[Ketamine i. v. for the treatment of cluster headaches : An observational study]. / Ketamin i. v. zur Behandlung von Clusterkopfschmerz : Eine Beobachtungsstudie.

Cluster headaches have an incidence of 1-3 per 10,000 with a 2.5:1 male-to-female gender ratio. Although not life threatening, the impact of the attacks on the individual patient can result in tremendous pain and disability. The pathophysiology of the disease is unclear, but it is known that the hypothalamus, the brainstem, and genetic factors, such as the G1246A polymorphism, play a role. A distinction is made between episodic and chronic cluster headaches. In a controlled setting, we treated 29 patients with cluster headaches (13 with chronic cluster and 16 with the episodic form), who had been refractory to conventional treatments, with a low dose of ketamine (an NMDA receptor antagonist) i.v. over 40 min to one hour every 2 weeks or sooner for up to four times. It was observed that the attacks were completely aborted in 100 % of patients with episodic headaches and in 54 % of patients with chronic cluster headaches for a period of 3-18 months. We postulated neuroplastic brain repair and remodulation as possible mechanisms.

Swiss recommendations for the management of varicella zoster virus infections.

Infections with varicella zoster virus (VZV) are common viral infections associated with significant morbidity. Diagnosis and management are complex, particularly in immunocompromised patients and during pregnancy. The present recommendations have been established by a multidisciplinary panel of specialists and endorsed by numerous Swiss medical societies involved in the medical care of such patients (Appendix). The aim was to improve the care of affected patients and to reduce complications.

Rhythmic activity of uptake hydrogenase in the prokaryote Rhodospirillum rubrum.

Growth of Rhodospirillum rubrum was followed in cultures kept under anoxic conditions at constant temperature in either continuous light (LL, 32 degrees C) or continuous darkness (DD, 32 degrees C and 16 degrees C). In DD, only small modifications of the turbidity were detected; linear regression analysis nevertheless gives a very significant slope (t(34) = 13.07, p < 10(-14), with R2 of 0.834). Mean generation times reflected these differences of growth with 11.9+/-0.5 h in LL and 43.2+/-1.1 h in DD at 32 degrees C and 37.4+/-1.0 h at 16 degrees C cultures. The uptake hydrogenase (Hup) activity has been followed in situ in whole cells of R. rubrum grown in the same conditions, and a clear ultradian rhythm of activity has been observed. Indeed, after about 12 h in the new media, a rapid rise of hydrogenase activity was observed in both LL and DD cultures after which it decreased again to very low values. The activity of Hup continued to show such fluctuations during the rest of the experiment, both in DD and in LL, during the growth and stationary phases. The Lomb-Scargle power periodogram method demonstrates the presence of a clear rhythmic Hup activity both in LL and DD. In the LL-grown cultures, the oscillating activity is faster and continues throughout the growth and the stationary phases, with an ultradian period of 12.1+/-0.5 h. In DD, the slow-growing bacteria showed an ultradian oscillatory pattern of Hup activity with periods of 15.2+/-0.5 h at 32 degrees C and 23.4+/-2.0 h at 16 degrees C. The different periods obtained for LL- and DD-grown bacteria are significantly different.

Work capacity and cardiopulmonary adaptation of the obese subject during exercise testing.

Twelve obese patients (six male subjects) aged 17 to 42 years with a mean body mass index (BMI) of 40 kg/m2 and 12 normal subjects (six male subjects) aged 19 to 39 years with a mean BMI of 22 kg/m2 underwent a cycloergometric test until exhaustion to assess work capacity and cardiopulmonary adaptations of the two groups. Minute ventilation, expiratory gas concentrations, and heart rate, together with anaerobic threshold (AT) were determined in each subject during the test. The same subjects were then submitted to normocapnic hyperpnea at rest to assess the oxygen cost of breathing. We found that in the obese patients, the maximal sustainable work rate was not different from that of controls (120 vs 136 W) while AT was significantly lower (78 vs 110 W). Nevertheless, there was no difference in maximum VO2 and in VO2 at AT levels (expressed in milliliters per minute) indicating that cardiac, pulmonary, vascular, and muscle performance did not differ from obese to normal subjects. Greater muscular effort was needed by obese patients when moving their heavier legs and less when doing external work with a decreased gross mechanical efficiency and an identical net mechanical efficiency between the two groups.

