MS, MN, Parkinsons, cerebellar lesions

Question 1

What is MS?

Answer 1

Multiple sclerosis (MS) is a chronic and progressive condition that involves demyelination of the myelinated neurones in the central nervous system. This is caused by an inflammatory process involving the activation of immune cells against the myelin.

Question 2

Who does MS typically present in?

Answer 2

20-40 year olds

Females

Question 3

What are the causes of MS?

Answer 3

The cause isn’t known!

Genetic factors…
HLA-DR2
Female

Environmental…
Vit D deficiency
Infections

Question 4

What is the presentation of MS?

Answer 4

Charcots neurologic triad…

1- dysarthria (difficult or unclear speech)
2- nystagmus (involuntary rapid eye movements)
3- intention tremor

Others...
Vision
- optic neuritis
- optic atrophy
- uhtoffs phenomenon- worsening of vision following a rise in body temperature 
- internuclear opthalmoplegia 

Sensory

• pins/needles
• numbness
• trigeminal neuralgia
• Lhermittes syndrome- parassthesia in limbs on neck flexion

Motor
- spastic weakness most commonly seen in the legs

Cerebellar

• ataxia
• tremor

Lhermitte’s sign- electric shock which runs down the back and radiates to the limbs when bending the neck forward

Plaques in autonomic nervous system leads to bowel and bladder symptoms as well as sexual dysfunction

Higher order activities of the brain…

• poor concentration and critical thinking
• depression and anxiety

Suspected when symptoms are spread over space and time

Question 5

What is clinically isolated syndrome of MS?

Answer 5

This describes the first episode of demyelination and neurological signs and symptoms. MS cannot be diagnosed on one episode as the lesions have not been “disseminated in time and space”. Patients with clinically isolated syndrome may never have another episode or develop MS. If lesions are seen on MRI scan then they are more likely to progress to MS.

Question 6

What is relapsing remitting MS?

Answer 6

Relapsing-remitting MS is the most common pattern at initial diagnosis. It is characterised by episodes of disease and neurological symptoms followed by recovery. In MS the symptoms occur in different areas with different episodes. This can be further classified based on whether the disease is active and/or worsening:

Active: new symptoms are developing or new lesions are appearing on MRI
Not active: no new symptoms or MRI lesions are developing
Worsening: there is an overall worsening of disability over time
Not worsening: there is no worsening of disability over time

Question 7

What is secondary progressive MS?

Answer 7

Secondary progressive MS is where there was relapsing-remitting disease at first, but now there is a progressive worsening of symptoms with incomplete remissions. Symptoms become more and more permanent. Secondary progressive MS can be further classified based on whether the disease is active and/or progressing.

Active: new symptoms are developing or new lesions are appearing on MRI
Not active: no new symptoms or MRI lesions are developing
Progressing: there is an overall worsening of disease over time (regardless of relapses)
Not progressing: there is no worsening of disease over time

Question 8

What is primary progressive MS?

Answer 8

Primary progressive MS is where there is a worsening of disease and neurological symptoms from the point of diagnosis without initial relapses and remissions. This can be further classified in a similar way to secondary progressive based on whether it is active and/or progressing.

Question 9

How do you diagnose MS?

Answer 9

Diagnosis is made by a neurologist based on the clinical picture and symptoms suggesting lesions that change location over time. Symptoms have to be progressive over a period of 1 year to diagnose primary progressive MS. Other causes for the symptoms need to be excluded.

Investigations can support the diagnosis:

MRI scans can show white matter plaques (loss of myelin)

Lumbar puncture shows high levels of antibodies- auto immune process

Visual evoked potential- measures the visual response to stimuli

Question 10

What does optic neuritis present with and what causes it?

Answer 10

Optic neuritis presents with unilateral reduced vision developing over hours to days. Key features are:

Central scotoma. This is an enlarged blind spot.
Pain on eye movement
Impaired colour vision
Relative afferent pupillary defect

Multiple sclerosis is the main cause of optic neuritis, however it can also be caused by:

Sarcoidosis
Systemic lupus erythematosus
Diabetes
Syphilis
Measles
Mumps
Lyme disease

Question 11

How do you treat MS?

Answer 11

RRMS

• corticosteroids
• cyclophosphamide
• IV immunoglobulins
• plasmopheresis (remove auto- antibodies)
• immunosuppressants

Progressive MS

• fewer options
• manage the symptoms of bladder dysfunction and depression
• physical therapy
• cognitive rehabilitation therapy
• vit D

Question 12

How do you treat relapses of MS?

