JOURNAL OF TROPICAL PEDIATRICS, VOL. 60, NO. 2, 2014
Case Report
Acute Disseminated Encephalomyelitis Presenting with Hypertensive Emergency by Samrat Ganguly, Mousumi Das, and Nilay Ranjan Bagchi Department of Pediatrics, North Bengal Medical College and Hospital, Sushruta Nagar, Siliguri, Darjeeling – 734 012, West Bengal, India Correspondence: Samrat Ganguly, Petua, Subhasgram, Kolkata – 700 148, West Bengal, India. E-mail: .
Key words: ADEM, hypertension, emergency, clonidine, demyelination, CNS
Introduction Acute disseminated encephalomyelitis (ADEM) is an inflammatory insult to the central nervous system, leading to demyelination and manifesting as multifocal neurological deficit, and associated with encephalopathy [1]. The hallmark of ADEM is encephalopathy, with ongoing confusion, irritability and coma. Other clinical manifestations are varied, including lethargy, fever, headache, vomiting, meningeal signs and seizures. Hypertension has rarely been reported in association with ADEM, with only one case report of ADEM presenting with autonomic dysreflexia, hypertension and tachycardia [2]. We report an atypical case of ADEM presenting with severe hypertensive encephalopathy, with demyelination of both cerebrum and spinal cord, which responded to clonidine. Case A 12-year-old girl was admitted with history of persistent headache, irritability and severe body ache for last 10 days. There was history of two episodes of seizure 1 day back. Low grade fever was present in the past 10 days but no history of vomiting, diarrhea, hemorrhagic lesions or any rashes or blurring of vision was obtained. On admission the child was conscious, alert, but irritable. Her weight was 25 kg and height was 130 cm. There were no pallor, icterus, edema and clubbing. Respiratory rate was 28/min with no breathlessness, the trachea was central and percussion of chest and air entry was normal on both sides. Heart rate was 130/min, regular in rhythm, no
murmur was heard. The blood pressure was 130/ 90 mm of Hg. There was no neck rigidity, Kernig’s sign was negative. Muscle tone appeared diminished in all four limbs, power in flexor and extensor muscle groups of both upper and lower limbs were 4/5. Deep tendon reflexes were diminished. Abdominal reflex was present on both sides, but planter response could not be elicited bilaterally. Pupils were normal in size and normally reacting to light. There was no history suggestive of bladder bowel involvement. No focal neurological sign was observed. On the day of admission, the patient suffered another episode of convulsion, which was managed with intravenous lorazepam (0.1 mg/kg) followed by phenytoin (loading dose of 20 mg/kg and maintenance dose of 5 mg/kg in two divided doses). The seizure episode was controlled, but the patient became unconscious and developed fever of 100.4 F and she was transferred to intensive care unit. Blood pressure was recorded to be 160/120 mm of Hg. Inj Furosemide was given at a dose of 1 mg/kg and repeated once at the same dose, but blood pressure remained at the same level. Sodium nitroprusside infusion was started at the rate of 0.5 mg/kg/min and increased in a titrated manner up to 2 mg/kg/min. Blood pressure was not allowed to fall more than 10% in the 1st hour and another 15% in the next 12 h [3]. Complete blood count (CBC), peripheral blood smear was normal. Tests for Malaria parasite, Dengue IgM and IgG antibody, typhoid antigen and Widal test were negative. The patient regained
ß The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected] doi:10.1093/tropej/fmt102 Advance Access published on 10 December 2013
171
Downloaded from http://tropej.oxfordjournals.org/ at East Carolina University on July 11, 2015
Summary We report a 12-year-old girl presenting with acute disseminated encephalomyelitis (ADEM) along with hypertensive emergency. Hypertension persisted for few weeks following recovery and subsided with oral clonidine. Although autonomic instability in ADEM has been reported before, hypertensive emergency was not previously documented as presenting feature of ADEM.
