Motor Neurone Disease Flashcards
What is motor neurone disease?
Motor neurone disease (MND) is a rare but devastating illness which leads to progressive paralysis and eventual death. Although rare, many patients are both aware and fearful of it
What are the types of MND?
Most cases of MND are due to ALS. However, other forms occasionally occur.
These include:
-Progressive bulbar palsy - about 2 in 10 people with MND have this type. The muscles first affected are those used for talking, chewing and swallowing.
Progressive muscular atrophy - this is an uncommon form of MND. The small muscles of the hands and feet are usually first affected, but muscle spasticity is absent.
Primary lateral sclerosis - this is another rare type of MND. It mainly causes weakness in the leg muscles. Some patients with this type may also develop clumsiness in the hands or develop speech problems.
What is the pathophysiology of MND?
This is a degenerative condition that affects motor neurons, namely the anterior horn cells of the spinal cord and the motor cranial nuclei.
It causes lower motor neurone (LMN) and upper motor neurone (UMN) dysfunction, leading to a mixed UMN/LMN picture of muscular paralysis, usually with LMN signs predominating.
The cause of the disease is unknown, although 5% of those affected have a familial form of the disease due to a mutation in the superoxide dismutase-1 gene
Current aetiological hypotheses focus on an abnormality of mitochondrial function causing oxidative stress in motor neurons. There may be several causes for such oxidative damage to motor neurons and the disease may just represent an end-stage phenotypic expression of these abnormalities.
What is the presentation of MND?
MND is mostly a sporadic disease of middle and elderly life presenting in the sixth and seventh decades. However, it can present in younger patients, usually with familial MND.
The classic form of the disease is also called amyotrophic lateral sclerosis (ALS). It tends to be focal in onset, with a particular group of muscles affected first.
This presents In three recognised patterns:
- Limb onset - by far the most common.
- Bulbar onset - 20% of cases.
- Respiratory onset - the least common.
What are the symptoms of MND?
Limb weakness - usually affects the upper limbs:
- Causes patients to drop objects or have difficulty manipulating objects with one hand (turning keys, writing and opening bottles).
- Wrist drop, stiffness, weakness or cramping of the hands may also occur.
- Patients may also notice a change in the appearance of their hands (due to wasting of the intrinsic muscles).
- Fasciculations of the muscles of the limbs may be noticed prior to weakness developing.
However, occasionally problems in the leg or legs may occur:
- Foot drop (early).
- Gait disorder.
- A sensation of heaviness of one or both legs.
- A tendency to trip.
- Difficulty in rising from low chairs and climbing stairs.
- Excessive fatigue when walking.
Bulbar onset:
- The first sign is usually slurring of the speech (impaired tongue movement).
- Wasting and fasciculation of the tongue.
- Dysphagia (usually a late feature with significant speech difficulties).
- Accompanying emotional lability (inappropriate laughing or crying) - as with pseudobulbar palsies.
- Other symptoms are difficulty eating, drooling, dysarthria, dysphonia, choking events with meals, nasal regurgitation of fluids or pulmonary aspiration.
Respiratory onset can present with:
- Dyspnoea and orthopnoea.
- Clinical features resulting from hypoventilation overnight (for example, waking, unrefreshing sleep, hypersomnolence and early morning headaches).
What are the rarer features of MND?
Pain or sensory disturbance is not unknown but is not a common feature of the disease; it is usually the absence of pain or sensory disturbance that helps to distinguish MND from radiculopathies (nerve root pathology) that can cause a similar presentation in peripheral limbs.
Symptoms due to impaired respiratory muscle function usually occur late in the disease but can occasionally be a presenting feature, causing ‘air hunger’. Acute respiratory failure has been reported.
Some patients with pseudobulbar palsy may have ‘emotional incontinence’, an over-reaction to sad or funny events that they are aware of as being abnormal.
Cognitive impairment is not a normal feature but can affect some patients with bulbar palsy.
What are the signs of MND?
LMN dysfunction in the limbs manifests as weakness, atrophy, fasciculations and hyporeflexia. The thighs are often a site of marked fasciculation. Fasciculation can be difficult to distinguish from arterial pulsation, so consider if there is an underlying arterial course before defining twitching movements as fasciculation.
UMN dysfunction manifests as weakness predominating in the arm extensors and leg flexors with evidence of hypertonia, hyper-reflexia and upgoing plantar responses; the bulbar muscles may also show spasticity with an exaggerated jaw jerk.
Ocular, sensory or autonomic dysregulation signs are usually late features of the disease.
