Caudal Nerve Research Articles

Enhancer of zeste acts as a major developmental regulator of Ciona intestinalis embryogenesis.

ABSTRACTThe paradigm of developmental regulation by Polycomb group (PcG) proteins posits that they maintain silencing outside the spatial expression domains of their target genes, particularly of Hox genes, starting from mid embryogenesis. The Enhancer of zeste [E(z)] PcG protein is the catalytic subunit of the PRC2 complex, which silences its targets via deposition of the H3K27me3 mark. Here, we studied the ascidian Ciona intestinalis counterpart of E(z). Ci-E(z) is detected by immunohistochemistry as soon as the 2- and 4-cell stages as a cytoplasmic form and becomes exclusively nuclear thereafter, whereas the H3K27me3 mark is detected starting from the gastrula stage and later. Morpholino invalidation of Ci-E(z) leads to the total disappearance of both Ci-E(z) protein and its H3K27me3 mark. Ci-E(z) morphants display a severe phenotype. Strikingly, the earliest defects occur at the 4-cell stage with the dysregulation of cell positioning and mitotic impairment. At later stages, Ci-E(z)-deficient embryos are affected by terminal differentiation defects of neural, epidermal and muscle tissues, by the failure to form a notochord and by the absence of caudal nerve. These major phenotypic defects are specifically rescued by injection of a morpholino-resistant Ci-E(z) mRNA, which restores expression of Ci-E(z) protein and re-deposition of the H3K27me3 mark. As observed by qPCR analyses, Ci-E(z) invalidation leads to the early derepression of tissue-specific developmental genes, whereas late-acting developmental genes are generally down-regulated. Altogether, our results suggest that Ci-E(z) plays a major role during embryonic development in Ciona intestinalis by silencing early-acting developmental genes in a Hox-independent manner.

Abstract 203: Visualization of drug delivery by using high resolution microscopic mass spectrometry

Abstract Pharmacokinetic (PK) and pharmacodynamic (PD) studies are important to evaluate the efficacy and toxicity of the drugs. In these analyses, tissue homogenates are generally used for the quantification by high-performance liquid chromatography (HPLC) or liquid chromatography mass spectrometry (LC-MS). However, they lack the information regarding the drug distribution in a specific anatomical area. The information of the drug distribution allows us to optimize the drug design enabling more efficient targeted delivery. We studied the tissue distribution of paclitaxel (PTX) and its micellar formulation (NK105) using a microscopic mass spectroscopy (MMS). A MMS in which a microscope is coupled with an atmospheric pressure matrix-assisted laser desorption/ionization (MALDI) and quadruple ion trap time-of-flight (TOF) analyser was used. The matrix-coated drug sample is ionised and then separated on the basis of its mass-to-charge ratio (m/z). Images were acquired from imaging mass spectrometry (IMS) or tandem mass spectrometry (MS/MS) data. (1) We established the drug imaging system with enhanced resolution and sensitivity. In the analysis, MS and MS/MS were used for quantification and validation, respectively. (2) NK105 showed much stronger antitumor effects on a human pancreatic cancer BxPC3 xenograft than PTX. In the drug imaging, we demonstrated that NK105 delivered more PTX to the whole tumor tissue (including the center lesion). In the mouse model, PTX caused the peripheral neurotoxicity but NK105 did not. Multiple high drug-signal areas surrounding and inside the caudal nerve were observed in the case of PTX, whereas the signals after NK105 injection were significantly low. We succeeded in visualising the EPR (Enhanced Permeability and Retention) effect using MMS. The data obtained by the drug imaging may be useful for facilitating DDS-drug design. The significance of microscopic mass spectrometry with high resolution in the visualisation of drug distribution. Sci Rep. 3:3050. 2013. Citation Format: Masahiro Yasunaga, Masaru Furuta, Koretsugu Ogata, Yoshikatsu Koga, Yasuhiro Matsumura. Visualization of drug delivery by using high resolution microscopic mass spectrometry. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 203. doi:10.1158/1538-7445.AM2015-203