CASE REPORT
consciousness the next day and blood pressure decreased to 120/100 mm of Hg. Na-nitroprusside was slowly tapered and stopped. The next day oral sublingual extended release nifedipine was given at a dose of 5 mg BID (0.5 mg/kg/day). Ophthalmoscopy did not reveal any papilledema. A lumbar puncture with cerebrospinal fluid (CSF) analysis revealed normal pressure, slightly elevated protein content (80 mg/dl), normal glucose content (52 mg/dl), (blood glucose at the time of drawing CSF being 90 mg/dl) and elevated cell count of 100 cell/mm3, with 90% lymphocytes. CSF microscopy and culture did not reveal any bacteria or AFB. CSF ADA level was normal. Next day an MRI was done which revealed multiple small hyper-intense lesions in cortex and subcortical white matter of both cerebral hemispheres suggesting ADEM (Fig. 1). CSF oligoclonal bands (IgG) were negative. Serology for HSV and JE were negative. Patient was administered Methyl prednisolone infusion over 1 h, at a dose of 30 mg/kg/day for 5 days followed by oral prednisolone at a dose of 1 mg/kg/ day for 10 days, with careful monitoring of blood pressure. The administration of corticosteroid did not cause any further increase of blood pressure and no acute elevation was noticed following end of methyl prednisolone infusion. The patient improved by fourth day following admission and regained full power in all four limbs and trunk. She was afebrile and her headache and body ache resolved. She was able to take adequate liquid and semisolid diet orally and her urine output was normal. The blood pressure did not fall below 130/100 mm of Hg, and it was above the 95th percentile for age, sex and height on more than three occasions [4]. 172
FIG. 2. MRI of Spine showing multiple areas of demyelination in C1–5 level.
Urine routine and microscopic examination, ultrasound of kidney, ureter and bladder, doppler ultrasound of renal arteries were normal. Serum urea and creatinine levels were normal. Doppler echocardiography, serum level of cortisol, ACTH, renin and angiotensin-converting enzyme were normal. An MRI of spine was done and patchy demyelination was observed at C1–5 level (Fig. 2). During the course of treatment, oral enalapril was added along with nifedipine, but still the blood pressure was persistently high more than 2 weeks following clinical recovery. Clonidine was given to the patient at a dose of 50 mg thrice daily and gradually the blood pressure declined to baseline. Other antihypertensive were withdrawn and clonidine was tapered. Finally clonidine was withdrawn 15 days after blood pressure returned to normal, about 6 weeks after the onset of the disease. Discussion ADEM is a monophasic inflammatory demyelinating disorder of central nervous system. This condition can affect persons of any age group, but most Journal of Tropical Pediatrics
Vol. 60, No. 2
Downloaded from http://tropej.oxfordjournals.org/ at East Carolina University on July 11, 2015
FIG. 1. MRI of Brain showing multiple areas of demyelination in cortex and subcortical white matter of both cerebral hemispheres.
CASE REPORT
Journal of Tropical Pediatrics
Vol. 60, No. 2
injury, and is characterized by unbalanced sympathetic discharge due to noxious stimuli from a site below the spinal cord lesion. In conclusion, ADEM can cause hypertensive emergency and elevation of blood pressure may persist for few weeks following recovery. Clonidine may be tried in such cases to control hypertension. References 1. Schor NF. Acute disseminated encephalomyelitis (ADEM). In: Kliegmann RM, Bonita FS, Behrman RE (eds). Nelson Textbook of Pediatrics. 19th edn. Philadelphia, PA: WB Saunders, 2011, 2079–80. 2. Jayakrishnan MP, Krishnakumar P, Gauthamen R, et al. Autonomic dysreflexia in acute disseminated encephalomyelitis. Pediatr Neurol 2012;47:309–11. 3. Lande MB. Systemic hypertension. In: Kliegmann RM, Bonita FS, Behrman RE (eds). Nelson Textbook of Pediatrics. 19th edn. Philadelphia, PA: WB Saunders, 2011, 1639–47. 4. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, treatment of high blood pressure in children and adolescents. Pediatrics 2004;114:555–76. 5. Menge T, Hemmer B, Nessler S, et al. Acute disseminated encephalomyelitis: an update. Arch Neurol 2005; 62:1673–80. 6. Leake JA, Albani S, Kao AS, et al. Acute disseminated encephalomyelitis in childhood: epidemiologic, clinical and laboratory features. Pediatr Infect Dis J 2004;23: 756–64. 7. Young NP, Weinshenker BG, Lucchinetti CF. Acute disseminated encephalomyelitis: current understanding and controversies. Semin Neurol 2008;28:84–94. 8. La Mantia L, Erbetta A. Headache and inflammatory disorders of the central nervous system. Neurol Sci 2004;25:148–53. 9. Marchioni E, Tavazzi E, Minoli L, et al. Acute disseminated encephalomyelitis. Neurol Sci 2008;29:286–8. 10. Parker K, Brunton L, Goodman LS, et al. Goodman & Gilman’s – the pharmacological basis of therapeutics. 13th edn. New York: McGraw-Hill, 2006, 854–5.
