Thin-film filter, wavelength-locked, multi-laser cavity for dense wavelength beam combining of broad-area laser diode bars.

We report on individual wavelength locking of a multiplet of 100-µm broad-area laser diode emitters arranged on a 50% fill-factor bar by means of a single external multi-laser cavity using an ultra-narrowband thin-film filter as a dispersive optical element. The achieved wavelength-locked output power is 216 W, corresponding to an electrical-to-optical conversion efficiency of about 49.7%. The 45 emitters of the laser diode bar are stabilized within a spectral range of about 6.4 nm. Our approach is suited for killowatt-class dense wavelength beam combining of direct diode lasers.

Color vision tests for early detection of antiepileptic drug toxicity.

A previous suggestion that antiepileptic drugs may induce color vision deficiencies prompted us to examine whether color vision deficiencies may occur at lower drug serum concentrations than those associated with symptoms of neurotoxicity. Eighty patients presenting with epilepsy received monotherapies of valproic acid, phenytoin, or carbamazepine; 18 patients did not receive antiepileptic drug therapy. Color vision was tested by the Farnsworth-Munsell 100-hue test, spectral sensitivity, and the newly developed tritan screening plates. Patients treated with phenytoin or carbamazepine developed blue-yellow color vision deficiencies. In contrast, patients exposed to valproic acid or receiving no drug treatment showed normal color vision. There was a significant correlation (p < 0.0001) between signs of neurotoxicity induced by phenytoin or carbamazepine and blue-yellow color vision deficiencies. In contrast, we found no correlation between these signs of neurotoxicity and the drug serum concentrations (p = 0.0637). Color vision testing in epileptic patients treated with phenytoin or carbamazepine appears to be a sensitive method for early detection and monitoring of clinical neurotoxicity.

Apomorphine-susceptible and apomorphine-unsusceptible Wistar rats differ in novelty-induced changes in hippocampal dynorphin B expression and two-way active avoidance: a new key in the search for the role of the hippocampal-accumbens axis.

The present study examines two characteristic traits of the hippocampus in apomorphine-susceptible (APO-SUS) and apomorphine-unsusceptible (APO-UNSUS) Wistar rat lines. Since hippocampal mossy fibers contain among others dynorphin B as transmitter, a radioimmunoassay was used to analyze the hippocampal dynorphin B expression in response to novelty in these lines. Dynorphin B expression at the end of the baseline condition was greater in APO-SUS rats than in APO-UNSUS rats, while exposure to novelty decreased and increased the dynorphin B expression in APO-SUS and APO-UNSUS rats, respectively. These interline differences in dynorphin B expression could be due to (a) an interline difference in the size of the mossy fiber terminal fields, (b) an interline difference in the regulation of the firing rate of mossy fibers by corticosteroids, and/or (c) an interline difference in the release of corticosteroids in response to novelty. Since the size of the mossy fiber infra/intrapyramidal terminal field is inversely related to two-way active avoidance performance, APO-SUS and APO-UNSUS rats (n = 9 per line) were given this task: APO-UNSUS rats performed much better than APO-SUS rats. It is concluded that the neurochemical and behavioural function of the hippocampus significantly differs between lines. Given the already known interline differences in the function of the nucleus accumbens, the present results provide a new avenue in search for the functional relationship between the hippocampus and the nucleus accumbens.

Comparison of EEG, MRI and PET in reading epilepsy: a case report.

The pathophysiological and neuroanatomical bases of reading epilepsy (RE) are unclear. We performed video-EEG, high quality MRI and [11C]diprenorphine PET in a patient with RE to detect structural and functional abnormalities. EEG showed multifocal seizure onset bilaterally in temporal and fronto-central regions. MRI was normal, whereas [11C]diprenorphine PET revealed peri-ictal opioid binding decreases in both temporal lobes and the left frontal lobe. These findings confirm that RE is due to abnormal activity in the network subserving reading.

Rehabilitation of children with brain tumors.

Brain tumors are the most common type of solid tumors in childhood. It has only been over the past 20 years that the majority of children with intracranial tumors are surviving. Children who survive their tumors may do so with significant disabilities resulting from the tumor or its treatment, and are presenting a new challenge in pediatric rehabilitation. In this article, we will discuss the epidemiology and characteristics of the major types of brain tumors that occur in children, the multimodality approach to tumor treatment along with the major complications of the interventions that have implications for the quality of survival, the types of deficits in function that occur most commonly in children who survive their tumors, and the team approach to rehabilitation of children with disabilities due to brain tumors.

