teesneuro.org

By Catherine Roberts (4th year, Newcastle University)

with occasional input from me - Ed

Overview

Quick facts:

• degenerative condition
• largely sporadic
• usually presents later in life
• typically, asymmetrical in onset
• 1/3 present with upper limb symptoms, 1/3 lower limb, <1/3 disorders of speech & swallowing
• currently the pathology is untreatable
• uniformly fatal (1 in 1000 death certificates list MND as the cause of death)¹

What is MND?

Motor neurone disease is a progressive syndrome, with signs of both upper and lower motor neuron dysfunction.

It is best thought of as a "motor systems degenerative disorder". Also, note that we talk about "motor neurons" but, for reasons that escape me, it is "motor neurone disease" - with an 'e' on the end.

What are the upper and lower motor neuron signs?

UPPER MOTOR NEURON DYSFUNCTION	Spasticity, brisk reflexes, weakness, extensor plantar responses
LOWER MOTOR NEURON DYSFUNCTION	Muscle wasting, weakness, fasciculation

these videos show the wasting and fasciculation often seen in MND. The wasting is usually more generalised than this,but it does help to see the normal side contrasted with the wasted side.

Does it just present with motor signs then?

No – although it is predominantly a motor disorder, ‘there is evidence of multi-system involvement (especially cognitive, but occasionally sensory or autonomic).’¹

Are ALS and MND the same thing?

No.

MND is an umbrella term for many different diagnoses that involve the motor neurons. ALS (or Amyotrophic lateral sclerosis) is just one of the conditions. Others include:

• Progressive bulbar palsy*
• Progressive muscular atrophy – a predominantly lower motor neuron presentation
• Primary lateral sclerosis – a predominantly upper motor neuron presentation

They all have various differences in presentation, which may give clues as to the exact type of MND that the patient has. See below and also Patient UK for more details.

*Progressive bulbar palsy is slightly contentious. Many view this as a presentation, rather than a distinct sub-type. Basically, if a patient presents with little limb weakness but lots of issues with speech and swallowing, we describe this as a "progressive bulbar palsy". Hope that isn't too confusing!

How common is it?

It is relatively uncommon, with an incidence annually of 2 cases per 100,000 people in the population³. Working as a GP, you might expect to see one or two cases in your career.
There are about 5000 people living with MND in the UK at present.

What’s the underlying pathology?

This is a degenerative condition that affects motor neurons, namely the anterior horn cells of the spinal cord, the motor cranial nuclei and the motor nerves in the cortex, that innervate these “lower” motor neurons³.

The cause is unknown.

Diagnosis and differential

How is it diagnosed?

The diagnosis is usually clinical; based on the presenting signs and symptoms with some other investigations, such as imaging, to rule out any possible differentials.

Due to the variability in the presentation, the El Escorial criteria were devised, to confirm the diagnosis and refute other possible causes. Criteria for diagnosis are as follows:

• Diagnosis requires:
  • 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.
• 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.

These criteria are generally used for research studies. In practice, they are rarely used clinically.

Are there any particularly useful investigations?

Electromyogragphy (EMG) and Nerve Conduction Studies (NCS) can show a characteristic pattern.

(Also the El Escorial criteria states that for diagnosis there must be absence of EMG findings for other conditions so that would be another reason to do these studies.)

CT and/or MRI are useful in excluding other pathologies with similar presentations (see below).

Blood tests: for example, TFTs, CK, serum protein electrophoresis, and various antibodies.

Muscle biopsy: to exclude other conditions in the differential diagnoses.

muscle biopsy is rarely used, but can be handy in complex cases

What type of clinical presentation would make you think MND?

ALS

Tends to be focal in onset; with a particular group of muscles affected first. Recognised patterns include: Limb onset – most common Bulbar onset Respiratory onset Presents with signs and symptoms of UMN and LMN leading to progressive weakness of muscles. Cognitive dysfunction can also occur, with around 15% of patients developing fronto-temporal dementia3.

What symptoms might the patient or family member report?

Limb weakness (usually affects the upper limbs)	History of dropping objects Difficulty in manipulating objects with one hand (turning keys, writing and opening bottles) Wrist drop, stiffness, weakness or cramping of the hands may also occur A change in the appearance of their hands (due to wasting of the intrinsic muscles) Fasciculation of the muscles of the limbs may be noticed prior to weakness developing
Lower limb	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	Slurring of the speech (usually the first sign. Results from 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 involvement	Dyspnoea and orthopnoea Clinical features resulting from hypoventilation overnight (for example, waking, unrefreshing sleep, hypersomnolence and early morning headaches)

 

The "bulb" of the brain is the medulla, which controls the tongue and palate. Lazy neuro shortspeak for dysarthria and dysphagia, therefore, is "bulbar". This works OK for symptoms but it gets confusing when we talk about SIGNS. Bulbar SIGNS are "lower" - flaccid weakness, wasting, fasciculation; in contrast, pseudobulbar SIGNS are "upper" - tight, stiff tongue, brisk jaw jerk. Bulbar signs are seen in MND (with a LMN flavour), myasthenia and Guillain-Barre Syndrome. Pseudobulbar signs are seen in MND (with an UMN flavour), bilateral stroke disease and some neurodegenerative disorders.

What are the other conditions under the MND umbrella?

Progressive bulbar palsy (2 in 10 MND cases)	The muscles that are first affected are those involved in: Talking Chewing Swallowing
Progressive muscular atrophy (uncommon)	The muscles that are usually first affected are the: Small muscles of hands and feet Muscle spasticity is absent Can affect one limb for ages, before gradually progressing Longer survival and slower progression
Primary lateral sclerosis (uncommon)	Causes weakness in leg muscles Occasional clumsiness in hands Occasional speech problems Absent LMN signs and very hard to diagnose as EMG/NCS are usually normal

What are the possible differentials for a MND presentation?