Right hemisphere emotional perception: evidence across multiple channels.

Emotional perception was examined in stroke patients across 3 communication channels: facial, prosodic, and lexical. Hemispheric specialization for emotion was tested via right-hemisphere (RH) and valence hypotheses, and relationships among channels were determined. Participants were 11 right-brain-damaged (RBD), 10 left-brain-damaged (LBD), and 15 demographically matched normal control (NC) adults. Experimental measures, with analogous psychometric properties, were identification and discrimination tasks, including a range of positive and negative emotions. Nonemotional control tasks were used for each channel. For identification, RBDs were significantly impaired relative to LBDs and NCs across channels and valences, supporting the RH hypothesis. No group differences emerged for discrimination. Findings were not influenced by demographic, clinical, or control variables. Correlations among the channels were more prominent for normal than for brain-damaged groups.

Neuropathology of a human hippocampus following long-term treatment with vigabatrin: lack of microvacuoles.

Vigabatrin (gamma-vinyl-GABA), an irreversible inhibitor of gamma-aminobutyric acid transaminase, has been reported to be effective in the treatment of refractory epilepsies. Animal toxicology studies have shown that long-term application of vigabatrin induces intramyelinic edema and microvacuolation of the white matter in non-primate species. However, clinical and neuropathological studies of patients exposed to long-term vigabatrin treatment have, so far, provided no evidence for microvacuolation in the human brain. We report on the histopathological findings of selective amygdalohippocampectomy specimens from a 36-year-old female patient treated with vigabatrin for a period of 11.5 months, and from 2 control patients with chronic refractory temporal lobe seizures. All specimens showed changes associated with chronic epileptic seizures including focal neuronal loss and hippocampal gliosis. Microvacuoles, intramyelinic edema or other manifestations of neurotoxic damage were not observed in vigabatrin exposed tissue, supporting the view that this compound may not exert hippocampal neurotoxicity in humans.

Plasma concentration of nine hormones and neurotransmitters during usual activities or constant bed rest for 34 H.

Thyroid-stimulating hormone (TSH), cortisol, melatonin, prolactin, luteinizing hormone (LH), delta-sleep-inducing peptide (DSIP), its phosphorylated form (P-DSIP), heart rate, and body temperature were measured every half hour during two 24-h periods in five normal men. tau-Amino-butyric acid (GABA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured less frequently. The first period, the "activity" condition, included usual daily activities. The second period, or "rest" condition, consisted of fasting, constant bed rest during 34 h, and partial light deprivation. Compared with the "rest" condition, the "activity" condition increased heart rate, temperature, LH, and TSH in most subjects, and cortisol in two of five subjects. It retarded the onset of nocturnal cortisol and melatonin secretion. The temporal pattern and the absolute values of the concentrations of DSIP, P-DSIP, MHPG, GABA, and prolactin showed no or minimal changes during the two conditions. In spite of the influence of the "activity" versus "rest" condition on several hormones, the mean concentrations as well as the temporal organization of their secretion into plasma were quite stable within each subject, whereas they varied much more between individuals. TSH, cortisol, and melatonin values were also stable within an 8-month period in one subject who was studied on four occasions. The results illustrate that the patterns of hormones rhythms and their reactivity to changes in the environment are, to a large extent, specific to each subject.

A modified Casson equation to characterize blood rheology for hypertension.

A modified Casson equation was established, verified satisficatorily for real conditions and suggested for use in clinical hemorheology. It provides 5 Casson parameters, i.e., Casson yield stress, Casson viscosity, the first critical point of shear rate to cause rouleaux to be broken down into smaller units, the second critical point of shear rate to completely disaggregate into individual erythrocytes, the difference between the two critical points, and also gives two series of the 5 above-mentioned Casson parameters, respectively, under original hematocrit and the standardized hematocrit of 45%. This equation not only reveals the apparent abnormalities of hypertensive patients and normalities of the healthy persons, but also reveals hidden abnormalities for patients with either low or high hematocrit. For 20 cases of hypertensive patients with low hematocrit, the 5 Casson parameters have lower values than control, but the modified equation reveals their hidden higher values than control when their hematocrit is standardized to 45%. For 7 cases of polycythemia complicated with hypertension, the 5 Casson parameters are higher at their original hematocrit, and the modified equation reveals the higher parameters than control also when the hematocrit is standardized to 45%. For 8 cases of polycythemia without complications, the 5 Casson parameters are higher at their original hematocrit than control, while the modified equation still reveals their normalities when standardizing their hematocrit to 45%.

