Intraoperative Neuromonitoring in Surgery of Cauda Equina and Conus Medullaris Tumors.

AIM: To demonstrate the value of special intraoperative neuromonitoring techniques for cauda equina and conus medullaris tumors (CECMT) by describing standard methods used at our center. MATERIAL AND METHODS: Neurophysiological records were retrospectively reviewed for 16 patients (eight females and eight males; age range: 27â€"60 years) who underwent surgery for CECMT at our department between 2016 and 2018. RESULTS: Motor and/or sensorial deficits were preoperatively identified in 10 patients; no patients had bladder or sexual dysfunction. Motor evoked potential (MEP) loss occurred in seven patients with full or partial recovery. No changes were seen in pudendal somatosensory evoked potential (SEP) or bulbocavernosus reflex (BCR), and morphological deterioration and amplitude loss of tibial SEPs were present in four patients. Postoperatively, no new neurological deficits and/or bladder and sexual dysfunction were present. CONCLUSION: Pudendal SEP and BCR are useful tests for monitoring CECMT surgeries. BCR is an easily obtainable modality for preserving sacral functions and recommended as a primary monitoring modality in conjunction with traditional neurophysiological techniques during CECMT surgery.

Structures of filum terminale and characteristics of ependymal cells of its central canal in rats.

The filum terminale (FT) is a potential source of ependymal cells for transplantation. The present study was performed to clarify the characteristics of ependymal cells of the central canal (CC) of the FT in rats. The FT was a thin strand continuous with the conus medullaris (CM), a caudal end of the main spinal cord, situated at the L3-4 level in adult rats. The border between the CM and FT was not visible, but could be defined as the site where the strand was as thin as its more caudal segment. While the CM contained an appreciable amount of white and grey matter associated with the CC at its center, the FT had no or only a negligible amount of such spinal cord parenchymal tissue. The FT was tracked ca. 4 cm from the site defined above to the level of S4-5 in adult rats. The rostral part of the FT (FTI) included within the cauda equina is exposed to cerebrospinal fluid, whereas the more caudal part (FTE) was surrounded by a dense layer of connective tissue. Almost all ependymal cells were immunostained for Sox2, Sox9, FoxJ1, and CD133, generally recognized immunochemical markers for ependymal cells of the CC in the spinal cord. Ependymal cells of the CC of FT exhibited almost the same structural and immunohistochemical characteristics as those of the CC of the main spinal cord. Ependymal cells of FTI covered by a thin layer of connective tissue are considered appropriate for transplantation.

Visualization of the electrical activity of the cauda equina using a magnetospinography system in healthy subjects.

OBJECTIVE: To establish a method to measure cauda equina action fields (CEAFs) and visualize the electrical activities of the cauda equina in a broadly aged group of healthy adults. METHODS: Using a 124-channel magnetospinography (MSG) system with superconducting interference devices, the CEAFs of 43 healthy volunteers (22-64 years of age) were measured after stimulation of the peroneal nerve at the knee. Reconstructed currents were obtained from the CEAFs and superimposed on the X-ray image. Conduction velocities were also calculated from the waveform of the reconstructed currents. RESULTS: The reconstructed currents were successfully visualized. They flowed into the L5/S1 foramen about 8.25-8.95 ms after the stimulation and propagated cranially along the spinal canal. In 32 subjects (74%), the conduction velocities of the reconstructed currents in the cauda equina could be calculated from the peak latency at the L2-L5 level. CONCLUSIONS: MSG visualized the electrical activity of the cauda equina after peroneal nerve stimulation in healthy adults. In addition, the conduction velocities of the reconstructed currents in the cauda equina could be calculated, despite previously being difficult to measure. SIGNIFICANCE: MSG has the potential to be a novel and noninvasive functional examination for lumbar spinal disease.

Electric field stimulation induced neuronal differentiation of filum terminale derived neural progenitor cells.

Adult filum terminale (FT) is an atypical region from where multipotent neural progenitor cells (NPCs) have been isolated. However, poor neuronal differentiation rate of FT-NPCs currently limits their clinical applications. Using custom-designed electric fields (EFs), this study sets up a method to significantly improve neuronal differentiation rate of rat FT-NPCs in vitro. We investigated the influence of EF strength on rat FT-NPCs differentiation. By adding reasonable strength of EF to FT-NPCs, our data shows a significant increase in neuronal differentiation rate. The present innovation provides a novel method of directional differentiation and efficient production of neurons from FT-NPCs in vitro. This improved approach for inducing neuronal differentiation can be applied to future research on autoplastic transplantation.

