Risk factors for survival of 106 surgically treated patients with symptomatic spinal epidural metastases.

PURPOSE: Evaluation of risk factors for survival in patients surgically treated for symptomatic spinal epidural metastases (SEM). METHODS: One hundred and six patients who were surgically treated for symptomatic SEM in a 10-year period in two cooperatively working hospitals were retrospectively studied for nine risk factors: age, gender, site of the primary tumor, location of the symptomatic spinal metastasis, functional and neurologic status, the presence of visceral metastases and the presence of other spinal and extraspinal bone metastases. Analysis was performed using the Kaplan-Meier method, univariate log-rank tests and Cox-regression models. RESULTS: Overall median survival was 10.7 months (0.2-107.5 months). Overall 30-day complication rate was 33 %. Multivariate Cox-regression analysis showed that fast growing primary tumors (HR 3.1, 95 % CI 1.6-6.2, p = 0.001), the presence of visceral metastases (HR 1.7, 95 % CI 1.0-2.9, p = 0.033) and a low performance status (HR 2.7, 95 % CI 1.1-6.6, p = 0.025) negatively influenced the survival. CONCLUSION: Primary tumor type, presence of visceral metastases and performance status are significant predictors for survival after surgery for symptomatic SEM and should be evaluated before deciding on the extent of treatment. More accurate prediction models are needed to select the best treatment option for the individual patient.

The SNAP Trial: 2-Year Results of a Double-Blind Multicenter Randomized Controlled Trial of a Silicon Nitride Versus a PEEK Cage in Patients After Lumbar Fusion Surgery.

STUDY DESIGN: Randomized controlled trial. OBJECTIVES: Lumbar interbody fusion with cages is performed to provide vertebral stability, restore alignment, and maintain disc and foraminal height. Polyetheretherketone (PEEK) is commonly used. Silicon nitride (Si3N4) is an alternative material with good osteointegrative properties. This study was designed to assess if Si3N4 cages perform similar to PEEK. METHODS: A non-inferiority double-blind multicenter RCT was designed. Patients presenting with chronic low-back pain with or without leg pain were included. Single- or double-level instrumented transforaminal lumbar interbody fusion (TLIF) using an oblique PEEK or Si3N4 cage was performed. The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ). The non-inferiority margin for the RMDQ was 2.6 points on a scale of 24. Secondary outcomes included the Oswestry Disability Questionnaire (ODI), Visual Analogue Scales (VAS), SF-36 Physical Function, patient and surgeon Likert scores, radiographic evaluations for subsidence, segmental motion, and fusion. Follow-up was planned at 3, 6, 12, and 24-months. RESULTS: Ninety-two patients were randomized (i.e. 48 to PEEK and 44 to Si3N4). Both groups showed good clinical improvements on the RMDQ scores of up to 5-8 points during follow-up. No statistically significant differences were observed in clinical and radiographic outcomes. Mean operative time and blood loss were statistically significantly higher for the Si3N4 cohort. Although not statistically significant, there was a higher incidence of complications and revisions associated with the Si3N4 cage. CONCLUSIONS: There was insufficient evidence to conclude that Si3N4 was non-inferior to PEEK.

Preventing ventriculostomy-related infections with antibiotic-impregnated drains in hospitals: a two-centre Dutch study.

This observational cohort study assessed the effect of the introduction of antibiotic-impregnated external ventricular drains (AI-EVDs), as opposed to plain silicone EVDs, on the occurrence of ventriculostomy-related infections (VRIs) in two Dutch hospitals, with no other changes to their clinical practice. VRI was defined using the criteria of the Centers for Disease Control and Prevention, and with a culture-based definition. A propensity-score-adjusted competing risks survival analysis showed that introduction of AI-EVDs did not significantly decrease the risk of VRIs in routine care, nor affect the bacterial aetiology, even after adjustment for confounding and competing events.

Morphological differences between projection neurons of the core and shell in the nucleus accumbens of the rat.

The somatodendritic morphology of projection neurons in the shell and core of the rat nucleus accumbens was studied. These cells were retrogradely labelled with Fast Blue from the ventral mesencephalon (substantia nigra/ventral tegmental area) and subsequently injected intracellularly with Lucifer Yellow and processed immunocytochemically. Digitized reconstructions revealed that the cell bodies of neurons located throughout the nucleus are small-to-medium in size. Neurons in the shell have significantly fewer dendritic arbours with fewer branch segments, fewer terminal segments, and lower spine densities than those in the core. Values for the same parameters are significantly greater for cells in lateral than in medial parts of the shell but the same for neurons located within and without enkephalin enriched parts of the core, with an exception of spine density being significantly greater in the enkephalin-rich compartment. Calculations based on these data reveal that neurons in the core have as much as 50% more surface area than those in the shell, which suggests that core neurons have a greater potential for collecting synaptic information than have shell cells. Furthermore, the differential distribution and action of various neurochemicals such as dopamine in the shell and core, supports the idea that different morphologies reflect the presence of distinct neuronal circuits in these two territories.

