Motor neurone disease
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Web Resources for Motor neurone disease
ICD 10 code: G12.2
Genetic Databases
Relevant Clinical Literature
UK Guidance
Motor neurone disease (Motor Neuron Disease, MND, Amyotrophic Lateral Sclerosis ALS) is a relentless progressive degenerative disease of motor neurons and their associated microglia.
Contents |
Introduction
Disease of motor nerves only, UMN and LMN only. No sensory symptoms.
Aetiology
Majority unknown with prevalance of about 6/100,000. No obvious initiating factor or single gene defect. Increased genetic risk is associated with mutations of:
- FLJ10986 gene on chromosome 1 which is believed to code for a carbohydrate kinase[1]
- Angiogenin at 14q11.2
- Charged multivesicular body protein 2B(CHMP2B) coded for at 2p11.2 - a mutation can also cause familial amyotrophic lateral sclerosis
- Neurofilament protein coded for at 22q12.2
- Survival motor neuron gene 1 (SMN1) - which codes for a protein that functions as an assembly factor for snRNPs and 2(SMN2) at 5q12.2-q13.3
- Vascular endothelial growth factor coded for at 6p12
- Single nucleotide polymorphisms have been mapped to suggest associations with[2]:
- LOXHD1 gene on chromosome 18
- PTPRT gene on chromosome 20 associated with cytosketal regulation
- MAG12 gene on chromosome 7
- IL18RAP gene on chromosome 2 associated with neuroinflammation
- Unknown genes on chromosome 12 and 2.
More common in athletes and males. Possible role of excitotoxins including cycad nuts (methylaminoalanine), chickling peas, seaweed and shell fish
Up to 10% are familial amyotrophic lateral sclerosis. Mice models reveal that SOD 1 expression in the motor neuron can determine the onset of the disease and the separate issue of how SOD 1 is expressed by the microglia can determine the progression of the disease.[3]
Classification
Three main types exist, depending on the motor neurone type affected:
- Upper motor neurone - Primary Lateral Sclerosis (very rare - 0.01 per 100,000)
- Lower motor neurone - Progressive Muscle Atrophy, and Spinal Muscle Atrophy
- Mixed upper and lower MN - Amyotrophic Lateral Sclerosis
Symptoms
In the older patient, usually presents with noticeable weakness or increasing clumsiness. Other variants, exist. These include those evident around birth, with floppy infant, or failure to thrive.
Signs
Different clinical patterns all of which can coexist
- Progressive muscle atrophy
- Weakness
- Wasting
- Fasiculations
- Progressive bulbar palsy
- Dysphagia
- Nasal regurgitation
- Altered speech
- Aspiration
- Wasted fasiculating tongue
- Amyotrophic lateral sclerosis
Diagnosis
- Presence of each of the following:
- LMN signs in at least 2 limbs
- UMN signs in at least one region
- Progression of disease as increasing symptomatic impairment by history
- Absence of:
- Sensory signs
- Neurogenic sphincter abnormalities
- Other CNS disease
- Other PNS disease
- Role of EMG in diagnosis:
- Extension of clinical examination
- Strict electrophysiological criteria - "El Escorial" criteria
- Blood tests:
- Imaging:
- MRI brain and/or cervical spine
- Muscle biopsy:
- No role in diagnosis, other than exclusion of primary muscle disorder.
- Lyme serology
Differentials
- Progressive muscle atrophy
- Primary lateral sclerosis
- Brainstem syndromes
- Cervical disc disease
- Paraneoplastic neuropathy
- Lyme disease
- Tay-Sachs disease
- GM2 ganglioside disease
- Primary muscle disease
- LEMS/Myasthenia gravis
- HIV related disease
Mimic syndromes
- Bulbospinal muscular atrophy (Kennedy's syndrome)
- Multifocal motor neuropathy
Treatment
- Supportive
- Education and counselling
- Hydration
- Skin care
- PEG feeding
- Riluzole - glutamate release inhibitor
- Inactivates voltage dependent sodium channels
- In SOD1 defective mice, delays median time to death
- Two trials may demonstrate delay in time to tracheostomy or death on riluzole
- This is not statistically significant
- Does produce early increase in survival
- Non-invasive ventilation is beneficial and increases survival by about 7 months with good bulbar function[4].
References
- ↑ Dunckley T, Huentelman MJ, Craig DW, Pearson JV, Szelinger S, Joshipura K, Halperin RF, Stamper C, Jensen KR, Letizia D, Hesterlee SE, Pestronk A, Levine T, Bertorini T, Graves MC, Mozaffar T, Jackson CE, Bosch P, McVey A, Dick A, Barohn R, Lomen-Hoerth C, Rosenfeld J, O'connor DT, Zhang K, Crook R, Ryberg H, Hutton M, Katz J, Simpson EP, Mitsumoto H, Bowser R, Miller RG, Appel SH, Stephan DA. Whole-genome analysis of sporadic amyotrophic lateral sclerosis. The New England journal of medicine. 2007 Aug 23; 357(8):775-88.(Link to article – subscription may be required.)
- ↑ Dunckley T, Huentelman MJ, Craig DW, Pearson JV, Szelinger S, Joshipura K, Halperin RF, Stamper C, Jensen KR, Letizia D, Hesterlee SE, Pestronk A, Levine T, Bertorini T, Graves MC, Mozaffar T, Jackson CE, Bosch P, McVey A, Dick A, Barohn R, Lomen-Hoerth C, Rosenfeld J, O'connor DT, Zhang K, Crook R, Ryberg H, Hutton M, Katz J, Simpson EP, Mitsumoto H, Bowser R, Miller RG, Appel SH, Stephan DA. Whole-genome analysis of sporadic amyotrophic lateral sclerosis. The New England journal of medicine. 2007 Aug 23; 357(8):775-88.(Link to article – subscription may be required.)
- ↑ Boillée S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA, Kassiotis G, et al. Onset and progression in inherited ALS determined by motor neurons and microglia. Science. 2006;312(5778):1389-92. (Direct link – subscription may be required.)
- ↑ Bourke SC, Tomlinson M, Williams TL, Bullock RE, Shaw PJ, Gibson GJ. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. Lancet neurology. 2006 Feb; 5(2):140-7.(Link to article – subscription may be required.)
