Computer analysis of the EEG as an aid in terminating diet therapy in phenylketonuria

In 6 patients with PKU, being on a low phenylalanine diet, the effect of reintroduction of phenylalanine on the E.E.G. was studied. The children, therefore, received daily loads of 100 or 150 mg phenylalanine/Kg bodyweight, equally divided over the meals. Computerized spectral analysis of the E.E.G's was performed during and after the loading tests. This made quantification possible of the following E.E.G. changes: 1) the increase of activities in the theta frequency band (4-8 Hz); 2) the frequency change of the alpha rhythm; 3) the change of the degree of synchrony between identical frequencies occurring in different derivations. A linear relation was found between these quantified E.E.G. parameters and the phenylalanine blood-level. After stopping the loading test E.E.G. abnormalities reversed suggesting that they could be considered as a measure for the degree of intoxication caused by the phenylalanine and/or its metabolites. It is suggested that the E.E.G. data may be useful parameters for alleviation or termination of the diet.     

Brain monoamines in human hepatic encephalopathy

Summary Dopamine (DA) serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA), and tryptophan (Trp) were assayed spectrofluorometrically in various brain regions of 10 patients with acute hepatic coma, in 3 cases of uremic coma, 4 cases of diabetic coma, in three patients with liver cirrhosis without coma, and in 5 cases of hepatic coma treated by parenteral nutrition withi-valine a branched-chain amino acid. The results were as follows: 1. In all types of coma, brain DA showed a mild general decrease, the average reduction being 20 to 30% of the controls. 2. In hepatic and other metabolic comata, brain 5-HT and 5-HIAA were generally increased, most significantly in the brainstem tegmentum and parts of the limbic system. 3. Brain Trp was significantly increased in hepatic coma, with the highest elevation in the brainstem tegmentum. 4. In liver cirrhosis without coma, brain 5-HT was within normal range, while Trp and 5-HIAA were elevated in the brainstem, their increase being much less than in untreated hepatic coma. 5. In hepatic coma treated by parenterali-valine, brain Trp showed slight elevation similar to non-comatose cirrhosis, while 5-HIAA showed almost normal values, and 5-HT was even decreased in most brain areas.These preliminary results in human postmortem brains confirm previous CSF and brain findings in experimental and human hepatic and uremic encephalopathies, indicating considerable derangement in central monoamine neurotransmitters which are attributed, at least in part, to amino acid imbalance in plasma and brain. Increased 5-HT synthesis or turn-over in the ascending serotonergic brainstem systems might represent one biochemical substrate of clinical disorders of consciousness in hepatic failure and other metabolic catastrophes. Manipulation of plasma and hence brain amino acids may influence neurological symptoms of hepatic encephalopathy by changing the brain neurotransmitter profile.     

The interpretation of the EEG in stupor and coma

This review discusses a variety of causes of stupor and coma and associated electroencephalographic (EEG) findings. These include metabolic disturbances such as hepatic or renal dysfunction, which are often characterized by slowing of background rhythms and triphasic waves. Hypoxia and drug intoxications can produce a number of abnormal EEG patterns such as burst suppression, alpha coma, and spindle coma. Structural lesions, either supra- or infratentorial, are reviewed. EEGs in the former may show focal disturbances such as delta and theta activity, epileptiform abnormalities, and attenuation of faster frequencies. In infratentorial lesions, the EEG may appear normal, particularly with a pontine lesion. Some patients may be encephalopathic because of ongoing epileptic activity with minimal or no motor movements. This entity, nonconvulsive status epilepticus (NCSE), is difficult to diagnose in obtunded/comatose patients, and an EEG is required to verify the diagnosis and to monitor treatment. Several EEG patterns and their interpretation in suspected cases of NCSE such as periodic lateralized epileptiform discharges (PLEDs), bilateral independent periodic lateralized epileptiform discharges (BIPLEDs), generalized periodic epileptiform discharges (GPEDs), and triphasic waves are reviewed. Other entities discussed include the locked-in syndrome, neocortical death, persistent vegetative state, brainstem death, and brain death.     

