Progressive disabling conditions

MULTIPLE SCLEROSIS

Multiple sclerosis (MS) is a chronic, progressive condition that involves cell-mediated autoimmune attack on myelinating cells of the CNS (oligodendrocytes).

🏘 Epidemiology

1. It is 3x more common in women.
2. Most commonly occurs in young adults (20-40 years).
3. More common in northern hemisphere (5x).

⚠️ Pathophysiology and risk factors

The function of myelin is to aid electrical impulse transmission. It insulates the axon as such. The myelinating cells of the CNS are the oligodendrocytes, while in the PNS it is the Schwann cell. MS only affects the CNS typically.

What occurs in MS is we get infiltration of auto reactive lymphocytes across the BBB, entering the CNS. These autoimmune cells then infiltrate the inflamed myelin → damage of the myelin and impaired electrical signalling. It is a type 4 hypersensitivity disease.

Early on we may see re-myelination of the axon and resolution of symptoms. However, later on in the disease progression, symptoms become more permanent.

Plaques of demyelination and later on axon all loss are the hallmarks of the disease. The lesions of MS are described as being “disseminated in time and space”.

The initiating factor is unclear but evidence indicates that some causes may be:

🔢 Classification

There are 3 types of MS that we can identify. However, preceding diagnosis of MS we usually see a clinically isolated syndrome (CIS).

1. Clinically isolated syndrome - it refers to the first neurological episode lasting at least 24 hours as a result of inflammation or demyelination in the CNS. The episode has no associated fever or infection. If the associated CIS is accompanied by MRI-detected brain lesions then there is a 60-80% chance of a secondary even and MS diagnosis within several years.It can be either:
1. Monofocal - a single neurological sign or symptom as a result of a single lesion (e.g. optic neuritis).
2. Multifocal - multiple symptoms experienced due to multiple diffuse lesions (e.g. optic neuritis and paraesthesia of the legs).

2. Relapsing-remitting MS - it is the most common disease pattern, characterised by disease and neurological symptoms followed by a period of recovery. It can be further classified as:
1. Worsening - level of disability is progressing with time.
2. Not worsening - disability is not advancing.
3. Active - new symptoms and lesions are developing and showing on MRI.
4. Inactive - no new symptoms or lesions are developing.

About 80% of MS courses are RRMS at presentation.

3. Primary progressive MS - steadily worsening from the onset of symptoms without relapse or remission from the start.
4. Secondary progressive MS - it is secondary to an initial course of RRMS, however, now there is progression without remission. It too can be classified the same way as RRMS as active/inactive and worsening/not worsening.

😷 Presentation

Lesions vary in their location, meaning that symptoms also change over time. We can say that lesions are disseminated in time and space.

Symptoms are progressive >24 hours. They usually last days-weeks before improving (depending on the disease course of course).

Some symptoms may include:

• Visual
• ⭐️ Optic neuritis - the most common presentation.
• Ophthalmoplegia
• Intranuclear ophthalmoplegia - occurs due to lesion of the medial longitudinal fasciculus within the brainstem. These fibres ensure that the eyes move together by coordinating the movements. It will present as a conjugate lateral gaze palsy. This means we have an inability of the eye to adduct. For example, when there is a left intranuclear ophthalmoplegia, the left eye can abduct and look left, but when looking right (addicting), it will remain in the middle.
• Optic atrophy
• Uhthoff’s phenomenon - worsening of vision when the body temperature rises.
• Sensory
• ⭐️ Paraesthesia
• Numbness
• Trigeminal neuralgia - pain on one side of the face.
• Lhermitte’s syndrome - paraesthesia in the limbs when flexing the neck, it indicates dorsal column pathology within the cervical spine.
• Motor
• ⭐️ Spastic weakness - commonly seen in the legs. MS is a disease of the CNS and so an UMN lesion is seen. LMN signs are not indicative of MS.
• Bell’s palsy
• Horners syndrome
• ⭐️ Incontinence
• Cerebellar
• Ataxia

🔍 Investigations and diagnosis

⭐️ Once again, we need to see lesions disseminated in time and space.

📷

Imaging:

MRI - we may see demyelinating features such as:

1. High signal T2 lesions (seen as very bright white lesions [hyperintense] against the greyer surrounding brain tissue) that are ovoid in shape.
2. Periventricular plaques - T2-hyperintertense lesions in direct contact with the lateral ventricles.
3. Dawson fingers - periventricular demyelinating plaques distributed along the endulzar veins, perpendicular to the lateral ventricles. Specific for MS.

💧

CSF (lumbar puncture):

• Oligoclonal bands - bands of immunoglobulins in the CSF. They indicate inflammation within the CNS. Sensitive to MS, but also found in Lyme disease and SLE.

McDonald criteria

This is the generally accepted standard for diagnosis:

🧰 Management

Acute relapse

Symptomatic treatment

Other progressive disabling conditions include:

• Rheumatoid arthritis and osteoarthritis - these will be covered in year 4 musculoskeletal block.
• Myasthenia gravis - to be covered in year 4 neurosciences block.
• Muscular dystrophy - to be covered in year 4 paediatrics block.