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BACKGROUND Differentiating foot drop due to upper motor neuron (UMN) lesions from that due to lower motor neuron lesions is crucial to avoid unnecessary surgery or surgery at the wrong location. Electrodiagnostic (EDX) studies are useful in evaluating patients with spastic foot drop (SFD). OBSERVATIONS Among 16 patients with SFD, the cause was cervical myelopathy in 5 patients (31%), cerebrovascular accident in 3 (18%), hereditary spastic paraplegia in 2 (12%), multiple sclerosis in 2 (12%), chronic cerebral small vessel disease in 2 (12%), intracranial meningioma in 1 (6%), and diffuse brain injury in 1 (6%). Twelve patients (75%) had weakness of a single leg, whereas 2 others (12%) had bilateral weakness. Eleven patients (69%) had difficulty walking. The deep tendon reflexes of the legs were hyperactive in 15 patients (94%), with an extensor plantar response in 9 patients (56%). Twelve patients (75%) had normal motor and sensory conduction, 11 of whom had no denervation changes of the legs. LESSONS This study is intended to raise awareness among surgeons about the clinical features of SFD. EDX studies are valuable in ruling out peripheral causes of foot drop, which encourages diagnostic investigation into a UMN source for the foot drop.

BACKGROUND Nerve injuries during carpal tunnel release (CTR) are rare. Electrodiagnostic (EDX) and ultrasound (US) studies may be helpful in evaluating iatrogenic nerve injuries during CTR. OBSERVATIONS Nine patients sustained a median nerve injury, and 3 patients experienced ulnar nerve damage. Decreased sensation occurred in 11 patients, and dysesthesia occurred in 1 patient. Abductor pollicis brevis (APB) weakness occurred in all patients with median nerve injury. Of the 9 patients with median nerve injury, the compound muscle action potentials (CMAPs) of the APB and sensory nerve action potentials (SNAPs) of the 2nd or 3rd digit were not recordable in 6 and 5 patients, respectively. Of the 3 patients sustaining ulnar nerve injuries, the CMAPs of the abductor digiti minimi (ADM) and SNAPs of the 5th digit were not recordable in 1 patient; 2 patients showed prolonged latency and decreased amplitude of CMAPs/SNAPs. US studies of 8 patients with a median nerve injury showed a neuroma within the carpal tunnel. One patient underwent surgical repair urgently, and 6 did so after variable intervals. LESSONS Surgeons should be cognizant of nerve injuries during CTR. EDX and US studies are useful in evaluating iatrogenic nerve injuries during CTR.

Slimmer’s paralysis refers to a common fibular nerve palsy caused by significant and rapid weight loss. This condition usually results from entrapment of the common fibular nerve due to loss of the fat pad surrounding the fibular head. Several etiologies of common fibular nerve palsy have been proposed, including trauma, surgical complications, improperly fitted casts or braces, tumors and cysts, metabolic syndromes, and positional factors. We present 5 cases of slimmer’s paralysis in patients who had lost 32–57 kg in approximately 1 year. In 2 cases, MR neurogram of the knee demonstrated abnormalities of the common fibular nerve at the fibular head. Two patients underwent a common fibular nerve decompression at the fibular head and attained improved gait and sensorimotor function. Weight loss, diabetes mellitus, and immobilization may have contributed to slimmer’s paralysis in 1 case. Awareness of slimmer’s paralysis in patients who have lost a significant amount of weight in a short period of time is imperative to detect and treat a fibular nerve neuropathy that may ensue.

Iatrogenic peripheral nerve injuries may result from transection, stretch, compression, injections, ligature, heat, anticoagulant use, and radiation. Iatrogenic median nerve palsy has been reported rarely. We report a case of a woman who underwent craniectomy for treatment of trigeminal neuralgia. Intraoperatively, a transient decline in the amplitude of the left upper extremity somatosensory evoked potentials (SSEPs) was noted. This finding was presumed to be due to the traction on the brachial plexus as it improved with repositioning. Immediately upon waking from anesthesia, the patient experienced sensorimotor deficits in the left median nerve distribution. Ecchymoses from venipuncture were observed in this area. Electrodiagnostic studies confirmed a left median nerve neuropathy localized in the antebrachial area. Neurosurgeons and neurologists should be alert to potential iatrogenic median nerve palsy following vascular access at the antebrachial region. Vascular access could be performed under the ultrasound guidance when a patient is under anesthesia or unable to give sensory feedback. Furthermore, placing an additional recording electrode over the proximal upper arm during intraoperative SSEP monitoring aids in distinguishing between brachial plexus and peripheral nerve injuries.

