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Background: Neurogenic detrusor overactivity (NDO) is a severe pathological condition characterized by involuntary detrusor contractions leading to urine leakage. This condition is frequent after spinal cord injury (SCI). Gene therapy for NDO requires the development of vectors that express therapeutic transgenes driven by sensory neuron-specific promoters. The aim of this study was to develop and assess tools for the characterization of sensory neuron-specific promoters in dorsal root ganglia (DRG) neurons after transduction with herpes simplex virus type 1 (HSV-1)-based amplicon defective vectors. Methods: The HSV-1 vector genome encoded two independent transcription cassettes: one expressed firefly luciferase (FLuc) driven by different promoters’ candidates (rTRPV1, rASIC3, rCGRP, or hCGRP), and the other expressed a reporter gene driven by an invariable promoter. The strength and selectivity of promoters was assessed in organotypic cultures of explanted adult DRG, or sympathetic and parasympathetic ganglia from control and SCI rats. Results: The rCGRP promoter induced selective expression in the DRG of normal rats. The rTRPV-1 promoter, which did not display selective activity in control rats, induced selective expression in DRG explanted from SCI rats. Conclusions: This study provides a methodology to assess sensory neuron-specific promoters, opening new perspectives for future gene therapy for NDO.

Significance Nanotechnology and neurobiology combined efforts might succeed in the design of hybrid microsystems that, once functionally integrated into the nervous tissue, might help in healing the injured spinal cord. A substantial challenge in this area is the development of structural scaffolds favoring spinal cord reconstruction. The future success of such smart devices resides also in the use of nanomaterials exploiting spinal microenvironment physical properties, such as mechanical and electrical ones, and their potential in promoting axonal regeneration. We synthesized an artificial scaffold based on nanomaterials with the necessary characteristics to guide axonal rewiring. The translational potential of introducing physics rules to neural tissue repair strategies was tested by implanting such a scaffold in spinal cord injury animal models., The regrowth of severed axons is fundamental to reestablish motor control after spinal-cord injury (SCI). Ongoing efforts to promote axonal regeneration after SCI have involved multiple strategies that have been only partially successful. Our study introduces an artificial carbon-nanotube based scaffold that, once implanted in SCI rats, improves motor function recovery. Confocal microscopy analysis plus fiber tracking by magnetic resonance imaging and neurotracer labeling of long-distance corticospinal axons suggest that recovery might be partly attributable to successful crossing of the lesion site by regenerating fibers. Since manipulating SCI microenvironment properties, such as mechanical and electrical ones, may promote biological responses, we propose this artificial scaffold as a prototype to exploit the physics governing spinal regenerative plasticity.

Nahezu alle Patienten mit Ruckenmarkschadigung (SCI) leiden unter einer neurogenen Blasenfunktionsstorung (nBFS). Eine unbehandelte BFS ist ein Risikofaktor fur eine Schadigung des Harntrakts, zudem kann sie die Lebensqualitat der Betroffenen massiv beeintrachtigen. Personen mit SCI benutzen oft komplementarmedizinische Therapien, besonders bei urologischen Problemen. Wir evaluierten, ob sich die urodynamischen Parameter bei Patienten, die eine homoopathische Therapie erhielten, signifikant veranderten. In einer retrospektiven Analyse wurden die urodynamischen Daten von Patienten mit SCI und nBFS, die an unserer Klinik eine homoopathische Behandlung erhielten, vor und unter Therapie evaluiert. Veranderungen der urologischen Therapie wurden miteinbezogen. Es wurden 35 homoopathisch behandelte Patienten (21 Manner, 14 Frauen, medianes Alter 46 Jahre; Paraplegie: n = 21; Tetraplegie: n = 14) identifiziert, bei denen urodynamische Messungen sowohl vor als auch unter Therapie vorlagen. Das Blasenmanagement erfolgte bei 20 Betroffenen mittels intermittierendem Katheterismus, bei 6 Patienten mittels Dauerkatheter und in 9 Fallen ohne Katheter. Beim Vergleich der urodyamischen Parameter ergaben sich fur das Gesamtkollektiv keine signifikanten Unterschiede zwischen den beiden Messzeitpunkten. Eine Veranderung der urologischen Therapie korrelierte mit einer signifikanten Verbesserung einiger urodynamischen Parameter. Da im Falle einer Befundverschlechterung unmittelbar eine urologische Intervention erfolgte, erwies sich ein retrospektives Studiendesign als nicht geeignet, mogliche Einflusse der homoopathischen Therapie auf urodynamische Parameter bei Patienten mit SCI zu detektieren. Eine prospektive randomisierte Studie ist daher unabdingbar.