[Hemorheologic characteristics in beta-thalassemic homozygotes before and after splenectomy]. / Caratteristiche emoreologiche nella beta-talassemia omozigote prima e dopo splenectomia.

In a group of 36 homozigous beta-thalassaemic children we studied the effect of splenectomy on hemorheologic characteristics. The aim of the work was to evaluate the importance of such operation either on anemia or on erythrocyte deformability. Whole blood viscosity was measured with a Brookfield Microviscometer (LVT) and erythrocyte deformability was evaluated with the erythrocyte filtration technique using policarbonate membranes. The more the erythrocyte deformability decreases, the more the erythrocyte filtration rate decreases. Our data show that splenectomized children, have worse hemorheologic characteristics according to the longer survival time of pathological red blood cells in spite of their reduced deformability. This behaviour can be modified only by blood transfusion that we have seen to be able to reduce whole blood viscosity and to increase erythrocyte filtration rate in splenectomized children. We think that splenectomy must be delayed as long as possible so that hemodinamyc conditions cannot be worsened. An hemorheologic monitorage could be useful for diagnostic and prognostic evaluations both in splenectomized and not splenectomized children.

Effectiveness of Petasites hybridus preparations in the prophylaxis of migraine: a systematic review.

The objective of this review was to evaluate the strength of evidence of effectiveness for Petasites hybridus in the prophylaxis of migraine. Several databases and other sources were searched to identify randomised-controlled trials investigating P. hybridus preparations. Two trials totalling 293 patients (60 and 233 patients) were included in this review. Both trials investigated the proprietary Petasites root extract Petadolex. The trials were described in narrative way, taking into consideration methodological quality scores. Pooling of data was not carried out due to the heterogeneity of the results. The extract at higher dose (150 mg) showed a greater decreased frequency of migraine attacks and a greater number of responders (improvement>50%) after treatment over 3-4 months than the extract at lower dose (100 mg) and placebo. Moderate evidence of effectiveness is, thus, available for a higher than the recommended dose of the proprietary Petasites root extract Petadolex in the prophylaxis of migraine. Further rigorous studies are required to confirm effectiveness and safety in long-term use before treatment with Petasites root extract can be recommended as an alternative option in the treatment schedule for the prophylaxis of migraine.

Headache patients in primary care and a tertiary care unit in Zürich, Switzerland.

The Headache and Pain Clinic (HPC) is a unit of the Zürich Neurology Department, established in 1966. In the present study demographic features, clinical characteristics and medical management of primary and tertiary care patients were compared in two groups of 181 patients each, seen by general practitioners (GPs) or the HPC, respectively, for primary headaches in 1998. There was a preponderance of women and the socially underprivileged in both samples. Chronic headache was overrepresented in the HPC (44.7%). Loss of work for >2 months was found exclusively in the HPC (9.9%). Of the GP patients, 40% were using triptans and 26.5% in the HPC. One-third of both groups had had complementary and alternative medical treatment. Differences in management strategies reflected differences in headache severity and chronicity. Results indicated that remaining shortcomings of diagnosis and treatment of headache in primary care could be minimized by involving GPs in similar non-commercial studies.

Normobaric hypoxia and nitroglycerin as trigger factors for migraine.

Migraine prevalence is increased in high-altitude populations and symptoms of acute mountain sickness mimic migraine symptoms. Here we tested whether normobaric hypoxia may trigger migraine attacks. As positive control we used nitrolgycerin (NTG), which has been shown to induce migraine attacks in up to 80% of migraineurs. Sixteen patients (12 females, mean age 28.9 +/- 7.2 years) suffering from migraine with (n = 8) and without aura (n = 8) underwent three different provocations (normobaric hypoxia, NTG and placebo) in a randomized, cross-over, double dummy design. Each provocation was performed on a separate day. The primary outcome measure was the proportion of patients developing a migraine attack according to the criteria of the International Headache Society within 8 h after provocation onset. Fourteen patients completed all three provocations. Migraine was provoked in six (42%) patients by hypoxia, in three (21%) by NTG and in two (14%) by placebo. The differences among groups were not significant (P = 0.197). The median time to attacks was 5 h. In conclusion, the (remarkably) low response rate to NTG is surprising in view of previous data. Further studies are required to establish fully the potency of hypoxia in triggering migraine attacks.

