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PubMed1999

Magnetic resonance imaging and neurological recovery in acute spinal cord injury: observations from the National Acute Spinal Cord Injury Study 3.

STUDY DESIGN: Data are from a multicenter, randomized, double blind clinical trial of acute spinal cord injury. OBJECTIVES: To evaluate the prognostic value of magnetic resonance imaging (MRI) for randomized patients in the National Acute Spinal Cord Injury Study 3 (NASCIS). SETTING: Sixteen spinal cord injury centers throughout the United States and Canada. METHODS: Of 499 patients randomized in NASCIS 3 between December 1991 and September 1995, MRI was electively done on 191 patients within 72 h of injury. Indications of hemorrhage, edema, and contusion were recorded by standard protocol. Neurological impairment as determined by motor function, response to pin prick and light touch was assessed at admission to the participating center and 6 weeks after injury. Change in neurological function was obtained by subtracting the score of each neurological parameter at admission from that measured at 6 weeks. Spinal cord surgery performed within the 3 days after injury was noted. Data were analyzed by: chi square, analysis of variance, multiple logistic regression and linear regression models. RESULTS: Patients with hemorrhage were much more likely to have a complete injury (OR=2.88, 95 Cl 1.32, 6.23); however this association was much reduced when the initial neurological examination was taken into account (AOR=1.43, 95% Cl 0.55, 3.73) and was no longer a significant predictor of injury. MRI evidence of cord edema was the strongest predictor of reduced improvement in motor function (-3.34 points, P=0.06) and light touch sensation (-3.41 points, P=0.05) at 6 weeks. CONCLUSIONS: Cord hemorrhage, contusion, and edema on MRI were not associated with diagnosis of a complete cord injury after neurological assessment from the initial clinical examination was taken into account. Prediction of a worse 6 week neurological status was weakly associated with the presence of edema diagnosed by MRI. As MRI technology improves, these diagnostic and predictive capabilities need to be re-assessed. SPONSORSHIP: NASCIS 3 was funded by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, Washington, DC, USA. Pharmacia and Upjohn provided study drugs and placebos; they also monitored data quality, and funded additional tests, in accordance with Food and Drug Administration regulatory requirements. Dr Bracken has served as an occasional paid consultant to Pharmacia and Upjohn.

Adolescent↗
PubMed2003

Conditioned blood reperfusion markedly enhances neurologic recovery after prolonged cerebral ischemia.

OBJECTIVES: To determine whether controlled reperfusion using conditioned leukodepleted blood can substantially limit cerebral reperfusion injury following prolonged ischemia. METHODS: Eighteen pigs (25-35 kg) underwent 90 minutes of hypothermic circulatory arrest (19 degrees C) to produce brain ischemia. At the start of rewarming, 10 pigs received uncontrolled reperfusion with unmodified (normal) blood. The other 8 pigs underwent 10 minutes of controlled reperfusion by selectively perfusing both common carotid arteries with blood passed through a CoBRA filter. This filter conditions the blood by removing white blood cells, platelets, and attenuating complement. Two other pigs underwent cooling and rewarming only (controls) without ischemia. Neurologic assessment was done using neurologic deficit scoring (0 = normal, 500 = brain death), and jugular venous samples were obtained for biochemical analysis postreperfusion. RESULTS: There were no statistical differences in hemodynamics between groups. At 6 hours postanesthesia, all animals receiving normal blood were substantially neurologically impaired. At 24 hours, they all had abnormal positioning and all but 1 were unable to sit or stand (neurologic score 124 +/- 19). In contrast, nonischemic controls and pigs receiving conditioned blood reperfusion showed only minor neurologic deficits at 6 hours, and at 24 hours all were considered normal (neurologic scores 0 and 6 +/- 5; P <.005 vs uncontrolled reperfusion). Compared with pigs receiving normal blood reperfusion, oxygen free radical formation (conjugated dienes 1.70 +/- 0.03 vs 1.60 +/- 0.02 Abs 240 nm; P <.05 vs uncontrolled reperfusion), and endothelin-1 release (2.12 +/- 0.09 vs 1.84 +/- 0.06 pg/mL; P <.05 vs uncontrolled reperfusion) were also significantly lower in animals receiving conditioned blood. CONCLUSIONS: Following prolonged cerebral ischemia, reperfusion injury is avoided by delivering conditioned blood, which is devoid of white cells, platelets, and membrane attack complex. These results suggest that this modality is clinically useful in situations where the brain is subjected to prolonged ischemia.

