Persistence of the blink reflex to sudden illumination in a comatose patient. A clinical and pathologic study

A persistent blink reflex to light (BRL) was observed in a patient who became comatose after a cardiac arrest. Postmortem examination revealed severe hypoxic ganglion cell necrosis of the cerebral and cerebellar cortex, the basal ganglia, the hypothalamus, nuclei in the brain stem, and the superior colliculi. The pretectum was unaffected. These findings suggest that the afferent fibers of the BRL enter the brain stem not in the superior colliculus, but in the pretectum.     

中药蝶脉灵注射液在心肺复苏中脑保护作用的实验研究

目的 探讨中药蝶脉灵注射在心脏骤停时对脑复苏的作用。方法 用电刺激导致室颤制备家兔心脏骤停模型，在光镜和电镜下观察大剂量肾上腺素治疗时，蝶脉灵注射液对脑组织的影响。结果 蝶脉灵注射液对脑细胞有明显的保护作用。结论 蝶脉灵注射液能明显改善心脏骤停时脑缺血性损害，因而有利于脑复苏。     

Solitary tract nuclei in acute heart failure

BACKGROUND AND PURPOSE: Symmetrical necrosis of the brain stem nuclei has been described as a consequence of severe transitory cerebral hypoxia mainly in neonates or young adults who experienced an episode of acute ischemia due to transitory acute heart failure. We report selective bilateral lesions of the solitary tract nuclei in 5 adults with short survival intervals after acute heart failure. METHODS: In 5 patients who died due to cardiovascular pathology, histological examination was performed on multiple samples of cerebral hemispheres, on transverse sections of the midbrain and pons, and on transverse serial sections of the medulla stained with hematoxylin-eosin, Klüver-Barrera, and Luxol fast blue. The 3-dimensional reconstruction of the extension and topography of the medullary lesions was obtained with computed image analysis. RESULTS: In 4 subjects who died soon after an episode of acute heart failure (range of survival 10 hours to 2 days), the dorsal portion of the solitary tract nuclei showed an eosinophilic roundish aspect bilaterally. In their context, the neurons showed changes characteristic of ischemic coagulation necrosis. In a fifth patient, a 32-year-old man who died 15 days after an episode of cardiac arrest, 2 circumscribed symmetrical infarcts with macrophagic and astrocytic reactions were found at the same level. The topography of the lesions and the inflammatory reaction and gliosis of patient 5 suggest that the findings in the other 4 patients correspond to initial features of selective lesions of the solitary tract nuclei after acute heart failure: the short interval of survival prevented the evolution of the reactive process. The nucleus is localized at the watershed zone between the terminal branches of the medullary collateral vessels of the vertebral arteries, thus representing the last meadow in the case of sudden fall of the systemic blood flow due to acute heart failure. The absence of lesions of other medullary and pontine nuclei accounts for a selective vulnerability of the neurons of the solitary tract nuclei, and the selective dendritic lesions suggest an excitotoxic component to ischemic cell death. CONCLUSIONS: The commonly accepted resistance of the medullary centers to ischemic hypoxia in adults apparently could be due to the rapidity of death, which prevents the evolution of lesions that can be diagnosed. In addition, minor lesions in the medullary tegmentum after acute heart failure could play a role in the prevention of the resumption of autonomous cardiac and respiratory functions despite life-saving procedures.     

Changes in brain,plasma and cerebrospinal fluid contents of β-endorphin in dogs at the moment of death

Abstract

To investigate the possible participation of endogenous opioids in the cerebral events that take place at the moment of death we studied brain, cerebrospinal fluid and serum contents of 13-endorphin in dogs that were either conscious or unconscious at the moment of sudden death induced by cardiac arrest. Although with great interindividual variations, the animals that were conscious at the moment of cardiac arrest, presented a significant increase in 3-endorphin when compared with their own previous values (p < 0.05) or with the values found in animals that were deeply anaesthetized at the time of cardiac arrest. There seems to be a sudden increment of fi-endorphin in brain tissue and body fluids of dogs who are conscious at the moment of sudden death, this change was not observed in dogs that were anaesthetized prior to death. Brain opioids could participate in the sensations narrated by subjects in the so called near-death experience. [Neurol Res 1995; 17: 223-225]     

Long survival after cardiac arrest: case report and neuropathological findings

A 14-year-old male survived for nearly 3 years following a cardiac arrest. During this period he remained unconscious and electroencephalogram recordings indicated a virtual absence of neocortical activity. Clinically there was some retention of brainstem function evidenced by spontaneous respiration, eye movements, cough and swallow reflex. He was in a persistent vegetative state until his death. We believe this to be one of the longest surviving cases to be recorded. Neuropathological findings correlated with the clinical picture, and demonstrated the selective vulnerability of various areas within the brain. The brain was reduced in weight to 880 g. There was extensive necrosis affecting the cortex and basal ganglia and the cerebellum showed severe loss of Purkinje and granule cells. In certain nuclei of the thalamus there was neuronal loss and gliosis. There was relative sparing of the brain stem. The superimposed effects of retrograde degeneration is demonstrated in various sites.     

