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The classic view of the vertebrate dorsal root ganglion is that it arises from trunk neural crest cells that migrate to positions lateral to the spinal cord, sending axons dorsally into the spinal cord and dendrites ventrally to meet with motor axons in the ventral root to form spinal nerves. As a result, the ganglion ends up lying in the dorsal root of the spinal nerve. Serial histological sections of parts of the trunk of juveniles of different snake species revealed that the ganglia lie distal to the junction of dorsal and ventral roots of spinal nerves and outside the neural canal. The anatomical position of spinal ganglia in snakes suggests that regulation of trunk neural crest migration in snakes differs from that in the model endotherms in which it has been most thoroughly explored. Dorsal roots have no distinct rootlets and the span of root entry to the spinal cord is short compared to that of ventral rootlets in the same segment. Comparing early developmental stages to juvenile spinal cords shows an increased separation of spinal nerve root sites and ventral migration of the ganglion in later development. Dorsal rami of the spinal nerves leave directly from the dorsal edge of the ganglion, and the ventral ramus leaves from the ventral tip of the ganglion. How these features relate to the developmental regulation of ganglion form and position and the extraordinary locomotor capabilities of the snake trunk are unclear.

BACKGROUND Axo-axonic contacts onto central terminals of primary afferents modulate sensory inputs to the spinal cord. These contacts produce primary afferent depolarization (PAD), which serves as a mechanism for presynaptic inhibition, and also produce dorsal root reflexes (DRRs), which may regulate the excitability of peripheral terminals and second order neurons. We aimed to identify changes in these responses as a consequence of peripheral inflammation. METHODS In vitro spinal cord recordings of spontaneous activities in dorsal and ventral roots were performed in control mice and following paw inflammation. We also used pharmacological assays to define the neurotransmitter systems implicated in such responses. RESULTS Paw inflammation increased the frequency and amplitude of spontaneous dorsal root depolarizations, the occurrence of DRRs and the amplitude of ventral roots depolarizations. PAD was classified in two different patterns based on their relation to ventral activity: time-locked and independent events. Both patterns increased in amplitude after paw inflammation, and independent events also increased in frequency. The circuits that were responsible for this activity implicated both glutamatergic and GABAergic transmission. Adrenergic modulation differentially affected both types of PAD, and this modulation changed after paw inflammation. CONCLUSIONS Our findings suggest the existence of independent spinal circuits at the origin of PAD and DRRs. Inflammation modulates these circuits differentially, unveiling varied mechanisms of spinal sensitization. This in vitro approach provides an isolated model for the study of the mechanisms of central sensitization and for the performance of pharmacological assays with the purpose of identifying and testing novel antinociceptive targets. SIGNIFICANCE Spinal circuits modulate activity of primary afferents acting on central terminals. Under in vitro conditions, dorsal roots show spontaneous activity in the form of depolarizations and action potentials. Our findings are consistent with the existence of several independent generator circuits. Experimental paw inflammation reduced mechanical withdrawal threshold and significantly increased the spontaneous activity of dorsal roots, which may be secondary to an enhanced output of spinal generators. This can be considered as a novel sign of central sensitization.

To analyze the increase in diameter of the nerve roots C5 and C6 in early childhood.The nerve roots of 56 children aged 0 days to 10 years (47 younger than 2 years) were examined by high-resolution ultrasound imaging. The correlation of diameter and age was statistically tested and a logarithmic regression analysis was performed to develop a logarithmic growth model.The increase in nerve root diameter is greatest during the first 2 years of life and then the growth rate decreases steadily. The relationship between age and diameter follows a logarithmic curve (p 10The main increase in the diameter of the nerve roots happens in the first 2 years of life. Comparing data from a previous study, our data also suggest that the maturation of the proximal part of the median nerve is comparable to the maturation of its distal segments. This suggests a synchronous maturation of the axons and myelin sheath for the whole extent of the nerve, from the radix to its very distal part.Normative values for the size of the cervical nerve roots C5 and C6; an insight into the maturation of the proximal parts of the peripheral nervous system; and the correlation between age and cervical root diameter.

Introduction Chronic immune polyradiculopathies (sensory, motor, and mixed) are uncommon. Methods In this single-center, retrospective study, the inclusion criteria for participants were progressive sensory ataxia and/or areflexic limb weakness; tibial somatosensory evoked potential (SSEP) abnormalities of the N22 and P40 potentials with normal sensory and motor nerve conduction studies or root involvement, according to magnetic resonance imaging (MRI); and albuminocytological dissociation. Results Eight patients were included in our study. Two had weakness, two had sensory ataxia, and four had both weakness and ataxia. Patients with weakness had abnormal SSEPs and patients with sensory ataxia also had absent F waves. Electromyography showed chronic denervation. MRI scans confirmed thickening and enhancement of roots. The patients responded to corticosteroid treatment. Discussion The overlapping clinicoelectrophysiological findings and similarities in radiological and therapeutic responses suggest that these entities are clinical variants of the same disease. The terms CIS(m)P, CI(s)MP, and CISMP (for chronic immune sensory motor polyradiculopathy) could be used to denote the predominant clinical involvement.

Persons with back, neck, and limb symptoms constitute a major referral population to specialists in electrodiagnostic (EDX) medicine. The evaluation of these patients involves consideration of both the common and less common disorders. The EDX examination with needle electromyography (EMG) is the most important means of testing for radiculopathy. This test has modest sensitivity but high specificity and well complements imaging of the spine. Needle EMG in combination with nerve conduction testing is valuable in excluding entrapment neuropathies and polyneuropathy-conditions that frequently mimic radicular symptoms. In this first of a two-part review, the optimal EDX evaluation of persons with suspected radiculopathy is presented. In part two, the implications of EDX findings for diagnosis and clinical management of persons with radiculopathy are reviewed.

Background Cervical selective nerve root blocks (C-SNRBs) maintain utility for presurgical planning in patients with cervical radiculopathy. Traditional fluoroscopic or stationary computed tomography (CT)-guided methods have been associated with complications, including catastrophic neurologic insults, while ultrasound guidance has been investigated based on its theoretical advantages. Maximizing patient safety by obtaining superior anatomic and procedural details promotes the exploration for better alternative guidance. Methods We describe a novel approach of posterolateral (PL) extraforaminal (EF) C4 SNRB using cone beam-based CT (CBCT)/fluoroscopy, which was performed on 3 separate occasions for 1 patient with suspected right C4 radiculopathy for presurgical evaluation. CBCT/fluoroscopy uniquely provides the function of both CT and fluoroscopy using a C-arm machine. It allows precise 3-dimensional needle planning and sophisticated 2-dimensional needle guidance, while ensuring tight needle control and detailed monitoring of contrast spread. Results A successful right C4 SNRB was repeatedly achieved, as evidenced by postprocedural paresthesias over the C4 dermatomal distribution and periradicular contrast spread. Additionally, the patient reported symptomatic relief (with regard to pain scores and neck range of motion), leading to cancelation of his surgical plan. Conclusion We propose the PL-EF approach as the safest protocol for C-SNRBs. When compared with fluoroscopy or CT, CBCT/fluoroscopy is an advanced imaging system that provides superior anatomic neurovascular detail, while offering precise needle control, contrast media monitoring, and easy operation in an office setting. These advanced features support it as the ideal guidance method for maximizing both the safety and efficiency of the PL-EF C-SNRB approach. However, the claimed advantages cannot be concluded without increasing its accessibility to pain specialists and conducting a prospective study with a large sample size.

