Effect of acute ammonia intoxication on cerebral metabolism in rats with portacaval shunts.

Rats were made chronically hyperammonemic by portal-systemic shunting and, 8 wk later, were subjected to acute ammonia intoxication by the intraperitoneal injection of 5.2 mmol/kg of ammonium acetate. In free-ranging animals, ammonia treatment induced a brief period of precoma (10-15 min) that progressed into deep, anesthetic coma lasting for several hours and was associated with a high mortality. In paralyzed, artificially ventilated animals that were lightly anesthetized with nitrous oxide, acute ammonia intoxication caused major disturbances of cerebral carbohydrate, amino acid, and energy metabolism that correlated in time with the change in functional state. At 10 min after injection (precoma), the concentrations of most glycolytic intermediates were increased, as was the lactate/pyruvate ratio. Citrate declined, despite a twofold rise in pyruvate, suggesting that the conversion of pyruvate to citrate had been impaired. Concentrations of phosphocreatine, and of the putative neurotransmitters, glutamate and aspartate, declined during precoma, but the concentrations of the adenine nucleotides in the cerebral hemispheres, cerebellum, and brain stem remained within normal limits. At 60 min after injection (coma), ATP declined in all regions of brain; the reduction in total high-energy phosphates was most notable in the brain stem. The findings indicate that cerebral dysfunction in chronic, relapsing ammonia intoxication is not due to primary energy failure. Rather, it is suggested that ammonia-induced depletion of glutamic and aspartic acids, and inhibition of the malate-asparate hydrogen shuttle are the dominant neurochemical lesions.

Are the vascular effects of naloxone attributable to the preservatives methyl- and propylparaben?

In vitro, the Nalonee preparation of naloxone caused a concentration-dependent relaxation of human pial cortical arteries contracted by potassium, noradrenaline, serotonin, prostaglandin F2 alpha (PGF2 alpha), and haemorrhagic cerebrospinal fluid, or inhibited contractions elicited by these agents. However, the preservatives in the Nalonee preparation, methyl- and propylparaben, had similar effects. Pure naloxone alone had no effect on potassium or PGF2 alpha-induced contractions. It is suggested that the relaxant effects on vascular smooth muscle of Nalonee can be attributed to the alkylparabens rather than to naloxone. The pronounced relaxations induced by the alkylparabens had a rapid onset, and they were stable and could easily be cleared after rinsing.

Antineural antibodies in Guillain-Barré syndrome and lymphocytic meningoradiculitis (Bannwarth's syndrome).

Antineural antibodies occur in Guillain-Barré syndrome (GBS), but have not been studied in lymphocytic meningoradiculitis (Bannwarth's syndrome), which has clinical features in common with GBS. Employing a sensitive complement-fixation assay with homogenates of nerve root and brain as antigens, we recorded positive serum reactions to either tissue in 14 of 18 samples from patients with GBS during the first three weeks of the disease. Five of nine samples were positive during the fourth to eighth weeks, whereas all seven patients sampled thereafter had negative reactions. Four GBS serum samples reacted only with nerve root, seven reacted only with brain, and eight reacted with both antigen preparations. One of 12 patients with meningoradiculitis and one of 50 supposedly healthy blood donors had serum antibodies to brain. Our results support the concept of an autoimmune mechanism in GBS, while in Bannwarth's syndrome an infectious cause related to that of Lyme disease may be suspected.

II. Improved dark adaptation after carotid endarterectomy. Evidence of a long-term ischemic penumbra?

We have reported that dark vision is impaired in symptomatic carotid artery disease and that the impairment correlates with internal carotid artery stenosis. To find out whether this impairment is reversible after carotid endarterectomy, dark adaptation was examined pre- and postoperatively. Twenty-one consecutive patients were examined by dark adaptometry. Two examinations were done for each eye on two consecutive days pre- and postoperatively. Thirty-one matched control subjects were examined under identical conditions. The control subjects did not have clinical evidence of carotid artery disease. Patients and control subjects were free of ophthalmologic disorders. Dark vision frequently improved remarkably after endarterectomy. The average retinal sensitivity to light in darkness on the operated side doubled, and there was also improvement on the nonoperated side. There was no significant change in dark vision in the control subjects, negating a learning effect. The findings suggest the existence of reversible neuronal ischemia secondary to hemodynamic causes or frequent subclinical microembolization. Because the circulatory conditions are optimized, formerly inactive, surviving neurons may regain function.

