Summary Multiple sclerosis (MS) is a progressive disease of the CNS that is characterised by widespread lesions in the brain and spinal cord. MS results in motor, cognitive, and neuropsychiatric symptoms, all of which can occur independently of one another. The common cognitive symptoms include deficits in complex attention, efficiency of information processing, executive functioning, processing speed, and long-term memory. These deficits detrimentally affect many aspects of daily life, such as the ability to run a household, participate fully in society, and maintain employment—factors that can all affect the overall quality of life of the patient. The increased use of neuroimaging techniques in patients with MS has advanced our understanding of structural and functional changes in the brain that are characteristic of this disease, although much remains to be learned. Moreover, examination of efforts to treat the cognitive deficits in MS is still in the early stages.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(08)70259-X.pdf

Cognitive impairment in multiple sclerosis

Although previous studies have shown that the lesions of multiple sclerosis may involve the cerebral cortex, there is little published research on the prevalence and distribution of such lesions. Using neuropathological techniques and MRI, a series of studies has been undertaken in order to assess this, in particular to identify their relationship to cortical veins. A serial MRI study showed that the use of gadolinium proffered an increase in cortical lesion detection of 140% and showed that 26% of active lesions arose within or adjacent to the cortex. In a post-mortem study, MRI under-reported lesions subsequently analysed neuropathologically, particularly those arising within the cortex. In a further 12 cases examined, 478 cortical lesions were identified, of which 372 also involved the subcortical white matter. Seven different lesion types were identified; the majority arose within the territory of the principal cortical veins, whilst the remaining quarter arose within the territory of the small branch or superficial veins. Small cortical lesions are common in multiple sclerosis and are under-reported by MRI. Investigation of the cortical venous supply shows how such lesions may arise, and why the majority also involve the underlying white matter.

/pdf/cortical-lesions-in-multiple-sclerosis-1abco8gaal.pdf

Cortical lesions in multiple sclerosis

Numerous lines of inquiry implicate connectivity as a central abnormality in schizophrenia. Myelination and factors that affect myelination, such as the function of oligodendroglia, are critical processes that could profoundly affect neuronal connectivity, especially given the diffuse distribution of oligodendrocytes and the widespread distribution of brain regions that have been implicated in schizophrenia. Multiple lines of evidence now converge to implicate oligodendroglia and myelin in schizophrenia. Imaging and neurocytochemical evidence, similarities with demyelinating diseases, age-related changes in white matter, myelin-related gene abnormalities, and morphologic abnormalities in the oligodendroglia demonstrated in schizophrenic brains are all examined in light of the hypothesis that oligodendroglial dysfunction and even death, with subsequent abnormalities in myelin maintenance and repair, contribute to the schizophrenic syndrome.

White matter changes in schizophrenia: evidence for myelin-related dysfunction.

Background: Cognitive impairment in MS impacts negatively on many patients at all disease stages and in all subtypes. Full clinical cognitive assessment is expensive, requiring expert staff and spe...

/pdf/recommendations-for-a-brief-international-cognitive-su41vrmmzo.pdf

Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)

In patients presenting with a clinically isolated syndrome, MRI can support and substitute clinical information in the diagnosis of multiple sclerosis by showing disease dissemination in space and time and by helping to exclude disorders that can mimic multiple sclerosis. MRI criteria were first included in the diagnostic work-up for multiple sclerosis in 2001, and since then several modifications to the criteria have been proposed in an attempt to simplify lesion-count models for showing disease dissemination in space, change the timing of MRI scanning to show dissemination in time, and increase the value of spinal cord imaging. Since the last update of these criteria, new data on the use of MRI to establish dissemination in space and time have become available, and MRI technology has improved. State-of-the-art MRI findings in these patients were discussed in a MAGNIMS workshop, the goal of which was to provide an evidence-based and expert-opinion consensus on proposed modifications to MRI criteria for the diagnosis of multiple sclerosis.

/pdf/mri-criteria-for-the-diagnosis-of-multiple-sclerosis-magnims-49e6ewajdo.pdf

MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines.

Deficits in executive function and the relationship to frontal lesion load as detected on MRI were investigated in 42 multiple sclerosis patients. A battery of neuropsychological test examining executive skills including computerized tests of planning and spatial working memory was administered to all subjects. Performance on these tests was impaired in the patient group when compared with a group of matched controls, but not all executive skills were affected to the same extent. Although a number of executive test scores correlated with the severity of frontal lesion load, it was difficult to disentangle the specific contribution of frontal lobe pathology to the impairment on executive tasks. This study highlights the difficulties in attempting to attribute specific cognitive abnormalities to focal brain pathology in the presence of widespread disease such as in multiple sclerosis.