Introduction Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and rarely develops after drug therapy. This study describes the clinical, electrodiagnostic (EDX), and ultrasound (US) findings in seven patients who experienced CTS due to anti-cancer therapeutic agents. Methods All patients underwent EDX testing, and four patients had an US study. Results CTS occurred in four patients with aromatase inhibitors, two with immune checkpoint inhibitors, and one with a selective estrogen receptor modulator. The mean duration between initiation of the anti-cancer therapeutic agents and symptom onset was 6 weeks (range: 2–12 weeks). Decreased digit sensation was noted in all patients; wasting and weakness of the abductor pollicis brevis (APB) was observed in three (42.8%) patients. The compound muscle action potentials (CMAP) of the APB and sensory nerve action potentials of the second or third digit could not be recorded in two (28.5%) and four (57.1%) patients, respectively. The needle EMG detected fibrillations and positive sharp waves in the APB in two patients. The motor unit potentials of the APB were decreased with large polyphasics in three (42.8%) patients. Of the four patients who underwent US testing, all had increased cross-sectional area of the median nerve at the carpal tunnel inlet, three (75%) had thenar muscle atrophy, and two (50%) had a loss of fascicular pattern. Three (42.8%) patients underwent a CTR. Conclusions Physicians should be cognizant of the relationship between anti-cancer therapeutic agents and CTS. EDX studies and US play important roles in the diagnostic assessment of such patients.

Multiple sclerosis is an autoimmune disease in which the immune system attacks the myelin sheath in the central nervous system. It is characterized by blood-brain barrier dysfunction throughout the course of multiple sclerosis, followed by the entry of immune cells and activation of local microglia and astrocytes. Glial cells (microglia, astrocytes, and oligodendrocyte lineage cells) are known as the important mediators of neuroinflammation, all of which play major roles in the pathogenesis of multiple sclerosis. Network communications between glial cells affect the activities of oligodendrocyte lineage cells and influence the demyelination-remyelination process. A finely balanced glial response may create a favorable lesion environment for efficient remyelination and neuroregeneration. This review focuses on glial response and neurodegeneration based on the findings from multiple sclerosis and major rodent demyelination models. In particular, glial interaction and molecular crosstalk are discussed to provide insights into the potential cell- and molecule-specific therapeutic targets to improve remyelination and neuroregeneration.

Parathyroid hormone-related peptide (PTHrP) acts under physiological conditions to regulate normal development of several tissues and organs. The role of PTHrP in spinal cord development has not been characterized. Pthrp knock in (Pthrp KI) mice were genetically modified to produce PTHrP in which there is a deficiency of the nuclear localization sequence (NLS) and C-terminus. Using this genetically modified mouse model, we have characterized its effect on spinal cord development early postnatally. The spinal cords from Pthrp KI mice displayed a significant reduction in its length, weight, and cross-sectional area compared to wild-type controls. Histologically, there was a decreased development of neurons and glial cells that caused decreased cell proliferation and increased apoptosis. The neural stem cells (NSCs) cultures also revealed decreased cell proliferation and differentiation and increased apoptosis. The proposed mechanism of delayed spinal cord development in Pthrp KI mice may be due to alteration in associated pathways in regulation of cell-division cycles and apoptosis. There was significant downregulation of Bmi-1 and upregulation of cyclin-dependent kinase inhibitors p27, p21, and p16 in Pthrp KI animals. We conclude that NLS and C-terminus peptide segments of PTHrP play an important role in inhibiting cell apoptosis and stimulation of cellular proliferation necessary for normal spinal cord development.

BACKGROUND Ependymomas are the most frequent tumors of the adult spinal cord, representing 1.9% of all central nervous system tumors and 60% of spinal cord tumors. Spinal ependymomas are usually solitary, intramedullary lesions. While intradural extramedullary (IDEM) ependymomas are infrequent, multifocal IDEM ependymomas are exceptionally rare. OBSERVATIONS The authors reported the first case in the literature of a patient diagnosed with multifocal IDEM ependymomas who was treated with tumor resection and brain and spinal radiotherapy. The patient presented with a 10-day history of bilateral leg numbness extending to the umbilicus and gait instability. Magnetic resonance imaging (MRI) studies revealed multiple enhancing nodular nodules throughout the entire spinal canal. Brain MRI revealed no abnormal lesions. A World Health Organization grade II ependymoma was confirmed histologically. At 31 months postoperatively, the patient remained clinically asymptomatic. Although cervical and thoracic MRI revealed stable intradural nodules and several areas of leptomeningeal enhancement, no malignant cells were seen in the cerebrospinal fluid (CSF). He underwent genetic testing to determine the appropriate chemotherapeutic agent if activation of the tumor should arise. LESSONS Because complete resection of multifocal IDEM ependymomas is not feasible, continued monitoring with brain and spine MRI is warranted to detect potential tumor dissemination in the CSF.