Aim To determine the effect of the lumbosacral ventral root avulsion (VRA) on the reflex activation of bladder, urethra, and activation of perineal muscles during micturition in female rabbits. Methods We allocated 14 virgin female rabbits to evaluate, first, the gross anatomy of lumbosacral spinal cord root (n = 5) and, second, to determine the effect of VRA on perineal muscles during micturition (n = 9). We recorded cystometrograms, urethral pressure, and electromyograms of the bulbospongiosus (Bsm) and ischiocavernosus (Ism) muscles before and after the L6-S2 VRA. Standard variables were measured from each recording and analyzed to identify significant differences (P Results We found that the L6-S2 VRA affected directly the bladder and urethral function and reduced the duration and the frequency of the bursting of Ism and Bsm muscles during voiding. The Ism and Bsm showed a phasic activation, of different frequencies, during the voiding phase and the L6-S2 VRA inhibited the co-contraction of the Ism and Bsm-bladder-urethra. Conclusions The Ism and Bsm are activated at different frequencies to trigger the voiding phase. The L6-S2 VRA affected the activity pattern of both perineal muscles. These modifications affected the bladder and urethra function. It is possible that the restoration of the activation frequency of perineal muscles contributed for an efficient bladder contraction.

Background Lumbar adhesive arachnoiditis is a debilitating neuropathic condition and is difficult to diagnose owing to lack of definitive diagnostic criteria. By focusing on the intrathecal mobility of nerve roots, we assessed whether useful diagnostic criteria could be established using MRI. Methods Seventeen patients with a high risk for lumbar adhesive arachnoiditis and 18 no-risk patients with chronic low back pain and/or leg pain participated in this study. The patients underwent MRI in both the supine and prone positions. Eleven axial T2-weighted images between the L2 and L5/S levels were obtained, and the proportion of the low-intensity area in the dorsal half to the total low-intensity area in the dural sac was calculated for each axial view. Results At some lumbar levels, the low-intensity area in the dorsal half of the dural sac was relatively larger in patients with a high risk for lumbar adhesive arachnoiditis than in the no-risk patients. In the no-risk group, the proportion of the low-intensity area in the dorsal half in the supine position was significantly higher than that in the prone position at all lumbar levels. However, in the high-risk group, at some levels, the proportions were not significantly different in the dorsal half of the dural sac between the supine and prone positions. Conclusion In patients with a known risk for lumbar adhesive arachnoiditis, nerve roots lose their potential to migrate in the dural sac in the gravitational force direction on MRI.

Muscle & nerve 60(6), 679-686 (2019). doi:10.1002/mus.26717, Published by Wiley, New York, NY [u.a.]

We report evidence that ephaptic interactions may occur between intact mammalian myelinated nerve fibres and not only between demyelinated or damaged mammalian nerve fibres or nerve cells as analysed in previous studies. The ephaptic interactions were investigated between nerve fibres traversing the lumbar dorsal roots and between bundles of fibres in the sciatic nerve in anaesthetized rats in vivo. The interactions were estimated by comparing the excitability of nerve fibres originating from one of the hindlimb nerves (peroneal or sural) under control conditions and when the stimulation of these fibres was combined with stimulation of another nerve (tibial). An increase in nerve volleys recorded from group I muscle afferents in the peroneal nerve and of the fastest skin afferents in the sural nerve was used as a measure of the increase in the excitability. The excitability of these fibres was increased during a fraction of a millisecond, coinciding with the period of passage of nerve impulses evoked by the conditioning stimulation of the tibial nerve. The degree of the increase was comparable to the increases in the excitability evoked by 1-2 min lasting fibre polarization. Ephaptic interactions were found to be more potent and with longer lasting after-effects within the dorsal roots than within the sciatic nerve. We postulate that ephaptic interactions may result in the synchronization of information forwarded via neighbouring afferent nerve fibres prior to their entry into the spinal cord and thereby securing the propagation of nerve impulses across branching points within the spinal grey matter.

There seems to be no complete demonstration of the suboccipital fascial configuration. In 30 human fetuses near term, we found two types of candidate myodural bridge: (1) a thick connective tissue band running between the rectus capitis posterior major and minor muscles (rectus capitis posterior major [Rma], rectus capitis posterior minori [Rmi]; Type 1 bridge; 27 fetuses); and (2) a thin fascia extending from the upper margin of the Rmi (Type 2 bridge; 20 fetuses). Neither of these bridge candidates contained elastic fibers. The Type 1 bridge originated from: (1) fatty tissue located beneath the semispinalis capitis (four fetuses); (2) a fascia covering the multifidus (nine); (3) a fascia bordering between the Rma and Rmi or lining the Rma (13); (4) a fascia covering the inferior aspect of the Rmi (three); and (5) a common fascia covering the Rma and obliquus capitis inferior muscle (nine). Multiple origins usually coexisted in the 27 fetuses. In the minor Type 2 bridge, composite fibers were aligned in the same direction as striated muscle fibers. Thus, force transmission via the thin fascia seemed to be effective along a straight line. However, in the major Type 1 bridges, striated muscle fibers almost always did not insert into or originate from the covering fascia. Moreover, at and near the dural attachment, most composite fibers of Type 1 bridges were interrupted by subdural veins and dispersed around the veins. In newborns, force transmission via myodural bridges was likely to be limited or ineffective. The postnatal growth might determine a likely connection between the bridge and headache. Clin. Anat. 32:914-928, 2019. © 2019 Wiley Periodicals, Inc.

The cause of cervical spondylotic radiculopathy could be related to the intraforaminal ligaments (IFLs) of the cervical spine. The aim of this study is to identify and describe the IFLs and assess their clinical significance. Six intact cervical spine specimens from adult embalmed cadavers were dissected to expose the cervical nerve roots and their surrounding intraforaminal tissues fully. From the C1-C2 to the C7-T1 intervertebral foramina (IVF), the connective structures between each nerve root and its surrounding foraminal wall were examined under a surgical microscope. The morphology, number, and attachment points of the IFLs of each segment were documented, and the length, width, or diameter and thickness of the ligaments were measured with a vernier caliper. IFLs were observed in all 84 IVFs of the cervical spine. According to their locations, they can be divided into two categories: the first is entrance-zone IFLs, which are radially distributed around the nerve root; the second is mid-zone IFLs, which are thin, strip-shaped fibrous tissues intertwined around the nerve roots, the number of ligaments being considerable but difficult to quantify. Ligament structures have been identified in the IVF of the cervical spine. Under physiological conditions, they could be protective in maintaining the position, shape, and function of nerve roots. However, under pathological conditions, the IFLs of the cervical spine could aggravate the symptoms of cervical nerve root radicular pain associated with other types of compression. Clin. Anat. 32:654-660, 2019. © 2019 Wiley Periodicals, Inc.

