Picture quiz: Muscle weakness and wasting

A 74 year old woman presented with a two month history of progressive weakness of her right hand, without sensory symptoms. She had no medical history of note and no family history of neurological or psychiatric problems.

On examination, sensation and cranial nerves were normal. Examination of the upper limbs identified bilateral fasciculation of the deltoid and triceps, however. On the right, the power of her grip was 3 on the Medical Research Council scale, as was her finger abduction and abductor pollicis brevis. Her digit muscles had spasticity, and the reflexes of her supinator and biceps were brisk. The power and reflexes of her left upper limb were normal. Coordination was normal in both upper limbs.

In the lower limbs the only finding was the presence of symmetrical exaggerated adductor reflexes. Figs 1(F1) and 2(F2) show the patient’s right hand at rest, a couple of months after presentation.

Fig 1

Fig 2

Questions

(1) What can you see in the fig 1 and fig 2?

(2) What is the differential diagnosis?

(3) What investigations would you do?

Answers

(1) The patient’s right hand is shown with marked wasting of the thenar and hypothenar eminences. The fingers are flexed more than normal because of the increased spasticity of the muscles that control them. The finger flexors are stronger than the extensors, and the result is increased flexion of the fingers at rest.

(2) The patient presented with upper and lower motor neurone signs in her right upper limb, with lower motor neurone signs in her left upper limb and upper motor neurone signs in her lower limbs. It is important to note that the patient has upper motor neurone signs above the lower motor neurone signs, which cannot be explained by a simple cord lesion—for example, interruption of the cord by adjacent structures.

Motor neurone disease should be high on the list of differential diagnoses, but it is a diagnosis of exclusion. Other conditions that can present with upper and lower motor neurone signs include cervical spondylosis with spinal cord and nerve root compression or spinal tumours that may be extradural (for example, metastases) or intradural. The latter may be extramedullary (for example, meningioma) or intramedullary (for example, ependymoma).

In the diagnosis of the weak and wasted hand, particularly when upper motor neurone signs are not present, it is important to consider peripheral nerve lesions, such as combined ulnar and median nerve damage; peripheral neuropathy; multifocal motor neuropathy; or a lesion at the lung apex (for example, Pancoast tumour), involving the medial cord of the brachial plexus.

(3) The absence of a diagnostic test, variable clinical presentations, and several disorders that mimic motor neurone disease make a diagnosis of motor neurone disease a challenge and dependent on the correlation of clinical, laboratory (for example, blood, lumbar puncture), electrophysiological (for example, nerve conduction, electromyography), neuroimaging (for example, magnetic resonance imaging), and, rarely, neuropathology (for example, muscle biopsy) investigations.

Discussion

Motor neurone disease, also known as amyotrophic lateral sclerosis, was first described by Jean-Martin Charcot in 1869.^w1 This progressive neurodegenerative condition is associated with loss of upper or lower motor neurones or both. The terminology is confusing: here we use motor neurone disease to cover the variations in the clinical syndrome that comprise predominantly spinal onset forms (classical amyotrophic lateral sclerosis of Charcot), progressive bulbar palsy, and progressive muscular atrophy.

Primary lateral sclerosis refers to a pure upper motor neurone syndrome, which progresses more slowly than motor neurone disease. Only very rarely do lower motor neurone signs evolve in primary lateral sclerosis. The variants within the syndrome of motor neurone disease are united in having a characteristic pathology, comprising ubiquitin and TDP-43 immunoreactive inclusions in lower motor neurone.^w2 Occasionally patients with motor neurone disease may present with or develop frontotemporal dementia.

The incidence of motor neurone disease is about 2 per 100000 population.^w3 About 60% of patients present with unilateral or asymmetrical weakness of the arms, with distal weakness and wasting. Some 20% present with bulbar symptoms (progressive bulbar palsy), and about 10% present with a pure lower motor neurone syndrome (progressive muscular atrophy).

