Somatosensory evoked potentials in severe traumatic brain injury: a blinded study.

OBJECT: Beginning in 1979, the results of somatosensory evoked potential (SSEP) monitoring have been used to predict outcome in patients who have suffered severe brain trauma. The data indicate that if the cortical components of the SSEPs were bilaterally absent, the outcome was always death or a vegetative state, but previous studies have not been blinded. The aims of this study were to correlate the results of SSEP recordings with the outcome in a prospectively blinded manner and to assess whether monitoring of SSEPs was a useful adjunct to clinical judgment in the prediction of outcome. METHODS: The authors studied 105 severely head injured patients (median Glasgow Coma Scale score of 6) who were admitted to the Waikato Intensive Care Unit. The upper limb SSEPs were classified according to the central conduction time (CCT) as normal, of increased latency, or absent. The outcome as assessed using the Glasgow Outcome Scale (GOS) score was evaluated 12 months after the injury. CONCLUSIONS: Of 51 patients with a bilaterally normal CCT, 29 (57%) had a good outcome (GOS Score 5). Any delay in CCT was associated with a decreased incidence of good outcome (30%). Unilateral absence of the cortical component of the SSEP was usually associated with a poor outcome (death or severe disability), and bilateral absence was always associated with a poor outcome. The authors conclude that SSEPs correlate well with outcome and that this is not the result of investigator bias.

Discovery of MC-02,331, a new cephalosporin exhibiting potent activity against methicillin-resistant Staphylococcus aureus.

A systematic approach toward building activity against methicillin-resistant staphylococci into the cephalosporin class of beta-lactam antibiotics is described. Initial work focused on finding the optimal linkage between the cephem nucleus and a biphenyl pharmacophore, which established that a thio linkage afforded potent activity in vitro. Efforts to optimize this activity by altering substitution on the pharmacophore afforded iodophenylthio analog MC-02,002, which although highly potent against MRSA, was also highly bound to serum proteins. Further work to decrease serum protein binding showed that replacement of the iodo substituent by the positively-charged isothiouronium group afforded potent activity and reduced serum binding, but insufficient aqueous solubility. Solubility was enhanced by incorporation of a second positively-charged group into the 7-acyl substituent. Such derivatives (MC-02,171 and MC-02,306) lacked sufficient stability to staphylococcal beta-lactamase enzymes. The second positive charge was incorporated into the cephem 3-substituent in order to utilize the beta-lactamase-stable aminothiazolyl(oximino)acetyl class of 7-substituents. These efforts culminated with the discovery of bis(isothiouroniummethyl)phenylthio analog MC-02,331, whose profile is acceptable with respect to potency against MRSA, serum binding, aqueous solubility, and beta-lactamase stability.

Conversational conduct and the symptoms of schizophrenia.

In an attempt to refine further the argument that certain patients with schizophrenia have problems understanding the mental states of other people, appreciation of the Gricean maxims of quantity, quality, and relation, and the more contextually specific need to be polite was examined amongst patients differing in their current symptom profiles. Five sets of five stories were given to the subjects who had to choose the likely final piece of speech of one of the characters. Subjects chose from two alternatives, one adhered to the rule under question whereas the other flouted that rule. Patients with negative symptoms were inclined to flout all maxims with the exception of the maxim of relation which was adhered to by all groups. It is argued that these patients have a severe ''theory of mind'' deficit that encompasses knowledge of conversational rules. The performance of patients with paranoid delusions was more selective in that they often failed to respond in a polite fashion when this was indicated by the context but performed at a level with controls on the stories involving the original Gricean maxims. These effects were largely independent of current intellectual level. The results suggest that although patients with negative behavioural signs suffer a ''theory of mind'' deficit similar to that seen in autism, those with paranoid symptoms have a more specific ''online'' mentalising deficit which becomes evident only when the skill is challenged by situations where context-dependent behaviour is determined by an appreciation of another's mental state.

Enzymatic quantification of 1,5-anhydro-D-glucitol: evaluation and clinical application.

