Motor neurone disease:
diagnosis & management
Dr Andria Merrison Consultant Neurologist
Director Bristol MND Centre
Director South West Neuromuscular
Disease Operational Delivery Network
Bristol MND Centre
• Online training modules for
GPs
• Booklet for GPs
• Diagnosis & management
• Suggested reading
www.mndassociation.org
NICE guideline NG42 2016
Motor Neurone Disease:
assessment & management
Motor neurone disease
• Neurodegenerative condition of anterior horn cells (lower motor
neurone) and corticospinal tracts (upper motor neurone)
• Rare, life-limiting, no curative treatment
• TDP43 inclusions
• 5-10% familial
• Prevalence 4-6/100,000
• Survival mean 2-3 years from time of diagnosis
Bristol MND Centre
MND: diagnosis
• Clinical diagnosis
• Investigations support diagnosis & rule out others
• No age, gender or risk factor clues
(family history of MND/other neurodegenerative disease)
• Progression
• Assymmetry: common
• Caution: prominent sensory symptoms, bladder/bowel symptoms, double vision, ptosis, facial weakness, prominent pain, weakness without wasting
Bristol MND Centre
MND: diagnosis - symptoms
• Limbs (65% at onset): painless progressive weakness
• Bulbar (30% at onset): dysarthria, dysphagia
• Respiratory (2% at onset): shortness of breath, orthopnoea, sleep
disruption, early morning headaches, daytime somnolence
• Cognitive (2-5% at onset): behavioural change, emotional lability,
memory impairment, dementia
• Axial weakness (3% at onset): head drop, posture
Bristol MND Centre
MND: diagnosis – UMN & LMN signs
• Lower motor neurone signs: wasting, fasciculation,
reduced tone, depressed reflexes,
weakness (focal)
• Upper motor neurone signs: increased tone,
brisk reflexes, jaw jerk, weakness (pyramidal)
• LMN = anterior horn cell death, muscle wasting
(amyotrophy)
• UMN = corticospinal tracts, lateral sclerosis or gliosis in
spinal cord (& motor cortex)
Bristol MND Centre
MND: diagnosis – forms of MND
• Amyotrophic lateral sclerosis (ALS) 80%
- mixed UMN & LMN
• LMN-predominant 5-15%
- no/little UMN signs clinically
- progressive muscular atrophy (PMA) is pure form
• UMN-predominant 4%
- no wasting, UMN signs only
- primary lateral sclerosis (PLS) is pure
form: no wasting after 4 years
Bristol MND Centre
Bristol MND Centre
MND: diagnosis - investigations
• Blood tests: FBC, U, E & Cr, LFTs, Ca, B12, folate, SEP, CK
(paraneoplastic antibodies, AIP, ANCA, ANA, ENA, HIV, Lyme,
hepatitis, anti-GM1 antibodies)
• NCS/EMG (Awaji criteria 2006)
- normal motor & sensory nerve conduction
- fibrillation & fasciculation potentials
- reduced motor unit potentials
- increased amplitude & duration of remaining motor units
• MRI: brain & spinal cord (as signs indicate)
• Lumbar puncture (paraneoplastic, inflammatory neuropathy, multiple
sclerosis)
Bristol MND Centre
Does this patient have MND?