Simultaneous characterization of efferent and afferent connectivity, neuroactive substances, and morphology of neurons.

We present a method for establishing in a single experiment four characteristics of individual neurons: the efferent and afferent connectivity, the morphology, and the content of a particular neuroactive substance. The connectivity of the neurons is determined by retrograde fluorescent tracing with Fast Blue and anterograde tracing with the lectin Phaseolus vulgaris leucoagglutinin (PHA-L). After fixation, the brain is cut into 300-micron thick slices. Neurons containing retrogradely transported Fast Blue are intracellularly injected with the fluorescent dye Lucifer Yellow to fill their dendritic trees. The slices are then resectioned at 20-40 microns. One section through the soma of a Lucifer Yellow-filled neuron is selected for the detection of a neuroactive substance contained by this cell [immunofluorescence, secondary antiserum conjugated to tetramethylrhodamine (TRITC)]. Using appropriate filtering, it can be determined in the fluorescence microscope whether a Lucifer Yellow-containing cell body has also been labeled with TRITC, i.e., whether it is immunoreactive for this neuroactive substance. The adjacent sections are subjected to dual peroxidase immunocytochemistry with different chromogens to visualize the PHA-L-labeled afferent fibers (nickel-enhanced diaminobenzidine, blue-black reaction product) and to stabilize the Lucifer Yellow (diaminobenzidine, brown reaction product) in the dendrites of the intracellular injected cells. The other sections are used for electron microscopic visualization of the transported PHA-L. The relationships between the PHA-L-labeled afferent fibers (blue color) and the dendrites of the intracellularly Lucifer Yellow-injected, retrogradely Fast Blue-labeled cells (brown color) are studied by light microscopy. The electron microscope supplies ultrastructural data on the PHA-L-labeled axon terminals.

Bilateral 6-hydroxydopamine lesion in the dopaminergic A8 cell group produces long-lasting deficits in motor programming of cats.

The effects of a small 6-hydroxydopamine lesion in the A8 cell group were studied in cats (N = 8) trained to walk on a treadmill. This setup allows the assessment of subtle changes in motor programming. The lesion produced long-lasting effects: (a) a decreased ability to switch arbitrarily motor patterns; (b) an increased ability to switch motor patterns with the help of stimuli provided by the apparatus; (c) alterations in the sequential patterning of motor behavior and in the kinetic melody of movements. It is suggested that the lesion produced a hypofunction of A9 cells that is compensated by a hyperfunction of A10 cells. It is concluded that subtle lesions in the A8 cell group produce long-lasting deficits in motor programming, implying that degeneration of this dopaminergic cell group may contribute to symptoms seen in Parkinson's disease.

Role of the retrorubral nucleus in striatally elicited orofacial dyskinesia in cats: effects of muscimol and bicuculline.

Orofacial dyskinesia (OFD) is a disorder characterized by involuntary movements of the oral and facial muscles. OFD attacks can be elicited acutely in cats by local injections of dopaminergic agents into the anterodorsal part (r-CRM) of the caudate nucleus. Because the dopaminergic A8 cell group, being embedded in the retrorubral nucleus (RRN), gives rise to fibres which terminate in the r-CRM, two questions arose: (1) whether the A8 cell group forms part of the circuitry that directs and/or modulates OFD, and (2) whether GABA-ergic compounds in the RRN play a role in OFD, and if so, whether a pharmacological GABA-ergic intervention of the activity in the RRN modulates or mediates OFD. For this purpose, the activity of the RRN was manipulated with local injections of the GABA(A) agonist muscimol and antagonist bicuculline. These local injections into the RRN were subsequently combined with manipulations of dopamine transmission in the r-CRM with local injections of the selective DAi receptor agonist (3,4-dihydroxyphenylimino)-2-imidazoline. The present study shows that local injections of GABA-ergic compounds into the RRN do not elicit OFD attacks in cats, but can modulate oral behaviour elicited from the r-CRM. The latter effect is dose dependent and GABA-ergic specific.

D1 and D2 dopamine receptor agonists improve deficits in motor programming of cats with a 6-hydroxydopamine lesion in the A8 cell group.

