![](https://webarchive.library.unt.edu/eot2008/20090117131329im_/http://www.cdc.gov/ncidod/eid/images/spacer.gif)
|
![](https://webarchive.library.unt.edu/eot2008/20090117131329im_/http://www.cdc.gov/ncidod/eid/images/spacer.gif) |
Letter
Rift Valley Fever Encephalitis
Abdulrahman A. Alrajhi,* Abdulaziz Al-Semari,* and Jehad Al-Watban*
*King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
Suggested citation
for this article:
Alrajhi AA, Al-Semari A, Al-Watban J. Rift Valley fever encephalitis.
Emerg Infect Dis [serial online] 2004 Mar [date cited] Available
from: http://www.cdc.gov/ncidid/EID/vol10no3/02-0817.htm
To the Editor: Rift Valley fever (RVF) is an undifferentiated
febrile illness caused by Rift Valley fever virus (RVFV). Several human
outbreaks occurred in Africa, resulting in tens of thousands of infections
(1,2). During fall 2000, an outbreak of RVF in the Arabian
Peninsula (the first recorded outside of Africa) resulted in many human
and animal fatalities (3,4). Severe and frequently fatal
encephalitis thought to be directly related to viral invasion of the central
nervous system develops in <1% of patients (5). Encephalitis
complicating RVF is poorly described in the literature, which offers no
detailed description of the clinical findings, results of cerebrospinal
fluid (CSF) studies, or imaging. We describe a case of RVF encephalitis
associated with retinitis, including CSF findings, viral culture results,
and neuroradiology findings
An 18-year-old woman from Jazan (southwest of Saudi Arabia) had a 3-day
history of confusion, fever, and blurred vision at the time an RVF outbreak
was peaking in Jazan. Philadelphia-chromosome–positive chronic myeloid
leukemia (CML) had been diagnosed in her several months before (leukocyte
count 108 x 109/L). She responded well to hydroxyurea, and
she had been in stable-phase CML for a few months. At the time of her
visit, her temperature was 39.2°C, blood pressure 110/70 mm Hg, pulse
120 beats/min, respiratory rate 22/min. She had no lymphadenopathy, pallor,
or jaundice. Results of her head, neck, and throat examinations were normal.
Her chest was clear, and her abdomen was soft and nontender. Her spleen
was 3 cm below the left costal margin. She was conscious and oriented.
No meningeal signs could be elicited. Pupils were equally reactive to
light with normal extraocular movements. Extremities had normal tone,
power, sensation, and reflexes. Plantar reflex was flexor bilaterally.
She had ataxic gait and bilateral retinal hemorrhages. She was unable
to count fingers. Hemoglobin was 100 g/L, leukocyte count 5.1 x 109/L,
and platelets 373 x 109/L. Renal and liver function tests were
normal. Contrast-enhanced computed tomography (CT) scan of the brain was
normal. Urine analysis and malaria smear were negative. CSF was clear.
CSF glucose was 3.9 mmol/L (serum 5.8), protein 455 mg/L. CSF leukocyte
count was 323 x 106/L, 58% lymphocytes, and 38% polynuclearleukocytes.
Tests for hepatitis B surface antigen, antibodies to hepatitis C virus,
HIV, cytomegalovirus antigenemia, rheumatoid factor, and antinuclear antibodies
were negative. Cultures from blood, CSF, and urine were negative for bacteria.
CSF viral culture was negative. Polymerase chain reaction for herpes simplex
virus and enterovirus from CSF was negative. Tests for serum anti-RVF
virus immunoglobulin M were positive. No other tests for RVFV were performed.
Bone marrow on admission day was consistent with CML in remission. Prednisone
was started on admission for 7 days.
On hospital day 5, the patient was noted to be agitated, confused, and
unresponsive to commands. She was transferred to the intensive care unit
after her level of consciousness decreased; she was moving all four limbs
but did not respond to verbal commands or painful stimuli. Pupils were
5 mm equal bilaterally with a sluggish reaction to light. Corneal reflexes
were reactive bilaterally. Gag reflex was present, and tone was increased
in all four limbs with brisk reflexes and extensor planter responses.
The next day, her condition deteriorated, and she became unresponsive
to painful stimuli. Repeated CT scan of the brain showed no pathologic
changes. Electroencephalogram showed generalized continuous rhythmic sharp
and spike wave activity consistent with nonconvulsive status epilepticus.
