Hydrocephalus due to marked enlargement of spinal roots in a patient with chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: Hydrocephalus or papilledema has rarely been reported in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: We report a 65-year-old woman with a 12-year history of CIDP presenting with progressive dementia, hallucination and deterioration of gait. RESULTS: Neurological examination revealed cognitive impairment, symmetric proximal and distal weakness with areflexia and muscle atrophy in the distal four limbs. The cerebrospinal fluid examination showed marked elevation of protein concentration. Magnetic resonance imaging revealed hydrocephalus and marked enlarged cervical and lumbar roots and plexus. The cervical cord and cauda equina were compressed by the swollen roots. A ventriculoperitoneal shunt resulted in reduction of the ventricles size along with improvement of her cognitive impairment. CONCLUSION: In our patient with CIDP, hydrocephalus was likely caused by hypertrophic nerve roots. Our findings suggest that CIDP patients with pronounced hypertrophic nerve roots require careful observation.

Anti-GQ1b antibody syndrome: anti-ganglioside complex reactivity determines clinical spectrum.

BACKGROUND AND PURPOSE: Anti-GQ1b antibodies have been found in patients with Miller Fisher syndrome as well as its related conditions. Our aim was to identify the mechanism by which autoantibodies produce various clinical presentations in 'anti-GQ1b antibody syndrome'. METHODS: Immunoglobulin G antibodies to ganglioside complex (GSC) of GQ1b or GT1a with GM1, GD1a, GD1b or GT1b were tested in sera from patients with anti-GQ1b (n = 708) or anti-GT1a (n = 696) IgG antibodies. Optical densities of the single anti-GQ1b or anti-GT1a antibodies were used as reference (100%), and those of anti-GSC antibodies were expressed in percentages to reference. The relationships between anti-GSC antibody reactivity and the corresponding clinical features were assessed by multivariate logistic regression analysis. RESULTS: Ophthalmoplegia and hypersomnolence were significantly associated with complex-attenuated anti-GQ1b and anti-GT1a antibodies. Ataxia was associated with GD1b- and GT1b-enhanced anti-GQ1b antibodies or GM1-enhanced anti-GT1a antibodies. Bulbar palsy was associated with GT1b-enhanced anti-GQ1b antibodies. Neck weakness was associated with GD1a-enhanced anti-GQ1b antibodies. Arm weakness was associated with GD1b-enhanced anti-GQ1b and GD1a-enhanced anti-GT1a antibodies. Leg weakness was associated with GD1a-enhanced anti-GQ1b and anti-GT1a antibodies. CONCLUSIONS: Differences in fine specificity of anti-GQ1b antibodies are associated with clinical features, possibly due to the different expression of gangliosides in different parts of the nervous system.

Sound velocities of majorite garnet and the composition of the mantle transition region.

The composition of the mantle transition region, characterized by anomalous seismic-wave velocity and density changes at depths of approximately 400 to 700 km, has remained controversial. Some have proposed that the mantle transition region has an olivine-rich 'pyrolite' composition, whereas others have inferred that it is characterized by pyroxene- and garnet-rich compositions ('piclogite'), because the sound velocities in pyrolite estimated from laboratory data are substantially higher than those seismologically observed. Although the velocities of the olivine polymorphs at these pressures (wadsleyite and ringwoodite) have been well documented, those of majorite (another significant high-pressure phase in the mantle transition region) with realistic mantle compositions have never been measured. Here we use combined in situ X-ray and ultrasonic measurements under the pressure and temperature conditions of the mantle transition region to show that majorite in a pyrolite composition has sound velocities substantially lower than those of earlier estimates, owing to strong nonlinear decreases at high temperature, particularly for shear-wave velocity. We found that pyrolite yields seismic velocities more consistent with typical seismological models than those of piclogite in the upper to middle parts of the region, except for the potentially larger velocity jumps in pyrolite relative to those observed at a depth of 410 km. In contrast, both of these compositions lead to significantly low shear-wave velocities in the lower part of the region, suggesting possible subadiabatic temperatures or the existence of a layer of harzburgite-rich material supplied by the subducted slabs stagnant at these depths.

