Motor neuron disease Flashcards
What is another name for MND?
Amyotrophic Lateral Sclerosis (ALS)
What is motor neuron disease?
Degeneration of upper and lower motor neurons
What is the cause of MND?
Unknown
How does MND progress?
It is progressive and usually fatal within 4 years of onset
What is the incidence of MND?
1.5/100,000
What is the prevalence of NMD?
6/100,000
How does NMD differ from peripheral neuropathies?
It is solely motor and not sensory
It involves upper and lower motor neurons
What is the prognosis from onset of MND?
50% die within 3-4 years
20% live > 5 years
10% live > 10 years
Occasionally patients live 20 years
What are risk factors for ALS?
Older age
Family history
Male gender
Unclear:
Occupational/environmental factors: job, military exposure, metals, pesticides, viruses
Lifestyle: smoking, low BMI, diet, physical exercise, trauma
Why might exercise be causing MND?
May be due to over-excitation of the nerves
Why might male gender be a risk factor?
May be due to hormones
More common in post-menopausal women
What is the average age of onset of MND?
~65 (wide range)
Which race is more likely to get MND?
White
What is known about the pathophysiology of MND?
ALS kills motor nerve cell, causing muscles to weaken
What does the amyotrophic in ALS refer to?
The muscles becoming thinner due to decreased lower motor neuron involvement
What does lateral sclerosis refer to?
The whiteness in the cortical spinal tract
What are the main sites affected by ALS?
Tongue (bulbar muscles)
Arms
Legs
What causes ALS death?
Respiratory muscle functions failing
What are the types of MND?
ALS
Progressive muscular atrophy – lower motor neuron
Progressive bulbar palsy – tongue and speech
Primary lateral sclerosis – upper motor neuron
What % of MND patients have a family history?
5-10% have family history
TRUE or FALSE?
Very few genes have been identified to be associated with MND
FALSE
Many have been identified (both in familial and apparently sporadic)
What are the symptoms of motor neuron disease?
Fasiculations
Wasting and weakness of muscles
Brisk reflexes
May have cognitive involvement
What causes fasiculations and muscle wasting?
Lower motor neurone degeneration
What causes brisk reflexes?
Upper motor neurone degeneration
What is the cognitive involvement similar to?
Frontal dementia
What are beginning signs of ALS?
Tripping, trouble buttoning, slowed speech and trouble swallowing
Which MND has the best survival?
Primary lateral sclerosis
What are the bulbar upper motor neuron signs?
Jaw jerk positive
Palatal spasticity
Tongue spasticity
What are the bulbar lower motor neuron signs?
Facial fasiculations
Tongue wasting
Palatal weakness and fasiculations
What are the cervical upper motor neuron signs?
Increased tone
Hyper-reflexia
Preserved reflexes in wasted muscles
What are cervical lower motor neuron signs?
Fasiculations and weakness
Muscle Wasting
Absent reflexes
What are lumbar upper motor neuron signs?
Increased tone and or extensor plantars
Hyper-reflexia
Preserved reflexes in wasted muscles
What are lumbar lower motor neurone signs?
Fasiculations and weakness
Muscle wasting
Absent reflexes
How do you diagnose MND?
Clinical history
Physical examination
EMG as support
Observe:
Progression of symptoms and signs
Normal Sensation
What should you find on physical examination of MND?
Lower motor neuron signs: weakness, wasting, fasiculations
Upper motor neuron signs: spasticity, brisk reflexes
Why do we do EMG?
To support findings of active denervation
TRUE or FALSE?
Upper and lower motor neurone features should be present in more than one region for MND
TRUE
What are the criteria used to diagnose ALS and when is it used?
El Escorial criteria
For research purposes
What tests do you do to rule out other conditions in MND?
Electromyogram Nerve conduction studies MRI of head and neck Muscle Biopsy Blood Tests CSF tests Consider DNA analysis
Why might we do an MRI of head and neck on a suspected ALS patients?
Might be a tumour (speech problems)
Is it common to do muscle biopsies in ALS-suspected patients?
No
How should CSF tests be in ALS?
Normal
TRUE or FALSE?
There are blood tests for ALS
FALSE
All they have found is increased CK (because of muscle wasting)
Which is the most common gene associated with familial ALS and what are some other top ones?
C9orf72
SOD1 - 20%
FUS and TARDBP - each 5%
There are many others
TRUE or FALSE?
Sporadic ALS is never associated with specific mutations
FALSE
A few have gene mutations like C9orf72
What kind of penetrance does C9orf72 have?
Incomplete
Which TARDBP is associated with ALS?
TDP43
What is the relationship of ALS with other neuropathies and FTD?