The Filum Terminale: A Cadaver Study of Anatomy, Histology, and Elastic Properties.

BACKGROUND: The filum terminale is a fibrous band, consisting of the filum terminale internum (FTI), connecting the conus medullaris (CM) with the dural sac (DS), and the filum terminale externum (FTE), connecting the DS with the coccyx. Despite its importance in tethered cord syndrome, published anatomic and physiologic data on the filum terminale remain scarce. We describe 1) the dimensions and position of the FTI and FTE; 2) the histology of the FTI-DS-FTE transition zone; and 3) the extensibility and elastic properties of the FTI and the CM. METHODS: Anatomic measurements were performed on 10 fresh and 10 embalmed human cadavers. Four other fresh cadavers were used for strain and elasticity measurements. RESULTS: The mean FTI and FTE lengths were 158.75 and 69.33 mm, respectively. From cranially to caudally, the FTI diameter decreased from 1.93 to 0.69 mm. The most frequent vertebral level of the CM-FTI and the FTI-DS-FTE junction were L1 and S2, respectively. FTE length correlates with body length (r = 0.54; P = 0.014) and with FTI-DS-FTE junction vertebral level (ρ =-0.76; P < 0.001). Histologically, the FTI fuses with DS fibers and continues as FTE. The FTI and the CM show an exponential loaded weight-strain relationship, with the FTI showing higher strain than the CM and almost perfect elastic properties. The CM strain is increased when the dentate ligaments are cut. CONCLUSIONS: The FTI is an overturned oblate cone-shaped structure, showing bigger strain under weight loading compared with the CM, thereby protecting the CM from traction, together with the dentate ligaments.

Stimulation of Cauda Equina With a Figure-of-Eight Magnetic Coil.

PURPOSE: To record responses in the abductor hallucis muscle after lumbosacral stimulation with a figure-of-eight magnetic coil. To compare magnetic stimulation (MS), electrical stimulation (ES), and the peripheral motor conduction time. METHODS: M and F waves and compound muscle action potentials were recorded after L1 MS, S1 MS, and L1 ES. RESULTS: The compound muscle action potential latency on L1 MS was 26.9 ± 2.6 milliseconds and on L1 ES was 25.6 ± 2.2 milliseconds, and the peripheral motor conduction time was 27.0 ± 2.5 milliseconds (analysis of variance P = 0.0008). The compound muscle action potential amplitude was 12 ± 11% of M-wave on L1 MS, 32 ± 18% on S1 MS, and 31 ± 17% on L1 ES. CONCLUSIONS: Dorsal MS reliably elicits responses in the abductor hallucis muscle. The latency of compound muscle action potentials on L1 MS is comparable to peripheral motor conduction time. A potential drawback of MS may be too weak stimulation at the proximal end of the cauda equina.

Magnetic resonance imaging assessment of spinal cord and cauda equina motion in supine patients with spinal metastases planned for spine stereotactic body radiation therapy.

PURPOSE: To assess motion of the spinal cord and cauda equina, which are critical neural tissues (CNT), which is important when evaluating the planning organ-at-risk margin required for stereotactic body radiation therapy. METHODS AND MATERIALS: We analyzed CNT motion in 65 patients with spinal metastases (11 cervical, 39 thoracic, and 24 lumbar spinal segments) in the supine position using dynamic axial and sagittal magnetic resonance imaging (dMRI, 3T Verio, Siemens) over a 137-second interval. Motion was segregated according to physiologic cardiorespiratory oscillatory motion (characterized by the average root mean square deviation) and random bulk shifts associated with gross patient motion (characterized by the range). Displacement was evaluated in the anteroposterior (AP), lateral (LR), and superior-inferior (SI) directions by use of a correlation coefficient template matching algorithm, with quantification of random motion measure error over 3 separate trials. Statistical significance was defined according to P<.05. RESULTS: In the AP, LR, and SI directions, significant oscillatory motion was observed in 39.2%, 35.1%, and 10.8% of spinal segments, respectively, and significant bulk motions in all cases. The median oscillatory CNT motions in the AP, LR, and SI directions were 0.16 mm, 0.17 mm, and 0.44 mm, respectively, and the maximal statistically significant oscillatory motions were 0.39 mm, 0.41 mm, and 0.77 mm, respectively. The median bulk displacements in the AP, LR, and SI directions were 0.51 mm, 0.59 mm, and 0.66 mm, and the maximal statistically significant displacements were 2.21 mm, 2.87 mm, and 3.90 mm, respectively. In the AP, LR, and SI directions, bulk displacements were greater than 1.5 mm in 5.4%, 9.0%, and 14.9% of spinal segments, respectively. No significant differences in axial motion were observed according to cord level or cauda equina. CONCLUSIONS: Oscillatory CNT motion was observed to be relatively minor. Our results support the importance of controlling bulk patient motion and the practice of applying a planning organ-at-risk margin.