∆∆	Presenting features
Benign cramp fasciculation syndrome	Fasciculation or cramps usually affecting large muscles (e.g. calves) Fasciculation is more common after exercise or lack of sleep No wasting or weakness on examination
Cervical radiculomyelopathy	Compression of spinal cord and nerve root leads to LMN signs at level of compression and UMN signs below MRI scan can confirm the diagnosis
Inclusion body myositis	An inflammatory myopathy which presents with distal weakness without sensory symptoms Clinically long finger flexors are affected (unusual in MND)
Diabetic amyotrophy	A sub-acute onset of weakness and wasting particularly of thigh/pelvic girdle muscles with pain and paraesthesiae (unusual in MND)
Multi-focal motor neuropathy with conduction block	demyelinating motor neuropathy that can mimic MND hard to diagnose and rare responds to immunotherpay, particularly IVIG, so important not to miss (but not core knowledge!)
Primary muscle disease	whole variety of causes – thyroid, autoimmune, hereditary always check a CK level if you suspect MND – if very high, then think again

Management and Prognosis

How is MND managed?

‘The cornerstone of management of MND is regular individualised follow-up, to assess the rate of change of the disease and facilitate planning and patient choice and, where possible, to maintain well-being’¹.

Patients with ALS, progressing at a typical rate, should be seen about every 3 months by a multidisciplinary clinic team consisting of:

• Neurologist: diagnosis, assessment of disease progression, coordination of research and management.
• Care coordinator: often a nurse, liaison between patients and clinical and para-clinical team to ensure interventions are appropriate and timely. Provision of information and support to patients and carers. Education and outreach for allied health care professionals.
• Physiotherapist: assessment of motor dysfunction and provision of ankle–foot orthoses, collars and aids to walking. Teaching exercises to prevent cramps and secondary disability.
• Occupational therapist: specialist in posture management and assessment for wheelchairs and other mobility and posture aids.
• Psychologist: assessment of cognitive dysfunction, management of adjustment reactions and support, and counselling for patients and relatives.
• Respiratory team: specialist nurse and physician for assessment of nocturnal sleep fragmentation with overnight oximetry and provision of non-invasive ventilation equipment.
• Dietician and enteral feeding specialist team: initially advice about changes to oral diet (softened and pureed food), then planning of percutaneous endoscopic gastrostomy (PEG) or radiologically inserted gastrostomy (RIG) and subsequent follow-up.
• Speech and language therapist: initial advice about how to avoid choking episodes and how to improve intelligibility. In selected patients with major communication problems, aids to communication such as the Lightwriter or voice synthesis software can be critical in maintaining personal autonomy.

What aids to communication are available for those with MND?

Lightwriter	A type of speech generating device. The person who struggles to speak types a message on the keyboard and this is then displayed on two screens, one facing the user and a second outfacing for the communication partner.
Voice synthesis software	The artificial production of speech. A text to speech system converts normal language text into speech.

So are there any medications that are used for management?

Yes; but mainly for symptomatic management of the disease (see table below). The only drug that is licensed for trying to treat MND is Riluzole, which is used for treating ALS in the UK. The licensed indication is to extend life or the time to mechanical ventilation.

It works by inhibiting the release of glutamate; a compound which is hypothesised to play an important role in destruction of motor neurones (when excessively stimulated) in MND². It has shown results: probability of survival at 1 year after starting the drug is 9% greater than placebo; equating to about 2-3 months more in life expectancy¹.

Are there any particular challenges of management in MND?

NUTRITION

Many patients will experience weight loss which can be multifactorial:

• reduced intake (due to dysphagia, fear of choking, social embarrassment),
• physical disability (due to arm weakness),
• increased calorie requirements and hypermetabolism,
• muscle atrophy,
• psychological factors (reduced appetite due to low mood etc.)
• recurrent chest infections

Therefore, it is important to continually assess nutritional status. Possible options include PEG feeding. This type of intervention should not be performed late in the disease as risks tend to outweigh benefits.

RESPIRATION

The provision of non-invasive ventilation for patients with MND has been a major advance in symptom management, and is likely to significantly extend life in selected patients. However, the mode of death for the overwhelming majority of MND patients is still respiratory failure and not all patients need symptom palliation. In some, especially those with significant bulbar problems, non-invasive ventilation is not tolerated.

Monitor patients by:

• symptom enquiry at every visit (breathlessness when lying flat, early morning headache, fatigue)
• measuring forced vital capacity (a fall of 15-20% on lying flat can indicate diaphragmatic weakness however may not be reliable in those with bulbar or corticobulbar involvement).

What is the prognosis after diagnosis?

The disease varies from patient to patient, which makes it challenging for Doctors to predict an individual’s likely prognosis. The ‘’average survival’’ is 2-3 years from diagnosis¹. Most patients will die from ventilatory failure, resulting from progressive weakness and wasting of limb, respiratory and bulbar muscles within approximately 3 years after onset of the symptoms².

References

1. Talbot K. Motor neuron disease:The Bare Essentials. Practical Neurology 2009; 9:5 303. link. talbot_2009_prac neurol_MND.
2. Guidance on the use of Riluzole (Rilutek) for the treatment of Motor Neurone Disease. [TA20]. link
3. Kavanagh S. Motor neurone disease. Patient UK. link
4. Lecture notes to accompany the TeesNeuro MND lecture. MND lecture notes