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A case of post-Japanese encephalitis with partial hypothalamic dysfunction showing repetitive hyperthermia in summertime
Journal of Infection (2006) 52, e143–e146
www.elsevierhealth.com/journals/jinf
CASE REPORT
A case of post-Japanese encephalitis with partial hypothalamic dysfunction showing repetitive hyperthermia in summertime Yoshiko Furiya*, Makito Hirano, Takuya Nakamuro, Hiroshi Kataoka, Satoshi Ueno Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara-city, Nara 634-8521, Japan Accepted 12 August 2005 Available online 25 October 2005
KEYWORDS Japanese encephalitis; Sequelae; Hypothalamus; b-endorphin; Insulin challenge test
Summary Japanese encephalitis (JE) virus is a mosquito-borne virus belonging to the flavivirus family, including the West Nile and St Louis encephalitis viruses endemic to North America. JE virus is prevalent in East Asian countries and can cause acute lethal encephalitis. Although vaccination programs have decreased the incidence of JE in Japan, the cases that do occur are often fatal or associated with considerable clinical sequelae. We report, for the first time to our knowledge, a patient who had repetitive bouts of hyperthermia in the summertime after recovery from acute JE. An insulin challenge test revealed only marginal increases in the levels of b-endorphin and growth hormone, indicating partial medial hypothalamic dysfunction. Magnetic resonance imaging showed T2 hyperintensity in both thalamic paraventricular subcortical regions, known to project to the hypothalamic paraventricular nucleus. We thus attributed the episodes of hyperthermia to secondary hypothalamic impairment with thalamic lesions. Q 2005 The British Infection Society. Published by Elsevier Ltd. All rights reserved.
Introduction Japanese encephalitis (JE) virus is a mosquitoborne virus belonging to the flavivirus family, including the West Nile and St Louis encephalitis viruses endemic to North America. JE virus is prevalent in East Asian countries to cause acute
* Corresponding author. Tel.: C81 744 29 8860; fax: C81 744 29 6065. E-mail address: [email protected] (Y. Furiya).
lethal encephalitis. Approx. 50 000 Asians are annually affected by JE, resulting in high mortality rates (20ÿ40%).1 Survivors of JE often have sequelae such as parkinsonism and involuntary movements,1,2 since the JE virus affects mainly the thalamus, brainstem, basal ganglia, and cerebral cortex.1,3,4 JE virus occasionally enters the anterior horns of the spinal cord, resulting in motor-neuron-disease-like symptoms;5 other symptoms are rare. We report, for the first time to our knowledge, a case of JE associated with repetitive episodes of hyperthermia in the summertime in a survivor who had no
0163-4453/$30.00 Q 2005 The British Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2005.08.012
e144 other evidence of recurrence. Various endocrinological challenge tests revealed partial hypothalamic dysfunction. A possible link between the patient’s symptoms and hypothalamic dysfunction was suggested.
Case report A 49-year-old woman was admitted to our hospital in September 1989 because of loss of consciousness, rough tremor, and a fever of 39.4 8C. She had been healthy until that time and had not been vaccinated for JE virus. She received assisted ventilation with hyperalimentation for 2 weeks. JE was diagnosed on the basis of a four-fold rise in the antibody titre against JE virus in serum and cerebrospinal fluid (CSF) during a 2-week interval. Magnetic resonance imaging (MRI) of the brain bilaterally revealed hypointense lesions on T1weighted images (WI) and hyperintense lesions on T2-WI in the substantia nigra, thalamic paraventricular nucleus, hippocampus, globus pallidus, and periventricular subcortical region. Five months after onset, she could follow simple commands and walked with support, but continued to have bradykinesia, loss of postural reflexes, impaired short-term memory, and retrograde amnesia. Treatment with levodopa (150 mg/day), amantadine hydrochloride (150 mg/day), imipramine hydrochloride (30 mg/day), and droxydopa (300 mg/day) improved her condition. After 6 months she was discharged. Her body weight increased from 54 to 63 kg. The fasting serum glucose level increased from 108 to 215 mg/dl. Despite anti-diabetic medication, the hemoglobin A1c level stabilized at about 8.0% (Fig. 1).
