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Hyperthermia Associated with Bilateral Mesencephalothalamic Infarction
Case Report
Hyperthermia Associated with Bilateral Mesencephalothalamic Infarction Murat Alemdar, MD
Central hyperthermia is characterized by the rapid onset of high body temperature, marked temperature fluctuation, and high mortality. It is usually associated with brainstem damage caused by direct destruction or indirect compression. Herein, we report a 79-year-old man with bilateral paramedian mesencephalothalamic infarction presenting with hyperthermia. On admission, his body temperature was 39.3 C aurically. Motor or sensorial deficit was not present. He was hospitalized at the infectious disease service. Upon the suspicious history and the absence of any infectious source on laboratory investigations, he was sent to our department on his first day of hospitalization. This case shows that upper paramedian mesencephalic and/or thalamic structures play a major role in the regulation of body temperature and that infarctions involved these structures could present with central hyperthermia. The history of this case also impresses the necessity of physicians’ awareness about the central causes of hyperthermia, particularly in patients with the rapid onset of high temperature with marked fluctuation. Key Words: Hyperthermia— mesencephalon—thalamus—thermoregulation. Ó 2012 by National Stroke Association
Thermoregulation is a vital process directed by the central nervous system through endocrine, autonomic, and behavioral mechanisms in humans. Hyperthermia is a thermoregulation defect without a change of set point of body temperature, whereas fever indicates an increased set point with intact thermoregulation. Central hyperthermia is characterized by the rapid onset of high body temperature with marked fluctuation. Hyperthermia is associated with a poorer prognosis in stroke.1 The later it occurs within the first week poststroke, the
From the Department of Neurology, Toyotasa First Aid and Traumatology Hospital, Sakarya, Turkey. Received July 2, 2011; revision received August 6, 2011; accepted August 9, 2011. Address correspondence to Murat Alemdar, MD, Department of Neurology, Toyotasa First Aid and Traumatology Hospital, Sakarya, Turkey. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2012 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2011.08.003
poorer the prognosis. Aggressive measures to prevent and treat hyperthermia could improve the clinical outcomes in patients with acute ischemic stroke.2 Central hyperthermia is usually associated with brainstem (mainly pons) damage by direct destruction or indirect compression.3 The severity of stroke and inflammation are important determinants of hyperthermia after ischemic stroke.2,4 In most cases, it does not occur as a sole symptom, but rather presents in concert with other neurologic symptoms, like lateralizing motor or sensorial deficits.5 Herein, we report on a patient with bilateral paramedian mesencephalothalamic infarction presenting with hyperthermia and impaired orientation.
Case Report A 79-year-old man was admitted to the emergency room with the complaint of hyperthermia and impaired orientation. The hyperthermia begun abruptly, leading to impaired orientation. On admission, his body temperature was 39.3 C aurically. Other vital signs were normal.
Journal of Stroke and Cerebrovascular Diseases, Vol. 21, No. 8 (November), 2012: pp 907.e13-907.e15
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Table 1. Measures of the patients body temperature Day Admission
Time
20:30 00:30 1 06:30 07:20 08:00 09:30 10:00 14:00 23:00 2 08:30 13:30 16:00 18:30 22:00 3 08:00 18:00 4 08:00 19:00 5 (discharge) 08:00
Temperature, C (aurically)
Service
39.3* 36.4 39.3* 38.4 38.2 38.4 36.7 36.8 37.3 37.0 37.2 37.5 36.7 36.7 36.5 36.4 36.4 36.9 36.7
Emergency room Infectious disease Infectious disease Infectious disease Infectious disease Infectious disease Infectious disease Infectious disease Neurology Neurology Neurology Neurology Neurology Neurology Neurology Neurology Neurology Neurology Neurology
*Intravenous paracetamol was administered twice when the patient’s body temperture was .39 C.
He was hospitalized at the infectious disease service. Intravenous paracetamol was administered twice when his body temperture was .39 C (Table 1). Upon the suspicious history and the absence of any infectious source on laboratory investigations, he was sent to our department on his first day of hospitalization.
