Impaired dark adaptation in polycythemia. Improvement after treatment.

PURPOSE: To determine if dark adaptation is reduced in individuals with polycythemia and if so whether there is any improvement in dark adaptation after treatment. METHODS: Dark adaptation was recorded monocularly by automatic dark adaptometry in ten consecutive patients with polycythemia before and after treatment. Analogue investigations were performed in 31 healthy control subjects. RESULTS: Dark adaptation was markedly impaired in the patients as compared with the control subjects. After reduction of the red cell count and normalization of the hematocrit and hemoglobin the dark adaptation was markedly improved. There was no significant change in dark vision in the control subjects negating a confounding learning effect. CONCLUSION: The findings indicate a sustained but reversible neuronal hypofunction secondary to polycythemia. As the rheological abnormality was normalized, dark adaptation was improved, probably secondary to normalized microcirculation within the retina or the brain, or both, possibly with reactivation of formerly inactive neuronal cells.

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.

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.

Dysphagia in stroke: a prospective study of quantitative aspects of swallowing in dysphagic patients.

This is a prospective study of 100 consecutive stroke patients. Within 24 h after stroke onset they were asked specifically about swallowing complaints and subjected to a clinical examination including neurologic examination, Mini-Mental test, and Barthel score. Dysphagic patients were examined with the repetitive oral suction swallow test (the ROSS test) for quantitative evaluation of oral and pharyngeal function at 24 h, after 1 week, and after 1 month. At 6 months, the patients were interviewed about persistent dysphagia. Seventy-two patients could respond reliably at 24 h after the stroke onset and 14 of these complained of dysphagia. Non-evaluable patients were either unconscious, aphasic, or demented. The presence of dysphagia was not influenced by age or other risk factors for stroke. Facial paresis, but no other clinical findings, were associated with dysphagia. Dysphagia 24 h after stroke increased the risk of pneumonia but did not influence the length of hospital stay, the manner of discharge from hospital, or the mortality. The initial ROSS test, during which the seated patient ingests water through a straw, was abnormal in all dysphagic stroke patients. One-third of the patients were unable to perform the test completely. Above all, dysfunction was disclosed during forced, repetitive swallow. All phases of the ingestion cycle were prolonged whereas the suction pressures, bolus volumes, and swallowing capacities were low. Abnormalities of quantitative swallowing variables decreased with time whereas the prevalences of swallowing incoordination and abnormal feeding-respiratory pattern became more frequent. After 6 months, 7 patients had persistent dysphagia. Five of these were initially non-evaluable because of unconsciousness, aphasia, or dementia.

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.

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.

The enhanced ciliospinal reflex in asymptomatic patients with cluster headache is due to preganglionic sympathetic mechanisms.

An amplified ciliospinal reflex response has been documented in patients with cluster headache, lacking a Horner-like syndrome. The mechanism is unknown. Tentatively, it may be due to an increased release of monoamines from post-ganglionic sympathetic nerve endings or an increased density of postsynaptic adrenergic receptors in the dilatator muscle of the iris. The instillation of a 1% phenylephrine solution into the conjunctival sac induces mydriasis by stimulating postsynaptic adrenergic receptors in the dilatator muscle of the iris, while the instillation of a 2% tyramine solution causes mydriasis by releasing noradrenaline from the presynaptic sympathetic nerve terminals in the iris. According to these premises, a positive correlation should be expected between the ciliospinal reflex response and the pupillary response to tyramine, if the enhanced ciliospinal reflex response was due to an increased presynaptic release of monoamines. No such correlation was found. Nor was there any positive correlation between the ciliospinal reflex response and the pupillary response to phenylephrine, contradicting an increased density of postsynaptic monoaminergic receptors in the dilatator muscle of the iris as the explanation. However, there was a significant positive correlation between the pupillary responses to phenylephrine and tyramine, ruling out any functionally caused "denervation" hypersensitivity in the dilatator muscle of the iris. It is concluded that the amplified ciliospinal reflex response in cluster headache patients (lacking a Horner-like syndrome) reflects compensatory pathophysiological mechanisms proximal to the third-order sympathetic neuron.

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.

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.

Gender and diurnal effects on specific open-field behavioral patterns in the portacaval shunted rat.

