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.     

Recurrent coma, papular mucinosis and benign dysglobulinemia

A woman presented with a history of three regressive comas of undetectable etiology between the age of 52 and 57 years. An IgG lambda benign monoclonal dysglobulinemia was combined with a papular mucinosis (myxedematous lichen or the generalized form of Arndt-Gotton's scleromyxedema). In the 6 analogous cases documented in the literature the onset of coma occurred generally several weeks after an aggravation of the cutaneous lesions. The coma was preceded by an influenza-like syndrome followed by asthenia, malaise with vertigo and frequently epileptic seizures. During recovery, hallucinations and transient hepatic disorders were noted. Pruritus with pronounced hypereosinophilia preceded desquamation and regression of dermatologic lesions. These comas can lead to a fatal outcome (2 of 7 cases) or regress in 2 to 20 days usually without sequelae. The disease is probably of immunologic origin. The paraprotein or a serum factor could exert a direct toxic effect on brain. As in neurologic manifestations of malignant dysglobulinemia, explained initially by a "toxic encephalosis, clinical, angiography, biologic and immunologic data exist in favor of blood hyperviscosity. This hyperviscosity could result from polymer formation through intermediates immunoglobulins and other protein chains, or again from alteration of deformability of red cells by binding of paraprotein. Hyperviscosity syndromes are frequent in system diseases that are often associated with papular mucinosis. Whatever the exact mechanism of these "comas due to papular mucinosis", a logical choice is their treatment by immunosuppressants and plasmapheresis: in the case reported, the use of plasmapheresis as soon as premonitory signs had appeared probably prevented a fourth coma.     

Medical technology assessment EEG and evoked potentials in the intensive care unit.

We review the principal aspects of EEG and evoked potential (EP) neuromonitoring in the intensive care unit. The electrophysiological methods allow functional assessment of comatose patients and can be used (a) as a help to diagnose the origin of coma, (b) as a means to predict outcome, and (c) for monitoring purposes. The combination of the EEG and long-, middle-, and short-latency EPs allows widespread assessment of the cerebral cortex, the brain-stem, and the spinal cord. The EEG and the EP interpretation first requires taking into account non-neurological factors that may interfere with the recorded activities (sensory pathologies, toxic or metabolic problems, body temperature). The sensitivity and the specificity of any neurophysiological technique depend on the etiology of coma. Anoxic comas are associated with a predominantly cortical involvement, while the cortical and brain-stem functions are to be taken into account to interpret the EEG and the EPs in head trauma. The EEG and the EPs can be used to differentiate the comas due to structural lesions from those of metabolic origin, to confirm brain death and help to diagnose psychogenic unresponsiveness or a de-efferented state. While the prognostic value of the EEG is markedly hampered by the widespread use of sedative drugs, it has been possible to design efficient systems based on early- and middle-latency multimodality evoked potentials in anoxic and traumatic comas and, more generally, in all comas associated with an increase of the intracranial pressure. Continuous neuromonitoring techniques are currently under development. They have already been proven useful for the early detection and for the prevention of subclinical seizures, transtentorial herniation, vasospasm, and other causes of brain or spinal-cord ischemia.     

Hypothalamic-midbrain dysregulation syndrome: hypertension, hyperthermia, hyperventilation, and decerebration

Certain decerebrate lesions of brain stem or hypothalamus induce pharmacologically reversible hypertension and hyperthermia in animals. We observed three young patients with episodic decerebration, hyperthermia, hypertension, and hyperventilation during recovery from comas of different etiologies. The shared pathology on neurologic examinations and computed tomographic scans was hypothalamic-mesencephalic dysfunction, suggesting a diencephalic-brain-stem disconnection syndrome or brain-stem release mechanism. Propranolol was the most effective drug tested, but only two patients responded, one dramatically. This novel clinical syndrome may have localizing and therapeutic significance in pediatric coma that needs to be further defined in future studies.     

EEG in the prognosis of toxic coma: reflections apropos of unusual data

During acute intoxications, the first EEG may show persistence or abolition of cerebral activity, but the possibility of recovery after isoelectric tracing in toxic comas must be emphasized. EEG patterns frequently suggest the probability of hypnotic tranquilizer poisoning; 4 types of EEG are encountered corresponding to different grades of toxic coma. Recurrent periods of electrical silence alternating with bursts of activity are habitually recorded in carus comas with hypothermia due to acute barbiturate intoxication, with good prognosis. The possibility of a neurological disturbance associated with drug overdose must be raised whenever an asymmetric tracing is encountered. Serial recordings may detect complications such as: a localized lesion, anoxia or, very rarely, typical paroxysmal abnormalities reappearing in comitial patients before emergence from a toxic coma. Paradoxical monomorphic delta activity corresponding to improvement must not be considered as an aggravation. Peculiar EEG findings occur after oral trichlorethylene poisoning, with temporary clinical deterioration and intermittent periods of electrical silence; recovery is possible. An alpha-like pattern after cardiac arrest of toxic origin has a poor prognosis. The appearance of alternating patterns suggests the development of irreversible brain damage.     

