Motor neuron diseases affect either upper motor neurons (UMN) or lower motor neurons (LMN), or both:

A motor neuron disease (MND) is any of several neurological disorders that selectively affect motor neurons, the cells that control voluntary muscles of the body. They include amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP), primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), progressive bulbar palsy (PBP) and pseudobulbar palsy. Spinal muscular atrophies (SMA) are sometimes included in the group by some neurologists but it is different disease with clear genetic cause. They are neurodegenerative in nature and cause increasing disability and eventually, death.

ALS is a motor neuron disease, also spelled "motor neurone disease", which is a group of neurological disorders that selectively affect motor neurons, the cells that control voluntary muscles of the body, including amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, progressive muscular atrophy, progressive bulbar palsy, pseudobulbar palsy, and spinal muscular atrophy.

ALS itself can be classified a few different ways: by how fast the disease progresses (slow vs fast progressors), by whether it is inherited or sporadic, and by where it starts. Most commonly (~70% of the time) the limbs are affected first. In this case, neurons in the brain (upper motor neurons) and in the spinal cord (lower motor neurons) are dying and this form is called "limb onset". In about 25% of cases, muscles in the face, mouth, and throat are affected first because motor neurons in the part of the brain stem called the medulla oblongata (formerly called the "bulb") start to die first along with lower motor neurons. This form is called "bulbar onset". In about 5% of cases muscles in the trunk of the body are affected first. In all cases the disease spreads and affects other regions. The symptoms may also be limited to one spinal region.

Those with leg amyotrophic diplegia and brachial amyotrophic diplegia have a longer survival compared to classic onset ALS.

The disorder causes muscle weakness and atrophy throughout the body due to the degeneration of the upper and lower motor neurons. Individuals affected by the disorder may ultimately lose the ability to initiate and control all voluntary movement, although bladder and bowel function and the muscles responsible for eye movement are usually spared until the final stages of the disorder.

Cognitive or behavioral dysfunction is present in 30–50% of individuals with ALS. Around half of people with ALS will experience mild changes in cognition and behavior, and 10–15% will show signs of frontotemporal dementia. Repeating phrases or gestures, apathy, and loss of inhibition are frequently reported behavioral features of ALS. Language dysfunction, executive dysfunction, and troubles with social cognition and verbal memory are the most commonly reported cognitive symptoms in ALS; a meta-analysis found no relationship between dysfunction and disease severity. However, cognitive and behavioral dysfunctions have been found to correlate with reduced survival in people with ALS and increased caregiver burden; this may be due in part to deficits in social cognition. About half the people who have ALS experience emotional lability, in which they cry or laugh for no reason.

Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with ALS maintain hearing, sight, touch, smell, and taste.

Onset of PLS usually occurs spontaneously after age 50 and progresses gradually over a number of years, or even decades. The disorder usually begins in the legs, but it may start in the tongue or the hands. Symptoms may include difficulty with balance, weakness and stiffness in the legs, and clumsiness. Other common symptoms are spasticity (involuntary muscle contraction due to the stretching of muscle, which depends on the velocity of the stretch) in the hands, feet, or legs, foot dragging, and speech and swallowing problems due to involvement of the facial muscles. Breathing may also become compromised in the later stages of the disease, causing those patients who develop ventilatory failure to require noninvasive ventilatory support. Hyperreflexia is another key feature of PLS as seen in patients presenting with the Babinski's sign. Some people present with emotional lability and bladder urgency, and occasionally people with PLS experience mild cognitive changes detectable on neuropsychological testing, particularly on measures of executive function.

PLS is not considered hereditary when onset is in adulthood; however, juvenile primary lateral sclerosis (JPLS) has been linked to a mutation in the ALS2 gene which encodes the cell-signalling protein alsin.

The issue of whether PLS exists as a different entity from ALS is not clear, as some patients initially diagnosed as having PLS ultimately develop lower motor neuron signs.

There are no specific tests for the diagnosis of PLS. Therefore, the diagnosis occurs as the result of eliminating other possible causes of the symptoms and by an extended observation period.

In contrast to amyotrophic lateral sclerosis or primary lateral sclerosis, PMA is distinguished by the "absence" of:

- brisk reflexes

- spasticity

- Babinski's sign

- Emotional lability

Primary lateral sclerosis (PLS) usually presents with gradual-onset, progressive, lower-extremity stiffness and pain due to muscle spasticity. Onset is often asymmetrical. Although the muscles do not appear to atrophy as in ALS (at least initially), the disabling aspect of PLS is muscle spasticity and cramping, and intense pain when those muscles are stretched, resulting in joint immobility. A normal walking stride may become a tiny step shuffle with related instability and falling.

As a result of lower motor neurone degeneration, the symptoms of PMA include:

- atrophy

- fasciculations

- muscle weakness

Some patients have symptoms restricted only to the arms or legs (or in some cases just one of either). These cases are referred to as "Flail Arm" (FA) or "Flail Leg" (FL) and are associated with a better prognosis.

