Q 2.14. Multiple sclerosis. MS vs other demyelinating diseases

Q 2.14. Multiple sclerosis. MS vs other demyelinating diseases


Multiple sclerosis is a disorder in which the body’s immune system attacks the protective covering of the nerve cells in the brain and spinal cord called the myelin sheath and this sheet is often compared to the insulation on an electrical wire, when that covering is damaged it exposes the actual nerve fiber which can slow or block the signals being transmitted within it.


It’s a chronic condition and often the damage disrupts the communication between the brain and the rest of the body, leading to a wide range of symptoms that can vary greatly among individuals.


Multiple sclerosis (MS) has several types that categorize the course and progression of the disease. The main types include:


1.    Relapsing-Remitting MS (RRMS):

·       Most Common: About 85% of people initially diagnosed with MS have this type.

·       Characteristics: Marked by clearly defined attacks of new or worsening symptoms (relapses) followed by partial or complete recovery (remission). In between relapses, there might be periods of stability.

2.    Secondary Progressive MS (SPMS):

·       Progression: Develops in some individuals with RRMS over time.

·       Characteristics: Initially, there are relapses and remissions, but eventually, the disease begins to progress more steadily without distinct relapses or remissions, leading to a gradual increase in disability.

3.    Primary Progressive MS (PPMS):

·       Less Common: Accounts for about 10-15% of MS cases.

·       Characteristics: A gradual worsening of symptoms from the beginning with no distinct relapses or remissions. Disability accumulates more steadily than in other forms of MS.

4.    Progressive-Relapsing MS (PRMS):

·       Rare: Represents a small percentage of MS cases.

·       Characteristics: Characterized by steady worsening of the disease from the onset but with occasional relapses where new symptoms might appear or existing ones worsen.




The exact cause of multiple sclerosis (MS) remains unknown, but it’s believed to result from a combination of genetic, environmental, and immunological factors:


1.    Immune System Dysfunction: This autoimmune attack leads to inflammation, damage to myelin, and, in some cases, damage to the underlying nerve fibers and the formation of lesions (areas of damage) in the CNS, disrupting nerve signals and leading to the characteristic symptoms of MS.

2.    Genetic Factors: There is evidence that genetics play a role in increasing the susceptibility to MS. Certain genetic variations on genes like: HLA DR-2 or combinations , and the XX chromosomes (females) , might make individuals more prone to developing the condition. 

3.    Environmental Factors: Factors like viral infections (such as Epstein-Barr virus or Human Herpes virus 6 ), low levels of vitamin D, smoking, and exposure to certain toxins might increase the risk of developing MS or trigger its onset in individuals with a genetic predisposition.




Treatment for MS aims to manage symptoms, modify the course of the disease, and improve the overall quality of life for individuals living with it.


1.    Disease-Modifying Therapies (DMTs):

·       These medications help reduce the frequency and severity of relapses and may slow disease progression.

·       Examples include interferons, glatiramer acetate, dimethyl fumarate, fingolimod, teriflunomide, and others.

2.    Corticosteroids:

·       Short courses of high-dose corticosteroids, such as oral prednisone or intravenous methylprednisolone, are often used to reduce inflammation during MS relapses, speeding up recovery.

3.    Symptomatic Treatments:

·       Medications and therapies to manage specific symptoms such as muscle spasms, fatigue, bladder or bowel dysfunction, pain, and depression. 

4.    Physical Therapy and Rehabilitation:

·       Physical therapy, occupational therapy, and speech therapy can help improve mobility, strength, balance, and overall functioning

5.    Lifestyle Modifications:

·       Healthy lifestyle choices, including regular exercise, a balanced diet, adequate rest, stress management, and avoiding smoking, can help manage symptoms and improve overall well-being.

6.    Experimental and Investigational Therapies:

·       Ongoing research investigates new treatment options, including stem cell therapies, novel immunomodulatory approaches, and other experimental treatments for MS.




Symptom Category


Sensory Symptoms

Numbness or tingling in the limbs or elsewhere in the body.


Altered sensations like the feeling of pins and needles.

Motor Symptoms

Weakness in the limbs or difficulty in coordination and balance.


Muscle stiffness or spasms.

Visual Disturbances

Blurred vision.


Double vision (diplopia).


Optic neuritis, which causes pain and temporary loss of vision in one eye.


A common and often debilitating symptom that can significantly impact daily activities.

Cognitive Changes

Problems with memory, attention, and processing information.


Difficulty in problem-solving or multitasking.

Emotional and Psychological

Mood swings.


Depression and anxiety.


MS-related pain can occur, including neuropathic pain (such as electric shock-like sensations)


and musculoskeletal pain.

Bladder and Bowel Dysfunction

Urinary urgency, frequency, or incontinence.


Constipation or bowel incontinence.

Speech and Swallowing

Some individuals may experience trouble speaking clearly or swallowing.






Neurological Examination Findings in MS


Lhermitte’s Sign

Electric shock-like sensation down the spine or limbs upon neck flexion.

Scanning Speech

Slow, deliberate, and monotone speech pattern due to cerebellar lesions.


Difficulty articulating speech, resulting in slurred or unclear speech.


Involuntary rapid eye movements, often indicating brainstem or cerebellar issues.

Hoffmann’s Sign

Reflex test showing flexion of thumb and index finger upon finger flicking.

Romberg Test

Assessing balance with eyes open and closed, revealing balance issues without visual input.


Difficulty performing rapid alternating movements due to cerebellar dysfunction.