Background The artery of Wollschlaeger and Wollschlaeger is a tentorial branch of the superior cerebellar artery that is usually not visualized on conventional cerebral angiography, unless it is pathologically enlarged. It can be recruited as part of the blood supply to tentorial dural arteriovenous fistulas (AVFs), although this occurs infrequently. Case Description Here we report the clinico-radiologic evaluation and treatment of a 48-year-old man referred to our institution for hitherto workup negative progressive, relapsing quadriparesis. This represents the first reported case of cervical myelopathy caused by venous congestion from a type V dural AVF supplied by the artery of Wollschlaeger and Wollschlaeger. Conclusions The anatomic discrepancy between the symptomatic spinal cord lesion and the etiologic intracranial fistula frequently results in delayed care in cases of myelopathy due to intracranial dural AVFs. Familiarity with these disorders and of their pathophysiologic mechanisms is important to avoid unnecessary diagnostic delays.

Spinal cord injury (SCI) is an untreatable neuropathology that causes severe disfunction and disability. Cell-based therapies hold neuroregenerative and neuroprotective potential and, although studied in SCI patients for more than two decades, long-term efficacy and safety remain unproven, and it is still debated which cell types result in higher functional recovery. This thesis comprises a comprehensive review of 100 SCI cell-based clinical trials, discussing its trends and critically analyzing their strengths and limitations. The type of cells used - olfactory ensheating cells (OECs), Schwann cells, macrophages, neural stem cells (NSCs) and other stem cells (SCs) derived from various tissues, including peripheral blood (PB) - were compared in terms of effectiveness, by using gold-standard efficacy outcome measures like the ASIA Impairment Scale (AIS). Most of the trials are in early phases of clinical development, involve patients with traumatic, chronic and complete injuries, and do not display a randomized comparative control arm. Bone marrow (BM-)SCs and OECs are the most used cells, and open surgery and injection the most common delivery methods. Amon the SCs, autologous PB-SCs transplants showed the highest percentage of patients with AIS improvement, while NSCs allotransplants (from human embryos/foetus) yielded the highest percentage of AIS improvement by 2 or more grades. Therefore, these cells may hold a promising potential for SCI cell therapy, but a standardization of the trials is needed to allow unbiased comparisons and draw more relevant conclusions. PB-SCs for autologous transplants are isolated within peripheral blood mononucleated cells (PBMCs). Further, NSC derived from induced-pluripotent stem cells (iPSCs), arising from reprogrammed PBMCs, could comprehend a safer and more easily-obtained NSC-based therapy. A pilot study was thus conducted on good practices for in vitro PBMCs culture, with the goal of implementing it in our lab and aiming to further explore them as a source of cells for SCI therapy. Blood samples from 3 healthy donors were used to optimize PBMCs’ isolation, expansion, and cryopreservation. A mean of 1.69x106 PBMCs could be isolated per mL of collected blood. When cultured in vitro for 7 days, PBMCs tend to decline in number but their metabolic activity increases in last days of culture. Hematopoietic SCs (CD45+/CD34+), a potential source for iPSCs, were slightly enriched. The best cryopreservation method was the one using 70% FBS. Overall, the implementation of PBMCs’ culture techniques was successful, but further studies with a bigger sample size need to be carried out to confirm these results. A lesão medular (LM) é uma neuropatologia intratável que causa disfunções e incapacidades graves. Terapias celulares possuem potencial neurorregenerativo e neuroprotetor e, embora estudadas em pacientes com LM há mais de duas décadas, a sua segurança e eficácia a longo prazo permanecem não comprovadas, e ainda se debate que tipos de células resultam em maior recuperação funcional. Uma revisão abrangente de 100 ensaios clínicos para