Case Review Journal of CLINICAL NEUROMUSCULAR DISEASE 113 Volume 12, Number 3 March 2011 Posterior Reversible Encephalopathy Syndrome Resulting From Guillain-Barré-Like Syndrome Secondary to West Nile Virus Infection Alon Abraham, MD,* Sari Ziv, MD,† and Vivian E. Drory, MD*‡ Abstract A 67-year-old woman developed hypertension, drowsiness, hemianopia, ascending flaccid tetraparesis, and areflexia. Nerve conduction studies revealed a demyelinating polyneuropathy. Brain magnetic resonance imaging demonstrated hyperintense white matter lesions. IgM antibodies against West Nile virus were positive. She was treated for hypertension and with intravenous immunoglobulins and recovered completely within 2 months. To our knowledge, this is the first case in which West Nile virus infection presented as posterior reversible encephalopathy syndrome associated with Guillain-Barré-like syndrome. Key Words: West Nile virus, posterior reversible encephalopathy syndrome, Guillain-Barré-like syndrome, polyneuropathy, hypertension ( J Clin Neuromusc Dis 2011;12:113–117) CASE REPORT A 67–year-old, previously healthy woman was admitted with shoulder and back pain that lasted for 3 days. The patient had a febrile illness with diarrhea 2 weeks previously. At admission, she was drowsy and had unspecific generalized weakness. Her vital signs were normal apart of elevated blood pressure of 190/90 mmHg. On neurologic examination she was drowsy without signs of meningeal irritation, had left homonymous hemianopia, and mild paraparesis. Deep tendon reflexes were absent in all extremities. There was no sensory disturbance. On ophthalmologic examination a few hours later, she had nearly complete bilateral cortical blindness with maintained light perception. Her blood count was normal besides a mild neutrophilic leukocytosis. Her sodium level was decreased to 127 mEq/L; the plasma and urine osmolality levels were consistent with a syndrome of inappropriate secretion of antidiuretic hormone. There was mild hypokalemia of 3.4 and her C-reactive protein was 20. Thyroid function tests were normal. A brain computed tomography scan on the day of admission showed hypodensities in both occipital lobes suspected to be of ischemic origin. Brain and neck computed tomography angiography did not demonstrate any arterial dissection or thrombosis. Thoracic computed tomography angiography did not show aortic dissection. A lumbar puncture showed elevated protein of 131 mg/dL with normal cerebrospinal fluid glucose and no cells. Polymerase chain reaction for herpes simplex virus was negative. Within hours after admission she developed a peripheral facial diplegia and a progressive ascending flaccid paralysis with disturbed proprioception. She was somnolent yet arousable, hypertensive with systolic blood pressure of 210 mmHg, and had a severe headache and shoulder and back pain. An electroencephalogram revealed bilateral temporal slowing. A subsequent brain magnetic resonance image (Fig 1) demonstrated multiple bilateral hyperintense signals on T2 and fluidattenuated inversion recovery mostly in the occipital and parietal white matter bilaterally, not enhanced by gadolinium, consistent with posterior reversible encephalopathy (PRES). The patient was started on titrated intravenous sodium nitroprusside for control of her hypertension. Progressive muscle From the Departments of *Neurology and †Internal Medicine, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; and ‡Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Reprints: Alon Abraham, MD, Department of Neurology, TelAviv Sourasky Medical Center, 6 Weizmann Street, Tel-Aviv 64239, Israel (e-mail: alonabmail@gmail.com). Copyright Ó 2011 by Lippincott Williams & Wilkins 114 Journal of CLINICAL NEUROMUSCULAR DISEASE Abraham et al Volume 12, Number 3 March 2011 FIGURE 1. Brain magnetic resonance image demonstrating multiple hyperintense signals on T2 and fluid-attenuated inversion recovery, mostly in the occipital and parietal white matter bilaterally, not enhanced by gadolinium. weakness, lack of tendon reflexes, and elevated protein raised the possibility of Guillain-Barré syndrome (GBS). A nerve conduction study done 2 days after admission showed a sensory and motor polyneuropathy with prominent demyelination of most distal and proximal segments as seen usually in early GBS (Table 1): prolonged distal latencies in all nerves examined (right median, ulnar, peroneal, and