Introduction Computed tomography-guided cervical nerve root corticosteroid injections are a commonly performed procedure for cervical radiculopathy. There have been major complications such as spinal cord infarction and posterior circulation stroke reported mostly with X-ray fluoroscopic-guided methods, however, there is relatively little data on the safety of newer CT-guided methods. The purpose of this study was to identify any major complications and evaluate the rate of minor complications from CT-guided cervical nerve root corticosteroid injections performed in a tertiary public hospital. Methods Four hundred and three CT-guided cervical nerve root injection procedures were identified over a period from July 2015 to January 2018 using the radiology information system (RIS) and data collected about the technique and any immediate complications. Patient follow-up and delayed complications were then reviewed, either via outpatient clinic records or telephone consultation. Results Two hundred and eighty-six procedures were performed by radiology registrars or fellows, and 117 by radiologists, most commonly via an anterolateral approach and injecting 4 mg (in 1 mL) of dexamethasone. Follow-up data were obtained for all 403 procedures and identified 16 minor complications, but no major neurovascular complications. Conclusion The overall recorded rate of minor complications with CT-guided nerve root injection was 4.0% with no major neurovascular complications, suggesting that CT-guided transforaminal cervical corticosteroid injection is a safe procedure.

Introduction Chronic immune sensorimotor polyradiculopathy (CISMP) is a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) variant affecting both sensory and motor nerve roots without evidence of peripheral nerve demyelination. Methods We report a case series of 9 patients with CISMP, identified from 2 tertiary centers. Clinical, electrodiagnostic, and neuroradiologic features, and treatment responses, were retrospectively reviewed. Results Patients presented with sensorimotor deficits and hypo-/areflexia, predominantly involving lower extremities. Three had cranial nerve involvement. Electrodiagnostic findings in all patients localized to roots proximal to dorsal root ganglia, without evidence of peripheral nerve demyelination. Cerebrospinal fluid examination revealed an albuminocytologic association. Eight patients exhibited gadolinium enhancement and thickening of multiple spinal nerve roots and/or cranial nerves. All patients demonstrated good responses to immunotherapies. Discussion CISMP is similar to CIDP in many aspects, but lacks typical electrodiagnostic findings of peripheral nerve demyelination. It is important to recognize this unusual and treatable entity. Muscle Nerve 59:658-664, 2019.

Astrogliosis and microglial reactions are correlated with the formation of scar tissue and synapse loss. 4-hydroxy-tempo (TEMPOL) is a reactive oxygen species scavenger with proven neuroprotective efficacy in experimental models of traumatic injury and cerebral ischemia. TEMPOL has not, however, been applied following ventral root lesions, which are particularly correlated with the degeneration of spinal motoneurons following brachial plexus injuries. Thus, the present study investigated the effects of TEMPOL on motoneurons and adjacent glial reactions, with a particular focus on the preservation of excitatory and inhibitory spinal circuits. Adult female Sprague Dawley rats were subjected to ventral root crush (VRC) at the lumbar intumescence. Animals were divided into the following experimental groups: (a) VRC-saline treatment; (b) VRC-TEMPOL treatment (12 mg/kg, n = 5), and (c) VRC-TEMPOL treatment (250 mg/kg, n = 5). The spinal cord tissue located contralateral to the lesion was used as the control. Fourteen days after lesioning, the rats were euthanized and the spinal cords were removed for motoneuron counting and immunolabeling with glial (GFAP and Iba-1) and synapse markers (synaptophysin, VGLUT-1, and GAD65). Although TEMPOL did not exert neuroprotective effects at the studied concentrations, the modulation of glial reactions was significant at higher doses. Thus, synaptophysin staining was preserved and, in particular, VGLUT-1-positive inputs were maintained, thereby indicating that TEMPOL preserved proprioceptive glutamatergic inputs without exacerbating the rate of motoneuron degeneration. Consequently, its administration with other efficient neuroprotective substances may significantly improve the outcomes following spinal cord lesioning.

The corticospinal tract (CST) forms the major descending pathway mediating voluntary hand movements in primates, and originates from ∼nine cortical subdivisions in the macaque. While the terminals of spared motor CST axons are known to sprout locally within the cord in response to spinal injury, little is known about the response of the other CST subcomponents. We previously reported that following a cervical dorsal root lesion (DRL), the primary somatosensory (S1) CST terminal projection retracts to 60% of its original terminal domain, while the primary motor (M1) projection remains robust (Darian-Smith et al., J. Neurosci., 2013). In contrast, when a dorsal column lesion (DCL) is added to the DRL, the S1 CST, in addition to the M1 CST, extends its terminal projections bilaterally and caudally, well beyond normal range (Darian-Smith et al., J. Neurosci., 2014). Are these dramatic responses linked entirely to the inclusion of a CNS injury (i.e., DCL), or do the two components summate or interact? We addressed this directly, by comparing data from monkeys that received a unilateral DCL alone, with those that received either a DRL or a combined DRL/DCL. Approximately 4 months post-lesion, the S1 hand region was mapped electrophysiologically, and anterograde tracers were injected bilaterally into the region deprived of normal input, to assess spinal terminal labeling. Using multifactorial analyses, we show that following a DCL alone (i.e., cuneate fasciculus lesion), the S1 and M1 CSTs also sprout significantly and bilaterally beyond normal range, with a termination pattern suggesting some interaction between the peripheral and central lesions.

Previous work from our laboratory showed that motor nerve injury by lumbar 5 ventral root transection (L5-VRT) led to interleukin-6 (IL-6) over-expression in bilateral spinal cord, and that intrathecal administration of IL-6 neutralizing antibody delayed the induction of mechanical allodynia in bilateral hind paws. However, early events and upstream mechanisms underlying spinal IL-6 expression following L5-VRT require elucidation. The model of L5-VRT was used to induce neuropathic pain, which was assessed with von Frey hairs and the plantar tester in adult male Sprague-Dawley rats. Calpain-2 (CALP2, a calcium-dependent protease) knockdown or over-expression and microglia depletion were conducted intrathecally. Western blots and immunohistochemistry were performed to explore the possible mechanisms. Here, we provide the first evidence that both IL-6 and CALP2 levels are increased in lumbar spinal cord within 30 min following L5-VRT. IL-6 and CALP2 co-localized in both spinal dorsal horn (SDH) and spinal ventral horn. Post-operative (PO) increase in CALP2 in ipsilateral SDH was evident at 10 min PO, preceding increased IL-6 at 20 min PO. Knockdown of spinal CALP2 by intrathecal CALP2-shRNA administration prevented VRT-induced IL-6 overproduction in ipsilateral spinal cord and alleviated bilateral mechanical allodynia. Spinal microglia activation also played a role in early IL-6 up-regulation. Macrophage/microglia markers ED1/Iba1 were increased at 30 min PO, while glial fibrillary acidic protein (astrocyte) and CNPase (oligodendrocyte) markers were not. Increased Iba1 was detected as early as 20 min PO and peaked at 3 days. Morphology changed from a small soma with fine processes in resting cells to an activated ameboid shape. Depletion of microglia using Mac-1-saporin partially prevented IL-6 up-regulation and attenuated VRT-induced bilateral mechanical allodynia. Taken together, our findings provide evidence that increased spinal cord CALP2 and microglia cell activation may have early causative roles in IL-6 over-expression following motor nerve injury. Agents that inhibit CALP2 and/or microglia activation may therefore prove valuable for treating neuropathic pain.