ALS has involvement with upper and lower motor neurons while CMT only involves lower ones and hereditary spastic parapalesia upper motor neurones
Frontotemporal dementia overlaps with ALS quite a lot
Why is there late diagnosis in MND?
It is often mistaken for something else
e.g. have to go to ENT clinics for trouble swallowing
What are the cognitive features of MND?
Behavioural change Emotional lability (not related to dementia) Frontotemporal dementia
Name the respiratory features of MND?
Shortness of breath on exertion Excessive daytime sleepiness Fatigue Early morning headache Un-refreshing sleep Orthopnoea Frequent unexplained chest infections Weak cough and sniff Nocturnal restlessness/ sweating
What are supporting factors for MND diagnosis?
Asymmetrical features
Age - any age can present
Family history for MND or other neurodegenerative disease
What are factors not supporting an MND diagnosis?
Bladder/bowel involvement
Prominent sensory symptoms
Improving symptoms
What % of MND patient present with bulbar symptoms?
25%
What % of MND patient present with limb features?
70%
What are bulbar features of MND?
Dysarthria Dysphagia Excessive saliva Chocking sensation when lying flat Weak cough
How can dysarthria present?
Quiet, hoarse or altered speech
Slurring of speech when tired
What are limb features of MND?
Focal weakness - painless preserved sensation
Distal weakness
Muscle wasting - hands, shoulders, asymmetrical
Muscle twitching and dasiculations
Cramps
How can distal weakness present?
Fall/trips - from foot drop
Loss of dexterity (problem with zip/buttons)
Why do people with NMD have early morning headache?
They don’t breathe well at night
Which muscles are least affected in MND?
Eye muscles
How to care for someone with MND?
Care for person and those that matter around them
Improve quality of life and symptom control
Respect patient autonomy and choice
Emphasis on open and sensitive communication
Describe the multidisciplinary care of patients with MND
Neurologist MND nurse Dietician Occupational therapist Physiotherapist MND association Respiratory physician Psychologist Speech and language therapist Social worker
Which symptoms in MND do we manage?
Muscle cramps Spasticity Respiratory symptoms Depression Cognition Pain Drooling Dysphagia Communication difficulties
What is a feature that is dominant and difficult to manage in MND?
Fatigue
Why might a person with MND have constipation?
Altered diet
Inadequate fluid
Lack of mobility
How do we treat sialorrhoea?
Anticholingergic drugs
Non-pharmacological approaches
Name some anticholinergic drugs
– Hyoscine (sublingual or transdermal)
– Atropine (orally)
– Tricyclic antidepressants (amitriptyline)
– Beta-blockers
– Glycopyrrolate
Name some non-pharmacological approaches to treating sialorrhoea
– Salivary gland irradiation
– Salivary duct ligation
– Botulinum toxin
How do we treat dysphagia?
Speech and language therapists
Dietitians
PEG (percutaneous endoscopic gastrostomy)
RIG (radiologically inserted gastrostomy)
How do PEGs work?
A tube is put in so that food is delivered directly to the stomach and a light is used to guide this procedure
When should patients get a PEG tube put in?
Earlier on - better survival
Because muscles must be preserved
How should communication difficulties be treated?
Speech and language therapists
Communication aids
What is used to treat muscle cramps?
- Quinine
- Diazepam
- Phenytoin
- Naftidrofuryl
How do you treat spasticity?
Physiotherapy
Specific interventions e.g. low tech equipment, environmental control systems
Drug treatment
What drugs treat spasiticity and what do they do?
– Baclofen
– Dantrolene
– Tizanidine
work by reducing excitability
How do we treat respiratory symptoms?
NICE guidance
Non-invasive respiratory support - e.g. for nocturnal hypoventilation (rare)
symptomatic treatment - e.g. opioids
Breathing Space Kit (MNDA)
Invasive ventilation
How do we treat depression and emotional lability?
- Amitriptyline
- SSRIs (selective serotonin re-uptake inhibitors) e.g. fluoxetine
- Psychiatric guidance
How do we treat pain?
• Anti-spasticity drugs
• Non-steroidal agents
Pain
- Analgesics - including oral morphine or transdermal fentanyl patches
- Principles of pain management include the WHO Ladder
- Physiotherapy
- Occupational therapy
What kinds of care planning can be done in advance?
- Advance directives
- Palliative care
- Multidisciplinary management
- End of life care
- Bereavement
What is the only licensed disease modifying med for ALS?
Riluzole (glutamate release inhibitor)
What are potential treatments for ALS?
Edaravone: Antioxidant treatment - only in Japan
Masitinib: tyrosine kinase inhibitor (targets mast cells and macrophages) - probably doesn’t work