I. Impaired dark adaptation in symptomatic carotid artery disease.

It has been known for more than a century that even slight hypoxemia reduces dark adaptation. We studied dark adaptation in symptomatic carotid artery disease. Twenty-one consecutive patients scheduled for first-time carotid endarterectomy and 31 age-matched control subjects with normal carotid arteries were examined by dark adaptometry monocularly and were tested repeatedly on consecutive days. The average degree of internal carotid stenosis on the symptomatic side was much greater than that on the contralateral side. Dark adaptation was markedly impaired in the patients as compared with the control subjects. In the patients there was no difference in dark adaptation between the symptomatic and nonsymptomatic sides. The existence of carotid stenosis correlated to the level of dark adaptation. Pupillary size and age correlated to the dark adaptational level but did not affect the effect of carotid stenosis on dark adaptation. The decreased dark adaptation may be due to insufficient blood supply or repeated subclinical microembolization to the retinae, the brain, or both.

Human ocular vasodynamic changes in light and darkness.

PURPOSE: To determine whether changes in the retinal blood flow in light and darkness occur in humans. METHODS; The systolic and diastolic flow velocities were measured by color Doppler in the ophthalmic and the central retinal arteries in 12 healthy individuals in light and darkness. RESULTS: In the ophthalmic artery there was a trend toward lower systolic velocity in darkness compared with that in the light, but there was no change in diastolic velocity. In the central retinal artery the systolic and the diastolic flow velocities were markedly increased in darkness. After re-exposure to light the systolic flow velocity decreased. CONCLUSIONS: Darkness is associated with increased blood flow velocity in the central retinal artery, probably reflecting increased retinal metabolic demands by the photoreceptors.

Altered open-field behavior in experimental chronic hepatic encephalopathy after single venlafaxine and citalopram challenges.

RATIONALE: Latent or manifest chronic hepatic encephalopathy (HE) symptomatology often includes affective symptoms. It is therefore warranted to investigate the functional outcome of novel antidepressants when chronic HE prevails. OBJECTIVE: Portacaval shunt (PCS) in rats is a widely used experimental model for chronic HE, a neuropsychiatric syndrome accompanying liver dysfunction. HE is believed to arise from a primary alteration in neurotransmission in the CNS. PCS has been reported to increase the metabolism of serotonin in the brain, and thus the central serotonin nerve of PCS rats may contain more serotonin than normal. However, the functional relevance of this serotonergic alteration in terms of affecting behavioral performance of PCS rats has been only rarely studied. METHODS: Locomotor and rearing activities were recorded in PCS and sham-operated control rats. A single subcutaneous challenge with saline versus either the mixed serotonin/noradrenaline reuptake inhibitor venlafaxine (10 mg x kg(-1)) or the selective serotonin reuptake inhibitor citalopram (5 mg x kg(-1)) were performed. RESULTS: The PCS-saline injected rats showed reduced locomotor and rearing activity compared with sham-saline treated rats. While no significant differences could be observed following the venlafaxine challenge to controls, the PCS-venlafaxine challenged rats displayed reduced behavioral activity as compared to PCS-saline treated rats. The PCS-citalopram rats, however, displayed increased activity compared with the PCS-saline rats while, again, no effect of the citalopram challenge to controls was found. CONCLUSIONS: The present study show altered but opposite behavior in PCS rats, when challenged with either venlafaxine or citalopram, compared to PCS control rats. These findings therefore support the contention that caution should be advocated when CNS monoamine active drugs are used in liver-impaired subjects until better delineation of the combined pharmacodynamic and pharmacokinetic outcome for each such drug in this condition has been made.

Diurnal and gender effects by chronic portacaval shunting in rats on spontaneous locomotor and rearing activities in an open-field.