Reye's syndrome a clinical and electrophysiological study of four patients (author's transl)

The authors studied four children with Reye's syndrome aged 16 months, 6 years, 8 years and 11 years respectively with severe liver failure and progressive coma. The laboratory investigations in all of them showed a marked elevation of serum transaminases, hyperammoniaemia and a prolongation of the prothrombin time. The electroencephalograms showed a grossly abnormal picture with generalised continuous delta activity. Three children survived with return to normal of the liver function tests whilst the fourth child died. In the last two patients an electroencephalogram carried out every six hours has enabled certain prognostic features to be determined. Improvement in the E.E.G. correlates closely with clinical improvement and vice versa. The authors also advocate serial E.E.G. recordings in Reye's syndrome. The role of hyperammonaemia in the genesis of encephalopathy and the electroencephalographic changed is discussed. The role played by raised intracranial pressure is stressed and the importance of controlling it in order to prevent further damage and improve the prognosis of this serious illness.     

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.     

Which EEG patterns in coma are nonconvulsive status epilepticus?

Nonconvulsive status epilepticus (NCSE) is common in patients with coma with a prevalence between 5% and 48%. Patients in deep coma may exhibit epileptiform EEG patterns, such as generalized periodic spikes, and there is an ongoing debate about the relationship of these patterns and NCSE. The purposes of this review are (i) to discuss the various EEG patterns found in coma, its fluctuations, and transitions and (ii) to propose modified criteria for NCSE in coma.Classical coma patterns such as diffuse polymorphic delta activity, spindle coma, alpha/theta coma, low output voltage, or burst suppression do not reflect NCSE. Any ictal patterns with a typical spatiotemporal evolution or epileptiform discharges faster than 2.5 Hz in a comatose patient reflect nonconvulsive seizures or NCSE and should be treated. Generalized periodic diacharges or lateralized periodic discharges (GPDs/LPDs) with a frequency of less than 2.5 Hz or rhythmic discharges (RDs) faster than 0.5 Hz are the borderland of NCSE in coma. In these cases, at least one of the additional criteria is needed to diagnose NCSE (a) subtle clinical ictal phenomena, (b) typical spatiotemporal evolution, or (c) response to antiepileptic drug treatment. There is currently no consensus about how long these patterns must be present to qualify for NCSE, and the distinction from nonconvulsive seizures in patients with critical illness or in comatose patients seems arbitrary.The Salzburg Consensus Criteria for NCSE [1] have been modified according to the Standardized Terminology of the American Clinical Neurophysiology Society [2] and validated in three different cohorts, with a sensitivity of 97.2%, a specificity of 95.9%, and a diagnostic accuracy of 96.3% in patients with clinical signs of NCSE. Their diagnostic utility in different cohorts with patients in deep coma has to be studied in the future.This article is part of a Special Issue entitled “Status Epilepticus”.     

Alpha coma

Six personal cases of alpha coma are reported: 3 following a cerebrovascular accident and 3 resulting from cerebral concussion. Two patients survived. On the basis of differences in pathogenesis, EEG characteristics and prognosis, the following classification is proposed: alpha coma resulting from brain stem vascular accident; cerebral concussion; diffuse cerebral hypoxia; drug intoxication. The clinical course of each of the classes of alpha coma is outlined. The alpha coma state is not restricted to cases with structural brain stem lesions c.q. lesions of the pontomesencephalic region.     

External ophthalmoplegia, alpha and spindle coma in imipramine overdose: case report and review of the literature

A 13-year-old boy with imipramine overdose developed seizures, respiratory arrest, and coma. Abnormalities of oculovestibular reflexes, electroencephalograms, and brainstem auditory evoked potentials were monitored in relation to measurements of drug levels. An alpha-coma electroencephalographic pattern evolved into one evidencing spindle coma and eventually into a normal pattern. Prolonged brainstem auditory evoked potentials also normalized as coma and oculocephalic reflex abnormalities resolved. In spite of the history that suggested hypoxic damage, the absence of reflex eye movements in a comatose patient and the presence of alpha- and spindle-coma electroencephalographic patterns, even with prolonged brainstem auditory evoked potentials, are not reliable prognostic indicators in tricyclic drug overdose.     