Positional Asphyxia in Individuals with Severe Cerebral Palsy

The authors report the accidental death by positional asphyxia of three individuals with cerebral palsy occurring after they had been placed in bed for the night. During the five-year period between 1984 and 1989, 12 per cent of deaths from positional asphyxia in King County, Washington, involved individuals with cerebral palsy. Such accidents are similar to those occurring among healthy young children, perhaps because both groups have limited motor skills. Further research into accidents among disabled persons may clarify their special risks and possibly lead to modifications in bed design.     

Crossed linguo-buccal reflex in post-stroke patients

A pathological crossed orofacial reflex, called crossed linguo-buccal reflex in the present study, was observed in approximately 1/3 of post-stroke patients with central facial palsy. Stroking with pressure two or three times with a split wooden tongue-blade to the tongue or palate contralateral to the central facial palsy elicited a reflex movement consisting of retraction of the angle of mouth and medio-posterior withdrawal of the buccal mucosa on the paretic side. Seventy-seven patients with central hemifacial palsy caused by a unilateral cerebral lesion were examined clinically, electromyographically and by computed tomography (CT) and magnetic resonance imaging (MRI). In addition, three men with bilateral cerebral lesions and bilateral crossed linguo-buccal reflexes were electromyographically examined. Twenty-two patients with unilateral cerebral lesions had this reflex. It was found that this reflex was most frequently observed in patients with a capsulo-caudate lesion involving the head of the caudate nucleus, the anterior limb and genu of the internal capsule. The electromyogram of the reflex showed increased activity in the orbicularis oris, depressor anguli oris, risorius, zygomaticus major and buccinator muscles on the paretic side with a long latency (254-856 ms), and a prolonged after-discharge after the stimulation. Reciprocal inhibition was observed in patients with bilateral positive reflexes. These findings suggest that liberation of the polysynaptic brainstem reflex in the medulla oblongata and pons from the indirect corticobulbar inhibition may underlie the occurrence of the crossed linguo-buccal reflex in post-stroke patients.     

Delayed ischemic hyperintensity on T1-weighted MRI in the caudoputamen and cerebral cortex of humans after spectacular shrinking deficit

BACKGROUND AND PURPOSE: Transient internal carotid artery (ICA)-middle cerebral artery (MCA) occlusion caused by cardiogenic embolus can lead to spectacular shrinking deficit (SSD): sudden hemispheric stroke syndrome followed by rapid improvement. The aim of this study was to investigate sequential neuroradiological changes in the brains of patients after SSD compared with those after brief cardiac arrest and hypoglycemia, which we previously studied with the same methods. METHODS: We serially studied CT scans and MR images obtained at 1.5 T in 4 patients with SSD. All 4 patients suffered from transient neurological deficits due to cardiogenic embolus in ICA-MCA. The symptoms began to disappear from 25 to 50 minutes after onset. RESULTS: Repeated CT scans demonstrated no abnormal findings in the affected cerebral hemisphere in 3 of the 4 patients and a small cortical infarct in the remaining 1. In each patient, repeated MRI between day 7 and month 23 after stroke showed basal ganglionic and cortical lesions. These lesions were hyperintense on T1-weighted and relatively hypointense on T2-weighted imaging. These ischemic lesions of hyperintensity on T1-weighted MRI subsided with time. CONCLUSIONS: Transient ICA-MCA occlusion leading to SSD produces a specific ischemic change with delayed onset in the basal ganglia and cerebral cortex in humans on MRI but not CT scans. We speculate that the lesions represent incomplete ischemic injury, including selective neuronal death, proliferation of glial cells, paramagnetic substance deposition, and/or lipid accumulation. Unlike brief cardiac arrest or hypoglycemia, the localized lesions on MRI of patients after SSD seem to be incomplete and to differ from infarction or hemorrhage.     