We investigated an enzymatic colorimetric procedure for quantification of plasma 1,5-anhydro-D-glucitol (AG) with respect to its reproducibility and application for evaluation of diabetes mellitus. Assay specificity is critically dependent on the two-layer ion-exchange column chromatography procedure to remove glucose from the sample. For female nondiabetic subjects (n = 110, ages 22-36 years) the median plasma AG concentration was 143 mumol/L (range 70-209 mumol/L); there was no relation to body mass index (BMI), fasting plasma glucose, or insulin, but an inverse association was noted for age. For a group of older subjects (n = 69, 70-85 years), no association between AG concentrations and sex, age, BMI, or various medical conditions was found. In diabetic subjects (n = 170) a significant inverse nonlinear relation existed between plasma AG and glycohemoglobin (GHb) such that at GHb > 8.5%, AG concentrations were typically < 50 mumol/L. The findings confirm that plasma AG, in the presence of normal renal function, is a reliable marker for hyperglycemia.

Pattern visual evoked potential luminance and multiple sclerosis.

Pattern visual evoked potentials (PVEPs) were recorded from 111 patients classified as having possible, probable or definite multiple sclerosis. Patients were stimulated with a checkerboard pattern using high and low luminances in order to test the hypothesis that an attenuated pattern luminance increases the detection rate of PVEP abnormalities. With increasing certainty of diagnosis, there was a concomitant increase in the incidence of PVEP abnormalities. However, there was no evidence that stimulating with a lower luminance pattern enhanced the sensitivity of the test. The same findings were also apparent when the patient data was analyzed according to the presence or absence of a history of optic neuritis or other visual symptoms. It is concluded that, within the luminance limits used in this study, the role of varied luminance in detecting demyelinating lesions in the optic nerves using the PVEP is minimal, although there was some limited evidence that a high level of luminance may be more appropriate than a low level.

A comparison between electroencephalography and somatosensory evoked potentials for outcome prediction following severe head injury.

The value of somatosensory evoked potentials (SEPs) for the prediction of outcome following severe head injury (HI) is established. The role of the electroencephalogram (EEG) in this setting is uncertain. In this comparative study, SEPs and EEGs were recorded within 3 days of severe HI in 90 patients, and the results related to outcome at 6 months. Patients with an isoelectric EEG or an EEG with repeated isoelectric intervals died. Reactivity of the EEG to external stimulation tended to be associated with favorable outcome. Grading of the EEGs on the basis of frequency composition otherwise provided no prognostic information. The presence of SEP scalp potentials bilaterally predicted favorable outcome, particularly if the central conduction times were normal. Conversely, the absence of one of both scalp potentials was associated with unfavorable outcome. EEGs thus provided useful prognostic information in only a minority of patients. By comparison, SEPs allowed prediction of both favorable and unfavorable outcomes in a much larger number of patients, and were therefore prognostically superior.

Induction of c-fos mRNA and protein in neurons and glia after traumatic brain injury: pharmacological characterization.

Focal brain injury in mice induced c-fos mRNA and protein in neurons throughout the damaged neocortex, including the piriform and the entorhinal cortices, as well as in nonneural brain cells (e.g., glia, pia, ependyma). The pattern of c-fos induction after injury suggested that injury led to spreading depression which then led to c-fos induction in neurons. Human neurons in the temporal cortex and hippocampus also showed c-fos protein induction after neurosurgical trauma. The c-fos mRNA and protein induction in mouse neurons was prevented by the noncompetitive NMDA antagonist ketamine but only partially inhibited by the voltage-dependent calcium channel antagonist nifedipine and the calmodulin antagonist trifluoperazine. The c-fos protein induction in nonneural brain cells after injury was not affected by these drugs. Thus, induction of c-fos in neocortical neurons after focal brain injury is partly NMDA receptor mediated.

The relationship of eyelid movement to the blink reflex.

Although the blink reflex is a standard neurophysiological investigation its relationship with eyelid movement has not been clearly established. We studied normal subjects and patients with unilateral facial paralysis to define the pattern of eyelid movement following glabellar tap, supraorbital nerve stimulation, facial nerve stimulation and direct corneal stimulation. We found that eyelid closure did not necessarily occur in a single movement. Following glabellar tap the first component of a two-stage movement was initiated by levator palpebrae relaxation while with supraorbital nerve stimulation orbicularis oculi contraction produced the first movement. The compound muscle action potential following direct facial nerve stimulation produced only minimal eyelid movement, the major closure being associated with a longer latency orbicularis oculi reflex. Corneal stimulation elicited a single component eyelid movement. Thus, the pattern of eyelid movement differed for each stimulus reflecting variations in orbicularis oculi contraction and levator palpebrae inhibition.

