Physical disability - neuro and muscular

Question 1

What happens in Motor Neurone Disease (MND)? Explain simply

Answer 1

MND:

Degeneration of UMN and LMN

Question 2

Signs and symptoms of UMN and LMN problems

Answer 2

Question 3

What’s the most common form of MND?

Answer 3

Amyotrophic Lateral Sclerosis (ALS)

Question 4

How many people diagnosed with ALS will die (and why) within 5 years following symptom onset?

Answer 4

70% will die within 5 years from symptoms onset of ALS -> due to respiratory muscles failure

Mean survival rate is 3 years

Question 5

Pathophysiology of ALS

Answer 5

Progressive destruction of UMN and LMN by the mechanisms that will destroy the neurones (e.g. excitotoxicity, excessive intracellular and mitochondrial Ca2+, apoptosis, free radicals)

Question 6

Investigations in MND/ALS

Answer 6

• MRI -> to exclude other structural lesions
• Electromyography (EMG) -> to look for muscle denervation
• Diagnosis is clinical

Question 7

Management of ALS

• general (supportive and meds)
• drooling
• dysphagia
• joint pain
• respiratory problems (Mx at home)

Answer 7

• MDT support
• anti-glutamatergic medication -> Riluzole (MoA: Na+ channel blocker -> inhibition of release of glutamate) as glutamate may cause CNS damage *life prolonged by 3 months
• drooling: amitriptyline (anti-depressant), propantheline (anti-muscarinic)
• dysphagia: blend food, NG tube, percutaneous endoscopic gastrostomy
• joint pain: analgesics ladder (NSAIDs then opioids)
• respiratory failure: non-invasive ventilation at home

Question 8

Complications of ALS

Answer 8

• depression
• frontal-type dementia
• immobility -> DVT. PE, aspiration pneumonia
• dysphagia -> malnutrition, weight loss
• respiratory failure -> weakness of respiratory muscles/ aspiration pneumonia

Question 10

• What’s cerebral palsy?
• When does it need to appear to be diagnosed as CP
• What’s its nature? (progressive or non-progressive)?

Answer 10

• Persistent motor disorder
• appearing before age 3 yr
• nonprogressive lesion of the brain

Question 11

Possible outcomes of cerebral palsy

Answer 11

• sensory abnormalities
• cognitive deficits
• epilepsy
• motor development may be impaired

*IQ is mostly nearly normal

Question 12

Types of Cerebral Palsy and what happens in them

Answer 12

Question 13

Possible causes of CP

Answer 13

Multiple - Can be divided into 3 groups

• Antenatal - maternal infection, intraventricular haemorrhage
• Perinatal – prematurity, hypoxia, birth trauma, neonatal jaundice (kernicterus)
• Postnatal – meningitis, encephalitis, CNS trauma, hypoglycaemia

Question 14

General features (early symptoms) of CP

Answer 14

• Failure to achieve normal developmental milestones
• ‘floppy baby’
• Feeding difficulties
• Asymmetric hand movement
• hand preference before 12 months

Question 15

Features of spastic CP

Answer 15

Spastic cerebral palsy (70%)

• UMN lesion signs -> Brief reflexes, Spasticity, Extensor plantar response Flexed arm, possibly extended leg, abnormal gait, trunk, the head may be affected (depends on type e.g. hemipelagic, diplegic, quadriplegic)
• Associated with seizures and reduced intellectual ability

Question 16

Features of Ataxic Hypotonic CP

Answer 16

Ataxic Hypotonic Cerebral Palsy (10%)

• Typically symmetrical signs
• Hypotonia
• poor balance
• delayed movements
• Uncoordinated movements/tremor
• May be cerebellar lesion

Question 17

Features of Dyskinetic CP

Answer 17

Dyskinetic (Choreoathetoid) Cerebral Palsy (20%)

• Fluctuating muscle tone
• Gives rise to involuntary movements
• Basal ganglia/extrapyramidal tract damage
• Usually affects all four limbs
• Especially apparent when stressed
• Chorea- irregular, sudden movements
• Athetosis (distal limbs) - simultaneous contraction then relaxation of opposing muscle groups

Question 18

Diagnosis of CP

Answer 18

• Mainly clinical diagnosis
• Usually between 6m and 2y of age

*Might be suspected earlier in high risk situations

• Brain imaging may be used

Question 19

Management of CP

Answer 19

• MDT (Physiotherapy OT Speech therapy Voluntary agencies Social services input)
• Medication – Baclofen (muscle relaxant = GABA agonist), Botulinum toxin injections (prevents the release of Ach -> flaccid paralysis is caused)
• Surgery - for contractures

Question 20

Complications of CP

Answer 20

• Contractures GI symptoms: reflux, oropharngeal muscle disorder (affects swallowing and saliva clearance)
• Pulmonary: aspiration pneumonia and bronchopulmonary dysplasia
• Learning disability
• Hearing loss (from hyperbilirubinaemia or exposure to ototoxic drugs)
• Epilepsy
• Squints
• Speech and language difficulties
• Behavioural disorders

Question 21

Simple pathophysiology of MS

Answer 21

1. Autoimmune attack of T cells on nerve fibre (demyelination)
2. Scar tissue forms in the place of damaged myelin
3. # nerve signals along the axons -> wide variety of symptoms

Question 22

Describe type of MS

• relapsing-remitting

Answer 22

Relapsing-remitting

• symptoms come and go
• period of good health and then sudden relapse
• no disease progression in between relapses (however the level of disability will be increasing as it will accumulate after each relapse over the time)

Question 23

Describe type of MS

Primary progressive

Secondary progressive

Answer 23

Primary progressive: progression of the disease from the onset is continuous

Secondary progressive: initially will be a relapsing-remitting type but then continuous progression

Question 24

Types of MS

Answer 24

Question 25

What pattern of symptoms is needed to make a clinical diagnosis ofMS??

