avery J, et al. Evidence based practice for the use of external aids as a memory rehabilitation technique. J Med Speech Lang Pathol 2007;15(1):xv–li. 42. Dahlberg CA, Cusick CP, Hawley LA, et al. Treatment efficacy of social communication skills training after traumatic brain injury: a randomized treatment and deferred treatment controlled trial. Arch Phys Med Rehabil 2007;88(12):1561–73. 43. Cicerone K, Dahlberg C, Kalmar K, et al. Evidence-based cognitive rehabilitation: recommendations for clinical practice. Arch Phys Med Rehabil 2000;81: 1596–615.
MS-CCC, BC-ANCDS
b
,
KEYWORDS Cognition Cognitive rehabilitation Cognitive retraining Multiple sclerosis Cognitive dysfunction KEY POINTS Nature of cognitive dysfunction in MS: complex attention, memory acquisition and retrieval, speed of information processing, and both the neurocognitive and neurobehavioral features of executive functions can all be disrupted in the context of often wellpreserved basic intelligence. Importance of comprehensive evaluation: this should include at a minimum a thorough neuropsychological evaluation and clinical observations of the treating cognitive rehabilitation specialist. Pathophysiology of MS: implications for neurocognitive and neurobehavioral changes: subcortical lesions exert a clear adverse effect on complex attention, memory retrieval, and frontal-subcortical executive functions, with inflammatory and degenerative processes each playing a unique role in the background strengths and weaknesses of the individual with particular forms of MS. Cognitive rehabilitation: sophisticated cognitive rehabilitation approaches combine clinicians’ understanding of each person’s particular neurocognitive and neurobehavioral strengths and difficulties, along with training of specific strategies designed to reduce the negative functional effects of the problem areas.
INTRODUCTION
Cognitive functioning problems are common in multiple sclerosis (MS), occurring in at least half of all persons with the disorder.1,2 Although the patterns of neuropsychological disruption in people with MS are well known (ie, attention, memory acquisition and
a
Department of Rehabilitation Medicine, University of Washington School of Medicine, Box 356490, 1959 Northeast Pacific Street, Seattle, WA 98195, USA; b Rehabilitation Therapy Department, University of Washington Medical Center, Box 356154, 1959 Northeast Pacific Street, Seattle, WA 98195, USA * Corresponding author. E-mail address: [email protected]
Phys Med Rehabil Clin N Am 24 (2013) 663–672 http://dx.doi.org/10.1016/j.pmr.2013.06.009 1047-9651/13/$ – see front matter Ó 2013 Elsevier Inc. All rights reserved.
pmr.theclinics.com
664
Pepping et al
retrieval, speed of information processing, and features of executive functions can be adversely affected1–8), much variability exists. A comprehensive neuropsychological evaluation is critical to effectively identify the set of neurologic and reactive disruptions for each person with MS.9 The expert cognitive rehabilitation specialist also gathers pertinent formal test data and important interview information at the start of therapy to guide the plan of treatment. Observations by the treating clinician of the person’s cognitive retraining needs as well as clinical data regarding effectiveness of selected strategies and approaches are key components of on-going evaluation for maximal treatment effectiveness. All of these strategies also allow the clinician to provide feedback to the person with MS about their residual strengths and the various practical applications of those strengths to support improved function and hope. The literature on typically preserved versus disrupted neuropsychological functions in people with MS has been well established over the last 25 years or more of study.1,2,6 The time of onset, range of affected features, and degree of severity may vary with each person’s disease presentation and subtype (relapsing remitting MS, primary progressive MS, secondary progressive MS, and clinical isolated syndrome10,11) in the particular context of their long-standing premorbid skills and difficulties. However, for most people with MS,1,2,4,7,8,12 the subcortical changes associated with white matter disease produce predictable problems in thinking. Lesion extension into cortical gray matter can occur,13 as can some degree of atrophy over lengthy disease course,14 in some individuals with MS. As we learn more about the underlying neurophysiology of MS (eg, lesion load, gray matter involvement, atrophy, and brain regions particularly vulnerable to disruption), we are in a better position to anticipate, understand, and treat residual neurocognitive and neurobehavioral difficulties. Given what is known about the initial primarily subcortical nature of disruptions and relative sparing in most instances of cortical functions, likely strengths can also be anticipated. This knowledge of residual strengths and difficulties can give clinicians and the patient a template to develop pertinent strategies and procedures to support current function and help establish effective overlearned systems for maximal future function to the fullest extent possible. Clinicians appreciate