'Oops!': performance correlates of everyday attentional failures in traumatic brain injured and normal subjects

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

Clinical outcome assessment in Multiple Sclerosis (MS) is challenging due to the diversity and fluctuating nature of MS symptoms. Traditional clinical scales such as the EDSS are inadequate in their assessment of key clinical dimensions of MS (e.g. , cognitive function), and they have psychometric limitations as well. Based on analyses of pooled data from natural history studies and from placebo groups in clinical trials, the National MS Society's Clinical Outcomes Assessment Task Force recently proposed a new multidimensional clinical outcome measure, the MS Functional Composite (MSFC). The MSFC comprises quantitative functional measures of three key clinical dimensions of MS: leg function/ambulation, arm/hand function, and cognitive function. Scores on component measures are converted to standard scores (z-scores), which are averaged to form a single MSFC score. Preliminary analyses confirm that: (1) the three clinical dimensions of the MSFC are relatively independent; (2) the MSFC is sensitive to clinical changes over 1- and 2-year intervals; and (3) the MSFC has acceptable criterion validity (i.e., predicts both concurrent and subsequent EDSS change). The advantages and potential limitations of incorporating quantitative functional outcome measures such as the MSFC into collaborative databases are discussed.

The Multiple Sclerosis Functional Composite measure (MSFC): an integrated approach to MS clinical outcome assessment:

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.

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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.

Previous research has suggested that cerebral lesions observed on magnetic resonance imaging (MRI) of MS patients are clinically “silent.” We examined the validity of this assertion by correlating neuropsychological test performance with MRI findings in 53 MS patients. We used a semiautomated quantitation system to measure three MRI variables: total lesion area (TLA), ventricular-brain ratio (VBR), and size of the corpus callosum (SCC). Stepwise multiple regression analyses indicated that TLA was a robust predictor of cognitive dysfunction, particularly for measures of recent memory, abstract/conceptual reasoning, language, and visuospatial problem solving. SCC predicted test performance on measures of mental processing speed and rapid problem solving, while VBR did not independently predict cognitive test findings. These findings suggest that cerebral lesions in MS produce cognitive dysfunction and that MRI may be a useful predictor of cognitive dysfunction.

https://n.neurology.org/content/neurology/39/2/161.full.pdf

Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis

We have recently proposed that the cognitive deficits of patients with multiple sclerosis (MS) share numerous characteristics associated with the syndrome of subcortical dementia. One such characteristic, slowness of mental processing, was evaluated in the present study. Thirty-six MS patients were compared to 26 normal controls of equivalent age, education, and verbal intelligence on the Sternberg memory scanning test. As anticipated, the motor-involved MS patients had an overall slower reaction time than did controls. Their scanning rate, a measure of pure cognitive speed, was also significantly slower than controls. These results suggest that MS patients exhibit a slowing of mental processing independent of motor involvement.

Information processing speed in patients with multiple sclerosis

Thirty-seven patients with multiple sclerosis (MS) were compared to 26 normal controls of equivalent age, education, and verbal intelligence on measures of verbal learning and memory (Digit Span and Supraspan, Brown-Peterson Distractor Task, Selective Reminding Test, Story Recall, and Free Verbal Recall) and verbal fluency (Letter and Animal Fluency). The MS patients exhibited deficits on measures of secondary (long-term) memory and verbal fluency, but performed normally on measures of primary (short-term) memory, recognition memory, and rate of forgetting from secondary memory. These results suggest that the memory disturbance in MS results primarily from an imparied ability to access information from secondary memory, while encoding and storage capacity is intact. Degree of memory impairment was unrelated to length of illness, severity of disability, or self-reported depression.

P. St. Aubin-Faubert

Papers

Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis

Information processing speed in patients with multiple sclerosis

On the nature of memory disturbance in multiple sclerosis.