Behavioural disturbances in chronic experimental hepatic encephalopathy (HE) have been investigated for several decades, but only in recent years, the possibility for gender-dependent reduction of spontaneous locomotor activity has come under attention. Unfortunately though, the results of such gender dependency have been discrepant. We therefore performed an open-field behavior study in unhabituated female and male portacaval shunted (PCS) rats during both day- and night-time, monitoring locomotor as well as rearing activity for a 60 min period. The results revealed lower locomotor and rearing activities in both male and female PCS rats during night-time, compared to sham-operated controls. Daytime differences could only be detected in the rearing activity of female PCS versus control rats. Female PCS rats also spent less cumulated time rearing, compared to controls but no differences regarding the overall locomotor/rearing activity ratio or portion of the behaviours exerted in the central area of the open-field could be detected between PCS and controls, or between the sexes. Diurnal activity differences were found between control groups of both sexes but not between the female versus male PCS rats. Thus, our results are not supportive of any major gender-dependent behavioural disturbance between PCS and control rats.

Altered adaptive behaviour expressed in an open-field paradigm in experimental hepatic encephalopathy.

Chronic hepatic encephalopathy (HE) encounters a neuropsychiatric syndrome arising as a complication to liver dysfunction. Patients with chronic HE display a great variety of neuropsychiatric symptoms including such mental derangements as adaptational difficulty, and deteriorated learning and memory capacity. The portacaval shunt (PCS) in the rat is a widely used model for experimental chronic HE. In the present study, the adaptive capacity of unhabituated PCS rats and sham-operated control rats were studied by measuring two exploratory behaviours (locomotion and rearing) during 5 or 60 min, at four consecutive days or nights with 24 h between sessions. The results revealed that PCS and sham-operated control rats showed parallel behavioural outcome over the four sessions in the 5-min trial. However, at the four consecutive test sessions in the 60-min trials, the sham-controls displayed a continuing decrease in overall activity between sessions whereas the PCS rats evidenced a repeated and stable activity level. These results indicate a presence of a long-term habituation deficiency as exhibited by the PCS rats. Additionally, the results indicate that differences in normal open-field motor behaviour between PCS rats and controls may not be found if such tests are conducted repeatedly during night-time but may emerge when tested repeatedly during daytime. The results may also be interpreted as a possible impaired learning/memory capacity in PCS rats. However, further investigations of how the PCS procedure affects entities of adaptation and learning ability are needed before any conclusions may be drawn since this is the first report of such an impairment in experimental chronic HE when represented by the PCS rat.

Experimental porta-caval anastomosis and motor nerve conduction velocity in the rat.

The influence of portal-systemic shunting on maximal motor nerve conduction velocity (MCV) was analyzed in rats with portacaval shunts. At 3 and 8 weeks after the shunting there was a marked but transient fall in MCV. This was not prevented by colectomy. At 16 weeks the MCV had almost normalized, despite sustained portal-systemic shunting. When examined at 3 weeks postoperatively, MCV was less affected by ischaemia than in control animals. The results favour hepatocellular failure as the more important pathophysiological mechanism in hepatic neuropathy.

The electrocardiogram in infratentorial infarcts.

Sixty-nine patients with infratentorial infarcts were studied with respect to associated electrocardiographic (ECG) abnormalities. ECG changes were encountered in about 70% of the patients, the most frequent abnormalities being arrhythmias, conduction disturbances and ST-T changes. No relationship was found between the localization of the brain-stem lesion and the accompanying ECG pattern. It is concluded that ischaemic lesions within the central nervous system do not per se affect the ECG and that associated ECG changes are merely coincidental, reflecting the same basic vascular disease.

Carotid fibromuscular dysplasia and paresis of lower cranial nerves (Collect-Sicard syndrome). Case report.

A patient suffered the acute onset of unilateral pareses of the ninth through 12th cranial nerves (Collet-Sicard syndrome). Ipsilateral retrograde jugular phlebography and carotid angiography revealed irregular aneurysmal changes of the internal carotid artery at the base of the skull, causing compression of the internal jugular vein below the jugular foramen. This finding is discussed in relation to the clinical symptoms and signs, and possible mechanisms are examined. Family history as well as the clinical and roentgenological findings were compatible with a diagnosis of fibromuscular dysplasia.