Immune responses to porphyromonas gingivalis infection suppress systemic inflammatory response in experimental murine model.

Periodontitis is a localized infectious disease caused by periodontopathic bacteria such as Porphyromonas gingivalis (P. gingivalis), and the severity correlates to significance of immune responses. Recently, it has been reported that periodontitis is associated with the development of systemic disease such as diabetes and atherosclerosis because of increasing invasion of oral pathogens to the circulation. However, the association between local and systemic infectious responses is still unclear. In the present study, we examined the differences of biological responses in animals with or without bacterial infection. After Balb/c mice were infected subcutaneously with live P. gingivalis W83, serum, skin and liver were collected according to experimental protocol. The skin and liver tissues were observed pathologically by haematoxylin-eosin staining, and serum IL-6 levels were measured using ELISA method. Throughout the experimental period, conditions of the mice were observed continuously. As expected, severe infiltration of leukocytes were observed at inflamed skin corresponding to the number of bacterial challenges. Although no inflammatory appearance of skin was observed, serum IL-6 levels were increased dramatically (P <0.01, Student's t-test) and liver tissues were injured in the mice without bacterial challenge. Interestingly, although severe inflammatory appearance of the skin was observed, serum IL-6 levels were not increased and no inflammatory responses were observed in the liver of the 3-times bacterially challenged group. Importantly, immunoglobulin G against P. gingivalis W83 was detected in the blood of mice with 3-times bacterial challenge corresponding to improvement of weight loss and survival. In conclusion, although multiple infections develop severe localized inflammation, the immune system should be sufficient to protect the systemic inflammatory responses.

A first-order liquid-liquid phase transition in phosphorus

First-order structural phase transitions are common in crystalline solids, whereas first-order liquid-liquid phase transitions (that is, transitions between two distinct liquid forms with different density and entropy) are exceedingly rare in pure substances. But recent theoretical and experimental studies have shown evidence for such a transition in several materials, including supercooled water and liquid carbon. Here we report an in situ X-ray diffraction observation of a liquid-liquid transition in phosphorus, involving an abrupt, pressure-induced structural change between two distinct liquid forms. In addition to a known form of liquid phosphorus--a molecular liquid comprising tetrahedral P4 molecules--we have found a polymeric form at pressures above 1 GPa. Changing the pressure results in a reversible transformation from the low-pressure molecular form into the high-pressure polymeric form. The transformation is sharp and rapid, occurring within a few minutes over a pressure range of less than 0.02 GPa. During the transformation, the two forms of liquid coexist. These features are strongly suggestive of a first-order liquid-liquid phase transition.

Clinical predictors of mechanical ventilation in Fisher/Guillain-Barré overlap syndrome.

BACKGROUND: Some patients with Fisher syndrome (FS) developed subsequent descending tetraparesis (Fisher/Guillain-Barré overlapping syndrome: FS/GBS). The assumption is that such descending progression may frequently lead to respiratory failure. OBJECTIVE: To investigate whether patients with FS/GBS more often require artificial ventilation than those with typical GBS and which clinical and serological findings are useful predictors. METHODS: Medical records were reviewed of patients who had acute ophthalmoplegia, ataxia and areflexia, as well as subsequent tetraparesis with monophasic course. Forty-five patients fulfilled the FS/GBS criteria. Clinical and serological features were analysed, and clinical predictors of mechanical ventilation were investigated. RESULTS: FS/GBS patients more frequently required mechanical ventilation than did GBS patients (24% vs 10%, p = 0.04). The former also needed artificial ventilation earlier than the latter (p = 0.03), but none of the FS patients required it. As the initial symptom, ventilated FS/GBS patients more frequently showed titubation than non-ventilated patients (55% vs 18%, p = 0.04). During the course of the illness, descending tetraparesis was more common in 11 ventilated FS/GBS patients than in the other 34 non-ventilated patients (64% vs 21%, p = 0.02). The need for artificial ventilation was not associated with anti-GQ1b IgG antibodies, monospecific anti-GT1a IgG antibodies or IgG antibodies to various ganglioside complexes. CONCLUSIONS: FS/GBS patients significantly needed mechanical ventilation more often. Such patients showing titubation and descending tetraparesis need to be carefully monitored as the illness progresses because those clinical features are helpful predictors of respiratory failure.

