Brain metabolism after recurrent insulin induced hypoglycaemic episodes: a PET study.

Neuropsychological testing was carried out and the rate of oxygen metabolism in the brain was measured by PET in 15 highly selected patients with type 1 diabetes. The aim was to investigate the impact on the brain of hypoglycaemic comas resulting from insulin treatment. No significant difference was found between nine patients with a history of more than 10 hypoglycaemic comas and six others who denied any history of such events. These data suggest that intensified insulin treatment, although increasing the frequency of hypoglycaemic coma, may not always be harmful for the brain. This may be explained by the limited duration of hypoglycaemic coma induced by conventional insulin treatment.     

The use of glucagon in insulin coma therapy

Summary The use of glucagon in the termination of insulin coma therapy has been discussed. The advantages over previous techniques of termination were described. Clinical experience with 41 patients who had a total of 739 comas showed no untoward reactions with the use of glucagon. No permanent residual effects were noted, and only transitory reactions, such as delayed coma, muscular twitching and secondary comas were reported in six instances.It has been demonstrated that glucagon is an effective, reliable and safe drug in the termination of insulin coma therapy. Its introduction as a therapeutic agent has demonstrated once more the many benefits which can be derived from basic medical research.From the department of neurology and psychiatry, Chicago Wesley Memorial Hospital and from the department of neurology and psychiatry, Northwestern University Medical School, Chicago, Ill.     

The use of hyaluronidase with insulin in insulin coma therapy

Summary A study of the use of hyaluronidase in conjunction with insulin, in deep coma insulin therapy, has been described. Fifty-one patients participated in this project—24 men and 27 women. Six patients were refractory to insulin; 12 were started on insulin coma therapy at the beginning of the study. Fifty-one received the mixture of insulin plus hyaluronidase for one month, during different phases of their treatment. A total of 2,968 injections of insulin were given. The property of hyaluronidase to reduce the number of spontaneous convulsions during insulin coma therapy, is pointed out. Alidase, a brand of hyaluronidase, was used in this project.     

A new aid to insulin coma therapy

Summary A new method of controlling insulin coma has been developed. It lessens some of the difficulties which have complicated deep insulin coma therapy.     

Electric stimulation and insulin coma

Summary Observations with nonconvulsive stimulation during insulin coma have been presented. The method is useful in arousing patients from coma, provided that they have not entered a deep phase. Adrenalin and blood sugar responses suggest that activation of the diencephalic pituitary-adrenal axis occurs. The theory that during insulin coma a successive inactivation of phylogenetic layers within the brain takes place is supported by the observations reported here. Therapeutic results suggest a favorable comparison with deep insulin coma, provided a differential and dynamic approach is followed. Complications, such as delayed and protracted coma, have not been encountered. Treatment time is shortened to about two hours, and the average number of treatments is about 40.Read at the 109th annual meeting of the American Psychiatric Association at Los Angeles, May 1953.     

SECRETION OF HUMAN GROWTH HORMONE DURING INSULIN COMA AND ELECTROSHOCK THERAPIES

The responses of plasma HGH during psychiatric shock therapies were investigated, and the mechanisms of HGH secretion and of shock therapies were discussed. 1. The response following a sinall dose of i.v. insulin administrotion. a) The plasma HGH following 0.1 U/kg of i.v. insulin in schizophrenic patients showed marked elevation in six out of seven cases. It reached to the peak value of 30.4±9.2 mμg/ml between 60 and 90 minutes after i.v. insulin. b) This type of response was not affected by the various psychotropic drugs that were administered orally in controlling the mental symptoms of the patients. c) Intramuscular injection of chlorpromazine (30–50 mg) did not alter the pattern of the plasma HGH response. 2. Insulin coma therapy a) A marked elevation of plasma HGH level was observed in all cases of schizophrenia during insulin coma therapy. The peak value was 9–32 mμg/ml (average 22.6±8.1 mμg/ml). b) A tendency of delay in reaching the peak value was observed in the determination performed in the second week of coma days as compared to the initial determination in the early days of insulin coma. A tendency was observed that better therapeutic results were correlated with the absence of or decrease in the delay in reaching the peak value in the course of insulin coma therapy. c) The protracted insulin coma was associated with the marked decrease in the magnitude of the peak value of plasma HGH as compared to the initial determination, suggesting the presence of a fatigued state of the central mechanism regulating the secretion of HGH. 3. Electroshock therapy a) Elevation of the plasma HGH level was observed after electroshock therapy in five of six cases of schizophrenia. A non-responsive case was found to be moderately obese. A case of depression and a case of atypical psychosis lacked HGH response after EST in the absence of obesity. b) The peak value after the electroshock therapy was lower than the one during insulin coma therapy or after administration of a small dose of i.v. insulin. The average peak value after EST was 8.1±6.8 mμg/ml. c) The responsivity of plasma HGH was found to be unrelated to the various prernedications, such as i.v. thiopental and succinylcholine chloride. It was also concluded that the presence or absence of generalized convulsion was not related to the responses of HGH following EST. d) No correlation was found between the changes of blood sugar level and the type of plasma HGH responses following the EST. It was suggested that the elevation of HGH at the time of electroshock therapy was induced by the direct electric stimulation of the hypothalamic center, but the effect of stimulating the HGH secretion was much lower than that induced by the insulin coma or i.v. insulin administration.     