[The undetected brain lesion in sports. Minor traumatic brain injury and its sequelae]. / Die unerkannte Hirnverletzung im Sport. Das leichte Schädel-Hirn-Trauma und seine Folgen.

The minor traumatic brain injury (mTBI) in sports is often looked at as a bagatelle. The treating physician underestimates the severity of the injury suspecting that a mTBI is a nonstructural lesion with an overall excellent prognosis in the majority of the cases. This paper shows that the minor traumatic brain injury may be a structural brain lesion with potentially life-threatening dangers. The therapy should follow exactly defined guidelines, e.g., stepwise protocol of the Concussion in Sports (CIS-) Group. Return to sports activities should happen only when all physical but also cognitive symptoms have subsided. All mTBIs that have been sustained prior to the actual injury have to be recorded properly because repeated mTBIs may cause chronic degenerative brain damage. Neuropsychological testing will aid in the correct diagnosis of a mTBI and is a useful parameter in the course of the injury. In the future biochemical markers may serve as indicators of the severity of the brain injury and may also aid in predicting the outcome after TBI. Today biochemical markers do not serve as a substitute for neuroimaging.

MR-spectroscopic imaging during visual stimulation in subgroups of migraine with aura.

Migraine pathophysiology possibly involves deficient mitochondrial energy reserve and diminished cortical habituation. Using functional magnetic resonance spectroscopic imaging (fMRSI), we studied cortical lactate changes during prolonged visual stimulation to search for different pathophysiological mechanisms in clinically distinct subgroups of migraine with aura. Eleven healthy volunteers (HV) and 10 migraine patients were investigated interictally: five with visual aura (MA) and five with visual symptoms and at least one of the following: paraesthesia, paresis or dysphasia (MAplus). Using MRSI (Philips, 1.5 T) (1)H-spectra were repeatedly obtained from a 25 mm-thick slice covering visual and non-visual cortex, with the first and fifth measurements in darkness and the second to fourth with 8-Hz checkerboard stimulation. In MAplus lactate increased only during stimulation, only in visual cortex; in MA resting lactate was high in visual cortex, without further increase during stimulation. This is compatible with an abnormal metabolic strain during stimulation in MAplus, possibly due to dishabituation, and a predominant mitochondrial dysfunction in MA.

Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial.

Riboflavin, which improves energy metabolism similarly to coenzyme Q10 (CoQ10), is effective in migraine prophylaxis. We compared CoQ10 (3 x 100 mg/day) and placebo in 42 migraine patients in a double-blind, randomized, placebo-controlled trial. CoQ10 was superior to placebo for attack-frequency, headache-days and days-with-nausea in the third treatment month and well tolerated; 50%-responder-rate for attack frequency was 14.4% for placebo and 47.6% for CoQ10 (number-needed-to-treat: 3). CoQ10 is efficacious and well tolerated.

Partial restitution of lesion-induced deficits in the horizontal vestibulo-ocular reflex performance measured from the bilateral abducens motor output in frogs.

The responses of the bilateral abducens nerves to small table velocity steps in the dark were measured in four groups of animals: One group was intact prior to recording (controls), one group was hemi-labyrinthectomized the day before the recordings (acute HL), the horizontal canal nerve was sectioned the day before the recordings (acute HCN) in another and the last group was hemi-labyrinthectomized between 60 and 90 days prior to recording (chronic HL). In controls (N = 6) the slopes of the change in discharge rate to increasingly larger velocity steps increased maximally with about 200 imp/s per 1 degree/s and decreased maximally with about -60 imp/s per 1 degree/s. This difference is explained by low resting rates and by recruitment of spontaneously inactive vestibular afferent, central vestibular and abducens neurons. Results obtained from acute HL (N = 4) and acute HCN (N = 4) animals were practically identical. In neither case was a spontaneous nystagmic activity pattern observed. Results differed from those obtained in controls due to an asymmetric reduction in responsiveness. Comparison of the slopes of the evoked increases and decreases in discharge rates of abducens nerves to increasingly larger velocity steps with those in controls show that normal abducens responses are predominantly controlled by crossed excitation and by uncrossed inhibition. Disinhibition and disfacilitation play minor roles. In chronic HL animals (N = 6) that had posturally recovered to a similar degree, responses evoked by steps towards the intact side at larger velocity steps were slightly reduced with respect to those in acute HL or HCN animals. Responses evoked by steps towards the lesioned side differed between individuals. They were either similar to those in controls (N = 1), to those in acute animals (N = 2) or lay between these two extremes (N = 3). The improvement in response to velocity steps towards the lesioned side in 4 of 6 animals is explained by an increase in activity released by disinhibition. This inhibition in turn is controlled by horizontal canal-dependent input from the intact side. Plugging of this canal abolished all direction-specific responses in this plane in the dark, suggesting that the partial restitution of function of horizontal reflex performance depends exclusively on signals derived from receptors of this canal.