Abstract 4503: Pharmacokinetics and pharmacodynamic analysis of eribulin mesylate and paclitaxel in mouse

Abstract Neuropathy arising from chemotherapy (CIPN) is a major clinical problem representing the dose-limiting side effect of many antineoplastic drugs. At their respective MTDs, we previously reported paclitaxel and ixabepilone produced more severe deficits in nerve conduction velocity, amplitude and degenerative changes in dorsal root ganglia (DRG) and sciatic nerve (SN) versus eribulin mesylate (Wozniak et al 2011). Similar trends for eribulin to cause less neuropathy have also been reported in the clinic (Cigler and Vadhat 2010, Jain and Cigler 2012, Vadhat et al 2013). The underlying reason for this differential effect remains elusive. Differences in tubulin binding may, in part, explain the differential effect (Perez et al 2009, Jordan et al 2005). Another potential explanation could reside in different pharmacokinetic (PK) and nervous tissue distribution of these agents. Toward this latter point, we conducted tissue distribution and pharmacokinetic studies following acute dosing of eribulin mesylate, paclitaxel and ixabepilone. We reported that while all three drugs rapidly cleared from plasma, they distributed into and cleared slowly (>3 days) from peripheral nervous system tissues (Wozniak et al 2014). We have now extended these studies to look out to 42 days following both acute and 2 week MTD-dosing paradigms evaluating drug pharmacokinetics in plasma, DRG and SN as well as pharmacodynamic measurements of nerve conduction and amplitude. We found plasma levels of eribulin mesylate and paclitaxel rapidly declined over 24h after infusion. In contrast, the levels of eribulin mesylate and paclitaxel persisted at above quantification levels (ranging from 5-10 ng/g) for 7 to 14 days post cessation of 2 week MTD dosing. Eribulin mesylate consistently showed greater distribution into DRG and SN over paclitaxel. When comparing the induced nerve conduction deficits, we found paclitaxel and eribulin mesylate caused reduction of nerve conduction parameters similar to our previous studies, most notably in caudal nerve amplitude (by 80.5% and 54.9% respectively). However these deficits, which were sustained for up to several weeks after cessation of dosing, were more severe with paclitaxel. The findings demonstrate that despite eribulin mesylate showing higher nervous tissue distribution than paclitaxel, eribulin mesylate caused less neurotoxicity as evidenced by milder reductions in nerve conduction and amplitude. This work was financially supported by Eisai. Citation Format: Krystyna Wozniak, Ying Wu, Bruce A. Littlefield, Kenichi Nomoto, Christopher DesJardins, Yanke Yu, George Lai, Larisa Reyderman, Barbara S. Slusher. Pharmacokinetics and pharmacodynamic analysis of eribulin mesylate and paclitaxel in mouse. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4503. doi:10.1158/1538-7445.AM2015-4503

Morphometric characteristics of caudal cranial nerves at petroclival region in fetuses.

Morphometric measurements of cranial nerves in posterior cranial fossa of fetus cadavers were carried out in an attempt to identify any asymmetry in their openings into the cranium. Twenty-two fetus cadavers (8 females, 14 males) with gestational age ranging between 22 and 38weeks (mean 30weeks) were included in this study. The calvaria were removed, the brains were lifted, and the cranial nerves were identified. The distance of each cranial nerve opening to midline and the distances between different cranial nerve openings were measured on the left and right side and compared. The mean clivus length and width were 21.2±4.4 and 13.2±1.5mm, respectively. The distance of the twelfth cranial nerve opening from midline was shorter on the right side when compared with the left side (6.6±1.1 versus 7.1±0.8mm, p=0.038). Openings of other cranial nerves did not show such asymmetry with regard to their distance from midline, and the distances between different cranial nerves were similar on the left and right side. Cranial nerves at petroclival region seem to show minimal asymmetry in fetuses.