Effects of indomethacin and prostacyclin on isolated human pial arteries contracted by CSF from patients with aneurysmal SAH.

In small human cerebral arteries preincubated with indomethacin, contractions induced by cerebrospinal fluid (CSF), from patients with subarachnoid hemorrhage were markedly increased. Also contractions induced by noradrenaline, but not 5-hydroxytryptamine, were augmented. Prostacyclin and its metabolite 6-keto-prostaglandin (PG)E1 reversed the contractions induced by CSF, as well as by noradrenaline, 5-hydroxytryptamine, and PGF2 alpha. The findings suggest that these substances are able to counteract the influence of vasoconstrictor material in hemorrhagic CSF. If the capacity to synthesize these "protective" arachidonic acid metabolites is reduced, the resulting imbalance between contractile and relaxant forces acting on the vessel wall may lead to sustained cerebral vasoconstriction.

Vasoconstrictive effects of human post-hemorrhagic cerebrospinal fluid on cat pial arterioles in situ.

Cat cortical arterioles were exposed in vivo to cerebrospinal fluid (CSF) from four patients with subarachnoid hemorrhage (SAH) due to a ruptured intracranial aneurysm. Pial arteriolar caliber was measured by the television image-splitting technique. There was a consistent vasoconstrictive response to CSF. This effect could be ascribed neither to the pH of the CSF nor to the potassium concentration. The vasoconstriction, which was more pronounced with decreasing arteriolar caliber, could be resolved by the perivascular application of nifedipine.

Outcome evaluation following subarachnoid hemorrhage.

Seventy-eight individuals among a population of 1.46 million suffered aneurysmal subarachnoid hemorrhage (SAH) during 1983. Within 24 hours after the bleed, 32 of the 78 patients were in Hunt and Hess neurological Grades I to II, 13 were in Grade III, 21 were in Grades IV to V, and 12 were dead on admission to a hospital or forensic department. When the amount of blood visualized on computerized tomography (CT) scanning was integrated with the Hunt and Hess neurological classification in order to improve prediction of prognosis, only 16 patients were considered to have a good prognosis (CT-modified Grades I to II), 21 had a less favorable prognosis (CT-modified Grade III), and 29 had a poor prognosis (CT-modified Grades IV to V). Assessment at 1 year revealed that only 32 patients (41%) had a good physical recovery. The physical morbidity rate was 22%, and the overall mortality rate was 37%. Twenty-six individuals with a good neurological outcome and five with a fair outcome also underwent reexamination 1 year or more post-SAH, which included a comprehensive evaluation of the quality of life, assessment of cognitive dysfunction, and determination of general adjustment. Five of the patients with a good neurological outcome and all five with a fair outcome (four of whom had had a poor prognosis in the acute stage) showed severe psychosocial and cognitive incapacitation. When functional morbidity, based upon persistent severe cognitive and psychosocial impairment, was included in the outcome assessment, only 33% of the total series was considered to have a favorable outcome. Approximately 60% of the initially good-risk patients (Grades I and II) showed a good physical outcome without concomitant indications of severe cognitive dysfunction and/or psychosocial impairment. Among the good-risk patients with a CT-modified grade, the figure was 70%. It is suggested that in any outcome grading system, persistent cognitive and psychosocial disturbances be taken into account.

Central vs. peripheral spontaneous behavioral abnormalities in experimental hepatic encephalopathy.

The most common behavioral disturbance reported in experimental chronic hepatic encephalopathy (HE) refers to changes in spontaneous activities in an open field in the portacaval-shunted (PCS) rat. A major problem at present is that not all of these findings of abnormal PCS behavior are in agreement. We, therefore, investigated the total, central, and peripheral locomotor and rearing activities in an open field 2 and 6 months after PCS surgery. The results revealed that, 2 months after surgery, locomotor and rearing activities were lower in PCS rats compared to controls. At 6 months, a partial remission of the behaviors had occurred. Clearly though, as pointed out by the peripheral behavioral recordings, the hypoactivity persisted and, interestingly, central locomotor activity as higher in PCS rats than in controls. This novel finding may be attributed to the special study of central vs. peripheral components of the spontaneous open-field behavior in experimental chronic HE. Our observations may also help explain some of the seemingly discrepant results available in the literature.