Diagnostic pointers in limb-onset MND
- Asymmetrical distal weakness frequently occurs.
- Brisk reflexes will occur in a wasted limb.
- There is an absence of major sensory symptoms and pain.
- There is a relentless progression of symptoms and signs.
What is the diagnostic criteria for MND?
Presence of:
- Evidence of LMN degeneration by clinical, electrophysiological or neuropathological examination.
- Evidence of UMN degeneration by clinical examination.
- Progressive spread of symptoms or signs within a region or to other regions, as determined by history or examination.
Together with the absence of:
- Electrophysiological and pathological evidence of other disease processes that might explain the signs of LMN and/or UMN degeneration.
- Neuroimaging evidence of other disease processes that might explain the observed clinical and electrophysiological signs
How does ALS present?
Presents with symptoms and signs of degeneration of the upper and lower motor neurons, leading to progressive weakness of the bulbar, limb, thoracic and abdominal muscles.
Other brain functions, including oculomotor and sphincter function, are relatively spared, but may be involved in some patients.
Cognitive dysfunction may occur and 5-15% of patients develop dementia, usually of frontotemporal type.
What are the differentials for MND?
Benign cramp fasciculation syndrome:
- No progression over time
- No wasting or weakness on examination
- Fasciculation is more common after exercise or with lack of sleep.
Cervical radiculomyelopathy
Multifocal motor neuropathy with conduction block:
- Often presents in young or middle-aged men as unilateral distal upper limb weakness with little evidence of wasting initially.
- This is an important rare diagnosis to consider in differential diagnosis of MND.
-In the correct clinical context, it can be diagnosed or excluded only by careful neurophysiological evaluation looking for conduction block. - It is treatable and has a markedly different prognosis than that for MND.
Diabetic amyotrophy
GBS
Myasthenia gravis
Diabetic neuropathy
Spinal cord tumours
Lyme disease
Charcot-Marie-Tooth syndrome
Glioma of brainstem
What are the investigations for MND?
There are no specific investigations that will confirm a diagnosis of MND.
A range of investigations is carried out to confirm consistent features and exclude other possible pathologies, usually under the direction of a neurologist.
- EMG and nerve conduction studies
- CT and/or MRI scanning
- Blood tests such as vitamin B12
- Muscle biopsy may be considered
What is the management of MND?
Break bad news in a sensitive manner.
Impart information honestly but without destroying hope.
Maintain a positive emphasis on what can be done to help.
MND is an incurable condition that usually, although not always, leads to death within a few years, with a period of distressing disability preceding it.
MDT approach
Regular physical, occupational and speech therapy to maintain strength and utility of the affected motor functions and allow use of aids designed to overcome specific disability problems.
Dietetic support to allow adequate hydration and nutrition whilst the patient is able to feed independently, or with the aid of carers.
Insertion of a gastrostomy tube should be considered when the patient is no longer able to feed by mouth.
When respiratory function is impaired, physiotherapy helps to clear pulmonary secretions and maintain respiratory health.
Positive pressure ventilation may be used in patients who are no longer able to maintain adequate ventilation.
NIV
Riluzole (a neuroprotective glutamate-release inhibitor) is the only drug of proven disease-modifying efficacy.
-Its effects are modest, probably only prolonging lifespan by between two and four months.
-It may have a more significant effect on prolonging tracheostomy-free survival.
-It appears to be well tolerated and of greater benefit the earlier it is started in the course of the disease.
-It has been shown to act by blocking muscle acetylcholine receptors.
Palliative care
Which medications are used to control the symptoms of MND?
Drooling may be reduced by the use of anticholinergics such as hyoscine.
Muscle cramps and spasticity can be treated with agents such as diazepam, baclofen, tizanidine, phenytoin and quinine.
Respiratory distress and the sensation of choking may respond to opioid medications but this must be balanced against their tendency to cause respiratory suppression; they are very useful to treat this symptom in the palliative phase.
Depression associated with MND may respond to the use of antidepressant medications.
Pain often goes under-recognised and undertreated. Non-steroidal anti-inflammatory drugs and opioids, such as oral morphine, subcutaneous diamorphine and fentanyl patches, are utilised, particularly in the palliative phase.
What are the complications of MND?
Respiratory failure and death.
Pneumonia due to infection or aspiration.
Urinary tract infections.
Constipation.
Spasticity and cramping of muscles.
Depression
Loss of speech as a means of communication.
Immobility and attendant disability.
Complications of immobility such as skin infections/bedsores and ulcers.
Cognitive deterioration is rare but is seen occasionally.
