Motor Neurone Disease PROF MOHAMMAD ABDULJABBAR

What is Motor Neurone Disease

Motor Neurone Disease Every person develops the disease in a different way Symptoms experienced depends on the area of nervous system affected 90% - 95% of people have the sporadic form. 5-10% Familial. Adult Illness – most people are over 50 Average survival 2-5 years from first symptoms. From diagnosis 14 months average. No cure but symptom management and medication that may improve quality or prolong life. Onset and progression is variable.

What is Motor Neurone Disease? Upper motor neurones (UMN) originate in the base of the cortex of the brain Lower motor neurones (LMN) originate in the spinal cord

USEFUL CLUES Progressive Incurable rare Group of related diseases Motor neurones are affected Upper and lower limb weakness Speech and swallowing difficulties Breathing difficulties

INCEDANCE Relatively uncommon Annual incidence of 2 in 100,000 Prevalence 5-7 per 100,000 More common in men but over 65 years becomes more even General practitioners can expect to see 1 or 2 cases during their career

Causes of MND

Environmental and Genetics 90% Mechanical/electrical trauma Military service High levels of exercise Agricultural chemicals and heavy metals Risk factors Environmental and Genetics Familial – 5-10% Rare Research found genetic faults SOD 1, FUS, VCP and TDP-43 genes Ubiquilin protein gene Chromosome 9 Evidence is often circumstantial and conflicting

Types of Motor Neurone Disease

Bulbar –refers to face/speech/swallowing Different Types Overlap is common Classified: 1) In terms of the motor neurones affected 2) Symptoms Bulbar –refers to face/speech/swallowing

Muscle weakness – often Develops in hands and feet first, spasticity. Amyotrophic Lateral Sclerosis (ALS) 65 - 66% of cases Involves UMNs and LMNs Muscle weakness – often Develops in hands and feet first, spasticity. Hyperactive reflexes Progressive Bulbar Palsy (PBP) 20% of cases Involves UMNs and LMNs Dysarthria Dysphagia Emotional lability Progressive weakness in upper limbs , neck and shoulders. AMYOTROPHIC LATERAL SCLEROSIS (ALS) Most common form of MND (approximately 66%) UMN and LMN involvement. Muscle weakness, Spasticity, Hyperactive reflexes and emotional lability. Age of onset 55+ Male : Female = 3:2 Onset to Death approximately 2-5 years. PROGRESSIVE BULBAR PALSY (PBP) Affects approximately 25% Possible combination of UMN & LMN involvement. DYSARTHRIA & DYSPHAGIA LMN = Nasal speech, regurgitation of fluid via the nose, tongue atrophy and fasciculation and pharangeal weakness. UMN = Spastic tongue, explosive dysarthria and emotional lability. Muscles in the upper Limbs and Shoulder girdle may also become progressively weaker. PBP occurs in older people – slightly more in females. Onset of symptoms to Death approximately 6 months to 3 years.

Progressive Muscular Atrophy (PMA) 7.5%-10% of cases Predominantly LMNs affected (may start in small muscles of hand) Muscle wasting, Weakness Fasciculation (may in time develop UMN involvement and may eventually develop some speech problems) Primary Lateral Sclerosis (PLS) 2% of cases Rare UMNs only Muscle weakness Stiffness Dysarthria Does not shorten survival PROGRESSIVE MUSCULAR ATROPHY (PMA) Affects approximately 7.5% of people with MND. LMN degeneration. Muscle wasting and weakness. (often starting in the intrinsic muscles of the hand) Loss of Weight and Fasciculation (Muscle Twitching) Age of onset 50+ Male : Female = 5:1 Survival beyond 5 years. PRIMARY LATERAL SCLEROSIS (PLS) Rare form UMN involvement only. Spastic Quadriparesis, pseudo bulbar affect, spastic dysarthria, and Hyper flexia. Survival rate of up to 20 years. Overlap evident between forms of MND People with PMA form in time develop UMN involvement. In both PMA and ALS people eventually experience some degree of speech and swallowing difficulties.

