Effects of intrathecal triamincinolone-acetonide treatment in MS patients with therapy-resistant spasticity.

OBJECTIVES: Multiple sclerosis (MS) is an autoimmune disease affecting young people and is a major cause of disability. In the course of time, disability progresses and symptoms like spasticity may occur. Spasticity is a major cost factor in MS patients. Various agents are approved for the treatment of spasticity, but each of those agents may have several side effects. Intrathecally administered steroids (triamcinolone-acetonide (TCA)) may be efficient in treating spasticity in patients with lesions in the spinal cord and no response to first-line therapeutics. The aim of this study is to show effects of TCA treatment on clinical parameters in patients with MS. METHODS: This multicentre open label study included 54 patients with MS. The clinical outcome parameters were spasticity, disability, maximum walking distance, bladder function and quality of life. All patients received physiotherapy in addition to TCA treatment to obtain optimal effects on clinical parameters. RESULTS: Spasticity, maximum walking distance as well as disability improved significantly (P ⩽ 0.001) during TCA applications. Bladder function improved in every seventh patient. CONCLUSION: We observed the effects of intrathecally administered TCA on different clinical parameters including bladder function. TCA administration is a safe method to treat different symptoms in MS patients. Longitudinal trials with repeated TCA cycles are needed to show long-term effects. Besides TCA treatment, physiotherapy contributes to the improvement of clinical parameters.

Effects of repeated intrathecal triamcinolone-acetonide application on cerebrospinal fluid biomarkers of axonal damage and glial activity in multiple sclerosis patients.

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults. Over time, the disease progresses and, with accumulating disability, symptoms such as spasticity may occur. Although several treatment options are available, some patients may not respond to first-line therapeutics. However, some of these patients may benefit from intrathecally administered triamcinolone-acetonide (TCA), a derivative of glucocorticosteroids (GCS). GCS may have neurotoxic effects, and cell apoptosis may occur. The aim of this study was to investigate the effects of TCA on biomarkers in the cerebrospinal fluid (CSF) suggestive of neurodegeneration. METHODS: In order to assess neurotoxic effects of TCA, neurofilament heavy-chain (NfH)(SMI35), tau protein, and S-100B protein levels were determined before and during treatment with TCA in 54 patients with primary progressive MS, as well as relapsing MS (relapsing-remitting and secondary progressive MS). RESULTS: NfH(SMI35) levels in the CSF of patients treated with TCA intrathecally did not increase significantly during the treatment cycle (p = 0.068). After application of TCA, tau protein levels were increased significantly at day 4 (p = 0.03) and at day 8 (p ≤ 0.001). S-100B protein levels decreased significantly (p ≤ 0.05) during treatment with TCA. CONCLUSION: NfH(SMI35) levels did not change significantly; however, tau protein levels did increase significantly within the reference range. Taking these findings together, the long-term effects of TCA on NfH(SMI35) and tau protein levels need to be investigated further to understand whether levels of both biomarkers will change over repeated TCA applications. Interestingly, S-100B protein levels decreased significantly during the first applications, which may have represented reduced astrocytic activity during TCA treatment.

Supercontinuum generation with a chirped-pulse oscillator.

We demonstrate the generation of a high power ultrabroadband supercontinuum by coupling the uncompressed pulses from a Ti:Sapphire Chirped-pulse oscillator into a photonic crystal fibre that exhibits a highly anomalous dispersion at the centre wavelength of the laser. Our simulations show that the pulses first undergo quasi-linear compression before the actual supercontinuum is generated by soliton fission dynamics. This two-step process results in an optical spectrum that is remarkably independent on the input pulse energy. Moreover, the reduced peak intensity at the input facet of the fibre mitigates damage problems and allows the generation of high power white-light radiation.

Acute fascioliasis with multiple liver abscesses.