tibial) and prolonged F-wave latencies in the upper limb with sural nerve sparing. Needle electromyography was not performed as a result of the early timing of the examination. She was started on a 5-day course of intravenous immunoglobulins on a 0.4-g/kg per day dose. After 3 days of intravenous sodium nitroprusside her blood pressure was almost normalized and the medication was switched to an oral combination of beta- TABLE 1. Nerve Conduction Studies Performed 2 Days After Onset of Weakness Motor Nerve and Site Latency Median nerve R Wrist 7.6 ms Elbow 12.1 ms Ulnar nerve R Wrist 5.3 ms Below elbow 9.4 ms Peroneal nerve L Ankle 6.9 ms Fibular head 13.5 ms Tibial nerve L Ankle 7.7 ms Popliteal fossa 19.0 ms Sural nerve L Sensory Amplitude Conduction velocity 2.4 mV 2.4 mV 42 m/s 3.9 mV 2.8 mV 51 m/s 1.4 mV 1.2 mV 42 m/s 1.3 mV 0.7 mV 37 m/s Ó 2011 Lippincott Williams & Wilkins F-wave Latency 33.9 ms Absent 33.1 ms Absent Amplitude 53.3 ms Absent 3.2 ms 11 mV PRES Resulting From GBS Secondary to WNV blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors. The mental status and the cortical blindness improved dramatically 2 days after her admission. Visual fields on computerized examination were intact; however, she continued to experience visual hallucinations (with intact visual perception). Muscle weakness improved gradually, and 12 days after her admission, she was already able to walk unassisted. While the patient was recovering, serologic tests for West Nile virus (WNV) were received positive for the presence of IgM antibodies in serum. The patient was discharged home after 3 weeks with mild weakness in all extremities (4/5 throughout), marked improvement in her facial muscle strength, and a normal mental status. One month after discharge she reported complete resolution of all symptoms. DISCUSSION WNV is an arthropod-borne flavivirus belonging to the Japanese encephalitis subgroup. The WNV is the most widespread of the flaviviruses with geographic distribution in Africa, West Asia, Europe, and the Middle East,1 including Israel which is endemic for WNV.2 West Nile fever has an incubation period of 5 to 15 days. Most people who become infected with WNV remain asymptomatic. Clinical illness is characterized by a flu-like syndrome including myalgia, arthralgia, headache, conjunctivitis, lymphadenopathy, and a maculopapular or roseolar rash. Occasionally pancreatitis, myocarditis, and hepatitis occur, especially in persons older than age 50 years.3 Approximately one of 150 patients develops nervous system manifestations, including meningitis, encephalitis, and a poliomyelitis-like acute flaccid paralysis syndrome. Risk factors for neuroinvasive disease include older age and immunosuppression. Magnetic resonance imaging changes include cauda equina enhancement and parenchymal spinal cord signal abnormalities and parenchymal or leptomeningeal signal changes in the brain. Cerebrospinal fluid findings include pleocytosis, elevated protein, and normal to decreased glucose.4,5 The diagnosis is made in most patients by serologic examination. Reverse transcription polymerase chain reaction tests are useful to screen blood products and for surveillance of birds and mosquitoes.6 In addition, various neuromuscular diseases with a presumed autoimmune mechanism have been described as a complication of WNV infection, eg, myasthenia gravis, brachial plexopathies, and stiff-person syndrome.7 GBS was described only in very few patients with WNV infection.8–10 The diagnosis of GBS in our patient was based on a characteristic clinical presentation of acute symmetric ascending flaccid paralysis and facial diplegia, areflexia, and proprioceptive sensory loss with a fast and full recovery and was supported by a lumbar puncture that showed elevated protein of 131 mg/dL with normal cerebrospinal fluid glucose and no cells and by the nerve conduction study that showed a demyelinating sensory and motor polyneuropathy. The syndrome is therefore different from the much more frequent acute flaccid paralysis of WNV infection secondary to anterior horn involvement.11 A clinical diagnosis of PRES includes the presence of headache, seizures, encephalopathy, and visual disturbances as well as radiologic findings of focal reversible vasogenic edema, best seen on magnetic resonance imaging of the brain. The syndrome is most commonly encountered in association with acute hypertension, preeclampsia