Magnetic resonance imaging (MRI) of the brain showed bilateral frontoparietal
high signal intensity on T2-weighted images and evidence of subtle right
posterior thalamic hyperintensity with no corresponding abnormalities
in T1-weighted images. The axial diffusion MRI images were more elaborative,
showing multiple bilateral asymmetrical cortical hyperintense areas consistent
with an ischemic or inflammatory process. Phenytoin was started. The next
day, the patient was able to open her eyes and responded to painful stimuli,
corneal reflexes were present bilaterally, oculocephalic reflex was present,
and planters were flexors bilaterally. Repeat CSF studies on day 30 showed
glucose of 3.8 mmol/L, protein 431 mg/L, leukocyte count of 12 x 106/L,
and 68% polynuclearleukocytes. Repeat CT scan of the brain showed new
bilateral temporo-occipital hypodensity more on the left side and a probable
right middle cerebellar and left thalamic internal capsule infarct. There
was no intracranial hemorrhage or hydrocephalus. She was discharged home
awake, blind, quadreparetic, and incontinent, on anticonvulsants. After
1 year, her neurologic condition had not changed.
Encephalitis and retinitis are severe complications of RVF, developing
1 or 2 weeks into the course of diseases. By that time, RVFV antigen assay
is negative. Our patient met the definition of an RVF case during the
outbreak (3). In one outbreak in Mauritania, 4.9% of
observed infections had encephalitis (6), although the
true frequency of encephalitis in RVF may be overestimated because infection
can go unrecognized. The literature contains limited clinical description
of this syndrome (6–8). Detailed neuroimaging findings,
including MRI and flow studies, have not been previously reported. These
findings, along with the patient’s clinical signs and symptoms, suggest
cerebral vasculitis; however, no angiogram was performed, and markers
of vasculitis were negative. A more likely cause would be direct viral
parenchymal invasion.
The pathogenesis of RVF encephalitis in humans is not clear. Animal studies
indicate that active viral replication and necrotizing encephalitis with
diffuse perivascular infiltrates of lymphocytes and macrophages occur
in cerebral parenchyma (9,10). Postmortem histopathologic
examination of brains of fatally infected rhesus monkeys have shown a
mild, nonsuppurative, multifocal, perivascular encephalitis in the cerebral
cortex, primarily of lymphoplasmacytic cells and nodular aggregates of
neutrophils in association with mild necrotic changes of neurons (11).
In one patient who died of meningoencephalitis in South Africa, brain
pathologic findings showed perivascular cuffing and round-cell infiltration
(2). In humans, we are not aware of positive RVFV cultures
from CSF, blood, or brain during encephalitis. We have no reason to suspect
CML to influence disease manifestations in this patient. CML was in stable
phase for several months and should not have affected immune response
of the patient towards RVFV.
Acknowledgment
We appreciate the
contribution of Thomas Ksiazek for the tests for serum anti-RVFV immunoglobulin
M.
References
- Laughlin LW, Meegan JM, Strausbaugh LJ, Morens DM,
Watten RH. Epidemic
Rift Valley fever in Egypt: observations of the spectrum of human illness.
Trans R Soc Trop Med Hyg 1979;73:630–3.
- McIntosh BM, Russell D, dos Santos I, Gear JH. Rift
Valley fever in humans in South Africa. S Afr Med J 1980;58:803–6.
- Centers for Disease Control and Prevention. Outbreak
of Rift Valley fever—Saudi Arabia, August–October. MMWR Morb Mortal
Wkly Rep 2000;49:905–8.
- Ahmad K. More
deaths from Rift Valley fever in Saudi Arabia and Yemen. Lancet
2000;356:1422.
- Peters CJ. California encephalitis, hantavirus pulmonary syndrome
and bunyavirid hemorrhagic fevers. In: Mandell GL, Dolin R, Bennett
JE, editors. Principles and practice of infectious diseases. 5th ed.
New York: Churchill Livingstone; 2000. p. 1849–954.
- Riou O, Philippe B, Jouan A, Coulibaly I, Mondo M, Digoutte JP. Neurologic
and neurosensory forms of Rift Valley fever in Mauritania. Bull
Soc Pathol Exot Filiales 1989;82:605–10.
- Maar SA, Swanepoel R, Gelfand M. Rift
Valley fever encephalitis. A description of a case. Cent Afr J Med
1979;25:8–11.
- Laughlin LW, Girgis NI, Meegan JM, Strausbaugh LJ, Yassin MW, Watten
RH. Clinical
studies on Rift Valley fever. Part 2: Ophthalmologic and central nervous
system complications. J Egypt Public Health Assoc 1978;53:183–4.
- Anderson GW Jr, Slone TW Jr, Peters CJ. The
gerbil, Meriones unguiculatus, a model for Rift Valley fever
viral encephalitis. Arch Virol 1988;102:187–96.
- Rippy MK, Topper MJ, Mebus CA, Morrill JC. Rift
Valley fever virus-induced encephalomyelitis and hepatitis in calves.
Vet Pathol 1992;29:495–502.
- Morrill JC, Jennings GB, Johnson AJ, Cosgriff TM,
Gibbs PH, Peters CJ. Pathogenesis
of Rift Valley fever in rhesus monkeys: role of interferon response.
Arch Virol 1990;110:195–212.
|