Human fascioliasis is distributed worldwide with several foci of high endemicity. Being a rare disease in Europe, we describe here a case in the initial hepatic phase of the disease. Therapeutic and, with reference to the 2 distinct stages of disease, diagnostic standards are discussed.

Treatment of accidental high dose intraventricular mezlocillin application by cerebrospinal fluid exchange.

An accidental high dose of intraventricular mezlocillin was given during antibiotic treatment for pneumonia in a patient admitted because of severe traumatic brain injury and occlusive hydrocephalus. Because of serial epileptic seizures not responsive to antiepileptic drug treatment, CSF exchange was performed. The CSF was drained through a ventricular catheter, while mock CSF was infused into the lumbar subarachnoid space. The patient soon recovered to her clinical status previous to intraventricular mezlocillin application. Side effects of CSF exchange were not seen. Under continued antiepileptic medication no more seizures occurred. It is concluded that high doses of intraventricular mezlocillin have proconvulsive effects. In this patient CSF exchange was a suitable means of preventing putatively permanent impairment of brain function caused by serial epileptic seizures due to intraventricular mezlocillin application.

What attributes determine quality and satisfaction with health care delivery?

Patient-based determinants of quality and satisfaction play an important role in choosing a health care provider. This study identifies five attributes of health care delivery that define patients' perceptions of quality and satisfaction. Managerial implications for diagnosing quality concerns of patients are discussed.

Implications of the baby bust generation upon the health care market.

Implications of the Baby Boomers upon the American society are well known. However, the effects of its successor generation, the Baby Busters, have not been as well documented nor reviewed. The next twenty years (1990-2010) will see the fabric of American society unfolded and rewoven as this phenomenon undergoes its place in history. It is not too early to examine the implications of the Baby Bust phenomenon. This study examines the implications and consequences of the Baby Bust for Health Care Marketers.

Morphology and mosaics of VIP-like immunoreactive neurons in the retina of the rhesus monkey.

Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide that has been demonstrated to reside in cells ( = VIP+ cells) of the retinae of various vertebrate species. In an attempt to study the morphology and distribution of VIP+ cells in the retina of the rhesus monkey in more detail, we subjected VIP+ cells observed in cryostat sections or wholemounts rhesus monkey retinae to a quantitative analysis. VIP+ cells were found to reside in the innermost row of the inner nuclear layer (INL) and in the ganglion cell layer (GCL) in similar numbers (estimate: 50 cells/mm2 at 6-10 mm eccentricity each) and only on rare occasions (12% of all VIP+ cells) in varying positions within the inner plexiform layer (IPL). Somata of VIP+ cells were circular and had a mean diameter of 9.1 microns. They gave rise to 1-3 main dendrites, which were usually oriented toward the IPL. Main dendrites ramified widely into thin fibers (dendritic field diameter less than = 1 mm), carrying varicose swellings. The fibers that contributed to one and the same plexus of VIP+ fibers preferred the middle third of the IPL, independent of the positions of the parent somata. A quantitative analysis of nearest-neighbour distances in the retinal wholemount preparation suggested that VIP+ cells in the GCL and in the INL might be distributed according to 2 independent mosaics. A comparison with Golgi-stained material leads to the tentative equation of VIP+ cells with the "spiny" A12 amacrine cell of Mariani ('90). Whereas the low density and large dendritic field size of VIP+ cells might suggest a more widespread function, the varicose dendritic morphology seems to be more compatible with functionally independent dendritic subunits mediating localized effects.

Influence of posture and voluntary background contraction upon compound muscle action potentials from anterior tibial and soleus muscle following transcranial magnetic stimulation.

