Physical disability - neuro and muscular Flashcards
(some on Anki)
What happens in Motor Neurone Disease (MND)? Explain simply
MND:
Degeneration of UMN and LMN
Signs and symptoms of UMN and LMN problems
What’s the most common form of MND?
Amyotrophic Lateral Sclerosis (ALS)
How many people diagnosed with ALS will die (and why) within 5 years following symptom onset?
70% will die within 5 years from symptoms onset of ALS -> due to respiratory muscles failure
Mean survival rate is 3 years
Pathophysiology of ALS
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)
Investigations in MND/ALS
- MRI -> to exclude other structural lesions
- Electromyography (EMG) -> to look for muscle denervation
- Diagnosis is clinical
Management of ALS
- general (supportive and meds)
- drooling
- dysphagia
- joint pain
- respiratory problems (Mx at home)
- 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
Complications of ALS
- depression
- frontal-type dementia
- immobility -> DVT. PE, aspiration pneumonia
- dysphagia -> malnutrition, weight loss
- respiratory failure -> weakness of respiratory muscles/ aspiration pneumonia
- What’s cerebral palsy?
- When does it need to appear to be diagnosed as CP
- What’s its nature? (progressive or non-progressive)?
- Persistent motor disorder
- appearing before age 3 yr
- nonprogressive lesion of the brain
Possible outcomes of cerebral palsy
- sensory abnormalities
- cognitive deficits
- epilepsy
- motor development may be impaired
*IQ is mostly nearly normal
Types of Cerebral Palsy and what happens in them
Possible causes of CP
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
General features (early symptoms) of CP
- Failure to achieve normal developmental milestones
- ‘floppy baby’
- Feeding difficulties
- Asymmetric hand movement
- hand preference before 12 months
Features of spastic CP
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
Features of Ataxic Hypotonic CP
Ataxic Hypotonic Cerebral Palsy (10%)
- Typically symmetrical signs
- Hypotonia
- poor balance
- delayed movements
- Uncoordinated movements/tremor
- May be cerebellar lesion
Features of Dyskinetic CP
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
Diagnosis of CP
- Mainly clinical diagnosis
- Usually between 6m and 2y of age
*Might be suspected earlier in high risk situations
- Brain imaging may be used
Management of CP
- 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
Complications of CP
- 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
Simple pathophysiology of MS
- Autoimmune attack of T cells on nerve fibre (demyelination)
- Scar tissue forms in the place of damaged myelin
- # nerve signals along the axons -> wide variety of symptoms
Describe type of MS
- relapsing-remitting
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)
Describe type of MS
Primary progressive
Secondary progressive
Primary progressive: progression of the disease from the onset is continuous
Secondary progressive: initially will be a relapsing-remitting type but then continuous progression
Types of MS
What pattern of symptoms is needed to make a clinical diagnosis ofMS??
Symptoms must be disseminated in time and space = 2 attacks in 2 different locations affected
How diagnosis of MS is made?
- the clinical picture of the symptoms
- MRI
- electrophysiology (measurement of flow of ions and electric voltage)
Symptoms of MS
What blood tests should be done to exclude other causes than MS?
- FBC
- CRP/ESR
- TFTs
- LFT’s
- U&Es
- Calcium
- Glucose
- vitamin B12
- HIV serology
MS management:
- general approach
- lifestyle
- notification
- 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
Symptoms relief (examples) in MS
- 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
-
Management of acute (relapse) attack of MS
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)
Pharmacological management of relapsing-remitting MS
Interferon Beta (immunosupressant)
Glatiramer (immunomodulator - to reduce frequency of relapses)
Dimethyl fumarate (anti-inflammatory)
Pharmacological management of active relapsing-remitting MS
Teriflunomide (immunomodulatory agent)
Alemtuzumab (a monoclonal antibody that binds to CD52 on the surface of lymphocytes and marks them for destruction)
New York HF criteria
Pharmacological treatment of RA
(names and class)
- 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
Methotrexate
mode of action
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
Methotrexate
side effects
contraindication
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
Monitoring in Methotrexate use
baseline then weekly FBCs, u+e, LFTs initially until stable then monthly
Hydroxychloroquine
MoA
Blocks toll-like receptors on plasmacytoid dendritic cells (innate immune cells that when activated produce high levels of interferon (IFN-α and IFN-β)) -> reducing activation and reducing production of interferon and the inflammatory process
Hydroxychloroquine
Side effects
Contraindications
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
Hydroxychloroquine
monitoring
visual acuity (before treatment and annually during treatment)
Sulfasalazine
Side effects
Contraindications
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
Sulfasalazine monitoring
- 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
Anti-TNF
MoA
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.
Anti- TNF
Side effects
Contraindications
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
Anti-TNF
monitoring
- 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