• It is MND but has not progressed sufficiently or typically to be
confident about diagnosis
• It is MND but part of an overlap syndrome
• It is MND with something else going on as well
• It is something different entirely
- other causes of mixed upper & lower motor neurone signs
- something else with overlapping features
Benign fasciculations
Bristol MND Centre
Revised diagnosis in suspected MND
Revised diagnosis No of patients
Cervical spondylytic
myeloradiculopathy
10
MND-plus syndromes 7
Cerebrovascular disease 5
Radiculopathy (cause
unknown)
4
Multiple sclerosis 4
Multiple system atrophy 4
Peripheral neuropathy 4
Multi-focal motor
neuropathy
2
Other/uncertain 13
Total 53
Bristol MND Centre Scottish Registry 1989-92: 8%
Differential diagnosis in MND
Structural
(cord & root compression) • Spondylotic
myeloradiculopathy
• Malignancy
• Syrinx
Metabolic • B12 deficiency
(B12 & homocysteine)
• Copper deficiency
• Zinc deficiency
• Adrenomyeloneuropathy
(VLCFA)
Infection • HIV
• HTLV1
• Polio
• Hepatitis
• Lyme
• TB
Vascular Ischaemic
Inflammatory
(vasculitis)
Neuropathy Chronic inflammatory demyelination
polyneuropathy
Multi-focal motor neuropathy
Toxic Radiation
Drugs
Mercury
Inflammatory Multiple sclerosis
(primary progressive)
Vasculitis
Sarcoid
Bristol MND Centre
Other anterior horn cell
disease Spinal muscular atrophy
Kennedy’s disease
Myopathy Inclusion body myositis
Polymyositis
Degenerative Overlap syndromes
Multiple system atrophy
SCA
HSP
FA
Differential diagnosis in bulbar-onset MND
• Brainstem disease
• Vascular: ischaemia, haemorrhage, aneurysm, vasculitis
• Multiple sclerosis & other demyelination
• Tumours
• Syrinx
• Neuromuscular junction
• Myasthenia gravis
• Lambert-Eaton myasthenic syndrome
• Botulism
• Myopathy
• Inclusion body myositis
• Polymyositis
• Muscular dystrophy
Neuropathy Facial onset
sensorimotor neuropathy
Bristol MND Centre
Cervical spondylotic myelopathy
• Commonest cause of spastic paraparesis
• Commonest mimic for MND
• Can have this & MND
• 4% of patients with MND have undergone
spinal surgery that has not helped
• Symptoms: stiff legs & loss of dexterity most common, pain is common
(including Lhermitte’s), 80% have sensory symptoms, sphincter involvement
(may only be late)
• Signs: mixed UMN & LMN with UMN signs above LMN signs
• MRI will help: make sure you image the right bit
• Neurophysiology will help
Bristol MND Centre
Genetics & MND
• Up to 10% have a genetic cause
• Gene panel: Sheffield
• C9ORF72 is the commonest, accounts for 40% of familial cases &
8-10% of sporadic cases; expanded GGGGCC hexanucleotide
repeat (anticipation); association with FTD, 2011
• Superoxide dismutase 1 (SOD1) gene on chromosome 21, accounts
for 20% of familial & 2% of sporadic MND, autosomal dominant,
>150 mutations, binds zinc & copper ions & destroy free radicals,
slow progression, distal weakness, young onset
Riluzole
• Only licensed drug treatment for MND: shared care protocol
• Glutamate antagonist
• First trials 1994, NICE approved 2001
• Survival benefit: 3 months
• Contraindications: hepatic/renal impairment, neutropenia,
pregnancy/breast feeding
• Side effects: nausea, lethargy, liver (2-3%)/renal toxicity, bone
marrow suppression
• Monitoring: U,E & Cr, FBC, LFTs monthly for 3 months, 3 monthly
thereafter
• LFTS < 5XULN: halve the dose, LFTs > 5XULN stop drug
RIG/PEG
• Consider early in patients with bulbar-onset & persistent
weight loss
• Prevention of malnutrition, dehydration, medication
route, reduced anxiety about eating, improved QoL
• Side effects: bleeding, infection, ileus, diarrhoea,
refeeding syndrome
• Bristol RIGs in MND: 1 death in 5 years (elderly,
FVC<50%)
Ventilation & MND
• NIV improves QoL (including improved cognition & reduced distress)
in patients with respiratory symptoms secondary to hypoventilation
• Survival benefits are more modest
• NICE guidelines: use of NIV in MND 2010
• 30% of MND population use NIV (mainly at night)
• Surveillance: spirometry, overnight oximetry & TOSCA
• Small numbers (2%) choose to have invasive (tracheostomy)
ventilation in UK
Saliva management
• SALT & dietetics: early involvement
• Hyoscine 1mg patch change every 72 hours
• Amitriptylline 10-30mg nocte
• Glycopyrrolate 1-2mg BD
• Atropine eye drops 1% 2 drops SL BD or TDS
• Carbocysteine 125-500mg QDS
• Botulinum toxin injections: parotid & submandibular
• Cough assist machine
Psychology & MND: what do we know so far?