173
Downloaded from http://tropej.oxfordjournals.org/ at East Carolina University on July 11, 2015
commonly seen among young children, with most series reporting a mean age between 5 and 8 years [1, 5]. The incidence is estimated to be 0.8 per 100 000/year [6]. This condition is thought to occur following a viral or bacterial infection (such as influenza, Epstein–Barr virus, Cytomegalo virus, Varicella, Mycoplasma, etc.), following a vaccination for rabies, measles, mumps, rubella, etc., or without a detectable preceding cause [1, 5]. Apart from encephalopathy, other focal or multifocal manifestations include convulsion, visual loss, cranial neuropathies, ataxia, generalized and symmetric weakness, hemiparesis, sensory deficits, etc. [5–9]. Our case presented with features suggesting ADEM. Hypertension was detected since admission and gradually increased to very high level which was controlled only after nitroprusside infusion. There after blood pressure was controlled with oral clonidine only. Clonidine acts through stimulation of central alpha-2 receptors in the brain stem vasomotor center and decreases sympathetic tone [10]. The basic pathology in ADEM is demyelination in various parts of central nervous system, including brain stem and spinal cord. In our case MRI showed affection of both cerebrum and spinal cord. Blood pressure is regulated through various centers in brainstem and it is possible that demyelination occurred near vasomotor centers in our case, causing dysregulation of blood pressure. Extensive investigations did not reveal any other abnormalities that can lead to the surge of blood pressure. Blood pressure returned to normal in this case and all antihypertensive drugs successfully withdrawn, indicating the patient was normotensive prior to this episode. Jayakrishnan et al. [2] reported an 11-year-old boy with ADEM and spinal cord involvement, presenting with episodes of intense flushing and sweating, confined to the head and neck region along with hypertension and tachycardia. His signs improved after changing a partly blocked bladder catheter. This was different from present case, as autonomic dysreflexia may occurs in any patient with spinal cord
Case Report
Acute Disseminated Encephalomyelitis Presenting with Hypertensive Emergency by Samrat Ganguly, Mousumi Das, and Nilay Ranjan Bagchi Department of Pediatrics, North Bengal Medical College and Hospital, Sushruta Nagar, Siliguri, Darjeeling – 734 012, West Bengal, India Correspondence: Samrat Ganguly, Petua, Subhasgram, Kolkata – 700 148, West Bengal, India. E-mail: .
Key words: ADEM, hypertension, emergency, clonidine, demyelination, CNS
Introduction Acute disseminated encephalomyelitis (ADEM) is an inflammatory insult to the central nervous system, leading to demyelination and manifesting as multifocal neurological deficit, and associated with encephalopathy [1]. The hallmark of ADEM is encephalopathy, with ongoing confusion, irritability and coma. Other clinical manifestations are varied, including lethargy, fever, headache, vomiting, meningeal signs and seizures. Hypertension has rarely been reported in association with ADEM, with only one case report of ADEM presenting with autonomic dysreflexia, hypertension and tachycardia [2]. We report an atypical case of ADEM presenting with severe hypertensive encephalopathy, with demyelination of both cerebrum and spinal cord, which responded to clonidine. Case A 12-year-old girl was admitted with history of persistent headache, irritability and severe body ache for last 10 days. There was history of two episodes of seizure 1 day back. Low grade fever was present in the past 10 days but no history of vomiting, diarrhea, hemorrhagic lesions or any rashes or blurring of vision was obtained. On admission the child was conscious, alert, but irritable. Her weight was 25 kg and height was 130 cm. There were no pallor, icterus, edema and clubbing. Respiratory rate was 28/min with no breathlessness, the trachea was central and percussion of chest and air entry was normal on both sides. Heart rate was 130/min, regular in rhythm, no