BACKGROUND Double crush syndrome consists of two compression sites along a peripheral nerve and is rare in the lower extremities. Electrodiagnostic and ultrasound (US) studies may be helpful in evaluating foot drop involving overlapping pathologies. OBSERVATIONS Case 1 involved a man who presented with left dorsiflexor weakness and left foot numbness. Electromyography (EMG) revealed a left common fibular nerve entrapment neuropathy and left L5 radiculopathy. US and magnetic resonance imaging (MRI) revealed a large cystic lesion of the left common fibular nerve treated by cyst removal. The left foot drop persisted postoperatively. Lumbar computed tomography myelography revealed severe left foraminal stenosis at L5–S1. Multilevel lumbar laminectomies and facetectomies with an L5–S1 fusion were performed. Within 1 month postoperatively, the left foot drop had improved. Case 2 involved a man who developed a right foot drop caused by right lumbar foraminal stenosis at L4–5 and L5–S1. EMG and US of the right common fibular neuropathy showed large fascicles involving the right common fibular nerve. MRI revealed a hyperintense signal of the right common fibular nerve. Spontaneous improvement occurred within 6 months without surgery. LESSONS Spine surgeons should recognize double crush in the lower extremities. EMG and US are valuable in detecting peripheral nerve abnormalities, especially in cases with overlapping lumbar pathology.

Accumulating evidence suggests that platelet-activating factor (PAF) increases the inflammatory response in demyelinating diseases such as multiple sclerosis. However, PAF receptor (PAFR) antagonists do not show therapeutic efficacy for MS, and its underlying mechanisms remain poorly understood. In the present study, we investigated the effects of PAF on an ex vivo demyelination cerebellar model following lysophosphatidylcholine (LPC, 0.5 mg/mL) application using wild-type and PAFR conventional knockout (PAFR-KO) mice. Demyelination was induced in cerebellar slices that were cultured with LPC for 18 h. Exogenous PAF (1 μM) acting on cerebellar slices alone did not cause demyelination but increased the severity of LPC-induced demyelination in both wild-type and PAFR-KO mice. LPC inhibited the expression of PAF-AH, MBP, TNF-α, and TGF-β1 but facilitated the expression of IL-1β and IL-6 in wild-type preparations. Of note, exogenous PAF stimulated microglial activation in both wild-type and PAFR-KO mice. The subsequent inflammatory cytokines TNFα, IL-1β, and IL-6 as well as the anti-inflammatory cytokine TGF-β1 demonstrated a diverse transcriptional profile with or without LPC treatment. PAF promoted TNF-α expression and suppressed TGF-β1 expression indiscriminately in wild-type and knockout slices; however, transcription of IL-1β and IL-6 was not significantly affected in both slices. The syntheses of IL-1β and IL-6 were significantly increased in LPC-induced demyelination preparations without PAF but showed a redundancy in PAF-treated wild-type and knockout slices. These data suggest that PAF can play a detrimental role in LPC-induced demyelination probably due to a redundant response of PAFR-dependent and PAFR-independent effects on inflammatory cytokines.

Background Brachioradial pruritus (BRP) is a neuropathic dysesthesia manifesting as pruritus over the dorsolateral forearm. While the etiology is unknown, intensive sun exposure and cervical spine disease have been proposed. This study describes the clinical, electrodiagnostic (EDX), and cervical MRI findings in nine patients diagnosed with BRP. Materials and methods All patients underwent EDX and cervical MRIs. Numerous metrics were documented including presenting symptoms, neurological examination, EDX findings, and cervical MRI features. Results All nine patients experienced pruritus of the arms/forearms, typical of BRP, which was unilateral in eight (89%) cases. Decreased pinprick sensation was noted in the arms/forearms (five [56%] patients) or of the thumbs, index, and/or middle fingers (four [44%] patients). Four (44%) patients had either decreased or absent biceps and brachioradialis deep tendon reflexes (DTRs), while one (11%) patient had decreased triceps and brachioradialis DTRs. The EDX revealed abnormalities in eight (89%) patients. Increased polyphasic units, decreased motor units, and/or denervation changes were recorded by needle electromyography (EMG) in eight (89%) patients: the biceps in seven (88%) and both the brachioradialis and triceps in four (50%) patients. The EMG abnormalities indicated chronic radiculopathy involving C6 in six patients and C5 and C6 in one patient. All nine patients had cervical spine disease, encompassing disc protrusions, spondylosis, spinal stenosis, and/or foraminal stenosis. Conclusions BRP in this series of patients was accompanied by chronic cervical radiculopathy involving predominantly C6 and C5. EDX and cervical spine MR imaging should be considered essential investigations in the evaluation of patients with BRP.

