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Persistence of habituation deficits after neurological recovery from severe thiamine deprivation.

Rats were fed a thiamine-deficient diet for 4 weeks and injected daily with pyrithiamine during the last two weeks of the diet. This regime induced severe neurological anomalies such as ataxia, loss of righting reflex and visual place reflex, and finally full tonic-clonic seizures. These symptoms are reminiscent of the clinical Wernicke-Korsakoff syndrome. Injection of thiamine dramatically reversed these symptoms within one or two hours as seen in Wernicke patients. Six weeks later these rats showed a marked deficit in habituation of exploratory behavior and of the auditory orienting response. To what extent this chronic deficit in habituation contributes to the cognitive dysfunctions seen in Wernicke-Korsakoff patients is discussed. Histological examination of the brains of 6 of the rats revealed a heterogeneous pattern of damage to the brainstem, including mamillary bodies and several thalamic nuclei, reminiscent of that seen in Korsakoff patients. In addition there were many dark abnormal cells in limited fields of hippocampus neocortex and thalamus in almost all animals.

Animals↗

Predicting neurologic recovery in cervical spinal cord injury with postoperative MR imaging.

STUDY DESIGN: Prospective, nonrandomized, observational cohort study. OBJECTIVES: To determine whether the presence of spinal cord hemorrhage and length of hematoma on magnetic resonance imaging (MRI) is predictive of recovery in cervical spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA: A clear picture of the location, extent, and severity of traumatic cervical cord injury can be obtained with MRI. Several prognostic studies looked for an association between the degree of SCI, as depicted by MRI, and neurologic outcome. Up to now, an association between the length of hemorrhage and the extent of SCI and motor recovery could not be demonstrated. METHODS: Twenty-nine patients with acute traumatic cervical spinal cord injury underwent surgery within 2 to 9 hours. MRI was performed within 2 weeks of injury. Neurologic impairment was classified using the ASIA classification. The effects of hemorrhage and length of hematoma on changes in the neurologic impairment were assessed at time of MRI and at median follow-up in 35 months (range, 24-65 months). RESULTS: Patients with hemorrhage were much more likely to have a complete injury at time of follow-up (odds ratio = 2.33, 95% confidence interval, 1.42-3.82). Patients admitted with complete SCI, ASIA A, showed a median length of hematoma of 10.5 mm and a median length of edema of 66.5 mm and no change at follow-up. Patients with incomplete SCI showed a median length of hematoma of 4 mm and small edema. Presence of hemorrhage less than 4 mm was associated with good prognosis. CONCLUSION: This study indicates that presence of hemorrhage of less than 4 mm was not associated with complete SCI and showed good prognosis.

Cervical Vertebrae↗

Rapid opening and closing of the hand as a measure of early neurologic recovery in the upper extremity after surgery for cervical spondylotic myelopathy.

OBJECTIVE: To compare the results of a simple bedside test with the Jebsen-Taylor hand function test, in the assessment of early improvement of neurologic function after surgery for cervical spondylotic myelopathy (CSM). DESIGN: Case series comparing the bedside test with the Jebsen-Taylor test of hand function as the criterion standard in a blinded comparison. SETTING: Referral center, institutional practice, hospitalized care. PARTICIPANTS: One hundred referent subjects and 26 consecutive patients undergoing surgery for CSM. INTERVENTION: Decompressive cervical spine surgery. Main outcome measures Complete, rapid opening and closing of the hand was timed for 20, 40, and 60 repetitions, the Rapid Hand Flick Time (RHFT), preoperatively and in the first week postoperatively. The results of this test were correlated with the Jebsen-Taylor test. RESULTS: There was a 40% to 50% prolongation in the RHFT compared with age-matched referent subjects. Postoperatively, there was a 3.84-second mean improvement in the RHFT for 20 repetitions in the right hand and 2.8 seconds in the left hand. A paired-samples t test, comparing the preoperative and postoperative day 1 and day 7 timings, showed a statistically significant improvement (P<.001). There was no significant change from postoperative day 1 to day 7. In the Jebsen-Taylor test, patients showed a significant postoperative improvement (P<.01) in the writing test, in simulated feeding, and in transfer of small objects in both hands. Pearson correlation coefficient testing for correlation between the RHFT and the Jebsen-Taylor subtests were low, which indicates that, although they both record an improvement after surgery, they probably do not test the same aspects of hand function. CONCLUSIONS: The RHFT is a simple and reliable method of assessing early improvement in hand function and spasticity in patients after surgery for CSM.