Hepatic encephalopathy (HE) is a frequently observed neuropsychiatric syndrome with unknown pathogenesis in patients suffering from chronic liver failure. The portacaval shunted (PCS) rat has been extensively used as an experimental model for HE and for studying the effects of portal-systemic shunting. Previous behavioral studies on PCS rats have shown a number of abnormalities but there is no consensus about which abnormalities are characteristic. We therefore made a thorough descriptive study of 100 male and female PCS rats and sham-operated controls four to six weeks after the shunting procedure in an open field. The frequency, duration and average time sequence of various kinds of defined spontaneous behavioral patterns were investigated during both night and day in order to assess behavioral differences between PCS rats and sham-operated controls. The results indicate differences especially regarding motor exploratory behaviors such as forward locomotion and rearing. There were also differences in eating and sniffing behaviors. Our results show that the overall behavioral alteration seen in PCS rats compared to sham-operated controls is that of hypoactivity.

Ciliospinal reflex response in cluster headache.

The ciliospinal reflex response is mainly mediated by second- and third-order sympathetic nerves to the dilatator muscle of the iris. As the pupillary response to various pharmacological agents indicates a sympathetic dysfunction in patients with cluster headache, the ciliospinal reflex was studied in 25 patients. Five of these patients with cluster headache exhibited a Horner-like syndrome (miosis, ptosis) on the symptomatic side. The pupillary responses to phenylephrine and tyramine showed that the Horner-like syndrome was due to postganglionic sympathetic nerve dysfunction. Their ciliospinal reflex response on the symptomatic side was significantly less than in controls and in other patients with cluster headache, lacking a Horner-like syndrome. This also applied to the nonsymptomatic side compared to the majority of cluster headache patients without any clinical evidence of sympathetic nerve dysfunction. These findings seem to delineate those patients with a Horner-like syndrome as a subgroup, distinctly separated from the majority of cluster headache patients. Furthermore, the findings indicate that the Horner-like syndrome is not a consequence of repeated attacks of headache over many years, but is a manifestation of bilateral cephalic sympathetic dysfunction being more marked on the symptomatic side. In 18 (72%) of our 25 patients, an asymmetric and lower ciliospinal reflex response on the symptomatic side was seen. In 3 (12%) patients, there was no difference in the response. In 4 patients (16%), the incorrect side was indicated by an asymmetric reflex response. Two of these patients (8%) had suffered from cluster headache on alternating sides. In summary, the findings support the concept that dysfunction of the sympathetic nervous system, whether peripheral or central is involved in the pathophysiology of cluster headache.

Cluster headache in two sisters. Pupillary response to phenylephrine and tyramine.

Two sisters with cluster headache were studied with respect to the pupillary responses to instillation into the conjunctival sac of a single drop of a 1% solution of phenylephrine and a 2% solution of tyramine. The changes in pupillary diameters were documented by photographic pupillometry prior to and at 15, 30, 60, and 90 minutes after the instillations. Of the two sisters, one (case A) was examined during a symptom-free interval, when she had been free from cluster headache attacks for 2 1/2 years. When the cluster headaches recurred, retesting was performed. The other sister (case B) had been free from cluster headaches for 9 years, when she was examined. The findings indicate hypofunction within the postganglionic sympathetic nerve fibers during a cluster headache period. The hypofunction is bilateral, and thus, can not be a consequence of the unilateral cluster headache attacks. During remissions, tyramine induces a marked mydriasis, particularly on the symptomatic side, tentatively indicating an excessive release of stored monoamines.

The pupillary response to tropicamide in Alzheimer's disease.

An increased pupillary response to a weak solution of tropicamide has recently been suggested to be diagnostic for Alzheimer's disease. If so, it would have far-reaching implications. We performed a masked study involving 17 patients with Alzheimer's disease and 20 mentally healthy controls with respect to the pupillary response induced by tropicamide. We found no significant difference in pupillary dilatation between patients and controls (19.7 +/- 11% versus 19.1 +/- 9%; p = 0.19).

Clusterlike headache in a patient with a pituitary adenoma. With a review of the literature.

A man had left-sided atypical clusterlike headache for 9 years before he developed symptoms and signs consistent with acromegaly. Preoperative evaluation revealed raised levels of somatomedin C and growth hormone. An MR indicated a left-sided intrasellar mass measuring 8 x 7.5 x 10 mm. He underwent surgery and microscopy confirmed the diagnosis of a benign hypophyseal adenoma. Postoperatively, the acromegalic features regressed, and for the last 4 years the patient has been completely free from headache attacks. On pharmacological testing of the pupillary response to 1% and 5% phenylephrine and 2% tyramine solutions, there was no convincing evidence of persistent sympathetic dysfunction on the earlier symptomatic side.

