Motor neuron diseases

(ALS). (A) He needs assistance to stand. (B) Advanced atrophy of the tongue. (C) There is upper limb and truncal muscle atrophy with a positive Babinski sign. (D) Advanced thenar muscle atrophy. Signs and symptoms depend on the specific disease, but motor neuron diseases typically manifest as a group of movement-related symptoms. They come on slowly, and worsen over the course of more than three months. Various patterns of muscle weakness are seen, and muscle cramps and spasms may occur. One can have difficulty breathing with climbing stairs (exertion), difficulty breathing when lying down (orthopnea), or even respiratory failure if breathing muscles become involved. Bulbar symptoms, including difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and excessive saliva production (sialorrhea), can also occur. Sensation, or the ability to feel, is typically not affected. Emotional disturbance (e.g. pseudobulbar affect) and cognitive and behavioural changes (e.g. problems in word fluency, decision-making, and memory) are also seen. • Asymmetric distal weakness without sensory loss (e.g. ALS, PLS, PMA, MMA) • Symmetric weakness without sensory loss (e.g. PMA, PLS) • Symmetric focal midline proximal weakness (neck, trunk, bulbar involvement; e.g. ALS, PBP, PLS) Lower and upper motor neuron findings Motor neuron diseases are on a spectrum in terms of upper and lower motor neuron involvement. Pure lower motor neuron diseases, or those with just LMN findings, include PMA. Motor neuron diseases with both UMN and LMN findings include both familial and sporadic ALS. == Causes ==

Most cases are sporadic and their causes are usually not known. TDP-43 is rapidly recruited to double-strand breaks where it acts as a scaffold for the recruitment of the XRCC4-DNA ligase protein complex that then acts to repair double-strand breaks. About 95% of ALS patients have abnormalities in the nucleus-cytoplasmic localization in spinal motor neurons of TDP43. In TDP-43 depleted human neural stem cell-derived motor neurons, as well as in sporadic ALS patients' spinal cord specimens there is significant double-strand break accumulation and reduced levels of NHEJ. Associated risk factors In adults, men are more commonly affected than women. == Diagnosis ==

Differential diagnosis can be challenging due to the number of overlapping symptoms, shared between several motor neuron diseases. Frequently, the diagnosis is based on clinical findings (i.e. LMN vs. UMN signs and symptoms, patterns of weakness), family history of MND, and a variation of tests, many of which are used to rule out disease mimics, which can manifest with identical symptoms. All types of MND can be differentiated by two defining characteristics: LMNs originate in the anterior horns of the spinal cord and synapse on peripheral muscles. Tests • Cerebrospinal fluid (CSF) tests: Analysis of the fluid from around the brain and spinal cord could reveal signs of an infection or inflammation. • Magnetic resonance imaging (MRI): An MRI of the brain and spinal cord is recommended in patients with UMN signs and symptoms to explore other causes, such as a tumor, inflammation, or lack of blood supply (stroke). • Tissue biopsy: Taking a small sample of a muscle or nerve may be necessary if the EMG/NCS is not specific enough to rule out other causes of progressive muscle weakness, but it is rarely used. == Treatment ==

There are no known curative treatments for the majority of motor neuron disorders. Physiotherapy helps maintain movement and function when someone is affected by disability, injury or illness. This is achieved through movement and exercise, manual therapy, education and advice. Although physiotherapy can't reverse the effects of MND, or Kennedy's disease, it can help maintain range of movement and comfort for as long as possible. == Prognosis ==

The table below lists life expectancy for patients who are diagnosed with MND. ==Terminology==

In the United States and Canada, the term motor neuron disease usually refers to the group of disorders while amyotrophic lateral sclerosis is frequently called ''Lou Gehrig's disease. In the United Kingdom and Australia, the term motor neuron(e) disease'' is used for amyotrophic lateral sclerosis, While MND refers to a specific subset of similar diseases, there are numerous other diseases of motor neurons that are referred to collectively as "motor neuron disorders", for instance the diseases belonging to the spinal muscular atrophies group. However, they are not classified as "motor neuron diseases" by the 11th edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-11), which is the definition followed in this article. == See also ==