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Transient reduced diffusion in the cortex in a child with prolonged febrile seizures
Brain & Development 34 (2012) 773–775 www.elsevier.com/locate/braindev
Case report
Transient reduced diffusion in the cortex in a child with prolonged febrile seizures Toru Kato a,⇑, Akihisa Okumura b, Fumio Hayakawa a, Takeshi Tsuji a, Jun Natsume c b
a Department of Pediatrics, Okazaki City Hospital, Okazaki, Japan Department of Pediatrics and Adolescent Medicine, Juntendo University School of Medicine, Tokyo, Japan c Department of Pediatrics, Nagoya University, Graduate School of Medicine, Nagoya, Japan
Received 5 October 2011; received in revised form 8 December 2011; accepted 13 December 2011
Abstract We report on a 4-year-old boy with transient reduced diffusion in the cortex, thalamus, and hippocampus on diffusion-weighted imaging (DWI) performed after prolonged febrile seizures (PFS). He had experienced intermittent right hemiconvulsions lasting about 90 min during the febrile illness, but his neurological symptom resolved completely after several hours. DWI performed immediately after the PFS showed abnormally high signal intensities in the left extended cortex and pulvinar of the ipsilateral thalamus. Two days later, these DWI lesions resolved completely, but abnormally high signal intensities were observed in the left hippocampus. Three months later, the DWI was normal, and no atrophy or gliosis was seen. This patient had unique lesions on DWI after PFS, but it is nevertheless important to attend to such lesions on the DWI of patients with PFS. Ó 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. Keywords: Diffusion-weighted imaging; Magnetic resonance imaging; Prolonged febrile seizure
1. Introduction Febrile seizures are the most common childhood seizures and occur in association with febrile illnesses in infants and young children. About 6% of these children have prolonged seizures that last longer than 30 min [1]. Commonly, febrile seizures, even if prolonged, have extremely low mortality and morbidity rates [2]. Several recent studies found hippocampal abnormalities, such as high signal intensity or enlargement on conventional magnetic resonance imaging (MRI), in patients within 3–5 days of prolonged febrile seizures (PFS) [3,4]. We previously reported that hyperintensity was seen in the hippocampus and thalamus on diffusion-weighted imaging ⇑ Corresponding author. Address: Department of Pediatrics, Okazaki City Hospital, 3-1, Goshoai, Koryuji-cho, Okazaki, Aichi 444-8553, Japan. Tel.: +81 564 21 8111; fax: +81 564 25 5531. E-mail address: [email protected] (T. Kato).
(DWI) in patients with PFS [5]. However, few reports on abnormalities in the cortex on DWI in children with PFS have been published. We report on a 4-year-old child who showed transiently reduced diffusion in the extended cortex, thalamus, and hippocampus of the affected hemisphere on DWI after PFS. 2. Case report A 4-year-old Japanese boy was admitted to our hospital due to prolonged febrile seizures. He had been healthy until pyrexia developed 2 days before admission. Two months earlier, he had had experienced short febrile seizures twice per day. On admission, he had intermittent clonic hemiconvulsions on the right side that lasted about 90 min; these stopped after the intravenous administration of diazepam. His temperature was 39.5 °C. Adenovirus type 2 was cultured from a throat swab and his stool. The laboratory findings and cerebrospinal
0387-7604/$ - see front matter Ó 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.braindev.2011.12.006
774
T. Kato et al. / Brain & Development 34 (2012) 773–775
fluid examinations were normal. Analyses of amino acids and organic acids produced normal results. His consciousness and neurological signs normalized after several hours. No electroencephalogram (EEG) was obtained during the PFS. One day after the PFS, the EEG showed left hemispheric insertion of high voltage delta activity, but this was normal 3 months later. Eight months after the PFS, he had no epilepsy and no morbidity. Brain MRI was performed using a 1.5-Tesla imager with conventional T1-weighted, T2-weighted, fluidattenuated inversion recovery (FLAIR), DWI, and apparent-diffusion-coefficient (ADC) mapping using a standard protocol. The left frontal, temporal, parietal, and occipital cortices and pulvinar of the left thalamus showed abnormally high signal intensities on the DWI performed immediately after the PFS (Fig. 1a–d). The ADC mapping showed abnormally low signal intensities in the same sites. Other pulse-sequence images were normal. Two days after the PFS, the DWI showed complete resolution in the cortex and thalamus (Fig. 1e, h) but abnormally high signal intensities in the left hippocampus (Fig. 1e). The ADC mapping showed abnormally low signal intensities in the same sites of the left hippocampus. Other pulse-sequence images were normal. All pulse sequences were normal 3 months after the PFS, and no left hippocampal atrophy was seen on visual assessment. 3. Discussion The neuroimaging findings of this patient raise two important issues. Reduced diffusion has been observed on DWI in the cortex, thalamus, and hippocampus of a child with PFS, and these changes can be transient and reversible. In this patient, the abnormally high signal intensities in the cortex, thalamus, and hippocampus on the DWI