Background Dissecting pseudoaneurysms of the craniocervical circulation are uncommon, accounting for only 3% of all cerebral aneurysms. These aneurysms pose a challenge due to their location and anatomic configuration. The Pipeline Embolization Device (PED) is a flow diversion technique that successfully treats aneurysms by diverting blood flow away from the aneurysm and reconstructing the diseased parent artery by altering its hemodynamics. Case Description We report 3 cases in which the PED was used to treat craniocervical carotid artery dissection with associated pseudoaneurysms. A single PED was used in the first case, 4 PEDs were used in the second case, and 3 PEDs and a PRECISE PRO RX carotid stent were placed in the third case. All 3 patients achieved full neurologic recovery postoperatively. Cerebral angiography performed postoperatively demonstrated revascularization, good laminar flow, and no in-stent or adjacent stenosis. Conclusions PED placement offers a safe and effective method of treating spontaneous or traumatic craniocervical carotid artery dissections with excellent neurologic outcomes postoperatively and complete long-term aneurysmal occlusion.

Background: Pseudotumor of the tensor fascia lata (TFL) consists of a rare, benign soft tissue mass/hypertrophy of the TFL that appears on the anterolateral aspect of the proximal thigh. Notably, this condition often mimics a malignant tumor and may be misdiagnosed as a sarcoma. Case Description: A 45-year-old male presented with left hip/groin pain, swelling, and a painful mass on the anterolateral aspect of the left hip/thigh. The symptoms had started 3 months ago following an L1-S1 lumbar laminectomy/fusion. The initial diagnosis was hip disease, and the patient underwent a left MR arthrogram. When this study demonstrated a tear of the left anterosuperior acetabular labrum plus an increased alpha angle causing femoroacetabular impingement, the patient then underwent a left hip arthroscopy. However, as he continued to complain of the hip mass, he was referred to an orthopedic oncologist whose presumptive diagnosis favored a sarcoma. Nevertheless, the pelvic MRI scan and ultrasound (US) confirmed the diagnosis of hypertrophy of the left TFL (US left 33.4 mm vs. right 14.4 mm). The patient was first treated with 50 units of locally injected botulinum. As there was no symptomatic relief, the plan was to repeat the injection within the next few months. Conclusion: Hypertrophy of TFL may mimic a neoplasm such as a sarcoma and contributes to what appears to be a lumbar radiculopathy. However, MR and US imaging should readily identify TFL and rule out malignant lesions such as sarcomas.

Background The acute presentation of carpal tunnel syndrome (CTS) is rare. When symptoms start acutely with no obvious causes, ultrasound (US) imaging may provide clues to the etiology. Objective This study describes the clinical, electromyographic, and US findings in 25 patients presenting with acute CTS (ACTS). Methods In this analysis, of the patients referred for electrodiagnostic confirmation of CTS over the past decade, 25 had an acute onset of symptoms. All patients underwent EMG/NCV and US of the median nerve at the carpal tunnel and forearm. Results Of the 25 cases with ACTS, 5 (20%) had bilateral involvement leading to the total hands studied to 30. In 14 (56%) patients, an inciting event was identified as a possible cause of ACTS. In 11 (44%) patients without an antecedent event, 7 (64%) had a persistent median artery (PMA) detected by US. Electrodiagnostic studies showed prolonged distal motor latency with normal motor conduction velocity proximal to the carpal tunnel in 24 (80%) of 30 hands, 6 (20%) hands showed absent compound muscle action potential s over the abductor pollicis brevis (APB), and 22 (73%) hands had absent sensory potentials. Denervation changes were seen in the APB in 13 (43%) hands, and motor unit potentials were absent in 6 (20%) hands. Sixteen (64%) patients underwent a carpal tunnel release for severe symptoms. Conclusion CTS may present acutely without a clinically identifiable cause. US complements electrodiagnostic studies and is particularly useful when electrodiagnostic tests are non-diagnostic (due to absent compound muscle and sensory action potentials). US may also provide clues to the underlying cause.