Vestibular nuclear neuron activity in chronically hemilabyrinthectomized cats.

The activity of central vestibular neurons (Vn) of the horizontal canal system was recorded in chronically hemilabyrinthectomized cats and compared with that of labyrinth intact animals. In both groups the cerebellar vermis was removed in order to assess the efficacy of the vestibular brainstem commissure alone by means of polarizing currents applied to the labyrinths. Experiments were carried out under Ketamine anaesthesia. In control animals the mean resting rates of type I and type II Vn measured 22.4 +/- 14.0 and 27.5 +/- 14.6 imp/s respectively, and the type I responses occurred ca. 3 X more frequently than type II. In the lesioned animals a drastic reduction of the number of type I responses was found on the deafferented side, while that on the intact side remained normal. The resting rates of type I Vn on the two sides did not differ significantly from each other but were significantly lower than those of control animals. In contrast, type II responses were present on the deafferented side, but almost completely missing on the intact side. Applying polarizing stimuli in control animals, it was found that both labyrinths have similar weight in driving Vn. In lesioned animals, no major changes in the efficacy of the commissural path were found when polarizing stimuli were applied to the intact side. It is concluded that vestibular nerve section causes a severe loss of type I responses in the vestibular nuclei on the side of the lesion which apparently is not compensated by an adaptive change in the commissural path and, therefore, may be mainly responsible for the VOR asymmetry observed concomitantly.

[Sensitive physiologic perceptual tests for ocular side effects of drugs exemplified by various anticonvulsants]. / Empfindliche sinnesphysiologische Testmethoden für okuläre Nebenwirkungen von Medikamenten am Beispiel verschiedener Antiepileptika.

Advanced psychophysical tests, performed in 42 patients who have seizures, showed that the widely used antiepileptic drugs, diphenylhydantoin and carbamazepine, can specifically affect retinal function, while valproic acid and the epileptic seizures do not. The Farnsworth-Munsell 100-Hue and Panel D-15 désaturé tests revealed an accumulation of errors along the tritan/tetartan axis and a high total error score. As shown by measurement of the so-called transient tritanopia and by determination of the spectral sensitivity, this blue vision defect is not only due to loss of postreceptoral interaction between long- and short-wavelength-sensitive cones, but is also based on a disturbance in the receptor mechanism itself. The dark adaptation curve was not affected. As determined by cone flicker thresholds during dark adaptation, the inhibitory action of rods on cones is reduced. The results obtained for mesopic vision and especially glare sensitivity measured by nyktometry were markedly affected in these patients compared to the normal population. The psychophysical methods provide a very sensitive test for early detection of drug-induced retinal dysfunction and allow clear differentiation between the loss of a receptor mechanism and a defect in the neuronal interaction between photoreceptors in the human visual system induced by antiepileptics.

[The nursing phenomenon "chronic confusion" in relation to the diagnosis "dementia"]. / Das Pflegephänomen "Chronische Verwirrtheit" im Kontext der Diagnose "Demenz"--Eine Literaturstudie.

This article is about the results of a literature analysis, focusing on the two questions: 1) What is the understanding of "Chronic confusion"? and 2) How is the nursing diagnosis "Chronic confusion" delineated from the diagnosis "Dementia"? The review is based on the databases CINAHL, MEDLINE and GEROLIT. A review of the literature revealed that there is basic agreement regarding the characteristic "cognitive impairment" but there are differences in the question as to how this cognitive impairment manifests itself in practice. Moreover most authors described socially and emotionally altered behaviors which accompany the phenomenon. There is, however, no clear vision on the status of such socially and emotionally altered behaviors: Do they have to be present for "Chronic confusion" to be diagnosed or not? In addition, it seems inconsistent to include the mild stage of Dementia in the "Chronic confusion" diagnosis. This analysis indicates that much work remains to be done to validate the characteristics of "Chronic confusion". As long as the diagnosis is not clear, imprecise labeling of patients and ineffective interventions cannot be avoided.

[Clinical relevance of calcium antagonists in the treatment of epilepsy]. / Klinische Relevanz von Calcium-Antagonisten in der Behandlung von Epilepsien.