The isolation, differentiation, and survival in vivo of multipotent cells from the postnatal rat filum terminale.

Neural stem cells (NSCs) are undifferentiated cells in the central nervous system (CNS) that are capable of self-renewal and can be induced to differentiate into neurons and glia. Current sources of mammalian NSCs are confined to regions of the CNS that are critical to normal function and surgically difficult to access, which limits their therapeutic potential in human disease. We have found that the filum terminale (FT), a previously unexplored, expendable, and easily accessible tissue at the caudal end of the spinal cord, is a source of multipotent cells in postnatal rats and humans. In this study, we used a rat model to isolate and characterize the potential of these cells. Neurospheres derived from the rat FT are amenable to in vitro expansion in the presence of a combination of growth factors. These proliferating, FT-derived cells formed neurospheres that could be induced to differentiate into neural progenitor cells, neurons, astrocytes, and oligodendrocytes by exposure to serum and/or adhesive substrates. Through directed differentiation using sonic hedgehog and retinoic acid in combination with various neurotrophic factors, FT-derived neurospheres generated motor neurons that were capable of forming neuromuscular junctions in vitro. In addition, FT-derived progenitors that were injected into chick embryos survived and could differentiate into both neurons and glia in vivo.

Magnetic-motor-root stimulation: review.

Magnetic stimulation can activate the human central and peripheral nervous systems non-invasively and virtually painlessly. Magnetic stimulation over the spinal enlargements can activate spinal nerves at the neuroforamina (magnetic-neuroforamina stimulation). This stimulation method provides us with information related to the latency of compound-muscle action potential (CMAP), which is usually interpreted as peripheral motor-conduction time (PMCT). However, this stimulation method has faced several problems in clinical applications. One is that supramaximal CMAPs were unobtainable. Another is that magnetic stimulation did not usually activate the spinal nerves in the spinal canal, i.e., the cauda equina, which prevented an evaluation of its conduction. For these reasons, magnetic-neuroforamina stimulation was rarely used to evaluate the conduction of peripheral nerves. It was mainly used to evaluate the conduction of the corticospinal tract using the parameter of central motor-conduction time (CMCT), which was calculated by subtracting PMCT from the latency of motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) over the primary motor cortex. Recently, supramaximal stimulation has been achieved in magnetic-neuroforamina stimulation, and this has contributed to the measurement of both CMAP size and latency. The achievement of supramaximal stimulation is ascribed to the increase in magnetic-stimulator output and a novel coil, the magnetic augmented translumbosacral stimulation (MATS) coil. The most proximal part of the cauda equina can be reliably activated using the MATS coil (magnetic-conus stimulation), thus contributing to the measurement of cauda equina conduction time (CECT) and cortico-conus motor-conduction time (CCCT). These recent developments in magnetic-motor-root stimulation enable us to more precisely evaluate the conduction of the proximal part of peripheral nerves and that of the corticospinal tract for lower-limb muscles. In this review article, we summarise the basic mechanisms, recent topics, clinical applications, comparison to electrical stimulation, pitfalls, safety and additional issues in magnetic-motor-root stimulation.

The postnatal human filum terminale is a source of autologous multipotent neurospheres capable of generating motor neurons.

BACKGROUND: Neural progenitor cells (NPCs) are undifferentiated and mitotic and can be induced to differentiate into neurons and glia, the building blocks of the nervous system. NPCs have great therapeutic potential for nervous system trauma and degenerative disorders. They have been identified in the mammalian central nervous system, but current sources are difficult to access surgically and come from regions that are critical for normal brain function. OBJECTIVE: To identify and characterize in detail a novel source of human NPCs in the filum terminale (FT), a vestigial structure at the caudal end of the spinal cord, which is easily accessed and plays no functional role in the postnatal nervous system. METHODS: Cells were isolated and cultured in vitro from the FT of terminated fetuses and from children and adolescents who had undergone surgical resections for tethered spinal cords. Cell culture techniques, immunohistochemistry, and immunocytochemistry were applied to examine FT cells. RESULTS: : FT cells gave rise to neurospheres that proliferated over extended periods of time in culture. These neurospheres were positive for neural stem/progenitor cell markers by immunocytochemical staining. The neurospheres were able to be induced to differentiate in vitro into neurons and glial cells, which were confirmed by the use of antibodies against the cell type-specific markers. Moreover, they have been induced to form motor neurons capable of innervating striated muscle in vitro. CONCLUSION: Multipotent NPC cells from the FT are both accessible and expendable. They may allow autologous cell-based transplantation therapy that circumvents immunological rejection.

