Something new is coming to Sketchy... ­čĹÇBe the first to know!

Spinal Muscular Atrophy, Amyotrophic Lateral Sclerosis (ALS) & Friedreich Ataxia

Tags:
No items found.

Pathophysiology

Summary

The motor cortex is the origin of upper motor neurons, which give rise to the corticospinal (pyramidal) tracts. These tracts descend through the medullary pyramids, and most of their fibers decussate (cross) at the medulla, forming the lateral corticospinal tracts. These upper motor neuron axons synapse with the lower motor neurons located in the anterior horns of the spinal cord.

Upper motor neuron (UMN) lesions result in muscle weakness, spastic paralysis, clasp-knife rigidity, hyperreflexia, and an upgoing plantar reflex known as a positive Babinski sign. Lower motor neuron lesions (LMN) lesions result in symptoms like flaccid paralysis with hypotonia, hyporeflexia, muscle fasciculations & atrophy, as well as a downgoing plantar reflex.

Spinal muscular atrophy (SMA) is an autosomal recessive congenital disease that results in degeneration of the anterior horns. SMA leads to LMN lesions, causing symptoms like hypotonia, hyporeflexia, and muscle fasciculations. SMA affects the anterior horns bilaterally, leading to bilateral LMN symptoms. The infantile form, known as Werdnig-Hoffman disease, presents before the age of 6 months.

Poliomyelitis, a result of the poliovirus, impacts the anterior horns, leading to asymmetric paralysis & weakness.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a progressive neurodegenerative disease of motor neurons. It causes both UMN & LMN lesions, leading to symptoms such as asymmetric distal extremity weakness, atrophy, and frontotemporal dementia in some cases. Mutations in the superoxide dismutase type 1 (SOD1) gene are often found in ALS. Treatment with riluzole can extend survival, as it decreases glutamate-induced excitotoxicity in neurons.

Friedreich ataxia is an autosomal recessive disorder resulting from an expanded GAA repeat in frataxin gene, causing a loss-of-function mutation. Frataxin is an important protein in mitochondrial iron homeostasis, and causes mitochondrial iron accumulation, oxidative stress, and cell death when deficient. This results in the degeneration of spinocerebellar tracts and the dentate nuclei, causing gait ataxia. The disease also leads to degeneration of the dorsal columns, causing impaired proprioception & vibration sensation, as well as the lateral corticospinal tract, leading to lower extremity weakness. Affected individuals might also exhibit foot abnormalities like pes cavus and hammer toes, and develop kyphoscoliosis. Other complications include insulin resistance & diabetes and hypertrophic cardiomyopathy. Cardiac abnormalities are the most common cause of death in FA.

Lesson Outline

Don't stop here!

Get access to 155 more Pathophysiology lessons & 13 more medical school learning courses with one subscription!

Try 7 Days Free

FAQs

What is the difference between the symptoms and effects of upper motor neuron (UMN) lesions and lower motor neuron (LMN) lesions?

Upper motor neuron (UMN) lesions typically cause symptoms such as muscle weakness, spastic paralysis, clasp-knife rigidity, hyperreflexia, and upgoing plantar reflexes (positive Babinski sign). On the other hand, lower motor neuron (LMN) lesions cause symptoms like flaccid paralysis with hypotonia, hyporeflexia, muscle atrophy, fasciculations and downgoing plantar reflexes.

What is spinal muscular atrophy (SMA) and how does it affect the body?

Spinal muscular atrophy (SMA) is a congenital condition that involves the degeneration of the anterior horns of the spinal cord, leading to lower motor neuron (LMN) lesions. Symptoms include hypotonia, hyporeflexia, and muscle fasciculations. SMA is known to affect the anterior horns of the spinal cord bilaterally, with symptoms presenting on both sides of the body. Infantile SMA, known as Werdnig-Hoffman disease, generally presents before the age of 6 months.

What are the distinguishing factors and characteristics of amyotrophic lateral sclerosis (ALS)?

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a progressive neurodegenerative disease of motor neurons. It causes both upper motor neuron (UMN) and lower motor neuron (LMN) lesions, leading to symptoms such as asymmetric distal extremity weakness, atrophy, and frontotemporal dementia in some cases. In ALS, the lateral corticospinal tracts typically show signs of atrophy and sclerosis bilaterally. ALS is often associated with mutations in the superoxide dismutase type 1 (SOD1) gene.

What is Friedreich ataxia and what are its effects on the body?

Friedreich ataxia is an autosomal recessive disorder resulting from an expanded GAA repeat in frataxin gene, causing a loss-of-function mutation. As a result of decreased frataxin, mitochondrial iron accumulates, causing oxidative stress and cell death. This leads to degeneration of multiple neural tracts and peripheral nerves, resulting in symptoms such as gait ataxia, impaired proprioception and vibration sensation, and lower extremity weakness. The motor neuropathy in Friedreich ataxia affects various organ systems, often manifesting as foot abnormalities such as pes cavus and hammer toe. kyphoscoliosis, hypertrophic cardiomyopathy, insulin resistance, and diabetes.

How does Friedreich ataxia lead to hypertrophic cardiomyopathy?

The loss of function mutation in the FXN (frataxin) gene in Friedreich ataxia leads to reduction of frataxin, a protein involved in iron homeostasis in the mitochondria. Lower levels of frataxin lead to mitochondrial iron accumulation, oxidative stress, and cell death which can affect various tissues, including cardiac myocytes. This causes the heart muscle to thicken (hypertrophic cardiomyopathy), leading to cardiac complications such as arrhythmias and heart failureÔÇöoften the most common cause of death in cases of Friedreich ataxia.