Aims Lumbar to sacral rerouting surgery can potentially allow voiding via a skin-central nervous system-bladder reflex pathway. Here, we assessed if this surgery was effective in treating neurogenic bladder dysfunction/sphincter in felines. Methods Eight cats underwent spinal cord transection (SCT) at thoracic level 10/11. Unilateral L7 to S1 ventral root anastomosis was performed 1 month later in six cats. Two cats served as transection-only controls. Electrical and manual stimulation of L6-S1 dermatomes, and urodynamics were performed at 3, 5, 7, and 9/10 months post transection. At 9/10 months, cats were also evaluated by direct electrophysiological testing of anastomosed roots with urodynamics, then tissue collection and examination of the root anastomosis site and lumbosacral cord ventral horns for cells retrogradely labeled from tracer dye injected 2 weeks earlier into the bladder wall. Results At 9/10 months, four of six rerouted cats exhibited increased detrusor pressure provoked by cutaneous stimulation, one cat bilaterally. Two cats presented with a voiding stream after ipsilateral cutaneous stimulation at 7 and 9 months. All six rerouted animals showed regrowth of axons from the L7 ventral horn to the bladder, although some aberrant axonal regrowth was also observed. Conclusion L7 to S1 ventral root rerouting below the level of SCT showed successful axonal regrowth to the bladder from the L7 spinal cord segment in all rerouted animals, and induced increased detrusor pressure response to cutaneous stimulation in a subset. This feasibility study paves the way for future animal studies for bladder reinnervation.

Introduction Age-associated muscle strength decline is a major contributing factor to increased late-life functional decline and comorbidity, and is strongly associated with early mortality. Although all parts of the neuromuscular system seem to be affected by aging, dying-back of motor axons likely plays a major role. Methods We compared the degeneration in ventral roots and neuromuscular junction denervation in young and aged mice and correlated the findings with strength and electrophysiological measures. Results With normal aging, there is little decline in motor axon numbers in the ventral roots, but the neuromuscular junctions show marked partial denervation that is associated with increased jitter on stimulated single fiber electromyography and a decrease in muscle strength. Conclusions These findings suggest that dying-back axonal degeneration may be partially responsible for the electrophysiological and strength changes observed with aging. Muscle Nerve 55: 894–901, 2017

BACKGROUND The rat has served usefully as a model for fecal incontinence and exploration of the mechanism of action of sacral neuromodulation. However, there is a gap in knowledge concerning representation(s) on the primary sensory cortex of this anatomical region. METHODS Multi-electrode array (32 channels) and intrinsic optical signal (IOS) processing were used to map cortical activation sites following anorectal electrical stimulation in the rat. A simple method for expanding a 32-electrode array to a virtual 2700 array was refined. KEY RESULTS The IOS method identified activation of parietal cortex following anorectal or first sacral nerve root (S1) stimulation; however, the signal was poorly localized and large spontaneous vasomotion was observed in pial vessels. In contrast, the resulting high-density maps showed two anatomically distinct cortical activation sites to anorectal stimulation. CONCLUSIONS & INFERENCES There are two distinct sites of activation on the parietal cortex following anorectal stimulation in the rat. The implications for sacral neuromodulation as a therapy for fecal incontinence are discussed.

AIMS To investigate the long-term course of the detrusor pressure during sacral anterior root stimulation in spinal cord injury (SCI) patients. METHODS Retrospective evaluation of 111 patients who had undergone sacral deafferentation and implantation of an anterior root stimulator at a single SCI rehabilitation center with a minimum follow-up time of 5 years. RESULTS The median follow-up time was 11.7 years (range 5.0-24.9 years). The maximum detrusor pressure (Pdet_max) during stimulation was higher in men compared to women (P = 0.0004) and decreased over time (P = 0.0006). However, there were no significant (P ≥ 0.06) differences in the median Pdet_max during stimulation between the first measurement time point and any follow-up time point. The Pdet_max during stimulation decreased from 62 cmH2O (95%CI 57-73 cmH2O) to 53 cmH2O (95%CI 47-69 cmH2O) (P = 0.9). The time had also a significant effect on Pdet_max during the storage phase (P

AIMS To determine the spinal segmental afferent contributions to tibial and pudendal inhibition of bladder overactivity. METHODS Intravesical infusion of 0.5% acetic acid was used to irritate the bladder and induce bladder overactivity in anesthetized cats. Tibial or pudendal nerve stimulation was used to suppress the bladder overactivity and increase bladder capacity during cystometry. L5-S3 dorsal roots ipsilateral to the stimulation were exposed by a laminectomy and transected sequentially during the experiments to determine the role of individual dorsal roots in tibial or pudendal neuromodulation. RESULTS Transection of L5 dorsal root had no effect. Transection of L6 dorsal root in four cats produced an average 18% reduction in tibial inhibition, which is not a significant change when averaged in the group of 10 cats. Transection of L7 dorsal root completely removed the tibial inhibition without changing reflex bladder activity or pudendal inhibition. Transection of S1 dorsal root reduced the pudendal inhibition, after which transection of S2 dorsal root completely removed the pudendal inhibition. Transection of S3 dorsal root had no effect. The control bladder capacity was increased only by transection of S2 dorsal root. CONCLUSIONS This study in cats revealed that tibial and pudendal neuromodulation of reflex bladder overactivity depends on activation of primary afferent pathways that project into different spinal segments. This difference may be related to the recent observation in cats that the two types of neuromodulation have different mechanisms of action.

Aims To investigate the effects of electrical stimulation of sacral dorsal/ventral roots on irritation-induced bladder overactivity, reveal possible different mechanisms under nociceptive bladder conditions, and establish a large animal model of sacral neuromodulation. Methods Intravesical infusion of 0.5% acetic acid (AA) was used to irritate the bladder and induce bladder overactivity in cats under α-chloralose anesthesia. Electrical stimulation (5, 15, or 30 Hz) was applied to individual S1–S3 dorsal or ventral roots at or below motor threshold intensity. Repeated cystometrograms (CMGs) were performed with/without the stimulation to determine the inhibition of bladder overactivity. Results AA irritation induced bladder overactivity and significantly (P

In classic anatomic atlases, the spinal cord is standardly represented in its anatomical form with symmetrically emerging anterior and posterior roots, which at the level of the intervertebral foramen combine into the spinal nerves. The parts of the cord delimited by the boundaries of the roots are called segments or myelomeres. Associated with their regular repetitive appearance is the notion that the cord is segmentally organized. This segmental view is reinforced by clinical practice. Spinal cord roots innervate specific body parts. The level of cord trauma is diagnosed by the de-innervation symptoms of these parts. However, systemically, the case for a segmentally organized cord is not so clear. To date, developmental and genetic research points to a regionally rather than a segmentally organized cord. In the present study, to what degree the fila radicularia are segmentally implanted along the cord was investigated. The research hypothesis was that if the fila radicularia were non-segmentally implanted at the cord surface, it would be unlikely that the internal neuron stratum would be segmented. The visual segmented aspect of the myelomeres would then be the consequence of the necessary bundling of axons towards the vertebral foramen as the only exits of the vertebral canal, rather than of an underlying segment organization of the cord itself. To investigate the research hypothesis, the fila radicularia in the cervical-upper thoracic part of five spinal cords were detached from their spinal nerves and dissected in detail. The principal research question was if the fila radicularia are separated from their spinal nerves and dissected from their connective tissues up to the cord, would it be possible to reconstruct the original spinal segments from the morphology and interspaces of the fila? The dissections revealed that the anterior fila radicularia emerge from the cord at regular regionally modulated interspaces without systematic segmental delineations. The posterior fila radicularia are somewhat more segmentally implanted, but the pattern is individually inconsistent. The posterior and anterior roots have notable morphological differences, and hypotheses are presented to help explain these. The macroscopic observations are consistent with a regionally but not a segmentally organized cord. This conclusion was visually summarized in photographs of spinal cords with ipsilateral intact roots and contralateral individually dissected fila radicularia. It was suggested that this dual view of the spinal cord be added to the standard anatomic textbooks to counterbalance the current possibly biased view of a segmented cord.

