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Letters to the Editor
437
Post-H1N1 vaccine acute disseminated encephalomyelitis Michele Michelin Becker, Josiane Ranzan, Luiza VS Magalhães, Lygia Ohlweiler, Maria Isabel Winckler, Michele Sampedro Ramos and Rudimar Riesgo Department of Pediatrics, Child Neurology Center, Clinical Hospital of Porto Alegre, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune demyelinating disorder of the central nervous system (CNS) that affects mainly children. Typically it happens after an infection and rarely after vaccination, with compromise of the white matter of the brain and/or spinal cord,1,2 characterized by a rapid development of encephalopathy in combination with multifocal and extremely varied neurological deficits. Brain and spinal cord magnetic resonance imaging (MRI) show disseminated demyelization in the CNS. Cerebrospinal fluid (CSF) examination can demonstrate unspecific alterations.3 We report the case of a previously healthy 8-year-old boy, who had fever, headache and somnolence 12 days after the first dose of vaccine against influenza H1N1. There was no previous history of infection or other vaccines in the previous 30 days, as well as no evidence of ongoing influenza H1N1 infection. The CSF was a crystalline fluid with 45 leukocytes/μL with 100% monocytes, glucose 62 mg/dL, and proteins 27 mg/dL. No infectious pathogens were identified in the blood or in the CSF. The patient had clinical seizures controlled with i.v. diazepam, became aphasic, and developed left hemiparesis. Electroencephalogram indicated slowing background activity with multifocal spikes and one electrographic seizure, after which i.v. phenytoin was initiated. He was transferred to the intensive care unit (ICU) due to coma and necessity of mechanical ventilation and did not have metabolic abnormalities. He was discharged from ICU with residual neurologic deficits, such as aphasia, paresis of extrinsic ocular muscles and ataxia. Brain MRI was compatible with ADEM (Fig. 1). Spine MRI showed no lesion. I.v. methylprednisolone pulse therapy (30 mg/kg per day) was given for 5 days, followed by 4 weeks of oral prednisone (2 mg/kg per day). The patient was discharged from hospital after 30 days. During follow up, a complete remission of symptoms occurred. According to the World Health Organization, in 2009 approximately 40 countries started national campaigns of vaccination against influenza A. Nearly 80 million doses of H1N1 vaccine were distributed and 65 million people were vaccinated. In this sense, rigorous surveillance of side-effects is necessary to establish the vaccine safety.4 ADEM usually occurs after unspecific viral upper respiratory airway infection. Only 5% are post-vaccine cases, more freCorrespondence: Rudimar Riesgo, MD PhD, Av. Juca Batista 8.000, Casa 415–91780-000 – Porto Alegre, RS, Brasil. Email: rriesgo@ hcpa.ufrgs.br Received 3 May 2011; revised 11 January 2013; accepted 20 May 2013. doi: 10.1111/ped.12148
quently after vaccination against measles, rubella and mumps.2 Only two case reports of ADEM after vaccine against H1N1 have been identified on publication database search.5,6 Obviously, vaccines are considered safe and provide one of the most cost-effective treatments. Vaccination campaigns have prevented thousands of deaths and disabling consequences, allowing the eradication of some diseases. In contrast, the worrying side-effects, although rare, must be promptly described in order to prevent undesirable events. Even recognizing that this is a description of a single case as well as that the causal association between this vaccine and the neurological alterations could not be totally proved, to our knowledge this paper represents the third description of a case of ADEM identified after H1N1 influenza vaccine. In the present case, early identification and treatment of ADEM were sufficient to ensure complete neurological recovery.
Fig. 1 Brain T1 magnetic resonance imaging showing several multifocal hyperintense areas in the cerebral white matter. © 2014 The Authors Pediatrics International © 2014 Japan Pediatric Society
438
Letters to the Editor
References 1 Tenembaum SN. Disseminated encephalomyelitis in children. Clin. Neurol. Neurosurg. 2008; 110: 928–38. 2 Huynh W, Cordato DJ, Kehdi E, Masters LT, Dedousis C. Postvaccination encephalomyelitis: Literature review and illustrative case. J. Clin. Neurosci. 2008; 15: 1315–22. 3 Tenembaum S, Chitnis JN, Hahn JS. Acute disseminated encephalomyelitis. Neurology 2007; 68 (16 Suppl. 2): S23–36. 4 World Health Organization. Global Alert and Response (GAR). Safety of pandemic vaccines. Pandemic (H1N1) 2009 briefing note
16. 2009 11_19_2009 [Cited 07/03/2012.] Available from URL: http://www.who.int/csr/disease/swineflu/notes/briefing_20091119/ en/ 5 Lee ST, Choe YJ, Moon WJ, Choi JW, Lee R. An adverse event following 2009 H1N1 influenza vaccination: A case of acute disseminated encephalomyelitis. Korean J. Pediatr. 2011; 54: 422–4. 6 Fujii K, Suyama M, Chiba K, Okunushi T, Oikawa J, Kohono Y. Acute disseminated encephalomyelitis following 2009 H1N1 influenza vaccine. Pediatr. Int. 2012; 54: 539–41.
