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Neonatal asphyxia: Vulnerability of basal ganglia, thalamus, and brainstem
Neonatal Asphyxia: Vulnerability of Basal Ganglia, Thalamus, and Brainstem
We studied 2 neonates with acute intrapartum asphyxia and profound encephalopathy, but who had no cerebral parenchymal abnormalities on CT. Magnetic resonance imaging (MRI) documented unequivocal brain lesions in both patients, with a pattern that is commonly seen in experimental neonatal asphyxia. Case Report
Cerebral imaging studies in neonates have been useful in identifying and quantifying hypoxic-ischemic brain damage (HIBD). Computed tomography (CT) has proved to be most accurate, identifying cerebral pathology acutely by abnormal parenchymal radiolucency (infarction) or radiodensity (hemorrhage), and later by atrophy [1,2]. On occasion, the evolution of abnormalities on serial CT provides insight into the timing of the insult. The combination of CT abnormalities and clinical encephalopathy accurately predicts adverse outcome and correlates with the degree and type of observed deficits [ 1].
Patient 1. During routine labor induction following an uneventful 41 week gestation, fetal heart tones abruptly decreased to 60 beats per min. There was no response to 02 and left lateral decubitus positioning. A 3,300 gm infant was delivered by emergency cesarean section 46 rain alter onset of bradycardia. A tight nuchal cord with 3 turns was present. The infant was pale, flaccid, apneic, and asystolic. Resuscitation was performed with intubation, intermittent positive pressure ventilation, epinephrine, volume expansion, albumin, and sodium bicarbonate. Apgar scores were 0, 2, 4, and 4 at 1, 5, 10, and 20 min, respectively. At 10 min of life, pH was 6.81, Pco2 44, and Po2 323 on 100% 02. Tremors were observed at 90 min and phenobarbital was administered. At 24 hours, electroencephalography (EEG) revealed burst-suppression with frequent, brief, electrical seizures, some with simultaneous extremity clonus. Pupils were small and nonreactive; eye movements, corneal reflexes, and gag responses were absent. Hands were fisted, extensor posture was preferred, and sluggish reflex withdrawal was observed. Urine output was only 10 cc during the first 24 hours of life. At 48 hours, BUN was 16 and serum creatine 3.3 mg/dl. The infant improved extremely slowly. Sluggish eye movements, pupillary responses, and corneal reflexes gradually returned. Extremity tone steadily increased, but purposeful movement was limited. Intubation was necessary until 32 days of age because of an inability to cope with secretions. CT demonstrated no brain abnormalities at 1, 6, and 14 days of age. MRI at 25 days disclosed increased signal on both Tt- and T2-weighted images in the putamen, thalamus, midbrain and pontine rectum, midline cerebellum, and parasagittal cortex (Fig 1). At 1 year of age, the child had a profound spastic quadriparesis and still required nasogastric feeding. Patient 2. While sitting at lunch after an uneventful 39 week gestation, this infant's mother suddenly collapsed to the floor, rapidly becoming apneic and cyanotic. Cardiopulmonary resuscitation was performed and spontaneous ventilation was rapidly re-established. In the emergency room 15 min later, the mother had regained consciousness, but had residual metabolic acidosis (pH 7.16). Fetal heart rate was 140 with late decelerations. A 3,470 gm infant was delivered by emergency cesarean section approximately 90 min after the initial maternal collapse. Postoperatively, the mother developed severe disseminated intravascular coagulation but ultimately recovered completely; a presumptive diagnosis of amniotic fluid embolism was made. The infant's Apgar scores were 2, 5, and 7 at 1, 5, and 10 rain. At 10 min, pH was 7.23, Po2 52, and Pco2 32. She was initially limp, but over the next hour increasing extremity tone, hand fisting, and intermittent tremulousness were observed. Frequent seizures required administration Of phenobarbital, phenytoin, and rectal paraldehyde. EEG at 16 hours demonstrated a burst-suppression pattern. Seizures peaked in intensity at 24-48 hours of age and slowly resolved over the next 2 days. Urine output was only 16 cc during the first 12 hours, but was 188 cc during the next 12 hours. BUN and serum creatine remained normal. Persistent fetal circulation necessitated supplemental oxygen and mechanical ventilation initially, but rapidly resolved. Oral feedings began on day 6,
From the *Division of Neurology and the Departments of tPediatrics and :~Radiology; Evanston Hospital; Evanston, Illinois; Departments of §Pediatrics, ¶Neurology, and **Radiology; Northwestern University Medical School; Evanston, Illinois,
Communications should be addressed to: Dr. Pastemak; Division of Neurology; Evanston Hospital; 2650 Ridge Avenue; Evanston, IL 60201, Received October 5, 1990; accepted November 14, 1990.
