Key points

Introduction

Cognitive functioning problems are common in multiple sclerosis (MS), occurring in at least half of all persons with the disorder. Although the patterns of neuropsychological disruption in people with MS are well known (ie, attention, memory acquisition and retrieval, speed of information processing, and features of executive functions can be adversely affected ), much variability exists. A comprehensive neuropsychological evaluation is critical to effectively identify the set of neurologic and reactive disruptions for each person with MS. 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. 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 syndrome ) in the particular context of their long-standing premorbid skills and difficulties. However, for most people with MS, the subcortical changes associated with white matter disease produce predictable problems in thinking. Lesion extension into cortical gray matter can occur, as can some degree of atrophy over lengthy disease course, 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.

Introduction

Cognitive functioning problems are common in multiple sclerosis (MS), occurring in at least half of all persons with the disorder. Although the patterns of neuropsychological disruption in people with MS are well known (ie, attention, memory acquisition and retrieval, speed of information processing, and features of executive functions can be adversely affected ), much variability exists. A comprehensive neuropsychological evaluation is critical to effectively identify the set of neurologic and reactive disruptions for each person with MS. 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. 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 syndrome ) in the particular context of their long-standing premorbid skills and difficulties. However, for most people with MS, the subcortical changes associated with white matter disease produce predictable problems in thinking. Lesion extension into cortical gray matter can occur, as can some degree of atrophy over lengthy disease course, 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 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. Axonal damage has been associated with loss of axonal integrity and degeneration, which can give rise to cerebral atrophy. MS-related disability is considered to stem from 2 processes: acute inflammatory demyelination and axonal degeneration.

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. 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.

Through structural neuroimaging, several MS-related pathophysiologic changes have been examined in the literature as risks for cognitive functioning difficulties. 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. For example, Moriarty and colleagues reported a positive correlation between juxtacortical lesion load and memory dysfunction in persons with MS. Bermel and colleagues 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. Neocortical volume loss has been shown to differentiate cognitively impaired and cognitively intact individuals with MS. Moreover, in 2 studies by Benedict and colleagues, 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, cognitive impairment and thalamic atrophy were linked in people with MS, particularly men. 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, 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. Hence, we typically use comprehensive standardized evaluations at the start of care. 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).