Y. Furiya et al. Two years after onset, the patient was readmitted because of loss of consciousness, a fever of 39.5 8C, and profuse sweating. The neurological findings were similar to those at discharge: Increased muscle tone and magnified deep tendon reflexes in the extremities, but no pathological reflexes. MRI of the brain demonstrated no new lesions; however, diffuse brain atrophy had progressed, especially around the third ventricle. The serum glucose level exceeded 300 mg/dl, and the serum protein level and hematocrit were slightly elevated because of dehydration. Extensive laboratory tests, including cerebrospinal fluid (CSF) analysis, failed to detect any evidence of inflammation, infection, malignancy, or collagen disease. The serum creatine phosphokinase level was normal, excluding the possibility of malignant neuroleptic syndrome. Intravenous infusion of saline solution normalized the serum glucose level, decreased fever, and restored alertness. Since, the initial episode, the patient had had a high fever at least once a week on hot summer days. Recurrence of JE infection was excluded because no JE-virus-specific IgM antibodies were detected in the CSF, and no viral antigen or JE virus was isolated from lymphocytes. Although the causes of the high fever remained unclear, inflammatory or malignant disease was apparently not involved; therefore, only symptomatic treatment was provided for several years. Head-up-tilt testing (100/62 to 90/60) failed to diagnose orthostatic hypotension, and the coefficient of variation of RÿR intervals was within the normal range. The results of nerve conduction studies of the limbs suggested mild diabetic polyneuropathy. Endocrinological tests showed normal concentrations of thyroxin, triiodotyrosine, thyroid stimulating hormone (TSH), cortisol, adrenocorticotropic hormone (ACTH), follicle stimulating hormone, luteinizing stimulating
Figure 1 Magnetic resonance imaging (MRI) of brain. Axial slices (a, b) and coronal slices (c) of T2-weighted images (1.0 T, TR 4500, TE 96), showing bilateral abnormal intensity areas in the thalamus (arrowheads), hippocampus, substantia nigra (arrows), globus pallidus, and white matter around the lateral ventricle. These abnormal lesions showed no changes since 1990, but brain atrophy increased. No abnormal intensity was detected in the hypothalamus.
A case of post-Japanese encephalitis with partial hypothalamic dysfunction
Figure 2 Hormonal challenge test. (a) Combined TRH/CRH challenge test: Before and 30, 60, and 120 min after injection of 500 mg of TRH and 100 mg of CRH. Dots indicate range of normal response. Our patient shows latent hypothalamic hyperprolactinemia and hypersecretion of ACTH and TSH. (b) Insulin challenge test: Before and 30, 60, 90, and 120 min after rapid injection of insulin (5 units). Dots indicate range of normal response. GH: Baseline is below 5 ng/ml and exceeded 10 ng/ml 60 min after injection. Insulin decreased the serum glucose level (BS) to below 50 mg/dl. There were only marginal increases in bendorphin (b-END) and GH.
hormone, adrenaline, noradrenaline, and dopamine. Prolactin (PRL, 16.7 ng/ml; normal 1.4– 14.6 ng/ml) and arginine vasopressin (AVP, 4.46 pg/ml; normal 0.3ÿ4.2 pg/ml) were mildly elevated. A combined thyrotropin-releasing hormone (TRH)/corticotropin-releasing hormone (CRH) test demonstrated hypersecretion of ACTH, TSH, and PRL. An insulin challenge test showed no b-endorphin peak and insufficient secretion of GH, indicating partial hypothalamic dysfunction (Fig. 2). The orexin concentration in CSF was within normal range (259.5 pg/ml, normal O196 pg/ml).6
Discussion In our patient, CRH/TRH and insulin challenge tests revealed partial hypothalamic dysfunction. Hypersecretion of PRL, TSH, and ACTH on CRH/TRH testing indicated that pituitary cells had become
e145