that these changes induced by MS do not occur in the abstract. They occur each time in a specific person who is trying to find the best way to live fully and with meaning despite the challenging constellation of symptoms caused by MS. It is the thesis of this article that the cognitive problems that result from MS can be anticipated, understood via appropriate examination, and then treated to support improved performance. We would also like the reader to expand their notion of cognitive changes to include both the neurocognitive (eg, memory retrieval problems) and neurobehavioral (eg, reduced awareness, impulsivity adversely affecting problem solving) dysfunction, which is important to address when designing treatment interventions. It is also important to appreciate premorbid personality strengths and vulnerabilities as well as reactive emotional concerns and physical symptoms that can adversely affect thinking performance. First, an overview is presented of the neuroanatomy, neuropathology, and neurophysiology relevant to MS and the particular brain structures and processes that underlie areas of disrupted versus preserved cognitive function. PATHOPHYSIOLOGY OF MS
MS is considered to be an autoimmune-related disorder of the central nervous system, affecting initially the myelin sheath of axons. The cause of this autoimmune
Cognitive Rehabilitation in MS
variant is unknown but is believed to involve an interaction of genetic and environmental factors. Brain and spinal cord regions are vulnerable. An inflammatory process at the myelin sheath site is considered to be a hallmark initial change in MS. As this process evolves, axonal damage and scarring have been shown.15,16 Axonal damage has been associated with loss of axonal integrity and degeneration, which can give rise to cerebral atrophy.17 MS-related disability is considered to stem from 2 processes: acute inflammatory demyelination and axonal degeneration.18 Although MS is often considered a disorder affecting only subcortical white matter, there is considerable evidence that cortical demyelination can also occur, even at the early stages of the disease.13 That both subcortical and cortical brain regions can be affected in MS indicates the diffuse nature of the disease and, in turn, the risk for a widespread set of cognitive functioning problems. However, despite the potential for diffuse brain involvement, MS lesions do tend to locate in the periventricular white matter, cerebellum, and brainstem.19,20 Through structural neuroimaging, several MS-related pathophysiologic changes have been examined in the literature as risks for cognitive functioning difficulties.21 Among these visualized changes, lesion load (also referred to as lesion burden), lesion location, and global or regional atrophy have received the most attention. Lesion load refers to the number of lesions identified on brain imaging within a given area and has been shown in numerous studies to be correlated positively with greater cognitive impairment.22,23 For example, Moriarty and colleagues24 reported a positive correlation between juxtacortical lesion load and memory dysfunction in persons with MS. Bermel and colleagues25 noted the role of frontal lobe disease in executive dysfunction in MS. Global atrophy and regional brain atrophy have also been found to be especially associated with cognitive dysfunction.14,25 Neocortical volume loss has been shown to differentiate cognitively impaired and cognitively intact individuals with MS.26 Moreover, in 2 studies by Benedict and colleagues,26,27 the relative contribution of brain atrophy to cognitive impairment was greater than lesion burden, whereas width of the third ventricle was more highly associated with cognitive dysfunction than was whole brain atrophy. More specifically, in some studies,28 cognitive impairment and thalamic atrophy were linked in people with MS, particularly men.29 The reason for the sex difference is not clear, but the central role of the thalamus as a relay station for transmission of information among and between frontal cortex, basal ganglia, and other cortical regions could explain why atrophy there would have such an important deleterious effect on key frontal-subcortical functions. COMPREHENSIVE ASSESSMENT
In the neurorehabilitation setting, effectively evaluating and treating patients with acquired brain dysfunction requires a thorough understanding of the person’s abilities, difficulties, reactions, and preferences. This understanding is essential to designing and delivering effective treatment. Although there is a role for briefer examinations in some circumstances to identify and document possible cognitive changes in MS,30 a brief examination alone is not typically sufficient to fully elucidate the nature of the person’s skills and deficits for optimal treatment planning purposes. It also does not obtain much information about personality style or features, which can augment or impede ability to participate and benefit from treatment, as natural premorbid factors or personality changes that may be developing with cortical atrophy.31 Hence, we typically use comprehensive standardized evaluations at the start of care.