Symptoms usually begin in later middle life and progress rapidly, causing death usually from respiratory failure 2-5 years after the symptoms started. Long survival is possible, however. The average delay from onset of symptoms to diagnosis is 13-18 months. When a diagnosis of motor neurone disease is reached, it should be given face to face by a neurologist experienced in caring for patients with motor neurone disease. It requires an empathic approach and an understanding of the patient’s cultural and social background.^w4

Some 5-10% of people diagnosed with motor neurone disease have a family history of first degree relatives with the condition. A fifth of familial cases have a mutation of the SOD1 gene on chromosome 21, which codes for the enzyme superoxide dismutase type 1, but its disease causing mechanism is unclear. Genetic testing for these mutations can now be offered.^w5

The only disease modifying drug available for motor neurone disease is riluzole. It may work by decreasing the toxic effect of glutamate on motor neurones. Its effect on survival is modest (2-4 months if the drug is taken continuously for an 18 month period), and patients' functioning does not improve.

Managing the patient

Good management of motor neurone disease incorporates multidisciplinary and palliative care. Weight loss caused by dysphagia is a good predictor of a patient’s survival, so its treatment is an important aspect of care. Initial advice includes altering fluid and food consistency. As the problem progresses, percutaneous endoscopic gastrostomy or even a nasogastric tube may be necessary. Clinical consensus is that they improve quality of life.

Respiratory insufficiency in motor neurone disease is usually caused by respiratory muscle weakness and is associated with decreased quality of life and cognitive function. Non-invasive positive pressure ventilation is the preferred method of treatment, increasing survival and quality of life.^{w6 w7} Initially used for intermittent night time support to relieve the symptoms of nocturnal hypoventilation, it can be used continuously at the end stage of the disease.^w8

Early referral to palliative care services is advised so that patients can be offered help with symptoms, emotional, spiritual, and psychological support, and a dignified and peaceful death. Support of the family after the bereavement is important.^w8

Competing interests: None declared.

Provenance and peer review: Not commissioned; externally peer reviewed.

1. Charcot JM and Joffroy A. Deux cas d’atrophie musculaire progressive avec lésions de la substance grise et de faisceaux anterolateraux de la moelle epiniere. Arch Physiol Norm Pathol; 1869; 1: 354-367.
2. Kato S, Shaw PJ, Wood-Allum CA, Leigh PN, Shaw C. Amyotrophic lateral sclerosis in neurodegeneration: the molecular pathology of dementia and movement disorders (ed Dickson D) ISN Neuropath Press, Basel; 2003; pp 350-368.
3. Rocha JA, Reis C, Simoes F, Fonseca J, Mendes Ribeiro J. Diagnostic investigation and multidisciplinary management in motor neurone disease. J Neurol; 2005; 252: 1435-1447.
4. Andersen PM, Borasio GD, Dengler R, Hardiman O, Kollewe K, Leigh PN et al. EFNS task force on management of amyotrophic lateral sclerosis: guidelines for diagnosing and clinical care of patients and relative. Eur J Neurol; 2005; 12: 921-938.
5. Goodall EF and Morrison KE. Amyotrophic lateral sclerosis (motor neuron disease): proposed mechanisms and pathways to treatment. Expert Rev Mol Med; 2006; 8(11).
6. Bourke S, Tomlinson M, Williams T, Bullock R, Shaw P, Gibson G. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis - a randomised controlled trial. Lancet Neurol; 2006; 5(2): 140-147.
7. Mustfa N, Walsh E, Bryant V, Lyall RA, Addington-Hall J, Goldstein LH et al. The effect of non-invasive ventilation on ALS patients and their caregivers. Neurology; 2006; 66:1211-1217.
8. Leigh PN, Abrahams S, Al-Chalabi A, Ampong MA, Goldstein LH, Johnson J et al and King's MND Care and Research Team. The management of motor neurone disease. J Neurol Neurosurg Psychiatry; 2003; 74 (suppl IV):iv32-iv47.

       

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