Animals↗
PubMed2003

Postinsult treatment with lithium reduces brain damage and facilitates neurological recovery in a rat ischemia/reperfusion model.

Lithium has long been a primary drug used to treat bipolar mood disorder, even though the drug's therapeutic mechanisms remain obscure. Recent studies demonstrate that lithium has neuroprotective effects against glutamate-induced excitotoxicity in cultured neurons and in vivo. The present study was undertaken to examine whether postinsult treatment with lithium reduces brain damage induced by cerebral ischemia. We found that s.c. injection of lithium dose dependently (0.5-3 mEq/kg) reduced infarct volume in the rat model of middle cerebral artery occlusionreperfusion. Infarct volume was reduced at a therapeutic dose of 1 mEq/kg even when administered up to 3 h after the onset of ischemia. Neurological deficits induced by ischemia were also reduced by daily administration of lithium over 1 week. Moreover, lithium treatment decreased the number of neurons showing DNA damage in the ischemic brain. These neuroprotective effects were associated with an up-regulation of cytoprotective heat shock protein 70 (HSP70) in the ischemic brain hemisphere as determined by immunohistochemistry and Western blotting analysis. Lithium-induced HSP70 up-regulation in the ischemic hemisphere was preceded by an increase in the DNA binding activity of heat shock factor 1, which regulates the transcription of HSP70. Physical variables and cerebral blood flow were unchanged by lithium treatment. Our results suggest that postinsult lithium treatment reduces both ischemia-induced brain damage and associated neurological deficits. Moreover, the heat shock response is likely to be involved in lithium's neuroprotective actions. Additionally, our studies indicate that lithium may have clinical utility for the treatment of patients with acute stroke.

Animals↗
PubMed1995

Successful myocardial revascularization and neurologic recovery in a patient with prolonged refractory cardiac arrest and a chronically occluded left internal carotid artery.

Heretofore, the longest successfully treated cardiac arrest reported in the literature, secondary to myocardial ischemia, was one that required 45 minutes of cardiopulmonary resuscitation before coronary bypass surgery. We present a unique case of successful resuscitation after a cardiac arrest secondary to myocardial ischemia. The arrest lasted 78 minutes (30 minutes of closed cardiac massage and 48 minutes of open cardiac massage). As soon as a perfusionist was available, cardiopulmonary bypass was initiated. After completion of the distal anastomosis and upon removal of the aortic cross clamp, the patient spontaneously recovered sinus rhythm for the 1st time since her cardiac arrest 2 hours and 10 minutes earlier. This 70-year-old woman, with a history of chronic occlusion of the left internal carotid artery, recovered fully, without evidence of neurologic or myocardial insult. We believe that vigorous closed and open cardiac massage, followed by cardiopulmonary bypass and the correction of myocardial ischemia, enabled this patient to survive a prolonged refractory cardiac arrest.

Aged↗
PubMed2004

[Complete neurological recovery in a patient with decerebrate rigidity following cardiac arrest from acute airway obstruction by advanced laryngeal cancer].

A 59-year-old man presented with severe dyspnea caused by advanced laryngeal cancer. As he had disregarded the dyspnea for a month, we did not have enough information about the extent of the tumor. The pulse oximeter showed 88% with oxygen inhalation. Because of severe dyspnea, he could not maintain supine position. Fiberoptic laryngoscopy showed tumor bulk obstructing airway directly. In the operating room, at first, a cricothyroid membrane puncture was attempted under local anesthesia but the procedure was abandoned when the patient became hypoxic and unconscious. Immediately tracheostomy and cardiopulmonary resuscitation were performed. Tumor bulk had displaced the trachea and surrounding structures, making a tracheostomy difficult. Nine min after loss of consciousness, a secure airway was obtained. However, he was still unconscious and developed characteristic decerebrate rigidity. Therefore the patient was treated with infusion of thiamylal and free radical scavenger and mild hypothermia therapy (bladder temperature 34 degrees C). On the fifth day of this treatment, after rewarming and discontinuation of thiamylal, the patient responded to command. He recovered with no neurological deficits. This case suggests that combined treatment with barbiturate, free radical scavenger, and mild hypothermia therapy is effective to minimize ischemic brain damage after cardiopulmonary resuscitation.