Consecutive Lacunar Strokes Mimicking Brainstem Symptoms in a Patient With Pseudobulbar Palsy

The pseudobulbar palsy affects both corticobulbar tracts leading to symptoms of the caudal brain nerves. These bulbar symptoms often may be misinterpreted and lead to a false localization of the ischemic lesion. Here we report on a patient with an acute small lacunar ischemic lesion who presented clinically with severe affection because of an identical old contralateral lesion. The patient presented with sudden onset of dysphagia, anarthria, and glossplegia. The clinical examination was suspicious of a brainstem lesion, however, stroke magnetic resonance imaging revealed a small ischemic lacuna within the right internal capsule. However, because of an old ischemic lesion within the left internal capsule, both corticobulbar tracts were involved and this pseudobulbar palsy was mimicking bulbar brainstem symptoms. Patients who suffer from a pseudobulbar palsy usually have—compared with the rather small lesions within the central nervous system—clinically dramatic presentations and due to bulbar symptoms severe medical secondary complications and social-economic consequences to deal with.

Macroanatomical Aspects of the Lumbar Plexus and its Branches in the Sparrowhawk.

This study examined the plexus lumbalis and its branches in the sparrowhawk (Accipiter nisus). Fifteen sparrowhawks were used in this study. After administering an anaesthetic to the birds, the body cavities were opened. The birds were fixed with formaldehyde after draining of the blood. The nerves of the plexus lumbalis were dissected separately and photographed. The plexus lumbalis was formed by the union of the branches of the synsacral spinal nerves, which left from the ventrolaterale of os lumbosacrale. The plexus consisted of three (2nd, 3rd and 4th) synsacral spinal nerves. The cranial and caudal nerves originating from the plexus lumbalis were the nervus cutaneous femoris, nervus coxalis cranialis, nervus femoralis, nervus saphenus and nervus obturatorius. The general macroanatomical shape of the plexus lumbalis and the distribution of the nerves originating from this plexus were similar to those of other bird species.

Comparison of postoperative analgesic efficacy of caudal block versus dorsal penile nerve block with bupivacaine for circumcision in children

Background: Circumcision is a frequently performed surgery in pediatric patient. Objective: Our aim is to compare postoperative analgesia of caudal block versus dorsal penile nerve block (DPNB) and to compare sedation score and complication associated with caudal block and DPNB in children undergoing circumcision. Materials and Methods: This prospective randomized study was performed for more than 50 patients of ASA grade I, aged 3–12 years, scheduled for elective circumcision. Patients were divided into two groups: DPNB for group I and caudal block for group II, using 0.25% 1 mL/kg (2 mg/kg) bupivacaine. Postoperative analgesia was evaluated for 6 hours with the FLACC Pain Scale for five categories: (F) face, (L) legs, (A) activity, (C) cry, and (C) consolability. Sedation was evaluated with Ramsey sedation score. For every child, supplementary analgesic amount and times and probable local or systemic complications were recorded. Results: No significant difference between both the groups was found in mean age, body weight, and surgery duration and sedation scores. Initially, for 2 hours, FLACC pain score was also insignificant; however, on subsequent measurements, a significant difference of FLACC pain score was noted in both the groups. No major complication was found when using either technique. Conclusion: Duration of postoperative analgesia is more in caudal group than that of DPNB. Supplementary analgesic need is also minimized.

English

The origin and distribution of the brachial plexus in wild boar ( Sus scrofa) , a mammal belonging to the Suidae family were studied. Twelve specimens of wild boar, which were fixed in 10% formalin solution through different points of subcutaneous, intravenous, intramuscular, and intracavitary injections, following by immersing the specimens in the same solution were used. In present study, the brachial plexus of wild boar was a set of nerve fibers formed by the ventral branches from the fifth (C5) to eighth (C8) cervical and the first (T1) thoracic spinal nerves. The subclavian nerve was originated from C5, while the suprascapular nerve had its origin from C5 to C7. The cranial and caudal subscapular nerves were predominantly originated from C6 and C7, as well was the axillary nerve. The origin of the cranial and caudal pectoral nerves was from C7-C8 and C8-T1, respectively. The musculocutaneous nerve was mostly originated from C6 and C7, while the median and radial nerves had origin from C7 to T1. The origin of the ulnar, thoracodorsal, and lateral thoracic nerves was mostly from C8 and T1, while the long thoracic nerve was predominantly originated from C7 and C8. All nerves were responsible for the innervation of scapular girdle structures, arm, forearm, thorax and abdomen. In conclusion, the origin and distribution of the brachial plexus nerves in wild boar ( Sus scrofa ) are similar to domestic swine rather than to other wild species described in the literature.