Fig. 1. Brain axial diffusion-weighted imaging. Upper row: On admission. Abnormally high intensities can be seen in (a–d) the cortex (arrows), (b) the pulvinar (arrowhead), Lower row: Two days later. (e) The left hippocampus shows abnormally high intensities (arrowhead); (e–h) the thalamus and cortex show no abnormality.
performed during the acute phase after the PFS were unique. Indeed, the literature contains no reports on such abnormalities on the DWI of children with PFS. Scott et al. [6] reported the chronological changes in the quantitative ADC values in the hippocampus in children with PFS using DWI, and found that the ADC values decreased between the acute and followup investigations of children examined within 2 days of a PFS. However, their study did not mention signal abnormalities in the hippocampus on the DWI. We previously reported that three children showed hyperintensities in unilateral hippocampus on DWI among seven children with intractable PFS lasting more than 60 min, and two of them also showed hyperintensities in ipsilateral thalamus [5]. However, abnormal intensity in cortex was not seen. The reason why cortical lesions on DWI were seen in the present patient is unclear, but one explanation may be that DWI was performed immediately after the PFS in this patient. In contrast to the findings in children with PFS, several studies have reported on transiently high signal intensities in the cortex, thalamus, and hippocampus on the DWI of adults with status epileptics. Szabo et al. [7] demonstrated that the hyperintensities in the cortex, pulvinar of the thalamus, or hippocampus were observed in all 10 adult patients with complex partial status epilepticus on peri-ictal DWI. All patients showed partial or complete resolution on follow-up MRI. Di Bonaventura et al. [8] also reported high signal intensities in the cortex, thalamus, or hippocampus on the peri-ictal DWI of all 10 adult patients with partial status epilepticus. They suggested that the DWI abnormality was closely related to the ictal activity. These findings on the DWI of adults with partial status epilepticus were very similar to those of our patient. Therefore, we postulate that the DWI abnormalities seen in our patient were caused by the PFS. In our patient, the DWI abnormalities were transient and resolved completely. His consciousness and neurological signs recovered completely several hours after the PFS, supporting our hypothesis. The PFS induced a transient reduction in diffusion in the cortex, thalamus, and hippocampus in this patient for reasons that remain unclear. One explanation may be that prolonged overactivation of epileptic neurons causes anaerobic glycolysis, a reduction in adenosine triphosphate, and the failure of Na+/K+ adenosine triphosphatase, leading to cytotoxic edema, as suggested by the findings in patients with partial status epilepticus [8]. Another explanation may be that the thalamic nuclei have reciprocal connections with the involved cortex, as seen in the patients with partial status epilepticus [9]. In this patient, the MRI performed 3 months after the PFS was normal on visual assessment, and no epilepsy was observed 8 months after the PFS. Further follow up and more detail volumetric evaluation of the
T. Kato et al. / Brain & Development 34 (2012) 773–775
hippocampus are needed to clarify whether subsequent lesions, such as hippocampal atrophy or mesial temporal sclerosis, develop. In conclusion, we presented a 4-year-old child who showed transient reduced diffusion in the cortex, thalamus, and hippocampus on the DWI performed after PFS. To our knowledge, these lesions are unique to patients with PFS, but it is nevertheless important to attend to such lesions on the DWI of patients with PFS. References [1] Berg AT, Shinnar S. Complex febrile seizures. Epilepsia 1996;37:126–33. [2] Shinnar S, Pellock JM, Berg AT, O’Dell C, Driscoll SM, Maytal J, et al. Short-term outcomes of children with febrile status epilepticus. Epilepsia 2001;42:47–53. [3] Scott RC, Gadian DG, King MD, Chong WK, Cox TC, Neville BG, et al. Magnetic resonance imaging findings within 5 days of status epilepticus in childhood. Brain 2002;125:1951–9.