Cerebrospinal fluid lactate in patients with diabetes mellitus and hypoglycaemic coma.

Cerebrospinal fluid (CSF) lactate and pyruvate concentrations were determined in 20 patients with diabetes mellitus but without disturbance of consciousness and five who recovered from hypoglycaemic coma. CSF lactate was slightly but significantly higher in diabetes mellitus (1.78, SEM 0.04 m mol/l) than that in 15 control subjects (1.40, SEM 0.05 m mol/l). In those who recovered from hypoglycaemic coma, CSF lactate was markedly elevated to 2.45-4.43 m mol/l. CSF glucose concentrations, however, were substantially the same between treated hypoglycaemic and diabetes mellitus groups. These findings indicate that CSF lactate levels increase with glycaemic levels in diabetes mellitus owing to enhanced glucose influx into glycolytic pathway of the brain, and also increases in treated hypoglycaemic coma probably due to mitochondrial dysfunction or damage.     

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。     

Insulin coma therapy: Decrease of plasma tryptophan in man

Summary A biochemical study was performed in two patients submitted to insulin coma therapy. The injection of insulin resulted in a decrease of free and total tryptophan as well as tyrosine in plasma, while NEFA were not influenced by this treatment. The ratio of tryptophan to tyrosine was enhanced. The administration of glucose after insulin provoked an increase of free and total tryptophan. The results support the hypothesis that in man insulin may favor the uptake of tryptophan by the brain, and enhance the synthesis of cerebral serotonin.     

Multi‐modal brain imaging showing brain damage to the orbitofrontal cortex and left hemisphere,in a case of prolonged hypoglycemia‐induced transient hemiplegia followed by persistent encephalopathy

A 21‐year‐old left‐handed male patient was admitted with a 19‐h history of coma after substantial insulin injection for suicide attempt. Although the patient recovered from coma 3 days after injury, he experienced transient hemiplegia followed by permanent brain damage. Electroencephalogram (EEG), brain magnetic resonance imaging (MRI), and brain single‐photon emission computed tomography (SPECT) identified the localization of this dysfunction, but consistency between clinical symptoms and brain images changed depending on the course of treatment. Transient hemiplegia corresponded to abnormal waveforms on EEG and decreased cerebral blood flow on SPECT, whereas persistent dysfunctions corresponded to abnormal brain regions on MRI and SPECT.     

Comparison of the effects of 4 psychiatric treatments on rat brain beta 5HT2 receptors]

Four psychiatric treatments, such as electro-convulsive treatment (ECT), insulin coma, electroacupuncture (EA) and antidepressants were given to rats chronically, and the brain cortex beta and serotonin2 receptors were measured. Comparing with their control groups we found that chronic ECT, insulin coma and EA have similar effect to down-regulate the specific coma and EA have receptor, but almost no effect on serotonin2 receptor. Antidepressants have various effects on brain monoamine receptors. The major effects of desipramine and imipramine were down-regulate B receptor, while of amitriptyline was down-regulate 5HT2 receptor. Our data suggested that different psychiatric treatment might effort their therapeutic effects mediated by different monoamine function in CNS.     

Recreational use of GHB is associated with alterations of resting state functional connectivity of the central executive and default mode networks

Gamma‐hydroxybutyrate acid (GHB) is a recreational drug with a high addictive potential. Severe side effects such as GHB‐induced coma are common and linked to increased emergency room attendances. Task‐based functional‐imaging studies have revealed an association between the regular use of GHB and multiple GHB‐induced comas, and altered neurocognitive function. However the effects of multiple GHB‐induced comas and regular GHB‐use on intrinsic brain connectivity during rest remain unknown. The study population consisted of 23 GHB‐users with ≥4 GHB‐induced comas (GHB‐Coma), 22 GHB‐users who never experienced a GHB‐induced coma (GHB‐NoComa) and 24 polydrug users who never used GHB (No‐GHB). Resting‐state scans were collected to assess resting‐state functional‐connectivity within and between the default mode network (DMN), the bilateral central executive network (CEN) and the salience network (SN). The GHB‐NoComa group showed decreased rsFC of the right CEN with a region in the anterior cingulate cortex (p_FWE = 0.048) and decreased rsFC between the right CEN and the DMN (p_FWE = 0.048) when compared with the No‐GHB group. These results suggest that regular GHB‐use is associated with decreased rsFC within the right CEN and between the right CEN and the DMN. The presence of multiple GHB‐induced comas is not associated with (additional) alterations in rsFC.     