/pdf/executive-function-in-multiple-sclerosis-the-role-of-frontal-4t8m4ruthw.pdf

Executive function in multiple sclerosis. The role of frontal lobe pathology.

Objective: To investigate psychiatric and neurological morbidity, diagnostic stability, and indicators of prognosis in patients previously identified as having medically unexplained motor symptoms. Design: Follow up study. Setting: National Hospital for Neurology and Neurosurgery, London—a secondary and tertiary referral hospital for neurological disorders. Subjects: 73 patients with medically unexplained motor symptoms admitted consecutively in 1989-91. 35 (48%) patients had absence of motor function (for example, hemiplegia) and 38 (52%) had abnormal motor activity (for example, tremor, dystonia, or ataxia). Main outcome measures: Neurological clinical diagnosis at face to face reassessment by a neurologist and a psychiatric diagnosis after a standardised assessment interview—the schedule for affective disorders and schizophrenia—conducted by a psychiatrist. Results: Good follow up data were available for 64 subjects (88%). Only three subjects had new organic neurological disorders at follow up that fully or partly explained their previous symptoms. 44/59 (75%) subjects had had psychiatric disorders; in 33 (75%) patients, the psychiatric diagnosis coincided with their unexplained motor symptoms. 31/59 (45%) patients had a personality disorder. Three subjects had developed new psychiatric illnesses at follow up, but in only one did the diagnosis account for the previous motor symptoms. Resolution of physical symptoms was associated with short length of symptoms, comorbid psychiatric disorder, and a change in marital status during follow up. Conclusions: Unlike Slater9s study of 1965, a low incidence of physical or psychiatric diagnoses which explained these patients9 symptoms or disability was found. However, a high level of psychiatric comorbidity existed. Key messages Motor symptoms that remain unexplained medically despite thorough investigation are a common clinical problem, but the emergence of a subsequent organic explanation for these symptoms is rare The prevalence of coexistent affective and anxiety disorders is high and many patients also have a personality disorder Patients with a shorter duration of symptoms and coexistent anxiety or depression are likely to do better at follow up Reinvestigation of these patients is both expensive and potentially dangerous and should be avoided where no clear clinical indication exists

https://www.bmj.com/content/bmj/316/7131/582.full.pdf

Slater revisited: 6 year follow up study of patients with medically unexplained motor symptoms

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(00)02096-1.pdf

Discrete neurophysiological correlates in prefrontal cortex during hysterical and feigned disorder of movement

Discrimination Learning, Reversal, and Set-Shifting in First-Episode Schizophrenia: Stability Over Six Years and Specific Associations with Medication Type and Disorganization Syndrome

There is a dearth of longitudinal studies on psychometric and psychiatric change in multiple sclerosis (MS) particularly on the evolution of these abnormalities early in the disease process. A 4 1/2 year follow up study documenting magnetic resonance imaging (MRI), psychometric, and psychiatric abnormalities was undertaken in a group of 48 patients with clinically isolated lesions--for example, optic neuritis--which are frequently the harbinger of MS. At follow up about half the subjects had developed clinically definite MS, with memory deficits becoming apparent. Deficits in attention documented at initial assessment were present but unchanged in those subjects who still had a clinically isolated lesion status. However, after MS was categorised into a relapsing-remitting or chronic progressive course, patients with a chronic progressive course were found to have significantly deteriorated with regard to auditory attention tasks. T1 relaxation times in apparently normal white matter correlated with certain indices of cognitive impairment. In developing a model to explain the pathogenesis of intellectual and emotional change in MS, the interaction of organic, psychological, and social factors needs to be emphasised.

https://jnnp.bmj.com/content/jnnp/55/10/869.full.pdf

Maria A. Ron

Papers

Executive function in multiple sclerosis. The role of frontal lobe pathology.

Slater revisited: 6 year follow up study of patients with medically unexplained motor symptoms

Discrete neurophysiological correlates in prefrontal cortex during hysterical and feigned disorder of movement

Discrimination Learning, Reversal, and Set-Shifting in First-Episode Schizophrenia: Stability Over Six Years and Specific Associations with Medication Type and Disorganization Syndrome

Clinically isolated lesions of the type seen in multiple sclerosis: a cognitive, psychiatric, and MRI follow up study.