Objectives We aimed to estimate the spread of injections for ultrasound-guided cervical nerve root blocks and to determine the optimal injectate volume required in this procedure. Methods A total of 32 ultrasound-guided injections (C5–C8) were made in 4 fresh cadavers. The target on each cervical root was the space between the posterior tubercle and the cervical root at the most proximal location possible on the sonogram. After ultrasound-guided needle insertion, 0.5 mL of a contrast medium was injected 4 times. The dye flow patterns were confirmed with fluoroscopy each time, and we recorded whether the contrast medium reached the dorsal root ganglion level or the epidural space. After the injections, the needle tip location was determined by computed tomography and image reconstruction. Results All injections produced typical neurograms. The contrast medium reached the dorsal root ganglion in 29 of 32 (90.6%) injections (mean ± SD, 0.84 ± 0.42 mL of contrast medium) and the epidural space in 10 of 32 (31.3%) injections (1.30 ± 0.54 mL of contrast medium). The mean distance between the needle tip and neural foramen was 9.64 ± 3.68 mm, and this distance correlated positively with the volume of contrast medium necessary to reach the dorsal root ganglion or the epidural space. Conclusions Ultrasound-guided cervical nerve root blocks show potential utility for targeting an anesthetic into the cervical root area. This study may be helpful for deciding the most appropriate volume for the procedure.

A diagnosis of child abuse is dependent on a comprehensive and accurate assessment of injury in the context of a thorough investigation. However, signatures of trauma are often subtle and interpretation can be very difficult. Recently, researchers have refocused their attention from the head to the neck in search of traumatic signatures of abusive head trauma. HCIFS has developed a technique to remove the cervical spinal cord with the ganglia attached that is less destructive and more time and cost efficient than alternative methods previously published. Once removed, the dorsal nerve roots and ganglia are evaluated for the presence of hemorrhage. The authors performed a small pilot study using the novel method to evaluate 20 decedents with a history of blunt force trauma and eight without a traumatic history. Fifteen of the traumatic deaths and two of the nontraumatic deaths were found to have dorsal nerve root and/or ganglia hemorrhage.

OBJECTIVES To report the magnetic resonance imaging and clinical features of suspected idiopathic bilaterally symmetric hypertrophic ganglioneuritis affecting the C2 nerve roots. METHODS Retrospective analysis of case records of dogs with imaging findings suggestive of idiopathic bilateral C2 neuritis. Data analysed included signalment, history, clinical signs, clinical pathology results and magnetic resonance imaging findings. Nerve root enlargement and spinal cord changes were classified as clinically significant or incidental, and further graded as mild, moderate or severe based on the degree of spinal cord distortion/compression. Imaging features were also correlated with severity of neurological deficits. RESULTS Twelve dogs, including nine Staffordshire bull terriers showed magnetic resonance imaging features suggestive of idiopathic hypertrophic neuritis of C2 nerve roots. Findings were considered incidental (4/12) or clinically significant (8/12) based on prior neurological examination. Changes were best visualised on transverse images at the level of the C1-2 intervertebral foramina. The degree of associated spinal cord compression subjectively correlated with the severity of the neurological deficits. All cases with clinically significant lesions that were treated with corticosteroids responded favourably. CLINICAL SIGNIFICANCE Bilaterally symmetric C2 neuritis likely represents idiopathic hypertrophic ganglioneuritis. Staffordshire bull terriers appear over represented. Immunosuppressive doses of corticosteroids should be considered for clinically significant lesions.

Skilled motor control is regulated by the convergence of somatic sensory and motor signals in brain and spinal motor circuits. Cervical deafferentation is known to diminish forelimb somatic sensory representations rapidly and to impair forelimb movements. Our focus was to determine what effect deafferentation has on the motor representations in motor cortex, knowledge of which could provide new insights into the locus of impairment following somatic sensory loss, such as after spinal cord injury or stroke. We hypothesized that somatic sensory information is important for cortical motor map topography. To investigate this we unilaterally transected the dorsal rootlets in adult rats from C4 to C8 and mapped the forelimb motor representations using intracortical microstimulation, immediately after rhizotomy and following a 2-week recovery period. Immediately after deafferentation we found that the size of the distal representation was reduced. However, despite this loss of input there were no changes in motor threshold. Two weeks after deafferentation, animals showed a further distal representation reduction, an expansion of the elbow representation, and a small elevation in distal movement threshold. These changes were specific to the forelimb map in the hemisphere contralateral to deafferentation; there were no changes in the hindlimb or intact-side forelimb representations. Degradation of the contralateral distal forelimb representation probably contributes to the motor control deficits after deafferentation. We propose that somatic sensory inputs are essential for the maintenance of the forelimb motor map in motor cortex and should be considered when rehabilitating patients with peripheral or spinal cord injuries or after stroke.

AIM Information regarding the selection procedure for selective dorsal rhizotomy (SDR) in children with spastic cerebral palsy (CP) is scarce. Therefore, the aim of this study was to summarize the selection criteria for SDR in children with spastic CP. METHOD A systematic review was carried out using the following databases: MEDLINE, CINAHL, EMBASE, PEDro, and the Cochrane Library. Additional studies were identified in the reference lists. Search terms included 'selective dorsal rhizotomy', 'functional posterior rhizotomy', 'selective posterior rhizotomy', and 'cerebral palsy'. Studies were selected if they studied mainly children (

Aims: To investigate the outcome and complications of sacral deafferentation (SDAF) and sacral anterior root stimulation (SARS) in patients with neurogenic lower urinary tract dysfunction (NLUTD) resulting from complete spinal cord injury (SCI). Methods: Retrospective chart analysis of 137 patients who underwent SDAF/SARS at a single institution. Patients were categorized as being at risk of renal damage when the maximum detrusor pressure was >40cmH2O or detrusor compliance was

Introduction Transforaminal epidural steroid injections (TFESI) are commonly performed for the treatment of lumbar herniated nucleus pulposus and lumbosacral radiculopathy. Although rare, documented complications including spinal cord infarction, paraparesis, epidural abscess, paraplegia, and epidural hematoma have been reported. Here, we present a case of perineural hematoma affecting the L4 nerve root resulting in progressive acute-on-chronic lumbar radiculopathy following TFESI. Case Report A 72-year-old female presented with 3 months of low back and right anterior thigh pain. She subsequently underwent right L3 and L4 TFESI for physical examination findings concordant with radiographic right foraminal stenosis at L3-4 and L4-5 with L3-4 spondylolisthesis. Over the following week, the patient reported progressive right lower extremity weakness, worsening sensory loss, and ambulatory dysfunction. Examination revealed mild L3/4 myotomal weakness, sensory changes, and areflexia at the right patella. A gadolinium-enhanced MRI was ordered, which showed focal abnormal signal with involvement of the right L4-L5 neuroforamina and extending slightly far laterally, consistent with a small hematoma, affecting the L4 nerve root. Within 2 months, her strength and reflexes normalized and sensory loss diminished following medical management. Discussion Although extremely rare, perineural or foraminal hematomas may occur as a serious complication of TFESI, even in the setting of a standardized procedure. Hematoma may cause worsening of symptoms in the acute and subacute phase following TFESI. Further investigation into the etiologies of such injuries is warranted and must be added to the considerations of pain physicians performing these procedures.