Oxaliplatin-induced peripheral neurotoxicity: morphological characterization in different mouse strains

Oxaliplatin is one of the most effective anticancer drug, particularly employed in the treatment of colorectal cancer, but one of the major limitation in its use is peripheral neurotoxicity. Oxaliplatin induced peripheral neurotoxicity (OIPN) has a high incidence and is frequently long lasting or permanent. Neuropathy is characterized by distal sensory impairment initially in the legs, then extending to the arms. A prominent manifestation of sensitive damage is ataxia. Besides chronic neurotoxicity, many patients experience an acute, rapidly developing cold-induced sensory neuropathy, usually resolving within one week. OIPN clinical manifestations reflect the involvement of dorsal root ganglia (DRG) as primary target of the drug toxicity. Although this assumption is largely accepted and some pathogenetic hypothesis have been proposed, mechanisms at the basis of OIPN need to be clearly defined. OIPN may vary in frequency and severity among different cancer patients despite equal treatment schedules. A genetic susceptibility for more severe oxaliplatin-induced peripheral neurotoxicity (OIPN) has been suggested but never confirmed. Therefore we designed a study to assess the phenotypic differences induced by oxaliplatin treatment in six different mice strains (Balb c, AJ, C57Bl6, FVB, DBA, CD1) aiming at identifying the more and less severely affected. Animals were treated with OHP 3.5 mg/Kg/iv twice weekly x 4 weeks and evaluated before and after treatment. In all strains we performed a multimodal characterization of its neurotoxicity through morphological and morphometrical assessment in caudal nerve and DRG at light and electron microscopy, intra-epidermal nerve fibers density quantification, evaluation of mechanical and cold allodynia/hypoaesteshesia, caudal and digital nerve conduction velocity, activity of wide dynamic range (WDR) neurons of the spinal dorsal horn. Our preliminary data suggest that all the strains show signs of OIPN but not the same modifications in the parameters examined. We will show these results with particular attention to morphological data. This study suggests that genetic variability might have a role in the type and severity of OHP-induced peripheral damage.

Anatomical aspects of the nerves of the leg and foot of the giant anteater (Myrmecophaga tridactyla, Linnaeus, 1758)

Although distal stifle joint nerve distribution has been well established in domestic animals, this approach is scarcely reported in wild animals. Therefore, the aim of this study was to describe the nerves of the leg and foot of Myrmecophaga tridactyla with emphasis on their ramification, distribution, topography and territory of innervation. For this purpose, six adult cadavers fixed and preserved in 10% formalin solution were used. The nerves of the leg and foot of the M. tridactylawere the saphenous nerve (femoral nerve branch), fibular and tibial nerves and lateral sural cutaneous nerve (branches of the sciatic nerve) and caudal sural cutaneous nerve (tibial nerve branch). The saphenous nerve branches to the skin, the craniomedial surface of the leg, the medial surface of the tarsal and metatarsal regions and the dorsomedial surface of the digits I and II (100% of cases), III (50% of cases) and IV (25% of cases). The lateral sural cutaneous nerve innervates the skin of the craniolateral region of the knee and leg. The fibular nerve innervates the flexor and extensor muscles of the tarsal region of the digits and skin of the craniolateral surface of the leg and dorsolateral surface of the foot. The tibial nerve innervates the extensor muscles of the tarsal joint and flexor, adductor and abductor muscles of the digits and the skin of the plantar surface. The caudal sural cutaneous nerve innervates the skin of the caudal surface of the leg. The nerves responsible for the leg and foot innervation were the same as reported in domestic and wild animals, but with some differences, such as the more distal division of the common fibular nerve, the absence of dorsal metatarsal branches of the deep fibular nerve and a greater involvement of the saphenous nerve in the digital innervation with branches to the digits III and IV, in addition to digits I and II.