Neuropathology of normothermic circulatory arrest in newborn dogs

Neuropathologic findings are described, for the first time, in a neonatal dog model of circulatory arrest in normothermic conditions, and the findings are compared to those reported in neonatal dogs with hypothermic circulatory arrest. Total circulatory arrest was produced in 3- to 6-day-old anesthetized, paralyzed and ventilated, normothermic dogs either by asphyxiation or cardioplegia. Duration of circulatory arrest was 8–20 min and 10–40 min in asphyxiated and cardioplegic animals, respectively. The animals were resuscitated and maintained under controlled systemic physiologic conditions until neuropathologic examination after 8 or 24 h of recovery. The results suggest that the minimal durations of circulatory arrest for brain damage to occur following asphyxia or cardioplegia are 10 and 15 min, respectively. Ischemic lesions in both groups consisted of neuronal necrosis and involved mainly the brain stem structures, particularly the reticular nuclei and the spinal cord gray matter. The medulla was more severely involved than midbrain and pons. There was a direct correlation between the length of circulatory arrest and the severity of damage in the medulla (P = 0.001) and overall brain stem damage (P = 0.004) in animals with cardioplegia, but not in animals with asphyxia. These findings are compared to the neuropathologic changes previously described in newborn dogs subjected to hypothermic circulatory arrest, in which ischemic lesions are focused on the cerebral cortex and basal ganglia. It is concluded that hypothermia in this model not only prolongs the period of circulatory arrest that is required to produce brain damage, but also shifts the pattern of regional ischemic vulnerability from caudal to more rostral structures. Received: 25 July 1996 / Revised, accepted: 29 October 1996     

The blink reflex in neonates with a subsequent poor outcome

We examined maturational changes in the electrical blink reflex in 11 handicapped children, i.e., 4 cases of developmental delay, 4 of cerebral palsy, 2 of congenital hydrocephalus, and 1 of congenital cytomegalovirus infection. The developmental delay and cerebral palsy cases were all born at 25–36 weeks' gestation. In all cases, prolonged latency, low amplitude, or the absence of the late component of the blink reflex was observed in the follow-up study. These results indicate that prematurity and some congenital impairment mainly influence the maturation of the long-loop reflex arc in the blink reflex.     

Cystic brain stem necrosis in a premature infant after prolonged bradycardia

Summary A case is described of symmetrical cavitating brain stem necrosis produced by cardiac arrest in a premature infant. Two months after birth this 25-week gestational age infant suffered a prolonged episode of bradycardia. She was resuscitated and then died 3 weeks later. The autopsy revealed striking bilateral cavitation of the brain stem tegmentum extending in a columnar fashion from the upper portion of the spinal cord to the hypothalamus. The findings in this case are identical to the brain stem injury experimentally produced by complete cardiac arrest in the rhesus monkey.     

Localization of Basal Ganglia and Thalamic Damage in Dyskinetic Cerebral Palsy

BackgroundDyskinetic cerebral palsy affects 15%-20% of patients with cerebral palsy. Basal ganglia injury is associated with dyskinetic cerebral palsy, but the patterns of injury within the basal ganglia predisposing to dyskinetic cerebral palsy are unknown, making treatment difficult. For example, deep brain stimulation of the globus pallidus interna improves dystonia in only 40% of patients with dyskinetic cerebral palsy. Basal ganglia injury heterogeneity may explain this variability.MethodsTo investigate this, we conducted a qualitative systematic review of basal ganglia and thalamic damage in dyskinetic cerebral palsy. Reviews and articles primarily addressing genetic or toxic causes of cerebral palsy were excluded yielding 22 studies (304 subjects).ResultsThirteen studies specified the involved basal ganglia nuclei (subthalamic nucleus, caudate, putamen, globus pallidus, or lentiform nuclei, comprised by the putamen and globus pallidus). Studies investigating the lentiform nuclei (without distinguishing between the putamen and globus pallidus) showed that all subjects (19 of 19) had lentiform nuclei damage. Studies simultaneously but independently investigating the putamen and globus pallidus also showed that all subjects (35 of 35) had lentiform nuclei damage (i.e., putamen or globus pallidus damage); this was followed in frequency by damage to the putamen alone (70 of 101, 69%), the subthalamic nucleus (17 of 25, 68%), the thalamus (88 of 142, 62%), the globus pallidus (7/35, 20%), and the caudate (6 of 47, 13%). Globus pallidus damage was almost always coincident with putaminal damage.ConclusionsNoting consistent involvement of the lentiform nuclei in dyskinetic cerebral palsy, these results could suggest two groups of patients with dyskinetic cerebral palsy: those with putamen-predominant damage and those with panlenticular damage involving both the putamen and the globus pallidus. Differentiating between these groups could help predict response to therapies such as deep brain stimulation.     