BACKGROUND Neck pain is often chronic and disabling. Cervical facet joint injections and epidural steroid injections are frequently used to manage chronic neck pain and cervicogenic headaches. While minimal side effects are commonly associated with these treatments, severe complications are exceedingly rare. OBSERVATIONS The authors report 4 cases of iatrogenic neurological injury after radiofrequency ablation (RFA) and epidural steroid injections. One patient experienced left shoulder, scapular, and arm pain with left arm and hand weakness that developed immediately after RFA for chronic neck pain. Electromyography/nerve conduction velocity (EMG/NCV) studies confirmed denervation changes in the left C8–T1 distribution. Three patients complained of numbness and weakness of the hands immediately after an interlaminar cervical epidural block. One of these patients underwent EMG/NCV that confirmed denervation changes occurring in the left C8–T1 distribution. LESSONS Spine surgeons and pain management specialists should be aware of neurological injuries that may occur after cervical RFA and epidural steroid injections, especially after a multilevel cervical procedure and with severe cervical spinal stenosis. EMG/NCV studies plays an important role in detecting and localizing neurological injury and in differentiating from conditions that mimic cervical root injuries, including brachial plexus trauma due to positioning and Parsonage-Turner syndrome.

Background: Differentiating between neurogenic and vascular claudication may be difficult. Vascular claudication due to aortic and iliac artery occlusions may present as low back, hip, and buttock pain while walking short distances. These findings are often very similar to those seen for neurogenic claudication attributed to lumbar stenosis. Case Description: A 68-year-old female presented with low back, right hip, and groin pain while walking short distances. She had previously undergone lumbar and cardiac surgery. Now, with negative repeated lumbar studies, the CT angiogram (CTA) revealed a dense calcified plaque in the right common iliac artery resulting in 90% stenosis at its origin and Conclusion: Spine surgeons should be aware that vascular and neurogenic claudication may mimic each other. Obtaining MR studies of the lumbar spine and EMG/NCV, along with the appropriate vascular studies (CTAs), help differentiate between the two, and result in the appropriate operative choices.

BACKGROUND Hemangioblastomas are rare, slow-growing, and highly vascularized tumors that typically occur in the cerebellum and spinal cord. The cervical and thoracic regions are the most common spinal sites, and the tumors are usually intramedullary. OBSERVATIONS The authors report the case of a man whose chest computed tomography performed for managing coronavirus disease 2019 incidentally revealed an enhancing area in the spinal canal at T12–L1. The patient reported low back pain as well as leg numbness and tingling. Magnetic resonance imaging of the lumbar region with and without gadolinium contrast demonstrated an intradural, extramedullary lesion with displacement of the conus medullaris. The differential diagnosis included a schwannoma and myxopapillary ependymoma. Bilateral T12–L1 laminectomies were performed with resection of the mass. The general pathologist rendered the frozen section diagnosis of a spindle cell neoplasm, suggesting the differential diagnosis of schwannoma or myxopapillary ependymoma. Immunohistochemistry was positive for inhibin, GFAP, reticulin, CD31, SOX-10, S100, and EMA. A World Health Organization grade 1 hemangioblastoma was confirmed. LESSONS Spinal surgeons should be cognizant of the presenting symptoms and differential diagnosis of hemangioblastomas at the level of the conus medullaris, especially when the tumor is diagnosed incidentally. Additional investigations should be performed to determine whether von Hippel-Lindau syndrome is associated with the hemangioblastoma, as this combination portends a different clinical presentation, multiple tumor locations, and tumor recurrence following resection.

BACKGROUNDPerson-in-the-barrel syndrome is characterized by bilateral brachial diplegia, intact cranial nerves, and preserved lower-extremity strength. Most cases are due to bilateral supratentorial brain lesions at the border zone of the anterior and middle cerebral artery vascular territories. This condition has been observed with spinal pathology, primarily involving vascular dissection and thromboembolism.OBSERVATIONSThe authors’ case is the first in the literature to highlight person-in-the-barrel syndrome immediately following cervical spine surgery. Weakness of the deltoids, biceps, infraspinatus, and brachioradialis was observed bilaterally postoperatively. Electromyograph (EMG)-nerve conduction velocity (NCV) studies revealed a cervical radiculopathy involving C5 and C6 bilaterally with denervation of the deltoids, biceps, and brachioradialis. Within 8 months of cervical spine surgery, the patient regained improvement of the bilateral brachial diplegia.LESSONSEMG/NCV studies play a valuable role in detecting cervical radiculopathy after cervical spine surgery in patients with bilateral brachial diplegia. The authors postulate that this condition may have occurred following neck hyperextension during cervical cage placement, increasing the foraminal stenosis at C4–5 and C5–6 and worsening the C5 and C6 radiculopathy. Spinal surgeons should be cognizant of person-in-the-barrel syndrome that may ensue following cervical spine surgery and promptly identify and treat this condition to offer the best prognosis for a favorable patient outcome.