Paraneoplastic lower motor neuronopathy associated with Hodgkin lymphoma.

INTRODUCTION: Paraneoplastic lower motor neuronopathies have been reported rarely with Hodgkin lymphoma. METHODS: We report a case of rapidly progressive motor neuronopathy preceding the diagnosis of Hodgkin lymphoma. RESULTS: A 31-year-old woman developed subacute rapidly progressive quadriparesis. Electrodiagnostic studies revealed a severe diffuse disorder of motor neurons and their axons. Symmetric enhancement of the cauda equina motor nerve roots was notable on magnetic resonance imaging scan. Further imaging demonstrated an enlarged supraclavicular lymph node, and biopsy revealed Hodgkin lymphoma. A final diagnosis of paraneoplastic motor neuronopathy was made after investigations for alternative causes of motor neuronopathy were unrevealing. Neurological improvement was seen with combined treatment of the underlying malignancy and intravenous immunoglobulin. CONCLUSIONS: Paraneoplastic causes should be considered in the differential diagnosis of subacute motor neuronopathy, as the neurological presentation may precede cancer detection. Combinations of lymphoma treatment and immunotherapy may result in a favorable outcome.

Aging influences central motor conduction less than peripheral motor conduction: a transcranial magnetic stimulation study.

INTRODUCTION: In this study we investigated the effects of aging on corticospinal tract conduction by measuring the corticoconus motor conduction time (CCCT). METHODS: Motor evoked potentials were recorded from the right tibialis anterior muscle in 100 healthy volunteers. To activate the most proximal part of the cauda equina, magnetic stimulation was performed using a MATS coil over the L1 spinous process (L1-level latency). Transcranial magnetic stimulation of the motor cortex was also conducted (cortical latency). To obtain the CCCT, the L1-level latency was subtracted from the cortical latency. RESULTS: Age was significantly correlated with L1-level latency, but it was not significantly correlated with CCCT. CONCLUSIONS: CCCT is the most direct indicator of corticospinal tract conduction, whereas L1-level latency reflects whole peripheral motor conduction. Central motor conduction was found to be relatively less affected by aging compared with peripheral motor conduction.

Neurophysiologic monitoring in neurosurgery.

This article focuses on the application of neurophysiologic monitoring in uniquely neurosurgical procedures. Neurophysiologic monitoring provides functional testing and mapping to identify neural structures. Once identified, the functionality of the central and peripheral nervous system areas at risk for neurosurgical injury can be monitored. It discusses the use of motor-evoked potentials, sensory evoked potentials, electromyography and electroencephalography to assess neurologic change.

Conductive neuromagnetic fields in the lumbar spinal canal.

OBJECTIVE: To measure neuromagnetic evoked fields in the lumbar spinal canal. METHODS: Using a newly developed superconducting quantum interference device (SQUID) fluxmeter, neuromagnetic fields of 5 healthy male volunteers were measured at the surface of the lower back after stimulation of the tibial nerves at the ankles. For validation, we inserted a catheter-type electrode percutaneously in the lumbar epidural space in 2 of the subjects and measured cauda equina action potentials after tibial nerve stimulation. RESULTS: Neuromagnetic fields propagating from the intervertebral foramina into the spinal canal were measured, and the latencies of the magnetic fields corresponded largely with those of the cauda equina action potentials. CONCLUSIONS: We successfully measured ascending neuromagnetic fields originating at the nerve root and the cauda equina with high spatial resolution. Future studies will determine whether neuromagnetic field measurement of the lumbar spine can be a useful diagnostic method for the identification of the disordered site in spinal nerves. SIGNIFICANCE: We successfully measured neuromagnetic fields in the lumbar spinal canal, which have previously been difficult to verify. Future studies will determine whether neuromagnetic field measurement of the lumbar spine can be a useful diagnostic method for identifying disorders of spinal nerves.

Motor nerve conduction study in cauda equina with high-voltage electrical stimulation in multifocal motor neuropathy and amyotrophic lateral sclerosis.