Unusual clinical course in a case of Creutzfeldt-Jakob disease

An unusual clinical course of Creutzfeldt-Jakob Disease (CJD) is described. After a rapid progression to coma, the patient has survived for 16 months to date. To our knowledge a terminal, preagonal stage of this duration in CJD has never been reported. Since Methisoprinol was administered, the drug may have had a beneficial effect on the duration of the disease.Two and half months after the submission of this paper, the patient died. Histological examination confirmed the clinical diagnosis of CJD.     

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.     

Short latency somatosensory evoked potentials and brain-stem auditory evoked potentials in coma due to CNS depressant drug poisoning. Preliminary observations

In patients in coma due to severe CNS depressant drug overdose the central somatosensory conduction time (CCT) after median nerve stimulation is prolonged and N20 is dispersed. Brain-stem auditory evoked potentials demonstrate delayed interpeak latencies (IPLs) I-III, III-V and I-V. This was observed in 4 out of 5 patients investigated after intake of an overdose of amitriptyline (2 cases), barbiturates, meprobamate and nitrazepam (one case each). Toxic levels of drug overdose were related to prolonged CCT and IPLs, whereas normal CCT and IPLs were found at therapeutic drug plasma levels. CCT, IPLs and dispersion of N20 decreased during the course of coma. All patients were successfully treated. It appeared that SSEP and BAEP investigations could make a distinction between a 'toxic' and a 'therapeutic' coma level in severe drug overdose. It further appeared that normalization of CCT and IPLs preceded clinical improvement.     

Delayed-onset encephalopathy and coma in acute organophosphate poisoning in humans

The objective of the study was to describe the clinical characteristics and course of delayed-onset organophosphate (OP) poisoning. In our clinical experience, we have noticed patients with onset of deep coma 4-7 days after hospital admission, clinical features that have not been previously described. We set up a prospective observational study over 1 year to formally characterize this observation. Thirty-five patients admitted to the intensive care unit (ICU) with severe OP poisoning and treated with atropine and supportive therapy were followed up. Oximes were not administered. Three patients developed delayed-onset coma after presenting with normal or near normal Glasgow coma score (GCS). They developed altered conscious state rapidly progressing to deep coma, 5.0+/-1.0 (mean+/-S.D.) days after OP ingestion. The GCS persisted at 2T for 4.3+/-2.1 days despite the cessation of sedative drugs at the onset of coma. During this period, the patients had miosed non-reacting pupils and no clinically detectable cortical or brainstem activity. Computed tomography of the brain and cerebrospinal fluid analysis were normal. Electroencephalogram showed bihemispheric slow wave disturbances. Two patients required atropine during this period to maintain heart rate and reduce secretions. In all three patients, no metabolic, infective or non-infective cause of altered conscious state was identified. With supportive therapy the GCS improved to 10T in 8.0+/-2.0 days. All patients survived to hospital discharge. Three other patients who developed a reduction in GCS (3T-7T) by 4.7+/-1.2 days but not progressing to coma and recovering (GCS 10T) in 3.3+/-0.6 days may have manifested delayed-onset encephalopathy. Delayed-onset coma appears to have a distinct clinical profile and course with complete resolution of symptoms with supportive therapy. Although persistent cholinesterase inhibition is likely to have contributed to the manifestations, the mechanism of coma and encephalopathy need to be explored in further trials. The good outcomes in these patients suggest that therapy should not be limited in OP-poisoned patients developing profound coma or encephalopathy during hospitalization.     

Electrogastroenterographic study of the digestive motor effects of prolonged psychotropic treatment]