Background Useless hand syndrome (UHS) refers to clumsiness of complex finger movements and loss of manual dexterity due to cervical cord lesions, often associated with multiple sclerosis (MS). This condition may represent the first demyelinating event in MS or may occur in a patient with pre-existing MS. Methods We report 3 patients with UHS, 2 of whom had not been previously diagnosed with MS. The history and physical examinations, EMG/NCV studies of the arms, and radiological findings are presented. Results Presenting symptoms in all 3 cases included paresthesia and difficulty with manual dexterity which led the family physician to refer these patients to a hand surgeon. Pre-EMG neurological examination detected myriad abnormalities such as loss of position sense, two-point discrimination, stereognosis, graphesthesia, and difficulty performing rapid alternating movements. EMG/NCV findings were normal in 2 cases and, in the third case, showed abnormalities which did not explain the clinical picture and pointed to involvement of the central somatosensory pathways. Cervical MRIs revealed demyelinating lesions in all patients. Conclusion Patients with acute onset of sensory disturbance and clumsy hands are often first referred for EMG/NCV studies. Absence of significant abnormalities may suggest central somatosensory pathway dysfunction and should alert to the possibility of UHS and underlying MS.

Introduction: Preterm birth poses a significant challenge. This study evaluated a real-time scoring algorithm to identify and stratify pregnancies to indicate preterm birth. Methods: All claims data of pregnant women were reviewed between 1 January 2014 and 31 October 2018 in Kentucky. Results: A total of 29,166 unique women who were matched to a live newborn were documented, with the pregnancy identified during the first trimester in 54.1% of women. Negative predictive values, sensitivity, and positive likelihood ratios increased from the first to third trimesters as pregnant women who were matched to a live newborn had more visits with their physicians. The area under the receiving-operating characteristics curve on test data classifying preterm birth was 0.59 for pregnancies identified during the first trimester, 0.62 for pregnancies identified in the second trimester, and 0.73 for pregnancies identified in the third trimester. Conclusions: This study presents a real-time scoring algorithm of indicating preterm birth in the first trimester of gestation which permits stratification of pregnancies to provide more efficient early care management.

Locomotor function, mediated by lumbar neural circuitry, is modulated by descending spinal pathways. Spinal cord injury (SCI) interrupts descending projections and denervates lumbar motor neurons (MNs). We previously reported that retrogradely transported neurotrophin-3 (NT-3) to lumbar MNs attenuated SCI-induced lumbar MN dendritic atrophy and enabled functional recovery after a rostral thoracic contusion. Here we functionally dissected the role of descending neural pathways in response to NT-3-mediated recovery after a T9 contusive SCI in mice. We find that residual projections to lumbar MNs are required to produce leg movements after SCI. Next, we show that the spared descending propriospinal pathway, rather than other pathways (including the corticospinal, rubrospinal, serotonergic, and dopaminergic pathways), accounts for NT-3-enhanced recovery. Lastly, we show that NT-3 induced propriospino-MN circuit reorganization after the T9 contusion via promotion of dendritic regrowth rather than prevention of dendritic atrophy., Neurotrophin-3 (NT-3) plays a key role in the growth, development, and function of the nervous system. Here the authors show that NT-3-induced propriospino-motoneuron circuit reorganization is critical for locomotor recovery in mice following spinal cord injury.

The chemokine CXCL12 plays a vital role in regulating the development of the central nervous system (CNS) by binding to its receptors CXCR4 and CXCR7. Recent studies reported that the CXCL12/CXCR4/CXCR7 axis regulates both embryonic and adult oligodendrocyte precursor cells (OPCs) in their proliferation, migration, and differentiation. The changes in the expression and distribution of CXCL12 and its receptors are tightly associated with the pathological process of demyelination in multiple sclerosis (MS), suggesting that modulating the CXCL12/CXCR4/CXCR7 axis may benefit myelin repair by enhancing OPC recruitment and differentiation. This review aims to integrate the current findings of the CXCL12/CXCR4/CXCR7 signaling pathway in the CNS and to highlight its role in oligodendrocyte development and demyelinating diseases. Furthermore, this review provides potential therapeutic strategies for myelin repair by analyzing the relevance between the pathological changes and the regulatory roles of CXCL12/CXCR4/CXCR7 during MS.