775
[4] Provenzale JM, Barboriak DP, VanLandingham K, MacFall J, Delong D, Lewis DV. Hippocampal MRI signal hyperintensity after febrile status epilepticus is predictive of subsequent mesial temporal sclerosis. AJR Am J Roentgenol 2008;190:976–83. [5] Natsume J, Bernasconi N, Miyauchi M, Naiki M, Yokotsuka T, Sofue A, et al. Hippocampal volumes and diffusion-weighted image findings in children with prolonged febrile seizures. Acta Neurol Scand 2007;115(s186):25–8. [6] Scott RC, King MD, Gadian DG, Neville BG, Connelly A. Prolonged febrile seizures are associated with hippocampal vasogenic edema and developmental changes. Epilepsia 2006;47:1493–8. [7] Szabo K, Poepel A, Pohlmann-Eden B, Hirsch J, Back T, Sedlaczek O, et al. Diffusion-weighted and perfusion MRI demonstrates parenchymal changes in complex partial status epilepticus. Brain 2005;128:1369–76. [8] Di Bonaventura C, Bonini F, Fattouch J, Mari F, Petrucci S, Carnı` M, et al. Diffusion-weighted magnetic resonance imaging in patients with partial status epilepticus. Epilepsia 2009;50(Suppl. ):45–52. [9] Katramados AM, Burdette D, Patel SC, Schultz LR, Gaddam S, Mitsias PD. Periictal diffusion abnormalities of the thalamus in partial status epilepticus. Epilepsia 2009;50:265–75.
Case report
Transient reduced diffusion in the cortex in a child with prolonged febrile seizures Toru Kato a,⇑, Akihisa Okumura b, Fumio Hayakawa a, Takeshi Tsuji a, Jun Natsume c b
a Department of Pediatrics, Okazaki City Hospital, Okazaki, Japan Department of Pediatrics and Adolescent Medicine, Juntendo University School of Medicine, Tokyo, Japan c Department of Pediatrics, Nagoya University, Graduate School of Medicine, Nagoya, Japan
Received 5 October 2011; received in revised form 8 December 2011; accepted 13 December 2011
Abstract We report on a 4-year-old boy with transient reduced diffusion in the cortex, thalamus, and hippocampus on diffusion-weighted imaging (DWI) performed after prolonged febrile seizures (PFS). He had experienced intermittent right hemiconvulsions lasting about 90 min during the febrile illness, but his neurological symptom resolved completely after several hours. DWI performed immediately after the PFS showed abnormally high signal intensities in the left extended cortex and pulvinar of the ipsilateral thalamus. Two days later, these DWI lesions resolved completely, but abnormally high signal intensities were observed in the left hippocampus. Three months later, the DWI was normal, and no atrophy or gliosis was seen. This patient had unique lesions on DWI after PFS, but it is nevertheless important to attend to such lesions on the DWI of patients with PFS. Ó 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. Keywords: Diffusion-weighted imaging; Magnetic resonance imaging; Prolonged febrile seizure
1. Introduction Febrile seizures are the most common childhood seizures and occur in association with febrile illnesses in infants and young children. About 6% of these children have prolonged seizures that last longer than 30 min [1]. Commonly, febrile seizures, even if prolonged, have extremely low mortality and morbidity rates [2]. Several recent studies found hippocampal abnormalities, such as high signal intensity or enlargement on conventional magnetic resonance imaging (MRI), in patients within 3–5 days of prolonged febrile seizures (PFS) [3,4]. We previously reported that hyperintensity was seen in the hippocampus and thalamus on diffusion-weighted imaging ⇑ Corresponding author. Address: Department of Pediatrics, Okazaki City Hospital, 3-1, Goshoai, Koryuji-cho, Okazaki, Aichi 444-8553, Japan. Tel.: +81 564 21 8111; fax: +81 564 25 5531. E-mail address: [email protected] (T. Kato).
