Neuromuscular Disease

Dr Andria Merrison MA MD MBChB FRCP

Consultant Neurologist & Clinical Director South West

Neuromuscular Operational Delivery Network

Director of the Bristol MND Care Centre

Content

• South West Neuromuscular Operational Delivery network: service, team & clinics

• Presentation of respiratory problems & diseases that include respiratory

impairment

• Neuromuscular conditions associated with respiratory (& cardiac) failure

• Assessment & treatment of respiratory problems in Neuromuscular Disease

• Cases • Discussion space/question time

BNSSG

& BANES

GLOUCESTER ROYAL HOSPITAL

CORNWALL

DEVON

SOMERSET

WILTSHIRE

GLOUCESTERSHIRE

SOUTHMEAD HOSPITAL

BRISTOL ROYAL CHILDREN’S HOSPITAL

MUSGROVE PARK HOSPITAL

ROYAL DEVON & EXETER HOSPITAL

TORBAY HOSPITAL

DERRIFORD HOSPITAL

ROYAL CORNWALL HOSPITAL

South West Neuromuscular Disease Network

6500 adults & children

85% adults presenting in

adulthood

DMD survival

Providing specialist holistic care, as close to home as possible, across traditional boundaries of health and social care and across organisational divides https://www.nbt.nhs.uk/south-west-neuromuscular-operational-delivery-network

The team

5 Consultants 3.5 Physiotherapists 4 Neuromuscular Advisors 2 0.4 Psychologists 1 ODN Network manager 1 ODN Network co-ordinator Consultant secretarial support

Joint Neuromuscular/Respiratory clinics

• Adult, paediatric & transition

• Joint collaborative working with

MDT approach

• Manage uncertainty: 50% of

patients with a muscle disorder:

diagnosis uncertain &

>50% of patients with a neuropathy aetiology is uncertain

• Rollercoaster: unexpected success & failure

Things that can go wrong with breathing in Neuromuscular Disease

• Breathing muscle weakness: intercostal muscles & diaphragm

• Upper airway muscles

• Weak cough &/or impaired swallowing

can lead to recurrent chest infections

• Reduced neurological drive to breath – Peripheral nervous system (autonomic neuropathy)

– Central nervous system (myotonic dystrophy)

Other areas of weakness that my affect breathing, respiratory assessment and/or treatment

• Facial weakness: facioscapulohumeral muscular dystrophy, myotonic dystrophy, myasthenia gravis, inflammatory muscle disease/IBM

• Dysphagia: dystrophy, NMJ, inflammatory muscle disease/IBM, MND, oculopharyngeal muscular dystrophy

• Neck: myasthenia gravia, MND, paraspinal myopathy

• Tongue: MND, myotonia, MG

Presentation of respiratory failure in Neuromuscular Disease

• Age of onset (Duchenne versus IBM or oculopharyngeal MD) • Likelihood of respiratory failure: a) inevitable (eg. DMD) b) common: rarely in a common disease (eg. Myotonic dystrophy) or commonly in a rare disease (nemaline myopathy) c) rarely: IBM, LGMD

• Progressive a) rapidly, unremitting, life-limiting (DMD) b) slowly (myotonic dystrophy) • Variable, may be with severe exacerbations (MG)

• Respiratory failure in isolation (or over & above limb weakness): MND, SMA,

LGMD, nemaline/myofibrillar myopathy, acid maltase deficiency

Muscle disease associated with respiratory failure

Dystrophies Duchenne muscular dystrophy Myotonic dystrophy* Limb girdle 1A,1B, 2A, 2I* Scapuloperoneal muscular dystrophy (Becker muscular dystrophy) (Facioscapulohumeral muscular dystrophy)

Congenital X-linked myotubular myopathy* Nemaline myopathy* Myofibrillar myopathy*

Metabolic Acid maltase deficiency* Primary carnitine deficiency* Debrancher enzyme deficiency*

Mitochondrial Generalised myopathy Leigh’s disease (CPEO)

Endocrine/electrolyte Hypokalaemia* Hypophosphataemia* Hypermagnesiumaemia* Barium intoxication* Hyperthyroidism*

Inflammatory (Polymyositis) (Dermatomyositis)

Muscle disease associated with

cardiac problems Dystrophies

DMD (HCOM, DCOM, rhythm, SD)

BMD (COM 30%, rhythm, SD)

EDMD (rhythm, COM, SD)

Myotonic (rhythm, COM, SD)

LGMD 1A (myotilin) (COM, rhythm)

LGMD 1B (laminin A/C) (rhythm, COM)

LGMD 2C-F (sarcoglycanopthies) (COM)

LGMD 2I (FKRP) (COM)

X-linked scapuloperoneal (HCOM)

Primary inflammatory (COM, rhythm)

Mitochondrial

Kearns-Sayre syndrome

(rhythm, DCOM, SD)

Channelopathy

Anderson-Tawil syndrome

(rhythm, valvular, SD)

Metabolic

Carnitine deficiency (COM)

Acid maltase deficiency (COM)

Debrancher enzyme deficiency (COM)

COM cardiomyopathy

HCOM hypertrophic cardiomyopathy

DCOM dilated cardiomyopathy

Rhythm arrhythmia

SD sudden death

Assessment of respiratory problems in Neuromuscular Disease

• History & examination • Lung function tests: FVC, MIPs/MEPs, SNIFF • Overnight oximetry • CO2 measurement: TOSCA • Measurements of diaphragmatic movement/strength