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These evaluations include at a minimum in-depth neuropsychological evaluation and may include formal speech and language evaluation and occupational therapy evaluation of higher-level activities of daily living. We would like to broaden readers’ view of cognitive evaluation in MS to include the kind of on-going evaluative observation that is an integral part of the treating clinician’s role as they actively modify or refine treatment strategies and advice to fit the problems observed in the person’s performance. This performance can include the quality of the person’s in-session work, completed homework assignments, or other functional behavior (eg, observations of relevant behavior in the waiting room). For example, is the person rifling through a large messy backpack full of papers trying to find a homework assignment despite all attempts to impose some organizational structure? Perhaps it is time to rethink the strategies or approaches being used. A clinic-based therapist can also make note of the person’s ability to keep appointments, to show up on time for those appointments, to bring with them requested materials, and to complete other scheduled activities for the week. It is easy to check if the person has important items with them every session (eg, wallet or purse, keys, phone, schedule, note-taking device or materials). Feedback in the form of test or course grades for those in college or work performance evaluations for employed people also provides objective information regarding improvements in function. Including the person’s family member periodically allows the clinician to obtain observer updates on accomplishments in the home and community setting (eg, taking medications independently, better follow-through with completion of chores, improved efficiency of verbal communication, jotting down notes to aid memory performance). COGNITIVE REHABILITATION (COGNITIVE RETRAINING)
Cognitive rehabilitation is indebted to the early pioneers of these techniques32 in the traumatic brain injury (TBI) population and evidence-based reviews of cognitive rehabilitation efficacy33 for people with TBI and other acquired neurologic dysfunction. Cognitive retraining focuses on reducing cognitive impairment, developing compensatory strategies to minimize the impact of the deficits, and increasing awareness of impact of those deficits in daily activities. Impaired learning and memory (ie, efficient acquisition and retrieval) as well as slowed information processing and impaired working memory, which can adversely affect complex attention and other cognitive abilities (eg, verbal fluency, executive functions), have all been identified as primary cognitive difficulties associated with MS.34,35 In addition to the known disruptions that can occur in attention, memory and new learning, speed of information processing, and features of executive function,36 people with MS have unique additional vulnerabilities. These vulnerabilities can include variability in day-to-day performance secondary to waxing and waning of MS symptoms as well as additional problems with fatigue, paresthesia, or heat sensitivity. This variability must be taken into account when designing and delivering strategies for effective cognitive retraining. Periodic review and updated modification of cognitive rehabilitation needs and strategies over time is also recommended for people with MS and their families to help maximize maintenance of adaptive functions. Even although research evaluating cognitive retraining for MS is in its infancy, it points toward neurorehabilitation being beneficial for people with various types of cognitive problems caused by MS.37 Research specifically related to MS supports cognitive rehabilitation of impairments in the area of executive functioning,37 as do expert opinion articles.38 The TBI literature shows evidence to support a practice standard of metacognitive approaches for treating deficits in planning and problem
Cognitive Rehabilitation in MS
solving.39 Both the MS and TBI literature identify training in the use of compensatory techniques for memory as a practice guideline.37,40–42 The TBI literature has long supported the use of cognitive rehabilitation for improved attention.33,43 Although additional evidence is still being gathered for specific MS populations,37 it is reasonable to consider that people with MS, for whom the ability to sustain attention on relevant targets or topics and to filter competing stimuli is a main concern of treatment, can benefit from established approaches. As further research is conducted, many of the treatment approaches in use based on clinical usefulness and observed improvements in function for people with MS seem likely to achieve practice standard or practice guideline status. Treatment Planning Interview with Patient and Family