Background Loss of urinary control after spinal cord injury increases risk of urinary tract disease and is problematical for owners of affected dogs. Objectives To design, implant, and test a sacral nerve stimulating device for controlling urine voiding in paraplegic dogs. Animals Nine pet dogs with severe thoracolumbar spinal cord injury causing paraplegia, loss of hindquarter sensation, and incontinence for more than 3 months. The procedure was offered prospectively to owners of suitable candidates after the irreversibility of the incontinence had been ascertained. Methods Open label clinical study. Surgically implantable electrode books were designed for insertion and retention of mixed sacral nerves. Sacral nerves were accessed via laminectomy and stimulated to test their ability to elicit detrusor contraction and then inserted into the electrode book, which was attached to a subcutaneously implanted, externally activated receiver. Results In 8/9 dogs, S2 nerves elicited the largest increases in intravesicular pressure with minimum stimulation and were placed in electrode books. Voiding efficiency was >90% in 8 of the 9 implanted dogs. No important detrimental effects of the procedure were observed. Conclusions and Clinical Importance This sacral nerve stimulating implant is a simple and apparently effective neuroprosthetic device that restores urine voiding in paraplegic dogs.

Dyssynergic reflexive external urethral sphincter (EUS) activity following spinal cord injury can prevent bladder voiding, resulting in significant medical complications. Irreversible sphincterotomies or neurotomies can prevent EUS activation and allow bladder voiding, but may cause incontinence or loss of sacral reflexes. We investigated whether kilohertz frequency (KF) electrical conduction block of the sacral roots could prevent EUS activation and allow bladder voiding.The S2 sacral nerve roots were stimulated bilaterally to generate bladder pressure in six cats. One S1 nerve root was stimulated proximally (20 Hz biphasic pulse trains) to evoke EUS pressure, simulating worst-case dyssynergic EUS reflexes. KF waveforms (12.5 kHz biphasic square wave) applied to an electrode implanted distally on the S1 nerve root blocked nerve conduction, preventing the increase in EUS pressure and allowing voiding.Applying KF waveforms increased bladder voiding in single, limited-duration trials from 3 ± 6% to 59 ± 12%. Voiding could be increased to 82 ± 9% of the initial bladder volume by repeating or increasing the duration of the trials.Sacral nerve block can prevent EUS activation and allow complete bladder voiding, potentially eliminating the need for a neurotomy. Eliminating neurotomy requirements could increase patient acceptance of bladder voiding neuroprostheses, increasing patient quality of life and reducing the cost of patient care.

G-CSF is a glycoprotein commonly used to treat neutropenia. Recent studies have shown that the G-CSF receptor (G-CSF-R) is expressed by neurons in the central nervous system (CNS), and neuroprotective effects of G-CSF have been observed. In this study, the influence of G-CSF treatment on the glial reactivity and synaptic plasticity of spinal motoneurons in rats subjected to ventral root avulsion (VRA) was investigated. Lewis rats (7 weeks old) were subjected to unilateral VRA and divided into two groups: G-CSF and placebo treated. The drug treated animals were injected subcutaneously with 200 μg/kg/day of G-CSF for 5 days post lesion. The placebo group received saline buffer. After 2 weeks, both groups were sacrificed and their lumbar intumescences processed for transmission electron microscopy (TEM), motoneuron counting, and immunohistochemistry with antibodies against GFAP, Iba-1, and synaptophysin. Furthermore, in vitro analysis was carried out, using newborn cortical derived astrocytes. The results indicated increased neuronal survival in the G-CSF treated group coupled with synaptic preservation. TEM analyses revealed an improved preservation of the synaptic covering in treated animals. Additionally, the drug treated group showed an increase in astroglial reactivity both in vivo and in vitro. The astrocytes also presented an increased cell proliferation rate when compared with the controls after 3 days of culturing. In conclusion, the present results suggest that G-CSF has an influence on the stability of presynaptic terminals in the spinal cord as well as on the astroglial reaction, indicating a possible neuroprotective action.

Purpose: In this report, we present our experience on the repair of brachial plexus root avulsion injuries with the use of contralateral C7 nerve root transfers with nerve grafting through a modified prespinal route. Methods: The outcomes of the contralateral C7 nerve root transfer to neurotize the upper trunk and C5/C6 nerve roots of the total or near total brachial plexus nerve root avulsion injury in a series of 41 patients were evaluated. The contralateral C7 nerve root that was dissected to the distal end of the divisions, along with the sural nerve graft, were placed underneath the anterior scalene and longus colli muscles, and then passed through the retro-esophageal space to neurotize the recipient nerve. The mean length of the dissected contralateral C7 nerve root was 6.5 ± 0.7 cm, and the mean length of sural nerve graft was 6.8 ± 1.9 cm. The suprascapular nerve was neurotized additionally by the phrenic nerve or the terminal motor branch of accessory nerve in some patients. Results: The mean length of the follow-up was 47.2 ± 14.5 months. The muscle strength was graded M4 or M3 for the biceps muscle in 85.4% of patients, for the deltoid muscle in 82.9% of patients, and for the upper parts of pectoral major in 92.7% of patients. The functional recovery of shoulder abduction in the patients with the additional suprascapular nerve neurotization was remarkably improved. Conclusions: The modified prespinal route could significantly reduced the length of nerve graft in the contralateral C7 nerve root transfer to the injured upper trunk in brachial plexus root avulsion injury, and it may improve the functional outcomes, which deserves further investigations. © 2011 Wiley Periodicals, Inc. Microsurgery, 2012.

The objective of this study was to analyze relationship of the intervertebral disc to the nerve root in the intervertebral foramen. Fourteen formalin-fixed cadavers were studied and measurements were performed. At the medial line of the neural foramen, the disc-root distance gradually increased from L1-L2 to L5-S1. The shortest distance between the disc to nerve root was L1-L2 (mean, 8.2 mm) and the greatest distance was found at L3-L4 (mean, 10.5 mm). In the mid-foramen, the disc-root distance decreased from L1-2 to L5-S1. The shortest distance from the disc to nerve root was found at L5-S1 (mean, 0.4 mm); and the greatest distance, at L1-L2 (mean, 3.8 mm). For the lateral line, the distance between an intersection point between the medial edge of the nerve root and the superior edge of the disc and lateral line of the foramen consistently increased from L1-L2 to L5-S1. The shortest distance from nerve root to the lateral border of the foramen, at the point where the nerve root crosses disc was at level L1-L2 (mean, 2.6 mm), the greatest distance, L5-S1 (mean, 8.8 mm). The width of the foramina progressively increased in a craniocaudal direction (mean, 8.3-17.8 mm from L1-2 to L5-S1, respectively). The mean height of the foramina was more or less the same for disc levels (range, 19.3-21.5). The results showed that nerve roots at lower levels traveled closer to the midline of the foramen. This morphometric information may be helpful in minimizing the incidence of injury to the lumbar nerve root during foraminal and extraforaminal approaches.