The physical examination revealed that the patient was conscious. He was not oriented to time, place, or person, but he was able to follow some 1-step commands with verbal orders. Spontaneous speech was present with insignificant sentences. His pupils were equal with a normal reaction to light. Oculocephalic and oculocaloric reflexes were preserved. The patient was not fully cooperated to the ocular movement examination. However, we did not detect any disturbance during the primary gaze and voluntary ocular movements. He could localize the painful stimuli. The Babinsky sign was negative bilaterally. There were no associated involuntary movements of any body parts. The patient did not have dyshidrosis. He had a history of hypertension and coronary artery disease for 10 years. Benign prostate hypertrophy was diagnosed 2 years ago. He had no history of stroke, convulsion, developmental delay in childhood, or history of neurotrauma. There was no family history of neurologic disease. A complete blood cell count (CBC), urine analysis, and a chest radiograph were all normal. Therefore, a possible infection was eliminated. Electrocardiography revealed a right bundle branch block. Cardiac enzymes, biochemical parameters, and hormone levels were normal. A magnetic resonance imaging (MRI) scan of the brain was obtained. It revealed bilateral paramedian mesencephalothalamic infarction. Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping were also performed. These regions were hyperintense on DWI and hypointense on ADC relative to the brain (Fig 1). Electrocardiography and cardiac enzyme measurements taken on his second day in the hospital did not reveal
Figure 1. Bilateral paramedian mesencephalothalamic infarction (arrows) is seen as hyperintense on diffusion-weighted imaging (A) and hypointense on apparent diffusion coefficient mapping (B). These regions are also seen as hyperintense on coronal T1-weighted images (C) and hyperintense on sagittal T2-weighted images (D) on magnetic resonance imaging scans.
HYPERTHERMIA AND BILATERAL MESENCEPHALOTHALAMIC INFARCTION
any changes. Measurements of blood pressure and heart rate were normal. Echocardiography did not detect any source of emboli. It showed only a mild tricuspid insufficiency. MRI angiography was normal. Acetyl salicylic acid (100 mg/day) was initiated for secondary prevention. The patient healed progressively. The body temperature was normal after the second day. His cooperation and orientation was complete on the third day. On the fifth day poststroke, antiplatelet treatment was prescribed and he was discharged. A neurologic examination was completely normal during the outpatient clinic visit 1 month after discharge.
Discussion Central hyperthermia is characterized by the rapid onset of high body temperature, marked temperature fluctuation, and high mortality. A recent analysis of 74 patients who developed hyperthermia ($39 C) within 24 hours after stroke onset revealed that the most common cause was brainstem hemorrhage (64%), followed by putaminothalamus hemorrhage (24%), cerebellum hemorrhage (4%), large cortical infarction (4%), basilar artery occlusion (3%), and intraventricular hemorrhage (1%).3 These pathologies usually present with other neurologic symptoms, such as impaired consciousness and motor or sensorial deficits. This case revealed only impaired orientation as a neurologic sign; therefore, the diagnosis of a cerebral infarction was delayed. Absence of the accompanying motor or sensorial deficits could cause diagnostic difficulties in central hyperthermia, as in this case. Hyperthermia, in acute ischemic stroke, is associated with a poor clinical outcome. Hyperthermic patients with total anterior circulation infarct, posterior circulation infarct, and supratentorial hemorrhage were reported as associated with a marked increase of 3 months’ mortality.5 The prognosis was good in this case in spite of a posterior circulation infarct, possibly because of the relatively small volume of damaged tissue and preservation of vital structures. Central hyperthermia is still an unresolved riddle. There is little information about its pathophysiology and anatomic correlates in the current literature. Several centers in the brain have been proposed as maintaining and stabilizing body temperature. One of the first regions of the brain to be linked with this process was the preoptic area, which includes temperature-sensitive neurons and receives and integrates input from ascending neural pathways carrying information derived from sensory receptors in the periphery.6 In previous observations, hyperthermia was associated with brainstem (mainly pons) damage by direct destruction or indirect compression.3 Human research with functional MRI also revealed that human rostral medullary raphe neurons are selectively activated in response to a thermoregulatory
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challenge and point to the location of thermoregulatory neurons homologous to those of the raphe pallidus nucleus in rodents.7 The hypothalamus is also known to play a major role in thermoregulation in humans.4,6 However, the infarction in this case did not include or compress the pons, medulla, or hypothalamus. One of possible explanations of hyperthermia in this case is that the damaged region interrupted the communications between the hypothalamus and thermoregulatory neurons in the brainstem. Therefore, hypothalamic regulation of body temperature failed. In an animal study, hyperthermia was observed in rats after the prepontine cut but not after the postmammillary cut, indicating a tonic inhibitory system that would be located somewhere between the lower midbrain and the upper pons.8 The hyperthermia observed in this case may result from the presence of such a system in humans. However, the damaged region in this case includes the upper part of midbrain. Additional studies or observations are needed to understand whether the upper paramedian mesencephalic region is a part of this tonic inhibitory system. In conclusion, this case shows that upper paramedian mesencephalic and/or thalamic structures play a major role in the regulation of body temperature. Mesencephalothalamic infarctions could present with central hyperthermia. The history of this case also impresses the necessity of physicians’ awareness about the central causes of hyperthermia, particular in patients with rapid onset of high temperature with marked fluctuation.
