Multiple Sclerosis: Symptoms, Causes and Treatments

The multiple sclerosis Is a progressive disease of the central nervous system (CNS) characterized by generalized brain injury and spinal cord (Chiaravalloti, Nancy and DeLuca, 2008). It is classified within demyelinating diseases of the CNS. These are defined by inadequate myelin formation or by affecting the molecular mechanisms to maintain it (Bermejo-Velasco, et al., 2011).

The clinical and pathological features of Multiple Sclerosis (MS) were described, in France and later in England, during the second half of the nineteenth century (Compson, 1988).

However, the earliest anatomical descriptions of Multiple Sclerosis were made early in the twentieth century (Poser and Brinar, 2003) by Crueilhier and Carswell. It was Charcot who, in 1968, provided the first detailed description of the clinical and evolutionary aspects of the disease (Fernández, 2008).

Causes of Multiple Sclerosis

Although the exact cause of MS is still unknown, it is currently thought to be the result of immunological, genetic and viral factors (Chiaravalloti, Nancy and DeLuca, 2008).

However, the most accepted pathogenic hypothesis is that MS is the result of the conjunction of a certain genetic predisposition and an unknown environmental factor that, when appearing in the same subject, would give rise to a broad spectrum of alterations in the immune response, Would be the cause of the inflammation present in MS lesions. (Fernández, 2000).

Symptoms of Multiple Sclerosis

MS is a progressive disease with a fluctuating and unpredictable course (Terré-Boliart and Orient-López, 2007), with variability being its most significant clinical feature (Fernández, 2000). This is because the clinical manifestations vary depending on the location of the lesions.

The most characteristic symptoms of MS include motor weakness, ataxia , the Spasticity , Optic neuritis, diplopia, pain, fatigue, sphincter incontinence, sexual disorders and dysarthria.

However, these are not the only symptoms that can be observed in the disease, as epileptic seizures may also occur, aphasia , Hemianopsia and dysphagia (Junqué and Barroso, 2001).

If we refer to statistical data, we can point out that motor alterations are 90-95% the most frequent, followed by sensory alterations in 77% and of cerebellar ones in 75% (Carretero-Ares et al. , 2001).

Since the 1980s research has indicated that the Cognitive impairment Is also related to MS (Chiaravalloti, Nancy and DeLuca, 2008). Some studies show that these alterations can be found in up to 65% of patients (Rao, 2004).

Thus, the most common deficits in MS affect information evocation, working memory, abstract and conceptual reasoning, information processing speed, sustained attention, and visuospatial skills (Peyser et al., 1990; Santiago-Rolanía et al, 2006).

On the other hand, Chiaravalloti and DeLuca (2008) point out that although most studies indicate that general intelligence remains intact in MS patients, other investigations have detected slight but significant decreases.

Histopathology of Multiple Sclerosis

The pathological anatomy of MS is characterized by the appearance of focal lesions in the White matter , Called plaques, characterized by loss of myelin (demyelination) and relative preservation of axons, since a variable degree of axonal destruction is always present (Fernández, 2000).

These demyelinating plaques are of two types depending on the activity of the disease on the one hand, are the plaques on which the acute lesion is recognized, the fundamental pathological phenomenon is inflammation and on the other hand plaques in which one recognizes Chronic injury, a product of progressive demyelination (Carretero-Ares et al., 2001).

As regards their location, they are selectively distributed throughout the SNC , With the regions most affected being the periventricular regions of the Encephalon , The nerve II, the optic chiasma , he hard body , The brainstem, the floor of the fourth ventricle, and the pyramidal pathway (Garcia-Lucas, 2004). Plaques may also appear on the gray matter, usually subpinal, but are more difficult to identify; The neurons are usually respected (Fernández, 2000).

The accumulation of axonal loss can cause irreversible damage to the CNS and neurological incapacity (Lassmann, Bruck, Luchhinnetti, & Rodríguez, 1997; Lucchinetti et al. 1996; Trapp et al., 1998).

Epidemiology

Epidemiological investigations have shown that MS is the most common chronic neurological disease in young adults in Europe and North America (Fernández, 2000), with the majority of diagnoses being diagnosed. Cases between 20 and 40 years of age (Simone, Carrara, Torrorella, Ceccrelli and Livrea, 2000).

The incidence and prevalence of MS in the world has increased at the expense of women, but this is not due to a decline in incidence and prevalence in men, which has remained stable since 1950-2000. The prevalence of the disease in our country ranges between 50-60 cases per 1000 inhabitants (Fernández, 1990).

Clinical course

Studies on the natural evolution of the disease have shown that in 80-85% of patients, the disease starts with outbreaks (De Andrés, 2003). These outbreaks according to the definition of Poser, can be considered as the appearance of symptoms of neurological dysfunction for another 24 hours and that also, as they are repeated, are leaving sequel.