LM baseados em células foi efetuada, discutindo tendências e analisando criticamente resultados e limitações. A eficácia das células usadas - olfactory ensheating cells (OECs), células de Schwann, macrófagos, células estaminais neurais (NSCs) e outas células estaminais (SC), derivadas de vários tecidos incluindo sangue periférico (PB) - foi comparada usando medidas de resultados de eficácia padrão, como a ‘ASIA Impairment Scale’ (AIS). A maioria dos ensaios encontra-se em fase I/II, não são controlados nem randomizados, e envolvem pacientes com lesões traumáticas, crónicas e completas. As OECs e SCs da medula óssea são as células mais utilizadas. Entre as SCs, transplantes autólogos de PB-SCs resultaram em maior percentagem de pacientes com melhoria na AIS, enquanto os alotransplantes de NSCs embrionárias geraram a maior percentagem de melhoria na AIS em 2 ou mais graus. Ambas estas células detêm um potencial promissor para a terapia celular de LM, mas será necessário padronizar os estudos clínicos futuros para tirar conclusões mais relevantes. PB-SCs para terapia autóloga são isoladas de células mononucleadas de sangue periférico (PBMCs). As PBMCs também podem ser reprogramados em células estaminais pluripotentes induzidas (iPSCs) e estas diferenciadas em NSCs, no que poderá vir a ser uma terapia de NSCs mais segura e fácil de obter. Um estudo piloto de boas práticas em cultura de PBMCs in vitro foi então conduzido de forma a implementar este protocolo no nosso laboratório para estudos futuros de terapia celular para LM. Amostras de sangue de 3 dadores saudáveis foram usadas para otimizar o isolamento, expansão e criopreservação de PBMCs. Foi possível isolar cerca de 1,69x106 PBMCs por mL de sangue recolhido. Quando cultivadas in vitro por 7 dias, o número de PBMCs diminui, embora a sua atividade metabólica aumente nos últimos dias. A subpopulação de SCs hematopoiéticas (CD45+/CD34+), uma potencial fonte de iPSCs, foi enriquecida. O melhor método de criopreservação correspondeu ao uso de 70% de FBS. No geral, a implementação das técnicas de cultura de PBMCs foi bem-sucedida, mas mais estudos com um tamanho amostral maior precisam de ser realizados para confirmar estes resultados. Mestrado em Biomedicina Molecular

A 76-year-old man was seen for a neurologic evaluation with concerns of progressive left lower extremity weakness. He had 2 lumbar spinal operations, the most recent being at age 68 years, and had a major motor vehicle accident with a pelvic fracture at age 67 years. He was documented to have new impairment in right ankle and distal lower extremity power after the operations and trauma. He began using a left-sided ankle-foot orthosis but used no other gait aid. Brain magnetic resonance imaging revealed 2 prominent and stable T2-signal hyperintensities in the frontal cerebral white matter, with some periventricular T2 hyperintensity with associated T1 hypointensity, and no gadolinium-enhancing lesions or posterior fossa lesions. Sagittal and axial magnetic resonance imaging of the thoracic spine showed an area of T2-signal abnormality without enhancement in the left hemicord at the T3 to T4 level. Nerve conduction studies and electromyography revealed a chronic right L5 radiculopathy without evidence of active denervation as the cause of the right lower motor neuron lower extremity weakness. He was diagnosed with progressive paucisclerotic multiple sclerosis with a primary progressive disease course. The use of ocrelizumab (anti-CD20) was considered initially. However, the exceedingly slow disease progression over many decades and the lack of new magnetic resonance imaging lesions or gadolinium-enhancing lesions, as well as his age, were taken into consideration, and conservative rehabilitation management was recommended instead. It is being increasingly recognized that the location of demyelinating disease lesions may be of crucial importance in the development of motor progression in multiple sclerosis. These critical demyelinating lesions are observed in patients with progressive unilateral hemiparetic impairment due to multiple sclerosis, in which unlimited lesion burden is allowable.