murmur was heard. The blood pressure was 130/ 90 mm of Hg. There was no neck rigidity, Kernig’s sign was negative. Muscle tone appeared diminished in all four limbs, power in flexor and extensor muscle groups of both upper and lower limbs were 4/5. Deep tendon reflexes were diminished. Abdominal reflex was present on both sides, but planter response could not be elicited bilaterally. Pupils were normal in size and normally reacting to light. There was no history suggestive of bladder bowel involvement. No focal neurological sign was observed. On the day of admission, the patient suffered another episode of convulsion, which was managed with intravenous lorazepam (0.1 mg/kg) followed by phenytoin (loading dose of 20 mg/kg and maintenance dose of 5 mg/kg in two divided doses). The seizure episode was controlled, but the patient became unconscious and developed fever of 100.4 F and she was transferred to intensive care unit. Blood pressure was recorded to be 160/120 mm of Hg. Inj Furosemide was given at a dose of 1 mg/kg and repeated once at the same dose, but blood pressure remained at the same level. Sodium nitroprusside infusion was started at the rate of 0.5 mg/kg/min and increased in a titrated manner up to 2 mg/kg/min. Blood pressure was not allowed to fall more than 10% in the 1st hour and another 15% in the next 12 h [3]. Complete blood count (CBC), peripheral blood smear was normal. Tests for Malaria parasite, Dengue IgM and IgG antibody, typhoid antigen and Widal test were negative. The patient regained
ß The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected] doi:10.1093/tropej/fmt102 Advance Access published on 10 December 2013
171
Downloaded from http://tropej.oxfordjournals.org/ at East Carolina University on July 11, 2015
Summary We report a 12-year-old girl presenting with acute disseminated encephalomyelitis (ADEM) along with hypertensive emergency. Hypertension persisted for few weeks following recovery and subsided with oral clonidine. Although autonomic instability in ADEM has been reported before, hypertensive emergency was not previously documented as presenting feature of ADEM.
CASE REPORT
consciousness the next day and blood pressure decreased to 120/100 mm of Hg. Na-nitroprusside was slowly tapered and stopped. The next day oral sublingual extended release nifedipine was given at a dose of 5 mg BID (0.5 mg/kg/day). Ophthalmoscopy did not reveal any papilledema. A lumbar puncture with cerebrospinal fluid (CSF) analysis revealed normal pressure, slightly elevated protein content (80 mg/dl), normal glucose content (52 mg/dl), (blood glucose at the time of drawing CSF being 90 mg/dl) and elevated cell count of 100 cell/mm3, with 90% lymphocytes. CSF microscopy and culture did not reveal any bacteria or AFB. CSF ADA level was normal. Next day an MRI was done which revealed multiple small hyper-intense lesions in cortex and subcortical white matter of both cerebral hemispheres suggesting ADEM (Fig. 1). CSF oligoclonal bands (IgG) were negative. Serology for HSV and JE were negative. Patient was administered Methyl prednisolone infusion over 1 h, at a dose of 30 mg/kg/day for 5 days followed by oral prednisolone at a dose of 1 mg/kg/ day for 10 days, with careful monitoring of blood pressure. The administration of corticosteroid did not cause any further increase of blood pressure and no acute elevation was noticed following end of methyl prednisolone infusion. The patient improved by fourth day following admission and regained full power in all four limbs and trunk. She was afebrile and her headache and body ache resolved. She was able to take adequate liquid and semisolid diet orally and her urine output was normal. The blood pressure did not fall below 130/100 mm of Hg, and it was above the 95th percentile for age, sex and height on more than three occasions [4]. 172
FIG. 2. MRI of Spine showing multiple areas of demyelination in C1–5 level.
Urine routine and microscopic examination, ultrasound of kidney, ureter and bladder, doppler ultrasound of renal arteries were normal. Serum urea and creatinine levels were normal. Doppler echocardiography, serum level of cortisol, ACTH, renin and angiotensin-converting enzyme were normal. An MRI of spine was done and patchy demyelination was observed at C1–5 level (Fig. 2). During the course of treatment, oral enalapril was added along with nifedipine, but still the blood pressure was persistently high more than 2 weeks following clinical recovery. Clonidine was given to the patient at a dose of 50 mg thrice daily and gradually the blood pressure declined to baseline. Other antihypertensive were withdrawn and clonidine was tapered. Finally clonidine was withdrawn 15 days after blood pressure returned to normal, about 6 weeks after the onset of the disease. Discussion ADEM is a monophasic inflammatory demyelinating disorder of central nervous system. This condition can affect persons of any age group, but most Journal of Tropical Pediatrics
Vol. 60, No. 2
Downloaded from http://tropej.oxfordjournals.org/ at East Carolina University on July 11, 2015
FIG. 1. MRI of Brain showing multiple areas of demyelination in cortex and subcortical white matter of both cerebral hemispheres.