Lysophosphatidic acid receptor (LPA1) signaling initiates neuropathic pain through demyelination of the dorsal root (DR). Although LPA is found to cause down-regulation of myelin proteins underlying demyelination, the detailed mechanism remains to be determined. In the present study, we found that a single intrathecal (i.t.) injection of LPA evoked a dose- and time-dependent down-regulation of myelin-associated glycoprotein (MAG) in the DR through LPA1 receptor. A similar event was also observed in ex vivo DR cultures. Interestingly, LPA-induced down-regulation of MAG was significantly inhibited by calpain inhibitors (calpain inhibitor X, E-64 and E-64d) and LPA markedly induced calpain activation in the DR. The pre-treatment with calpain inhibitors attenuated LPA-induced neuropathic pain behaviors such as hyperalgesia and allodynia. Moreover, we found that sciatic nerve injury activates calpain activity in the DR in a LPA1 receptor-dependent manner. The E-64d treatments significantly blocked nerve injury-induced MAG down-regulation and neuropathic pain. However, there was no significant calpain activation in the DR by complete Freund’s adjuvant treatment, and E-64d failed to show anti-hyperalgesic effects in this inflammation model. The present study provides strong evidence that LPA-induced calpain activation plays a crucial role in the manifestation of neuropathic pain through MAG down-regulation in the DR.

Cervicogenic headache (CeH) is a well-recognized headache syndrome, distinguishable from other primary and secondary headaches. Although in some cases a cervical lesion may be detected in connection with the headache, many CeH patients have no demonstrable lesion. Besides, most of the frequent cervical diseases, such as spondylosis and disc herniations, do not present with headache of the cervicogenic type. This suggests that the neck is not an independent headache generator. CeH may depend in addition on a central predisposition counterpart, leading to the activation of the trigeminovascular system and pain generation.

Background: Inguinal herniorrhaphy can be successfully performed using general, regional or local anaesthesia. Paravertebral block (PVB) has been used for unilateral procedures such as thoracotomy, breast surgery, chest wall trauma, hernia repair or renal surgery. Methods: We compared unilateral lumbar PVB with conventional spinal anaesthesia (SA) in 60 consenting ASA I and II males aged 18–65 years, scheduled for unilateral inguinal hernia repair. Patients were randomly assigned into two groups, P (n=30) or S (n=30) to receive either PVB or SA, respectively. Two patients (7%) in group P had to be converted to general anaesthesia due to block failure. During surgery, patients of both groups received intravenous infusion of propofol titrated to light sedation. Results: The time to first post-operative analgesic requirement (primary outcome measure) as 342 ± 73 min in group P and 222 ± 22 min in group S (P

We report autopsy cases of two siblings who developed muscular atrophy and dementia, clinically considered to be familial motor neuron disease (MND). They presented with motor neuron signs predominantly in the distal limbs without sensory impairment. At autopsy, severe neuronal loss in the anterior horn consistent with MND was found, but histopathological hallmarks like Bunina bodies and skein-like inclusions were absent. Surprisingly, numerous huge axonal swellings (about 30 microm in diameter) and onion-bulb-like structures were found in the spinal ventral roots. These changes were not observed in spinal dorsal roots or peripheral nerves. However, obvious segmental demyelination of the ventral root was not found. In addition, neurofibrillary tangles (NFTs) and neuritic plaques were present in the frontal cortex, temporal cortex and hippocampus, and to a lesser degree, in the amygdala, substantia nigra and thalamus. Our two cases are a hitherto unreported type of MND, which shows focal giant axonopathy and prominent formation of onion-bulb-like structures due to Schwann cell proliferation restricted to the spinal ventral roots.

blacksquare, square, filled Abstract Introduction: Treatment of functional anorectal pain disorders remains a challenge. The purpose of this study is to describe a single center experience with sacral neuromodulation for the treatment of chronic functional anorectal pain. Methods: This is a retrospective study based on prospectively collected data of patients treated with sacral neuromodulation for functional anorectal pain from April 2005 to August 2008. Symptoms were analyzed using a visual analog scale pain score (0 to 10). A 7-point Likert scale was used to rate global perceived effect. All patients had a percutaneous nerve evaluation and subsequent test stimulation to assess sacral neuromodulation outcome prior to permanent implantation. Patients were eligible for permanent sacral neuromodulation in case of a pain score 50% decrease in the pain score compared to baseline. Results: Nine patients (2 males) were included in this study. Mean age was 53.8 years (27.6 to 74.0). Four patients (1 male) had successful test stimulation and were eligible for permanent implantation. Median pain score decreased from 8.0 (6.0 to 9.0) to 1.0 (0 to 2.0). All patients experienced a lasting improvement during the follow-up till 24 months. Global perceived effect in successful patient was 1 (completely recovered) in one patient and 2 (much improved) in three patients. Conclusion: This study showed that sacral neuromodulation can be a successful treatment for functional anorectal pain not responding to other treatments. Improvement obtained during test stimulation is a good predictor (diagnostic) for sustained success of permanent sacral neuromodulation. blacksquare, square, filled.

Cocaine- and amphetamine-regulated transcript (CART) peptides have been implicated in spinal pain transmission. A dense plexus of CART-immunoreactive fibres has been described in the superficial laminae of the spinal cord, which are key areas in sensory information and pain processing. We demonstrated previously that the majority of these fibres originate from nociceptive primary afferents. Using tract tracing, multiple immunofluorescent labelling and electronmicroscopy we determined the proportion of peptidergic primary afferents expressing CART, looked for evidence for coexistence of CART with galanin in these afferents in lamina I and examined their targets. Almost all (97.9%) randomly selected calcitonin gene-related peptide (CGRP)-immunoreactive terminals were substance P (SP)-positive (+) and CART was detected in approximately half (48.6%) of them. Most (81.4%) of the CGRP/SPergic boutons were galanin+ and approximately half (49.0%) of these contained CART. Many (72.9%) of the CARTergic boutons which expressed CGRP were also immunoreactive for galanin, while only 8.6% of the CARTergic terminals were galanin+ without CGRP. Electron microscopy showed that most of the CART terminals formed asymmetrical synapses, mainly with dendrites. All different morphological and neurochemical subtypes of spinoparabrachial projection neurons in the lamina I received contacts from CART-immunoreactive nociceptive afferents. The innervation density from these boutons did not differ significantly between either the different neurochemical or the morphological subclasses of these cells. This suggests a nonselective innervation of lamina I projection neurons from a subpopulation of CGRP/SP afferents containing CART peptide. These results provide anatomical evidence for involvement of CART peptide in spinal pain transmission.

Although sacral nerve root stimulation (SNS) can result in a symptomatic improvement of faecal incontinence, the mechanism of action remains unknown. The aim of this study was to assess whether short-term magnetic SNS can inhibit pharmacologically induced propulsive colonic contractions. Twelve healthy volunteers (median age: 43.5 years old) were studied on two separate occasions and randomized into either active (15 Hz, 100% output intensity for 5 s min−1 for 30 min) or sham rapid rate lumbosacral magnetic stimulation (rLSMS). Colorectal motility was recorded with a manometric catheter located at the most proximal transducer in the left colon and the most distal, in the rectum. Colonic contractions were provoked by instilling Bisacodyl. The effects of rLSMS on colonic, sigmoid and rectal contractions were monitored and recorded after Bisacodyl instillation. The appearance of high-amplitude contractions propagated or not (HAC/HAPC) provoked by Bisacodyl instillation was significantly delayed during active compared to sham stimulation (P = 0.03). There was no difference in the characteristics of HAC/HAPC (i.e. frequency, amplitude, duration, velocity of propagation) or the motility index with active or sham stimulation. The perception of urgency tended to be decreased with rLSMS following Bisacodyl instillation. The catheter was expulsed within a median of 16.5 min (range 8–39) after Bisacodyl administration during active stimulation compared to 14 min (range 5–40) during sham stimulation (P = 0.03). This study suggests that rLSMS could delay the appearance of the first Bisacodyl-induced colonic contractions.