Forms of clinical evolution

According to the Advisory Committee for Clinical Trials in MS of the US National Multiple Sclerosis Society (NMSS), four clinical courses of the disease can be distinguished ( Figure 1 ): Recurrent-sender (EMRR), Progressive primary (EMPP), Progressive secondary (PMSCs) and finally , Recurrent (EMPR).

Chiaravalloti and DeLuca (2008), define MS Recurrent-sender Characterized by periods in which the symptoms worsen (period of acute worsening, also called exacerbation, outbreak, or recurrence), although recovery of the outbreaks is observed. About 80% of people with EMRR later develop MS Progressive secondary .

In this type of MS, symptoms gradually worsen with or Without occasional relapses, or minor referrals. The MS Progressive recurrent Is characterized by a progressive worsening after the onset of the disease, with some acute periods. Finally, the MS Progressive primary Or progressive chronic disease has a continuous and gradual improvement of symptoms without exacerbation or remission of symptoms.

Diagnosis

For its diagnosis, the diagnostic criteria described by Charcot , Based on anatomopathological descriptions of the disease. However, these have now been replaced by the criteria described by McDonald in 2001 and revised in 2005.

McDonald's criteria are based primarily on the clinic, but incorporate in a prominent place the magnetic resonance (MRI), allowing the establishment of spatial and temporal dissemination and, therefore, an earlier diagnosis (ad hoc committee of the group of demyelinating diseases, 2007).

The diagnosis of MS is made taking into account the existence of clinical criteria for spatial dissemination (presence of symptoms and signs that indicate the existence of two independent lesions in the CNS) and temporal dispersion (two more episodes of neurological dysfunction), Fernández, 2000).

In addition to diagnostic criteria, the integration of clinical history information, neurological examination and complementary tests is required in order to rule out differential diagnoses of MS and to demonstrate the findings that are characteristic of MS. cerebrospinal fluid (Intrathecal secretion of immunoglobulins with oligoclonal profile) and magnetic resonance imaging (MRI) (Ad-hoc Committee of the group of demyelinating diseases, 2007).

Treatment

Terré-Boliart and Orient-López, 2007). In general, the therapeutic objectives in this disease will be to improve acute episodes, slow disease progression (through immunomodulatory and immunosuppressive drugs) and treat symptoms and complications.

Due to the symptomatic complexity that these patients may present, the most appropriate treatment framework will be within an interdisciplinary team (Terré-Boliart and Orient-López, 2007).

Cognitive Function in MS

Memory

Starting with memory , It should be considered that this is one of the neuropsychological functions most sensitive to brain damage and, therefore, one of the most evaluated in people with MS (Tinnefeld, Treitz, Haasse, Whilhem, Daum and Faustmann, 2005; Arango-Laspirilla et al. Al., 2007).

As indicated by numerous studies, memory deficit seems to be one of the most frequent disorders associated with this pathology (Armstrong et al., 1996; Rao, 1986; Introzzini et al., 2010). Such deterioration usually Episodic memory Long-term and working memory (Drake, Carrá and Allegri, 2001). However, it seems that not all components of memory would be affected, since the Semantic memory , The implicit memory and the Short-term memory appear to be unaffected.

On the other hand it is also possible to find alterations in the visual memory of patients with MS as the results obtained in the studies of Klonoff et al, 1991; Landro et al, 2000; Ruegggieri et al, 2003; And Santiago, Guardiola and Arbizu, 2006.

Early work on memory impairment in MS suggested that difficulty in long-term storage recovery was the main cause of memory deficit (Chiaravalloti and DeLuca, 2008).

Many authors believe that memory disorder in MS derives from a difficulty in"retrieving"information, rather than a storage deficit (DeLuca et al., 1994; Landette and Casanova, 2001). More recently, however, research has shown that the primary memory problem lies in the initial learning of information.

Patients with MS require more repetition of information to reach a predetermined learning criterion, but once information has been acquired, recall and recognition reach the same level as healthy controls (Chiaravalloti and DeLuca, 2008, Mataró and Pueyo, 2013).

The deficit in the realization of new learning causes mistakes in the decision making and seems to affect the potential capacities of memory. Several factors have been associated with low learning ability in people with MS, such as impairment of processing speed, susceptibility to interference, executive dysfunction and perceptual deficits. (Chiaravalloti and DeLuca, 2008, Jurado, Mataró and Pueyo, 2013).

Information Processing

Efficiency in information processing refers to the ability to maintain and manipulate information in the brain for a short period of time (working memory) and the speed at which that information can be processed (processing speed) .

The reduced rate of information processing is the most common cognitive deficit in MS. These deficits in processing speed are seen in conjunction with other cognitive deficits that are common in MS, such as deficits in working memory and long-term memory.