Adult↗

Improved short-term neurological recovery with flunarizine in a canine model of cardiac arrest.

A 10-minute cardiac arrest was produced in dogs by electrical fibrillation of the heart. Recovery of cerebral function was monitored by estimating the cerebral metabolic rate of oxygen consumption (CMRO2), cerebral blood flow (CBF), electroencephalograph (EEG) and extent of neurological deficit. The study group received flunarizine (0.1 mg/kg intravenously) at the beginning of resuscitation, while control animals were given the drug vehicle. By four hours after resuscitation, CMRO2 in flunarizine-treated dogs was 121 +/- 43% of pre-arrest baseline, as compared with 37 +/- 9% in control animals (P less than 0.02). In the flunarizine group, CBF was 83 +/- 21% of baseline, while it was only 31 +/- 8% in controls (P less than 0.01). As compared with the control group, no other significant changes were detected in electrocardiographic, hemodynamic, or biochemical parameters in the flunarizine-treated dogs. A significant improvement in the visual EEG score (P less than 0.001) and neurological deficit (P less than 0.05) was seen in flunarizine-treated dogs six hours after ischemic insult.

Animals↗

Neurological recovery after prolonged verapamil-induced cardiac arrest.

A 15-year-old female survived a total of 65 minutes cardiac arrest following ingestion of verapamil and selective serotonin re-uptake inhibitors. We consider that the lack of neurological damage, despite evidence of significant renal and myocardial injury, may be related to the possible neuroprotective effect of a large dose of verapamil.

Adolescent↗

[Effects of thyrotropin-releasing hormone on neurologic recovery and biogenic amine metabolites of cerebrospinal fluid in spinal disorders].

The pharmacological effects of the thyrotropin-releasing hormone (TRH) in relation to biogenic amine metabolism in cerebrospinal fluid were examined in 35 patients with various spinal disorders. Neurologic conditions before and after TRH treatment were evaluated using subjective symptoms and Frankel's classification. Biogenic amine metabolism in cerebrospinal fluid was examined before and after TRH treatment measuring the metabolites by high performance liquid chromatography with electrochemical detection. Significant decreases in metabolites of norepinephrine and dopamine were seen in most cases of spinal disorders. The amount of serotonin metabolite, however, was not changed. In many acute cases, the neurologic condition was improved, and a significant increase in the dopamine metabolite was seen in the improved cases after TRH treatment. In chronic cases, TRH treatment was not as effective as in acute cases. TRH was therefore thought to be an effective agent in the treatment of acute spinal disorders. When an increase in the dopamine metabolite is seen after TRH treatment, neurologic improvement would probably be expected.

3-Methoxy-4-hydroxyphenylethanol↗

The effects of dizocilpine maleate (MK-801), an antagonist of the N-methyl-D-aspartate receptor, on neurologic recovery and histopathology following complete cerebral ischemia in primates.

The present study was designed to determine if the noncompetitive excitatory amino acid antagonist, dizocilpine maleate, when administered after a 17 min period of complete cerebral ischemia in primates, would improve postischemic neurologic function and hippocampal histopathologic outcome when compared to placebo-treated animals. Ten pigtail monkeys were anesthetized and subjected to complete cerebral ischemia using an established neck tourniquet model. Five minutes postischemia, five monkeys received dizocilpine 300 micrograms/kg i.v. over 5 min, followed by an infusion of 150 micrograms/kg/h for 10 h. This produced plasma levels of the drug in excess of 30 ng/ml for the duration of the infusion. An additional five monkeys were treated with an identical volume of saline placebo. All monkeys received intensive care for the initial 24 to 48 h postischemia. At 96 h postischemia, there was no significant difference in neurologic function between the two groups (p = 0.53, with the placebo group having the numerically better outcome). There also was no significant difference between hippocampal histopathology scores between dizocilpine and placebo-treated monkeys. The authors conclude that dizocilpine is not an efficacious therapy in the treatment of neurologic injury that occurs following complete cerebral ischemia in this primate model.