The two survival cases of alpha-pattern coma caused by large amounts of hypnotica and neuroleptica

The EEGs of two men (42 and 63 years old) in coma who took large amounts of hypnotica and neuroleptica for intended suicides were occupied by an alpha pattern, and the patients were diagnosed as alpha-pattern coma. The prominent pattern in their EEGs changed from an alpha pattern to a theta pattern, and subsequently into an alpha pattern of low amplitude. The patients recovered without any residual neurological symptoms. It has been confirmed by our two cases, as well as by other reported cases, that the outcome of the alpha-pattern coma caused by drug poisoning is favorable. It is concluded that a longitudinal EEG recording should be performed as early as possible when the patient is in a comatose state.     

Cerebral mitochondrial respiration in diabetic and chronically hypoglycemic rats

The respiratory function of cerebral mitochondria harvested from genetically diabetic (BB/W) and streptozotocin-diabetic rats deprived of insulin for 3-4 weeks was found to be unchanged from control values. Furthermore, insulin-deprived BB/W rats subjected to 30 min of insulin-induced hypoglycemic coma demonstrated a normal mitochondrial respiration following a 60 min period of glucose restitution, a finding consistent with earlier results in non-diabetic rats. However, in rats exposed to 1 week of moderate hypoglycemia (plasma glucose = 3.0 mumol.ml-1), both state 3 respiration and the respiratory control ratio (RCR) were reduced from control. In fact, when the chronic hypoglycemia was imposed following a 3-4 week period of diabetic hyperglycemia, the state 3 rate and RCR were found to be reduced to a greater degree than in chronically hypoglycemic, non-diabetic, previously normoglycemic rats. Finally, when 1 week of moderate hypoglycemia preceded a 30 min period of insulin-induced hypoglycemic coma, a disturbed pattern of mitochondrial respiration (i.e. increased state 4, decreased RCR) was found at 60 min of recovery following coma. These results indicate that chronic increases in glucose (and insulin deprivation) have no effect on cerebral mitochondrial respiratory function, whereas prolonged, albeit moderate, reductions in cerebral glucose supply result in perturbations in mitochondrial respiration. These results demonstrate the importance of an adequate glucose supply for normal mitochondrial activity.     

The Two Survival Cases of Alpha-Pattern Coma Caused by Large Amounts of Hypnotica and Neuroleptica

Abstract: The EEGs of two men (42 and 63 years old) in coma who took large amounts of hypnotica and neuroleptica for intended suicides were occupied by an alpha pattern, and the patients were diagnosed as alphapattern coma. The prominent pattern in their EEGs changed from an alpha pattern to a theta pattern, and subsequently into an alpha pattern of low amplitude. The patients recovered without any residual neurological symptoms.
It has been confirmed by our two cases, as well as by other reported cases, that the outcome of the alpha-pattern coma caused by drug poisoning is favorable. It is concluded that a longitudinal EEG recording should be performed as early as possible when the patient is in a comatose state.     

Central pontine myelinolysis followed by frequent hyperglycemia and hypoglycemia--report of an autopsy case

A case of central pontine myelinolysis (CPM) followed by hyperglycemia and hypoglycemia was reported. The case was 53-year-old female. Diabetes mellitus was found when she was 32 years old, insulin therapy was started at 37 years of age. Since she was 50 years old, proteinuria and ankle edema had developed and she was admitted to The Keihin Hospital. The peritoneal dialysis (PD) was performed next year, followed by the hemodialysis (HD). In January 1978, strange movements and the disturbance of her consciousness were occurred during PD, then blood glucose level showed over 1,800 mg/dl and serum osmolarity was over 390 mosm/KgH2O. Then she was diagnosed as non-ketotic hyperosmolar coma. After that, during HD and PD, hyperglycemia (approximately 1,200 mg/dl) and hypoglycemia (approximately 40 mg/dl) developed frequently. She died soon after HD on 19th December 1979. The autopsy disclosed bilateral atrophic kidneys due to diabetic changes and atrophic pancreas. Gross neuropathological findings revealed a few small infarcts at the putamen and the globus pallidus, however, other area were observed to be normal. The most remarkable change in microscopical finding was nearly symmetrical demyelinative lesion in the center of the basis pontis. The nerve cells and axon cylinders were relatively well preserved in the demyelinative lesion. The hyaline degeneration was observed in the arterial wall, however, any arterial obstruction was not found. Recent studies would suggest that the electrolyte disturbance, such as hyponatremia, may lead to CPM, particularly when this disturbance was rapidly corrected. On the other hand, CPM induced by diabetic coma has been reported, however, its pathogenesis has been unclear.(ABSTRACT TRUNCATED AT 250 WORDS)     

