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. Some have just lower or upper motor neuron findings, while others have a mix of both. Lower motor neuron (LMN) findings include muscle atrophy and fasciculations, and upper motor neuron (UMN) findings include hyperreflexia, spasticity, muscle spasm, and abnormal reflexes.Pure upper motor neuron diseases, or those with just UMN findings, include PLS.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. It is thought that environmental, toxic, viral, or genetic factors may be involved. DNA damage
TARDBP (TAR DNA-binding protein 43), also referred to as TDP-43, is a critical component of the non-homologous end joining (NHEJ) enzymatic pathway that repairs DNA double-strand breaks in pluripotent stem cell-derived motor neurons. 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.
Both motor neurons are necessary for the strong contraction of a muscle, but damage to an UMN can be distinguished from damage to a LMN by physical exam. 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). Electromyogram (EMG) & nerve conduction study (NCS): The EMG, which evaluates muscle function, and NCS, which evaluates nerve function, are performed together in patients with LMN signs. For patients with MND affecting the LMNs, the EMG will show evidence of: (1) acute denervation, which is ongoing as motor neurons degenerate, and (2) chronic denervation and reinnervation of the muscle, as the remaining motor neurons attempt to fill in for lost motor neurons. By contrast, the NCS in these patients is usually normal. It can show a low compound muscle action potential (CMAP), which results from the loss of motor neurons, but the sensory neurons should remain unaffected. 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. Please refer to the articles on individual disorders for more details.