Acute Disease↗
PubMed1985

'Some thoughts about neurological recovery in spinal cord injuries: a philosophical review'.

In 1969 Michaelis published an inquiry on diagnosis and prognosis in traumatic spinal cord lesions based on an international level of experience. Fifteen years later our own answers from 1967 are revised. The result of the first assessment depends on the patient's condition and the physician's experience during the examination in the early stage. A correction of the first diagnosis in due course is not rare. There was no great alteration necessary for comparison in 1983 with the answers given in 1969. Firm diagnosis and prognosis are urgently needed by patients, relatives, employers and insurance bodies as early as possible. They are required also in order to compare the results of different methods of treatment. In addition, we treated a greater number of incomplete tetraplegics below C5/6, accompanied by a complete irreversible paralysis of the M. deltoideus. The pathology of this syndrome is still unknown.

Humans↗
PubMed1993

Detoxification with hemabsorption after cardiac arrest does not improve neurologic recovery. Review and outcome study in dogs.

We and others hypothesized that noxious substances released after prolonged cardiac arrest from malfunctioning liver, kidneys, or intestine (e.g. bacterial toxins, aromatic amino acids), might hamper recovery of the brain. The highly detoxifying effect of hemabsorption (i.e. hemoperfusion) with microencapsulated activated carbon has been demonstrated in other diseases. We used our dog model of ventricular fibrillation cardiac arrest of 15 min (n = 2 x 4) or 12.5 min (n = 2 x 6), reversed by brief (high flow) cardiopulmonary bypass (CPB). In half of the dogs in each insult group, a charcoal filter (HemoKart) was inserted into the circuit of CPB at low flow, from start of reperfusion to 4 h. Intermittent positive pressure ventilation was to 20 h and intensive care to 96 h after cardiac arrest. Bacterial blood cultures were positive in most of the dogs in both groups 30 min to 20 h after cardiac arrest (but not later) and were uninfluenced by hemabsorption. In the control groups to 4 h after cardiac arrest, serum levels of potentially injurious aromatic amino acids (e.g. phenylalanine, tyrosine) and of branched-chain/aromatic amino acid ratios, remained unchanged. From 12 to 48 h after cardiac arrest, aromatic amino acid levels increased (worsened). The branched-chain/aromatic amino acid ratios changed accordingly in the opposite direction. In the hemabsorption groups to 4 h after cardiac arrest, all amino acid levels were reduced, aromatic amino acids more so than branched-chain amino acids, thus increasing (improving) the ratio, compared with controls (P < 0.01). There was no group difference after discontinuance of hemabsorption at 4 h. Outcome in terms of overall performance categories and neurologic deficit scores from 24 to 96 h and brain histopathologic damage scores 96 h after cardiac arrest, were not significantly different between groups. The lack of a beneficial outcome effect of hemabsorption to 4 h after cardiac arrest does not support the self-intoxication hypothesis. The amino acid levels later after cardiac arrest suggest that more prolonged hemabsorption and more encompassing detoxification treatments, such as plasma phoresis or total body blood washout, might be evaluated.

Amino Acids↗
PubMed2004

Longitudinal clivus fracture associated with trapped basilar artery: unusual survival with good neurological recovery.

A 46-year-old motorcyclist sustained severe cranio-facial fractures from a fall at 60 km/h. He gradually developed a left hemiparesis and diplopia but retained a GCS of 15. CT head scan revealed a longitudinal clivus fracture. MRA of intracranial vessels identified a trapped basilar artery. The patient made an excellent recovery with residual left abducens palsy on follow-up at 10 weeks. Such recovery with minimal residual deficit in the context of this injury has not previously been reported. Reported cases to date are reviewed and causative mechanisms discussed.