Experimental autoimmune neuritis (EAN) is a well‐known animal model of Guillain‐Barré Syndrome. In this study, we studied the spatiotemporal expression of interleukin‐16 (IL‐16) in the nervous system of EAN rats and pharmacological effects of minocycline on IL‐16 expressions in EAN rats. In sciatic nerves and dorsal/ventral roots of EAN rats, IL‐16(+) cells, identified as macrophages and T cells, were mainly found to concentrate around blood vessels. However, in spinal cords, IL‐16(+) microglial cells were mainly found in lumbar dorsal horns. Massive IL‐16(+) cell accumulation in sciatic nerves and spinal roots was temporally correlated with severity of neurological signs of EAN. Furthermore, a strong correlation of IL‐16(+) cell accumulation with local demyelination in perivascular areas of sciatic nerves, and significant reduction of IL‐16(+) cell numbers in sciatic nerves and spinal cords by minocycline suggested a pathological contribution of IL‐16(+) cells in EAN. Taken together, robust IL‐16(+) cell accumulation in the nervous system and its temporal correlation with severity of neurological signs in EAN might suggest a pathological role of IL‐16 in EAN, which makes IL‐16 a potential pharmacological target.

An 18-month-old European shorthair cat was presented with a two week history of progressive decrease in consciousness, ambulatory tetraparesis, moderate ataxia and generalised decreased-to-absent postural reactions. Bilateral facial and nasal hypalgesia, absent menace response and anisocoria were found, and segmental spinal reflexes were normal. Neurological signs progressed to nonambulatory tetraparesis, tremor and spinal hyperalgesia. Histopathological examination revealed a mild-to-moderate lymphoplasmacytic and histiocytic infiltration, predominantly in the dorsal spinal roots, cranial nerves and ganglia in association with marked demyelination and proliferation of Schwann cells. Neurons and axons were preserved. Lesions were multi-focal and varied in severity. A predominantly sensory polyganglioradiculoneuritis was diagnosed. This lesion has not been reported previously in cats. Rabies, herpesviruses, feline infectious peritonitis, feline immunodeficiency virus, Toxoplasma gondii and feline leukaemia virus were excluded as possible aetiologies. Infections by other viruses or an autoimmune disease are discussed.

The relation between abnormal electrophysiological responses to intraoperative stimulation during selective dorsal rhizotomy (SDR) and the degree of spasticity and motor dysfunction was explored in 92 children with spastic cerebral palsy (CP) who underwent SDR at a single center. The proportion of abnormally responding rootlets was compared with the degree of spasticity measured with the modified Ashworth Scale (MAS) and with the spasticity measurement system (SMS) at discrete segmental levels. Motor impairment measured with the Gross Motor Function Measure (GMFM) was also compared with the proportion of abnormally responding dorsal rootlets. A consistent relation between the proportion of abnormally responding rootlets and the degree of spasticity and gross motor abnormality at the corresponding muscles could not be demonstrated. There was also no consistent association between the proportion of rootlets ablated during SDR and the change in spasticity measured with the MAS and SMS, or to the change in motor function as measured with the GMFM. These data suggest that the intraoperative monitoring technique most commonly used for SDR is unlikely to identify accurately those neural elements which contribute to spasticity in children with CP.

SUMMARY The medical records were reviewed of 83 children with Guillain-Barre syndrome, with reference to the age-associated changes found in the initial symptoms, the intervals between the preceding illness and the onset of disease, and the patterns of affected cranial nerves. A close correlation was observed between cranial nerve involvement and respiratory complications. The findings suggest the involvement of nervous system maturation in the clinical manifestations of Guillain-Barre syndrome in children. RESUME Modifications associees a l'âge dans la symptomatolgie dy syndrome de Guillain-Barre chez l'enfant Les dossiers medicaux de 83 enfants presentant un syndrome de Guillain-Barre, ont eteetudies en fonction des modifications liees a l'âge trouvees dans (1) les symptomes initiaux, (2) l'intervalle entre l'affection precedente et le debut de la maladie, et (3) la distribution de l'atteinte des nerfs craniens touches. Une correlation etroite a ete observee cntre l'implication des nerfs craniens et les complications respiratoires. Les donnees suggerent l'influence d'une maturation du systeme nerveux dans les manifestations cliniques du syndrome de Guillain-Barre chez l'enfant. ZUSAMMENFASSUNG Altersabhangige Veranderungen der Symptomatologie des Guillain-Barre Syndroms bei Kindern Die Anamnesen von 83 Kindern mit Guillain-Barre Syndrom wurden im Hinblick auf die altersabhangigen Veranderungen uberpruft, die bei (1) den anfanglichen Symptomen, (2) den Intervallen zwischen den vorausgehenden Erkrankungen und dem Beginn dieser Erkankung und (3) der Symptomatologie der betroffenen Hirnnerven gefunden wurden. Es fand sich eine enge Beziehung zwischen Hirnnervenbeteiligung und respiratorischen Komplikationen. Die Befunde spechen dafur, das die Reifungsprozesse des Nervensystems fur die klinische Manifestation des Guillain-Barre Syndroms bei Kindern eine Rolle spielt. RESUMEN Cambios asociados con la edad en la sintomatologia del sindrome de Guillain-Barre Se revisaron las historias medicas de 83 ninos con sindrome de Guillain-Barre para observar los cambios, en relacion con la edad, hallados en los sintomas iniciales, los intervalos entre la enfermedad anterior y el inicio de la enfermedad, y patrones de afectacion de los pares craneales. Se observo una relacion estrecha entre la alteracion de nervios craneales y las complicaciones respiratorias. Los hallazgos sugieren la afectacion de la maduracion del sistema nervioso en las manifestaciones clinicas del sindrome de Guillain-Barre en ninos.

The objective of this single-center investigator-masked randomized clinical trial was to investigate the efficacy and safety of selective dorsal rhizotomy (SDR) in children with spastic diplegia. Forty-three children with spastic diplegia were randomly assigned on an intention-to-treat basis to receive SDR plus physical therapy (PT), or PT alone. Thirty-eight children completed follow-up through 24 months. Twenty-one children received SDR (SDR+PT group) and 17 received PT (PT Only group). SDR was guided with electrophysiological monitoring and performed by one experienced neurosurgeon. All subjects received equivalent PT. Spasticity was quantified with an electromechanical torque measurement device (spasticity measurement system [SMS]). The Gross Motor Function Measure (GMFM) was used to document changes in functional mobility. Primary outcome measures were collected at baseline, 6, 12, and 24 months by evaluators masked to treatment. At 24 months, the SDR+PT group exceeded the PT Only group in mean reduction of spasticity by SMS measurement (-8.2 versus +5.1 newton meters/radian, P=0.02). The SDR+PT group and the PT Only group demonstrated similar improvements in independent mobility on the GMFM (7.0 versus 7.2 total percent score, P=0.94). Outcomes on secondary variables were consistent with primary outcomes. There were no serious adverse events. We conclude that SDR is safe and reduces spasticity in children with spastic diplegia. SDR plus PT and equivalent PT without SDR result in equal improvements in independent mobility at 24 months. SDR may not be an efficacious treatment for children with mild spastic diplegia.