Screening for anemia: Is this ready for prime time? Mark J Rice, Nikolaus Gravenstein and Timothy E Morey Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida, USA
In their study regarding the use of a non-invasive hemoglobin (Hb) measurement device for screening children for anemia, Amano and Murakami concluded that “. . . this device offers many possibilities in the context of primary screening.”1 We believe that these possibilities need to be carefully considered for the following reasons. When comparing the gold standard Hb measurement (Microsemi® LC-667CRP; Fukuda Denshi, Tokyo, Japan) and the non-invasive device (Radical-7® Pulse CO-Oximeter; Masimo, Irvine, CA, UA), the authors appropriately constructed a Bland–Altman analysis. In the results, however, they state “Using this method, 95.3% of the measurements fell within the limits of agreement.” This is not a statement of results, but rather a statement of fact regarding basic statistics. By definition, the 95% limits of agreement bound the bias by 95%. Therefore, approximately 95% of the data points must fall within these limits and this statement does not inform the reader about the accuracy of the device. In table 1 of the article, the limits of agreement are noted to be between −2.76 and + 1.56 g/dL. This
means that 95% of the data as measured by the non-invasive device were within a spread of 4.32 g/dL when compared to the traditional method. This is not accurate, unless one considers that being within approximately 20% of the actual number (95% of the time) for anemia screening is sufficiently accurate. Additionally, the authors state that “The bias was not significantly different from 0.” Although it may sound like a bias of zero suggests an accurate device, it is in fact a poor metric for accuracy. A bias of zero merely points out that an approximately equal number of data points are above and below zero by the same amount.2 We agree that there is only a moderate correlation between the non-invasive technology and a corresponding “wet” lab value. We applaud the design used by Amano and Murakami in assessing the accuracy of a non-invasive Hb device,1 but we suggest that the statistical discussion of these data needs further examination.
Correspondence: Mark J Rice, MD, Department of Anesthesiology, University of Florida College of Medicine, 1600 SW Archer Road, PO Box 100254, Gainesville, FL 32610, USA. Email: [email protected] .edu Received 18 February 2014; accepted 26 March 2014. doi: 10.1111/ped.12358
1 Amano I, Murakami A. Use of non-invasive total hemoglobin measurement as a screening tool for anemia in children. Pediatr. Int. 2013; 55: 803–5. 2 Morey TE, Gravenstein N, Rice MJ. Assessing point-of-care hemoglobin measurement: Be careful we don’t bias with bias. Anesth. Analg. 2011; 113: 1289–91.
© 2014 Japan Pediatric Society
References
Letters to the Editor
437
Post-H1N1 vaccine acute disseminated encephalomyelitis Michele Michelin Becker, Josiane Ranzan, Luiza VS Magalhães, Lygia Ohlweiler, Maria Isabel Winckler, Michele Sampedro Ramos and Rudimar Riesgo Department of Pediatrics, Child Neurology Center, Clinical Hospital of Porto Alegre, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune demyelinating disorder of the central nervous system (CNS) that affects mainly children. Typically it happens after an infection and rarely after vaccination, with compromise of the white matter of the brain and/or spinal cord,1,2 characterized by a rapid development of encephalopathy in combination with multifocal and extremely varied neurological deficits. Brain and spinal cord magnetic resonance imaging (MRI) show disseminated demyelization in the CNS. Cerebrospinal fluid (CSF) examination can demonstrate unspecific alterations.3 We report the case of a previously healthy 8-year-old boy, who had fever, headache and somnolence 12 days after the first dose of vaccine against influenza H1N1. There was no previous history of infection or other vaccines in the previous 30 days, as well as no evidence of ongoing influenza H1N1 infection. The CSF was a crystalline fluid with 45 leukocytes/μL with 100% monocytes, glucose 62 mg/dL, and proteins 27 mg/dL. No infectious pathogens were identified in the blood or in the CSF. The patient had clinical seizures controlled with i.v. diazepam, became aphasic, and developed left hemiparesis. Electroencephalogram indicated slowing background activity with multifocal spikes and one electrographic seizure, after which i.v. phenytoin was initiated. He was transferred to the intensive care unit (ICU) due to coma and necessity of mechanical ventilation and did not have metabolic abnormalities. He was discharged from ICU with residual neurologic deficits, such as aphasia, paresis of extrinsic ocular muscles and ataxia. Brain MRI was compatible with ADEM (Fig. 1). Spine MRI showed no lesion. I.v. methylprednisolone pulse therapy (30 mg/kg per day) was given for 5 days, followed by 4 weeks of oral prednisone (2 mg/kg per day). The patient was discharged from hospital after 30 days. During follow up, a complete remission of symptoms occurred. According to the World Health Organization, in 2009 approximately 40 countries started national campaigns of vaccination against influenza A. Nearly 80 million doses of H1N1 vaccine were distributed and 65 million people were vaccinated. In this sense, rigorous surveillance of side-effects is necessary to establish the vaccine safety.4 ADEM usually occurs after unspecific viral upper respiratory airway infection. Only 5% are post-vaccine cases, more freCorrespondence: Rudimar Riesgo, MD PhD, Av. Juca Batista 8.000, Casa 415–91780-000 – Porto Alegre, RS, Brasil. Email: rriesgo@ hcpa.ufrgs.br Received 3 May 2011; revised 11 January 2013; accepted 20 May 2013. doi: 10.1111/ped.12148
quently after vaccination against measles, rubella and mumps.2 Only two case reports of ADEM after vaccine against H1N1 have been identified on publication database search.5,6 Obviously, vaccines are considered safe and provide one of the most cost-effective treatments. Vaccination campaigns have prevented thousands of deaths and disabling consequences, allowing the eradication of some diseases. In contrast, the worrying side-effects, although rare, must be promptly described in order to prevent undesirable events. Even recognizing that this is a description of a single case as well as that the causal association between this vaccine and the neurological alterations could not be totally proved, to our knowledge this paper represents the third description of a case of ADEM identified after H1N1 influenza vaccine. In the present case, early identification and treatment of ADEM were sufficient to ensure complete neurological recovery.