Developing a treatment plan for cognitive retraining must begin, as noted earlier, with effective evaluation. One of the most critical yet sometimes neglected elements of evaluation for treatment planning is a systematic interview with the patient and family member or significant other by the treating clinician at the outset of treatment. It is important to understand the functional impact of impairment in order to tailor the treatment plan and compensatory strategies to meet an individual’s needs. Interview questions can probe for specific examples of how deficits affect daily life. The answers to these questions are used in conjunction with test results to develop compensatory strategies for these situations as well as strategies that can be generalized to all aspects of daily life. The treatment plan includes education of the patient and family about the nature of the deficits and why it adversely affects them and development of compensatory strategies and therapeutic activities to target specific difficulties. Memory and New Learning
Memory and new learning are especially problematic when it is difficult to quickly determine main ideas and filter distracting versus relevant details. As a result, memory acquisition, storage, and retrieval become inefficient. Treatment targets memory deficits via extensive practice in synthesizing main elements and filtering out extraneous details with increasingly complex material. This skill is also effective for learning to take effective notes. The person’s ability and willingness to take structured and consistent notes during treatment and at home have been observed in clinical practice as one of the best strategies for improved spontaneous recall and follow-through. It is vital to develop a consistent system that uses a single location for notes and includes prompts to write and review the notes. A commercial day planner is a simple, inexpensive, and effective strategy for this system. It is also important to break new information into smaller units to be rehearsed and practiced, then summarized and noted. This strategy maximizes the chance that it will be stored and ready for later retrieval, before moving on to new material. Speed of Information Processing
Reduced speed of information processing can also adversely affect daily activities on many levels, including in conversation, when following directions, and mentally juggling ideas. Strategies are taught to slow the speed of incoming information by taking notes and asking clarifying questions in conversations or lectures. Receiving the same information in multiple complementary modalities (visual, auditory, written) seems to be beneficial to maximizing accuracy of input and retention. For example, a person may request an e-mail follow-up of quickly presented verbal auditory instructions to reinforce memory and understanding and maximize the chances for successful follow-through. It is also not an incidental factor for the person facing new
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information to enter the situation prepared (eg, to heighten their awareness of the techniques that they need to succeed and when to use them, to put extra effort into focused attention, to try to make use of settings that minimize distractions and tools that maximize understanding). Attention
The ability to shift attention without succumbing to internal or external distractions is a significant challenge. Many people with MS describe this phenomenon as “going down the rabbit hole” and then losing track of what was important. The first line of defense is to assess the environment to see what kinds of distractions are present so that those can then be minimized. Distractions can be visual, auditory, or internal. Simple strategies include wearing headphones or earplugs to decrease nonrelevant auditory distractions. For visual distractions, an environment can be created with limited clutter and fewer people present. To manage internal distractions, a person can quickly jot down intrusive ideas as they come to mind if these are items that should not be forgotten, rather than shifting attention to the new thought. It is also helpful to have a written plan for the day to focus on completing a particular set of tasks, few in number and manageable in size. Cognitive rehabilitation treatment also helps the person identify those tasks that are performed routinely, either at home or at work, and to develop a plan that helps decrease the number of times when shifts in attention are required. An example of this strategy is to check e-mail only at scheduled times and only for a certain period, rather than having alerts sound throughout the day that require the person to shift attention at every announcement. Executive Functions: Use of Structure and Routines