J o s e p h F. P a s t e r n a k , MD**§ 4, T h o m a s A. P r e d e y , MD~**, a n d M i c h a e l A. M i k h a e l , MD~**
Two infants who suffered acute intrapartum asphyxia resulting in severe neonatal encephalopathy are described. Although computed tomography revealed no abnormalities, magnetic resonance imaging documented unequivocal lesions in the thalamus, basal ganglia, parasagittal cortex, brainstem rectum, and midline cerebellum in one patient and in the basal ganglia and parasagittal cortex in the other. Thus, magnetic resonance imaging was more sensitive than computed tomography in detecting acute brain damage after neonatal asphyxia and may become an important tool in improving our understanding of the relationship between adverse perinatal events, neonatal encephalopathy, and neurologic morbidity. Pasternak JF, Predey TA, Mikhael MA. Neonatal asphyxia: Vulnerability of basal ganglia, thalamus, and brainstem. Pediatr Neurol 1991 ;7:147-9.
Introduction
Pastemak et al: Neonatal Asphyxia
147
A
B
("
Figure I, MRI of Patient I. (A) TI-weighted parasagittal image using ,spin-echo technique (TR: 000 reset, T[.: 20 m,~ec. Genoal Electric Signa Scanner. 1.5 T fieM strength). High signal is seen in the thalamus (arrow) and in the parietal cortex (douhle arrowsJ. Similar changes were dentonstrated in the midline slice (not shown), in the rectum c!f the midbrain, posteri()r pons, and me~hdla. (B) first echo ~!/'the T,~-weighted axial image using spin-echo technique (TR: 2.000 msee, TE: 20 reset). High-intensi O, signal c~['basal ganglia (arrow) and thalamn,s (double arrow) bilaterally is demonstrated. The image is somewhat degraded hy motion art~i/~lct. (C) Transverse CT intage c~)rre,v~onding to Fi~,ttr~" I B (d~tained at 14 days (~['aee.
and by day 14 the infant was alert but demonstrated mildly increased trunk and extremity tone. CT on days t and 14 of age revealed no brain abnormalities. MRI on day I3 demonstrated increased signal intensity in the globus pallidus and parasagittal cortex bilaterally (Fig 2). At 3 months of age, MRI disclosed moderate to severe atrophy of the parasagittal cerebrum bilaterally. At that time, the infant demonstrated moderale spastic quadriparesis, was irritable and inattentive, had developed myoclonic seizures, and had bilateral independent frontocentrotemporal epileptiform discharges on EEG.
Discussion Two distinct clinical pathologic syndromes are o b s e r v e d in experimental neonatal HIBD [3]. Partial prolonged as-
A
B
phyxia lasting 1-3 hours causes infarction in the cerebral cortex, cerebral white matter, and basal ganglia; the parasagittal cerebrum is most vulnerable and cerebral e d e m a is c o m m o n [3,4]. Acute total asphyxia of 10-25 rain duration produces infarction in the nuclei of the brainstem and thalamus; gross brain swelling is absent [31. C T in asphyxiated human infants frequently reveals patterns o f cerebral infarction as described for chronic partial asphyxia. Parasagittal radiolucency occasionally has been o b s e r v e d early [5]: parasagittal atrophy and ulegyria are frequently demonstrated later [6]. In the extreme, diffuse lucency with swelling o f the entire cerebrum with relative-
C
Figure 2, MRI of Patient 2. (A) Tl-weighted parasagittal image using sptn-echo technique (TR: 600 reset. TE: 20 reset). High-intensity signal is seen in the globu ~ pallidus (arrow) and parietal cortex (double arrows). (B) First echo of T2-weighted axial image using spin-echo technique (TR: 2,000, TE: 25 msec). High-intensity signal is observed in the globu~ pallidus bilaterally (arrow). (C) Transverse CT image corresponding to Figure 2B obtained at 14 days of age.