In this study we aim to establish a motor nerve conduction study (NCS) for the cauda equina and examine its usefulness in multifocal motor neuropathy (MMN) and amyotrophic lateral sclerosis (ALS). NCS of the tibial nerve proximal to the knee was performed with an optimized high-voltage electrical stimulation (HV-ES) method in 21 normal subjects, 5 with MMN, and 11 with ALS. HV-ES, but not magnetic stimulation, could supramaximally stimulate the cauda equina. Cauda equina motor conduction time determined by HV-ES, but not that with F-waves, correlated well with cauda equina length on magnetic resonance imaging. HV-ES revealed proximal lesions in 4 MMN patients but in none of the ALS patients. Importantly, 1 patient with "MMN without conduction block (CB)" had a CB in the cauda equina. Cauda equina motor conduction is better evaluated by HV-ES than with F-wave study or magnetic stimulation. HV-ES can help to distinguish MMN and "MMN without CB" from ALS.

Cortico-conus motor conduction time (CCCT) for leg muscles.

OBJECTIVE: To measure the conduction time from the motor cortex to the conus medullaris (cortico-conus motor conduction time, CCCT) for leg muscles using magnetic stimulation. METHODS: Motor evoked potentials (MEPs) were recorded from tibialis anterior muscles in 51 healthy volunteers. To activate spinal nerves at the most proximal cauda equina level or at the conus medullaris level, magnetic stimulation was performed using a MATS coil. Transcranial magnetic stimulation of the motor cortex was also conducted to measure the cortical latency for the target muscle. To obtain the CCCT, the latency of MEPs to conus stimulation (conus latency) was subtracted from the cortical latency. RESULTS: MATS coil stimulation evoked reproducible MEPs in all subjects, yielding CCCT data for all studied tibialis anterior muscles. CONCLUSIONS: MATS coil stimulation provides CCCT data for healthy subjects. SIGNIFICANCE: This novel method is useful for evaluation of corticospinal tract function for leg muscles because no peripheral component affects the CCCT.

Flexibility of motor pattern generation across stimulation conditions by the neonatal rat spinal cord.

Previous studies have demonstrated that "locomotor-like" rhythmic patterns can be evoked in the isolated neonatal rat spinal cord by several means, including pharmacological neuromodulation and electrical stimulation of various pathways. Recent studies have used stimulation of afferent pathways to evoke rhythmic patterns, relying on synaptic activation of interneuronal systems rather than global imposition of neuromodulatory state by pharmacological agents. We use the in vitro neonatal rat spinal cord with attached hindlimb to examine the muscle activation patterns evoked by stimulation of these different pathways and evaluate whether stimulation of these pathways all evoke the same patterns. We find that the patterns evoked by bath application of serotonin (5-HT) and N-methyl-D-aspartic acid (NMDA) consisted of alternation between hip flexors and extensors and similar alternation was observed in the patterns evoked by electrical stimulation of the cauda equina (CE) or contralateral fifth lumbar (L(5)) dorsal nerve root. In contrast, the knee extensor/hip flexor rectus femoris (RF) and knee flexor/hip extensor semitendinosus (ST) were activated differentially across stimulation conditions. In 5-HT/NMDA patterns, RF was active in late flexion and ST in late extension. In CE patterns, these two muscles switched places with RF typically active in late extension and ST active in flexion. In L(5) patterns, ST was activated in extension and RF was silent or weakly active during flexion. There were also systematic differences in the consistency of rhythms evoked by each stimulation method: patterns evoked by electrical stimulation of CE or L(5) were less consistently modulated with the rhythm when compared with 5-HT/NMDA-evoked patterns. All differences were preserved following deafferentation, demonstrating that they reflect intrinsic properties of spinal systems. These results highlight the intrinsic flexibility of motor pattern generation by spinal motor circuitry which is present from birth and provides important information to many studies examining spinal pattern generating networks.

A new method to study sensory modulation of locomotor networks by activation of thermosensitive cutaneous afferents using a hindlimb attached spinal cord preparation.

The use of isolated in vitro spinal cord preparations to examine the underlying networks that control locomotion has become popular. It is also well known that afferent feedback can excite and modulate these networks. However, it is often difficult to selectively activate classes of afferents that subserve specific modalities using in vitro preparations. Here, we describe a technique where afferent receptors that detect temperature were selectively activated. To accomplish this we used an in vitro preparation of the mouse where the spinal cord was isolated (T5-cauda equina) with one hind limb left attached. We designed a special chamber allowing the hind paw to be placed in such a way that it remained attached to the spinal cord but received a separate supply of artificial cerebrospinal fluid (aCSF). This allowed us to alter the temperature of the hind limb compartment without affecting the temperature of the central compartment containing the spinal cord. We also demonstrate using this approach that agonists which activate receptors which detect noxious heat could be intradermally injected into the hind limb without it diffusing into the central compartment.