Functional digestive complaints are frequent in psychiatri patients: simple constipation, which cannot be explained solely by the loss of the sensation of rectal fullness; occlusions, occasionally hemorragies; the late complication of dolichomegacolon (Bourgeois, 1973). In 160 subjects, an attempt to understand the physio-pathology were made by recording diurnal digestive motor activity using skin electrodes placed on the abdomen and extremities (electrogastroenterography or E.G.E.G.). A hypoactive E.G.E.G. was observed in 2/3 of 18 psychotic depressive patients, in 3/4 of 36 schizophrenies. The nocive effect of giving sedative phenothiazine and antiparkinsonian drugs (trihexyphenidyl or ethybenzatropine) during long periods is clear. Whereas non sedative phenothiazine and clotiapine gicen in small doses, do not have an undesirable effect. Sulpiride has been used in gastroduodenal dyskinesia. The dyskinesia noted by the E.G.E.G., sometimes found in the large intestin, were found in 55% of 30 patients with caracter disorders; they coincide with the high frequency of electro-encephalogram dysrythmies. Finally, in hysterical patients, one usually observes normal E.G.E.G., tracings which confirms the clinical observation that hysterical and psychosomatic symptoms, may succeed each other, but do not appear at the same time. In the same categories of patients, no longer treated in a classical psychiatric environment but in a group with institutional objectives, the same clinic results were obtained with fewer digestive disturbances. This tends to show the inutility and nocivity of excessive doses of psychotropic drugs given alone or in complexe association.     

Therapeutic coma for the treatment of status epilepticus

Background

There are scarce data available on the treatment of refractory status epilepticus (SE) where general anesthetics are recommended. However, these may be related to increased morbidity (and possibly mortality).

Question

When and how should therapeutic coma be used in this clinical setting?

Methods

Critical review of available international literature in the past 50 years as well as of personal experience.

Results

Patients with generalized convulsive or nonconvulsive SE in coma not responding to benzodiazepines and an antiepileptic drug should be treated under electroencephalographic (EEG) monitoring with coma induction and general anesthetics. Initially, midazolam/propofol seem to represent the safest options. A progressive weaning attempt should be made after 24?h without EEG seizures. Patients with absence SE should never be treated with coma, and in those with focal SE with preserved consciousness coma should be deferred after the trial of other nonsedating compounds. In cases of super-refractory SE, ketamine and/or a ketogenic diet may be considered.

Conclusion

In view of the limited current evidence, it seems reasonable to avoid indiscriminate use of general anesthetics in SE.

     

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.     

Gating of myotonic Na channel mutants defines the response to mexiletine and a potent derivative.

BACKGROUND: Myotonia and periodic paralysis caused by sodium channel mutations show variable responses to the anti-myotonic drug mexiletine. OBJECTIVE: To investigate whether variability among sodium channel mutants results from differences in drug binding affinity or in channel gating. METHODS: Whole-cell sodium currents (I(Na)) were recorded in tsA201 cells expressing human wild-type (WT) and mutant skeletal muscle sodium channels (A1156T, hyperkalemic periodic paralysis; R1448C, paramyotonia congenita; G1306E, potassium-aggravated myotonia). RESULTS: At a holding potential (hp) of -120 mV, mexiletine produced a tonic (TB, 0.33 Hz) and a use-dependent (UDB, 10 Hz) block of peak I(Na) with a potency following the order rank R1448C > WT approximately equal A1156T > G1306E. Yet, when assayed from an hp of -180 mV, TB and UDB by mexiletine were similar for the four channels. The different midpoints of channel availability curves found for the four channels track the half-maximum inhibitory value (IC50) measured at -120 mV. Thus differences in the partitioning of channels between the closed and fast-inactivated states underlie the different IC50 measured at a given potential. The mexiletine-derivative, Me7 (alpha-[(2-methylphenoxy)methyl]-benzenemethanamine), behaved similarly but was approximately 5 times more potent than mexiletine. Interestingly, the higher drug concentrations ameliorated the abnormally slower decay rate of myotonic I(Na). CONCLUSIONS: These results explain the basis of the apparent difference in block of mutant sodium channels by mexiletine and Me7, opening the way to a more rationale drug use and to design more potent drugs able to correct specifically the biophysical defect of the mutation in individual myotonic patients.     

Fatal disseminated hemorrhagic toxoplasmic encephalitis as the initial manifestation of AIDS

A 28-year-old woman presented with progressive coma after being asymptomatic for 1 year after the demonstration of seropositivity for human immunodeficiency virus and high serum immunoglobulin G toxoplasma titers. Computed tomographic scanning showed multiple rounded cerebral hemorrhages and massive cerebral edema. Postmortem examination disclosed Toxoplasma gondii cysts scattered throughout the brain. An overwhelming fatal toxoplasmosis associated with multiple cerebral hemorrhages may be the first presentation of the acquired immunodeficiency syndrome. We raise the possibility that frequent neuroradiological monitoring may be indicated in asymptomatic human immunodeficiency virus-infected patients with high immunoglobulin G toxoplasma titers.     

