What is multiple sclerosis? - Chapter 23

How can multiple sclerosis be defined?

Multiple sclerosis (MS) is a fluctuating, chronic central nervous system (CNS) disorder characterized by progressive multifocal demyelination and inflammation of the white matter (Kuks & Pike, 2007). It usually develops between the age of 20 and 40 years, and it is the most common neurological disorder in young adults.

What is the clinical picture?

The inflammation of the white matter mainly occurs in the optic nerve, brainstem, spinal cord and cerebellum. The first characteristics are sensitivity problems and temporary vision problems such as optic neuritis (inflammation of the optic nerve: in a third of patients this is the first symptom of MS). Loss of strength, speech disorders, sexual dysfunctions, pain, fatigue, bladder disorders and disturbed coordination are other common complaints. In addition, there will also be neuropsychiatric and cognitive characteristics. The Uthoff phenomenon is that some patients experience more symptoms when it gets warmer. With a scale known as EDSS, a neurologist can map the severity of the neurological deficits.

How is the disease progressing?

Three subtypes of MS can be distinguished:

1. Relapsing-remitting MS (RRMS): 70-80% of patients have this subtype, which is characterised by periods of recurrence (exacerbations or relapses) alternating with periods of remission in which the patient is almost free of symptoms. 

2. Secondary progressive MS (SPMS): three-quarters of the RRMS patients develop the SPMS after a few years: there is progressive decline with almost no remission.

3. Primary progressive MS (PPMS): this variant affects 10-20% of MS patients. There is a continuous progression of the symptoms right from the beginning.

The course is unpredictable and a distinction is often made between a benign MS and a malignant form of MS. Premorbid life expectancy is only a few years away.

What are the diagnostic criteria?

The clinical picture is very heterogeneous and the course is very variable. The diagnosis is dependent on the occurrence of at least two periods of clinical manifestations and multiple white matter lesions in the CNS made visible by MRI (McDonald and colleagues, 2001). The MRI also showed that 9 out of 10 patients also have abnormalities of the cerebral fluid. The diagnosis is facilitated by MRI scans, but sometimes it can take a long time before a definitive diagnosis is made (the symptoms are then grouped under the term 'possible MS'). The prevalence is higher in cold countries compared to subtropical countries. The male to female ratio is 3: 1.

Can MS be treated?

Treatment consists of the administration of a single high concentration of corticosteroids, which alleviate clinical symptoms. It cannot be given continuously in a low dose due to the many side effects. There are many medicines on the market that prevent exacerbations by around 30-40% annually. The following also applies here: optimal care is multidisciplinary care.

What causes MS?

MS is seen as an autoimmune disease with a genetic (familial) component that is triggered by exogenous factors. The universal differences suggest an important role of the environment: as mentioned earlier, the prevalence increases as the distance to the equator increases. This can possibly be explained by the lack of sunlight and vitamin D. According to the inflammatory hypothesis, immunological factors make a major contribution to pathogenesis: the exacerbation causes an inflammatory reaction whereby T lymphocytes pass through the blood-brain barrier and attack the myelin. Proteins in the cerebral fluid also indicate an inflammatory response and thus the breakdown of myelin sheaths. In addition to demyelination, there is also (axonal and neuronal) degeneration or global atrophy. This is demonstrated by post-mortem studies which also show that the ventricles are often dilated and the cortex is 30% less thick. This means that MS is no longer just a white matter disorder.

Which cognitive impairments are there?

Only 5-10% of MS patients develop dementia. The motor and / or visual limitations can have an influence on the performance subtests, so that there is a possible IQ decrease. The cognitive disorders are often subtle. In most cases the memory and the speed of information processing are affected. The PASAT is a very sensitive multimodal test (unfortunately not really specific) that can mainly map the capacity of information processing but can also map other impairments. Simple attention tasks are not a problem for MS patients; the specific functions (such as focusing attention, maintaining or dividing) are often affected. It is unclear whether there is a problem of attention or whether it is caused by the slow speed of processing information. The most frequently reported memory problem concerns the deepening of information, but there is a global pattern; memory deficits in auditory and visual modality. The recognition is intact (Zakanis, 2000). In addition to the two core deficits, there are often also mild disorders in executive functions, emotion perception and ToM. Language disorders are very rare as well as agnosias.

Is there a relationship between the severity of cognitive impairment and the severity of MS?

Surprisingly, there is no strong relationship between the severity of cognitive impairment and the severity of MS. The amount of cortical atrophy (especially in subcortical structures) and the width of the third ventricle predicts cognitive functioning better than the white matter lesions. The cognitive impairment is worse with PPMS and SPMS compared to RRMS. The prognosis is worse if the disorders are already present at an early stage. Patients with SPMS have worse cognitive performance within the subtypes with a progressive course (PPMS and SPMS) (Chiaravaloti & DeLuca, 2008). As mentioned earlier, memory disorders are at the forefront of RRMS and deficits in the executive functions are at the forefront of SPMS and PPMS. All research findings are based on research on MS patients whose disease was not currently active: due to ethical and methodological reasons, patients with an exacerbation are excluded from the study. The only study that did examine such patients concluded that attention disorders during such a relapse are related to transient inflammatory changes.

Are emotional disorders common in MS?

The prevalence of anxiety disorders, psychotic disorders and bipolar disorders is higher in MS patients than in the normal population (Feinstein, 1999). 27-54% suffer from depression. Suicide is responsible for 15% of deaths in MS. So-called forced laughter and compulsive crying are also common. The only complaint that occurs more often than the depressive complaint is fatigue. 92% of MS patients characterize fatigue as the most restrictive syndrome. There is no cure for fatigue yet.