Uvulopalatopharyngoplasty in severe idiopathic obstructive sleep apnoea syndrome.

Eleven patients with severe obstructive sleep apnoea syndrome, which was fully reversed by treatment with nasal continuous positive airways pressure, underwent uvulopalatopharyngoplasty. All patients were followed for at least 12 months after surgery. One patient with large tonsils was cured. Of the remaining 10 patients, two showed minimal objective improvement at 12 months and the rest were unchanged. Four patients subsequently developed cardiac failure due to obstructive sleep apnoea. Thus uvulopalatopharyngoplasty was not effective in these patients with severe idiopathic obstructive sleep apnoea syndrome.

Somatosensory evoked potentials following severe head injury: loss of the thalamic potential with brain death.

The thalamic component (P17) of the short-latency somatosensory evoked potential (SEP) was assessed to determine its usefulness in patients with severe head injury. Subjects were a group of patients admitted to the Auckland Hospital Critical Care Unit who subsequently died from head injury. In all instances where brain death was unequivocally established and a SEP recording made in close temporal proximity to the time of brain death the P17 potential was absent. When there was evidence of continuing brainstem activity and particularly where prolonged survival occurred following the last SEP recording the P17 potential remained intact bilaterally. This study shows that the presence or absence of the thalamic component of the short-latency SEP provides a reliable electrophysiological measure of brainstem function in patients where brain death has been suspected.

A new case of Creutzfeldt-Jakob disease associated with human growth hormone therapy in New Zealand.

A clinically atypical, neuropathologically verified case of Creutzfeldt-Jakob disease is described in a 32-year-old New Zealand woman with idiopathic hypopituitarism who had been treated in late adolescence (1970 to 1973) with human growth hormone processed from pooled cadaveric pituitary glands.

Origin of reprint requests.

One thousand consecutive reprint requests were classified according to their countries of origin. One third came from the United States of America and over 70% originated in six countries (USA, Czechoslovakia, France, West and East Germany and Canada). When reprint requests were adjusted for population size, a different order became apparent with Czechoslovakia requesting proportionally the most, followed by Israel, East Germany, Canada, Switzerland and Belgium. Approximately half of the reprint requests came from European countries with the overall rates for western and eastern European nations being similar. There were comparatively few requests received from Third World nations. The analysis questions several of the reasons commonly given for honouring reprint requests.

Somatosensory evoked potentials in syringomyelia.

The two types of upper limb somatosensory evoked potential abnormality observed in nine patients with syringomyelia were reduced amplitude or absent cervical potentials and an abnormal central conduction time. Although this pattern of abnormalities resembles that observed in other intrinsic spinal cord lesions, it differs from peripheral nerve diseases and cervical radiculopathy in which the central conduction time is normal.

Stationary waves recorded at the shoulder after median nerve stimulation.

A new recording method with a reference electrode on the stimulated arm defined two discrete far-field potentials just before the propagated near-field nerve action potential was recorded at Erb's point. Both potentials were stationary waves with the same latency at all recording sites. The first potential had the same onset and peak latencies as the propagated wave at the axilla; it corresponded to the first component of the P9 far-field potential recorded with scalp to noncephalic reference montages. The latency of the second potential coincided with that of the propagated wave entering the neck and corresponded to the peak of the P9 potential. The occurrence of these potentials where there are significant changes in the morphology of the volume conductor suggests that the P9 far-field potential is due to a change in the conducting medium that surrounds the nerve.

Obstructive sleep apnoea in Auckland: diagnosis and treatment.

In 1982 facilities for investigation of patients with sleep disorders were established at Auckland Hospital on a trial basis. Twenty patients with the obstructive sleep apnoea syndrome had been investigated and treated by the end of 1983. All were advised to avoid alcohol and sedatives and the obese patients were encouraged to lose weight. In the more severely affected patients either nasal continuous positive airway pressure or tracheostomy was used. The method of diagnosis and treatment are discussed.