The results of Recent studies with large samples have shown that people with MS have a significantly greater incidence of processing speed deficits rather than working memory, particularly in patients with a progressive secondary course.

Attention

According to Plohmann et al. (1998) attention is possibly the most prominent aspect of cognitive impairment in some MS patients, thus it is usually one of the first neuropsychological manifestations in people with MS (Festein, 2004, Arango-Laspirilla, DeLuca and Chiaravalloti, 2007 ).

In this paper we present the results of a series of tests that evaluate both sustained and divided attention (Arango-Laspirilla, DeLuca and Chiaravalloti, 2007).

Typically, basic care tasks (eg, digit repetition) are not affected in MS patients. The deterioration in sustained attention is more common and specific affections have been described in divided attention (that is to say, tasks that could be done to the patients that attend to several tasks) (Chiaravalloti and DeLuca, 2008)

F executive functions

There is empirical evidence that a high proportion of MS patients present alterations in their executive functions (Arnett, Rao, Grafman, Bernardin, Luchetta et al., 1997; Beatty, Goodkin, Beatty and Monson, 1989) at Frontal lobe , Caused by the processes of demyelination, may lead to a deficit of executive functions such as reasoning, conceptualization, task planning or problem solving (Introzzi, Urquijo, López-Ramón, 2010)

Visoperceptive Functions

Difficulties in visual processing in MS can have a detrimental effect on visoperceptive processing, although they are found Perceptual deficits independent of primary visual disturbances. The visoperceptive functions not only include the recognition of a stimulus Visual, but also the ability to perceive the characteristics of this stimulus accurately.

Although up to a quarter of people with MS may have a deficit in visual perceptual functions, little work has been done on The processing of visual perception.

Evaluation

The first phase of managing cognitive difficulties involves evaluation. The evaluation of cognitive function requires several neuropsychological tests focused on specific fields such as memory , Attention and processing speed (Brochet, 2013).

Usually, cognitive deterioration is evaluated by neuropsychological tests, which have shown that this deterioration in MS patients is already present in early stages of this disease (Vázquez-Marrufo, González-Rosa, Vaquero-Casares, Duque, Borgues and Izquierdo , 2009).

Cognitive rehabilitation

Currently, there are no effective pharmacological treatments for cognitive impairment related to MS. In response, another type of treatment arises, non-pharmacological treatments, among which we find the Cognitive rehabilitation , Whose ultimate goal is to improve cognitive function through practice, exercise, compensation strategies and adaptation to maximize the use of residual cognitive function (Amato and Goretti, 2013).

Rehabilitation is a complex intervention that poses many challenges for traditional research designs. Unlike a simple pharmacological intervention, rehabilitation includes a variety of different components.

Few studies have been done on the treatment of cognitive deficits and several authors have highlighted the need for additional neuropsychological techniques effective in the rehabilitation of MS. The few cognitive rehabilitation programs for MS aim to improve attentional deficits, communication capacity and memory impairments. (Chiaravalloti and De Luca, 2008).

To date, the results obtained in the cognitive rehabilitation of MS patients are contradictory. Thus, while some researchers have failed to observe an improvement in cognitive function, other authors, such as Plohmann et al. They claim to have demonstrated the efficacy of some cognitive rehabilitation techniques (Cacho, Gamazo, Fernández-Calvo and Rodríguez-Rodríguez, 2006).

In a comprehensive evidence-based review of available data on the use of cognitive rehabilitation in MS patients, O'Brien and colleagues concluded While this research is still in its infancy, there have been some well-designed studies that can provide a basis from which Advance in the field (Chiaravalloti and De Luca, 2008).

The rehabilitation program will focus on the consequences of illness rather than medical diagnosis, and the overriding goal will be to prevent and reduce disability and disability, although at times it may also eliminate deficits (Cobble, Grigsb and Kennedy 1993; Thompson , 2002; Terré-Boliart and Orient-López, 2007).

It should be individualized and integrated into an interdisciplinary team, so therapeutic interventions must be performed on different occasions with different objectives given the evolution of this pathology (Asien, Sevilla, Fox, 1996; Terré-Boliart and Orient-López, 2007).

Together with other therapeutic alternatives available in MS (such as inommomodular and symptomatic treatments), neurorehabilitation should be considered an intervention that complements the remains and is oriented toward the best quality of life Of patients and their family group (Cárceres, 2000)

The realization of a rehabilitative treatment can lead to an improvement in some quality of life indices both in physical health - physical and general health - as well as in mental health - social function, emotional role and mental health - ( Delgado-Mendilívar, et al., 2005) this may be key since most patients with this disease will live more than half their life with it (Hernández, 2000).

Cognitive rehabilitation can bring considerable benefits to people with MS, although research in this field is still too limited to draw definitive conclusions about optimal approaches and strategies (Amato and Goretti, 2013).