Animals↗

Recovery of neurologic function after spinal cord injury in Israel.

STUDY DESIGN: A retrospective cohort study was conducted. OBJECTIVE: To assess neurologic recovery and the manner in which it is affected by the severity of the neurologic damage after spinal cord injury. SUMMARY OF BACKGROUND DATA: Studies from various countries, but not from Israel, have shown considerable potential for recovery of the damaged human spinal cord. METHODS: The study sample included 250 patients with a traumatic spinal cord lesion treated between 1962 and 1992 at the major referral hospital for rehabilitation in Israel. Demographic and clinical data were collected from the hospital charts. The degree of neurologic recovery in each patient was determined by comparing the Frankel grade of neurologic deficit at first admission for rehabilitation with the grade at discharge from that hospitalization. RESULTS: There was median delay of 36 days between injury and admission for rehabilitation. During rehabilitation, full or substantial neurologic recovery (upgrade to Frankel Grade D or E) occurred in 27% of all the patients who were Grade A, B, or C on admission, and in 54% of those who were Grade C. The neurologic recovery was negatively associated with severity of the neurologic deficit. CONCLUSIONS: The outcome findings are similar to those reported from spinal rehabilitation units in other countries. The study is a further demonstration of the considerable potential for neurologic recovery after spinal cord injury, when posttraumatic or postsurgical management is focused on prevention of complications and maximal use of functional ability.

Adolescent↗

Combined PGI2, indomethacin, and heparin improves neurological recovery after spinal trauma in cats.

Anesthetized cats were subjected to standardized cervical spinal trauma produced by a modification of the Allen weight-dropping method. One hour after injury, animals were randomly allocated to one of three treatment groups, in which they received 1) saline, 2) naloxone, or 3) combined treatment, consisting of indomethacin, heparin, and prostacyclin (PGI2). Treatment was continued for 4 hours. Neurological function was evaluated weekly by a neurologist unaware of the treatment group, and was graded by means of a scale modified from that of Tarlov. Functional recovery in animals receiving combined drug therapy was significantly better than in saline-treated control animals, and was similar to that observed in naloxone-treated animals. The findings are discussed with respect to "blood-damaged tissue interaction" and may have implications both with regard to the pharmacological management of acute spinal injury and to the mechanism of action of opiate antagonists.

Animals↗

[A case of central pontine myelinolysis with neurological recovery after administration of glucocorticoid].

A survival case of central pontine myelinolysis (CPM) is reported herein with a review of 22 MRI-analyzed CPM survivors in the literature. A 65-year-old male was struck on the forehead while in a traffic accident. He was almost fully conscious and neurologically free on admission. Laboratory data were normal except hyponatremia [122 mEq/l] and hypoproteinemia [5.8 g/dl]. 2 hours later he became drowsy and left hemiparesis. The CT scan showed right frontal cerebral hematoma leading to a remarkable midline shift. Immediately, aspiration of the hematoma was performed. On the next day, he returned to the initial neurological level. On the third day, however, he again became comatose followed by tetraparesis and ataxic respiration. While the CT scan at that time did not display any abnormality in the pons, the severe dysfunction of the brain stem occurred after the correction of hyponatremia strongly suggesting CPM. The serum Na levels were kept between 110 and 125 [mEq/l]. In addition, 375 mg of methylprednisolone had been daily administrated during and after a gradual correction of the hyponatremia, because glucocorticoid proved to be effective in the models of CPM. The neurological condition began to improve on the 14th day after admission. Eventually, he became conscious and independent in his daily activities, the time span being 8 months after the trauma. The trident MRI lesion in the basis pontis was 5 mm in diameter and much smaller than clinically expected. The 23 MRI-analyzed CPM survivors were reviewed in the literature including the present case. There were 7 males and 16 females, with a mean age of 48.5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Predicting survival with good neurological recovery at hospital admission after successful resuscitation of out-of-hospital cardiac arrest: the OHCA score.