After experiencing growth in a neuroscience service line, nurse leaders identified a need for increased competencies among clinical staff. This hospital met the need by developing a unique multidisciplinary neuroscience nursing course to improve the clinical competence, confidence, and professional development of bedside nurses.

BackgroundThe glial response in multiple sclerosis (MS), especially for recruitment and differentiation of oligodendrocyte progenitor cells (OPCs), predicts the success of remyelination of MS plaques and return of function. As a central player in neuroinflammation, activation and polarization of microglia/macrophages (M/M) that modulate the inflammatory niche and cytokine components in demyelination lesions may impact the OPC response and progression of demyelination and remyelination. However, the dynamic behaviors of M/M and OPCs during demyelination and spontaneous remyelination are poorly understood, and the complex role of neuroinflammation in the demyelination-remyelination process is not well known. In this study, we utilized two focal demyelination models with different dynamic patterns of M/M to investigate the correlation between M/M polarization and the demyelination-remyelination process.MethodsThe temporal and spatial features of M/M activation/polarization and OPC response in two focal demyelination models induced by lysolecithin (LPC) and lipopolysaccharide (LPS) were examined in mice. Detailed discrimination of morphology, sensorimotor function, diffusion tensor imaging (DTI), inflammation-relevant cytokines, and glial responses between these two models were analyzed at different phases.ResultsThe results show that LPC and LPS induced distinctive temporal and spatial lesion patterns. LPS produced diffuse demyelination lesions, with a delayed peak of demyelination and functional decline compared to LPC. Oligodendrocytes, astrocytes, and M/M were scattered throughout the LPS-induced demyelination lesions but were distributed in a layer-like pattern throughout the LPC-induced lesion. The specific M/M polarization was tightly correlated to the lesion pattern associated with balance beam function.ConclusionsThis study elaborated on the spatial and temporal features of neuroinflammation mediators and glial response during the demyelination-remyelination processes in two focal demyelination models. Specific M/M polarization is highly correlated to the demyelination-remyelination process probably via modulations of the inflammatory niche, cytokine components, and OPC response. These findings not only provide a basis for understanding the complex and dynamic glial phenotypes and behaviors but also reveal potential targets to promote/inhibit certain M/M phenotypes at the appropriate time for efficient remyelination.

Background: Spinal stenosis may result in myelopathy, radiculopathy, and neurogenic claudication. It is often difficult to differentiate between these conditions. A comprehensive history and physical examination and a magnetic resonance imaging (MRI) of the entire spine accurately confirm the diagnosis. Case Description: Here, we report a patient with low back and progressive bilateral lower extremity pain, numbness, and weakness with bowel incontinence, urinary retention, and gait abnormalities. A lumbar MRI demonstrated multilevel severe spondylosis/stenosis from L3-S1. The patient underwent a decompressive lumbar laminectomy from L3-5. However, the patient continued to experience the same symptoms postoperatively along with flexor spasms of the left leg, dystonic posturing of the left foot, hyperactive bilateral patellar and Achilles deep tendon reflexes, and a Babinski sign. An NCV of the legs revealed no lumbar radiculopathy. The thoracic MRI, however, demonstrated severe spondylosis at the T11-12 level attributed to a large synovial cyst. Following decompression/cyst resection, the patient’s symptoms partially resolved within 1 postoperative month. Conclusion: Spinal surgeons should be alert to the potential for overlapping symptoms/signs of thoracic myelopathy and lumbar myeloradiculopathy. If there are features of upper and lower motor neuron disease, MR scans of the entire spine are necessary before lumbar surgical decompression to identify significant cephalad surgical pathology.

Manipulation of developmentally regulated genes presents a promising strategy to enhance the intrinsic growth capability of adult neurons. Inhibitor of DNA binding 2 (Id2), a negative regulator of bHLH transcriptional factors, promotes axonal growth after its forced expression in post-mitotic neurons. Neurogenin2 (Ngn2) is a neural specific bHLH factor which controls neuronal fate and drives neuronal differentiation during development. In this study, we investigated the mechanism of Id2 in promoting axonal growth and revealed that Ngn2 contributed to the growth-activating role of Id2 in neurons. Ngn2 expression was upregulated with increased Id2 activity by assessing RNA and protein levels. Forced expression of Id2 or Ngn2 in cortical neurons significantly promoted axonal growth with little effect on dendrites. Furthermore, knockdown of Ngn2 impaired the axonal growth promoting effect of Id2, implying that the effect of Id2 on axonal growth depends on Ngn2. These findings suggest that elevation of neuronal Ngn2 may be a new therapeutic strategy to stimulate axonal regeneration.