hypersensitive to CRH and TRH, since the endogenous release of these two hormones is decreased by dysfunction of the hypothalamic paraventricular nucleus (PVH). Insufficient secretion of b-endorphin and GH during insulin-induced hypoglycemia suggested partial dysfunction of the hypothalamic ventromedial nucleus (VMH), which harbors glucoreceptors sensitive to hypoglycemia.7 Both of these nuclei are located in the medial part of the hypothalamus. By contrast, the concentration of orexin in CSF, an indicator of the function of the hypothalamic lateral nucleus,8 was normal. These findings suggested that the medial part of the hypothalamic region was selectively impaired in our patient. Partial dysfunction of the medial hypothalamus in our patient might have caused the hyperthermia on hot summer days. This notion is supported by a previous study showing that disruption of the preoptic nucleus and anterior nucleus, located in the medial region of the hypothalamus near the PVH and VMH, increases body temperature on exercise.9 Furthermore, insufficient function of b-endorphin decreased water intake, possibly leading to dehydration and hyperthermia. We, therefore, speculated that hypothalamic dysfunction was responsible for the hyperthermia. Another possible cause of the patient’s hyperthermia, was JE recurrence. JE virus sometimes causes persistent or latent infections in the human nervous system or leucocytes, which then induce recurrent infections.10,11 This possibility is unlikely, however, because there was no evidence of JE-specific IgM antibody in CSF or of JE virus itself, markers of JE recurrence, 10,12 during illness. Other chronic inflammatory diseases, such as collagen disease, were also unlikely, because no clinical signs, symptoms, or autoantibodies were detected. Dopaminergic drugs occasionally cause hyperthermia, generally in association with high serum creatine kinase activity, which was not found in our patient. Furthermore, dopaminergic drugs were continued during and after hyperthermia. Thus, the hyperthermia in our patient was mostly likely not due to side effects of these drugs. The cause of the hypothalamic dysfunction in our patient was unclear; however, it might have been associated with the bilateral thalamic paraventricular lesions. The PVH, which was not functioning normally in our patient, receives afferent input from the thalamic nuclei.13 Thus, secondary hypothalamic impairment may be caused by thalamic lesions. Alternatively, JE virus infection may directly impair the hypothalamus. However, this possibility seems unlikely in our patient because
e146 MRI of the brain showed no signal changes in the hypothalamus. The thalamus is the region most consistently affected by JE virus and other JE group viruses, including the West Nile virus epidemic in North America and Europe,14 tick borne encephalitis virus in eastern Europe,15 and Murray Valley virus in Australia.16 The JE group viruses has common neurotropism leading to similar neurological symptoms and sequelae. Because, JE group viruses are prevalent worldwide and the survival rate of patients has recently increased, physicians should be aware that dysfunction of the hypothalamus possibly due to thalamic lesions may play a role in the clinical manifestations caused by these viruses.
Acknowledgement We thank Dr Tsutomu Takegami of the Medical Research Institute, Kanazawa University for testing for persistent JE viral infection of peripheral lymphocytes, and Dr Takeshi Kanbayashi of the Department of Psychiatry, Akita University for the measurement of orexin concentrations in CSF.
References 1. Burke D, Leake C. Japanese encephalitis. In: Monath TP, editor. The arboviruses: Epidermology and ecology. In: The arboviruses: Epidermology and ecology, vol. 3. Boca Raton, FL, USA: CRC Press; 1998. p. 63–92. 2. Murgod UA, Muthane UB, Ravi V, Radhesh S, Desai A. Persistent movement disorders following Japanese encephalitis. Neurology 2001;57:2313–5.