(DWI) in patients with PFS [5]. However, few reports on abnormalities in the cortex on DWI in children with PFS have been published. We report on a 4-year-old child who showed transiently reduced diffusion in the extended cortex, thalamus, and hippocampus of the affected hemisphere on DWI after PFS. 2. Case report A 4-year-old Japanese boy was admitted to our hospital due to prolonged febrile seizures. He had been healthy until pyrexia developed 2 days before admission. Two months earlier, he had had experienced short febrile seizures twice per day. On admission, he had intermittent clonic hemiconvulsions on the right side that lasted about 90 min; these stopped after the intravenous administration of diazepam. His temperature was 39.5 °C. Adenovirus type 2 was cultured from a throat swab and his stool. The laboratory findings and cerebrospinal
0387-7604/$ - see front matter Ó 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.braindev.2011.12.006
774
T. Kato et al. / Brain & Development 34 (2012) 773–775
fluid examinations were normal. Analyses of amino acids and organic acids produced normal results. His consciousness and neurological signs normalized after several hours. No electroencephalogram (EEG) was obtained during the PFS. One day after the PFS, the EEG showed left hemispheric insertion of high voltage delta activity, but this was normal 3 months later. Eight months after the PFS, he had no epilepsy and no morbidity. Brain MRI was performed using a 1.5-Tesla imager with conventional T1-weighted, T2-weighted, fluidattenuated inversion recovery (FLAIR), DWI, and apparent-diffusion-coefficient (ADC) mapping using a standard protocol. The left frontal, temporal, parietal, and occipital cortices and pulvinar of the left thalamus showed abnormally high signal intensities on the DWI performed immediately after the PFS (Fig. 1a–d). The ADC mapping showed abnormally low signal intensities in the same sites. Other pulse-sequence images were normal. Two days after the PFS, the DWI showed complete resolution in the cortex and thalamus (Fig. 1e, h) but abnormally high signal intensities in the left hippocampus (Fig. 1e). The ADC mapping showed abnormally low signal intensities in the same sites of the left hippocampus. Other pulse-sequence images were normal. All pulse sequences were normal 3 months after the PFS, and no left hippocampal atrophy was seen on visual assessment. 3. Discussion The neuroimaging findings of this patient raise two important issues. Reduced diffusion has been observed on DWI in the cortex, thalamus, and hippocampus of a child with PFS, and these changes can be transient and reversible. In this patient, the abnormally high signal intensities in the cortex, thalamus, and hippocampus on the DWI
Fig. 1. Brain axial diffusion-weighted imaging. Upper row: On admission. Abnormally high intensities can be seen in (a–d) the cortex (arrows), (b) the pulvinar (arrowhead), Lower row: Two days later. (e) The left hippocampus shows abnormally high intensities (arrowhead); (e–h) the thalamus and cortex show no abnormality.
