We appreciate Dr. Rison’s interest in our article. [1] We are also disappointed with the negative results of clinical trials for fatigue in patients with post-polio syndrome (PPS). Dr. Rison points out the overlapping similarities of the fatigue experienced by survivors of poliomyelitis and West Nile virus infection. Moreover, he stresses the difficulties with managing fatigue in both patient populations, and relates his discouraging results with pyridostigmine and modafinil in West Nile virus survivors.
We agree with Dr. Rison that fatigue is a vexing problem in a myriad of diseases. We also sympathize with clinicians challenged with treating fatigue associated with chronic disorders such as post-polio syndrome or post-West Nile virus infections. As mentioned, the prevalence of West Nile virus infection survivors seems to be increasing in certain areas of the United States. [5]
It is conceivable that community neurologists will care for a growing number of survivors, particularly those patients who are debilitated by the asymmetric flaccid paralysis (AFP) form of the disease. [2] AFP closely resembles poliomyelitis and is often followed by incapacitating fatigue that significantly hinders patients’ function.
As pointed out by Dr. Rison, the clinical similarity between the two conditions suggests a common mechanism for fatigue. Unfortunately, the pathophysiology of fatigue in PPS and West Nile virus is still unclear. Fatigue in these patients appears to result from processes involving multiple domains of function.
Specifically, the neuromuscular fatigue likely originates from different pathophysiological etiologies. In PPS, it is hypothesized that fatigue results from "exhausted neurons that have been chronically overtaxed as a result of axonal sprouting after loss of neighboring motor neurons". [6] In patients with PPS, disabling fatigue starts several decades after recovery. [7] It manifests after a long latent period.
The fatigue associated with West Nile virus infection manifests immediately after the acute ailment, missing the latent element so unique in PPS. Consequently, it suggests the etiology of this motor fatigue would be different for reasons that are yet unknown.
In conclusion, the direct insult to anterior horn cells in Polio and West Nile virus infections suggests a basic pathway for fatigue. The mechanism(s) underlying fatigue in both conditions are only partially understood. In PPS, this may explain why previous hypothesis-driven therapeutic trials failed.
Further research is necessary in order to elucidate the pathways driving symptoms of fatigue, a necessary step for the development of effective therapies.
References
6. Cashman NR, Trojan DA. Correlation of electrophysiology with pathology, pathogenesis, and anticholinesterase therapy in post-polio syndrome. Ann N Y Acad Sci 1995; 753:138-150.
7. Dalakas MC. The post-polio syndrome as an evolved clinical entity. Definition and clinical description. Ann N Y Acad Sci 1995; 753:68-80.
Disclosure: The authors report no conflicts of interest.
We appreciate Dr. Rison’s interest in our article. [1] We are also disappointed with the negative results of clinical trials for fatigue in patients with post-polio syndrome (PPS). Dr. Rison points out the overlapping similarities of the fatigue experienced by survivors of poliomyelitis and West Nile virus infection. Moreover, he stresses the difficulties with managing fatigue in both patient populations, and relates his discouraging results with pyridostigmine and modafinil in West Nile virus survivors.
We agree with Dr. Rison that fatigue is a vexing problem in a myriad of diseases. We also sympathize with clinicians challenged with treating fatigue associated with chronic disorders such as post-polio syndrome or post-West Nile virus infections. As mentioned, the prevalence of West Nile virus infection survivors seems to be increasing in certain areas of the United States. [5]
It is conceivable that community neurologists will care for a growing number of survivors, particularly those patients who are debilitated by the asymmetric flaccid paralysis (AFP) form of the disease. [2] AFP closely resembles poliomyelitis and is often followed by incapacitating fatigue that significantly hinders patients’ function.
As pointed out by Dr. Rison, the clinical similarity between the two conditions suggests a common mechanism for fatigue. Unfortunately, the pathophysiology of fatigue in PPS and West Nile virus is still unclear. Fatigue in these patients appears to result from processes involving multiple domains of function.
Specifically, the neuromuscular fatigue likely originates from different pathophysiological etiologies. In PPS, it is hypothesized that fatigue results from "exhausted neurons that have been chronically overtaxed as a result of axonal sprouting after loss of neighboring motor neurons". [6] In patients with PPS, disabling fatigue starts several decades after recovery. [7] It manifests after a long latent period.
The fatigue associated with West Nile virus infection manifests immediately after the acute ailment, missing the latent element so unique in PPS. Consequently, it suggests the etiology of this motor fatigue would be different for reasons that are yet unknown.
In conclusion, the direct insult to anterior horn cells in Polio and West Nile virus infections suggests a basic pathway for fatigue. The mechanism(s) underlying fatigue in both conditions are only partially understood. In PPS, this may explain why previous hypothesis-driven therapeutic trials failed.
Further research is necessary in order to elucidate the pathways driving symptoms of fatigue, a necessary step for the development of effective therapies.
References
6. Cashman NR, Trojan DA. Correlation of electrophysiology with pathology, pathogenesis, and anticholinesterase therapy in post-polio syndrome. Ann N Y Acad Sci 1995; 753:138-150.
7. Dalakas MC. The post-polio syndrome as an evolved clinical entity. Definition and clinical description. Ann N Y Acad Sci 1995; 753:68-80.
Disclosure: The authors report no conflicts of interest.