Y. Furiya et al. 3. Misra UK, Kalita J, Goel D, Mathur A. Clinical, radiological and neurophysiological spectrum of JEV encephalitis and other non-specific encephalitis during post-monsoon period in India. Neurol India 2003;51:55–9. 4. Shoji H, Hiraki Y, Kuwasaki N, Toyomasu T, Kaji M, Okudera T. Japanese encephalitis in the Kurume region of Japan: CT and MRI findings. J Neurol 1989;236:255–9. 5. Misra UK, Kalita J. Anterior horn cells are also involved in Japanese encephalitis. Acta Neurol Scand 1997;96:114–7. 6. Nishino S, Kanbayashi T, Fujiki N, Uchino M, Ripley B, Watanabe M. CSF hypocretin levels in Guillain–Barre syndrome and other inflammatory neuropathies. Neurology 2003;61:823–5. 7. Polinsky RJ, Brown RT, Lee GK, Timmers K, Culman J, Foldes O. Beta-endorphin, ACTH, and catecholamine responses in chronic autonomic failure. Ann Neurol 1987;21:573–7. 8. Gerashchenko D, Murillo-Rodriguez E, Lin L, Xu M, Hallett L, Nishino S. Relationship between CSF hypocretin levels and hypocretin neuronal loss. Exp Neurol 2003;184:1010–6. 9. Hasegawa H, Ishiwata T, Saito T, Yazawa T, Aihara Y, Meeusen R. Inhibition of the preoptic area and anterior hypothalamus by tetrodotoxin alters thermoregulatory functions in exercising rats. J Appl Physiol 2005;98:1458–62. 10. Pradhan S, Gupta RK, Singh MB, Mathur A. Biphasic illness pattern due to early relapse in Japanese-B virus encephalitis. J Neurol Sci 2001;183:13–18. 11. Mathur A, Kulshreshtha R, Chaturvedi UC. Evidence for latency of Japanese encephalitis virus in T lymphocytes. J Gen Virol 1989;70(Pt 2):461–5. 12. Ravi V, Desai AS, Shenoy PK, Satishchandra P, Chandramuki A, Gourie-Devi M. Persistence of Japanese encephalitis virus in the human nervous system. J Med Virol 1993;40:326–9. 13. Roth G, Grunwald W, Dicke U. Morphology, axonal projection pattern, and responses to optic nerve stimulation of thalamic neurons in the fire-bellied toad Bombina orientalis. J Comp Neurol 2003;461:91–110. 14. Rosas H, Wippold 2nd FJ. West Nile virus: Case report with MR imaging findings. AJNR Am J Neuroradiol 2003;24:1376–8. 15. Bender A, Schulte-Altedorneburg G, Walther EU, Pfister HW. Severe tick borne encephalitis with simultaneous brain stem, bithalamic, and spinal cord involvement documented by MRI. J Neurol Neurosurg Psychiatry 2005;76:135–7. 16. Einsiedel L, Kat E, Ravindran J, Slavotinek J, Gordon DL. MR findings in Murray Valley encephalitis. AJNR Am J Neuroradiol 2003;24:1379–82.
www.elsevierhealth.com/journals/jinf
CASE REPORT
A case of post-Japanese encephalitis with partial hypothalamic dysfunction showing repetitive hyperthermia in summertime Yoshiko Furiya*, Makito Hirano, Takuya Nakamuro, Hiroshi Kataoka, Satoshi Ueno Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara-city, Nara 634-8521, Japan Accepted 12 August 2005 Available online 25 October 2005
KEYWORDS Japanese encephalitis; Sequelae; Hypothalamus; b-endorphin; Insulin challenge test
Summary Japanese encephalitis (JE) virus is a mosquito-borne virus belonging to the flavivirus family, including the West Nile and St Louis encephalitis viruses endemic to North America. JE virus is prevalent in East Asian countries and can cause acute lethal encephalitis. Although vaccination programs have decreased the incidence of JE in Japan, the cases that do occur are often fatal or associated with considerable clinical sequelae. We report, for the first time to our knowledge, a patient who had repetitive bouts of hyperthermia in the summertime after recovery from acute JE. An insulin challenge test revealed only marginal increases in the levels of b-endorphin and growth hormone, indicating partial medial hypothalamic dysfunction. Magnetic resonance imaging showed T2 hyperintensity in both thalamic paraventricular subcortical regions, known to project to the hypothalamic paraventricular nucleus. We thus attributed the episodes of hyperthermia to secondary hypothalamic impairment with thalamic lesions. Q 2005 The British Infection Society. Published by Elsevier Ltd. All rights reserved.