Demonstrating the effectiveness of rehabilitation in a heterogeneous disease of progressive course such as MS is complex, and it is necessary to perform more Studies with better design and evaluation scales, which will allow us to better evaluate what we do and, ultimately, to contribute to improve the treatment that we can offer our patients (Terré-Boliart and Orient-López, 2007).

Bibliography

1. Amato, M; Goretti, B; Viterbo, R; Portaccio, E; Niccolai, C; Hakiki, B; Et al. (2014). Computer-assisted rehabilitation of patients with multiple sclerosis: results of a randomized double-blind trial. Mult Scler, 20 (1), 91-8.
2. Arango-Laspirilla, JC; DeLuca, J; Chiaravalloti, N.; (2007). The neurological profile in multiple sclerosis. Psicothema, 19 (1), 1-6.
3. Bermejo Velasco, PE; Blasco Quílez, MR; Sánchez López, AJ; García Merino, A;. (2011). Demyelinating diseases of the central nervous system. Concept, classification and epidemiology. Medicine, 10 (75), 5056-8.
4. Brassington, JC; Marsh, NV;. (1998). Neuropsychological aspects of multiple sclerosis. Neurology Review, 8 , 43-77.
5. Cacho, J; Gamazo, S; Fernández-Calvo, B; Rodríguez-Rodríguez, R.; (2006). Cognitive alterations in multiple sclerosis. Spanish Journal of Multiple Sclerosis, 1 (2).
6. Chiaravalloti, N. (2013). Daily life with cognitive problems of MS. MS in focus: Cognition and MS .
7. Chiaravalloti, ND; DeLuca, J.; (2008). Cognitive impairment in multiple sclerosis. Lancet Neurol, 7 (12), 1139-51.
8. Chiaravalloti, ND; DeLuca, J; Moore, ND; Ricker, JH.; (2005). Treating learning impairments improves memory performance in multiple sclerosis: a randomized Clinical trial. Mult Scler, 11 , 58-68.
9. Chiaravalloti, ND; Wylie, G; Leavitt, V; DeLuca, J.; (2012). Increased cerebral activation after behavioral treatment for memory deficits in MS. J Neurol, 259 (7), 1337-46.
10. Fernández, O. (2000). Relational basis for new treatments in multiple sclerosis. Rev Neurol, 30 (12), 1257-1264.
11. Flavia, M; Stampatori, C; Zanotti, D; Parrinello, G; Capra, R.; (2010). Efficacy and specificity of intensive cognitive rehabilitation of attention and executive functions in multiple sclerosis. J Neurol Sci, 208 (1-2), 101-5.
12. Hernández, M. (2000). Treatment of multiple sclerosis and quality of life. Rev Neurol, 30 (12), 1245-1245.
13. Introzzi, I; Urquijo, S; López Ramón, MF; (2010). Coding processes and executive functions in patients with multiple sclerosis. Psicothema, 22 (4), 684-690.
14. Junqué, C; Barroso, J.; (2001). Neuropsychology. Madrid: Madrid Synthesis.
15. Nieto, A; Barroso, J; Olivares, T; Wollmann, T; Hernández, MA; (nineteen ninety six). Neurological alterations in multiple sclerosis. Behavioral Psychology, 4 (3), 401-416.
16. Poser, C., Paty, D., Scheinberg, L., Mcdonald, W., Davis, F., Ebers, G., et al. . . Tourtellotte, W. (1983). New diagnostic criteria for multiple sclerosis: guildelines for research protocols. Ann Neurol, 3 , 227-231.
17. Rao, S. (2004). Cognitive function in patients with multiple sclerosis: Impairment and treatment. Int MS care, 1 , 9-22.
18. Santiago-Rolania, O; Guàrdia Olmos, J; Arbizu Urdiain, T.;. (2006). Neuropsychology of patients with relapsing remitting multiple sclerosis with mild disability. Psicothema, 18 (1), 84-87.
19. Sastre-Garriga, J; Alonso, J; Renom, M; Arévalo, MJ; González, I; Galán, I; Montalban, X; Rovira, A;. (2010). A functional magnetic resonance proof of concept pilot trial of cognitive rehabilitation in multiple sclerosis. Mult Scler, 17 (4), 457-467.
20. Simone, IL; Carrara, D; Tortorella, C; Ceccarelli, A; Livrea, P.; (2000). Early onestep multiple sclerosis. Neurol Sci, 21 , 861-863.
21. Terré-Boliart, R; Orient-López, F;. (2007). Treatment Rehabilitator in multiple sclerosis. Rev Neurol, 44 (7), 426-431.
22. Trapp, B., Peterson, J., Ransohoff, R., Rudick, R., Mork, S., & Bö, L. (1998). Axonal transection in the lesions of multiple sclerosis. N Engl J Med, 338 (5), 278-85.