Signs and symptoms of multiple sclerosis
can cause a variety of symptoms varying significantly in severity and progression among individuals: changes in sensation, muscle weakness, abnormal muscle spasms, or difficulty moving; difficulties with coordination and balance; problems in speech or swallowing, visual problems, fatigue and acute or chronic pain syndromes, bladder and bowel difficulties, cognitive impairment, or emotional symptomatology. The main clinical measure in progression of the disability and severity of the symptoms is the Expanded Disability Status Scale or EDSS.
The initial attacks are often transient, mild, and self-limited. They often do not prompt a health care visit and sometimes are only identified in retrospect once the diagnosis has been made after further attacks. The most common initial symptoms reported are: changes in sensation in the arms, legs or face, complete or partial vision loss , weakness, double vision, unsteadiness when walking, and balance problems ; but many rare initial symptoms have been reported such as aphasia or psychosis. Fifteen percent of individuals have multiple symptoms when they first seek medical attention.
Fatigue
is very common and disabling in MS. Some 65% of people with MS experience fatigue symptomatology, and of these some 15-40% report fatigue as their most disabling MS symptom. A 2023 study found that effect on fatigue was the most valued attribute of MS therapy, and that participants would accept six additional relapses in 2 years and a decrease of 7 years in time to disease progression to improve either cognitive or physical fatigue from "quite a bit of difficulty" to "no difficulty."The pathophysiology and mechanisms causing MS fatigue are not well understood.
MS fatigue can be affected by body heat and this may differentiate MS fatigue from other primary fatigue.
Perceived fatigue and fatigability are regarded independently. Primary MS fatigue is sometimes called "lassitude". MS fatigue may reduce during periods of other MS symptom remission.
Knowledge of MS fatigue pathophysiology, diagnosis and treatment is very limited.
Primary vs. secondary
In some areas it has been proposed that fatigue be separated into primary fatigue, caused directly by a disease process, and secondary fatigue, caused by more general impacts on the person of having a disease.Contributory factors to secondary fatigue
Factors such as disturbed sleep, chronic pain, poor nutrition, or even some medications can all contribute to secondary fatigue and medical professionals are encouraged to identify and modify them.Association with depression
Early 2000s commentary saw a close relationship of secondary fatigue with depressive symptomatology. When depression is reduced fatigue also tends to reduce and it is recommended that patients should be evaluated for depression before other therapeutic approaches are used.Correlation with brain changes
Studies have found MS fatigue correlates, not with lesion volume or brain atrophy, but with damage to NAWM . The correlation becomes unreliable due to ageing in patients aged over 65.A 2008 study found MS fatigue correlated with lesion load and brain atrophy.
A 2024 study found results suggested that fatigue was not driven by neuroinflammation or neurodegeneration measurable by current structural MRI in early RRMS.
Medications
Medications used to treat MS fatigue include amantadine, pemoline, methylphenidate, and modafinil, as well as cognitive behavioral therapy and psychological interventions of energy conservation; but their effects are limited. For these reasons fatigue is a difficult symptom to manage.Technology
As of 2022 apps were being experimented with in the field of MS fatigue.Bladder and bowel
problems appear in 70–80% of people with multiple sclerosis and they have an important effect both on hygiene habits and social activity.Bladder problems are usually related with high levels of disability and pyramidal signs in lower limbs.
The most common problems are an increase in frequency and urgency but difficulties to begin urination, hesitation, leaking, sensation of incomplete urination, and retention also appear. When retention occurs secondary urinary infections are common.
There are many cortical and subcortical structures implicated in urination and MS lesions in various central nervous system structures can cause these kinds of symptoms.
Treatment objectives are the alleviation of symptoms of urinary dysfunction, treatment of urinary infections, reduction of complicating factors and the preservation of renal function. Treatments can be classified in two main subtypes: pharmacological and non-pharmacological.
Pharmacological treatments vary greatly depending on the origin or type of dysfunction and some examples of the medications used are:
alfuzosin for retention,
trospium and flavoxate for urgency and incontinency,
and desmopressin for nocturia.
Non pharmacological treatments involve the use of pelvic floor muscle training, stimulation, biofeedback, pessaries, bladder retraining, and sometimes intermittent catheterization.