BACKGROUND Papillary tumors of the pineal region are highly unusual lesions of unknown incidence. These are neuroepithelial tumors with papillary and solid areas. There is no standardized treatment because of the difficulty to make randomized prospective trials due to its rarity. We report three patients with papillary tumor of the pineal region. MATERIAL AND METHODS Retrospective review of the clinical records of patients with papillary tumor of the pineal region at a tertiary neurological center in Buenos Aires, Argentina was done between 2/2012-04/2021. Clinical characteristics, imaging, pathology, treatment and follow-up data were obtained. RESULTS Two patients were male and one female. All three patients were adults, two in the fourth decade of life and one in the seventh. Clinical presentation included headache along with either visual symptoms, gait disturbance, or both. Imaging workup included brain and spinal magnetic resonance imaging, finding expanding lesions in the pineal region, hyperintense in FLAIR/T2 sequences, with gadolinium enhancement in T1 with contrast sequence and variable degrees of hydrocephalus. Spinal lesions were not found in these patients. Cerebrospinal fluid cytology was negative in all cases. Tumor biopsy was the initial approach in all cases. Two patients underwent an initial third ventriculostomy procedure but all were submitted to a supracerebellar infratentorial approach for major resection. Posterior treatment included chemoradiotherapy with temozolomide. One patient had a distant recurrence after seven years with and remained with stable disease for two more years, and the other two patients are under control with no recurrence after 2 and 2.5 years respectively. CONCLUSION Papillary tumors in the pineal regions are aggressively treated as recurrence is very frequent regarding previous reports (> 70%). Total resection is the only predictive factor associated to better outcome, however, more information is needed in order to achieve treatment consensus.

Study Design.A case series of dual time-point 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) for the diagnosis of spinal cord sarcoidosis.Objective.The aim of this study was to illustrate three cases of spinal sarcoidosis with occult presentation and subsequent identification with the use of dual time-point 18F-FDG PET/CT.Summary of Background Data.Sarcoidosis of the spinal cord is very rare and when it occurs without systemic manifestations of disease can be a challenging diagnostic dilemma frequently resulting in the need for spinal cord biopsy in order to establish a diagnosis.Methods.Case series presentation and report.Results.This manuscript presents a case series experience of dual time-point 18F-FDG PET/CT for the diagnosis of spinal cord sarcoidosis. We review the cases of three patients who presented with myelopathy and underwent 18F-FDG DTPI as part of the evaluation for enhancing spinal cord lesions of unknown etiology for 2 years at a university-based cancer hospital. 18F-FDG DTPI was vital in making the diagnosis of sarcoidosis, and in two of the cases, the patients were able to avoid biopsy, thereby avoiding potential morbidity from an invasive procedure.Conclusion.18F-FDG PET/CT imaging is a noninvasive imaging technique that can be crucial in the diagnosis of sarcoidosis of the spinal cord and help avoid unnecessary procedures.Level of Evidence: 4. © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Spinal imaging in multiple sclerosis remains challenging because of its small size and numerous artifacts. To compare 3D Phase-Sensitive Inversion Recovery (PSIR) to a conventional dataset of 3D Short Tau Inversion Recovery (STIR) and T2-weighted imaging at 3 Tesla to detect multiple sclerosis spinal cord lesions. This prospective single-center study was approved by a national research ethics board and included 54 patients (median age 44) enrolled from December 2016 to August 2018. Two neuroradiologists individually analyzed the two datasets separately and in random order. Discrepancies were resolved by consensus with a third neuroradiologist. The primary judgment criterion was the number of spinal cord lesions. Secondary judgment criteria included location of the lesions, reader-reported confidence and conspicuity assessed with the lesion-to-cord contrast ratio (LCCR). 3D PSIR detected significantly more lesions than the conventional dataset (371 versus 173, respectively, p

