Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. The loss of these motor neurons leads to muscle weakness, atrophy, and eventually paralysis due to the inability to control voluntary movements. While ALS can impact muscles throughout the body, there are some parts that are generally spared from symptoms. Understanding which areas remain unaffected can provide insight into the underlying mechanisms of ALS pathogenesis. This article will provide an overview of the parts of the body that are typically unaffected in ALS.
The Brain
One of the key features of ALS is that it does not directly affect the brain itself. Cognitive functions such as personality, reasoning, judgment, and intelligence are usually preserved, especially in the early stages. The cortex and subcortical structures remain anatomically intact. Patients maintain awareness and consciousness of their surroundings.
While the actual brain tissue is not impacted, ALS does affect the motor cortex in the region that controls voluntary movements. The degeneration of upper motor neurons projecting from the motor cortex to the brainstem and spinal cord is a hallmark of ALS. But the cognitive areas of the brain generally remain unaffected.
The Sensory System
The sensory nervous system, including sensations of touch, pain, temperature, and proprioception (body position), is also not directly impaired in ALS. Sensory neurons that transmit signals from sensory receptors in the peripheral nervous system into the central nervous system remain intact. Patients retain normal sensitivity to external stimuli.
The pathways for sensory information, including the dorsal columns of the spinal cord, are preserved in ALS. Sensory symptoms are uncommon, although some patients may experience mild numbness or tingling. Overall, the sensory system remains functional despite the motor deficits associated with ALS.
The Autonomic Nervous System
The autonomic nervous system controls involuntary bodily functions such as heart rate, digestion, respiratory rate, salivation, perspiration, and pupil dilation. This system is divided into the sympathetic and parasympathetic nervous systems, which work in opposition to regulate organ function. Autonomic neuropathy is not considered a feature of ALS.
Patients with ALS maintain normal autonomic control early in their disease. As ALS progresses, severe muscle weakness can indirectly impact respiration, speech, and swallowing which are controlled by skeletal muscles. But the autonomic nerves that regulate unconscious activities remain intact. Heart rate and digestion are preserved until late stages. The autonomic nervous system is generally unaffected by the motor neuron degeneration seen in ALS.
The Extraocular Muscles
The extraocular muscles control eye movement and allow for actions such as looking side-to-side, up and down, and focusing the eyes on objects at varying distances. These small skeletal muscles are responsible for precise, coordinated eye movements and alignment.
One of the most unusual features of ALS is that the extraocular muscles are typically spared, even as weakness progresses in other muscle groups. Patients retain the ability to move their eyes voluntarily in all directions. Eye tracking remains smooth and intact, although some may have difficulty looking upward or downward.
The neuroprotective mechanism that preserves the extraocular muscles in ALS remains unknown. But involvement of the extraocular muscles is very rare in ALS patients, even in end-stage disease.
The Bladder and Bowel
The smooth muscles of the bladder and bowel, which control urine storage/urination and feces elimination respectively, are generally not impacted by ALS. Spinal cord or brainstem lesions can sometimes affect bladder or bowel function, but this is not due to ALS itself.
Normal control of bowel and bladder function tends to be maintained as long as voluntary motor function allows patients to use the bathroom. In the late stages, severe weakness can make it difficult or impossible to voluntarily control urination or defecation. But the nerves controlling the bladder and bowel directly remain unaffected.
Sexual Function
ALS does not directly damage the sex organs or interfere with sexual function or arousal. Male patients often maintain the ability to achieve erections, have sexual intercourse, and ejaculate normally. The muscles involved in sexual activity can sometimes become weak, but sensory function remains intact.
Women continue to experience menstruation and the physical sensations of sexual arousal. Lubrication and ability to achieve orgasm are preserved. Some patients report a loss of interest in sex due to psychological factors or frustration with physical limitations. But sexual dysfunction is not a core feature of ALS. The nerves and pathways that control basic sexual function are undamaged.
The Vestibular Apparatus
The vestibular apparatus located in the inner ear regulates balance and spatial orientation. It contains three semicircular canals that sense head rotation and otolithic organs (utricle and saccule) that detect linear motion and gravity. While limb weakness and loss of proprioception can make ALS patients prone to falls and injury, the vestibular apparatus itself remains unaffected.
Patients retain a normal sense of balance when upright or lying down. The vestibular nerves sending signals about head position and movement to the brainstem vestibular nuclei remain intact. Ataxia or true vertigo are not characteristic of ALS, although imbalance may occur from muscle pathology. But the vestibular apparatus is spared from the neuronal degeneration underpinning ALS.
Cranial Nerve Control of Eyes, Face, and Throat
The cranial nerves emerge from the brainstem and control motor and sensory functions of the eyes, face, and throat. In ALS patients, five out of the twelve cranial nerves are generally unaffected:
- Oculomotor nerve (CN III) – controls extraocular muscles that allow eye movement and pupillary constriction.
- Trochlear nerve (CN IV) – innervates the superior oblique extraocular muscle.
- Abducens nerve (CN VI) – stimulates the lateral rectus extraocular muscle.
- Vestibulocochlear nerve (CN VIII) – involved in hearing and balance.
- Glossopharyngeal nerve (CN IX) – provides sensory innervation of the throat and tongue.
These cranial nerves governing eye movements, pupillary response, balance, and throat/tongue sensation are unaffected in ALS patients. Preservation of these functions contrasts with impairment of functions controlled by vulnerable motor cranial nerves such as the facial (CN VII) and hypoglossal (CN XII) nerves.
Summary Table of Unaffected regions in ALS
| Body Region | Function |
|---|---|
| Brain | Cognition and intelligence |
| Sensory pathways | Touch, pain, temperature, proprioception |
| Autonomic nervous system | Heart rate, respiration, digestion, etc. |
| Extraocular muscles | Eye movements and alignment |
| Bladder and bowel | Waste elimination and continence |
| Sex organs | Sexual function and arousal |
| Vestibular apparatus | Balance and spatial orientation |
| Cranial nerves III, IV, VI, VIII, IX | Eye movement, balance, throat sensation |
Conclusion
While ALS causes relentless destruction of motor neurons leading to progressive paralysis, some parts of the nervous system remain remarkably spared. Understanding why certain regions are resistant to the neurodegenerative process may unlock insights into potential protective mechanisms that could be augmented or leveraged for therapeutic benefit. Additional research is needed, but the structures unaffected in ALS provide clues about the complex underlying pathology of this devastating disease. Focusing treatment approaches on enhancing nervous system functions that are retained, rather than attempting to restore lost functions, could represent a promising neuroprotective strategy for the future.