AIMS: Out-of-hospital cardiac arrest (OHCA) is common and carries a bleak prognosis. Early prediction of unfavourable outcomes is difficult but crucial to improve resource allocation. The aim of this study was to develop a simple tool for predicting survival with good neurological function in the overall population of patients with successfully resuscitated cardiac arrest. METHODS AND RESULTS: We used logistic regression analysis to identify clinical and laboratory variables that were both readily available at admission and predictive of poor outcomes (death or severe neurological impairment) in a development cohort of 130 consecutive OHCA patients admitted to a French intensive care unit (ICU) between 1999 and 2003. To test the prediction score built from these variables, we used a validation cohort of 210 patients recruited in four French ICUs between 2003 and 2005. Initial rhythm, estimated no-flow and low-flow intervals, blood lactate, and creatinine levels determined using whole blood analyzers were independently associated with poor outcomes and were used to build a continuous severity score. Goodness-of-fit tests indicated good performance (P=0.79 in the development cohort and P=0.13 in the validation cohort). The area under the receiver-operating characteristics curve was 0.82 in the development cohort and 0.88 in the validation cohort. CONCLUSION: The outcome can be accurately predicted after OHCA using variables that are readily available at ICU admission.

Adult↗

Complete neurological recovery after 13 minutes of hypovolemic hypotension.

It has been shown experimentally that irreversible brain injury and death may follow after 5-7 min of cerebral ischemia and that even brief periods, 2 min or less, can produce focal damage to the nervous system. All published studies demonstrating a protective effect of barbiturates have been performed in animals. A patient is presented who recovered full neurological function after 13 min of hypovolemic hypotension. This remarkable outcome may have been due to the rapid institution of high-dose barbiturate therapy. The extent to which such therapy affected his outcome is unclear, but does add to the growing body of evidence suggesting a favorable effect from this type of barbiturate therapy.

Brain Damage, Chronic↗

Successful resuscitation and neurologic recovery from refractory ventricular fibrillation after magnesium sulfate administration.

A 46-year-old man suffered a witnessed cardiac arrest. Ventricular fibrillation persisted despite 62 minutes of basic and advanced cardiac life support measures in the field. On arrival in the emergency department, he received 4 g magnesium sulfate IV and was defibrillated successfully to normal sinus rhythm with the next countershock. The patient was discharged neurologically intact. We discuss the possible mechanisms of action and clinical use of IV magnesium sulfate in cardiac arrest.

Cardiopulmonary Resuscitation↗

[The characteristics of the adaptive behavior, neurological recovery and a morphometric analysis of the cerebral cortex in rats in the postresuscitation period].

Rats recovered after a 10-min circulation arrest, were examined in the early postresuscitation period (within 10-12 days after resuscitation) in an open field (OF) test and during elaboration and reproduction of passive avoidance conditioned reflex (PACR); morphometric analysis of sensorimotor brain cortex was performed on days 4, 7, 14, and 30 after resuscitation. It has been shown that directly after compensation of external neurological deficit which took place in the majority of animals within 3 days the process of adaptation to new situation (OF test) in resuscitated rats, unlike the intact ones, was associated with high motor activity and not with the elaboration of stable correlations between various behavioral acts. At the same time disorders in learning and memory have been observed in PACR test. Morphometric studies have revealed changes in neuroglial relations by day 14 and considerable dystrophic neuronal changes by month 1 after resuscitation. All these disturbances took place with the overall density of neuron population preserved.

Adaptation, Physiological↗

[Complete neurological recovery following prolonged cardiac arrest. Description of a clinical case].

We report a case of protracted intraoperative cardiac arrest (15 minutes), occurring in a patient with haemorrhagic shock in consequence of a bullet wound to the right hemithorax; external cardiac massage was immediately started and carried on until the restoration of spontaneous cardiac activity. In the immediate postoperative period, the patient presented seizure activity, treated with TPS in continuous infusion (2 mg/kg/h) and DPH (250 mg/die). Anticonvulsant therapy didn't allow a correct neurologic evaluation of the patient; that was possible only when treatment was suspended (4 days after ICU admission). Neurophysiological investigations (EEG and Somato-Sensorial Evoked Potentials) were undertaken; particularly SSEPs recorded no pathologic alteration of the cortical response. At the discharge from ICU the patient was completely awake after coma, a residual paresis of the right lower limb was present. We suggest that in post-anoxic coma, when anticonvulsant therapy is required, neurophysiological investigations improve the accuracy of early outcome prediction.