Cerebrospinal fluid filtration in a case of severe pneumococcal meningitis.

Current therapy of bacterial meningitis includes high doses of antibiotics and, sometimes, addition of corticosteroids in order to reduce a harmful inflammatory response. The persisting high mortality and rate of sequelae, particularly regarding pneumococcal meningitis, calls for new therapeutic approaches. We report a case of a 71-year-old female with a pneumococcal meningitis treated with extra-corporeal filtration of cerebrospinal fluid (CSF) after 3 days of coma on conventional treatment. The treatment was carried out without complications and the clinical outcome was favourable. We suggest that filtration of the CSF should be considered as a tool to eliminate noxious substances playing a harmful role in deteriorating course of bacterial meningitis.

Quantitative aspects of swallowing in an elderly nondysphagic population.

The prevalence of swallowing impairment increases with age and is a major health care problem in the elderly. It has been assumed that age-related changes in nerves and muscles hamper muscle strength and coordination of swallowing. However, it is unclear what impairment is related to primary aging and what is the consequence of diseases prevalent in the elderly (secondary aging). In order to quantify swallowing in nondysphagic elderly we used the noninvasive ROSS (Repetitive Oral Suction Swallow) test. A total of 53 individuals aged 76 +/- 5 years (mean +/- SD) were examined. We found that the nondysphagic elderly demonstrated significant differences compared with young individuals in 10 of 17 measured variables, i.e., decreased peak suction pressure, increased frequency of multiple swallows after one ingestion, increased frequency of polyphasic laryngeal movements, increased frequency of inspiration after swallowing, and increased frequency of coughing during or after swallowing. Therefore, primary aging mainly seems to influence coordination of swallowing, but oral and pharyngeal swallow per se seem to be unaffected.

Quantitative assessment of swallowing in healthy adults.

Swallowing has hitherto been evaluated during physical examination, radiologic barium studies, manometry, and cervical auscultation. Radiography principally demonstrates qualitative aspects of oral and pharyngeal function, whereas quantitative aspects have primarily been documented by manometry. To evaluate swallowing quantitatively, without using invasive methods or radiation, we have applied a combined test of water drinking, i.e., the Repetitive Oral Suction Swallow test (ROSS). The test provides reliable measurements of suction pressure, bolus volume, timing of important events in oral and pharyngeal swallow, and respiration. The test is described and results from 292 healthy, non-dysphagic subjects are presented. We found a mean bolus volume of 25.6 +/- 8.5 ml during single swallow and 21.1 +/- 8.2 ml during stress (forced, repetitive swallow). During forced, repetitive swallow, the bolus volume was more strongly associated with suction time (r2 = 0.55) than with peak suction pressure (r2 = 0.04), indicating that suction time is more important than suction pressure in determining the bolus volume. The oral-pharyngeal transit time decreased: single swallow 0.56 +/- 0.36 sec, forced repetitive swallow 0.23 +/- 0.11 sec, as did the coefficient of variation (48% and 64%, respectively) indicating a more automatic neural process for pharyngeal function in forced, repetitive swallow. The postswallow respiration started with inspiration in 10% of studied individuals, but did not correlate with deviations in other variables in the test. Thus, postswallow inspiration must be considered as normal. The ROSS test offers a rapid and easy quantitative assessment of swallowing.

Swallowing in hereditary sensory ataxia.

The oral, pharyngeal, and esophageal stages of swallowing were evaluated in 8 patients with recessively or dominantly inherited pure sensory ataxia. Six patients had swallowing difficulties: solid bolus obstruction, coughs during eating, and choking episodes. One patient had chronic bronchitis and another had recurrent pneumonia. The patients underwent a biphasic radiological barium swallow, including videofluoroscopy. No patient had a completely normal swallow. All had normal oral function, whereas pharyngeal function was abnormal in 6 patients. Esophageal function was abnormal in 6 patients. The swallowing dysfunction did not correlate with the severity of motor or sensory dysfunction in the limbs, nor with age or duration of ataxia. Our study shows that swallowing dysfunction is common in hereditary sensory ataxia. This dysfunction is likely to be due to involvement of the nucleus of the solitary tract in the brainstem. Despite some of the patients having suffered from choking episodes and others from bronchopulmonary complications, they did not spontaneously admit dysphagia. Swallowing should be evaluated thoroughly in patients with hereditary sensory ataxia since dysphagia in these patients might bring serious and potentially fatal complications.