Pseudobulbar Affect (PBA)

Uncontrollable episodes of laughter or crying unrelated to actual emotions.


! Optic neuritis, characterized by inflammation of the optic nerve and often causing sudden vision changes, is closely associated with multiple sclerosis (MS). This condition, affecting one or both eyes, can serve as an early symptom or a precursor to MS development, with about 20-50% of optic neuritis cases progressing to MS. Typically presenting as blurred vision or eye pain, optic neuritis results from immune system attacks on the optic nerve’s myelin sheath. Diagnosis involves imaging and neurological examinations, and treatment may include corticosteroids to reduce inflammation.


There are other conditions that also involve damage to the myelin sheath or the nerves in the central nervous system (CNS). Some of these conditions might share similarities with MS, while others have distinct features. Here are a few examples:


1.   Neuromyelitis Optica (NMO) or Devic’s Disease:

·       Characteristic Features: NMO primarily affects the optic nerves and the spinal cord, causing inflammation and demyelination. It’s often characterized by severe attacks of optic neuritis (inflammation of the optic nerve) and transverse myelitis (inflammation of the spinal cord), leading to vision loss and spinal cord damage.

·       Distinguishing Factor: NMO is associated with antibodies against a specific protein called aquaporin-4 (AQP4), which helps differentiate it from MS.

2.   Acute Disseminated Encephalomyelitis (ADEM):

·       Characteristic Features: ADEM is characterized by widespread inflammation and demyelination in the brain and spinal cord. It often occurs after viral infections or vaccinations and can present with symptoms similar to those seen in MS, such as optic neuritis or limb weakness.

·       Distinguishing Factor: ADEM typically has a more sudden and acute onset than MS, and it’s often a one-time event without recurrence.

3.   Chronic Inflammatory Demyelinating Polyneuropathy (CIDP):

·       Characteristic Features: CIDP affects the peripheral nerves (outside the CNS) and causes chronic inflammation and demyelination of nerve fibers. It leads to weakness, sensory disturbances, and sometimes pain in the limbs.

·       Distinguishing Factor: Unlike MS, which primarily affects the CNS, CIDP predominantly involves the peripheral nervous system.

4.   Transverse Myelitis:

·       Characteristic Features: Transverse myelitis is a condition involving inflammation and demyelination of the spinal cord. It can cause symptoms such as weakness, sensory disturbances, and sometimes paralysis in the affected area of the body.

·       Distinguishing Factor: While it shares some similarities with MS, transverse myelitis often presents as a single episode of spinal cord inflammation without the characteristic relapses seen in MS.


Diagnosis of MS by MRI (MRI findings)


Magnetic Resonance Imaging is a crucial tool in the diagnosis and monitoring of MS. Following are some common MRI signs used in the diagnosis of MS:


*In the context of multiple sclerosis , the term “plaques/lesions” refers to areas of demyelination and inflammation in the central nervous system, particularly in the brain and spinal cord.


1.   Lesions in the Central Nervous System (CNS):

·       MS typically presents with white matter lesions in the CNS, particularly in the brain and spinal cord.

·       Lesions may appear as hyperintense (bright) areas on T2-weighted images and as hypointense (dark) areas on T1-weighted images.

2.   Distribution of Lesions:

·       MS lesions are often disseminated in space and time, meaning they are found in different locations within the CNS and occur at different points in time.

·       The lesions are commonly seen in periventricular areas, corpus callosum, brainstem, cerebellum, and spinal cord.

3.   Gadolinium Enhancement:

·       Gadolinium is a contrast agent used in MRI to enhance the visibility of active inflammation and blood-brain barrier disruption.

·       Gadolinium-enhanced lesions indicate active inflammation and may be seen as bright areas on post-contrast T1-weighted images.

4.   T1 Hypointense “Black Holes”:

·       Some chronic lesions may appear as T1 hypointense “black holes,” indicating more severe tissue damage and axonal loss.


Active-Inactive plaques


Active Plaques:

  • Gadolinium Enhancement: Active plaques often exhibit contrast enhancement when a gadolinium-based contrast agent is administered during the MRI scan. Gadolinium enhances the visibility of areas with a disrupted blood-brain barrier, indicating ongoing inflammation.


Inactive Plaques:

  • No Gadolinium Enhancement: Inactive or chronic plaques do not typically exhibit gadolinium enhancement, indicating a more stable phase of the disease without active inflammation.


Cerebrospinal fluid examination


While the diagnosis of MS is primarily based on a combination of clinical symptoms, neurological examination, and imaging studies such as MRI, CSF analysis can provide additional information to support the diagnosis and rule out other conditions.


1.   Oligoclonal Bands (OCBs):

·       OCBs are abnormal bands of immunoglobulins that can be detected in the CSF.

·       The presence of OCBs, along with a normal pattern in the blood, is considered a supportive finding for MS. OCBs are found in a significant proportion of MS patients.

2.   Elevated Immunoglobulin G (IgG) Index:

·       The IgG index is a measure of the ratio of IgG in the CSF to IgG in the blood.

·       An elevated IgG index may indicate increased production of immunoglobulins within the central nervous system, which can be associated with MS.

3.   Cell Count and Protein Levels:

·       CSF analysis includes the assessment of cell count and protein levels.

·       In MS, the cell count is usually within the normal range, but a mildly elevated protein level may be observed.

4.   Cytology:

·       Examination of CSF for abnormal cells is performed to rule out other potential causes of neurological symptoms.




Verified by Dr. Petya Stefanova