• Echocardiogram

Symptoms associated with impaired breathing

• Orthopnoea • Daytime sleepiness • Early morning headaches • Poor/disrupted sleep pattern • Reduced concentration • Loss of appetite/unexplained weight loss • Recurrent chest infections

• Diaphragmatic weakness: SOB swimming

Treatable Neuromuscular Diseases

• Myasthenia gravis: pyridostigmine, steroids, azathioprine, methotrexate, ivIg, plasma exchange

• Other NMJ disorders: Lambert Eaton myasthenic syndrome, botulism • Inflammatory myopathy (polymyositis): steroids, other

immunosuppressants, ivIG

• Pompe’s disease (acid maltase deficiency): enzyme replacement therapy

• Acute neuropathy (Guillan Barre syndrome): ivIG, immunosuppression

• Malignant hyperthermia: preventative measures, dantrolene, treat electrolyte imbalance & cardiac dysrhythmia

Treatment

• Physiotherapy & assisted cough techniques (eg breath stacking)

• Cough assist • CPAP for obstructive sleep apnoea

• BiPAP for respiratory muscle weakness

• May need triggered ventilation in central hypoventilation/apnoeas

• Other preventative measures: flu & pneumonia vaccines (patient &

carers), antibiotics at home

• End-of-life issues, tracheostomy, palliative medicine, ventilator withdrawal

Reasons for treatment

• Reduction or resolution of symptoms: improved quality of life

• Improved cognition

• Increased longevity for some patients

• Long-term health benefits of treating nocturnal hypoventilation: cardiac complications, diabetes etc

• ?Benefits of early ventilation on respiratory muscle decline in DMD

Saliva management & nutrition

• SALT input

• Amytriptylline 10-50mg nocte

• Hyoscine: drops, patches, pumps

• Glycopyrronuim: up to 2mg BD

• Carbocysteine 375mg BD-TDS

• Inadequate nutrition will lead to inadequate ventilation & high risk of respiratory complications (LRTI)

• Inadequate nutrition will lead to poor outcomes

Case RL • 82 year old man, known MG, anti-AChR Abs >20, no thymic abnormality

• June 2012: RL discontinued all medication • August 2012: readmitted with progressive dysarthria, dysphagia, neck

flexion weakness, bilateral ptosis, diplopia & mild proximal muscle weakness

• FVC 1.14 litres • NGT • Pyridostigmine 90mg X 6 daily • Prednisolone 60mg daily • Alendronic acid, calcium & omeprazole

Case RL: readmission 2012

• Deteriorated rapidly & was admitted to ITU • 5 days of ivIG, physiotherapy, plasma exchange • Started on azathioprine 75mg BD • Discharged 1/12 later

• Now committed to pyridostigmine & azathioprine

Case: PO

• 56 year old man admitted for a laparoscopic cholecystectomy

• First degree heart block, mild bradycardia intra-operatively

• Surgery went well but poor anaesthetic post-op recovery: unable to extubate, drowsy, admitted to ITU

• Previous history of early cataracts & impaired glucose tolerance

• Family history: sudden death in father age 54, early cataracts

• Frontal balding, proximal muscle thinning

Case: PO

• Mild proximal weakness all 4 limbs

• Facial weakness & mild swallowing difficulties

• Grip & eyelid myotonia

• Lung function tests & overnight oximetry: respiratory muscle weakness, hypoventilation with an obstructive component

• EMG: widespread electrical myotonia, mild myopathic changes

• BiPAP at night

• Subsequently: pacemaker

Case: DA

• 26 year old man, recreational drug user

• 5 day history of progressive weakness: descending, speech & swallowing difficulties, bilateral ptosis, double vision

• Facial weakness & dilated pupils, depressed reflexes

• Rapidly progressive respiratory failure

• Intubated and ventilated

• Initially treated with ivIG but not real improvement

Case: DA

• Turned him over: large wound in left buttock

• Wound debrided: contained botulism and black tar heroin

• Treatment: ongoing respiratory support, further debridement of the wound, botulinum antitoxin

• Returned home 21 months later

Merrison et al (2002) BMJ 325: 1020-1

Case: CH

• Arrest call to A&E

• 36 year old man with known severe asthma (on steroids & one previous ITU admission)

• Increased use of inhalers over several days & sleep disruption

• Treatment for asthma provided on arrival: nebulised salbutamol, oxygen, iv steroids

• Progressive, rapid hypoxia & respiratory distress

• Eyes open, fearful

• Chest wall not moving much, he wasn’t moving at all

Case: IT

• 24 year old man

• Assault with baseball bat: subdural haematoma; initial GCS 13

• 48 hours later: fluctuating GCS, growing frontal contusion

• Transferred to Frenchay for ICP monitor & EVD: 1 month in ITU

• ICP difficult to manage (NMJ blockers used) • Sepsis: LRTI

• CK1200

• Neurophysiology & muscle biopsy performed

Case: IT

• Acquired, non-necrotising myopathy, complex aetiology

• Prevalence unknown, associated with critical illness neuropathy

• No known effective treatment • Prognosis uncertain: increased mortality & difficulty weaning

• Risk factors: sepsis, multi-organ failure, steroids, hyperglycaemia, duration of ventilation, renal replacement, transplantation, severe asthma, neuromuscular blockers, aminoglycosides, parenteral nutrition

Case: CH

• 50 ml syringe in the bed

• Lots of vials on a small trolley next to the bed

• Mg2+ administration

• Taken to ITU for 24 hours of ventilation and further asthma management

• Excellent recovery

Hope is the thing with feathers that perches in the soul – and sings the tunes without the words – and never stops at all. Emily Dickinson 1830-1886

Thank-you