The antiepileptic effects of dihydropyridine derivates and flunarizine are currently evaluated in controlled clinical trials following earlier reports of their antiepileptic action in experimental animal models of epilepsy and promising pilot studies in human epilepsy. Other calcium antagonists such as verapamil or diltiazem have proved less effective in experimental models. They penetrate poorly into the CNS (Verapamil) and are difficult to evaluate clinically due to relevant pharmacokinetic interactions with antiepileptic drugs.

Short- and long-term modifications of vestibulo-ocular response dynamics following unilateral vestibular nerve lesions in the cat.

The dynamics of the horizontal vestibuloocular reflex (VOR) were determined in the dark prior to and at various time periods after unilateral removal of the vestibular nerve. One chronic group, consisting of cats that were operated at the age of 6 weeks or as adults, was studied 10.5 to 22 months later; an adult-operated group was measured 1-244 days postoperatively (p.o.). Between measurements cats were kept in a normal environment. In control animals the VOR gain was close to unity only up to certain stimulus velocities which varied amongst cats; thereafter a sharp drop in gain occurred probably due to saturation of central and peripheral neuronal responses. Therefore, VOR gains in lesioned animals were compared to the control responses yielding high gain. It is only at these small stimulus amplitudes that the two labyrinths maximally interact and, therefore, one would expect the largest changes. The gain was computed after correction for the ocular imbalance induced by the lesion. Immediately after the lesion a drop in gain to stimulations in both directions was noted; the reduction was larger for the VOR evoked on rotation to the lesioned side. Contrary to control animals, no partial response saturation occurred in lesioned animals but, following rotation to the lesioned side, complete saturation was noted with larger stimuli. Ocular balance was greatly improved within the first 3-4 days p.o. as indicated by the strong reduction of nystagmus. The time course of p.o. adaptive gain changes could be divided into three stages: in the initial stage (1-5 days p.o.) no improvement was visible; between p.o. days 5-10 one group of cats showed an abrupt increase in gain while it remained low in others. Response symmetry showed no consistent change in either group; the 3rd stage starting p.o. day 10 and extending throughout the observation period (22 months) is characterized by slowly developing changes reducing significantly response asymmetry. The incremental gain was higher in the young than in the adult-operated chronic cats. Compared to controls the phase plot of the VOR of lesioned animals shows a parallel shift of ca. 10 degrees towards larger lead over the frequency range tested (0.05-1.0 Hz) independent of direction of rotation or p.o. stages. All lesioned animals showed a clear failure to hold eye position in the dark even in the chronic stage; a drift with an exponentially decreasing velocity of ca. 2-4 degrees/s was typical.(ABSTRACT TRUNCATED AT 400 WORDS)

From clinical observation to long-term monitoring: diagnostic developments in conservative epileptology.

The diagnostic goals in nonsurgical (conservative) epileptology differ from presurgical diagnostic aims. The resulting development of diagnostic methods in a tertiary-level epilepsy center is shown and the major technical and organizational consequences of this difference for diagnostic long-term monitoring (LTM) as opposed to presurgical LTM are investigated. A total of 133 consecutive daytime LTM investigations using radio telemetry were reviewed and seizure parameters such as type, duration, method of seizure detection, and need of mobility were evaluated and compared to presurgical LTM. Compared to presurgical LTM, partial seizures were relatively rare (17.8%) and short epileptic or nonepileptic motor events lasting <1 s, such as myoclonic, atonic, short tonic seizures, spasms, tics, or startle reactions, are frequent (34.9%). Of all seizures, 23% had no or minor ictal EEG changes, subtle symptomatology without signaling by a patient or accompanying person, and could be detected only by continuous online surveillance by an experienced EEG technician. Due to the nature of the patient population in diagnostic LTM, there is an increased need for ictal and interictal mobility (radio telemetry). LTM in conservative epileptology requires more intense human surveillance for seizure detection and increased patient mobility compared to presurgical LTM.

Neuroleptically induced dystonia in Huntington's disease: a case report.

A patient with Huntington's disease developed acute dystonia whilst treated with tiapride. Sulpiride and tetrabenazine also induced dystonia. The anticholinergic biperiden depressed the syndrome but worsened psychopathology. Finally a combination of tetrabenazine and clozapine was successful in treatment of both chorea and dystonia. According to this observation, acute dystonia may occur in Huntington's disease as a consequence of neuroleptic treatment.

Abolition of photoparoxysmal response in progressive myoclonus epilepsy.