Answer 12

Relapses can be treated with steroids. NICE recommend methylprednisolone:

500mg orally daily for 5 days
1g intravenously daily for 3–5 days where oral treatment has failed previously or where relapses are severe

Question 13

What is the symptomatic treatment of MS?

Answer 13

It is important to treat the symptom that result from the disease process along with treating the disease process itself:

Exercise to maintain activity and strength
Neuropathic pain can be managed with medication such as amitriptyline or gabapentin
Depression can be managed with antidepressants such as SSRIs
Urge incontinence can be managed with anticholinergic medications such as tolterodine or oxybutynin (although be aware these can cause or worsen cognitive impairment)
Spasticity can be managed with baclofen, gabapentin and physiotherapy

Question 14

What Is MND?

Answer 14

Motor neurone disease is an umbrella term that encompasses a variety of specific diagnoses. Motor neurone disease is a progressive, ultimately fatal condition where the motor neurones stop functioning. There is no effect on the sensory neurones and patients should not experience any sensory symptoms.

Question 15

What are the types of MN?

Answer 15

Amyotrophic lateral sclerosis (ALS) is the most common and well-known specific motor neurone disease. Stephen Hawking had amyotrophic lateral sclerosis.

Progressive bulbar palsy is the second most common form of motor neurone disease. It affects primarily the muscles of talking and swallowing.

Other types of motor neurone disease to be aware of are progressive muscular atrophy and primary lateral sclerosis.

Question 16

What is the pathophysiology behind MN?

Answer 16

There is a progressive degeneration of both upper and lower motor neurones. The sensory neurones are spared.

The exact cause is unclear although several mechanisms have been considered. There is a genetic component and many genes have been linked with an increased risk of developing the condition. Taking a good family history is important as around 5-10% of cases are inherited. There also seems to be an increased risk with smoking, exposure to heavy metals and certain pesticides.

Question 17

What is the presentation of MN?

Answer 17

The typical patient is a late middle aged (e.g. 60) man, possibly with an affected relative. There is an insidious, progressive weakness of the muscles throughout the body affecting the limbs, trunk, face and speech. The weakness is often first noticed in the upper limbs. There may be increased fatigue when exercising. They may complain of clumsiness, dropping things more often or tripping over. They can develop slurred speech (dysarthria).

Signs of lower motor neurone disease:

Muscle wasting
Reduced tone
Fasciculations (twitches in the muscles)
Reduced reflexes

Signs of upper motor neurone disease:

Increased tone or spasticity
Brisk reflexes
Upgoing plantar responses

Question 18

What id the diagnosis of MN?

Answer 18

The diagnosis of motor neurone disease needs to be made very carefully. It is based on the clinical presentation and excluding other conditions that can cause motor neurone symptoms. It should only be made by a specialist when there is certainty. Unfortunately, the diagnosis is often delayed, which causes considerable anxiety and stress.

Question 19

What is the management of MN?

Answer 19

Unfortunately, there are no effective treatments for halting or reversing the progression of the disease.

Riluzole can slow the progression of the disease and extend survival by a few months in ALS. It is licensed in the UK and should be initiated by a specialist.

Edaravone is currently used in the United States but not the UK. Recent studies suggest it has the potential to slow the progression of the disease and it may come in to use in the future.

Non-invasive ventilation (NIV) used at home to support breathing at night improves survival and quality of life.

The key to management of the condition is supporting the person and their family.

Effectively breaking bad news
Involving the multidisciplinary team (MDT) in supporting and maintaining their quality of life
Advanced directives to document the patient’s wishes as the disease progresses
End of life care planning
Patients usually die of respiratory failure or pneumonia

Question 20

What is Parkinsons?

Answer 20

Parkinson’s disease is a condition where there is a progressive reduction of dopamine in the basal ganglia of the brain, leading to disorders of movement. The symptoms are characteristically asymmetrical, with one side affected more than the other.

Question 21

What is parkinsonism?

Answer 21

A symptom complex, often caused by parkinsons (primary parkinsonism) or others (secondary parkinsonism)

• resting tremor
• problems with balance
• slow movements (like being in a pool)
• stiffness

Question 22

What is the pathophysiology of parkinsons?

