Diseases and Disorders

Neurotoxic Vestibulopathy: A Review of Drug-Induced Toxicity

Christian Gonzalez


Abstract

Since the beginning of the 1980s, soldiers working in malaria-ridden areas have received drugs for the prevention and treatment of malaria, resulting in serious neurological side effects. Specifically, the anti-malarial drug Mefloquine, and other widely-used treatments in malaria prophylaxis known as quinolines, leads to the poisoning of neurons that are responsible for regulating balance. The neuronal damage sustained when this occurs is permanent, and as a result, so is the loss of balance. Broadly speaking, the loss of balance and its accompanying symptoms, such as dizziness and fatigue, are referred to as neurotoxic vestibulopathy. Neurotoxic vestibulopathy is a disorder of the central nervous system that causes a disruption of the proper communication between sense organs, particularly between the inner ear and the brain, which leads to the inability to experience regular vestibular function. The disease is chronic, resulting in irreversible neurological damage, and there is no cure available [1].


 

Overview and Symptoms

    The majority of patients with neurotoxic vestibulopathy are soldiers and other military personnel who were exposed to malaria while residing in a region where the condition is prevalent. The symptoms experienced in neurotoxic vestibulopathy are not due to malaria itself, but rather are the result of the pharmacological treatments used to treat the disease. The most common symptoms in neurotoxic vestibulopathy are difficulty with balance, disequilibrium, dizziness, and vertigo. Alongside these balance-related symptoms, many patients also experience fatigue and difficulty with changing focus between tasks, a problem known as accommodative dysfunction. Although less common, oscillopsia is also experienced by some patients as well. These symptoms are also experienced in patients with central vestibulopathy, a similar neurological disorder, but vary highly based on the degree of neuronal damage. If a patient's pharmacological treatment does not cause widespread neuronal damage, the symptoms are significantly less severe than those exhibited by patients who have suffered pharmacologically induced symptoms [1, 2].

 

Causes

    Neurotoxic vestibulopathy is the result of toxin-induced neuronal damage in the brain. The antimalarial drug class known as quinolines can be quite useful in the treatment of malaria, but in a great deal of patients, these drugs have neurotoxic effects on cells in the central nervous system. Depending on which drug is used, certain patients may show greater neurotoxic side-effects. Although thorough studies have not yet been conducted to establish a relationship between approximate dose ranges and corresponding neurotoxic damage, it is known that the most frequent causal drugs are Mefloquine (Lariam), Clioquinol, and Pamaquine [1].
 

Pathophysiology

    When quinolines are used to treat malaria, they can directly impact the functions of the central nervous system through causing neurotoxicity in a number of brain regions. Areas of the brain that are involved in communication with sense organs, mainly the inner ear, are most noticeably affected. These areas include the vestibular nuclei, brainstem, hindbrain, midbrain, and  limbic system. In addition to vestibular difficulties caused by damage to these regions, neurotoxicity can occur in places that are involved in the control of vision, such as the tracts of the visual reflex, as well as in the extrapyramidal system [1].

 

Diagnosis

    There is no single test that can reliably diagnose the disorder on its own. As neurotoxic vestibulopathy is the result of microscopic damage to neurons in the central nervous system, there are no neuroimaging techniques that can accurately identify the disorder as well. Only when an autopsy is performed on a patient can neurotoxic vestibulopathy be confirmed with entire certainty through histopathological examination of damaged brain tissue [1].


 

Treatment

    Since neurotoxic vestibulopathy involves the irreversible damage of neurons, treatments for this disorder are quite limited. There are no specific treatments such as drugs or procedures that can mitigate the effects of the neurotoxicity. However, therapies that aim to placate symptoms by regaining certain vestibular functions may be helpful. Current research focuses on improving the outcome of patients with the disorder through development of novel therapies. Moreover, another primary goal is to gain a better understanding of the relationship between the physical and mental symptoms of neurotoxic vestibulopathy and other disorders, such as PTSD, that are commonly brought about after being in military settings [3].
 

Advocacy and Awareness

    If you would like to find out more information on how to get involved in helping patients with Neurotoxic Vestibulopathy, please contact the following organizations listed below.

Vestibular Disorders Association - https://vestibular.org/

Academy of Neurologic Physical Therapy - http://www.neuropt.org/


Key Terms

Mefloquine (Lariam) - Anti-parasitic drug used to treat and prevent malaria

Malaria Prophylaxis - Preventative treatment of malaria

Quinolines- Aromatic class of drugs made from organic compounds that is used to treat malaria

Disequilibrium - Loss of equilibrium and balance experienced in neurotoxic vestibulopathy

Accommodative Dysfunction - Difficulty or inability to change focus between two or more tasks

Oscillopsia - Optical illusion in which objects appear to be oscillating

Clioquinol - Antifungal drug of the hydroxyquinolines that is a neurotoxin in large doses

Pamaquine- Drug that is used to treat malaria

Vestibular Nuclei- Cranial nuclei of the vestibular nerve in the brainstem

Limbic System - Group of brain structures involved in memory, emotion, motivation, and learning


References


  1. Military Resources: Vestibular Disorders Affect Soldiers and Veterans. (2015) Vestibular Disorders Association. Retrieved January 21, 2017. https://vestibular.org/military

  2. Mccarthy, Stuart. (2015) Malaria Prevention, Mefloquine Neurotoxicity, Neuropsychiatric Illness, and Risk-Benefit Analysis in the Australian Defence Force. Journal of Parasitology Research. Retrieved January 21, 2017. https://www.hindawi.com/journals/jpr/2015/287651/

  3. Nevin, Remington L. (n.d.). Neurotoxic Vestibulopathy: Antimalarial Drugs That Can Cause Vestibular Dysfunction. Retrieved January 21, 2017. https://vestibular.org/sites/default/files/page_files/Documents/Mefloquine_Neurotoxicity.pdf

Christian Gonzalez

Christian Gonzalez


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