Adult neurogenesis with 5-HT expression in lesioned goldfish spinal cord.

In contrast to mammals, spontaneous nerve regeneration occurs in the teleost spinal cord. In the present study, we examined whether neurogenesis is involved in posttraumatic regeneration in the goldfish spinal cord. In intact fish, many spinal cells positive for both a monoclonal neuronal marker (Hu) and bromodeoxyuridine (BrdU) were observed 24 h after i.p. injection of BrdU, suggesting that constant neurogenesis occurs in the goldfish spinal cord. After hemisection of the spinal cord, the number of spinal cells positive for Hu and BrdU was significantly increased around the lesion site. The number of Hu- and BrdU-positive cells reached the maximum level 7 days after hemisection. In intact fish, spinal cells positive for both Hu and BrdU were also observed 5 weeks after BrdU injection, suggesting that newborn neurons survive for a long time. Six weeks after hemisection, the number of surviving Hu- and BrdU-positive cells at the lesion site was significantly increased as compared with that in intact fish, and some of them were also positive for 5-HT. A retrograde tract tracing study showed that the 5-HT+ neurons were close to the regenerated axons passing through the lesion site. These results suggest that adult neurogenesis occurs in the goldfish spinal cord, and that neurogenesis is activated by spinal cord lesion. The newly produced neurons survive a long time at the lesion site, and might participate in the repair of injured tissue and in the regeneration of descending long axons beyond the lesion site.

Clinical classification of 103 Japanese patients with Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is the commonest cause of flaccid paralysis worldwide. Miller Fisher syndrome (MFS) is a variant of GBS characterized by ophthalmoplegia and ataxia. Together GBS and MFS form a continuum of discrete and overlapping subtypes, the frequency of which remains unknown. We retrospectively analysed the clinical features (antecedent symptoms, pattern of neurological weakness or ataxia, presence of hypersomnolence) of 103 patients at a single hospital in Japan. Patients were then classified according to new diagnostic criteria (Wakerley et al., 2014). Laboratory data (neurophysiology and anti-ganglioside antibody profiles) were also analysed. According to the new diagnostic criteria, the 103 patients could be classified as follows: classic GBS 73 (71%), pharyngeal-cervical-brachial weakness 2 (2%), acute pharyngeal weakness 0 (0%), paraparetic GBS 1 (1%), bifacial weakness with paraesthesias 1 (1%), polyneuritis cranialis 0 (0%), classic MFS 18 (17%), acute ophthalmoparesis 1 (1%), acute ptosis 0 (0%), acute mydriasis 0 (0%), acute ataxic neuropathy 1 (1%), Bickerstaff brainstem encephalitis 3 (3%), acute ataxic hypersomnolence 0 (0%), GBS and MFS overlap 1 (1%), GBS and Bickerstaff brainstem encephalitis overlap 1 (1%), MFS and pharyngeal-cervical-brachial weakness overlap 1 (1%). Application of the new clinical diagnostic criteria allowed accurate retrospective diagnosis and classification of GBS and MFS subtypes.

Compensatory projections of primary sensory fibers in lumbar spinal cord after neonatal thoracic spinal transection in rats.

Complete spinal transection in adult rats results in poor recovery of hind limb function, whereas significant spontaneous recovery can occur following spinal cord transection in rat neonates. The mechanisms underlying the recovery, however, are poorly understood. Recent studies in rodents suggested that the recovery is not due to axonal regeneration, but rather due to reorganization of the neural circuits in the spinal cord below the injury site, including central pattern generators. Few studies have reported histological evidence for changes in the primary sensory fibers or terminals. Thus, in the present study, we transected spinal cords of rats at thoracic level 8 at postnatal day 5. Four weeks after the injury, biotinylated-dextran amine (BDA), an anterograde tracer, was injected into the dorsal root ganglion of the lumbar spinal cord to examine the localization of sensory fibers and their terminal buttons in the spinal cord. BDA-positive axons in the rat spinal cord following neonatal spinal transection (neo ST) were longer than those in sham-operated or normal rats. The number of terminal buttons was also higher in spinal cords of neo ST rats compared with sham-operated or normal rats. These findings suggest that sensory fibers project more strongly and make more synapses following neo ST to compensate for the lack of supraspinal projections.