Fig. 1 Brain T1 magnetic resonance imaging showing several multifocal hyperintense areas in the cerebral white matter. © 2014 The Authors Pediatrics International © 2014 Japan Pediatric Society
438
Letters to the Editor
References 1 Tenembaum SN. Disseminated encephalomyelitis in children. Clin. Neurol. Neurosurg. 2008; 110: 928–38. 2 Huynh W, Cordato DJ, Kehdi E, Masters LT, Dedousis C. Postvaccination encephalomyelitis: Literature review and illustrative case. J. Clin. Neurosci. 2008; 15: 1315–22. 3 Tenembaum S, Chitnis JN, Hahn JS. Acute disseminated encephalomyelitis. Neurology 2007; 68 (16 Suppl. 2): S23–36. 4 World Health Organization. Global Alert and Response (GAR). Safety of pandemic vaccines. Pandemic (H1N1) 2009 briefing note
16. 2009 11_19_2009 [Cited 07/03/2012.] Available from URL: http://www.who.int/csr/disease/swineflu/notes/briefing_20091119/ en/ 5 Lee ST, Choe YJ, Moon WJ, Choi JW, Lee R. An adverse event following 2009 H1N1 influenza vaccination: A case of acute disseminated encephalomyelitis. Korean J. Pediatr. 2011; 54: 422–4. 6 Fujii K, Suyama M, Chiba K, Okunushi T, Oikawa J, Kohono Y. Acute disseminated encephalomyelitis following 2009 H1N1 influenza vaccine. Pediatr. Int. 2012; 54: 539–41.
Screening for anemia: Is this ready for prime time? Mark J Rice, Nikolaus Gravenstein and Timothy E Morey Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida, USA
In their study regarding the use of a non-invasive hemoglobin (Hb) measurement device for screening children for anemia, Amano and Murakami concluded that “. . . this device offers many possibilities in the context of primary screening.”1 We believe that these possibilities need to be carefully considered for the following reasons. When comparing the gold standard Hb measurement (Microsemi® LC-667CRP; Fukuda Denshi, Tokyo, Japan) and the non-invasive device (Radical-7® Pulse CO-Oximeter; Masimo, Irvine, CA, UA), the authors appropriately constructed a Bland–Altman analysis. In the results, however, they state “Using this method, 95.3% of the measurements fell within the limits of agreement.” This is not a statement of results, but rather a statement of fact regarding basic statistics. By definition, the 95% limits of agreement bound the bias by 95%. Therefore, approximately 95% of the data points must fall within these limits and this statement does not inform the reader about the accuracy of the device. In table 1 of the article, the limits of agreement are noted to be between −2.76 and + 1.56 g/dL. This
means that 95% of the data as measured by the non-invasive device were within a spread of 4.32 g/dL when compared to the traditional method. This is not accurate, unless one considers that being within approximately 20% of the actual number (95% of the time) for anemia screening is sufficiently accurate. Additionally, the authors state that “The bias was not significantly different from 0.” Although it may sound like a bias of zero suggests an accurate device, it is in fact a poor metric for accuracy. A bias of zero merely points out that an approximately equal number of data points are above and below zero by the same amount.2 We agree that there is only a moderate correlation between the non-invasive technology and a corresponding “wet” lab value. We applaud the design used by Amano and Murakami in assessing the accuracy of a non-invasive Hb device,1 but we suggest that the statistical discussion of these data needs further examination.
Correspondence: Mark J Rice, MD, Department of Anesthesiology, University of Florida College of Medicine, 1600 SW Archer Road, PO Box 100254, Gainesville, FL 32610, USA. Email: [email protected] .edu Received 18 February 2014; accepted 26 March 2014. doi: 10.1111/ped.12358
1 Amano I, Murakami A. Use of non-invasive total hemoglobin measurement as a screening tool for anemia in children. Pediatr. Int. 2013; 55: 803–5. 2 Morey TE, Gravenstein N, Rice MJ. Assessing point-of-care hemoglobin measurement: Be careful we don’t bias with bias. Anesth. Analg. 2011; 113: 1289–91.
© 2014 Japan Pediatric Society
References