148 PEDIATRIC NEUROLOGY
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ly normal radiodensity of the thalamus, brainstem, and cerebellum is observed [ 1], a pattern that correlates well with the dramatic redistribution of cerebral blood flow from the anterior to the posterior circulation in severely asphyxiated animals [7,8]. Multicystic cerebral encephalomalacia may follow this acute abnormality. In contrast, CT images of acute damage exclusively or predominantly involving the basal ganglia, thalamus, and brainstem (as described in experimental acute total asphyxia) have proved elusive, even though centrencephalic atrophy or calcification occasionally can be visualized on subsequent scans [9-11]. Our patients most likely were previously uncompromised term fetuses who developed acute hypoxic-ischemic insults. In Patient 1, clinical signs of profound brainstem damage were unequivocal, yet CT was repeatedly normal. MRI dramatically demonstrated symmetric lesions in the basal ganglia, thalamus, midbrain and pontine tectum, midline cerebellum, and parasagittal cortex. In Patient 2, the clinical syndrome was typical of neonatal HIBD with stupor punctuated by frequent seizures. Because CT was normal, MRI was performed and revealed abnormalities in the globus pallidus and parasagittal cortex. The distribution of abnormalities in Patient 1 is similar to that found in experimental acute total asphyxia [3] and reported in postmortem studies of asphyxiated human infants [ 12,13]. The lesions in the basal ganglia and parasagittal cortex in Patient 2 are more restricted in distribution but similar to those of Patient 1, suggesting that both patients experienced a similar insult. In both patients, increased signal on both T1- and Te-weighted images suggests that we are imaging infarcted tissue containing a small amount of subacute blood, pathology for which MRI is much more sensitive than CT [14,15] and that is characteristic of neonatal HIBD [121. MRI may be more sensitive to some forms of acute HIBD in newborns, especially when damage is present in the thalamus, basal ganglia, and brainstem. If more widespread use of MRI confirms this hypothesis, our understanding of the relationships between adverse perinatal
events, neonatal encephalopathy, and neurologic morbidity may be enhanced. References
[1] Adsett DB, Fitz CR, Hill A. Hypoxic-ischemic cerebral injury in the term newborn: Correlation of CT findings with neurological outcome. Dev Med Child Neurol 1985;27:155-60. [2] Fitzhardinge PM, Flodmark O, Fitz CR, Ashby S. The prognostic value of computed tomography as an adjunct to assessment of the term infant with postasphyxial encephalopathy. J Pediatr 1981;99: 777-81. [3] Myers RE. Two patterns of perinatai brain damage and the conditions of occurrence. Am J Obstet Gynecol 1977; 112:246-76. [4] Brann AW, Myers RE. Central nervous system findings in the newborn monkey following severe in utero partial asphyxia. Neurology 1975;25:327-38. [5] Pasternak .IF. Parasagittal infarction in neonatal asphyxia. Ann Neurol 1987;21:202-4. [6] Volpe JJ. Hypoxic-ischemic encephalopathy: Neuropathology and pathogenesis. In: Neurology of the newborn. Philadelphia: WB Saunders, 1987;209-35. [7] Ashwal S, Majcher JS, Longo L. Patterns of fetal lamb regional cerebral blood flow during and after prolonged hypoxia: Studies during the post hypoxic recovery period. Am J Obstet Gynecol 1981;139: 365-72. [8] Behrman RE, Lees MH, Peterson EN, de Lannoy CW, Seeds AE. Distribution of the circulation in the normal and asphyxiated fetal primate. Am J Obstet Gynecol 1970; 108:956-69. [9] DiMario FJ, Claney R. Symmetrical thalamic degeneration with calcifications of infancy. Am J Dis Child 1989;143:1056-60. [10] Roland EH, Hill A, Norman MG, Flodmark O, MacNab AJ. Selective brainstem injury in an asphyxiated newborn. Ann Neurol 1988;23:89-92. [111 Voit T, Lemberg P, Neuen E, Lumenta C, Stork W. Damage of thalamus and basal ganglia in asphyxiated full-term neonates. Neuropediatrics 1987;18:176-81. [12] Azzarelli B, Meade P, Muller J. Hypoxic lesions in areas of primary myelination. Childs Brain 1980;7:132-45. [13] Leech RW, Alvord EC. Anoxic ischemia encephalopathy in the human neonatal period: The significance of brainstem involvement. Arch Neurol 1977;34:109-13. [14] Barkovieh AJ. Metabolic and destructive brain disorders. Pediatric neuroimaging. New York: Raven Press, 1990;35-76. [15] Mikhael MA. Neuroradiology of cerebral infarction. In: Sarwar M, Barnitzky S, eds. Imaging of non-traumatic ischemic and hemorrhagic disorders of the central nervous system. Boston: Kluwer Academic Publishers, 1989; 193-220.