Bowel problems affect around 70% of patients. Around 50% of patients experience constipation and up to 30% experience fecal incontinence. Cause of bowel impairments in MS patients is usually either a reduced gut motility or an impairment in neurological control of defecation. The former is commonly related to immobility or secondary effects from drugs used in the treatment of the disease. Pain or problems with defecation can be helped with a diet change which includes among other changes an increased fluid intake, oral laxatives or suppositories and enemas when habit changes and oral measures are not enough to control the problems.
Cognitive deficits
Deficits
Some of the most common deficits affect recent memory, attention, processing speed, visual-spatial abilities and executive function. Symptoms related to cognition include emotional instability and fatigue including neurological fatigue. Cognitive deficits are independent of physical disability and can occur in the absence of neurological dysfunction.Appraisal
Reviews have recommended annual appraisal using the Symbol Digit Modalities Test or similarly validated test.Effects
Severe cognitive impairment is a major predictor of a low quality of life, unemployment, caregiver distress, and difficulty in driving; limitations in a patient's social and work activities are also correlated with the extent of impairment.Prevalence
Cognitive impairments occur in about 40 to 60 percent of patients with multiple sclerosis,with the lowest percentages usually from community-based studies and the highest ones from hospital-based.
Impairments may be present at the beginning of the disease. Probable multiple sclerosis patients, meaning after a first attack but before a secondary confirmatory one, have up to 50 percent of patients with impairment at onset. Dementia is rare and occurs in only five percent of patients.
Causation
Cognitive deficits have been linked to greater lesion load, white matter lesion location, microstructural injury, gray matter lesions, cortical and subcortical gray matter brain atrophy, and discrepant patterns of cerebral activation.Measures of tissue atrophy are well correlated with, and predict, cognitive dysfunction. Neuropsychological outcomes are highly correlated with linear measures of sub-cortical atrophy. Cognitive impairment is the result of not only tissue damage, but tissue repair and adaptive functional reorganization.
Postulated treatments
As of 2018 efficacy of possible interventions was low, inconclusive, or preliminary.Neuropsychological rehabilitation may help to reverse or decrease the cognitive deficits although studies on the issue have been of low quality. Acetylcholinesterase inhibitors are commonly used to treat Alzheimer's disease related dementia and so are thought to have potential in treating the cognitive deficits in multiple sclerosis. They have been found to be effective in preliminary clinical trials.
Prevention
Primary prevention by interventions and healthy lifestyles that promote brain maintenance has been proposed.Emotional
Emotional symptoms are also common and are thought to be both a normal response to having a debilitating disease and the result of damage to specific areas of the central nervous system that generate and control emotions.Clinical depression is the most common neuropsychiatric condition: lifetime depression prevalence rates of 40–50% and 12-month prevalence rates around 20% have been typically reported for samples of people with MS; these figures are considerably higher than those for the general population or for people with other chronic illnesses. Brain imaging studies trying to relate depression to lesions in certain regions of the brain have met with variable success. On balance the evidence seems to favour an association with neuropathology in the left anterior temporal/parietal regions.
Other feelings such as anger, anxiety, frustration, and hopelessness also appear frequently. Suicide is a possibility, since it accounts for 15% of MS deaths.
Rarely psychosis may also be featured.
Internuclear ophthalmoplegia
Internuclear ophthalmoplegia is a disorder of conjugate lateral gaze. The affected eye shows impairment of adduction. The partner eye diverges from the affected eye during abduction, producing diplopia; during extreme abduction, compensatory nystagmus can be seen in the partner eye. Diplopia means double vision while nystagmus is involuntary eye movement characterized by alternating smooth pursuit in one direction and a saccadic movement in the other direction.Internuclear ophthalmoplegia occurs when MS affects a part of the brain stem called the medial longitudinal fasciculus, which is responsible for communication between the two eyes by connecting the abducens nucleus of one side to the oculomotor nucleus of the opposite side. This results in the failure of the medial rectus muscle to contract appropriately, so that the eyes do not move equally.
Different drugs as well as optic compensatory systems and prisms can be used to improve these symptoms.
Surgery can also be used in some cases for this problem.