颅脑损伤合并非酮性高血糖高渗性昏迷

目的 探讨颅脑损伤并发非酮性高血糖高渗性昏迷病人的诊断、治疗及预后。方法 对1997年7月～2002年1月期间收治的17例中、重型颅脑损伤合并非酮性高血糖高渗性昏迷的病人进行回顾性分析。结果 17例颅脑损伤合并非酮性高血糖高渗性昏迷的病人，除1例之外，其余均在静滴胰岛素及胃内注水治疗后2d内，高血糖、高血渗得到控制。17例非酮性高血糖高渗性昏迷病例占同期中、重型颅脑损伤病人的1．76％。死亡3例，死亡率17．6％。结论 对非酮性高血糖高渗性昏迷，静滴胰岛素极其有效，救治的关键是及早发现行采取有效的治疗措施。治疗中连续性监测血糖、血清渗透压、电解质、严密的病情监护，及时有效调整胰岛素用量至关重要。     

The clinical significance of EEG cyclic alternating pattern during coma.

To define the clinical significance of EEG "cyclic alternating pattern" (ECAP). ECAP is the periodic presence of a high-voltage slow waves alternating with low voltage irregular faster activity. This term was first described in comatose patients in 1944. It has been less recognized and may be underreported since then. The clinical significance of ECAP in the state of coma remains unknown. We reviewed our prospective EEG database for consecutive patients studied over a period of 4 years (n = 4,819) looking for patterns consistent with ECAP. We reviewed the charts of the patients with the above EEG pattern to define the clinical setting and the eventual outcome. Eleven patients were identified. All patients identified were found to be in the coma state at the time of the EEG. The majority of patients (n = 10) survived the coma, and half returned to the community in good functional status. ECAP is seen rarely in comatose patients. Regardless of the cause of the coma, the presence of ECAP carries an overall good prognosis for both survival and recovery.     

Modulation of dopamine receptor supersensitivity by chronic insulin: implication in schizophrenia

Haloperidol-induced increases in the number of dopamine receptors, as measured by [³H]spiperone binding to striatal membranes, do not occur in rats repeatedly treated with insulin in doses eliciting pronounced hypoglycemia. Given alone, however, insulin has no effect on [³H]spiperone binding in normal rats. These findings demonstrate a modulating effect of insulin on brain dopamine receptor sensitization. This effect might be relevant to the mechanism of insulin coma therapy in schizophrenia and is consistent with and supports the dopaminergic hypothesis of this disorder.     

Diabetes mellitus in Kearns-Sayre syndrome

A 20-year-old woman with Kearns-Sayre syndrome (KSS) suddenly experienced two episodes of diabetic coma. She was studied to determine whether diabetes mellitus (DM) resulted from insulin resistance or from an insulin secretion abnormality, using the euglycemic glucose clamp technique and the glucagon tolerance test. She had a deficiency of insulin secretion from beta cells. It is important to recognize in practice the onset of DM in patients with mitochondrial myopathy. We would suggest that a genetic linkage or mitochondrial dysfunction may be responsible for the association of both disease states.     

Paediatric coma scales

Traumatic and non-traumatic coma is a common problem in paediatric practice with high mortality and morbidity. Early recognition of the potential for catastrophic deterioration in a variety of settings is essential and several coma scales have been developed for recording depth of consciousness that are widely used in clinical practice in adults and children. Prediction of outcome is probably less important, as this may be able to be modified by appropriate emergency treatment, and other clinical and neurophysiological criteria allow a greater degree of precision. The scales should be reliable, i.e. with little variation between observers and in test-retest by one observer, since this promotes confidence in the assessments at different time points and by different examiners. This is particularly important when the patient is being assessed by personnel dealing with adults as well as children, discussed on the telephone, handed over at shift change, or transferred between units or hospitals. The British Paediatric Neurology Association has recommended one of the modified child's Glasgow coma scales (CGCS) for use in the UK. This review looks at the recent history of the development of coma scales and the rationale for recommending the CGCS.     

