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.

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.

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.

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.

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.

Increased migration of IgA lymphocytes to VIP nerve fibers after DSS-induced colitis.

Immunoglobulin-positive lymphocytes are present close to vasoactive intestinal polypeptide-positive (VIP(+)) nerve fibers in the lamina propria of the intestinal tract, and have an important role in mucosal defense. The number of immunoglobulin A-positive (IgA(+)) cells close to the epithelial basement membrane and nerve fibers is increased by the administration of lipopolysaccharides, which induce IgA secretion into the intestinal lumen. The relationship between immunoglobulin-positive lymphocytes and the VIP(+) nerve fibers during inflammation, such as in inflammatory bowel disease, however, is not well known. The morphological relationship between immunoglobulin-positive cells and the basement membrane or the VIP(+) nerve fibers in the colon was examined using double immunofluorescent labeling in an inflammatory bowel disease mouse model created by oral administration of dextran sodium sulfate (DSS). DSS administration induced goblet cell loss, crypt loss, intestinal epithelium deformation and infiltration of inflammatory cells in the mucosa. In the colon, the number and percentage of IgA(+) lymphocytes close to the basement membrane and the VIP(+) nerve fibers in the lamina propria increased after DSS administration, in parallel with the pathologic progress in the inflamed tissue. On the other hand, the percentage of immunoglobulin G-positive (IgG(+)) lymphocytes close to the basement membrane and the VIP(+) nerve fibers decreased, although the total number of IgG(+) lymphocytes in the lamina propria increased. We suggest that the immunoglobulin-producing lymphocytes and enteric nerve fibers in the colon normally have a close morphological relationship, and that this relationship is reinforced in a cell-specific manner during inflammation.

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.

Invasion process of Candida albicans to tongue surface in early stages of experimental murine oral candidiasis.

We analyzed the morphologic and microbiologic aspects of the process of adhesion and invasion in the early stages of Candida albicans oral infection in a murine system. ICR mice were anesthetized by intramuscular injection with chlorpromazine chloride and then orally inoculated by swabbing with the C. albicans yeast cells. Their tongues were resected 1-3h after inoculation, washed sequentially with a physiological saline and 0.25% trypsin-solution and then homogenized. The number of viable C. albicans cells on the tongue surface was counted and fround to increase from 1-3h after inoculation. Most of the Candida cells attached to the tongue surface were present in clusters, mainly located in the gaps between lingual papillae and were covered with a mucoidal substance. By 3h after inoculation, these clusters frequently formed mycelia and could not be easily detached from the tongue surface by trypsin treatment. Observation of SEM and histological sections stained by Fungiflora Y revealed that the Candida hyphae at 3h stretched out of the cluster and entered the tongues through the surface. These results indicate that Candida hyphae begin to invade the tongue surface within 3h after inoculation and suggest that the mucus-like substance covering these cells may have an important early role in the interaction between the Candida cells and the tongue mucosal epithelium.

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.

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.

Prospective study on anti-ganglioside antibodies in childhood Guillain-Barré syndrome.

BACKGROUND: Antiganglioside antibodies have been reported to play a part in the pathophysiology of Guillain-Barré syndrome (GBS). AIMS: To investigate the prevalence and correlation of anti-ganglioside antibodies with clinical data in children with GBS in a multicentre clinical trial. METHODS: Immunoglobin (Ig)G and IgM to GM1, GM1b, GD1a, GalNAc-GD1a, GD1b, GT1a, and GQ1b were measured by ELISA in sera obtained before treatment. In addition, serological testing for Campylobacter jejuni was carried out. In parallel, a group of adults with GBS and a control group of children without GBS or other inflammatory diseases were evaluated. RESULTS: Sera from 63 children with GBS, 36 adults with GBS and 41 children without GBS were evaluated. Four of the children with GBS showed positive IgG to GM1, in one case combined with anti-GalNAc-GD1a and in one with anti-GD1b. Two others showed isolated positive IgG to GD1b and GT1a. One showed increased anti-GalNAc-GD1a IgM. In 5 of the 63 children, serological evidence of a recent infection with C jejuni was found, and this correlated significantly with the raised antibodies (p = 0.001). In the control group without GBS, no child showed positive IgG, but one showed anti-GalNAc-GD1a IgM. Compared with the adults with GBS, the frequency of antibodies in children was insignificantly lower. In our study, patients with positive antibodies did not show a more severe GBS course or worse outcome than those who were seronegative, and we could not show an increased incidence of axonal dysfunction. CONCLUSIONS: In some children with GBS, one can detect raised IgG against various gangliosides, similar to that in adults. A recent infection with C jejuni is markedly associated with the presence of these antibodies. However, in contrast with what has been reported in adults, in this study we were unable to show a negative effect of these findings on the clinical course.

Nonviscous metallic liquid Se.

Viscosity is one of the fundamental physical properties of liquids; for different melts it varies in an extremely wide range. Selenium is among the first elementary substances to have manifested, at compression, a phase transformation in the liquid state accompanied by melt metallization. Direct measurements by means of a real-time radiography show that the viscosity of liquid Se under pressure drops by 500 times to a very low level of 8 mPa s. This is the first case of viscosity measurements being performed both for a relatively viscous semiconducting state and a low-viscous metallic state of the same liquid substance. The viscosity of the Se melt strongly decreases with pressure along the melting curve in a semiconducting state and experiences a further significant drop at melt metallization. A similar phenomenon is expected to be observed in many chalcohenide, halogenide, and oxide melts.