Compound muscle action potentials (CMAPs) were recorded from anterior tibial (TA) and soleus (SOL) muscles following transcranial magnetic stimulation of motor cortex in 10 healthy subjects: (1) while standing upright without support, (2) while sitting, and (3) while lying supine. The results of this study demonstrate a significant influence of posture upon the amplitudes of CMAPs. Postural facilitation presented itself, firstly, in terms of a higher incidence of bilateral activation of distal leg muscles during stance and, secondly, as significant enhancement of the amplitude of CMAPs while standing as compared to lying supine. The onset latency, however, did not disclose a significant shortening during stance. To assess the effects of preinnervation subjects voluntarily adjusted the level of TA activity to 5%, 10% and 20% of maximum isometric force respectively before cortex stimulation. Voluntary background contraction resulted in a significant increase of amplitude of CMAPs but, in contrast to postural facilitation, concomitant with a significant decrease in onset latency. These results point to a somewhat different mechanism of facilitation during stance as compared to voluntary preinnervation. But it cannot be decided whether cortical mechanisms, different descending systems, the spinal circuitry or a combination of these factors is responsible for the observed effects.

Visual and vestibular signals in the lateral mesencephalic tegmental region of the cat.

Single unit recordings from two alert cats were used in an attempt to further elucidate the function of the lateral mesencephalic tegmental region (LTR), a part of the mesencephalon forming a link between the superior colliculus and the lower brain stem. A total of 155 units recorded from the LTR were tested with visual, vestibular and acoustic stimuli. Of these, 54 cells (36%) were characterized as either visually (n = 33) or vestibularly (n = 21) responsive and an additional 13 cells were driven by complex acoustic stimuli. Visually responsive cells typically were directionally selective with large, mainly contralateral receptive fields. Vestibularly responsive cells were modulated by stimulation of either the horizontal canals (yaw stimulation; n = 16) or of both pairs of vertical canals (pitch stimulation; n = 5). About half of the cells with activity modulated by rotation about the yaw axis increased discharge during ipsiversive (Type I), the other half during contraversive rotation (Type II). Of the 5 cells with activity modulated by pitch stimulation, 4 preferred the nose-down and only 1 the nose-up direction. Although the discharge of units responsive to yaw stimulation was roughly in phase with head velocity (mean phase lag with respect to head velocity: 10.6 deg), none of the vestibular cells had activity correlated with eye position, eye velocity or movement of visual stimuli. Our observations suggest that the LTR might introduce visual and vestibular signals into the tecto- facial pathway which may be used to adjust the size of pinna movements with respect to the size of ongoing head- or body movements.

Investigation of the dorsolateral basilar pontine grey of the alert monkey.

The dorsolateral basilar pontine grey is assumed to play an essential role in a cortico-ponto-cerebello-pontine pathway subserving smooth-pursuit eye movements. The dorsolateral basilar pontine grey interconnects those cerebral and cerebellar cortical areas known to be involved in the generation of smooth-pursuit eye movements. In the present study three categories of neurons presumably contributing to smooth pursuit eye movements were recorded: visual-only neurons, visual-tracking neurons, and neurons combining both properties. Preference for directions of visual stimulation could be either iso- or antidirectional.

Neuronal activity in the dorsolateral pontine nucleus of the alert monkey modulated by visual stimuli and eye movements.

The activity of neurons in the dorsolateral pontine nucleus (dlpn) was studied in two awake rhesus monkeys trained to participate in a variety of visual and oculomotor tests. The visual and eye movement related responses of 73 neurons encountered in the more caudal part of the dlpn were analyzed. Thirty eight of these could be assigned to one of the three following groups. Visual-only neurons (Type 1, n = 10) responded to movement of a broad range of visual stimuli in certain preferred directions. Their receptive fields were usually large, not restricted to the contralateral visual field and always included the fovea. Visual-tracking (VT) neurons (n = 28) discharged in relation to smooth pursuit of a small target in particular preferred directions. Nine of these (Type 2) did not respond to visual stimulation during stationary fixation. Nineteen VT-cells (Type 3) discharged in relation to both visual tracking and visual stimulation. In 9 of the Type 3 neurons, the preferred directions for visual stimulation and tracking were opposite, whereas they were the same in the other 10. Visual responses of Type 3 neurons were indistinguishable from those of Type 1 neurons. Testing of an additional 9 neurons driven by either visual-tracking or pattern movement was not sufficient to allow a definite assignment to one of the groups 1, 2 or 3. The distribution of preferred directions for both visual stimulation and visual tracking was widely scattered between 0 and 360 deg. Our results suggest that the dlpn is a constituent in a cerebro-cerebellar loop important for the generation of smooth pursuit eye movements.