References 1. Castillo J, D avalos A, Noya M. Aggravation of acute ischemic stroke by hyperthermia is related to an excitotoxic mechanism. Cerebrovasc Dis 1999;9:22-27. 2. Saini M, Saqqur M, Kamruzzaman A, Lees KR, Shuaib A. VISTA Investigators. Effect of hyperthermia on prognosis after acute ischemic stroke. Stroke 2009;40:3051-3059. 3. Sung CY, Lee TH, Chu NS. Central hyperthermia in acute stroke. Eur Neurol 2009;62:86-92. 4. Konaka K, Miyashita K, Ishibashi-Ueda H, Naritomi H. Severe hyperthermia caused by four-vessel occlusion of main cerebral arteries. Intern Med 2009;48:2137-2140. 5. Kumral E, Tarlaci S, Acarer A. Effect of etiology and topography of lesion on body temperature at stroke onset. J Stroke Cerebrovasc Dis 2001;10:150-156. 6. Toni R, Malaguti A, Benfenati F, Martini L. The human hypothalamus: A morpho-functional perspective. J Endocrinol Invest 2004;27(6 Suppl):73-94. 7. McAllen RM, Farrell M, Johnson JM, Trevaks D, Cole L, McKinley MJ, et al. Human medullary responses to cooling and rewarming the skin: A functional MRI study. Proc Natl Acad Sci U S A 2006;103:809-813. 8. Shibata M, Benzi RH, Seydoux J, Girardier L. Hyperthermia induced by pre-pontine knife-cut: Evidence for a tonic inhibition of non-shivering thermogenesis in anaesthetized rat. Brain Res 1987;436:273-282.
Hyperthermia Associated with Bilateral Mesencephalothalamic Infarction Murat Alemdar, MD
Central hyperthermia is characterized by the rapid onset of high body temperature, marked temperature fluctuation, and high mortality. It is usually associated with brainstem damage caused by direct destruction or indirect compression. Herein, we report a 79-year-old man with bilateral paramedian mesencephalothalamic infarction presenting with hyperthermia. On admission, his body temperature was 39.3 C aurically. Motor or sensorial deficit was not present. He was hospitalized at the infectious disease service. Upon the suspicious history and the absence of any infectious source on laboratory investigations, he was sent to our department on his first day of hospitalization. This case shows that upper paramedian mesencephalic and/or thalamic structures play a major role in the regulation of body temperature and that infarctions involved these structures could present with central hyperthermia. The history of this case also impresses the necessity of physicians’ awareness about the central causes of hyperthermia, particularly in patients with the rapid onset of high temperature with marked fluctuation. Key Words: Hyperthermia— mesencephalon—thalamus—thermoregulation. Ó 2012 by National Stroke Association
Thermoregulation is a vital process directed by the central nervous system through endocrine, autonomic, and behavioral mechanisms in humans. Hyperthermia is a thermoregulation defect without a change of set point of body temperature, whereas fever indicates an increased set point with intact thermoregulation. Central hyperthermia is characterized by the rapid onset of high body temperature with marked fluctuation. Hyperthermia is associated with a poorer prognosis in stroke.1 The later it occurs within the first week poststroke, the
From the Department of Neurology, Toyotasa First Aid and Traumatology Hospital, Sakarya, Turkey. Received July 2, 2011; revision received August 6, 2011; accepted August 9, 2011. Address correspondence to Murat Alemdar, MD, Department of Neurology, Toyotasa First Aid and Traumatology Hospital, Sakarya, Turkey. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2012 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2011.08.003
poorer the prognosis. Aggressive measures to prevent and treat hyperthermia could improve the clinical outcomes in patients with acute ischemic stroke.2 Central hyperthermia is usually associated with brainstem (mainly pons) damage by direct destruction or indirect compression.3 The severity of stroke and inflammation are important determinants of hyperthermia after ischemic stroke.2,4 In most cases, it does not occur as a sole symptom, but rather presents in concert with other neurologic symptoms, like lateralizing motor or sensorial deficits.5 Herein, we report on a patient with bilateral paramedian mesencephalothalamic infarction presenting with hyperthermia and impaired orientation.