Origens e ramificações do plexo braquial no cachorro-do-mato Cerdocyon thous (Linnaeus, 1766)

Este estudo teve o objetivo de descrever a origem e ramificação dos nervos de vinte plexos braquiais de cachorro-do-mato (Cerdocyon thous). Dez animais da espécie, obtidos post mortem por atropelamento em rodovias, foram utilizados para o estudo, de acordo com a autorização do IBAMA/SISBIO nº33667-1. Depois de coletados, os cadáveres foram fixados em solução de formaldeído a 50% e conservados por pelo menos 14 dias em solução de formaldeído a 10% antes das dissecções. Após remoção da pele, incisões na musculatura peitoral e afastamento dos membros, acessou-se o espaço axilar e os nervos do plexo tiveram seu trajeto dissecados individualmente até sua inserção muscular. Para melhorar a visualização dos ramos ventrais cervicais e torácicos que originavam cada nervo, removeram-se a musculatura que encobria os forames intervertebrais, os processos transversos e os corpos vertebrais ventralmente, expondo inclusive a medula espinhal. Registros fotográficos e desenhos esquemáticos documentaram a origem e ramificação dos nervos. Os vinte plexos braquiais foram resultantes das conexões entre os ramos ventrais dos três últimos nervos espinhais cervicais (C6, C7 e C8) e do primeiro torácico (T1). Estes ramos derivaram os nervos supra-escapular, subescapular, axilar, musculocutâneo, radial, mediano, ulnar para a musculatura intrínseca e os nervos braquiocefálico, toracodorsal, torácico lateral, torácico longo, peitoral cranial e peitoral caudal para a musculatura extrínseca do membro torácico. Constatou-se que os ramos ventrais de C7 foram os que mais contribuíram na formação de nervos (61,5%), seguido de C8 (55,4%), de T1 (41,2%) e de C6 (30,8%). O teste t de comparação entre as médias, ao nível de significância de 5%, não demonstrou diferenças na origem do plexo quando comparados os antímeros e os sexos. Do total dos 260 nervos dissecados, 68,8% foram originados pela combinação de dois ou três ramos, enquanto apenas 31,2% tiveram formação por um único ramo. A combinação entre C8 e T1 foi a que mais formou nervos para o plexo (23,8%) nesta espécie. Quando comparadas a origem, ramificação e área de inervação do plexo braquial do C. thous com outras espécies domésticas e silvestres, verificou-se maior semelhança com o cão doméstico. Os resultados deste estudo podem embasar o diagnóstico de disfunções neuromusculares, as técnicas de bloqueios anestésicos e análises morfofuncionais comparativas envolvendo esta espécie.

Gluteal nerves in Crab-eating fox

Abstract Introduction: The Crab-eating fox is a medium-sized South American canid. Although there are several studies regarding this species, especially in epidemiology and parasitology studies, only few data regarding the morphology has been reported. The aim of our study was to describe the gluteal nerves of the Crab-eating fox and compare them with the domestic dogs for homology concerns and surgical application. Materials and Methods: We used four pelvic limbs of Crab-eating foxes fixed with 10% formalin and injected with red neoprene latex. Muscles, arteries and nerves were anatomically dissected. Results: The Cranial gluteal nerve supplied the Middle gluteal, Deep gluteal and Tensor Fasciae Latae muscles, while the Caudal gluteal nerve supplied the Middle Gluteal, Superficial Gluteal, Pirirformis, Gemilli and Coccygeus muscles. Conclusions: Our results presented a variable relation between muscles and nerve supplies between the Crab-eating fox and the domestic dogs. The indings also suggested morphological differentiation in lumbosacral plexus during canids species evolution. Finally, for surgical approaches to hip joint and pelvis, the domestic dog can be used as model for the Crab-eating fox.