Pasternak et al: Neonatal Asphyxia
149
We studied 2 neonates with acute intrapartum asphyxia and profound encephalopathy, but who had no cerebral parenchymal abnormalities on CT. Magnetic resonance imaging (MRI) documented unequivocal brain lesions in both patients, with a pattern that is commonly seen in experimental neonatal asphyxia. Case Report
Cerebral imaging studies in neonates have been useful in identifying and quantifying hypoxic-ischemic brain damage (HIBD). Computed tomography (CT) has proved to be most accurate, identifying cerebral pathology acutely by abnormal parenchymal radiolucency (infarction) or radiodensity (hemorrhage), and later by atrophy [1,2]. On occasion, the evolution of abnormalities on serial CT provides insight into the timing of the insult. The combination of CT abnormalities and clinical encephalopathy accurately predicts adverse outcome and correlates with the degree and type of observed deficits [ 1].
Patient 1. During routine labor induction following an uneventful 41 week gestation, fetal heart tones abruptly decreased to 60 beats per min. There was no response to 02 and left lateral decubitus positioning. A 3,300 gm infant was delivered by emergency cesarean section 46 rain alter onset of bradycardia. A tight nuchal cord with 3 turns was present. The infant was pale, flaccid, apneic, and asystolic. Resuscitation was performed with intubation, intermittent positive pressure ventilation, epinephrine, volume expansion, albumin, and sodium bicarbonate. Apgar scores were 0, 2, 4, and 4 at 1, 5, 10, and 20 min, respectively. At 10 min of life, pH was 6.81, Pco2 44, and Po2 323 on 100% 02. Tremors were observed at 90 min and phenobarbital was administered. At 24 hours, electroencephalography (EEG) revealed burst-suppression with frequent, brief, electrical seizures, some with simultaneous extremity clonus. Pupils were small and nonreactive; eye movements, corneal reflexes, and gag responses were absent. Hands were fisted, extensor posture was preferred, and sluggish reflex withdrawal was observed. Urine output was only 10 cc during the first 24 hours of life. At 48 hours, BUN was 16 and serum creatine 3.3 mg/dl. The infant improved extremely slowly. Sluggish eye movements, pupillary responses, and corneal reflexes gradually returned. Extremity tone steadily increased, but purposeful movement was limited. Intubation was necessary until 32 days of age because of an inability to cope with secretions. CT demonstrated no brain abnormalities at 1, 6, and 14 days of age. MRI at 25 days disclosed increased signal on both Tt- and T2-weighted images in the putamen, thalamus, midbrain and pontine rectum, midline cerebellum, and parasagittal cortex (Fig 1). At 1 year of age, the child had a profound spastic quadriparesis and still required nasogastric feeding. Patient 2. While sitting at lunch after an uneventful 39 week gestation, this infant's mother suddenly collapsed to the floor, rapidly becoming apneic and cyanotic. Cardiopulmonary resuscitation was performed and spontaneous ventilation was rapidly re-established. In the emergency room 15 min later, the mother had regained consciousness, but had residual metabolic acidosis (pH 7.16). Fetal heart rate was 140 with late decelerations. A 3,470 gm infant was delivered by emergency cesarean section approximately 90 min after the initial maternal collapse. Postoperatively, the mother developed severe disseminated intravascular coagulation but ultimately recovered completely; a presumptive diagnosis of amniotic fluid embolism was made. The infant's Apgar scores were 2, 5, and 7 at 1, 5, and 10 rain. At 10 min, pH was 7.23, Po2 52, and Pco2 32. She was initially limp, but over the next hour increasing extremity tone, hand fisting, and intermittent tremulousness were observed. Frequent seizures required administration Of phenobarbital, phenytoin, and rectal paraldehyde. EEG at 16 hours demonstrated a burst-suppression pattern. Seizures peaked in intensity at 24-48 hours of age and slowly resolved over the next 2 days. Urine output was only 16 cc during the first 12 hours, but was 188 cc during the next 12 hours. BUN and serum creatine remained normal. Persistent fetal circulation necessitated supplemental oxygen and mechanical ventilation initially, but rapidly resolved. Oral feedings began on day 6,
From the *Division of Neurology and the Departments of tPediatrics and :~Radiology; Evanston Hospital; Evanston, Illinois; Departments of §Pediatrics, ¶Neurology, and **Radiology; Northwestern University Medical School; Evanston, Illinois,
Communications should be addressed to: Dr. Pastemak; Division of Neurology; Evanston Hospital; 2650 Ridge Avenue; Evanston, IL 60201, Received October 5, 1990; accepted November 14, 1990.