Aberrant migration of Spirocerca lupi into the spinal cord is an important cause of severe progressive neurological dysfunction in dogs. Although early diagnosis is essential to prevent deterioration, ante-mortem diagnosis of this condition remains challenging. The aim of this study was to evaluate the detection of the 18S ribosomal DNA (rDNA) S. lupi gene in the cerebrospinal fluid (CSF) of presumptively-affected dogs using polymerase chain reaction (PCR). Dogs with a non-compressive spinal cord lesion, pleocytosis with presence of eosinophils in the CSF and a characteristic clinical presentation were included. CSF samples from eight dogs were available for the study, of which seven were definitively diagnosed with intraspinal spirocercosis by PCR of either the CSF samples (6/7) or tissue samples obtained at necropsy examination (3/7), or both (2/7). Of these seven positive cases, only one dog had a negative CSF PCR, indicating a sensitivity of 86% for detecting nematode DNA in the CSF of infected dogs using this PCR protocol. The nematode DNA sequences obtained from the CSF of six dogs and the spinal cord tissue of three dogs were 98-100% identical to the publicly available sequences of S. lupi, confirming the diagnosis. These findings indicate that PCR targeting the 18S rDNA of S. lupi in CSF is useful for the ante-mortem diagnosis of canine intraspinal spirocercosis.

Primary central nervous system vasculitis (PCNSV) is an uncommon vasculitis restricted to the small- and medium-sized vessels in the brain and spinal cord. Previously, only 9 cases have been reported that initially manifested as an isolated spinal cord lesion with subsequent brain involvement, where the longest interval from the onset to brain involvement was 1 year and 11 months. We herein report the case of an isolated spinal cord lesion with subsequent brain involvement appearing seven years and five months later. This case shows that brain lesions can develop after an extended interval from spinal onset in PCNSV.

AIMS Antimuscarinic drugs are the first-line choice in the treatment of patients with neurogenic Detrusor Overactivity (nDO). Fesoterodine fumarate is the newest antimuscarinic drug. Limited data are published about the use of fesoterodine fumarate in patients suffering from neurogenic lower urinary tract dysfunction. Our study aims to determine the efficacy of fesoterodine fumarate on patients with nDO due to spinal cord lesion or multiple sclerosis (MS). METHODS This is an open-label prospective interventional study. Eligible patients were 18-80 years old with SCL or MS and nDO confirmed by a urodynamic study (UDS). At baseline, patients underwent a UDS to confirm nDO. Quality of life (QoL) was assessed by the Short-Form (SF) Qualiveen questionnaire. Patients received fesoterodine 8 mg/day for 3 months and were re-evaluated with UDS and SF-Qualiveen. The primary endpoint was the confirmation of the maximum detrusor pressure (Pdetmax ) reduction after treatment. Secondary endpoints were: evaluation of maximum bladder capacity and compliance and QoL effect. Statistical analysis included Wilcoxon-test using SPSSv26. RESULTS One hundred and twenty-four patients completed the study. Ninety-five of them (76.6%) had SCL, while 29 (23.4%) had MS. Pdetmax , maximum bladder capacity, and compliance had significant reduction after treatment (p

The present review discusses recent data regarding rodent models of spinal cord and peripheral nerve injuries in terms of gait analysis using the CatWalk system (CW), an automated and exceptionally reliable system for assessing gait abnormalities and motor coordination. CW is a good tool for both studying improvements in the walking of animals after suffering a peripheral nerve and spinal cord lesion and to select the best therapies and procedures after tissue destruction, given that it provides objective and quantifiable data. Most studies using CW for gait analysis that were published in recent years focus on injuries inflicted in the peripheral nerve, spinal cord, and brain. CW has been used in the assessment of rodent motor function through high-resolution videos, whereby specialized software was used to measure several aspects of the animal’s gait, and the main characteristics of the automated system are presented here. CW was developed to assess footfall and gait changes, and it can calculate many parameters based on footprints and time. However, given the multitude of parameters, it is necessary to evaluate which are the most important under the employed experimental circumstances. By selecting appropriate animal models and evaluating peripheral nerve and spinal cord lesion regeneration using standardized methods, suggestions for new therapies can be provided, which represents the translation of this methodology into clinical application.