Accidents, Traffic↗
PubMed1998

Involvement of nicotinergic mechanisms in thyrotropin-releasing hormone-induced neurologic recovery after concussive head injury in the mouse.

A behavioral study was performed in an attempt to understand the neuronal mechanisms involved in the thyrotropin-releasing hormone (TRH)-induced improvement of consciousness after concussive head injury in the mouse. Intravenous administration of TRH dose dependently shortened the duration of unconsciousness after concussion in the mouse (ED50 = 3.2 mg/kg). The improvement of recovery evoked by TRH (3 mg/kg i.v.) after concussion was not affected by i.p. pretreatment with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, alpha-methyl-para-tyrosine, p-chlorophenylalanine, scopolamine or methylscopolamine. However, mecamylamine or hexamethonium i.p. pretreatment completely inhibited the TRH-induced improvement of outcome in traumatic brain injury. The results imply that TRH-induced improvement of recovery after concussion is not associated with increased activity of monoaminergic neurons in the brain. These results suggest that the inhibitory effect of TRH upon unconsciousness after concussion in mice is mainly produced by activation of central cholinergic systems via nicotinic receptors whereas muscarinic receptors seem to be not implicated.

Animals↗
PubMed2001

An exceptional case of complete neurologic recovery after more than 5-h cardiac arrest.

We describe a case of more than 5 h cardiac arrest in a 60-year-old patient who underwent general anesthesia for a urologic operation. Before extubation, the patient suddenly developed ventricular fibrillation, pulseless ventricular tachycardia and asystole which was immediately treated by advanced life support (ALS) measures. Thirty minutes later seizures developed and were controlled by 200 mg of thiopentone and 10 mg of diazepam. A pattern of ventricular tachycardia, coarse ventricular fibrillation and asystole lasted for nearly 120 min. Termination of resuscitation maneuvers was considered, but long-term life support was continued for 5 h. After this time, peripheral pulses, with a supraventricular tachycardia-like rhythm and regular spontaneous breathing reappeared. Seven hours later, the patient had a Glasgow Coma Scale (GCS) of 5, dilated unresponsive, absence of pupils, and a systolic arterial pressure of 100 mmHg. He was then transferred to intensive care unit (ICU). The morning after, the patient was awake, responded to simple orders, breathing spontaneously, and free from sensomotor deficit. He was, therefore, extubated. Subsequently, other episodes of transitory ST-line upper wave followed by ventricular fibrillation appeared, suggesting Prinzmetal angina. This was successfully treated by percutaneous coronary angioplasty. The first electroencephalogram recorded the day after cardiac arrest showed a mild widespread background slowing. An electroencephalogram 6 days later showed a return to alpha rhythm with only mild theta-wave abnormalities. Four weeks after the first cardiac arrest the patient was discharged. This is an exceptional experience compared with the others reported. We believe that all the efforts must not be given up when such an event occurs during anesthesia and there are optimal conditions for resuscitation maneuvers.

Cardiopulmonary Resuscitation↗
PubMed1998

Selective neurological recovery or dissociated cardiac death--to be or not to be--during cardiopulmonary resuscitation.

Of 111 victims of circulatory arrest, 93 (84%) retained or regained some brain function during the resuscitation process. Twenty-six of these (24%) did not have spontaneous circulation restored, and a further 18 (16%) were left in cardiogenic shock and died within 24 h. Bradyarrhythmia or asystole during the resuscitation efforts or prolonged resuscitative attempts beyond 20 min were related to the irreversible failure of heart pump function. Individuals developing either this type of 'dissociated cardiac death' or cardiogenic shock could not be identified prior to resuscitation by the cause of the arrest nor by the initial cardiac arrhythmia. 'Dissociated cardiac death' and cardiogenic shock are major problems in cardiopulmonary resuscitation. A code of practice is urgently needed.

Arrhythmias, Cardiac↗