Cognitive dysfunction in MS: current approaches to clinical management
Articolo pubblicato il 26/02/2006

Multiple sclerosis (MS) is the most important demyelinating disease of the CNS. In Northern Europe and the UK, the prevalence of the disease is about 100 per 100000 population. It is twice as common in women as in men and occurs during the most productive period of life, usually between 20 and 50 years of age [1]. The course is chronic and the clinical picture may include different neurological symptoms and signs, which reflect the presence and distribution of the areas of demyelination in the CNS. Frequent symptoms include:

• Motor weakness and ataxia
• Spasticity
• Optic neuritis
• Diplopia
• Numbness and paresthesia
• Pain
• Bowel and bladder dysfunction
• Sexual disturbances
• Dysarthria
• Fatigue
• Depression

Although the disease does not dramatically reduce life expectancy, patients experience disability and deterioration of quality of life (QoL). The primary etiology of MS remains unknown, but there is extensive evidence that the pathogenesis is dysimmune [1]. Therapeutic approaches with ‘disease-modifying’ agents are therefore based on different types of immunomodulatory or immunosuppressive drugs. Among these, the therapeutic agents currently approved for MS include interferon (IFN)beta-1a (IFNbeta-1a: Avonex® and Rebif®) and 1b (IFNbeta-1b: Betaferon®), glatiramer acetate (Copaxone®) and mitoxantrone (Novantrone®) [2]. Pharmacological therapies to treat specific disease-related symptoms, such as spasticity, fatigue, or bladder dysfunction, are also available [2]. As is true for other symptoms of MS, cognitive dysfunction is highly variable: estimates of its frequency range between 43 and 72% [3]. Severe dementia is observed in approximately 20–30% of cognitively impaired MS patients [3]. Cognitive dysfunction can have a dramatic impact on several aspects of the QoL, independent of the degree of physical disability. In fact, cognitive impairment significantly affects the ability to maintain employment [4–6]. Moreover, patients with cognitive impairment require greater personal assistance in carrying out activities of daily living and are less likely to engage in social activities than cognitively intact MS patients [4–6]. Interestingly, cognitive impairment can also limit the capacity of the patient to benefit from inpatient rehabilitation [7]. Few authors have studied the natural history of cognitive dysfunction in MS patients. In a 3-year followup study, incipient cognitive decline seemed to be widespread and progressive in nature, in another, the percentage of patients with cognitive impairment increased from 26 to 56% over a 10-year follow-up period and the profile of cognitive deficits tended to expand [8,9]. Due to the frequency of cognitive dysfunction in MS, its severity and impact on everyday functioning, there is an increasing consensus that neuropsychological (NP) assessment should accompany the neurological examination of the patients and become a factor in therapeutic decision-making. This article is divided into two sections. The first provides an overview of current knowledge about the pattern of cognitive dysfunction in MS and its clinical and neuroimaging correlates. The second part deals with the clinical assessment and management of cognitive dysfunction and reviews existing data on treatment, both with pharmacological therapies and rehabilitative programs.

Cognitive dysfunction in MS: current approaches to clinical management