Clinical Manifestations
This disease includes Progressive weakness begins in either the limbs or bulbar muscles, eventually spreading throughout the body.
What is Progressive motor weakness
A nuclear protein becomes mislocalized to the cytoplasm in motor neurons, forming toxic aggregates and impairing RNA regulation.
TDP-43 proteinopathy
This electrodiagnostic study evaluates the electrical activity of muscles. In this condition, it often reveals active denervation and reinnervation in multiple regions, with normal sensory nerve function, supporting a motor neuron disorder.
Electromyography (EMG) showing widespread denervation and reinnervation
This glutamate pathway modulator modestly extends survival by reducing excitotoxicity in the CNS.
Riluzole
This enzyme mutation was the first genetic cause discovered and is still studied
Superoxide dismutase 1 (SOD1) mutation
This disease has early symptoms may include difficulty speaking, slurred speech, and trouble swallowing, often leading to weight loss.
Bulbar onset symptoms
A hexanucleotide repeat expansion in a specific gene results in the production of toxic RNA and abnormal proteins that contribute to motor neuron loss.
C9orf72 mutation
Diagnosis is primarily clinical but requires exclusion of other conditions through imaging, bloodwork, and neurophysiological testing.
Diagnosis of exclusion
Approved in 2017, this antioxidant slows functional decline and is often given intravenously in cycles.
Edaravone
This familial form of the condition follows an autosomal dominant inheritance pattern and may appear in multiple generations.
autosomal dominant inheritance
This disease includes, muscle twitching and muscle cramps occur frequently, especially in the arms, legs, shoulders, and tongue.
Fasciculations and cramps
Degeneration of both upper and lower motor neurons leads to a combination of spasticity, hyperreflexia, muscle atrophy, and muscle twitching.
motor neuron degeneration
normal sensory nerve conduction studies help differentiate this condition from peripheral neuropathies.
Preserved sensory nerve conduction on NCS
Coordinated care involving neurology, physical therapy, respiratory therapy, and palliative services improves symptom management and survival, especially when assisted ventilation is used.
Multidisciplinary care with non-invasive ventilation
Most individuals with this condition eventually require assistive devices for mobility and respiratory support, due to lack of muscle strength
Progressive physical disability
As the disease progresses, breathing becomes more difficult due to weakening of the diaphragm and intercostal muscles.
Respiratory muscle weakness
Excess extracellular glutamate, due to impaired astrocytic uptake, leads to excitotoxicity and neuronal injury.
Glutamate excitotoxicity
This imaging technique may be used to rule out structural causes of upper motor neuron signs, such as cervical spondylotic myelopathy.
MRI of the brain and spinal cord
Management includes interventions tailored to specific symptoms, such as feeding tube placement for dysphagia, antispasmodic medications for muscle stiffness, and assistive communication devices for speech loss.
Supportive symptom management
About 10% of cases are inherited, often through an autosomal dominant mutation in genes like SOD1 or TARDBP.
Familial inheritance patterns
Despite widespread motor decline, sensation, bowel/bladder control, and eye movements typically remain intact.
Preserved sensory and autonomic function
The condition presents with progressive limb weakness, muscle twitches, and spasticity, often with preserved sensory and cognitive function.
Progressive motor neuron disease
This simplified diagnostic framework requires progressive motor impairment with clinical signs of both upper and lower motor neuron dysfunction, and was introduced in 2019 to allow earlier diagnosis of motor neuron disease.
Gold Coast Criteria
This approach emphasizes comfort, psychological support, and quality of life in advanced stages. It involves pain control, respiratory support, and end of life planning, often provided alongside standard medical care.
Palliative care
A well known physicist who made groundbreaking contributions to cosmology despite living with this condition for over 50 years
Stephen Hawking