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Motor neuron disease

The motor neurone diseases (MND) are a group of progressive neurological disorders that destroy motor neurons, the cells that control voluntary muscle activity such as speaking, walking, breathing, and swallowing. Amyotrophic lateral sclerosis (ALS), sometimes called Lou Gehrig's disease, progressive muscular atrophy (PMA), spinal muscular atrophy (SMA), progressive bulbar palsy (PBP) and primary lateral sclerosis (PLS) are all motor neurone diseases. more...

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Terminology

MND is the term often used internationally while ALS is often used in the United States (where it is also known as Lou Gehrig's disease, after the legendary baseball player) to cover all forms of MND. It was first described by Jean-Martin Charcot, a French neurologist, in 1869 and in France the disease is therefore known as Maladie de Charcot (Charcot's disease).

Signs and symptoms

Characteristic symptoms of MND include gradual weakening, wasting away, and uncontrollable twitching of the muscles; spasticity or stiffness in the arms and legs; and overactive tendon reflexes. Sensation, intellect, memory, and personality are not affected in MND. In some types of MND, such as ALS, muscle weakness is progressive and eventually leads to death when the muscles that control breathing no longer work. Other types of MND progress slowly and last over a lifetime.

In adults, symptoms usually appear after age forty, and may be similar to those of other diseases, making diagnosis difficult. In children, particularly in inherited forms of the disease, symptoms are present from birth.

Diagnosis

The diagnosis of ALS is established based on the history of the patient and the findings on neurological examination. There is no diagnostic test for ALS. Electromyography (EMG) examination are useful to demonstrate the diffuse loss of motor neurones innervating muscles of extremities, face and abdomen and to rule out other disorders that may mimic ALS, but interpretation of the result is not necessarily straight forward. A set of diagnostic criteria called the El Escorial criteria have been defined by the World Federation of Neurologists and are widely used by neurologists and ALS researchers.

Clinically, upper motor neuron damage signs (such as spasticity, brisk reflexes and Babinski signs) can be found, while the lower motor neurones demonstrate weakness and muscle atrophy. Weakness of bulbar musculature can also be seen (difficulty breathing, swallowing, coughing, or speaking).

Neuroimaging examinations are usually performed to rule out alternative causes, such as a mass lesion of upper parts of spinal cord

Pathology

Causes

Nonhereditary (also called sporadic) MND are caused by unknown factors. Nonhereditary MND include ALS, progressive bulbar palsy, pseudobulbar palsy, primary lateral sclerosis, progressive muscular atrophy, and post-polio syndrome. There are no specific tests to diagnose the MND.

About 90% of cases of MND are "sporadic", meaning that the patient has no family history of ALS and the case appears to have occurred sporadically in the community. The cause of sporadic ALS is unknown, though genetic factors are suspected to be important in determining an individual's susceptibility to disease. There is weak evidence to the suggestion that the onset can be triggered by a viral infection, but this is not widely believed in the ALS research community. The remaining 10% of cases are "familial", defined as more than one case of ALS in a family. Familial ALS is genetic in aetiology and the following genes are known to be linked to ALS: Cu/Zn superoxide dismutase SOD1, ALS2, NEFH(a small number of cases), senataxin (SETX) and vesicle associated protein B (VAPB).

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