Axonal regeneration through the fibrous scar in lesioned goldfish spinal cord.

Spontaneous nerve regeneration beyond the scar frequently occurs in fish after spinal cord lesions, in contrast to mammals. Here we examined the spatiotemporal relationship between the fibrous scar and axonal regeneration in the goldfish. Within 1 week after hemisection of the spinal cord, the open wound was closed by a fibrous scar that was demarcated from the surrounding nervous tissue by the glia limitans, which was immunoreactive for laminin. Within 1 week after hemisection, regenerating axons entered the fibrous scar, and were surrounded by laminin-coated tubular structures continuous with the glia limitans. Regenerating axons that initially entered the fibrous scar were usually accompanied by glial processes. Within 2-3 weeks after hemisection, the tubular structures became enlarged, and the regenerating axons increased in number, fasciculating in the tubules. Glial processes immunoreactive for glial fibrillary acid protein and 5-hydroxytryptamine neurons then entered the tubular structures to associate with the regenerating axons. The tubular structures developed further, creating tunnels that penetrated the fibrous scar, through which the regenerating axons passed. At 6-12 weeks after hemisection, the fibrous scar was smaller and the enlarged tunnels contained many glial processes and several axons. The findings of present study demonstrated that, following spinal lesions in goldfish, regenerating axons enter and pass the scar tissue. The regenerating axons first enter the fibrous scar with glial elements and then grow through laminin-coated tubular structures within the fibrous scar. Invasion by glial processes and neuronal elements into the tubular structures reduces the fibrous scar area and allows for more regenerating axons to pass beyond the fibrous scar.

Trigeminal, vagal, and spinal projections of supramedullary cells in the puffer fish, Takifugu niphobles.

The supramedullary cells (SMCs) of teleosts have been studied for nearly 100 years, but their peripheral connections have remained obscure. We examined the supramedullary cells of the puffer fish, Takifugu niphobles, using horseradish peroxidase transport. Horseradish peroxidase labeling was found bilaterally after application to the trigeminal, the posterior branch of the vagal, and the spinal nerves. No labeled neurons were found after application to the anterior or visceral branches of the vagal nerve. Thus, labeled SMCs were found only after application to the nerves containing cutaneous branches. Some rostrocaudal topographical labeling was found after selective application to each of the four branches of the trigeminal nerve. Labeled neurons were more common in the rostral than in the central or caudal part of the SMC region. Some topographical labeling was also found after application to the first, second, and third spinal nerves, but the topography was not very clear, and there was considerable overlap in the distribution of labeled cells. The sum total of labeled SMCs after unilateral horseradish peroxidase application to each peripheral nerve was more than three times the total number of ipsilateral SMCs, indicating that a single SMC projects several peripheral processes into different nerves. From these results, and taking previous studies into consideration, we propose that supramedullary neurons have a phylogenetic relationship with the spinal dorsal cells of the lamprey and with the extramedullary cells of the amphibian embryo.

Differential distribution of nerve terminals immunoreactive for substance P and cholecystokinin in the sympathetic preganglionic cell column of the filefish Stephanolepis cirrhifer.