Abstract 4653: Pharmacokinetics and biodistribution of eribulin mesylate, paclitaxel, and ixabepilone in mouse

Abstract Chemotherapy-induced peripheral neurotoxicity is a major clinical problem representing the dose-limiting side effect of many antineoplastic drugs. The degree and type of neuropathy incurred is dependent on the chemotherapeutic drug, dose intensity, and cumulative dose. In an earlier study by our group, we found that paclitaxel and ixabepilone, administered to mice at their respective MTDs, produced dose dependent deficits in caudal nerve conduction velocity, caudal amplitude and digital nerve amplitudes, as well as moderate to severe degenerative pathologic changes in dorsal root ganglia (DRG) and sciatic nerve (SN). In contrast, eribulin mesylate produced no significant deleterious effects on any nerve conduction parameter measured and caused milder, less frequent effects on morphology. Similar trends for eribulin to cause less neuropathy (including later onset and resolution) in the clinic have also been reported (Cigler and Vadhat, 2010; Jain and Cigler 2012, Vadhat et al., 2013). Differences in tubulin binding may, in part, potentially explain the differential effect (Perez et al 2009; Jordan et al 2005). Another potential explanation may reside in different pharmacokinetic (PK) and peripheral nerve distribution of these agents. To elucidate this, mice received a single dose of paclitaxel, ixabepilone or eribulin mesylate (30, 3 and 1.75mg/kg respectively, based on an MTD regimen), administered IV into the caudal vein. Plasma, DRG and SN samples were obtained at 0.25, 1, 3, 6, 8, 24, 48, and 72 h post dose. Tissues were homogenized and after extraction, concentrations of eribulin mesylate, ixabepilone and paclitaxel were determined in each matrix using LC/MS/MS. PK parameters were calculated using noncompartmental analysis in WinNonLin v 5.0.3. We report that all 3 chemotherapies rapidly penetrated both SN and DRG with maximal concentrations seen at, or within 15 mins after administration. Concentrations of all 3 agents in DRG and SN then declined by 30-50% over the first 1-3h and thereafter remained relatively stable in the tissue for up to 72 h, despite clearing rapidly from plasma to reach levels below quantification, (<5 ng/ml), by 24 h. Overall, dose normalized AUC in SN was similar for eribulin mesylate and ixabepilone and higher than for paclitaxel (1927 vs 2451 vs 793 ng/h/per g tissue, respectively). The ranking for the dose normalized AUC in DRG was eribulin mesylate < paclitaxel < ixabepilone (3894 vs 7217 vs 22800 ng/h/per g tissue, respectively). These findings suggest that peripheral nerve exposure is likely not the underlying mechanism for the differential propensity of eribulin mesylate, paclitaxel and ixabepilone to produce neurotoxicity. This work was financially supported by Eisai. Citation Format: Krystyna Wozniak, Ying Wu, Kenichi Nomoto, Bruce A. Littlefield, Christopher DesJardins, Edgar Schuck, Phil Saxton, Nancy Wong, Barbara S. Slusher. Pharmacokinetics and biodistribution of eribulin mesylate, paclitaxel, and ixabepilone in mouse. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4653. doi:10.1158/1538-7445.AM2014-4653

Electrophysiological, behavioral and histological characterization of paclitaxel, cisplatin, vincristine and bortezomib-induced neuropathy in C57Bl/6 mice.

Polyneuropathy is a frequent and potentially severe side effect of clinical tumor chemotherapy. The goal of this study was to characterize paclitaxel-, cisplatin-, vincristine- and bortezomib-induced neuropathy in C57BL/6 mice with a comparative approach. The phenotype of the animals was evaluated at four time points with behavioral and electrophysiological tests, followed by histology. Treatment protocols used in this study were well tolerated and induced a sensory and predominantly axonal polyneuropathy. Behavioral testing revealed normal motor coordination, whereas all mice receiving verum treatment developed mechanical allodynia and distinct gait alterations. Electrophysiological evaluation showed a significant decrease of the caudal sensory nerve action potential amplitude for all cytostatic agents and a moderate reduction of nerve conduction velocity for cisplatin and paclitaxel. This finding was confirmed by histological analysis of the sciatic nerve which showed predominantly axonal damage: Paclitaxel and vincristine affected mostly large myelinated fibers, bortezomib small myelinated fibers and cisplatin damaged all types of myelinated fibers to a similar degree. Neuropathic symptoms developed faster in paclitaxel and vincristine treated animals compared to cisplatin and bortezomib treatment. The animal models in this study can be used to elucidate pathomechanisms underlying chemotherapy-induced polyneuropathy and for the development of novel therapeutic and preventative strategies.