J o s e p h F. P a s t e r n a k , MD**§ 4, T h o m a s A. P r e d e y , MD~**, a n d M i c h a e l A. M i k h a e l , MD~**
Two infants who suffered acute intrapartum asphyxia resulting in severe neonatal encephalopathy are described. Although computed tomography revealed no abnormalities, magnetic resonance imaging documented unequivocal lesions in the thalamus, basal ganglia, parasagittal cortex, brainstem rectum, and midline cerebellum in one patient and in the basal ganglia and parasagittal cortex in the other. Thus, magnetic resonance imaging was more sensitive than computed tomography in detecting acute brain damage after neonatal asphyxia and may become an important tool in improving our understanding of the relationship between adverse perinatal events, neonatal encephalopathy, and neurologic morbidity. Pasternak JF, Predey TA, Mikhael MA. Neonatal asphyxia: Vulnerability of basal ganglia, thalamus, and brainstem. Pediatr Neurol 1991 ;7:147-9.
Introduction
Pastemak et al: Neonatal Asphyxia
147
A
B
("
Figure I, MRI of Patient I. (A) TI-weighted parasagittal image using ,spin-echo technique (TR: 000 reset, T[.: 20 m,~ec. Genoal Electric Signa Scanner. 1.5 T fieM strength). High signal is seen in the thalamus (arrow) and in the parietal cortex (douhle arrowsJ. Similar changes were dentonstrated in the midline slice (not shown), in the rectum c!f the midbrain, posteri()r pons, and me~hdla. (B) first echo ~!/'the T,~-weighted axial image using spin-echo technique (TR: 2.000 msee, TE: 20 reset). High-intensi O, signal c~['basal ganglia (arrow) and thalamn,s (double arrow) bilaterally is demonstrated. The image is somewhat degraded hy motion art~i/~lct. (C) Transverse CT intage c~)rre,v~onding to Fi~,ttr~" I B (d~tained at 14 days (~['aee.
and by day 14 the infant was alert but demonstrated mildly increased trunk and extremity tone. CT on days t and 14 of age revealed no brain abnormalities. MRI on day I3 demonstrated increased signal intensity in the globus pallidus and parasagittal cortex bilaterally (Fig 2). At 3 months of age, MRI disclosed moderate to severe atrophy of the parasagittal cerebrum bilaterally. At that time, the infant demonstrated moderale spastic quadriparesis, was irritable and inattentive, had developed myoclonic seizures, and had bilateral independent frontocentrotemporal epileptiform discharges on EEG.
Discussion Two distinct clinical pathologic syndromes are o b s e r v e d in experimental neonatal HIBD [3]. Partial prolonged as-
A
B
phyxia lasting 1-3 hours causes infarction in the cerebral cortex, cerebral white matter, and basal ganglia; the parasagittal cerebrum is most vulnerable and cerebral e d e m a is c o m m o n [3,4]. Acute total asphyxia of 10-25 rain duration produces infarction in the nuclei of the brainstem and thalamus; gross brain swelling is absent [31. C T in asphyxiated human infants frequently reveals patterns o f cerebral infarction as described for chronic partial asphyxia. Parasagittal radiolucency occasionally has been o b s e r v e d early [5]: parasagittal atrophy and ulegyria are frequently demonstrated later [6]. In the extreme, diffuse lucency with swelling o f the entire cerebrum with relative-
C
Figure 2, MRI of Patient 2. (A) Tl-weighted parasagittal image using sptn-echo technique (TR: 600 reset. TE: 20 reset). High-intensity signal is seen in the globu ~ pallidus (arrow) and parietal cortex (double arrows). (B) First echo of T2-weighted axial image using spin-echo technique (TR: 2,000, TE: 25 msec). High-intensity signal is observed in the globu~ pallidus bilaterally (arrow). (C) Transverse CT image corresponding to Figure 2B obtained at 14 days of age.