Course of Disease Onset and progression variable Is always progressive with no remissions Usually affects both the upper and lower motor neurons 90% develop some bulbar symptoms Death often through respiratory failure

Site of Onset Limbs (usually distal) Bulbar Respiratory

Early Symptoms Stumbling Foot drop loss of dexterity Weakened grip Cramps Change of voice quality Slurred speech Early swallowing difficulties Muscle wasting Fatigue

Diagnosis of Motor Neurone Disease

Diagnosis On average, it takes 14 months from first symptoms to diagnose MND First signs and symptoms often subtle and non-specific, similar to other diseases Person often not referred to a neurologist directly No definitive diagnostic test

(How is MND Diagnosed) Interpretation of clinical symptoms and signs Investigations to exclude other causes MRI Lumbar puncture You have to exclude, other conditions.

Tests Bloods : Raised CPK – can be seen in MND but not diagnostic EMG : Taken from each limbs-abnormal in MND as the electrical activity of the muscles is changed Nerve conduction tests normal Trans-cranial magnetic stimulation – tests upper motor neurones MRI : Eliminates other diseases May need Lumbar puncture or muscle biopsy

Effects of Motor Neurone Disease

Effects of MND Progressive muscle weakness and wasting Loss of weight Fasciculation, cramp and spasticity Dysarthria-slurred effortful speech Saliva and Mucus Problems Dysphagia - poor swallow due to weakness and paralysis of bulbar muscles Respiratory muscle weakness Emotional liability Cognitive changes Dysphagia – Problems with lip seal Chew – propel food with the tongue And/or form bolus Poor or absent swallow reflex Failure to close airway Muscle spasm

Clues to respiratory muscle involvement in MND Breathlessness on minimal exertion on lying flat Poor sleep Excessive daytime sleepiness Headaches on awakening Excessive nocturnal sweating Occasionally respiratory problems will be the presenting symptom but more usually the problems develop as the disease progresses. It is the muscles that govern voluntary control of breathing that are affected. Increased respiratory muscle weakness contributes to fatigue and decreased physical ability. Some of the symptoms may include shortness of breath, but if a person is not very mobile, it may be hard to see this. However if someone complains of headaches on waking, difficulty lying flat and sleepiness during the day, they may well be retaining CO2 overnight, which gives them the headaches and other symptoms. Care Workers may well be in a crucial position to notice these symptoms, especially with those who live alone. The person can be reassured and careful positioning may well help. Liaison with the Occupational Therapist, the Physiotherapist and particularly with the GP and/or Consultant, will ensure the person is referred appropriately for respiratory assessment.

Psychosocial Impact Multiple losses: physical loss, loss of control, and independence. Self image and confidence. Financial. Home environment. Communication difficulties. Increasing isolation and dependence on carers. Anxiety, Fear and Anger. Knowledge of own impending deterioration and death. Mention carers/ isolation for both

Cognitive changes MND has been traditionally viewed at a disease affecting the motor system Compromise of cognitive abilities Recent research shows that 25% Show some cognitive changes 3-5% will have fronto-temporal dementia

What isn’t affected by MND Senses: touch, taste, sight, smell and hearing Bowel and bladder function Sexual function and sexuality Eye Muscles Heart muscles

Treatments and Interventions

Support at home as much as possible. Plan appropriate interventions. Aims of Management Control of symptoms. Promote independence Support at home as much as possible. Plan appropriate interventions.

Treatments/interventions in MND Multidisciplinary approach Sensitive Management Palliative care Person with MND Nutritional support PEG/RIG Rehabilitation medicine Pharmaceutical management of symptoms Respiratory care Disease modifying therapy

Life Prolonging Interventions Riluzole only drug to have beneficial effect on survival : 3-4 months. Respiratory care: Non-invasive ventilation (NIV). To improve quality of life. Median survival extended 205 days (Miller et all 2009).

Medications for symptoms Muscle cramps (Carbamazepine and Phenytoin) Muscle Stiffness (Muscle relaxants) Botox and intrathecal baclofen Drooling (Hyosine and atropine) Pain (analgesia/Gabapentin)

End of Life Decisions Advanced Care Planning. Advanced decision to refuse treatment (ADART). Advanced Statement of wishes and preferences. Preferred Priorities of Care (PPC). Withdrawal of treatments. Tissue donations. Milestones/decision points Decision making Why advance planning? When is the right time? Ethical issues:MND

THANK YOU