Answer 22

The basal ganglia are a group of structures situated in the middle of the brain. They is responsible for coordinating habitual movements such as walking or looking around, controlling voluntary movements and learning specific movement patterns. Part of the basal ganglia called the substantia nigra produces a neurotransmitter called dopamine. Dopamine is essential for the correct functioning of the basal ganglia. In Parkinson’s disease, there is a gradual but progressive fall in the production of dopamine.

Question 23

What is the presentation of parkinsons?

Answer 23

Unilateral tremor
Cogwheel rigidity
Bradykinesia
There are a number of other features that often affect patients with Parkinson’s disease:

Depression
Sleep disturbance and insomnia
Loss of the sense of smell (anosmia)
Postural instability
Cognitive impairment and memory problems

Question 24

How is parkinsons diagnosed?

Answer 24

Parkinson’s disease is diagnosed clinically based on symptoms and examination. The diagnosis should be made by a specialist with experience in diagnosing Parkinson’s. NICE recommend using the UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria.

Question 25

What is the management of parkinsons?

Answer 25

Levodopa

This is synthetic dopamine given orally to boost their own dopamine levels. It is usually combined with a drug that stops levodopa being broken down in the body before it gets the chance to enter the brain. These are peripheral decarboxylase inhibitors. Examples are carbidopa and benserazide.

Combination drugs are:

Co-benyldopa (levodopa and benserazide)
Co-careldopa (levodopa and carbidopa)
Levodopa is the most effective treatment for symptoms but becomes less effective over time. It is often reserved for when other treatments are not managing to control symptoms.

The main side effect of dopamine is when the dose is too high patients develop dyskinesias. Theses are abnormal movements associated with excessive motor activity. Examples are:

Dystonia: This is where excessive muscle contraction leads to abnormal postures or exaggerated movements.
Chorea: These are abnormal involuntary movements that can be jerking and random.
Athetosis: These are involuntary twisting or writhing movements usually in the fingers, hands or feet.

COMT Inhibitors

The main example of this is entacapone. These are inhibitors of catechol-o-methyltransferase (COMT). The COMT enzyme metabolises levodopa in both the body and brain. Entacapone is taken with levodopa (and a decarboxylase inhibitor) to slow breakdown of the levodopa in the brain. It extends the effective duration of the levodopa.

Dopamine Agonists

These mimic dopamine in the basal ganglia and stimulate the dopamine receptors. They are less effective than levodopa in reducing symptoms. They are usually used to delay the use of levodopa and are then used in combination with levodopa to reduce the dose of levodopa that is required to control symptoms. One notable side effect with prolonged use is pulmonary fibrosis. Examples are:

Bromocryptine
Pergolide
Carbergoline

Monoamine Oxidase-B Inhibitors

Monoamine oxidase enzymes break down neurotransmitters such as dopamine, serotonin and adrenaline. The monoamine oxidase-B enzyme is more specific to dopamine and does not act on serotonin or adrenalin. These medications block this enzyme and therefore help increase the circulating dopamine. Similarly to dopamine agonists, they are usually used to delay the use of levodopa and then in combination with levodopa to reduce the required dose. Examples are:

Selegiline
Rasagiline

Question 26

What are the types of MS?

Answer 26

This is based on the pattern of symptoms over time

1) relapsing remitting RRMS (most common)
2) secondary progressive MS
3) primary progressive MS
4) progressive relapsing (PRMS)

Question 27

What would you look for on general examination of a patient with suspected parkinsons?

Answer 27

Typical patient is an older aged man around aged 70

On general exam-
Facial masking/ tremors

On inspection of gait-
Forward tilt
Reduced arm swing
Shuffling gait

Question 28

What is ataxia caused by?

Answer 28

Peripheral ataxia (finger- nose) is caused by cerebellar hemisphere damage

Gait ataxia is caused by cerebellar vermis damage

Question 29

What problems are associated with the basal ganglia?

Answer 29

Parkinsons- patient would be hypokinetic

Huntingtons- patient would be hyperkinetic

Question 30

What would you get with parietal lobe damage?

Answer 30

Sensory symptoms
Dyslexia
Dysgraphia

Question 31

What are the symptoms of frontal lobe damage?

Answer 31

Motor symptoms
Expressive aphasia
Disinhibition

Question 32

What is uhthoffs phenomenon?

Answer 32

This is where neurological symptoms are exacerbated by increases in temperature.