Prognosis for PBP patients is poor. Progressive bulbar palsy symptoms can include progressive difficulty with chewing, talking, and swallowing. Patients can also exhibit reduced gag reflexes, weak palatal movements, fasciculations, and weak movement of the facial muscles and tongue. In advanced cases of PBP, the patient may be unable to protrude their tongue or manipulate food in their mouth.

Patients with early cases of PBP have difficulty with pronunciations, particularly lateral consonants (linguals) and velars, and may show problems with drooling saliva. If the corticobulbar tract is affected a pseudobulbar affect with emotional changes may occur. Because PBP patients have such difficulty swallowing, food and saliva can be inhaled into the lungs. This can cause gagging and choking, and it increases the risk of pneumonia. Death, which is often from pneumonia, usually occurs 1 to 3 years after the start of the disorder.

Symptoms of JPLS begin in early childhood and progress over a period of 15 to 20 years. Early symptoms include clumsiness, muscle spasms, weakness and stiffness in the legs, and difficulty with balance. As symptoms progress, they become more serious and include weakness and stiffness in the arms and hands, slurred speech, drooling, difficulty swallowing, and an inability to walk.

Signs and symptoms of pseudobulbar palsy include:

- Slow and indistinct speech

- Dysphagia (difficulty in swallowing)

- Small, stiff and spastic tongue

- Brisk jaw jerk

- Dysarthria

- Labile affect

- Gag reflex may be normal, exaggerated or absent

- Examination may reveal upper motor neuron lesion of the limbs

Progressive bulbar palsy (PBP) is a medical condition. It belongs to a group of disorders known as motor neuron diseases. PBP is a disease that attacks the nerves supplying the bulbar muscles. These disorders are characterized by the degeneration of motor neurons in the cerebral cortex, spinal cord, brain stem, and pyramidal tracts. This specifically involves the glossopharyngeal nerve (IX), vagus nerve (X), and hypoglossal nerve (XII).

This disorder should not be confused with pseudobulbar palsy or progressive spinal muscular atrophy. The term Infantile progressive bulbar palsy is used to describe progressive bulbar palsy in children. Some neurologists consider this disorder to be a subset of amyotrophic lateral sclerosis (ALS), but others disagree with that classification.

Pseudobulbar palsy is a medical condition characterized by the inability to control facial movements (such as chewing and speaking) and caused by a variety of neurological disorders. Patients experience difficulty chewing and swallowing, have increased reflexes and spasticity in tongue and the bulbar region, and demonstrate slurred speech (which is often the initial presentation of the disorder), sometimes also demonstrating uncontrolled emotional outbursts.

The condition is usually caused by the damage (bilateral degeneration) to the neurons of the brain stem, specifically to the corticobulbar tract (upper motor neuron tract to cranial nerve motor nuclei).

Juvenile primary lateral sclerosis (JPLS) ", also known as primary lateral sclerois (PLSJ)," is a rare genetic disorder, with a small number of reported cases, characterized by progressive weakness and stiffness of muscles in the arms, legs, and face. The disorder damages motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement.

Upper motor neuron syndrome (UMNS) is the motor control changes that can occur in skeletal muscle after an upper motor neuron lesion.

Following upper motor neuron lesions, affected muscles potentially have many features of altered performance including:

- weakness (decreased ability for the muscle to generate force)

- decreased motor control including decreased speed, accuracy and dexterity

- altered muscle tone (hypotonia or hypertonia) – a decrease or increase in the baseline level of muscle activity

- decreased endurance

- exaggerated deep tendon reflexes including spasticity, and clonus (a series of involuntary rapid muscle contractions)

Such signs are collectively termed the "upper motor neuron syndrome". Affected muscles typically show multiple signs, with severity depending on the degree of damage and other factors that influence motor control. In neuroanatomical circles, it is often joked, for example, that hemisection of the cervical spinal cord leads to an "upper lower motor neuron syndrome and a lower upper motor neuron syndrome". The saying refers to lower motor neuron symptoms in the upper extremity (arm) and upper motor neurons symptoms in the lower extremity (leg).

The upper motor neuron syndrome signs are seen in conditions where motor areas in the brain and/or spinal cord are damaged or fail to develop normally. These include spinal cord injury, cerebral palsy, multiple sclerosis and acquired brain injury including stroke. The impact of impairment of muscles for an individual is problems with movement, and posture, which often affects their function.

Health professionals' understanding of impairments in muscles after an upper motor neuron lesion has progressed considerably in recent decades. However, a diagnosis of "spasticity" is still often used interchangeably with upper motor neuron syndrome, and it is not unusual to see patients labeled as spastic who demonstrate an array of UMN findings.

Spasticity is an exaggerated stretch reflex, which means that a muscle has a reflex contraction when stretched, and that this contraction is stronger when the stretch is applied more quickly. The commonly quoted definition by Lance (1980) describes "a motor disorder, characterised by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks, resulting from hyper-excitability of the stretch reflex as one component of the upper motor neurone (UMN) syndrome".

