Clinical characteristics of cortical multiple sclerosis

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Abstract

There are several articles in this special issue in which authors eloquently describe neurobehavioural and cognitive complications of multiple sclerosis with relevant neuropsychological assessments and neuroimaging findings. However behavioural and cognitive presentation of multiple sclerosis remains poorly understood. Two years ago, we reported a series of patients with multiple sclerosis who presented with neurobehavioural symptoms and had neuropsychological deficits consistent with cortical dysfunction. Based on previous case reports, pathological studies of cerebral cortex in multiple sclerosis and advanced neuroimaging studies we suggested that neurobehavioural presentation of multiple sclerosis represents a new variant called “cortical multiple sclerosis”. The condition is characterised by predominant or exclusive cortical pathology presenting with neurobehavioural symptoms, such as depression, amnesia or distinct cortical syndromes. Since the publication of our report, there has been further neuroimaging and neuropathological findings that further supported the above concept. In addition, observation of more patients with this condition helped us to formulate a logical approach in the detection of these patients. This article focuses on their clinical characteristics.

Introduction

Charcot recognized neurobehavioural problems associated with multiple sclerosis. Kurtzke placed neurobehavioural symptoms in the “cerebral” category of MS symptoms [65]. A wide range of cerebral symptoms including disturbances of mood, memory, language and visuospatial ability have been described to be associated with multiple sclerosis [1], [2], [3]. Multiple sclerosis can present with pyramidal, cerebellar, brainstem, sensory, sphincter or visual symptoms, though cerebral presentation of multiple sclerosis is hardly considered in daily practice. Most neurology textbooks teach us that cerebral symptoms occur at later stages of the disease. However, there are overwhelming evidence showing that cerebral symptoms can be present at early stages of the disease [4], [5], [6], [7], [8], [9], [10].

A retrospective epidemiological study showed that 32% of patients with multiple sclerosis had significant psychiatric complaints prior to sensory and motor presentations that ultimately led to the diagnosis of multiple sclerosis [11]. There are reports of cases with multiple sclerosis that presented solely with neurobehavioural symptoms [12], [13], [14], [15]. These evidences support the notion that multiple sclerosis can present with cognitive symptoms alone.

We reported a series of cases and reviewed previous case reports of cognitive presentation of multiple sclerosis and discovered a clinical pattern that suggested an exclusive or predominant cortical involvement in these patients, hence the term cortical multiple sclerosis [16].

Section snippets

Clinical picture of cortical multiple sclerosis

Information on cortical multiple sclerosis as a variant of multiple sclerosis is limited. Current understanding is based on our direct observation, assessment of case reports in the literature and indirect supportive evidence from neuropathological, neuroimaging and neuropsychological assessments. Systematic study of this condition is clearly warranted.

Cortical multiple sclerosis occurs mostly in the third to fourth decade of life but reported cases ranged from 18 to 60 with female

MRI findings

MRI study of the brain is the most sensitive and commonly used diagnostic test for multiple sclerosis but for the diagnosis of cortical multiple sclerosis the test is far less sensitive. Indeed, brain MRI scans of patients with cortical multiple sclerosis can be normal because conventional MRI scan is not able to visualize intracortical lesions due to the prolonged relaxation time of the cerebral cortex. However, if cortical lesions extend to juxtacortical region, they are commonly detected on

Depression

Although disturbances of mood in multiple sclerosis were known since Charcot, it was not until the 1980s that depression was recognized as a major problem in multiple sclerosis and took the centre stage in multiple sclerosis research [18]. Early reports assumed that depression is a psychological reaction to a chronic disabling disease [19], [20]. However, later studies showed that depression is independent of the degree of disability and is a direct product of brain damage in multiple sclerosis

Memory impairment

The most common cause of memory impairment in multiple sclerosis is poor attention and concentration that is often associated with depression and/or anxiety. It is well recognized that patients with multiple sclerosis can develop dementia with a subcortical pattern. This type of dementia in patients with multiple sclerosis is typically characterised by a relative decline in recent memory, attention, information processing speed, visuospatial abilities, and executive functions whilst language

Distinct cortical symptoms

These symptoms are most useful in the diagnosis of cortical multiple sclerosis, however they appeared in only 36% of cases reported in the literature [16]. There are reports that multiple sclerosis presents with only distinct cortical symptoms. For example, there are four reports of alexia without agraphia [40], [41], [42], [43], three reports of pure alexia [13], [44], [45], eleven reports of aphasia [14], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], one report of visual agnosia

Conversion symptoms

The notion that multiple sclerosis can present as hysteria is not new. Many neurologists experience occasional difficulty in differentiating multiple sclerosis from conversion disorder in patients with atypical sensory or motor symptoms. In most cases a diagnosis of conversion disorder is made after ruling out a neurological cause, however, very rarely such syndromes would be found to have a neurological cause. Early literature claimed that a considerable number of people with multiple

Conclusion

Recognition of cortical multiple sclerosis as a clinical entity is important. Whilst depression is the most common symptom in cortical multiple sclerosis, clearly it is not practical to consider multiple sclerosis in every patient with depression. In order to be able to detect appropriate cases, a clinician has to have a high degree of suspicion and perform a thorough neurobehavioural examination. If the patient was found to have neurobehavioural deficit at bedside then a more comprehensive

Acknowledgement

I am grateful to Dr. David Francis for his valuable comments on the manuscript. I am also indebt of Dr. Basil Sharrack from Royal Hallamshire Hospital in Sheffield, Dr. Abdullah Shehu from Walsgrave Hospital in Coventry, Drs. Richard Abbott, Peter Critchley, Mark Lawdon and Yusuf Rajabally from Leicester Royal Infirmary in Leicester in Birmingham for letting me study clinical information related to their patients.

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