Structure is a critical component to successfully maintaining attention and completing tasks in a day. Often, the person with MS is completely overwhelmed by the number and complexity of the tasks that they must complete. They may also believe they have no control over their schedule. However, by creating some structure, it is easier to stay on task. Because it is difficult for someone with MS to predict how their symptoms will affect them each day, the schedule has to have some flexibility. Helping the person develop daily and weekly anchors (eg, routine scheduled tasks such as the morning get-ready process or a regular exercise time with activities that can be modified if needed) and a time to plan each day is more effective than a rigid weekly schedule that was developed a priori to complete tasks. It is also helpful to schedule blocks of time to work without interruption. Using consistent routines facilitates increased attention and follow-through of tasks as well as providing effective structure to the day/week. These routines are more successful if they are sequence based rather than time based, because of the variability of physical symptoms (eg, fatigue). Executive Functions: Techniques for Project Completion
People with MS are frequently unable to complete projects because they do not know how best to start or become distracted in carrying out the project. In treatment, the clinician helps develop a system to plan the steps in the projects, put those steps in order, and then schedule a time to complete each of the steps. Additional strategies to prompt the person to initiate the task or to pause and assess how they are progressing may also need to be taught. Use of timers or posting and checking the plan are suggestions for additional prompts. Another component of difficulty with project completion is time management. People with MS sometimes report a diminished or absent sense of elapsed time, or that tasks take longer as a result of fatigue. Further, they may be calculating their estimates of how long a project will take based on
Cognitive Rehabilitation in MS
premorbid experience and speed of performance, without taking into consideration the effects of MS. In addition, physical limitations, heightened distractibility, and memory retrieval disruptions can all contribute to more time needed. We encourage patients to double or triple the amount of estimated time needed to complete each step in the project. If they finish more quickly than estimated, that is bonus time, rather than having the stress of approaching deadlines that are impossible to meet given inaccurate planning. Education and Awareness
The importance of the person’s awareness of deficits (as well as of residual strengths) was alluded to earlier. An important aspect of overall neurorehabilitation (of which cognitive retraining/cognitive rehabilitation is a fundamental component) revolves around on-going education. By helping the person understand the relationship between specific kinds of cognitive impairments and their functional difficulties, they are better able to implement appropriate strategies. This kind of education can also facilitate ability to generalize strategies to additional tasks. By understanding the cause of the problem, (ie, why the difficulty manifests in the ways that it does), the person is less likely to be overwhelmed by it and more likely to be empowered to take control of the problem and its negative repercussions. Unique Challenges for Cognitive Function in MS
There are particular challenges to providing treatment to people with MS, which are not typical of other forms of acquired brain injury. One of the most pressing issues for people with MS is the variability in functional deficits that they may experience day to day related to fatigue, pain, or other sensory, motor, and physical symptoms. The combination, intensity, and unpredictability of symptoms can also be demoralizing from a psychological stand-point, leading to reactive emotional distress, which can aggravate the negative impact of residual neurologic difficulties. As a function of these problems in day-to-day variability, people with MS need some degree of flexibility in their schedules as well as time for scheduled rest breaks to pace energy expenditure. Generalization and Follow-Through with Strategies at Home
Another challenge for people with compromise in executive functions is to achieve a level of basic organization in one’s home or work life to make most effective use of all strategies. Working together to identify a family member, friend, or professional organizer who can assist in creating a work or home environment where visual and auditory distractions are minimized and a truly sustainable functional organizational system is in place may be necessary for application and maintenance of strategies. Individuals with MS, especially given the progressive nature of the illness, also benefit from a return to treatment periodically to review relevant strategies, modify them further for current needs, and identify new compensatory techniques as appropriate. SUMMARY
It is our observation over a combined 70 years or more of experience in neurorehabilitation that the cognitive rehabilitation specialist is the instrument of change for improved function in people with cognitive deficits caused by neurologic injury or illness. Although computer-based tasks can be fun, or allow practice with word games or other academic skills, unless they translate into practical applications for improved day-to-day function, they are not the best use of the person’s time and resource to achieve specific real-world improvements in cognitive performance.
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