Correction for the presence of intravascular oxygen-15 in the steady-state technique for measuring regional oxygen extraction ratio in the brain: 2. Results in normal subjects and brain tumour and stroke patients

Values of regional cerebral oxygen extraction ratio and oxygen utilisation obtained with the oxygen-15 steady-state inhalation technique have been found to be overestimated due to the signal from intravascular oxygen-15. A previously described method to correct for this intravascular component has been applied to a series of studies on normal subjects, and on brain tumour and stroke patients. With this correction the regional cerebral oxygen extraction ratio in normals becomes comparable to the global values previously reported with arteriovenous sampling techniques. Within the lesions of brain tumour and stroke patients, the corrections have been found to be variable and often substantial. It is concluded that failure to apply this correction may result in major errors in the values for regional oxygen extraction ratio and oxygen utilisation. This is especially true when the regional blood flow and oxygen extraction ratio of a tissue is low and regional blood volume is high.     

Electro-oculographic study of caloric vestibular reactions in patients with severe head injuries.

In this study electro-oculographic recordings were made after caloric vestibular stimulation (C.O.G.) in 42 patients with severe head-injuries. The curves with eyes open and the changes when eyes were closed were evaluated and scored. A correlation was found between the C.O.G. and the state of consciousness but only the degree of improvement of the C.O.G. showed a good correlation with the clinical improvement. The presence of a paradoxical response in patients with a prolonged coma was found to predict possibilities of further improvement. It was proposed that in the patients with a paradoxical response a rather diffuse biochemical dysfunction of the brain-stem was present, which could be influenced by treatment. In the second part of this study the results of the trials with a treatment with L-Dopa and physostigmine are given. It was found that patients in a vegetative state or in a state of prolonged coma could be stimulated with the therapy only when the paradoxical response had been present. L-Dopa and physostigmine respectively improved the motor pattern and the contact activities.     

EEG abnormality grades and subdivisions of prognostic importance in traumatic and anoxic coma in adults

The EEG has long been established as an important laboratory test when assessing cerebral function in comatose states. During the last three decades, several grading scales regarding severity of the EEG abnormality in coma have been suggested to increase the prognostic power of the EEG for survival. Their main limitation was, that the majority of EEG abnormalities in coma fell in the middle of the five point scaling systems, i.e. Grade 3 abnormality on the five grade abnormality scales. In addition, it was considered that non-reactivity of EEG pattern in coma is confined only to the most advanced grades. The purpose of the present article is to define precisely the main five abnormality grades and their subdivisions, and to allocate them in five principal categories regarding their significance for survival. The five categories are: 1 = optimal, 2 = benign if persistent, 3 = uncertain, 4 = malignant if persistent, and 5 = fatal unless caused by drug effect or hypothermia. After the inclusion of more recently described coma patterns, it was possible to outline prognostic significance for survival in eleven types of abnormalities with assurance. Only four remain of uncertain prognostic significance. The EEG abnormalities as discussed in this article are generally applicable only to coma after diffuse brain trauma and cerebral hypoxia. However, they may also be found in some other diffuse encephalopathies associated with coma.     

Non-invasive brainstem monitoring: the ocular microtremor

The ocular microtremor (OMT) is mediated by the oculomotor area of the brainstem and is altered in several pathologic states, including traumatic brain injury, general anesthesia, brain death, coma, Parkinsonism and multiple sclerosis. The EYETECT tremor monitor is a non-invasive means of measuring the frequency and amplitude of this microscopic tremor. It has been clinically tested in these clinical scenarios and has been found to be a reliable means of detecting the depth of anesthesia, and has been useful in predicting outcome in coma and traumatic brain injury patients and in confirming brain death. This paper reviews the scientific literature on the EYETECT OMT monitor, describes the underlying physiology and discusses the potential for future works and clinical use of this innovative technology.     

Prevalence of nonconvulsive status epilepticus in comatose patients

BACKGROUND: Nonconvulsive status epilepticus (NCSE) is a form of status epilepticus (SE) that is an often unrecognized cause of coma. OBJECTIVE: To evaluate the presence of NCSE in comatose patients with no clinical signs of seizure activity. METHODS: A total of 236 patients with coma and no overt clinical seizure activity were monitored with EEG as part of their coma evaluation. This study was conducted during our prospective evaluation of SE, where it has been validated that we identify over 95% of all SE cases at the Medical College of Virginia Hospitals. Only cases that were found to have no clinical signs of SE were included in this study. RESULTS: EEG demonstrated that 8% of these patients met the criteria for the diagnosis of NCSE. The study included an age range from 1 month to 87 years. CONCLUSION: This large-scale EEG evaluation of comatose patients without clinical signs of seizure activity found that NCSE is an underrecognized cause of coma, occurring in 8% of all comatose patients without signs of seizure activity. EEG should be included in the routine evaluation of comatose patients even if clinical seizure activity is not apparent.