148 PEDIATRIC NEUROLOGY
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ly normal radiodensity of the thalamus, brainstem, and cerebellum is observed [ 1], a pattern that correlates well with the dramatic redistribution of cerebral blood flow from the anterior to the posterior circulation in severely asphyxiated animals [7,8]. Multicystic cerebral encephalomalacia may follow this acute abnormality. In contrast, CT images of acute damage exclusively or predominantly involving the basal ganglia, thalamus, and brainstem (as described in experimental acute total asphyxia) have proved elusive, even though centrencephalic atrophy or calcification occasionally can be visualized on subsequent scans [9-11]. Our patients most likely were previously uncompromised term fetuses who developed acute hypoxic-ischemic insults. In Patient 1, clinical signs of profound brainstem damage were unequivocal, yet CT was repeatedly normal. MRI dramatically demonstrated symmetric lesions in the basal ganglia, thalamus, midbrain and pontine tectum, midline cerebellum, and parasagittal cortex. In Patient 2, the clinical syndrome was typical of neonatal HIBD with stupor punctuated by frequent seizures. Because CT was normal, MRI was performed and revealed abnormalities in the globus pallidus and parasagittal cortex. The distribution of abnormalities in Patient 1 is similar to that found in experimental acute total asphyxia [3] and reported in postmortem studies of asphyxiated human infants [ 12,13]. The lesions in the basal ganglia and parasagittal cortex in Patient 2 are more restricted in distribution but similar to those of Patient 1, suggesting that both patients experienced a similar insult. In both patients, increased signal on both T1- and Te-weighted images suggests that we are imaging infarcted tissue containing a small amount of subacute blood, pathology for which MRI is much more sensitive than CT [14,15] and that is characteristic of neonatal HIBD [121. MRI may be more sensitive to some forms of acute HIBD in newborns, especially when damage is present in the thalamus, basal ganglia, and brainstem. If more widespread use of MRI confirms this hypothesis, our understanding of the relationships between adverse perinatal
events, neonatal encephalopathy, and neurologic morbidity may be enhanced. References
[1] Adsett DB, Fitz CR, Hill A. Hypoxic-ischemic cerebral injury in the term newborn: Correlation of CT findings with neurological outcome. Dev Med Child Neurol 1985;27:155-60. [2] Fitzhardinge PM, Flodmark O, Fitz CR, Ashby S. The prognostic value of computed tomography as an adjunct to assessment of the term infant with postasphyxial encephalopathy. J Pediatr 1981;99: 777-81. [3] Myers RE. Two patterns of perinatai brain damage and the conditions of occurrence. Am J Obstet Gynecol 1977; 112:246-76. [4] Brann AW, Myers RE. Central nervous system findings in the newborn monkey following severe in utero partial asphyxia. Neurology 1975;25:327-38. [5] Pasternak .IF. Parasagittal infarction in neonatal asphyxia. Ann Neurol 1987;21:202-4. [6] Volpe JJ. Hypoxic-ischemic encephalopathy: Neuropathology and pathogenesis. In: Neurology of the newborn. Philadelphia: WB Saunders, 1987;209-35. [7] Ashwal S, Majcher JS, Longo L. Patterns of fetal lamb regional cerebral blood flow during and after prolonged hypoxia: Studies during the post hypoxic recovery period. Am J Obstet Gynecol 1981;139: 365-72. [8] Behrman RE, Lees MH, Peterson EN, de Lannoy CW, Seeds AE. Distribution of the circulation in the normal and asphyxiated fetal primate. Am J Obstet Gynecol 1970; 108:956-69. [9] DiMario FJ, Claney R. Symmetrical thalamic degeneration with calcifications of infancy. Am J Dis Child 1989;143:1056-60. [10] Roland EH, Hill A, Norman MG, Flodmark O, MacNab AJ. Selective brainstem injury in an asphyxiated newborn. Ann Neurol 1988;23:89-92. [111 Voit T, Lemberg P, Neuen E, Lumenta C, Stork W. Damage of thalamus and basal ganglia in asphyxiated full-term neonates. Neuropediatrics 1987;18:176-81. [12] Azzarelli B, Meade P, Muller J. Hypoxic lesions in areas of primary myelination. Childs Brain 1980;7:132-45. [13] Leech RW, Alvord EC. Anoxic ischemia encephalopathy in the human neonatal period: The significance of brainstem involvement. Arch Neurol 1977;34:109-13. [14] Barkovieh AJ. Metabolic and destructive brain disorders. Pediatric neuroimaging. New York: Raven Press, 1990;35-76. [15] Mikhael MA. Neuroradiology of cerebral infarction. In: Sarwar M, Barnitzky S, eds. Imaging of non-traumatic ischemic and hemorrhagic disorders of the central nervous system. Boston: Kluwer Academic Publishers, 1989; 193-220.
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