Immunoreactivity for substance P and cholecystokinin-8 was examined in the nerve fibers in the central autonomic nucleus, a cell column for sympathetic preganglionic neurons, in the filefish Stephanolepis cirrhifer. Substance P-immunoreactive fibers were distributed throughout the entire rostrocaudal extent, but were more abundant in the caudal part of the column, where substance P-immunoreactive varicosities sometimes made contacts with the sympathetic preganglionic neurons. Cholecystokinin-8-immunoreactive fibers were found almost entirely in the rostral part of the column, where a dense network of varicosities was in close apposition to a considerable number of the sympathetic preganglionic neurons. Double labeling immunohistochemistry showed that substance P fibers and cholecystokin-8 fibers were entirely different, and distinct from serotonin-immunoreactive fibers. By using immunoelectron microscopy, synaptic specialization was sometimes observed between the dendrites of preganglionic neurons and varicosities immunoreactive for substance P and cholecystokinin-8. Substance P- and cholecystokinin-8 fibers were seen from the descending trigeminal tract, through the dorsolateral funiculus and the ventral portion of the dorsal horn, to the central autonomic nucleus. After colchicine treatment, substance P-immunoreactive perikarya were found in the cranial and spinal sensory ganglia. These results suggest that the sympathetic preganglionic neurons of the filefish receive innervation by substance P fibers and cholecystokinin fibers, and that the former might be of primary sensory origin. Topographical distribution of cholecystokinin-8-immunoreactive terminals in the central autonomic nucleus along the rostrocaudal extent might underlie the differential regulation of sympathetic activity via a distinct population of sympathetic preganglionic neurons.

Comparative studies of the biological activities of human tumor necrosis factor and its derivatives.

Biological activities of human tumor necrosis factor (TNF) and its derivatives were compared. In cytotoxicity assay with L929 cells, one derivative, designated as TNF(Asn), showed significantly lower activity than any other TNF examined. In binding assay, this derivative was also shown to have lower affinity for TNF receptors on L929 cells, suggesting that the cytotoxic activity of TNFs on L929 cells correlates with their affinity for receptors. We also found that the cytotoxic activity of TNF on A673 cells and its inhibitory effect on lipoprotein lipase were parallel with the cytotoxic activity on L929 cells, but the growth-enhancing activity on FS-4 cells and the cytotoxic activity on endothelial cells were not. It was also shown that TNF(Asn) had lower affinity than any other TNF for receptors on these target cells tested. These results suggested that there might be at least two types of cellular responses to TNF; one might correlate with the receptor-binding affinity of TNFs and the other not.

Substance P immunoreactivity in the vagal nerve of mice.

After horseradish peroxidase was applied to the main trunk of the mouse vagal nerve, anterogradely labeled cells in the vagal ganglia and fibers in the solitary complex, and retrogradely labeled cells in the dorsal motor nucleus and the ambiguous nucleus were observed. Most of the cells in the nodose ganglion were labeled, but only a few cells in the jugular ganglion were labeled. Heavily labeled nerve terminals and fibers were found in 3 areas in the solitary nucleus: i.e., the lateral half of the medial nucleus, the ventrolateral nucleus, and the commissural nucleus. There was only weak labeling in the dorsolateral nucleus, ventral nucleus, and intermediate nucleus. Substance P immunoreactive neurons in the vagal ganglia were found in the jugular ganglion and the dorsal part of the nodose ganglion, but not in the ventral part of the nodose ganglion. Substance P immunoreactivity in the solitary nucleus was moderate in the commissural nucleus and the intermediate nucleus, but was lacking or very weak in the lateral half of the medial nucleus, ventral nucleus, dorsolateral nucleus, and ventrolateral nucleus. We conclude that most substance P containing fibers in the main trunk of the vagal nerve project centrally to the commissural nucleus and peripherally to some of the thoracic viscera.

Direct projections from the spinal cord to the trigeminal sympathetic ganglion of the puffer fish, Takifugu niphobles.

The sympathetic trunk of teleosts extends into the cranial levels, forming the cranial sympathetic ganglia. When horseradish peroxidase was applied to the trigeminal sympathetic ganglion (a sympathetic ganglion at the level of the trigeminal nerve) of the puffer fish, Takifugu niphobles, retrogradely labeled neurons were found in the central autonomic nucleus (a distinct cell column in the rostral part of the spinal cord). The central autonomic nucleus has been known to contain preganglionic neurons projecting to the sympathetic ganglia at the spinal levels. Thus, the present results indicate that the central autonomic nucleus in the spinal cord of teleosts contains not only preganglionic neurons projecting to the sympathetic ganglia at the spinal levels, but also neurons projecting to the sympathetic ganglia at the cranial levels.

