11th August 2024

Types of MND

Amyotrophic lateral sclerosis (ALS)

ALS is the most common MND of adult onset with incidence peaking at the age of 75 years. It is a fatal disorder characterised by progressive skeletal muscle weakness, fasciculation, spasticity and atrophy due to UMN and LMN degeneration. Therefore ALS presents with a combination of both UMN and LMN signs.

ALS has sporadic and familial forms; 5-10% of cases are due to a superoxide dismutase-1 (SOD1) gene mutation.

It often presents with asymmetric lower limb motor neuropathy. However, regardless of which muscles are first affected, the symptoms spread to affect all four limbs and bulbar muscles. Death in ALS occurs due to progressive respiratory muscle paralysis.

Riluzone, a glutamate release inhibitor, is licensed for slowing down ALS progression, but there is no cure.

Primary lateral sclerosis (PLS)

PLS is a rare idiopathic disorder involving mostly UMNs. It is characterised by progressive spinobulbar weakness, and usually presents with lower limb spasticity with hyperactive reflexes and clonus. LMNs are generally spared.

Hereditary spastic paraparesis

This group of genetic disorders is characterised by a slowly progressive spastic, UMN pattern of weakness. Early presentations are with gait disturbance; upper limb involvement is usually mild.

Genetically they are classified by mode of inheritance, with the autosomal dominant form most common, however autosomal recessive and X-linked forms also occur. There can be significant clinical overlap with PLS.

Progressive bulbar palsy

This presents with LMN weakness of the glossopharyngeal, vagus, accessory and hypoglossal nerves (CN IX-XII) due to degeneration of their motor nuclei in the medulla. Symptoms include tongue weakness and fasciculations, dysarthria and dysphagia. Patients may present with a history of regurgitation of food and  fluids, tongue wasting and  fasciculations. Spinal cord involvement often occurs late in the disease course. Infantile forms also exist.

Spinal muscular atrophy

This is a genetic disorder characterised by degeneration of LMNs with no sensory or UMN involvement. The commonest inheritance pattern is autosomal recessive, however autosomal dominant and X-linked forms do exist. It is often first diagnosed in childhood and presents with weakness and progressive muscle atrophy

X-linked spinobulbar muscular atrophy (Kennedy disease)

This is an adult-onset X-linked recessive trinucleotide expansion disorder, with CAG repeats in the androgen receptor gene. It is characterised by progressive bulbar and limb muscle weakness, but also presents with endocrine disturbances such as androgen insensitivity. As an X-linked disorder it exclusively affects males but is transmitted by female carriers.

Post-polio syndrome

This presents after an acute attack of paralytic poliomyelitis and is characterised by late-onset skeletal and bulbar muscle weakness. Is a diagnosis of exclusion.