Assessment of respiration during video fluoroscopy of dysphagic patients.

RATIONALE AND OBJECTIVES: The authors evaluated the coordination of swallowing and respiration in dysphagic patients. MATERIALS AND METHODS: Video fluoroscopy and respirometry were performed simultaneously during 98 swallows in 33 patients (18 women, 15 men) with a median age of 70 years (interquartile range, 52-78 years). Pharyngeal transit time, deglutition apnea, and the ratio between the two (swallowing safety index) were calculated. Presence of a misdirected swallow (aspiration or penetration) was indicated. RESULTS: Pharyngeal transit time was not associated with deglutition apnea. Misdirected swallow was associated with a slightly prolonged pharyngeal transit time, a slightly shorter deglutition apnea, and a significantly lower swallowing safety index (1.8 [1.0-4.2] vs 4.5 [2.4-6.7]; P < .001) compared with normally directed swallow. The association between misdirected swallow and lower swallowing safety index was independent of pharyngeal transit time. CONCLUSION: Assessment of respiration is important in the evaluation of dysphagia. Aspiration, especially in elderly dysphagic patients, may be a consequence of primarily disturbed respiration. A low swallowing safety index may indicate risk of misdirected swallow.

Visually evoked slow eye movements, visual-vestibular interaction, and infratentorial lesions.

The maximum velocity gain of smooth pursuit and optokinetic, vestibular, and optovestibular slow phases was examined in 15 patients with pontine, 10 with medullary, 10 with cerebellar, and 5 with combined cerebello-brain stem disorders. Marked dissociations were observed between smooth pursuit and optokinetic slow phases, especially in medullary disease. A cerebellar deficit enhanced slow phase velocity gain during rotation in darkness, whereas the corresponding gain during rotation in light was normal.

Eye movements in cerebellar and combined cerebellobrainstem diseases.

We report a quantitative analysis of eye movement disturbances in patients with isolated cerebellar disorders and patients with cerebellar disorders and concomitant brainstem involvement. The most characteristic abnormalities in the exclusively cerebellar patients were increased velocities of the slow phases of vestibular nystagmus induced by rotation in the dark and increased peak velocities of the fast phases of optokinetic nystagmus induced by full-field optokinetic stimuli. Dysmetria of saccades was found in three of six cerebellar patients and gaze nystagmus in all six patients. The typical findings in the combined cerebellobrainstem group were reduced peak velocities of voluntary saccades, defective smooth pursuit and reduced peak velocities of the fast component of nystagmus during rotation in both the dark and light. All patients with combined cerebellobrainstem disorder had dysmetric voluntary saccades and gaze nystagmus. The numbers of superimposed saccades during smooth pursuit were uniformly increased. Release of inhibition in cerebellar disorders may explain the hyperresponsiveness and inaccuracy of eye movements found in this study. In addition, when lesions also involve the brainstem, however, integrative centers coding eye velocity are affected, leading to slow and inaccurate eye movements. These features elicited clinically may be useful in the diagnosis of cerebellar and brainstem disorders.

Eye movements in brainstem lesions.

The eye movements of 10 patients with brainstem lesions were examined, using an electro-oculo-graphic technique. An analysis was made of the responses in the following tests: smooth pursuit, saccade, rotation, optokinetic, optovestibular and caloric. Chief interest was directed towards the peak velocity. The results were compared with the corresponding velocities in 20 normal subjects. In the same patient, one or several types of eye movements could be normal, while others were pathological. In the whole group, voluntary eye movements (smooth pursuits and voluntary saccades) were more vulnerable than reflexive ones (nystagmus). Next to the smooth pursuit test and the voluntary saccade test, the optovestibular test was the most sensitive in discriminating patients with brainstem lesions from normal subject.