• The diagnosis, onset & progression of MND all have significant psychological impact for the individual, families & carers
• Psychological support (CBT, meditation, music, mindfulness) can improve quality of life
and reduce anxiety & depression for patients, families & carers (Dublin, The Walton Centre, Milan)
• Importance in accepting/declining gastrostomy & NIV;
“personalised care” (Al-Chalabi, Leigh & others)
• NICE guidance 2016: coping with change, relationships, changing identity & roles, sexuality, employment, anxiety/depression, respite
• Alignment with NHS Outcomes Framework domain 2, NHSE Five Year Forward View for
Mental Health 2016
• Cost benefits: NHSE Mental Health, The King’s Fund
Counselling psychology approach
• Provide a space, a platform for discussion, directed by the patient & hope to provide a means of making sense (normalisation) of that discussion • How do we find a way of talking?: talk about not talking, make it
safer, there are no taboo subjects
• Endings (goodbyes): prominent, multiple – need for open-ended sessions
• Enable not being alone/reduce isolation: humane response, bearing
witness, being alongside, paying attention/listening
Psychology service: themes
• Themes: life & death, death is ever present, loss & bereavement, uncertainty, relationships & meaning, stages of adaptation to loss & disability • Continuous process of multiple losses with ever lesser
agency and diminishing personal world
• Helplessness, hopelessness
• Specific behavioural intervention, uncommon but can be helpful (OCD, disinhibition, apathy)
Psychology & existentialism
• Life overshadowed by death: keep mortality in mind to highlight the value of life, attend to the present (not distracted) & be mindful, to live well • Life events (including illness) awaken that sense of mortality & can be harnessed for positive change (death anxiety as a fulcrum for change) • To be in the face of death, not alone & without fear • Emphasising interconnectivity with others: we all have that
diagnosis – being mortal
Psychology service • For patients & families: flexible, open-ended and
bereavement • Available at the time of clinic • Over 50% of population referred, 25-30% uptake at time of
diagnosis • Men less likely to access the service, those that do are less
likely to express distress • Men who do not access the service may benefit from their
partner accessing it • High levels of patient satisfaction & improved QoL
Case 1
• 55 year old travelling salesman. Ex-smoker, overweight.
Previous history of bowel cancer. Clumsy hands.
Intermittent tingling in hands. Distal weakness in upper
limbs. Widespread fasciculations in upper limbs.
Reflexes in upper limbs depressed as compared with
lower limbs. Right extensor plantar.
• What do you think might be the diagnosis?
• What tests would you do?
Case 2
• 43 year old man running his own office furniture
business. Ex-smoker. Limping for 18 months. Distal
weakness & wasting left lower limb. Few fasciculations in
both lower limbs. Increased tone left lower limb. Brisk
reflexes left lower limb and extensor plantar on left.
• Family history: brother in a wheelchair at age 37 and
mother in a wheelchair in her 70s. Thought to have a
form of muscular dystrophy.
Case 3
• 37 year old lady, hairdresser. Previous history of asthma
and family history of rheumatoid arthritis. Progressive
difficulties with walking. Weakness & wasting in right leg,
followed by similar problems in left leg over 3 years.
Distal weakness marked, mild distal wasting,
fasciculations in lower limbs. Reflexes depressed
generally. Sensation normal.
• What do you think might be the diagnosis?
• What tests would you do?
Case 4
• 47 year old man with MND, slowly progressive,
diagnosis 8 years ago. He has been using NIV at night.
He has expressed a wish that he not want to be
resuscitated or invasively ventilated. He has a
respiratory event at home and his wife calls for an
ambulance. An air ambulance arrives and he is
successfully resuscitated but there is concern that he will
not manage without invasive respiratory support.
• What do you do now?
Thank-you