Morphology, number, and distribution of putative GABA-ergic neurons in the basilar pontine gray of the monkey.

We used an antibody raised against the inhibitory transmitter gamma-aminobutyric acid (GABA) in the basilar pontine gray (bpg) of the monkey. Somata, dendrites, and a plexus of probably axonal fibers exhibited GABA-like immunoreactivity. Labeled neurons were small with oval, triangular, or circular soma shape. They gave rise to 2 to 4 dendrites with little branching. No axons were seen issuing from the soma. Occasionally, appendages consisting of spheroidal bodies positioned at the distal end of tenuous stalks and (in 1 cell) axonlike processes were observed to originate from dendrites. According to their morphology, we suggest that these putative GABA-ergic neurons may correspond to the type II neurons observed in Golgi material. The average number of putative GABA-ergic cells in 40-micron sections was about 30/mm2. When compared with Nissl-stained sections, these amounted to about 5% of all cells. There was no substantial variation in average density in different parts of the bpg. However, labeled cells tended to lie in clusters, perhaps related to the well-established input-output compartments of the bpg. The demonstration of a significant population of putative inhibitory neurons challenges the traditional view of the bpg, which suggests that this brainstem cell group functions as a simple relay exchanging signals between cortex and cerebellum.

Event-related cross-correlations between spike trains illustrated on interactions between motor units and muscle spindle afferents.

A method is presented for computing correlation coefficients of two (or more) output spike trains in temporal relation to one (or more) input even trains. These event-related correlation functions are computed by convolving the output spike trains, represented as point processes, with rectangular pulses of selectable width, and by then calculating linear correlation coefficients for the pairs of amplitude values obtained from the two convolved processes in temporal relation to the input events. The merits of this technique are illustrated on stimulus trains delivered to motor units (MUs) and output spike trains recorded from muscle spindle afferents of the same cat hindlimb muscle. The correlation functions obtained show the temporal course of the correlated firings of the two afferents (mostly Ia afferents from primary muscle spindle endings) as a function of time from MU activation; they are compared with the conventional cross-correlation histograms (CCHs) between afferents and with peri-stimulus time histograms (PSTHs) between stimulus and afferent firing patterns. Stimulus-related cross-correlation functions as displayed here can be calculated for any three spike trains. Possible extensions of the method to larger numbers of input and output channels are also discussed.

Amplitude reduction of motor unit twitches during repetitive activation is accompanied by relative increase of hyperpolarizing membrane potential trajectories in homonymous alpha-motoneurons.

In anaesthetized cats, medial gastrocnemius motor units (MUs) were electrically stimulated via their ventral-root axons with independent random patterns. Isometric muscle tension and homonymous alpha-motoneuron (MN) membrane-potential fluctuations in response to these stimuli were recorded simultaneously, usually for periods of about 2 min. The tension and membrane potential were averaged with respect to a stimulus train over two disjoint time intervals, one stretching 20-40 s at record beginning, and the other a similar duration at the end of recording. Whereas average MU twitch amplitudes usually decreased between these periods, average membrane potential trajectories did not do so, such that, when normalized to the change in twitch amplitude, the membrane potential trajectories usually increased in size. This suggests that the decline in the mechanical effect of MU activation was accompanied by an increase in the gain of the afferent pathway to homonymous MNs, which was confirmed by gain computations in the frequency domain. This compensation could be a mechanism to maintain the high quality of information about MU contractions transmitted to MNs in the course of MU fatigue.