Brainstem auditory evoked potential in Japanese encephalitis.

Japanese encephalitis (JE) is associated with varying degrees of coma and brainstem involvement is frequent which can be evaluated and monitored by brainstem auditory evoked potential (BAEP). The present study has been undertaken to evaluate the BAEP changes and their role in predicting the outcome. Twelve adult patients with JE were subjected to CT scan, MRI and BAEP studies after detailed neurological evaluation. The severity of coma was assessed by Glasgow coma scale and outcome was defined at the end of 3 months into good and poor recovery on the basis of Barthel Index score (BI). The mean age of the patients was 28.3 years (range 14-50), and four of them were females. Most of the patients were comatose. The mean Glasgow coma scale (GCS) score was 7 (range 4-11). There were no brainstem signs or cranial nerve palsy. Cranial CT scan revealed thalamic hypodensity in four, whitematter oedema in three and left putaminal hypodensity in one patient. Cranial MRI was carried out in eight patients which revealed bilateral thalamic lesions in all, basal ganglia and midbrain lesions in three each and pontine and cerebellar lesions in one patient each. Brainstem auditory evoked potentials were recordable bilaterally. The absolute latency of wave I, II, III, IV and V and interpeak latencies (IPL) of I-V, III-V, and I-III were normal. The V/I amplitude ratio were significantly reduced in five patients. The BAEP abnormalities correlated with brainstem lesions on CT or MRI but not with severity of coma or outcome. The reduced amplitude ratio of wave V/I may be due to raised intracranial tension or brainstem involvement in JE.     

P300在鉴别闭合性颅脑外伤患者真假昏迷的价值

目的：研究P300在鉴别闭合性颅脑外伤患者真假昏迷的价值。方法：将237例闭合性颅脑外伤患者根据其有否昏迷史分为有昏迷组,无昏迷组,假昏迷组及不详组,并对各组视觉（图像）刺激诱发的异常P300波潜伏期和波幅进行比较分析。结果：昏迷组与无昏迷组的P300潜伏期和波幅有非常显著的差异（P＜0．001）;昏迷组与假昏迷的P300潜伏期和波幅亦有非常显著的差异（P＜0．001）;但无昏迷组与假昏迷组间无明显差异（P＞0．05）;昏迷史不详组与无昏迷组间有显著差异（P＜0．05）。结论P300波的变化可作为判断闭合性颅脑外伤患者有无昏迷的一项客观指标,在外伤事故鉴定中有重要的参考价值。     

昏迷危险因素的病例对照研究

目的研究昏迷发病的危险因素。方法连续收集223例住院的昏迷病人作为病人组(昏迷组).以同期住院的223例危重非昏迷病人为对照组(非昏迷组)。采用统一调查表和诊断标准对所有对象的一般情况、原发或主要疾病、急性并发症或器官衰竭、慢性脏器功能障碍等进行调查。应用单因素和多因素分析方法对有关因素进行分析。结果单因素分析表明,符合3项和4项标准的全身炎症反应综合征(SIRS 3-4)、急性呼吸衰竭、休克、急性肾衰、血糖过高、继发性全身性癫痫、第二原发疾病、原有脑软化,是昏迷的危险因素(P<0.05)。Logistic回归在校正了休克等因素后,SIRS3-4(OR=7.8,95％CI=4.307-14.001)、急性呼吸衰竭(OR=5.2,95％CI=1.683-16.242),继发性全身性癫痫(OR=2.6,95％CI=1.095-5.998)仍与昏迷密切有关。结论除昏迷的原发疾病外,多种急性并发症或器官衰竭,包括SIRS 3-4、急性呼吸衰竭、继发性全身性癫痫等,也是昏迷的主要危险因素。这些危险因素可以联合或单独作用引起昏迷。