SUDEP, suspected positional airway obstruction, and hypoventilation in postictal coma

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of mortality in patients with chronic uncontrolled epilepsy. Despite intense interest in SUDEP from the medical and scientific communities in recent years, its etiologies are still largely unresolved. A 35-year-old woman had SUDEP after having a generalized seizure in the prone position. The cause of her death was likely asphyxia from the convergence of postictal coma and suspected positional airway obstruction and hypoventilation, rather than the commonly suspected periictal cardiac arrhythmia or central apnea. SUDEP may share a similar etiology with sudden infant death syndrome (SIDS) and is likely preventable, at least in a proportion of cases.     

An autopsied case of unclassifiable sporadic four‐repeat tauopathy presenting with parkinsonism and speech disturbances

A 48‐year‐old Japanese woman experienced slow‐onset parkinsonism and speech disturbances. Neurological examinations revealed rigidity in the trunk and extremities, bradykinesia and postural instability, although cognitive impairments and psychiatric symptoms were not apparent in the early disease stage. Neuroimaging revealed progressive bilateral frontotemporal lobe atrophy with cerebral blood flow hypoperfusion. No apparent signs of lower motor neuron involvement were observed, such as fasciculation or electromyogram findings. She eventually reached the akinetic mutism state, and gastrostomy and tracheotomy were performed at 4 years after onset. A clinical diagnosis of progressive supranuclear palsy was made prior to her death, which occurred 6 years after onset. Post mortem examinations revealed that the brain weighed 1200 g and showed atrophy of the frontotemporal lobe and brainstem. Severe neuron loss and gliosis were observed in the frontotemporal lobe. The superior and middle frontal gyri were the most severely affected and showed spongiform changes in the superficial layer. The globus pallidus, subthalamic nucleus, cerebellar dentate nucleus, substantia nigra and inferior olivary nucleus also showed neuronal loss with gliosis. Using hyperphosphorylated tau (AT‐8) immunostaining, pretangle‐like neurons, numerous short threads and glial tau pathology were extensively observed. Using Gallyas?Braak silver staining, thin and short threads were also extensively observed, but considerably fewer than those observed by AT‐8 immunostaining. Neither astrocytic plaques nor tuft‐shaped astrocytes were observed. Examination by immunoelectron microscopy showed straight fibrils approximately 15 nm in diameter in the neuronal cytoplasmic inclusions in the cerebral cortex and in the fibrillary structures in the cerebral white matter. Western blot analysis of sarkosyl‐insoluble tau revealed predominantly four‐repeat tau and a banding pattern similar to that seen in progressive supranuclear palsy. No pathogenic mutations were found during the gene analysis of microtubule‐associated protein tau. After completing our comprehensive investigation, we diagnosed this patient with unclassifiable four‐repeat tauopathy.     

Sudden cardiac arrest in a patient with epilepsy induced by chronic inflammation on the cerebral surface

The present study analyzed a patient with epilepsy due to chronic inflammation on the cerebral surface underwent sudden cardiac arrest. Paradoxical brain discharge, which occurred prior to ep-ileptic seizures, induced a sudden cardiac arrest. However, when the focal brain pressure was re-lieved, cardiac arrest disappeared. A 27-year-old male patient underwent pre-surgical vid-eo-electroencephalogram monitoring for 160 hours. During monitoring, secondary tonic-clonic sei-zures occurred five times. A burst of paradoxical brain discharges occurred at 2-19 seconds (mean 8 seconds) prior to epileptic seizures. After 2-3 seconds, sudden cardiac arrest occurred and lasted for 12-22 seconds (average 16 seconds). The heart rate subsequently returned to a normal rate. Results revealed arachnoid pachymenia and adhesions, as well as mucus on the focal cerebral surface, combined with poor circulation and increased pressure. Intracranial electrodes were placed using surgical methods. Following removal of the arachnoid adhesions and mucus on the local ce-rebral surface, paradoxical brain discharge and epileptic seizures occurred three times, but sudden cardiac arrest was not recorded during 150-hour monitoring. Post-surgical histological examination indicated meningitis. Experimental findings suggested that paradoxical brain discharge led to car-diac arrest instead of epileptic seizures; the insult was associated with chronic inflammation on the cerebral surface, which subsequently led to hypertension and poor blood circulation in focal cerebral areas.     