Spasticity is a common feature of muscle performance after upper motor neuron lesions, but is generally of much less clinical significance than other features such as decreased strength, decreased control and decreased endurance. The confusion in the use of the terminology complicates assessment and treatment planning by health professionals, as many confuse the other findings of upper motor neuron syndrome and describe them as spasticity. This confusion potentially leaves health professionals attempting to inhibit an exaggerated stretch reflex to improve muscle performance, potentially leaving more significant UMNS changes such as weakness unaddressed. Improved understanding of the multiple features of the upper motor neuron syndrome supports more rigorous assessment, and improved treatment planning.

Tourette syndrome is a disorder that is characterized by behavioral and motor tics, OCD, and Attention-deficit hyperactivity disorder (ADHD). For this reason, it is commonly believed that pathologies involving limbic, associative, and motor circuits of the basal ganglia are likely. Since the realization that syndromes such as Tourette Syndrome and OCD are caused by dysfunction of the non-motor loops of basal ganglia circuits, new treatments for these disorders, based on treatments originally designed to treat movement disorders are being developed.

Sydenham's chorea is a disorder characterized by rapid, uncoordinated jerking movements primarily affecting the face, hands and feet. It is a result of an autoimmune response that occurs following infection by group A β-hemolytic streptococci that destroys cells in the corpus striatum of the basal ganglia.

Individuals with SBMA have muscle cramps and progressive weakness due to degeneration of motor neurons in the brain stem and spinal cord. Ages of onset and severity of manifestations in affected males vary from adolescence to old age, but most commonly develop in middle adult life. The syndrome has neuromuscular and endocrine manifestations.

Ataxia is a motor disorder that affects the spinal cord, brain and brainstem. Symptoms of ataxia include tremors, lack of coordination, loss of balance, instability, inaccuracy, clumsiness, gait problems, speech problems, and involuntary eye movements. Medication is the main treatment of ataxia. Some of these medicines include selegiline, amantadine, entacapone, dopamine agonists, and anticholinergics (“Movement Disorders”).

Early signs often include weakness of tongue and mouth muscles, fasciculations, and gradually increasing weakness of limb muscles with muscle wasting. Neuromuscular management is supportive, and the disease progresses very slowly, but can eventually lead to extreme disability. Further signs and symptoms include:

Usually beginning in one or both hands, MMN is characterized by weakness, muscle atrophy, cramping, and often profuse fasciculations (muscle twitching). The symptoms are progressive over long periods, often in a stepwise fashion, but unlike ALS are often treatable.

Sensory nerves are usually unaffected.

Wrist drop and foot drop (leading to trips and falls) are common symptoms. Other effects can include gradual loss of finger extension, leading to a clawlike appearance. Cold & hot temperatures exacerbates MMN symptoms to such an extent, unlike other neuropathies, that it is being investigated as a diagnostic tool.

Motor disorders are malfunctions of the nervous system that cause involuntary or uncontrollable movements or actions of the body (Stone). These disorders can cause lack of intended movement or an excess of involuntary movement (Mandal). Symptoms of motor disorders include tremors, jerks, twitches, spasms, contractions, or gait problems.

Flaccid dysarthria is a motor speech disorder resulting from damage to peripheral nervous system (cranial or spinal nerves) or lower motor neuron system. Depending on which nerves are damaged, flaccid dysarthria affects respiration, phonation, resonance, and articulation. It also causes weakness, hypotonia (low-muscle tone), and diminished reflexes., Perceptual effects of flaccid dysarthria can include hypernasality, imprecise consonant productions, breathiness of voice, and affected nasal emission.

Neuroferritinopathy has several distinguishing signs and symptoms. These fall into two categories: diagnostic findings and physically visible symptoms.

Symptoms categorized as medically tested and diagnosed include iron accumulation in the brain, basal ganglia cavitation, and neurodegeneration. Patients who are diagnosed with neuroferritinopathy have abnormal iron accumulation in the brain within the neurons and glia of the striatum and cerebellar cortices. Along with the accumulation of iron in the brain, neuroferritinopathy typically causes severe neuronal loss as well.

Secondary symptoms may also arise. It is possible that the initial iron accumulation will cause additional neuronal damage and neuronal death. The damaged neurons may be replaced by other cells in an effort to reverse the neurodegeneration. These cells often have a higher iron content. The breakdown of the blood brain barrier may also occur due to the loss of neurons and will subsequently allow more iron to access the brain and accumulate over time.

Neuroferritinopathy is mainly seen in those who have reached late adulthood and is generally seen to slowly progress throughout many decades in a lifetime with the mean age of onset being 39 years old. A loss of cognition is generally only seen with late stages of the disease. Diagnosed patients are seen to retain most of their cognitive functioning until the most progressive stages of the illness sets in.