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By Joanna K. Nelson MD, Fellow, Division of Infectious Diseases,
Dr. Nelson reports no financial relationships in this field of study
The in vivo antibacterial effect of beta-lactam antibiotics is time-dependent. That is, it depends on the proportion of the inter-dosing interval that the serum concentration of free (non-protein bound) drug
A 52-year-old woman with no significant past medical history presented to Stanford Hospital in July, 2014, with fever and progressive weakness. She had been in her usual state of health until the day prior to admission, when she began to feel fatigued with subjective fevers and "restless legs."
The following day, she had progressive lower extremity weakness such that by evening she was unable to get out of bed. On presentation to the Emergency Department, she complained, in addition to the symptoms noted above, of diffuse headache and mild neck stiffness of two days duration. She denied chills, rigors, nausea, vomiting, rash, diarrhea, dysuria, bowel or bladder incontinence, or paresthesias. Her past medical history was significant only for hyperlipidemia. She was not on any medications, and denied toxic ingestions. She lived in Fresno County, California, and had no significant travel history. She was an avid outdoors-woman, participating in golf, swimming, hiking, and running on a regular basis. She reported occasional interactions with mosquitos but no known bites. She had no other significant exposures.
Physical exam: On initial presentation, her temperature was 38.8 degrees Celsius, heart rate was 90 beats per minute, blood pressure was 132/86, respiratory rate was 16 breaths per minute, and oxygen saturation was 96% on room air. She was a fatigued but nontoxic appearing female. She had shotty cervical lymphadenopathy, but no appreciable meningismus. Her neurologic exam was notable for markedly reduced lower extremity strength with 2/5 strength on right lower extremity and 1/5 on left lower extremity. Her sensation to touch was intact. Patellar reflexes were absent bilaterally. The remainder of her physical exam was normal.
Lab tests/Clinical management: Laboratory values revealed a normal WBC at 4.9/mm3, hemoglobin 11.3 gm/dl, platelets 178,000/ mm3. Her serum creatinine was 0.8 mg/dL and liver function tests were within normal limits. Examination of cerebrospinal fluid (CSF) revealed 0 RBC, 323 WBC/mm3 (84% lymphs, 11% neutrophils, 5% mononuclear cells), glucose 80 mg/dL, and protein 84 mg/dL. CSF Gram stain examination was negative and bacterial culture showed no growth. MRI of the thoracic and lumbar spines showed focal signal abnormality from the conus to T7 vertebra suggestive of an inflammatory process. Electromyography showed decreased motor amplitudes with preserved sensory response and no significant denervation suggestive of central process such as myelitis.
Further workup revealed the following tests to be negative: serum HIV antibody, CSF cryptococcal antigen, serum and CSF Treponemal pallidum screen, CSF coccidioidomycosis immunodiffusion, and CSF HSV PCR. Serum West Nile virus IgM antibody by EIA was positive at 1.26 (normal <0.89), IgG was negative. CSF West Nile virus IgM was inconclusive.
The patient was diagnosed with acute flaccid paralysis secondary to West Nile virus. She was treated with supportive care in addition to administration of intravenous immunoglobulin (IVIG) at a dose of 500 mg/kg IV daily for 4 days. Her weakness remained stable throughout her hospital stay, and she was ultimately discharged to a rehabilitation facility.
West Nile virus is a flavivirus transmitted by Culex mosquitoes. It is the most frequently identified arboviral disease in the United States. Most cases occur during the months of August and September. The majority of patients are asymptomatic when infected, but 20-40% will go on to develop symptoms, usually manifested as a flu-like syndrome. Less than 1% will develop more serious neuroinvasive disease, which can manifest as meningitis, encephalitis, flaccid paralysis or any combination of these three entities.1
Acute flaccid paralysis occurs due to selective damage of anterior horn cells. The paralysis usually progresses quickly and plateaus within hours.1 Unlike Guillain-Barré syndrome, in West Nile poliomyelitis-like illness there is generally minimal to no sensory loss.2 There is minimal data regarding the long term outcome of WNV poliomyelitis-like illness; however, follow up of patients involved in a previous outbreak suggest that about one third have complete recovery, one third have partial recovery, and one third have no improvement.3
Treatment largely consists of supportive care. There are case reports and case series describing improved outcomes in some patients after the administration of IVIG.4,5 IVIG has been shown in mouse models of neuroinvasive West Nile virus to be beneficial if administered early in the course.6 In addition, there are case reports of clinical improvement in immunocompromised patients after IVIG administration.7 Overall, more rigorous controlled trials are needed to draw any conclusions on the benefits of any adjunctive therapies.
Diagnosis: West Nile virus infection with flaccid paralysis.
Acknowledgements: Dr. Brian Blackburn and Dr. Gina Suh also participated in the care of this patient.