We have investigated the effect of piracetam on photoparoxysmal responses in 3 patients with progressive myoclonus epilepsy. With doses of up to 10 g/day, elimination of photoparoxysmal responses was achieved in all 3 patients. Corresponding to EEG improvement, the clinical performance improved slightly in 2 patients and definitely in 1 patient when piracetam was added to their medication of valproate and clonazepam. According to our data, medical treatment of myoclonus with piracetam is justified particularly in myoclonus of cortical origin.

[Disorders of color perception and increase glare sensitivity in phenytoin and carbamazepine therapy. Ocular side effects of anticonvulsants]. / Farbsinnstörungen und erhöhte Blendungsempfindlichkeit unter Phenytoin- und Carbamazepintherapie. Okuläre Nebenwirkungen von Antiepileptika.

Advanced psychophysical tests, performed in 42 epileptic patients, show that the antiepileptic drugs phenytoin and carbamazepine can specifically affect the retinal function, while Valproic Acid and the epileptic seizures do not. The Farnsworth-Munsell 100-Hue and Panel D-15 désaturé tests revealed an accumulation of errors along the tritan/tetartan axis (blue colour vision deficiencies) and a high total error score. The same defect was shown by measurement of the spectral sensitivity functions. The results obtained for mesopic vision and especially glare sensitivity measured by nyktometry were markedly affected in these patients compared to a normal population. The enhanced sensitivity to glare is mainly the only one symptom complained by the patient. We propose a screening method for early detection of phenytoin- and carbamazepine-induced neurotoxicity. The literature of ocular side effects of anticonvulsant drugs is carefully reviewed.

Functional outcome of paediatric stroke survivors.

OBJECTIVE: To examine the medical and functional outcome of paediatric stroke survivors. PATIENTS: Patients aged 1 month to 18 years diagnosed with stroke over a 10 year period. MAIN OUTCOME MEASURES: Discharge functional outcome data were collected by reviewing therapy, nursing, and other chart notes relating to specific functional tasks. Current functional information, living situation, school placement, and medical outcome data were obtained in the telephone survey. RESULTS: Fifty patients responded. The mean age at event was 8.0 years (range: 7 months to 17 years, 7 months). The mean follow-up time was 70 months. Diagnoses included: haemorrhagic (30%), thrombotic/embolic (46%), and undiagnosed (24%). At follow-up, 76% of the patients were independent in all activities of daily living (ADL), compared to 64% at hospital discharge. Younger age at onset, female gender, history of cardiac disease, and presentation with hemiparesis were significant risk factors for dependence in ADL (p < 0.05), while thrombotic/embolic aetiology demonstrated a trend (p = 0.06). Eighty-four per cent were independent in mobility, compared to 74% at discharge. Forty per cent of the patients had speech and language deficits. Of the school age children, only 50% were in a regular classroom. CONCLUSIONS: Children and adolescents who survive stroke have good outcome for mobility and ADL skills, but more difficulty with language and cognitive recovery. Functional recovery is maintained after discharge, and functional gains occur over time with very little evidence of functional regression. Comorbidities are relatively low. All children in the group returned to a home setting.

Subcutaneous sumatriptan in the treatment of headache during withdrawal from drug-induced headache.

In a pilot study (5 patients) we investigated the effects of subcutaneous sumatriptan, a 5-HT1-like receptor agonist, on headache experienced during the withdrawal period of drug-induced headache. The pilot study indicated that the substance was effective mostly in patients who originally suffered from migraine. In a patient with tension headache the substance was less effective. In a second double-blind study on six migraine patients with severe drug-induced headache, the drug was highly effective in ameliorating headache and autonomic disturbances. Blood flow velocities measured in extracranial parts of internal and external carotid arteries by duplex-sonography and in middle cerebral and basilar arteries by transcranial Doppler showed no changes after administration of sumatriptan or placebo. This result suggests sumatriptan does not act primarily via constriction of the large cerebral arteries.

MOSES: an educational program for patients with epilepsy and their relatives.