Analysis of microsatellite polymorphism around the HLA-B locus in Iranian patients with Behçet's disease.

We have previously suggested that in a Japanese population the susceptible locus for Behçet's disease (BD) is HLA-B51 itself. To confirm this finding in another population, we performed HLA class I typing using the PCR-SSP method and analyzed eight polymorphic markers distributed within 1100 kb around the HLA-B gene using automated sequencer and subsequent automated fragment detection by fluorescent-based technology with the DNA samples of 84 Iranian patients with BD and 87 healthy ethnically matched controls. As a result, three microsatellite alleles (MICA-A6, MIB-348, C1-4-1-217) and HLA-B51 were found to be strongly associated with BD. Of these alleles HLA-B51 is the most strongly associated allele. There were no alleles that were increased in allele frequency at any microsatellite loci centromeric of MICA or telomeric of HLA-B51. Therefore, HLA-B51 was confirmed to be by far the most strongly associated gene with BD in an Iranian population.

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.

Nutrient arteries of the temporomandibular joint: an anatomical and a pathological study.

We have identified an artery which is a sub-branch of the inferior alveolar artery, and propose to call it the temporomandibular branch. Mandibular bones of 36 autopsy cases (ages 23-85; 20 males and 16 females) were examined. Contrast media were injected into the inferior alveolar artery, decalcification was conducted, and photographs were taken using soft X-ray equipment (Softex: Nippon Softex, co. CSM type). Then, an examination was conducted concerning sclerosis of these arteries. Next, H.E., Azan, and Pap silver stains were used for microscopic specimens to examine arteriosclerosis of the temporomandibular joint. The artery that sub-branches toward the temporomandibular branch, branches out immediately after the inferior alveolar artery and enters the mandibular foramen, becoming the artery that supplies the temporomandibular joint. This temporomandibular branch travels slightly downward, forward of the inferior alveolar artery, and turns back toward the mandibular base. It advances to the mandibular joint almost directly. The route taken was classified into three types. Toward the head of the mandible, the temporomandibular branch, after passing over the neck of the mandible, divides into two sub-branches, anterior and posterior. In our pathological study of the temporomandibular branch, there were a small number of cases with slight intimal thickening and mild elastosis. As regards sclerotic changes, particularly in cases more than 50 years old. There were very few cases showing intimal changes. Sclerotic changes of the artery supplying the head of the mandible increase with age. The same can be said of the about the constriction rate. These findings correlated with subject age.

Histomorphometric analysis of age changes in the human inferior alveolar artery.

Angiography is often used to investigate age-related changes in the inferior alveolar artery, the major nutrient artery of the mandible. Although histological examinations have been made from several viewpoints, e.g. age change, pathogenesis of osteoradionecrosis, and relation to tooth extraction, these studies have used a limited number of samples and simple histometric methods. The purpose here was to describe histopathological and histomorphometric age-related changes, and to investigate the relation between dentate status and the histomorphometry of the artery. Inferior alveolar arteries from 162 autopsy cases (age range 3-86 years) were examined histometrically with a mathematically standardized method. Histologically, there was diffuse fibrous intimal thickening, but no atheroma formation. Histometric analyses revealed a very gradual increase in both the radius of the artery and the thickness of the media with age, but the luminal radius did not correlate with age. Intimal thickness increased exponentially with age with very different features from those of the increase in the media. The relative radius of the lumen decreased with age after the sixth decade; this is thought to be an index for senile changes in the artery. Among the variables of arterial architecture examined, no particular difference was found between the dentate and non-dentate cases in the molar region.

Nervous control of blood flow microkinetics in the infrared organs of pit vipers.

The pit organ of pit vipers contains a membrane which serves as an infrared retina, processing infrared information by the degree to which the temperature of trigeminal nerve receptors (terminal nerve masses) is raised. The receptors are arranged in a monolayer array within the pit membrane and irrigated by a capillary network which both supplies energy to the terminal nerve masses and serves as a heat exchange mechanism. This mechanism maintains the receptors at a stable temperature level to increase or decrease their sensitivity and to reduce to a minimum the afterimage effect of a moving stimulus. We used a Doppler laser blood flow meter to measure the local changes in blood flow in response to a point heat source (a small soldering iron) and to direct stimuli (red and infrared lasers). Resection of any one of the trigeminal A-delta fiber trunks innervating the pit membrane abolished blood flow response in the area innervated, but resection of the main trunk between the primary neurons and the medulla left the response intact. In addition to the A-delta fibers the pit membrane contains autonomic and sensory C-fiber innervation, but preganglionic resection of parasympathetic neurons, and chemical blocking of postganglionic fibers with atropine and capsaicin had no influence on the blood flow changes. Therefore, on the basis of the rapid response time and the similarity of the blood flow curves to electrophysiological recordings from the receptors, we surmised that all blood flow changes were due to a vasomotor reaction, modulated by the terminal nerve masses directly, resulting in a change in local heat capacity that cools the stimulated receptors back to a basal temperature.