Recently, it has been shown that a small 6-hydroxydopamine lesion in the A8 cell group of cats trained to walk on a treadmill produces long-lasting deficits (Arts and Cools, 1998, Behav. Neurosci. 112; pp. 102-105). Some deficits could be attributed to a hypofunction of A9 cells, that is a reduced ability to switch arbitrarily motor patterns, and other deficits to a hyperfunction of A10 cells, that is an improved ability to switch motor patterns with the help of cues. This experiment was repeated in this study and the elicited behavioural symptoms were systemically treated with the dopamine D1 receptor agonist SKF 81297 and dopamine D2 receptor agonist LY 171555. The results show that a cocktail of these agonists restored both the lesion-induced reduced ability to switch arbitrarily motor patterns and the lesion-induced increased ability to switch motor patterns with the help of cues, suggesting that this treatment restored the functional misbalance between the A9 and A10 cells.

6-hydroxydopamine lesion in the A8 cell group of cats produces a short-lasting decreased accuracy in goal-directed forepaw-movements.

Recently, feline studies have shown that a lesion in the retrorubral area, which includes the dopaminergic A8 cell group, produces motor programming deficits inherent to a hypofunction of the A9 system. A hypofunction in the striatal terminal area of A9 fibers, in turn, is known to produce a hypofunction of its first-order output station, namely the substantia nigra pars reticulata (SNR). The integrity of the SNR allows animals to execute (1) 'postural adjustments that rely on proprioceptive stimuli that originate in body parts at rest' and (2) 'non-externally guided' targeting movements. In view of these considerations, the (dys)function of the SNR of cats with a bilaterally 6-hydroxydopamine lesion of A8 cells in the retrorubral area was tested in an experimental set-up that allows the assessment of changes in these functions. The A8 lesion produced: (a) a short-lasting increase in the number of accurate targeting movements as well as an increase in the time required for the collection of six pellets: these deficits disappeared 4-7 days after the lesion; (b) a long-lasting disappearance of (1) 'postural adjustments that rely on proprioceptive stimuli that originate in body parts at rest' and (2) 'non-externally guided targeting movements'; and (c) a long-lasting display of a new strategy that allowed the lesioned cat to collect its pellets despite of its other deficits. These data led to the conclusion that a lesion of A8 cells even disrupts the function of the SNR, being one of the outputstations of the A8 cell group.

Efferent projections of the retrorubral nucleus to the substantia nigra and ventral tegmental area in cats as shown by anterograde tracing.

The aim of the present study was to determine whether the retrorubral nucleus projects to the dopaminergic nuclei in the ventral midbrain of the cat. For this purpose, injections of biotinylated dextran-amine or Phaseolus vulgaris-leucoagglutinin were placed into the retrorubral nucleus under stereotaxic guidance. The tracers were visualized by means of (immuno) histochemical procedures. In addition, tyrosine hydroxylase immunohistochemistry was used to evaluate the location of the injection sites and the distribution of the anterogradely labeled fibers. Both tracers reveal the same topography of labeled fibers in the ventral mesencephalon. Labeled fibers with varicosities were found ipsilaterally in the substantia nigra pars compacta, the substantia nigra pars lateralis, the ventral tegmental area and, contralaterally, in the substantia nigra pars compacta, the ventral tegmental area, and the retrorubral nucleus. A considerable number of labeled axons with varicosities were observed to be wrapped around the dendrites and perikarya of tyrosine hydroxylase-positive neurons in these areas. The present results are discussed in view of the possible role of the A8 dopaminergic cell group in the coordination of A9 nigrostriatal and A10 mesolimbic systems, as well as in the progressive pathology seen in patients suffering from Parkinson's disease.

Surgical treatment of idiopathic transdural spinal cord herniation: a new technique to untether the spinal cord.

Idiopathic transdural spinal cord herniation is a rare but treatable cause of thoracic myelopathy caused by herniation of the spinal cord through a defect in the dura. The diagnosis is frequently missed or delayed, but the latest imaging techniques can document spinal cord herniation through a dural defect. Surgical treatment, consisting of reducing the herniation by closing the dural defect or widening the aperture to prevent spinal cord compression, is rather successful. We describe a new technique to untether the spinal cord by wrapping a dura graft around the myelum to prevent recurrent transdural herniation. Two patients and a review of the literature are discussed. We conclude that high-resolution T2 magnetic resonance imaging is the best imaging modality to detect the entity, and wrapping the myelum is an effective surgical technique to untether the spinal cord.

Thoracic meningocele, meningomyelocele or myelocystocele? Diagnostic difficulties, consequent implications and treatment.