[A case of fetal sacro-coccygeal teratoma]. / Un caso di teratoma sacro-coccigeo fetale.

Here is described a case of sacro-coccygeal teratoma observed in a 26th week still-born fetus characterized by differentiating aspects of the three embryonal layers with immature features of the ectodermal and mesodermal derivatives but not those of the entoderm. On the base of the findings observed, the classifying approach of these neoplasms has been reconsidered.

Effect of chloride ions on the kinetic parameters of the potato tuber and mung bean pyrophosphate-dependent phosphofructokinase.

The affinity constant Ka of PPi-PFK for Fru 2,6-P2 is equal to 1.56 nM for the potato enzyme and to 6.67 nM for that of the mung bean in the absence of chloride ions. These results are notably lower than the currently reported 5.5 nM and 30, 50 nM respectively. It is shown that the chloride ion is a competitive inhibitor of Fru 2,6-P2 for both enzymes. The inhibition constant Ki is equal to 15.6 mM for potato PPi-PFK up to 40 mM chloride. For the mung bean enzyme, the Ki is 19.0 mM up to 30 mM chloride. No effects are detected on the Michaelis-Menten constants Km of the substrates Fru-6-P and PPi up to 40 mM chloride. Other halide ions are also found to inhibit the potato PPi-PFK: bromide is competitive like chloride, whereas fluoride and iodide have a mixed inhibition towards Fru 2,6-P2.

Effect of hematocrit on the blood viscosity of patients with chronic respiratory failure and secondary polycythemia.

The blood of patients with chronic global respiratory failure and polycythemia exhibits higher viscosity than that of normal subjects. Plasma changes have been excluded as causal factors. The viscosity of whole blood, plasma and blood after correction of hematocrit (Ht; 45%) with autologous plasma, has been determined. The results indicate that in such patients the increase in Ht is not the most important factor affecting the rheological properties (increased viscosity) of blood. A high Ht value may be only pat of the mechanism that increases the blood viscosity of patients with chronic obstructive pulmonary disease. There is evidence that other factors are responsible for increased blood viscosity in chronic respiratory failure.

Small infarctions of cochlear, retinal, and encephalic tissue in young women.

BACKGROUND AND PURPOSE: Recently, a rare syndrome that involves uniformly the brain, inner ear, and retina in previously healthy young women has been described. Brain biopsies and ophthalmologic examinations disclosed small infarcts as a pathoanatomical substrate of the disease. In previous reports, an autoimmune disorder or a coagulopathy have been suggested as possible etiologies. CASE DESCRIPTIONS: Both patients (aged 22 and 20 years) had brain involvement with neurological and neuropsychological deficits. Multifocal small hyperintensities were shown in magnetic resonance imaging of the brain. Findings of cerebrospinal fluid examination and electroencephalography were pathological in case 1 and of cerebral angiography in case 2. Both patients had a neurosensory hearing loss and multiple retinal branch arteriolar occlusions. Both women were on fenfluramine before onset of the disease. In case 1, attacks recurred during a follow-up of 34 months. At onset of the disease the 5-hydroxyindoleacetic acid and homovanillic acid levels of the cerebrospinal fluid were reduced; 13 months later the 5-hydroxyindoleacetic acid level was still reduced and the homovanillic acid level was low-normal. In case 2, with the longest follow-up of 13 years, the disease was active during only the initial 2 1/4 years. During this period a combination of oral anticoagulant and antiplatelet agents was ineffective. CONCLUSIONS: Our findings could not support current etiologic hypotheses. Whether changes in 5-hydroxyindoleacetic acid and homovanillic acid levels in the cerebrospinal fluid and/or fenfluramine intake play a role in the pathogenesis of the disease remains to be elucidated.