Treatment of basilar invagination.

Basilar invagination is a rare craniocervical malformation which may lead to neurological deficits related to compression of brainstem and upper cervical cord as well as instability of the craniocervical junction. This study presents results of a treatment algorithm developed over a 20-year period focussing on anatomical findings, short-term and long-term outcomes. 69 patients with basilar invagination (mean age 41 ± 18 years, history 64 ± 85 months) were encountered. The clinical courses were documented with a score system for individual neurological symptoms for short-term results after 3 and 12 months. Long-term outcomes were analyzed with Kaplan-Meier statistics. Patients with (n = 31) or without (n = 38) ventral compression were distinguished. 25 patients declined an operation, while 44 patients underwent 48 operations. Surgical management depended on the presence of ventral compression and segmentation anomalies between occiput and C3, signs of instability and presence of caudal cranial nerve dysfunctions. 16 patients without ventral compression underwent foramen magnum decompressions without fusion. 19 patients with ventral compression and abnormalities of segmentation or evidence of instability underwent a foramen magnum decompression with craniocervical (n = 18) or C1/2 (n = 1) stabilization. In nine patients with severe ventral compression and caudal cranial nerve deficits, a transoral resection of the odontoid was combined with a posterior decompression and fusion. Within the first postoperative year neurological scores improved for all symptoms in each patient group. In the long-term, postoperative deteriorations were related exclusively to instabilities either becoming manifest after a foramen magnum decompression in three or as a result of hardware failures in two patients. The great majority of patients with basilar invagination report postoperative improvements with this management algorithm. Most patients without ventral compression can be managed by foramen magnum decompression alone. The majority of patients with ventral compression can be treated by posterior decompression, realignment and stabilization alone, reserving anterior decompressions for patients with profound, symptomatic brainstem compression.

Microvascular decompression in patients with coexistent trigeminal neuralgia, hemifacial spasm and glossopharyngeal neuralgia

Trigeminal neuralgia(TN), hemifacial spasm (HFS) and glossopharyngeal neuralgia (GPN) were referred to hyperactive dysfunction syndromes (HDSs) of the cranial nerves. These symptoms may occur synchronously or metachronously, but the combination of three diseases is extremely rare. From 2007 through 2013, six patients with coexistent GPN-HFS-TN were treated in our department. The combined symptoms occurred on the same side in three and on both sides in three. These patients underwent nine microvascular decompression (MVD) procedures in total. The clinical data including operative findings were respectively analyzed, and the etiological factors as well as treatment strategies were discussed. Intraoperatively, in all the cases a small posterior fossa was found, which was crowded with cranial nerve roots and cerbellar vesels. Postoperatively, spasm was stopped immediately in four and within 3 months in two; the symptom of TN disappeared immediately in four and within 2 weeks in two; the symptom of GPN was relieved immediately in four and improved with medication in two. During the up to 77 months' follow-up, no changes, recurrence or any dysfunctions of cranial nerves were observed in any of the patients. The combination of HFS-TN-GPN is extremely rare and is often associated with a looped VBA and a smaller posterior fossa. However, MVD is still a good choice for treatment. To achieve a safe and effective outcome, dissection of the caudal cranial nerves and proximal transposition of the vertebral artery before decompression of the affected nerve roots are strongly recommended.