Spina bifida cystica is a closing disorder of the neural tube which infrequently occurs in the thoracic region. A rare lesion called myelocystocele is a variant of spina bifida cystica and is associated with syringomyelia, Chiari type 2 malformation and hydrocephalus. Usually the patient has no neurological deficit, but future deterioration can occur due to posterior tethering of the spinal cord by adhesions. The prenatal diagnosis by ultrasound study can be misleading and in order to attain the correct diagnosis, especially if abortion is considered, a prenatal MRI scan should be done before the parents are counselled, and should be repeated prior to operative treatment. Surgical correction of myelocystocele is not only for cosmetic reasons, but also to untether the spinal cord prophylactically to prevent future neurological deterioration. In this case report, we present a child born with a thoracic myelocystocele, the diagnostic difficulties, consequent implications and surgical treatment.

Effects of nucleus prepositus hypoglossi lesions on visual climbing fiber activity in the rabbit flocculus.

The caudal dorsal cap (dc) of the inferior olive is involved in the control of horizontal compensatory eye movements. It provides those climbing fibers to the vestibulocerebellum that modulate optimally to optokinetic stimulation about the vertical axis. This modulation is mediated at least in part via an excitatory input to the caudal dc from the pretectal nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic system. In addition, the caudal dc receives a substantial GABAergic input from the nucleus prepositus hypoglossi (NPH). To investigate the possible contribution of this bilateral inhibitory projection to the visual responsiveness of caudal dc neurons, we recorded the climbing fiber activity (i.e., complex spikes) of vertical axis Purkinje cells in the flocculus of anesthetized rabbits before and after ablative lesions of the NPH. When the NPH ipsilateral to the recorded flocculus was lesioned, the spontaneous complex spike firing frequency did not change significantly; but when both NPHs were lesioned, the spontaneous complex spike firing frequency increased significantly. When only the contralateral NPH was lesioned, the spontaneous complex spike firing frequency decreased significantly. Neither unilateral nor bilateral lesions had a significant influence on the depth of complex spike modulation during constant velocity optokinetic stimulation or on the transient continuation of complex spike modulation that occurred when the constant velocity optokinetic stimulation stopped. The effects of the lesions on the spontaneous complex spike firing frequency could not be explained when only the projections from the NPH to the inferior olive were considered. Therefore we investigated at the electron microscopic level the nature of the commissural connection between the two NPHs. The terminals of this projection were found to be predominantly GABAergic and to terminate in part on GABAergic neurons. When this inhibitory commissural connection is taken into consideration, then the effects of NPH lesions on the spontaneous firing frequency of floccular complex spikes are qualitatively explicable in terms of relative weighting of the commissural and caudal dc projections of the NPH. In summary, we conclude that in the anesthetized rabbit the inhibitory projection of the NPH to the caudal dc influences the spontaneous firing frequency of floccular complex spikes but not their modulation by optokinetic stimulation.

Short- and long-term plasticity of the hippocampus to nucleus accumbens and prefrontal cortex pathways in the rat, in vivo.

The pathways from the hippocampal formation to the nucleus accumbens and the prefrontal cortex are likely to play a role in several aspects of learning and memory. In the present study we addressed the question of how plastic changes in these structures may occur simultaneously. This question can be studied in an appropriate way in the hippocampal/fornix-fimbria to prefrontal cortex/nucleus accumbens system, since electrical stimulation of the fornix-fimbria fibre bundle evokes characteristic field potentials in the two target areas simultaneously. First, we examined the termination field in the nucleus accumbens (medial shell and core region with an extension into the ventro-medial caudate-putamen) and the prefrontal cortex (deeper layers of the ventral prelimbic and ventral infralimbic areas) by recording single unit activity evoked by stimulation of fornix-fimbria fibres in halothane anaesthetized rats. Second, we studied short-term plasticity, namely paired pulse facilitation, in these two areas upon stimulation of the fornix-fimbria fibres. In the nucleus accumbens, paired pulse facilitation was encountered for double pulse intervals between 25 and 500 ms, peaking around 100 ms. In the medial prefrontal cortex it was confined to intervals between 25 and 200 ms, with a peak around 75 ms. Third, we investigated whether LTP could be elicited simultaneously in the two target structures by a single tetanic stimulation (50 Hz, 2 s) of the fornix-fimbria fibres. LTP that was sustained for more than 90 min in the medial prefrontal cortex, reached levels of 130% of control values. In the nucleus accumbens, however, only a transient form of potentiation was found which lasted no more than 60 min. These data show that synaptic weights can be changed in several target structures of the hippocampal formation, simultaneously, in a distributed way.