Relationships between hypoglycaemia and gastric emptying abnormalities in insulin-treated diabetic patients.

We hypothesize that hypoglycaemia in insulin-treated diabetic patients may result from gastric emptying abnormalities causing insulin and food absorption mismatching. We tested gastric emptying in insulin-treated diabetic patients with unexplained hypoglycaemia and without dyspepsia and in diabetic patients without hypoglycaemia, prospectively. Thirty-one diabetic patients with unexplained hypoglycaemic events within 2 h of insulin injection and 18 insulin-treated diabetic patients without hypoglycaemic events underwent gastric emptying breath tests, glycaemic control and autonomic nerve function. Gastric emptying tests were abnormal in 26 (83.9%) and in four (22.2%) patients with and without hypoglycaemia, respectively (P < 0.001). Gastric emptying was significantly slower in hypoglycaemic diabetic patients (t1/2 139.9 +/- 74.1 vs 77.8 +/- 23.3 and t(lag) 95.8 +/- 80.3 vs 32.84 +/- 16.95 min, P < 0.001 for both comparisons; t-tests). A significant association between hypoglycaemic patients and abnormal values of t1/2 and t(lag) was found (P < 0.001). Gastric emptying abnormalities were more frequent in hypoglycaemic patients. We suggest gastric emptying tests for diabetic patients with unexplained hypoglycaemic events.     

Some aspects of carbohydrate metabolism in Prader-Willi syndrome.

Three patients with Prader-Willi syndrome are reported. The subjects presented chemical diabetes mellitus. All patients were hypersentsiive to exogenous insulin and they showed poor adrenal medullary response to hypoglycaemics. It was postulated that the poor adrenal medullary response to the insulin injection may be a contributing factor in the excessive hypoglycaemic response, and that the diabetes mellitus observed in the patients could be due to inactivation of endogenous insulin.     

急性一氧化碳中毒后迟发性脑病发病的危险因素分析

目的探讨急性一氧化碳中毒后迟发性脑病(DEACMP)发病的相关危险因素。方法以2001—2014年在豫北地区10家医院符合入组标准和排除标准的急性一氧化碳中毒(ACMP)752例住院患者为研究对象,收集临床资料,并随访90d以上,根据以后是否发生DEACMP分为ACMP组和DEACMP组,对所有患者的年龄、昏迷时间、昏迷程度、吸烟饮酒史等26个指标进行统计归纳,分析ACMP后患者发生DEACMP的可能危险因素。结果 752例ACMP患者中127例发生DEACMP,发生率16.9%。单因素分析结果显示,ACMP患者男性较女性更易患DEACMP,差异有统计学意义(P0.05);昏迷时间12h者DEACMP发生率明显升高,48h者58.3%发生DEACMP;中度以上昏迷、病理征阳性、丧偶、吸烟史、饮酒史、重大精神刺激等患者发生DEACMP风险大于无此类病史者,差异均有统计学意义(P0.05);ACMP急性期颅脑CT异常、并存其他疾病其DEACMP发生率较高,差异有统计学意义(P0.05)。多因素回归分析显示,性别、丧偶、头颅CT异常、昏迷程度、昏迷时间是发生DEACMP的独立危险因素。结论发生DEACMP的危险因素较多,尤其对40岁以上、男性、有丧偶史、头颅CT异常、中度昏迷以上、昏迷时间12h的ACMP患者应特别注意加强临床监测,提前采取干预措施给予病前预防性治疗。     

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.     

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.     

HYPOGLYCAEMIC NEUROPATHY: OCCURRENCE OF AXON TERMINALS IN PLANTAR SKIN AND PLANTAR MUSCLE OF DIABETIC BB/WOR RATS TREATED WITH INSULIN IMPLANTS

It is generally believed that diabetic neuropathy is due to chronic hyperglycaemia. However, experience from insulinoma patients and experimental studies show that hypoglycaemia may also cause neuropathy. Accordingly, the plantar nerves of diabetic eu-/hypoglycaemic BB/Wor rats treated with insulin implants exhibit a distinct neuropathy. To what extent hypoglycaemic neuropathy affects axon terminals in skin and muscle is unknown. In the present study we examine the occurrence of epidermal axon profiles and the neuropeptide calcitonin gene-related peptide (CGRP) in plantar skin, and of end plate axon terminals in a plantar muscle of diabetic BB/Wor rats subjected to long periods of hypoglycaemia. The number of protein gene product-immunoreactive axon profiles was found to be normal in heel skin biopsy specimens from eu-/hypoglycaemic rats, but many profiles were short and thin. The content of CGRP in the skin biopsy samples was significantly below normal. After staining with antibodies against the vesicular acetyl choline transporter protein, the occurrence of end plate axon terminals was significantly reduced in sections from the flexor hallucis brevis muscle of eu-/hypoglycaemic rats. Moreover, the end plate axon terminals tended to be abnormally small in these rats. We conclude that the hypoglycaemic neuropathy seen in plantar nerve trunks of diabetic BB/Wor rats treated with insulin implants is accompanied by mild alterations in the epidermal innervation of plantar skin and a more obviously abnormal nerve terminal pattern in plantar muscle.     