Answer 25

Symptoms must be disseminated in time and space = 2 attacks in 2 different locations affected

Question 26

How diagnosis of MS is made?

Answer 26

- the clinical picture of the symptoms - MRI - electrophysiology (measurement of flow of ions and electric voltage)

Answer 27

Symptoms of MS

Question 28

What blood tests should be done to exclude other causes than MS?

Answer 28

- FBC - CRP/ESR - TFTs - LFT's - U&Es - Calcium - Glucose - vitamin B12 - HIV serology

Question 29

**MS management:** - general approach - lifestyle - notification

Answer 29

- **MDT**: consultant neurologist, specialist nurse, physio, OT, SALT, psychologicts, social care, continence specialist - **lifestyle**: quit smoking - as it will increase the progression, flu vaccines - but may induce relapse, pregnancy - will cease the relapse but induce it 3-6months following birth - notify **DVLA** **- exercise**

Question 30

Symptoms relief (examples) in MS

Answer 30

- supervised exercise programme -\> for mobility issues - **Sildenafil** (viagra - increase NO release) -\> for erectile dysfunction - ***gabapentin*** (GABA analogue) or ***baclofen*** (GABA agonist -\> relax skeletal muscles)-\> for spasticity -

Question 31

Management of acute (relapse) attack of MS

Answer 31

0.5 mg oral ***methylprednisolone*** for 5 days or IV 1g for 3-5 days (if oral does not work or the attack is severe)

Question 32

Pharmacological management of relapsing-remitting MS

Answer 32

***Interferon Beta*** (immunosupressant) ***Glatiramer*** (immunomodulator - to reduce frequency of relapses) ***Dimethyl fumarate*** (anti-inflammatory)

Question 33

Pharmacological management of **active** relapsing-remitting MS

Answer 33

***Teriflunomide*** (immunomodulatory agent) ***Alemtuzumab*** (a monoclonal antibody that binds to CD52 on the surface of lymphocytes and marks them for destruction)

Answer 34

New York HF criteria

Question 35

Pharmacological treatment of RA | (names and class)

Answer 35

* ***Methotrexate*** - antimetabolite - stops growing cells and suppresses immune system * ***Hydroxychloroquine -*** anti-malaria, but also RA and SLE * ***Sulfasalazine -*** anti-inflammatory * ***Anti-TNF (e.g. etanercept or infliximab) -*** monoclonal antibody

Question 36

***Methotrexate*** mode of action

Answer 36

**MoA:** Inhibits enzymes involved in **purine metabolism** → accumulation of adenosine, inhibition of T-cell activation and suppression of intracellular adhesion molecule expression by T-cells, selective down-regulation of B-cells, increasing CD95 sensitivity of activated T-cells (death receptor), inhibition of methyltransferase activity

Question 37

***Methotrexate*** side effects contraindication

Answer 37

**Side effects:** bone marrow suppression (fbc check if sore throat, fever, symptoms/signs infection), pulmonary fibrosis and pneumonitis, liver toxicity **Contraindication:** pregnancy, breast feeding, hepatic impairment, severe renal impairment, bone marrow suppression

Question 38

Monitoring in ***Methotrexate*** use

Answer 38

baseline then weekly FBCs, u+e, LFTs initially until stable then monthly

Question 39

***Hydroxychloroquine*** MoA

Answer 39

Blocks toll-like receptors on plasmacytoid dendritic cells (innate immune cells that when activated produce high levels of interferon (IFN-α and IFN-β)) -\> r**educing activation** and r**educing production** of **interferon and the inflammatory process**

Question 40

***Hydroxychloroquine*** Side effects Contraindications

Answer 40

**Side effects**: GI disturbance, headache, skin reactions (rashes, pruritus), retinal damage (stop drug if any vision change), convulsions, blood disorders (inc agranulocytosis) **Contraindications**: ocular abnormalities (should be screened before commencing treatment). use with caution in neurological disorders (esp epilepsy), severe GI disorders. May exacerbate psoriasis

Question 41

***Hydroxychloroquine*** monitoring

Answer 41

visual acuity (before treatment and annually during treatment)

Question 42

***Sulfasalazine*** Side effects Contraindications

Answer 42

**Side effects:** GI disturbance, lung disorders (eosinophilia, fibrosing alveolitis), renal dysfunction (nephrotic syndrome, interstitial nephritis), blood disorders (agranulocytsis, thrombocytopenia – FBC check if any bruising/bleeding/purpura/sore throat/malaise), hepatitis. **Contraindications:** salicylate hypersensitivity

Question 43

Sulfasalazine monitoring

Answer 43

* FBC and LFT (every 2 weeks for 3/12 then every 4 weeks for 3/12 then every 3/12 once stable) * U+E monthly for 3/12 then as clinically indicated

Question 44

***Anti-TNF*** MoA

Answer 44

TNF-α is a pro-inflammatory mediator; part of the destructive process that occurs in joints in RA. Biologics that inhibit the action of TNF-α are used to modify the disease process in RA.

Question 45

***Anti- TNF*** Side effects Contraindications

Answer 45

**Side effects:** Hypersensitivity reactions, infections (greatest risk in first 6m), GI disturbance, hepatic impairment, increased risk of malignancy (esp non-melanoma skin cancers), interstitial lung disease **Contraindications:** active/latent TB, severe infections, heart failure (moderate/severe), history of malignancy, demyelinating CNS disorders

Question 46

***Anti-TNF*** monitoring

Answer 46

* FBC, CRP, U+E, LFT every 3-6 months * TB screening before treatment, during and 6m after tx if develops any symptoms * hepatitis B for those at risk