Introduction Japanese encephalitis (JE) virus is a mosquitoborne virus belonging to the flavivirus family, including the West Nile and St Louis encephalitis viruses endemic to North America. JE virus is prevalent in East Asian countries to cause acute
* Corresponding author. Tel.: C81 744 29 8860; fax: C81 744 29 6065. E-mail address: [email protected] (Y. Furiya).
lethal encephalitis. Approx. 50 000 Asians are annually affected by JE, resulting in high mortality rates (20ÿ40%).1 Survivors of JE often have sequelae such as parkinsonism and involuntary movements,1,2 since the JE virus affects mainly the thalamus, brainstem, basal ganglia, and cerebral cortex.1,3,4 JE virus occasionally enters the anterior horns of the spinal cord, resulting in motor-neuron-disease-like symptoms;5 other symptoms are rare. We report, for the first time to our knowledge, a case of JE associated with repetitive episodes of hyperthermia in the summertime in a survivor who had no
0163-4453/$30.00 Q 2005 The British Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2005.08.012
e144 other evidence of recurrence. Various endocrinological challenge tests revealed partial hypothalamic dysfunction. A possible link between the patient’s symptoms and hypothalamic dysfunction was suggested.
Case report A 49-year-old woman was admitted to our hospital in September 1989 because of loss of consciousness, rough tremor, and a fever of 39.4 8C. She had been healthy until that time and had not been vaccinated for JE virus. She received assisted ventilation with hyperalimentation for 2 weeks. JE was diagnosed on the basis of a four-fold rise in the antibody titre against JE virus in serum and cerebrospinal fluid (CSF) during a 2-week interval. Magnetic resonance imaging (MRI) of the brain bilaterally revealed hypointense lesions on T1weighted images (WI) and hyperintense lesions on T2-WI in the substantia nigra, thalamic paraventricular nucleus, hippocampus, globus pallidus, and periventricular subcortical region. Five months after onset, she could follow simple commands and walked with support, but continued to have bradykinesia, loss of postural reflexes, impaired short-term memory, and retrograde amnesia. Treatment with levodopa (150 mg/day), amantadine hydrochloride (150 mg/day), imipramine hydrochloride (30 mg/day), and droxydopa (300 mg/day) improved her condition. After 6 months she was discharged. Her body weight increased from 54 to 63 kg. The fasting serum glucose level increased from 108 to 215 mg/dl. Despite anti-diabetic medication, the hemoglobin A1c level stabilized at about 8.0% (Fig. 1).
Y. Furiya et al. Two years after onset, the patient was readmitted because of loss of consciousness, a fever of 39.5 8C, and profuse sweating. The neurological findings were similar to those at discharge: Increased muscle tone and magnified deep tendon reflexes in the extremities, but no pathological reflexes. MRI of the brain demonstrated no new lesions; however, diffuse brain atrophy had progressed, especially around the third ventricle. The serum glucose level exceeded 300 mg/dl, and the serum protein level and hematocrit were slightly elevated because of dehydration. Extensive laboratory tests, including cerebrospinal fluid (CSF) analysis, failed to detect any evidence of inflammation, infection, malignancy, or collagen disease. The serum creatine phosphokinase level was normal, excluding the possibility of malignant neuroleptic syndrome. Intravenous infusion of saline solution normalized the serum glucose level, decreased fever, and restored alertness. Since, the initial episode, the patient had had a high fever at least once a week on hot summer days. Recurrence of JE infection was excluded because no JE-virus-specific IgM antibodies were detected in the CSF, and no viral antigen or JE virus was isolated from lymphocytes. Although the causes of the high fever remained unclear, inflammatory or malignant disease was apparently not involved; therefore, only symptomatic treatment was provided for several years. Head-up-tilt testing (100/62 to 90/60) failed to diagnose orthostatic hypotension, and the coefficient of variation of RÿR intervals was within the normal range. The results of nerve conduction studies of the limbs suggested mild diabetic polyneuropathy. Endocrinological tests showed normal concentrations of thyroxin, triiodotyrosine, thyroid stimulating hormone (TSH), cortisol, adrenocorticotropic hormone (ACTH), follicle stimulating hormone, luteinizing stimulating
Figure 1 Magnetic resonance imaging (MRI) of brain. Axial slices (a, b) and coronal slices (c) of T2-weighted images (1.0 T, TR 4500, TE 96), showing bilateral abnormal intensity areas in the thalamus (arrowheads), hippocampus, substantia nigra (arrows), globus pallidus, and white matter around the lateral ventricle. These abnormal lesions showed no changes since 1990, but brain atrophy increased. No abnormal intensity was detected in the hypothalamus.