or eclampsia, renal disease, sepsis, and exposure to immunosuppressants. Until recently it has been infrequently described in the setting of autoimmune disease, but lately a substantial proportion of patients affected by underlying autoimmune and inflammatory conditions have been described in a series of patients with PRES.12 The prognosis is generally favorable with complete recovery within a few days.13 The diagnosis of PRES in our patient was based on a typical clinical presentation of drowsiness, headache, left homonymous www.jcnmd.com Journal of CLINICAL NEUROMUSCULAR DISEASE Volume 12, Number 3 March 2011 115 116 Journal of CLINICAL NEUROMUSCULAR DISEASE Volume 12, Number 3 March 2011 Abraham et al hemianopia with acute hypertension, and a brain magnetic resonance image demonstrating multiple bilateral hyperintense signals on T2 and fluid-attenuated inversion recovery mostly in the occipital and parietal white matter bilaterally, not enhanced by gadolinium. The pathophysiology of PRES, although not completely understood, points to two main risk factors: hypertension and autonomic dysfunction.14 There are two possible etiologies for hypertension and autonomic dysfunction leading to PRES in our patient. First, GBS is occasionally associated with both hypertension and dysautonomia. Almost two thirds of patients who have GBS have transient hypertension.15 Second, GBS is an inflammatory peripheral neuropathy with increased levels of cytokines in serum and cerebrospinal fluid.16 This inflammatory process may have a role in PRES by changing capillary permeability. The high percentage of patients with PRES who have autoimmune disorders may support the theory that PRES is in part caused by endothelial dysfunction, a process in which the host autoimmune response is essential.17,18 Another possible explanation that we cannot rule out for the development of PRES in our patient is WNV infection itself, even without associated GBS. A possible mechanism could be endothelial cell activation and damage by an inflammatory cytokine response to WNV infection and/or autonomic instability. Although anterior horns are the major site of spinal cord pathology in cases of WNV infection with neuromuscular involvement, inflammatory changes may also involve spinal sympathetic neurons and ganglia,7 providing an explanation for the autonomic instability seen in some patients with WNV infection. It should be emphasized, however, that as far as we know, PRES has not been described as one of the complications of autonomic instability with hypertension in these patients. The cerebral abnormalities seen clinically and radiologically in our patient point to PRES and not to the much more common viral encephalitis seen with WNV infections, because the patient had no cerebrospinal fluid pleocytosis and the localization of the Ó 2011 Lippincott Williams & Wilkins magnetic resonance imaging findings was characteristic for PRES, and not for WNV encephalitis, in which more diffuse white matter changes involving also anterior brain areas were reported.19 In conclusion, to the best of our knowledge, this is the first report of WNV infection complicated by GBS and PRES. Although PRES was described in association with GBS, even as an initial manifestation,20 we cannot rule out the possibility that WNV itself caused, or at least contributed to, PRES development in our patient and thereby add to the growing list of etiologies or conditions associated with PRES. REFERENCES 1. Hubalek Z, Halouzka J. West Nile fever: a reemerging mosquito-borne viral disease in Europe. 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Kieseir BC, Tani M, Mahad D, et al. Chemokines and chemokine receptors in inflammatory demyelinating neuropathies: a central role for IP-10. Brain. 2002; 125:823–834. 17. Dekker GA, Sibai BM. Etiology and pathogenesis of preeclampsia: current concepts. Am J Obstet Gynecol. 1998;179:1359–1375. 18. Aird WC. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood. 2003;101:3765–3777. 19. Ali M, Safriel Y, Sohi J, et al. West Nile virus infection: MR imaging findings in the nervous system. AJNR Am J Neuroradiol. 2005;26: 289–297. 20. Elahi A, Kelkar P, St Louis EK. Posterior reversible encephalopathy syndrome as the initial manifestation of Guillain-Barré syndrome. Neurocrit Care. 2004;1:465–468. www.jcnmd.com Journal of CLINICAL NEUROMUSCULAR DISEASE Volume 12, Number 3 March 2011 117