Case Report A 79-year-old man was admitted to the emergency room with the complaint of hyperthermia and impaired orientation. The hyperthermia begun abruptly, leading to impaired orientation. On admission, his body temperature was 39.3 C aurically. Other vital signs were normal.
Journal of Stroke and Cerebrovascular Diseases, Vol. 21, No. 8 (November), 2012: pp 907.e13-907.e15
907.e13
M. ALEMDAR
907.e14
Table 1. Measures of the patients body temperature Day Admission
Time
20:30 00:30 1 06:30 07:20 08:00 09:30 10:00 14:00 23:00 2 08:30 13:30 16:00 18:30 22:00 3 08:00 18:00 4 08:00 19:00 5 (discharge) 08:00
Temperature, C (aurically)
Service
39.3* 36.4 39.3* 38.4 38.2 38.4 36.7 36.8 37.3 37.0 37.2 37.5 36.7 36.7 36.5 36.4 36.4 36.9 36.7
Emergency room Infectious disease Infectious disease Infectious disease Infectious disease Infectious disease Infectious disease Infectious disease Neurology Neurology Neurology Neurology Neurology Neurology Neurology Neurology Neurology Neurology Neurology
*Intravenous paracetamol was administered twice when the patient’s body temperture was .39 C.
He was hospitalized at the infectious disease service. Intravenous paracetamol was administered twice when his body temperture was .39 C (Table 1). Upon the suspicious history and the absence of any infectious source on laboratory investigations, he was sent to our department on his first day of hospitalization.
The physical examination revealed that the patient was conscious. He was not oriented to time, place, or person, but he was able to follow some 1-step commands with verbal orders. Spontaneous speech was present with insignificant sentences. His pupils were equal with a normal reaction to light. Oculocephalic and oculocaloric reflexes were preserved. The patient was not fully cooperated to the ocular movement examination. However, we did not detect any disturbance during the primary gaze and voluntary ocular movements. He could localize the painful stimuli. The Babinsky sign was negative bilaterally. There were no associated involuntary movements of any body parts. The patient did not have dyshidrosis. He had a history of hypertension and coronary artery disease for 10 years. Benign prostate hypertrophy was diagnosed 2 years ago. He had no history of stroke, convulsion, developmental delay in childhood, or history of neurotrauma. There was no family history of neurologic disease. A complete blood cell count (CBC), urine analysis, and a chest radiograph were all normal. Therefore, a possible infection was eliminated. Electrocardiography revealed a right bundle branch block. Cardiac enzymes, biochemical parameters, and hormone levels were normal. A magnetic resonance imaging (MRI) scan of the brain was obtained. It revealed bilateral paramedian mesencephalothalamic infarction. Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping were also performed. These regions were hyperintense on DWI and hypointense on ADC relative to the brain (Fig 1). Electrocardiography and cardiac enzyme measurements taken on his second day in the hospital did not reveal
Figure 1. Bilateral paramedian mesencephalothalamic infarction (arrows) is seen as hyperintense on diffusion-weighted imaging (A) and hypointense on apparent diffusion coefficient mapping (B). These regions are also seen as hyperintense on coronal T1-weighted images (C) and hyperintense on sagittal T2-weighted images (D) on magnetic resonance imaging scans.
HYPERTHERMIA AND BILATERAL MESENCEPHALOTHALAMIC INFARCTION
any changes. Measurements of blood pressure and heart rate were normal. Echocardiography did not detect any source of emboli. It showed only a mild tricuspid insufficiency. MRI angiography was normal. Acetyl salicylic acid (100 mg/day) was initiated for secondary prevention. The patient healed progressively. The body temperature was normal after the second day. His cooperation and orientation was complete on the third day. On the fifth day poststroke, antiplatelet treatment was prescribed and he was discharged. A neurologic examination was completely normal during the outpatient clinic visit 1 month after discharge.