Experimental contusion spinal cord injury (SCI) is the most frequently used in vivo model to provide insight into the mechanisms of secondary injury. Many criteria have been utilized to control the severity of SCI, including the height of the weight drop, the magnitude of the force striking the spinal cord, and the degree of spinal cord tissue displacement. The tissue displacement method is the most reliable technique of producing experimental SCI after the target spine has been stabilized. We have described the creation of a contusion SCI model using the LISA that is versatile and may be adapted for use in mice, rats, and monkeys with minor adjustments in the mechanical settings. Reproducible and reliable contusion SCI may be produced using this method of tissue displacement that may be characterized by gradable behavioral and morphological assessment.

Experimental laceration spinal cord injury (l-SCI) is an important in vivo model to investigate mechanisms of axonal regeneration and neurite plasticity following SCI. l-SCI is customarily performed freehand under visual guidance that results in variable lesion depths and shapes. In this chapter, a precise l- SCI model will be described for rodents using the Louisville Injury System Apparatus (LISA). This method incorporates: (1) reliable vertebral stabilization and spinal cord exposure and (2) accurate tissue laceration without contusion.

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome characterized by headaches, altered mental status, seizures, and visual disturbances. Classic MRI findings include white matter changes of the parieto-occipital regions. This syndrome has been encountered in myriad medical illnesses, including hypertension, preeclampsia/eclampsia, and immunosuppressive conditions. While the pathogenesis of the disorder is unclear, vasoconstriction and hypoperfusion leading to brain ischemia and vasogenic edema have been implicated as potential mechanisms. The authors present, to the best of their knowledge, the first case of PRES following a thoracic spinal surgery–induced dural leak noted on resection of the fifth rib during a thoracotomy for a T4–5 discectomy. Brain MRI revealed large areas of increased FLAIR and T2 hyperintensity in the superior posterior frontal lobes, superior and medial parietal lobes, and bilateral occipital lobes. Following repair of the CSF leak, the patient's symptoms resolved. Spinal surgeons should be alert to the potentially life-threatening condition of PRES, especially in a hypertensive patient who experiences surgery-induced dural leakage. The development of a severe positional headache with neurological signs is a red flag that suggests the presence of PRES. Prompt attention to the diagnosis and treatment of this condition by repairing the dural leak via surgery or expeditious blood patch increases the likelihood of a favorable outcome.

Most in vivo spinal cord injury (SCI) experimental models use rodents. Due to the anatomical and functional differences between rodents and humans, reliable large animal models, such as non-human primates, of SCI are critically needed to facilitate translation of laboratory discoveries to clinical applications. Here we report the establishment of a controlled spinal contusion model that produces severity-dependent functional and histological deficits in non-human primates. Six adult male rhesus macaque monkeys underwent mild to moderate contusive SCI using 1.0 and 1.5mm tissue displacement injuries at T9 or sham laminectomy (n=2/group). Multiple assessments including motor-evoked potential (MEP), somatosensory-evoked potential (SSEP), MR imaging, and monkey hindlimb score (MHS) were performed. Monkeys were sacrificed at 6 months post-injury, and the lesion area was examined for cavitation, axons, myelin, and astrocytic responses. The MHS demonstrated that both the 1.0 and 1.5mm displacement injuries created discriminative neurological deficits which were severity-dependent. The MEP response rate was depressed after a 1.0mm injury and was abolished after a 1.5mm injury. The SSEP response rate was slightly decreased following both the 1.0 and 1.5mm SCI. MRI imaging demonstrated an increase in T2 signal at the lesion site at 3 and 6months, and diffusion tensor imaging (DTI) tractography showed interrupted fiber tracts at the lesion site at 4h and at 6 months post-SCI. Histologically, severity-dependent spinal cord atrophy, axonal degeneration, and myelin loss were found after both injury severities. Notably, strong astrocytic gliosis was not observed at the lesion penumbra in the monkey. In summary, we describe the development of a clinically-relevant contusive SCI model that produces severity-dependent anatomical and functional deficits in non-human primates. Such a model may advance the translation of novel SCI repair strategies to the clinic.