performed during the acute phase after the PFS were unique. Indeed, the literature contains no reports on such abnormalities on the DWI of children with PFS. Scott et al. [6] reported the chronological changes in the quantitative ADC values in the hippocampus in children with PFS using DWI, and found that the ADC values decreased between the acute and followup investigations of children examined within 2 days of a PFS. However, their study did not mention signal abnormalities in the hippocampus on the DWI. We previously reported that three children showed hyperintensities in unilateral hippocampus on DWI among seven children with intractable PFS lasting more than 60 min, and two of them also showed hyperintensities in ipsilateral thalamus [5]. However, abnormal intensity in cortex was not seen. The reason why cortical lesions on DWI were seen in the present patient is unclear, but one explanation may be that DWI was performed immediately after the PFS in this patient. In contrast to the findings in children with PFS, several studies have reported on transiently high signal intensities in the cortex, thalamus, and hippocampus on the DWI of adults with status epileptics. Szabo et al. [7] demonstrated that the hyperintensities in the cortex, pulvinar of the thalamus, or hippocampus were observed in all 10 adult patients with complex partial status epilepticus on peri-ictal DWI. All patients showed partial or complete resolution on follow-up MRI. Di Bonaventura et al. [8] also reported high signal intensities in the cortex, thalamus, or hippocampus on the peri-ictal DWI of all 10 adult patients with partial status epilepticus. They suggested that the DWI abnormality was closely related to the ictal activity. These findings on the DWI of adults with partial status epilepticus were very similar to those of our patient. Therefore, we postulate that the DWI abnormalities seen in our patient were caused by the PFS. In our patient, the DWI abnormalities were transient and resolved completely. His consciousness and neurological signs recovered completely several hours after the PFS, supporting our hypothesis. The PFS induced a transient reduction in diffusion in the cortex, thalamus, and hippocampus in this patient for reasons that remain unclear. One explanation may be that prolonged overactivation of epileptic neurons causes anaerobic glycolysis, a reduction in adenosine triphosphate, and the failure of Na+/K+ adenosine triphosphatase, leading to cytotoxic edema, as suggested by the findings in patients with partial status epilepticus [8]. Another explanation may be that the thalamic nuclei have reciprocal connections with the involved cortex, as seen in the patients with partial status epilepticus [9]. In this patient, the MRI performed 3 months after the PFS was normal on visual assessment, and no epilepsy was observed 8 months after the PFS. Further follow up and more detail volumetric evaluation of the
T. Kato et al. / Brain & Development 34 (2012) 773–775
hippocampus are needed to clarify whether subsequent lesions, such as hippocampal atrophy or mesial temporal sclerosis, develop. In conclusion, we presented a 4-year-old child who showed transient reduced diffusion in the cortex, thalamus, and hippocampus on the DWI performed after PFS. To our knowledge, these lesions are unique to patients with PFS, but it is nevertheless important to attend to such lesions on the DWI of patients with PFS. References [1] Berg AT, Shinnar S. Complex febrile seizures. Epilepsia 1996;37:126–33. [2] Shinnar S, Pellock JM, Berg AT, O’Dell C, Driscoll SM, Maytal J, et al. Short-term outcomes of children with febrile status epilepticus. Epilepsia 2001;42:47–53. [3] Scott RC, Gadian DG, King MD, Chong WK, Cox TC, Neville BG, et al. Magnetic resonance imaging findings within 5 days of status epilepticus in childhood. Brain 2002;125:1951–9.
775
[4] Provenzale JM, Barboriak DP, VanLandingham K, MacFall J, Delong D, Lewis DV. Hippocampal MRI signal hyperintensity after febrile status epilepticus is predictive of subsequent mesial temporal sclerosis. AJR Am J Roentgenol 2008;190:976–83. [5] Natsume J, Bernasconi N, Miyauchi M, Naiki M, Yokotsuka T, Sofue A, et al. Hippocampal volumes and diffusion-weighted image findings in children with prolonged febrile seizures. Acta Neurol Scand 2007;115(s186):25–8. [6] Scott RC, King MD, Gadian DG, Neville BG, Connelly A. Prolonged febrile seizures are associated with hippocampal vasogenic edema and developmental changes. Epilepsia 2006;47:1493–8. [7] Szabo K, Poepel A, Pohlmann-Eden B, Hirsch J, Back T, Sedlaczek O, et al. Diffusion-weighted and perfusion MRI demonstrates parenchymal changes in complex partial status epilepticus. Brain 2005;128:1369–76. [8] Di Bonaventura C, Bonini F, Fattouch J, Mari F, Petrucci S, Carnı` M, et al. Diffusion-weighted magnetic resonance imaging in patients with partial status epilepticus. Epilepsia 2009;50(Suppl. ):45–52. [9] Katramados AM, Burdette D, Patel SC, Schultz LR, Gaddam S, Mitsias PD. Periictal diffusion abnormalities of the thalamus in partial status epilepticus. Epilepsia 2009;50:265–75.