The spinal cord contains a diverse array of sensory and motor circuits that are essential for normal function. Spinal cord injury (SCI) permanently disrupts neural circuits through initial mechanical damage, as well as a cascade of secondary injury events that further expand the spinal cord lesion, resulting in permanent paralysis. Tissue clearing and 3D imaging have recently emerged as promising techniques to improve our understanding of the complex neural circuitry of the spinal cord and the changes that result from damage due to SCI. However, the application of this technology for studying the intact and injured spinal cord remains limited. Here, we optimized the passive CLARITY technique (PACT) to obtain gentle and efficient clearing of the murine spinal cord without the need for specialized equipment. We demonstrate that PACT clearing enables 3D imaging of multiple fluorescent labels in the spinal cord to assess molecularly defined neuronal populations, acute inflammation, long-term tissue damage, and cell transplantation. Collectively, these procedures provide a framework for expanding the utility of tissue clearing to enhance the study of spinal cord neural circuits, as well as cellular- and tissue-level changes that occur following SCI.

Acute non-traumatic paraparesis is usually caused by vascular, inflammatory or neoplastic myelopathies; however, it is sometimes caused by non-myelopathic pathologies, including polyradiculoneuropathies, myopathies, psychogenic aetiologies or parasagittal cortical pathologies. A 73-year-old woman reported weakness of the bilateral lower limbs and urinary incontinence. Together with the sensory level at the left T6 dermatome, we initially considered thoracic myelopathy as the most likely diagnosis. However, MRI of the cervicothoracic cord was negative and subsequent cranial CT revealed a bilateral subdural haematoma. A parasagittal cortical pathology should not be excluded from differential diagnoses as a rare cause of paraparesis until its possibility is carefully ruled out.

The spinal cord contains a diverse array of sensory and motor circuits that are essential for normal function. Spinal cord injury (SCI) permanently disrupts neural circuits through initial mechanical damage, as well as a cascade of secondary injury events that further expand the spinal cord lesion, resulting in permanent paralysis. Tissue clearing and 3D imaging have recently emerged as promising techniques to improve our understanding of the complex neural circuitry of the spinal cord and the changes that result from damage due to SCI. However, the application of this technology for studying the intact and injured spinal cord remains limited. Here we optimized the passive CLARITY technique (PACT) to obtain gentle and efficient clearing of the murine spinal cord without the need for specialized equipment. We demonstrate that PACT clearing enables 3D imaging of multiple fluorescent labels in the spinal cord to assess molecularly defined neuronal populations, acute inflammation, long-term tissue damage, and cell transplantation. Collectively, these procedures provide a framework for expanding the utility of tissue clearing to enhance the study of spinal cord neural circuits, as well as cellular- and tissue-level changes that occur following SCI.

A 36-year-old woman presented with a subacute, relapsing myelitis, manifesting as bilateral ascending lower limb paraesthesia, partially responsive to steroids. Imaging demonstrated a longitudinal spinal cord lesion, with a unique and characteristic sign (the 'trident sign') on axial views, which is specific to a diagnosis of neurosarcoidosis. This case highlights the importance of using this feature to distinguish a longitudinal cord lesion of sarcoidosis from other differentials.

A 63-year-old man was admitted to our hospital with a 2-month history of anxiety. He presented with cognitive impairment and muscle weakness. On MRI, T2-weighted images showed longitudinally extensive spinal cord lesion (LESCL) from C2 to T6 and gadolinium-enhanced T1-weighted images showed fan-shaped multiple linear enhancements converging to the lateral ventricles. He was diagnosed as primary central nervous system vasculitis (PCNSV) by brain biopsy. After using high dose corticosteroids, cognitive impairment and muscle weakness were dramatically improved. In patients with cognitive impairment, PCNSV should be included in the differential diagnosis of LESCL.