A case of post-Japanese encephalitis with partial hypothalamic dysfunction
Figure 2 Hormonal challenge test. (a) Combined TRH/CRH challenge test: Before and 30, 60, and 120 min after injection of 500 mg of TRH and 100 mg of CRH. Dots indicate range of normal response. Our patient shows latent hypothalamic hyperprolactinemia and hypersecretion of ACTH and TSH. (b) Insulin challenge test: Before and 30, 60, 90, and 120 min after rapid injection of insulin (5 units). Dots indicate range of normal response. GH: Baseline is below 5 ng/ml and exceeded 10 ng/ml 60 min after injection. Insulin decreased the serum glucose level (BS) to below 50 mg/dl. There were only marginal increases in bendorphin (b-END) and GH.
hormone, adrenaline, noradrenaline, and dopamine. Prolactin (PRL, 16.7 ng/ml; normal 1.4– 14.6 ng/ml) and arginine vasopressin (AVP, 4.46 pg/ml; normal 0.3ÿ4.2 pg/ml) were mildly elevated. A combined thyrotropin-releasing hormone (TRH)/corticotropin-releasing hormone (CRH) test demonstrated hypersecretion of ACTH, TSH, and PRL. An insulin challenge test showed no b-endorphin peak and insufficient secretion of GH, indicating partial hypothalamic dysfunction (Fig. 2). The orexin concentration in CSF was within normal range (259.5 pg/ml, normal O196 pg/ml).6
Discussion In our patient, CRH/TRH and insulin challenge tests revealed partial hypothalamic dysfunction. Hypersecretion of PRL, TSH, and ACTH on CRH/TRH testing indicated that pituitary cells had become
e145
hypersensitive to CRH and TRH, since the endogenous release of these two hormones is decreased by dysfunction of the hypothalamic paraventricular nucleus (PVH). Insufficient secretion of b-endorphin and GH during insulin-induced hypoglycemia suggested partial dysfunction of the hypothalamic ventromedial nucleus (VMH), which harbors glucoreceptors sensitive to hypoglycemia.7 Both of these nuclei are located in the medial part of the hypothalamus. By contrast, the concentration of orexin in CSF, an indicator of the function of the hypothalamic lateral nucleus,8 was normal. These findings suggested that the medial part of the hypothalamic region was selectively impaired in our patient. Partial dysfunction of the medial hypothalamus in our patient might have caused the hyperthermia on hot summer days. This notion is supported by a previous study showing that disruption of the preoptic nucleus and anterior nucleus, located in the medial region of the hypothalamus near the PVH and VMH, increases body temperature on exercise.9 Furthermore, insufficient function of b-endorphin decreased water intake, possibly leading to dehydration and hyperthermia. We, therefore, speculated that hypothalamic dysfunction was responsible for the hyperthermia. Another possible cause of the patient’s hyperthermia, was JE recurrence. JE virus sometimes causes persistent or latent infections in the human nervous system or leucocytes, which then induce recurrent infections.10,11 This possibility is unlikely, however, because there was no evidence of JE-specific IgM antibody in CSF or of JE virus itself, markers of JE recurrence, 10,12 during illness. Other chronic inflammatory diseases, such as collagen disease, were also unlikely, because no clinical signs, symptoms, or autoantibodies were detected. Dopaminergic drugs occasionally cause hyperthermia, generally in association with high serum creatine kinase activity, which was not found in our patient. Furthermore, dopaminergic drugs were continued during and after hyperthermia. Thus, the hyperthermia in our patient was mostly likely not due to side effects of these drugs. The cause of the hypothalamic dysfunction in our patient was unclear; however, it might have been associated with the bilateral thalamic paraventricular lesions. The PVH, which was not functioning normally in our patient, receives afferent input from the thalamic nuclei.13 Thus, secondary hypothalamic impairment may be caused by thalamic lesions. Alternatively, JE virus infection may directly impair the hypothalamus. However, this possibility seems unlikely in our patient because
e146 MRI of the brain showed no signal changes in the hypothalamus. The thalamus is the region most consistently affected by JE virus and other JE group viruses, including the West Nile virus epidemic in North America and Europe,14 tick borne encephalitis virus in eastern Europe,15 and Murray Valley virus in Australia.16 The JE group viruses has common neurotropism leading to similar neurological symptoms and sequelae. Because, JE group viruses are prevalent worldwide and the survival rate of patients has recently increased, physicians should be aware that dysfunction of the hypothalamus possibly due to thalamic lesions may play a role in the clinical manifestations caused by these viruses.