NADPH-diaphorase activity in the sympathetic preganglionic neurons of the filefish, Stephanolepis cirrhifer.

Enzyme histochemistry combined with horseradish peroxidase retrograde tracing demonstrated NADPH-diaphorase activity in the spinal sympathetic preganglionic neurons in the spinal cord of the filefish, Stephanolepis cirrhifer, these neurons with NADPH-diaphorase activity were located just dorsal and lateral to the central canal. The results indicate that nitric oxide is synthesized in the spinal sympathetic preganglionic neurons of filefish.

NADPH-diaphorase activity in the vagal afferent pathway of the dogfish, Triakis scyllia.

Nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity was examined in the cranial sensory ganglia and brainstem of the banded dogfish, Triakis scyllia. Positive neurons were found in the vagal sensory ganglion projecting to the coelomic organs, but not in those projecting to the gills or the lateral line organs. Nerve terminals in the vagal lobe were also positive. No positive neurons were found in the glossopharyngeal, facial, or trigeminal sensory ganglia. These results suggest that use of nitric oxide in the vagal sensory transmission from the coelomic organs may have been maintained in the evolutionary process from fish to mammals.

Selective projections of cholecystokinin-8 immunoreactive fibers to galanin immunoreactive sympathetic preganglionic neurons in a teleost, Stephanolepis cirrhifer.

In the cellular column of sympathetic preganglionic neurons (SPNs) of the filefish Stephanolepis cirrhifer, neurons containing galanin (GAL) form a distinct population projecting specifically to non-adrenergic postganglionic neurons in the celiac and cranial sympathetic ganglia. The present study showed that virtually all of the GAL-immunopositive SPNs made contact with many nerve terminals immunopositive for cholecystokinin octapeptide (CCK-8). GAL-negative preganglionic neurons made contact with only 26% of this type of nerve terminal; CCK-8-immunopositive nerve fibers appeared to project selectively to GAL-immunopositive SPNs with projections to specific targets. The CCK-8-positive nerve fibers might be of primary sensory origin, and participate in the visceral reflexes.

Serotonin-immunoreactive axons in the cell column of sympathetic preganglionic neurons in the spinal cord of the filefish Stephanolepis cirrhifer.

Serotonin-immunoreactive axonal components were observed in the central autonomic nucleus (CAN), a cell column of sympathetic preganglionic neurons in the rostral spinal cord of the filefish Stephanolepis cirrhifer. Serotonin-positive axonal varicosities were seen around neuronal perikarya through the whole rostrocaudal extent of the CAN, although their distribution pattern in the rostral CAN was different from that in the caudal CAN. Electron microscopically, serotonin-positive axonal varicosities were found to make axodendritic and axosomatic synapses on CAN neurons. Many serotonin-positive neuronal cell bodies were seen in the raphe nuclei in the lower brainstem, whereas only a few were found in the spinal cord. Thus most of serotoninergic axons within the CAN were considered to originate from the raphe nuclei in the lower brainstem.

Gastrin/CCK-ergic innervation of cutaneous mucous gland by the supramedullary cells of the puffer fish Takifugu niphobles.

The supramedullary cells (SMCs) are spinal neurons lying at the dorsal surface of teleosts. In the present study, we examined whether the SMCs of the puffer fish (Takifugu niphobles) might express gastrin/cholecystokinin-immunoreactivity, as observed in some other teleosts. All the SMCs were immunoreactive for gastrin/cholecystokinin. On the other hand, many immunoreactive varicose nerve fibers were also found terminating in the mucous glands in the skin. In addition, immunoreactive fibers were sparsely distributed in the epidermal layer. No neuronal cells other than the SMCs showed gastrin/cholecystokinin-immunoreactivity centrally or peripherally. The results suggest that gastrin/cholecystokinin-immunoreactive axons in the cutaneous mucous glands and epidermal layer are axons of the SMCs. In view of the present findings, the possible nature of SMCs was discussed.