The knowledge of patients with epilepsy about their own condition is poor, and thus the need for educational programs for people with epilepsy has long been recognized. However, no such programs have been established in their routine care. The Modular Service Package Epilepsy (MOSES) now tries to fill this gap for patients in German-speaking countries. The program was developed by a multidisciplinary group (neurologists, nonmedical professional helpers, and representatives of national epilepsy associations) for people with epilepsy older than 16 years, independent of the kind and severity of their epilepsy. MOSES is designed for group education and can be used in inpatient and outpatient settings in epilepsy centers, in clinics, and by neurologists in private practice. The program aims to help patients achieve a better understanding of their disease, to gain more self-confidence, and to take over responsibility, thus supporting patients to become experts in managing their own illness. Being modular in structure, MOSES includes nine units: living with epilepsy, epidemiology, basic knowledge, diagnostics, therapy, self-control, prognosis, psychosocial aspects, and network epilepsy. MOSES consists of a workout manual for patients and a trainer manual. For potential trainers, special "train-the-trainer seminars" are offered and considered mandatory. About 400 patients have participated in a MOSES training program in Germany, Switzerland, and Austria. The efficacy of the program is currently been evaluated.

Activation mechanisms of the urokinase-type plasminogen activator promoter by hepatocyte growth factor/scatter factor.

Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effector inducing invasion and metastasis of tumor cells that express the Met tyrosine kinase receptor. One of the effectors of HGF/SF is the urokinase-type plasminogen activator, a serine protease that facilitates tumor progression and metastasis by controlling the synthesis of the extracellular matrix degrading plasmin. Stimulation of NIH 3T3 cells that were stably transfected with the human Met receptor (NIH 3T3-Methum) with HGF/SF induced a trans-activation of the urokinase promoter and urokinase secretion. Induction of the urokinase promoter by HGF/SF via the Met receptor was blocked by co-expression of a dominant-negative Grb2 and Sos1 expression construct. Further, the expression of the catalytically inactive mutants of Ha-Ras, RhoA, c-Raf, and Erk2 or addition of the Mek1-specific inhibitor PD 098059 abrogated the stimulation of the urokinase promoter by HGF/SF. A sequence residing between -2109 and -1870 base pairs (bp) was critical for stimulation of the urokinase gene by HGF/SF. Mobility shift assays with oligonucleotides spanning an AP-1 site at -1880 bp or a combined PEA3/AP-1 site at -1967 bp showed binding of nuclear factors from NIH 3T3-Methum cells. Expression of an expression plasmid that inhibits DNA binding of AP-1 proteins (A-Fos) abrogated inducible and basal activation of the urokinase promoter. Nuclear extract from unstimulated NIH 3T3-Methum cells contained more JunD and showed a stronger JunD supershift with the AP-1 oligonucleotides, compared with HGF/SF-stimulated cells. Consistent with the levels of JunD expression being functionally important for basal expression of the urokinase promoter, we found that overexpression of wild type JunD inhibited the induction of the urokinase promoter by HGF/SF. These data suggest that the induction of urokinase by HGF/SF is regulated by a Grb2/Sos1/Ha-Ras/c-Raf/RhoA/Mek1/Erk2/c-++ +Jun-dependent mitogen-activated protein kinase pathway.

The variants of reading epilepsy. A clinical and video-EEG study of 17 patients with reading-induced seizures.

We present the clinical and electrographic data of 17 patients with reading-induced seizures documented with ictal video-EEG studies during provocation with language related tasks. The median age at onset was 15 years (range 11-22 years) and the male:female ratio was 2.4. Fourteen patients had no spontaneous seizures of any type while the remaining three had infrequent generalized tonic-clonic seizures during nocturnal sleep. Two distinct electroclinical ictal patterns were confirmed on video-EEG analysis. (i) Fifteen patients had reading-induced jerks which invariably involved the region of the jaw but also included the upper limbs in five of them. Ictal EEG discharges were noted in 12 patients; these were brief but varied in terms of morphology and spatial distribution, with a clear tendency for left-sided predominance. All but one of these patients had similar myoclonic seizures induced by linguistic activities other than reading, the phenomenon probably justifying the term 'language-induced epilepsy'. Some patients had evidence of transient cognitive impairment associated with the reading-induced jaw or limb jerks. Three patients had a sibling with reading epilepsy but there was no other family history of epileptic seizures. (ii) Two patients had reading-provoked paroxysmal alexia without motor symptoms, associated with prolonged focal ictal EEG abnormalities. Reading provoked a subclinical, continuous and reproducible EEG activation over the left posterior temporal area. We propose that ictogenesis in reading or language-induced epilepsy is based on the reflex activation of a hyperexcitable network that subserves the function of speech and extends over multiple cerebral areas on both hemispheres. The parts of this network responding to the stimulus may, secondarily, drive the relative motor areas producing the typical regional myoclonus. This network hyperexcitability can be genetically determined and its clinical expression is age-related.