Acknowledgement We thank Dr Tsutomu Takegami of the Medical Research Institute, Kanazawa University for testing for persistent JE viral infection of peripheral lymphocytes, and Dr Takeshi Kanbayashi of the Department of Psychiatry, Akita University for the measurement of orexin concentrations in CSF.
References 1. Burke D, Leake C. Japanese encephalitis. In: Monath TP, editor. The arboviruses: Epidermology and ecology. In: The arboviruses: Epidermology and ecology, vol. 3. Boca Raton, FL, USA: CRC Press; 1998. p. 63–92. 2. Murgod UA, Muthane UB, Ravi V, Radhesh S, Desai A. Persistent movement disorders following Japanese encephalitis. Neurology 2001;57:2313–5.
Y. Furiya et al. 3. Misra UK, Kalita J, Goel D, Mathur A. Clinical, radiological and neurophysiological spectrum of JEV encephalitis and other non-specific encephalitis during post-monsoon period in India. Neurol India 2003;51:55–9. 4. Shoji H, Hiraki Y, Kuwasaki N, Toyomasu T, Kaji M, Okudera T. Japanese encephalitis in the Kurume region of Japan: CT and MRI findings. J Neurol 1989;236:255–9. 5. Misra UK, Kalita J. Anterior horn cells are also involved in Japanese encephalitis. Acta Neurol Scand 1997;96:114–7. 6. Nishino S, Kanbayashi T, Fujiki N, Uchino M, Ripley B, Watanabe M. CSF hypocretin levels in Guillain–Barre syndrome and other inflammatory neuropathies. Neurology 2003;61:823–5. 7. Polinsky RJ, Brown RT, Lee GK, Timmers K, Culman J, Foldes O. Beta-endorphin, ACTH, and catecholamine responses in chronic autonomic failure. Ann Neurol 1987;21:573–7. 8. Gerashchenko D, Murillo-Rodriguez E, Lin L, Xu M, Hallett L, Nishino S. Relationship between CSF hypocretin levels and hypocretin neuronal loss. Exp Neurol 2003;184:1010–6. 9. Hasegawa H, Ishiwata T, Saito T, Yazawa T, Aihara Y, Meeusen R. Inhibition of the preoptic area and anterior hypothalamus by tetrodotoxin alters thermoregulatory functions in exercising rats. J Appl Physiol 2005;98:1458–62. 10. Pradhan S, Gupta RK, Singh MB, Mathur A. Biphasic illness pattern due to early relapse in Japanese-B virus encephalitis. J Neurol Sci 2001;183:13–18. 11. Mathur A, Kulshreshtha R, Chaturvedi UC. Evidence for latency of Japanese encephalitis virus in T lymphocytes. J Gen Virol 1989;70(Pt 2):461–5. 12. Ravi V, Desai AS, Shenoy PK, Satishchandra P, Chandramuki A, Gourie-Devi M. Persistence of Japanese encephalitis virus in the human nervous system. J Med Virol 1993;40:326–9. 13. Roth G, Grunwald W, Dicke U. Morphology, axonal projection pattern, and responses to optic nerve stimulation of thalamic neurons in the fire-bellied toad Bombina orientalis. J Comp Neurol 2003;461:91–110. 14. Rosas H, Wippold 2nd FJ. West Nile virus: Case report with MR imaging findings. AJNR Am J Neuroradiol 2003;24:1376–8. 15. Bender A, Schulte-Altedorneburg G, Walther EU, Pfister HW. Severe tick borne encephalitis with simultaneous brain stem, bithalamic, and spinal cord involvement documented by MRI. J Neurol Neurosurg Psychiatry 2005;76:135–7. 16. Einsiedel L, Kat E, Ravindran J, Slavotinek J, Gordon DL. MR findings in Murray Valley encephalitis. AJNR Am J Neuroradiol 2003;24:1379–82.