Cranial Neuropathy Due to Intradural Disc Herniation

Herniated intervertebral disc fragments rarely penetrate the thecal sac, and intracranial hypotension attributable to such penetrating fragments is even more unusual. We describe the first reported case of a cranial neuropathy due to intradural herniation of a disc fragment, in which intracranial hypotension from a resulting cerebrospinal fluid leak caused bilateral abducens palsies. A 45-year-old man presented with a positional headache after having experienced a "popping" sensation in his back while lifting a heavy object. He also reported blurred vision and was noted to have lateral gaze palsies bilaterally. Magnetic resonance imaging (MRI) of the brain revealed bilateral subdural collections, abnormal pachymeningeal enhancement, and cerebellar tonsillar herniation, suggesting intracranial hypotension. T2-weighted MRI of the spine revealed extrusion of the T12-L1 disc and suggested the presence of a disc fragment in the intradural space, displacing the caudal nerve roots. A myelogram demonstrated a filling defect extending into the subarachnoid space adjacent to the disc herniation, consistent with a free disc fragment in the intradural space. A diagnosis of intracranial hypotension due to a cerebrospinal fluid leak resulting from an intradural herniated disc was made. The diagnosis was confirmed intraoperatively. Surgical removal of the herniated disc fragment and repair of the dural defect resulted in complete resolution of the cranial neuropathy. This rare etiology of a cranial neuropathy, arising from pathology in the thoracolumbar spine, illustrates the clinical teaching that the sixth cranial nerve is highly sensitive to deformation induced by intracranial hypotension.

Anatomical and #1615;tudy of Pig Biceps Femoris Muscle Applied to Sampling for Assessment of Meat Quality.

The relationship between muscle characteristics and meat quality remains controversial, likely because the existence of neuromuscular compartments (NMCs) is often overlooked. The aim was to determine in the NMCs the fibre types and its percentages, absolute areas (AA) and relative areas (RA) to quantify the heterogeneity of the muscle. The left biceps femoris (BF) muscles were removed from the carcasses of ten pigs of commercial breeds, preserving the primary branches of the caudal gluteal and sciatic nerves for identifying the NMCs. Muscle samples were obtained from the centre of the NMCs to identify the fibre types. Myosin heavy chains were determined by myofibrillar adenosine triphosphatase (mATPase) reaction and by using monoclonal antibodies. The pig biceps femoris muscle contains four NMCs grouped by RA values in oxidative (BR3-BR4) and glycolytic (BR1, BR2) compartments. The RAs of these NMCs varied significantly for fibre types I and IIB (p≤0.05). The RA accurately typifies NMCs, and the relationship between their values enables efficient study of compartmentalisation by studying only capillaries after the primary branches of the nerve were identified. Our results highlight the complexity of muscle structure and the importance of its consideration when assessing muscle, sampling and muscle processing for meat production.

Assessment of Paclitaxel Induced Sensory Polyneuropathy with “Catwalk” Automated Gait Analysis in Mice

Neuropathic pain as a symptom of sensory nerve damage is a frequent side effect of chemotherapy. The most common behavioral observation in animal models of chemotherapy induced polyneuropathy is the development of mechanical allodynia, which is quantified with von Frey filaments. The data from one study, however, cannot be easily compared with other studies owing to influences of environmental factors, inter-rater variability and differences in test paradigms. To overcome these limitations, automated quantitative gait analysis was proposed as an alternative, but its usefulness for assessing animals suffering from polyneuropathy has remained unclear. In the present study, we used a novel mouse model of paclitaxel induced polyneuropathy to compare results from electrophysiology and the von Frey method to gait alterations measured with the Catwalk test. To mimic recently improved clinical treatment strategies of gynecological malignancies, we established a mouse model of dose-dense paclitaxel therapy on the common C57Bl/6 background. In this model paclitaxel treated animals developed mechanical allodynia as well as reduced caudal sensory nerve action potential amplitudes indicative of a sensory polyneuropathy. Gait analysis with the Catwalk method detected distinct alterations of gait parameters in animals suffering from sensory neuropathy, revealing a minimized contact of the hind paws with the floor. Treatment of mechanical allodynia with gabapentin improved altered dynamic gait parameters. This study establishes a novel mouse model for investigating the side effects of dose-dense paclitaxel therapy and underlines the usefulness of automated gait analysis as an additional easy-to-use objective test for evaluating painful sensory polyneuropathy.

Aminergic toxins: What they are, what they do and what we can do with

Aminergic toxins: What they are, what they do and what we can do with