Neurologic Myopathy
Neurologic myopathy refers to secondary muscle dysfunction that arises from primary abnormalities in the nervous system rather than from intrinsic muscle disease. It is commonly seen in conditions affecting the central or peripheral nervous system and may lead to muscle weakness, atrophy, and altered muscle tone.
Myopathy Secondary to Upper Motor Neuron Diseases
Upper motor neuron (UMN) diseases are characterized by lesions in the corticospinal tract or motor cortex, resulting in spasticity, hyperreflexia, and weakness, with preserved muscle bulk in the early stages. However, over time, chronic UMN involvement may lead to secondary myopathic changes due to disuse, spasticity, and altered neuromuscular signaling. These secondary myopathies are not due to primary muscle pathology but represent muscle adaptation or degeneration in response to chronic neural dysfunction.
Myopathy in Cerebral Palsy
Cerebral palsy (CP) is a group of permanent disorders of movement and posture caused by non-progressive disturbances in the developing fetal or infant brain. Although the primary lesion is located in the central nervous system (CNS), many individuals with cerebral palsy (CP) also develop secondary myopathic changes over time.
In CP, chronic muscle overactivity (e.g., spasticity or dystonia), disuse, and altered muscle growth contribute to muscle fiber changes, including:
These changes can result in progressive contractures, weakness, and impaired motor function, even in the absence of a primary myopathy.
Multiple Sclerosis (MS)
In multiple sclerosis, demyelination and axonal injury within the central nervous system disrupt motor pathways, leading to impaired motor function. Although MS is primarily a CNS disease, several mechanisms can lead to muscle pathology:
These muscle changes are generally mild and secondary but can significantly impact functional mobility.
Hereditary Spastic Paraplegia (HSP)
Hereditary spastic paraplegia is a group of inherited disorders characterized by progressive spasticity and weakness of the lower limbs. As in other UMN disorders, spasticity and decreased voluntary muscle activity can result in:
Amyotrophic Lateral Sclerosis (ALS)
ALS affects both upper and lower motor neurons, but UMN signs (e.g., spasticity and hyperreflexia) dominate in some forms. In these cases, chronic spasticity and reduced voluntary control can lead to:
Although ALS is primarily neurogenic, muscles undergo secondary degeneration that may mimic or exacerbate myopathic features.
Myopathy Secondary to Spinal Cord Disease
Introduction
Spinal cord diseases can lead to a variety of neuromuscular consequences, including muscle weakness and atrophy. While these changes are primarily neurogenic in origin, chronic spinal cord involvement may result in secondary myopathic alterations due to disuse, denervation, and altered neuromuscular signaling. In some cases, structural and metabolic changes within the muscle fibers develop over time, contributing to what may be described as a secondary myopathy.
Pathology and Pathophysiology
Damage to upper motor neurons (UMNs) within the spinal cord typically results in increased muscle tone (spasticity), hyperreflexia, and weakness due to disrupted descending control. In contrast, the involvement of lower motor neurons (LMNs), such as in anterior horn cell damage, leads to flaccid weakness, muscle atrophy, and reduced tone and reflexes. In spinal cord diseases with mixed UMN and LMN involvement—as seen in specific traumatic injuries, transverse myelitis, or compressive myelopathies—both increased and decreased muscle tone may coexist in different muscle groups.
Over time, disuse, immobility, and altered neuromuscular input contribute to muscle fiber atrophy, fibrosis, and changes resembling a disuse or neurogenic myopathy. Chronic spasticity may also lead to structural changes in the muscle, including shortened fibers and increased connective tissue, further impairing function.
Clinical Manifestations
Patients may present with a combination of spasticity and flaccidity, depending on the level and completeness of spinal cord involvement. Muscle weakness is common and may be accompanied by visible atrophy, contractures, and impaired voluntary control. Increased tone is usually noted below the level of injury in UMN syndromes, while reduced tone and fasciculations are seen in LMN-damaged regions. Reflexes may be exaggerated or absent depending on the segmental involvement. In longstanding cases, reduced mobility and altered loading contribute to further muscle degradation. The clinical picture reflects a complex interplay between neurogenic dysfunction and secondary muscle pathology.
Myopathy Secondary to Peripheral Neuropathy
Introduction
While myopathies and peripheral neuropathies are classically regarded as distinct neuromuscular disorders affecting muscle fibers and peripheral nerves, respectively, there are circumstances where muscle pathology arises as a consequence of neuropathic processes. This phenomenon is referred to as neurogenic myopathy or myopathy secondary to peripheral neuropathy. It is particularly relevant in chronic or severe neuropathies in which denervation leads to secondary muscle changes that resemble primary myopathic processes, both clinically and histologically.
Pathology and pathophysiology
Muscle tissue relies on intact innervation for trophic support, activity, and structural maintenance. In peripheral neuropathies—especially those affecting motor fibers—denervation disrupts the neuromuscular unit, leading to secondary muscle changes. Denervation atrophy primarily affects type II (fast-twitch) fibers due to loss of neural input. Surviving motor neurons may reinnervate adjacent fibers, resulting in fiber-type grouping, but continued denervation leads to group atrophy.
Over time, chronic denervation may cause fatty infiltration, fibrosis, and mitochondrial abnormalities within the muscle. These changes are secondary to nerve damage, with the primary pathology localized to the peripheral nervous system.
Clinical manifestations
Myopathy secondary to peripheral neuropathy can exhibit features that resemble both neuropathic and primary myopathic disorders. The clinical presentation varies depending on the extent, distribution, and duration of the underlying neuropathy. Muscle weakness typically begins distally but may progress to involve proximal muscles as the disease advances. Denervated muscles often exhibit atrophy, with fasciculations and cramps being especially pronounced in cases of motor neuron involvement. Reflexes may be preserved in early stages but are usually diminished or absent in chronic cases, and sensory symptoms such as numbness, paresthesias, or pain may occur if sensory fibers are affected. In advanced neuropathies like Charcot-Marie-Tooth disease or CIDP, the resulting muscle wasting can closely mimic a primary myopathy.
