Anterior Horn Cell Disease

Introduction

Motor neuron disease (MND) is a condition that can be passed down through genetics. One type of MND is known as anterior horn cell (AHC) disease. Motor neuron diseases that run in families are thought to be the most common cause of AHC disease.¹ Most patients report having a sudden onset of symptoms. These can affect neurons on the spinal cord or the brainstem and manifest different symptoms, depending on the location of degeneration. Other than genetics, this can be caused by paralytic poliomyelitis viruses such as polio, spinal muscle atrophy and amyotrophic lateral sclerosis. 

What is Anterior Horn Cell Disease?

Anterior horn cells, also known as motor neurons, can be found in each segment of the spinal cord. However, the majority of these cells/nerves are found in the cervical and lumbosacral enlargements. They can be functionally divided into a set of nerves that controls the extensor muscles and another set that controls the flexor muscles. Because these groups of neurons are concentrated in a small area, it is possible for harmful influences to affect cells from multiple muscle groups, resulting in widespread weakness.

The brainstem can also be affected by AHC diseases. The motor neurons that are found in the cranial nerve nuclei of the brainstem are similar to the cells that are found in the anterior horn of the spinal cord. Thus, it is possible for pathological mechanisms to also cause symptoms and signs that are comparable to those seen in spinal cord anterior horn cell dysfunction. Symptoms of neuronal degradation in this area include muscle atrophy, severe weakness, and fasciculations (twitches) are all symptoms of anterior horn cell disease, but the disease does not cause a sensory deficit⁴. If sensory functions are impaired in the presence of anterior horn cell disease, this dysfunction may then manifest itself in other tracts of the spinal cord or the peripheral nerves.²

Causes/Risk Factors

The following diseases can affect anterior horn cells and result in AHC disease.

Spinal muscle atrophy

People who have Spinal Muscular Atrophy (SMA), a form of inherited autosomal recessive motor neuron disease, experience progressive muscle weakness over time. This is because SMA causes the degeneration and loss of anterior horn cells in the spinal cord and brain stem nuclei.

Brief pathology

Patients who have spinal muscular atrophy have a shortage of motor neurons and gliosis in the motor cranial nerve nuclei V, VII, IX, and XII, respectively. This occurs in the anterior horns of the spinal cord. This can be seen in the changes that occur in muscle tissue as a result of acute and chronic denervation, including the grouping of different types of fibres. In addition, evidence of massive hypertrophy in particular muscle fibres can be found through the use of muscle histology.

Paralytic Poliomyelitis

Polioviruses are members of the Enterovirus genus, which is part of the Picornaviridae family, and there are three antigenically distinct serotypes for these viruses (types 1, 2, and 3). The only known reservoir for this disease is humans, and it is transmitted from feces to the mouth through the oral route. When kept at room temperature, polioviruses can retain their ability to replicate and cause disease for several days.

Brief Pathology

Before entering the body through the digestive tract, polioviruses are capable of causing disease by attaching themselves to poliovirus receptors. They can remain dormant in oral secretions and faeces for weeks or even months at a time. Through the peripheral nerves, wild-type poliovirus, as well as neurovirulent revertant vaccine strains, have the potential to enter the central nervous system (CNS). Around 70% of poliovirus infections are asymptomatic and around 20% experience mild symptoms.⁶ In patients infected with wild-type poliovirus and lymphocytic meningitis, paralytic poliomyelitis develops in approximately 0.1% of cases.⁷ Many of the nuclei of the cranial nerves are found in the motor neuron cells of the anterior horn of the spinal cord (AHC) and the medulla oblongata of the brain, which is also where the majority of the pathological changes are found. The reticular formation in the brainstem causes disruptions in the functioning of the vital centres, which are responsible for regulating important functions like breathing and circulation. The involvement of the spinal cord in the intermediate and dorsal horns, as well as the spinal root ganglia, can be the cause of these symptoms: hypoesthesia (partial or total loss of sensation) and myalgia (muscle aches and pains).

Amyotrophic lateral sclerosis

One disease that exemplifies the debilitating effects of this category is amyotrophic lateral sclerosis (ALS), which is the most prevalent form of motor neuron disease. It can be challenging to diagnose ALS and other diseases that affect the motor neurons.

Brief Pathology

As the disease worsens, pyramidal Betz cells in the motor cortex as well as large anterior horn cells in the spinal cord and lower cranial motor nuclei in the brainstem experience degeneration. Additionally, the disease affects the lower cranial motor nuclei in the brainstem.

Symptoms

Signs that the lower motor neurons have been affected by anterior horn cell disease can be defined with respect to the relevant region of the brain or spinal cord involved:⁵

• Motor Neuron Signs
  • Reduced tone 
  • Muscle atrophy 
  • Fasciculations
  • Reduced muscle stretch
  • Reflexes

• Bulbar region sign
  • Tongue fasciculations and atrophy

• Cervical region signs
  • Wasting of intrinsic hand muscles, especially the first dorsal interosseous muscle

• Thoracic signs
  • Fasciculations (contractions) in the back and abdominal area.

• Lumbosacral signs
  • Foot drop and muscle atrophy.

Diagnosis

In order to diagnose diseases affecting the motor neuron, clinical tests are utilised. Confirmation of denervation of the motor neuron can be achieved through the use of supportive diagnostic procedures like nerve conduction studies and electromyography (EMG). In certain situations, the confirmation of an underlying pathology can be accomplished through the use of a genetic test or a titer for an infectious disease. Imaging is not helpful in the diagnosis of motor neuron disease; the only purpose it serves is to rule out potential mimics.

Treatments

SMA treatment

Supportive therapies are the only options for people with SMA who want to address the underlying molecular issue. However, several experimental therapies are currently being tested on humans. Intrathecally administered antisense oligonucleotide therapy has shown promise in human clinical trials and is the most prominent of these. The field of gene therapy is also undergoing active research and development, with human pilot studies having already been completed.

ALS treatment

The glutamate antagonist Riluzole 50 mg twice daily may slow the progression of ALS, but it is an incurable disease. Currently, additional drug trials are being conducted.

How long can you live with Anterior Horn Cell  Disease?

After being diagnosed, the median survival time is 3 years. The presence of a paraprotein in 5% of patients indicates the presence of a lymphoma or plasma cell disorder, which can further impact this life expectancy.

Conclusion

The health of an individual is severely compromised when the cells of the anterior horn are damaged in MND and AHC disease. The anterior horn cells are responsible for the regulation of all voluntary movement, respiration, speech and swallowing, in addition to motor activity.  When patients notice the symptoms of anterior horn cell loss (such as weakness, falling, choking), they are advised to make an appointment to see a doctor as soon as possible. Some risk factors that contribute to this development include paralytic poliomyelitis viruses such as polio, spinal muscle atrophy and amyotrophic lateral sclerosis. Neurologists are able to detect and diagnose any damage or loss of anterior horn cells that may have occurred to give an accurate diagnosis, as well as a treatment plan.