CASE REPORT
Journal of Tropical Pediatrics
Vol. 60, No. 2
injury, and is characterized by unbalanced sympathetic discharge due to noxious stimuli from a site below the spinal cord lesion. In conclusion, ADEM can cause hypertensive emergency and elevation of blood pressure may persist for few weeks following recovery. Clonidine may be tried in such cases to control hypertension. References 1. Schor NF. Acute disseminated encephalomyelitis (ADEM). In: Kliegmann RM, Bonita FS, Behrman RE (eds). Nelson Textbook of Pediatrics. 19th edn. Philadelphia, PA: WB Saunders, 2011, 2079–80. 2. Jayakrishnan MP, Krishnakumar P, Gauthamen R, et al. Autonomic dysreflexia in acute disseminated encephalomyelitis. Pediatr Neurol 2012;47:309–11. 3. Lande MB. Systemic hypertension. In: Kliegmann RM, Bonita FS, Behrman RE (eds). Nelson Textbook of Pediatrics. 19th edn. Philadelphia, PA: WB Saunders, 2011, 1639–47. 4. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, treatment of high blood pressure in children and adolescents. Pediatrics 2004;114:555–76. 5. Menge T, Hemmer B, Nessler S, et al. Acute disseminated encephalomyelitis: an update. Arch Neurol 2005; 62:1673–80. 6. Leake JA, Albani S, Kao AS, et al. Acute disseminated encephalomyelitis in childhood: epidemiologic, clinical and laboratory features. Pediatr Infect Dis J 2004;23: 756–64. 7. Young NP, Weinshenker BG, Lucchinetti CF. Acute disseminated encephalomyelitis: current understanding and controversies. Semin Neurol 2008;28:84–94. 8. La Mantia L, Erbetta A. Headache and inflammatory disorders of the central nervous system. Neurol Sci 2004;25:148–53. 9. Marchioni E, Tavazzi E, Minoli L, et al. Acute disseminated encephalomyelitis. Neurol Sci 2008;29:286–8. 10. Parker K, Brunton L, Goodman LS, et al. Goodman & Gilman’s – the pharmacological basis of therapeutics. 13th edn. New York: McGraw-Hill, 2006, 854–5.
173
Downloaded from http://tropej.oxfordjournals.org/ at East Carolina University on July 11, 2015
commonly seen among young children, with most series reporting a mean age between 5 and 8 years [1, 5]. The incidence is estimated to be 0.8 per 100 000/year [6]. This condition is thought to occur following a viral or bacterial infection (such as influenza, Epstein–Barr virus, Cytomegalo virus, Varicella, Mycoplasma, etc.), following a vaccination for rabies, measles, mumps, rubella, etc., or without a detectable preceding cause [1, 5]. Apart from encephalopathy, other focal or multifocal manifestations include convulsion, visual loss, cranial neuropathies, ataxia, generalized and symmetric weakness, hemiparesis, sensory deficits, etc. [5–9]. Our case presented with features suggesting ADEM. Hypertension was detected since admission and gradually increased to very high level which was controlled only after nitroprusside infusion. There after blood pressure was controlled with oral clonidine only. Clonidine acts through stimulation of central alpha-2 receptors in the brain stem vasomotor center and decreases sympathetic tone [10]. The basic pathology in ADEM is demyelination in various parts of central nervous system, including brain stem and spinal cord. In our case MRI showed affection of both cerebrum and spinal cord. Blood pressure is regulated through various centers in brainstem and it is possible that demyelination occurred near vasomotor centers in our case, causing dysregulation of blood pressure. Extensive investigations did not reveal any other abnormalities that can lead to the surge of blood pressure. Blood pressure returned to normal in this case and all antihypertensive drugs successfully withdrawn, indicating the patient was normotensive prior to this episode. Jayakrishnan et al. [2] reported an 11-year-old boy with ADEM and spinal cord involvement, presenting with episodes of intense flushing and sweating, confined to the head and neck region along with hypertension and tachycardia. His signs improved after changing a partly blocked bladder catheter. This was different from present case, as autonomic dysreflexia may occurs in any patient with spinal cord