Adult↗

Effect of AMPA receptor antagonist YM872 on cerebral hematoma size and neurological recovery in the intracerebral hemorrhage rat model.

[2,3-dioxo-7-(1H-imidazol-1-yl)-6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl]-acetic acid monohydrate (YM872 or zonampanel), an AMPA receptor antagonist, is in clinical development for acute ischemic cerebral infarction. Stroke patients are prone to have subsequent intracerebral hemorrhages. In order to predict potential adverse effects, YM872 was tested in a rat model with collagenase-induced intracerebral hemorrhage. The morphologically determined hematoma volumes after 24 h were compared between animal groups intravenously infused with 3600 U/kg/h heparin for 30 min, or with 20 or 40 mg/kg/h of YM872, or placebo for 4 h. Heparin enlarged hematoma volume, but neither dose of YM872 affected hematoma size. In a separate study, neurological deficits were scored at various days after intracerebral hemorrhage induction in animals with intravenous infusion for 24 h of 10 or 20 mg/kg/h YM872, or saline. The YM872 groups scored significantly better than the saline group at 14 days. These data suggest that YM872 does not exacerbate intracerebral hemorrhage and might accelerate recovery.

Animals↗

Complete neurological recovery of an adult patient with type II citrullinemia after living related partial liver transplantation.

Type II citrullinemia is an adult-onset hepatocerebral disease caused by a deficiency of argininosuccinate synthetase in liver. A 25-year-old Japanese man suddenly developed encephalopathy, showing disorientation and flapping tremor. Plasma concentrations of ammonia and citrulline were extremely high, and hepatic argininosuccinate synthetase activity was deficient. The patient's condition deteriorated rapidly in spite of intensive medications. Therefore, we performed a partial liver transplantation using a graft obtained from his healthy 61-year-old father. After surgery, his neurological symptoms soon disappeared and plasma levels of ammonia and citrulline were normalized within 3 months after operation. Type II citrullinemia is one fulminant form of various liver-based metabolic diseases, and immediate liver transplantation is necessary to rescue patients with this disease. As liver transplantation from cadaveric donor is still not possible in Japan, it seems justifiable to use living related partial liver transplantation for our patient.

Adult↗

Effect of aluminum on neurological recovery in rats following spinal cord injury.

OBJECT: This investigation was undertaken to study the effect of aluminum on neurobehavioral, electrophysiological, structural, and biochemical changes in rats following spinal cord injury (SCI). METHODS: Adult male Sprague-Dawley rats classified into different groups were given aluminum sulfate-dosed drinking water in the concentrations of 0%, 0.25%, 0.5% and 1%, respectively. After 30 days of aluminum treatment, the animals were subjected to spinal cord trauma. Laminectomy was performed at T7-8 in anesthetized rats, followed by placement of a compression plate (2.2 x 5 mm) loaded with a 35-g weight over the exposed spinal cord for 5 minutes. Control animals underwent the same surgical procedure, but the compression injury was not induced (sham). Postoperative neurological function was assessed using the inclined-plane test and by obtaining a modified Tarlov score and vocal/sensory score daily for 10 days. Electrophysiological changes were assessed using corticomotor evoked potentials, whereas pathological changes were assessed by light microscopy. The level of vitamin E in the spinal cord was measured as an index of antioxidant defense. The behavioral, biochemical, and histological analyses were performed in a blinded fashion. CONCLUSIONS: Analysis of results obtained in the behavioral studies revealed that the compression of spinal cord produced transient paraparesis in which a maximum motor deficit occurred at Day 1 following SCI and resolved over a period of 10 days. Administration of aluminum significantly impaired the recovery following SCI. Analysis of the results of the biochemical, electrophysiological, and histopathological studies also confirmed the deleterious effects of aluminum on recovery from SCI in rats.

Aluminum↗