Discussion Central hyperthermia is characterized by the rapid onset of high body temperature, marked temperature fluctuation, and high mortality. A recent analysis of 74 patients who developed hyperthermia ($39 C) within 24 hours after stroke onset revealed that the most common cause was brainstem hemorrhage (64%), followed by putaminothalamus hemorrhage (24%), cerebellum hemorrhage (4%), large cortical infarction (4%), basilar artery occlusion (3%), and intraventricular hemorrhage (1%).3 These pathologies usually present with other neurologic symptoms, such as impaired consciousness and motor or sensorial deficits. This case revealed only impaired orientation as a neurologic sign; therefore, the diagnosis of a cerebral infarction was delayed. Absence of the accompanying motor or sensorial deficits could cause diagnostic difficulties in central hyperthermia, as in this case. Hyperthermia, in acute ischemic stroke, is associated with a poor clinical outcome. Hyperthermic patients with total anterior circulation infarct, posterior circulation infarct, and supratentorial hemorrhage were reported as associated with a marked increase of 3 months’ mortality.5 The prognosis was good in this case in spite of a posterior circulation infarct, possibly because of the relatively small volume of damaged tissue and preservation of vital structures. Central hyperthermia is still an unresolved riddle. There is little information about its pathophysiology and anatomic correlates in the current literature. Several centers in the brain have been proposed as maintaining and stabilizing body temperature. One of the first regions of the brain to be linked with this process was the preoptic area, which includes temperature-sensitive neurons and receives and integrates input from ascending neural pathways carrying information derived from sensory receptors in the periphery.6 In previous observations, hyperthermia was associated with brainstem (mainly pons) damage by direct destruction or indirect compression.3 Human research with functional MRI also revealed that human rostral medullary raphe neurons are selectively activated in response to a thermoregulatory
907.e15
challenge and point to the location of thermoregulatory neurons homologous to those of the raphe pallidus nucleus in rodents.7 The hypothalamus is also known to play a major role in thermoregulation in humans.4,6 However, the infarction in this case did not include or compress the pons, medulla, or hypothalamus. One of possible explanations of hyperthermia in this case is that the damaged region interrupted the communications between the hypothalamus and thermoregulatory neurons in the brainstem. Therefore, hypothalamic regulation of body temperature failed. In an animal study, hyperthermia was observed in rats after the prepontine cut but not after the postmammillary cut, indicating a tonic inhibitory system that would be located somewhere between the lower midbrain and the upper pons.8 The hyperthermia observed in this case may result from the presence of such a system in humans. However, the damaged region in this case includes the upper part of midbrain. Additional studies or observations are needed to understand whether the upper paramedian mesencephalic region is a part of this tonic inhibitory system. In conclusion, this case shows that upper paramedian mesencephalic and/or thalamic structures play a major role in the regulation of body temperature. Mesencephalothalamic infarctions could present with central hyperthermia. The history of this case also impresses the necessity of physicians’ awareness about the central causes of hyperthermia, particular in patients with rapid onset of high temperature with marked fluctuation.
References 1. Castillo J, D avalos A, Noya M. Aggravation of acute ischemic stroke by hyperthermia is related to an excitotoxic mechanism. Cerebrovasc Dis 1999;9:22-27. 2. Saini M, Saqqur M, Kamruzzaman A, Lees KR, Shuaib A. VISTA Investigators. Effect of hyperthermia on prognosis after acute ischemic stroke. Stroke 2009;40:3051-3059. 3. Sung CY, Lee TH, Chu NS. Central hyperthermia in acute stroke. Eur Neurol 2009;62:86-92. 4. Konaka K, Miyashita K, Ishibashi-Ueda H, Naritomi H. Severe hyperthermia caused by four-vessel occlusion of main cerebral arteries. Intern Med 2009;48:2137-2140. 5. Kumral E, Tarlaci S, Acarer A. Effect of etiology and topography of lesion on body temperature at stroke onset. J Stroke Cerebrovasc Dis 2001;10:150-156. 6. Toni R, Malaguti A, Benfenati F, Martini L. The human hypothalamus: A morpho-functional perspective. J Endocrinol Invest 2004;27(6 Suppl):73-94. 7. McAllen RM, Farrell M, Johnson JM, Trevaks D, Cole L, McKinley MJ, et al. Human medullary responses to cooling and rewarming the skin: A functional MRI study. Proc Natl Acad Sci U S A 2006;103:809-813. 8. Shibata M, Benzi RH, Seydoux J, Girardier L. Hyperthermia induced by pre-pontine knife-cut: Evidence for a tonic inhibition of non-shivering thermogenesis in anaesthetized rat. Brain Res 1987;436:273-282.