Common Symptoms

Symptoms of Multiple Sclerosis

Multiple sclerosis (MS) is characterized by a broad array of symptoms. Despite this variability, most individuals with MS will exhibit a distinct set of symptoms during their initial clinical attack. This initial clinical attack in MS, usually referred to as Clinically Isolated Syndrome (CIS; see Overview), is an unpredictable episode reflecting an inflammatory demyelinating event in the central nervous system (CNS). Symptoms of a clinical attack usually begin acutely or subacutely, worsen over several days or weeks, and reach peak severity within 2-3 weeks. While some symptoms can become permanent, most improve over time. The degree of this improvement varies widely, from minimal to complete recovery, with improvement typically occurring 2-4 weeks after the symptoms have peaked. An episode lasting less than 24 hours is unlikely to represent a relapse and raises concern for a pseudorelapse. Pseudorelapse risk factors include infection, stress and heat. Multiple sclerosis can affect different parts of the CNS, such as the optic nerve, spinal cord, brainstem, cerebellum and the cerebral cortex, leading to sensory, motor and psychological disturbances. The most common clinical presentations of MS include optic neuritis, transverse myelitis, and internuclear ophthalmoplegia (INO).

Optic neuritis is typically unilateral (affecting one eye at a time). It occurs as a result of inflammatory demyelination of the optic nerve, which can cause visual disturbances such as blurry vision and desaturation of color (especially red). A blind spot in the visual field is usually present as well. Another very common sign of an ongoing optic neuritis episode is pain with eye movement, experienced by approximately 92% of patients during the optic neuritis treatment trial. This pain most likely results from stretching of the dural sheath around an inflamed optic nerve. Optic neuritis occurs in 70% of patients with MS, and around 25% will experience it as the first neurological episode. Afferent pupillary defect is often noted following inflammatory demyelination of the optic nerve. An estimated 50% of MS patients who have experienced an episode of optic neuritis will also have an afferent pupillary defect on exam. However, this condition can also be observed in patients without a distinct clinical episode of optic neuritis.

Myelitis occurs as a result of the inflammatory demyelination of the spinal cord. It includes motor deficits such as muscular weakness, sensory deficits, and/or ataxia. In acute, partial transverse myelitis, bilateral leg weakness with or without sensory level involvement is a common presentation. Weakness usually worsens with physical activity and often appears alongside upper motor neuron symptoms like hyperreflexia, spasticity and an extensor plantar response. In 30–40% of patients, motor manifestations are the first symptoms to appear, and nearly all patients experience them at some point during the progression of the disease. Myelitis also includes a variety of sensory impairments, such as paresthesia (the feeling of tingling, pins-and-needles, tightness, numbness, coldness and/or swelling of the limbs or trunk), Lhermitte’s sign (electric shock-like sensation that occurs down the spine or in the limbs with flexion of the neck), reduced sense of vibration and proprioception and decreased pain and light touch perception.

Internuclear ophthalmoplegia is a syndrome that results from demyelination along the medial longitudinal fasciculus in the brainstem. This demyelination disrupts the communication between the oculomotor and abducens nerve nuclei, leading to eye movement abnormalities. Both unilateral and bilateral INO can occur in MS, although the former is more prevalent. Typically, individuals with INO experience difficulty in moving the affected eye inward past the midline, while the eye moving outward may exhibit nystagmus. Other brainstem-related abnormalities in MS include sixth nerve palsy, facial sensory loss, vertigo and hearing loss.

Cognitive impairment is a prominent MS symptom, resulting from brain atrophy and cortical demyelination. It affects 40-70% of MS patients, primarily impacting information processing speed, episodic memory recall, sustaining attention and executive function. Additionally, fatigue, urogenital and gastrointestinal tract disfunction, as well as psychological disorders, all represent non-specific symptoms that are frequently reported in patients with MS. Fatigue affects over 75% of individuals with MS, often becoming a chronic aspect of daily life. It can further be promoted by sleep disturbances, especially considering the prevalence of insomnia, affecting nearly 50% of MS patients. Depression and anxiety rates range from 25% to 50%, with studies suggesting a direct relationship between the MS effects on the brain and the prevalence of depressive disorders. Finally, bowel and bladder symptoms are reported by 80% of patients with MS, while sexual dysfunction, including issues such as reduced libido, orgasmic difficulties and erectile dysfunction, affects up to 50%.

Early Indicators and Red Flags

Sensory and motor symptoms are often the initial indicators of multiple sclerosis, each presenting as the first sign in approximately 40% of patients. Retrospective data from health administrative and clinical databases in Canada and the UK revealed that people with MS had significantly higher rates of hospital admissions, physician visits and prescriptions up to ten years before their diagnosis, compared to those without MS. Most of these visits were related to non-specific symptoms, such as gastrointestinal and urinary issues, anxiety, depression, fatigue, insomnia and pain, and they were affecting people of all ages. Research has also shown that patients experience cognitive impairment early in the disease course, even when significant physical disability is not yet apparent. Some of the initial signs of MS that could prompt further investigation are shown in Table 2-1. Recognizing symptom patterns and their time course is crucial for diagnosing MS accurately. The first step in conducting a patient evaluation is obtaining a detailed medical history. Along with standardized questioning, it is important to gather information on: past or present episodes of CNS dysfunction, chronology of symptom onset (including symptom onset speed, symptom duration and symptom occurrence frequency), spontaneous improvement of neurological deficits and recurrence or worsening of symptoms due to a sudden increase in body temperature.

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