Reversible coma: a rare presentation of spontaneous intracranial hypotension

BACKGROUND: Spontaneous intracranial hypotension (SIH) is a well-recognized neurologic disorder that typically presents with orthostatic headaches, low cerebral spinal fluid pressures and distinct abnormalities on magnetic resonance imaging. METHODS: We present a case of a rare presentation of SIH. RESULTS: A 49-year-old man presented with a two week history of orthostatic headaches that rapidly progressed to encephalopathy and coma, requiring intubation. Neuroimaging revealed abnormalities typical of SIH; diffusely enhancing pachymeninges, subdural fluid collections, and descent of the brain. Treatment with an epidural blood patch reversed his coma within minutes. Following a second blood patch, the patient became asymptomatic. No cerebral spinal leak could be identified on magnetic resonance imaging or on a nuclear medicine technetium cerebral spinal fluid flow study. At six month follow-up, he remained symptom free. CONCLUSION: The mechanism of coma in SIH is presumed to be compression of the diencephalon from downward displacement of the brain. Although it is very unusual for patients with SIH to present with coma, it is important to recognize since the coma may be reversible with epidural blood patches.     

Hypoglycaemic neuropathy: occurrence of axon terminals in plantar skin and plantar muscle of diabetic BB/Wor rats treated with insulin implants

It is generally believed that diabetic neuropathy is due to chronic hyperglycaemia. However, experience from insulinoma patients and experimental studies show that hypoglycaemia may also cause neuropathy. Accordingly, the plantar nerves of diabetic eu-/hypoglycaemic BB/Wor rats treated with insulin implants exhibit a distinct neuropathy. To what extent hypoglycaemic neuropathy affects axon terminals in skin and muscle is unknown. In the present study we examine the occurrence of epidermal axon profiles and the neuropeptide calcitonin gene-related peptide (CGRP) in plantar skin, and of end plate axon terminals in a plantar muscle of diabetic BB/Wor rats subjected to long periods of hypoglycaemia. The number of protein gene product-immunoreactive axon profiles was found to be normal in heel skin biopsy specimens from eu-/hypoglycaemic rats, but many profiles were short and thin. The content of CGRP in the skin biopsy samples was significantly below normal. After staining with antibodies against the vesicular acetylcholine transporter protein, the occurrence of end plate axon terminals was significantly reduced in sections from the flexor hallucis brevis muscle of eu-/hypoglycaemic rats. Moreover, the end plate axon terminals tended to be abnormally small in these rats. We conclude that the hypoglycaemic neuropathy seen in plantar nerve trunks of diabetic BB/Wor rats treated with insulin implants is accompanied by mild alterations in the epidermal innervation of plantar skin and a more obviously abnormal nerve terminal pattern in plantar muscle. Received: 10 May 1999 / Revised, accepted: 9 July 1999     

The minimally conscious state: definition and diagnostic criteria

OBJECTIVE: To establish consensus recommendations among health care specialties for defining and establishing diagnostic criteria for the minimally conscious state (MCS). BACKGROUND: There is a subgroup of patients with severe alteration in consciousness who do not meet diagnostic criteria for coma or the vegetative state (VS). These patients demonstrate inconsistent but discernible evidence of consciousness. It is important to distinguish patients in MCS from those in coma and VS because preliminary findings suggest that there are meaningful differences in outcome. METHODS: An evidence-based literature review of disorders of consciousness was completed to define MCS, develop diagnostic criteria for entry into MCS, and identify markers for emergence to higher levels of cognitive function. RESULTS: There were insufficient data to establish evidence-based guidelines for diagnosis, prognosis, and management of MCS. Therefore, a consensus-based case definition with behaviorally referenced diagnostic criteria was formulated to facilitate future empirical investigation. CONCLUSIONS: MCS is characterized by inconsistent but clearly discernible behavioral evidence of consciousness and can be distinguished from coma and VS by documenting the presence of specific behavioral features not found in either of these conditions. Patients may evolve to MCS from coma or VS after acute brain injury. MCS may also result from degenerative or congenital nervous system disorders. This condition is often transient but may also exist as a permanent outcome. Defining MCS should promote further research on its epidemiology, neuropathology, natural history, and management.