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ARTICLES: O. M. Vasconcelos, O. A. Prokhorenko, M. K. Salajegheh, K. F. Kelley, K. Livornese, C. H. Olsen, A. H. Vo, M. C. Dalakas, L. S. Halstead, B. Jabbari, and W. W. Campbell Modafinil for treatment of fatigue in post-polio syndrome: A randomized controlled trial Neurology 2007; 68: 1680-1686 [Abstract] [Full text] [PDF]

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Modafinil for treatment of fatigue in post-polio syndrome: A randomized controlled trial

Richard A. Rison   (9 September 2007)

Reply from the authors

Olavo M. Vasconcelos, Kimbra Kenney, William W. Campbell.   (9 September 2007)

Modafinil for treatment of fatigue in post-polio syndrome: A randomized controlled trial 9 September 2007
Richard A. Rison, Neurology Consultants Medical Group 12291 E. Washington Blvd. Suite #303, Whittier, CA 90606 Send Correspondence to journal: Re: Modafinil for treatment of fatigue in post-polio syndrome: A randomized controlled trial rison{at}usc.edu Richard A. Rison	I read with interest the article by Vasconcelos et al on the use of modafinil for the treatment of fatigue in post-polio syndrome. [1] Like many clinicians caring for post-polio patients, the overall negative results and expanding list of past failures are disappointing. Poliomyelitis has recently been identified as a cause of muscle weakness in patients with West Nile virus (WNV) infection, and a syndrome of acute asymmetric flaccid paralysis (AFP) has been described in numerous patients. [2] This acute asymmetric flaccid paralysis resembles that of the anterior horn cell poliomyelitis seen in polio victims and is often associated with disabling fatigue and frequently hinders physical therapy and rehabilitation efforts. I am unaware of any reported medication trials in WNV-AFP patients for symptomatic relief of disabling fatigue. In the summer of 2003, WNV invaded Southern California and then dispersed to every county in the state. [3,4] Shortly thereafter in my community, we started seeing our first cases of WNV-induced neurologic complaints including monoplegic patients. Following workup on the medical floors including serologies, cerebrospinal fluid analysis, and electrodiagnostic studies, they all eventually completed rehabilitation stays that were plagued with fatigue. I treated with both pyridostigmine and modafinil in varying doses in these patients (n=3) with mixed and overall discouraging results. West Nile virus is the leading cause of arboviral encephalitis in the United States and surveillance data for 2006 suggest a 14% increase in cases of WNV neuroinvasive disease from 2005 and the largest number reported since 2003. [5] Therefore, it is probable that the number of WNV-AFP patients that will increase. Given the overlapping similarities of neuromuscular manifestations in the anterior horn cell poliomyelitis of WNV-AFP and polio/post-polio disease, clinicians should all be aware of and monitor for the development of any “post-West Nile virus” fatigue syndrome. This letter is a call for randomized controlled medication trials in WNV-AFP patients with fatigue as has been so aptly done in post-polio patients. Wishful thinking and my “n=3” aside, perhaps this time the list of failures will be shorter. References 1. Vasconcelos OM, Prokhorenko OA, Salajegheh MK, et al. Modafinil for treatment of fatigue in post-polio syndrome: A randomized controlled trial. Neurology 2007;68;1680-1686. 2. Leis AA, Stokic DS, Webb RM, Slavinski SA, Fratkin J. Clinical spectrum of muscle weakness in human West Nile virus infection. Muscle Nerve 2003;28:302-308. 3. Reisen W, Lothrop H, Chiles R, et al. West Nile virus in California. Emerg Infect Dis. 2004;10:1369-1378. 4. Reisen WK, Fang Y, Lothrop HD, et al. Overwintering of West Nile virus in Southern California. J Med Entomol 2006;43:344-355. 5. West Nile virus activity--United States, 2006 MMWR Morb Mortal Wkly Rep. 2007;56:556-559. Disclosure: The author reports no conflicts of interest.
Reply from the authors 9 September 2007
Olavo M. Vasconcelos, Uniformed Services University 6608 Greyswood Rd, Bethesda, MD 20817, Kimbra Kenney, William W. Campbell. Send Correspondence to journal: Re: Reply from the authors ovasconcelos{at}usuhs.edu Olavo M. Vasconcelos, et al.	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.