Symmetrical necrosis in the gray matter of the brainstem and spinal cord. Two adult cases of anoxic encephalopathy]

We describe distinctive necrosis in the brainstem of two adult patients of anoxic encephalopathy. The patients were a 75-year-old man and an 82-year-old woman, who were resuscitated after cardiac arrest that lasted about 20 minutes and artificially ventilated. The first patient remained comatose without recovery of brainstem reflexes and had persistent hypotension requiring continuous infusion of catecholamine until death that occurred two weeks after the onset of illness. In the second patient, her general circulation recovered on the next day resuscitation, and traces of brainstem reflexes reappeared thereafter, while her consciousness was severely disturbed throughout the three weeks' clinical course. Both of the patients failed to regain spontaneous respiration and required the ventilatory support. On general autopsy, the first patient had small cell carcinoma of the lung with metastasis to the pleura, hilar lymph nodes and liver. In the second patient, an old myocardial infarction and pneumothorax were found. The neuropathological findings in the two patients were similar, varying only in their severity, except for the presence of the degenerative changes compatible with those of progressive supranuclear palsy in the second patient. There were laminar necrosis in the cerebral cortex and severe ischemic changes in the basal ganglia, thalamus and cerebellum. The cerebral white matter, however, exhibited only myelin pallor without apparent destruction. There was no herniation in the brain. In the first patient, fresh hemorrhages were noted in the bilateral globus pallidus. In the brainstem, symmetrical necrosis was present exclusively in the gray matter: the superior and inferior colliculi, periaqueductal gray matter, substantia nigra and the several cranial nuclei including the spinal nucleus of the trigeminal nerve, solitary and vestibular nuclei. In the second patient the symmetrical necrotic foci were also found in the substantia gelatinosa of the lower lumbar and sacral cords which were available for examination. Around these sharply demarcated necrotic lesions of the brainstem and spinal cord were there rarefaction and pronounced astrogliosis. Unlike the cases of neonates or infants, symmetrical necrosis in the brainstem has been reported to be exceptional in adult patients of anoxic encephalopathy. Now that the medical technology of resuscitation is well advanced, the adult patients exhibiting the pathology presented here may be encountered more frequently than previously thought.     

Blink reflex elicited by auditory stimulation: clinical study in newborn infants

Blink reflex can be elicited by sudden strong auditory stimulation. Using a special transducer wer recorded this reflex which appears as a microvibration of the eyelid, and named it auditory-evoked eyelid microvibration (AMV). As the reflex pathway of AMV exists in the brainstem, AMV is an easy and useful way of knowing the function of the brainstem, especially in newborn periods. AMV was studied in infants from 25 to 43 weeks in conceptional age, to establish the normal value and to analyse the change of AMV in cases of neonatal asphyxia and intracranial hemorrhage. The mean latency of AMV in full-term infants was 31.0 +/- 67. msec. After 33 weeks in conceptional age, AMV was observed constantly with almost the same latency and amplitude as adult values. AMV appeared during both waking and sleep stages, except in active sleep. Marked change in AMV was noted such as delayed latency or disappearance of the response in neonatal asphyxia or intracranial hemorrhage. Infants who continued to have these abnormalities for a certain period, died or exhibited neurological sequelae.     

Magnetic resonance imaging in children with bilateral spastic forms of cerebral palsy

We analyzed the relationship between magnetic resonance image findings in children with bilateral spastic cerebral palsy and its stages of severity in term and preterm children. Magnetic resonance image findings of 102 children (66 male and 36 female) with bilateral spastic cerebral palsy (median age, 2.5 years; range, 3 months to 15 years) were reevaluated. The study group consisted of children with confirmed perinatal asphyxia. Hypoxic-ischemic events were diagnosed in 64% of the children. Significant abnormalities relevant to cerebral palsy were evident on imaging in 85/102 (83%) children (in 77% of term and 93% of preterm children). Enlargement of the ventricles alone (48%) or accompanied by periventricular white-matter damage (25%) was the most frequent finding in term and preterm children, but was more highly expressed in preterm children (P < 0.05). White-matter damage was more often found in preterm children (P < 0.05). Enlargement of the lateral ventricles and periventricular leukomalacia may be attributable to ischemic damage to the neonatal brain. Significant correlations were found between magnetic resonance image findings and severity of cerebral palsy (P < 0.05). Detection of brain abnormalities in children with cerebral palsy may prove useful in prognoses as well as in medical consultations and management.     

Results of N-methyl-D-aspartate antagonists in perinatal cerebral asphyxia therapy

Perinatal cerebral asphyxia, which results in significant neurologic and cognitive disabilities in infants and children, remains a major health problem. Potential neurologic sequelae include cerebral palsy, mental retardation, and epilepsy. Over the next few years, neuroprotective agents that prevent asphyxial neuronal injury and death are likely to be developed. These agents may also be effective in prophylaxis and treatment of chronic neurologic disorders, including epilepsy and neurodegenerative disorders, such as Huntington disease.