Previous studies have shown that epidural stimulation of the lumbosacral spinal cord (scES) can re-enable lower limb volitional motor control in individuals with chronic, clinically motor complete spinal cord injury (SCI). This observation entails that residual supraspinal connectivity to the lumbosacral spinal circuitry still persisted after SCI, although it was non-detectable when scES was not provided. In the present study, we aimed at exploring further the mechanisms underlying scES-promoted recovery of volitional lower limb motor control by investigating neuroimaging markers at the spinal cord lesion site via magnetic resonance imaging (MRI). Spinal cord MRI was collected prior to epidural stimulator implantation in 13 individuals with chronic, clinically motor complete SCI, and the spared tissue of specific regions of the spinal cord (anterior, posterior, right, left, and total cord) was assessed. After epidural stimulator implantation, and prior to any training, volitional motor control was evaluated during left and right lower limb flexion and ankle dorsiflexion attempts. The ability to generate force exertion and movement was not correlated to any neuroimaging marker. On the other hand, spared tissue of specific cord regions significantly and importantly correlated with some aspects of motor control that include activation amplitude of antagonist (negative correlation) muscles during left ankle dorsiflexion, and electromyographic coordination patterns during right lower limb flexion. The fact that amount and location of spared spinal cord tissue at the lesion site were not related to the ability to generate volitional lower limb movements may suggest that supraspinal inputs through spared spinal cord regions that differ across individuals can result in the generation of lower limb volitional motor output prior to any training when epidural stimulation is provided.

Up to 500,000 people worldwide suffer from spinal cord injuries (SCI) annually, according to the WHO. Animal models are essential for searching novel methodological guidelines and therapeutic agents for SCI treatment. We developed an original model of posttraumatic spinal cord glial scar in rats using cryoapplication. The method is based on cryodestruction of spinal cord tissue with liquid nitrogen. Thirty six male SD linear rats of SPF category were included in this experimental study. A T13 unilateral hemilaminectomy was performed with an operating microscope, as it was extremely important not to penetrate the dura mater, and liquid nitrogen was applied into the bone defect for one minute. The animals were euthanized at various intervals ranging from 1 to 60 days after inducing cryogenic trauma, their Th12-L1 vertebrae were removed “en bloc” and the segment of the spinal cord exposed to the cryoapplicator was carefully separated for histological examination. The study results demonstrated that cryoapplication of liquid nitrogen, provoking a local temperature of approximately minus 20°C, produced a highly standardized transmural defect which extended throughout the dorsoventral arrangement of the spinal cord and had an “hour-glass” shape. During the entire study period (1-60 post-injury days), the glial scarring process and the spinal cord defect were located within the surgically approached vertebral space (Th13). Unlike other available experimental models of SCI (compression, contusion, chemical, etc.), the present option is characterized by a minimal invasiveness (the hemilaminectomy is less than 1 mm wide), high precision and consistency. Also, there was a low interanimal variability in histological lesions and dimensions of the produced defect. The original design of cryoapplicator used in the study played a major role in achieving these results. The original technique of high-precision cryoapplication for inducing consistent morphodynamic glial scarring could facilitate a better understanding of the self-recovery processes of injured spinal cord and would be helpful for proposing new platforms for the development of therapeutic strategies.

Previous evidence from electrophysiological experiments in anaesthetized cats with a chronic lateral lesion of the lower thoracic spinal cord indicated an expansion of the functional projections of expiratory bulbospinal neurones (EBSNs) in the segment above the lesion, measured at 16 weeks post-lesion. Here we investigate connections made by the same EBSNs to motoneurones in that segment, using cross-correlations between their discharges. The connections to the internal intercostal nerve motoneurones were found to be no different from controls. However, a significant increase was found in the number of connections between EBSNs and γ motoneurones of the external intercostal nerve (8/24, compared to 1/16) with possibly additional connections to the α motoneurones of the same nerve. Increased connections to the γ motoneurones of the internal intercostal nerve could not be ruled out. The expanded functional projections are thus likely to include new connections to γ motoneurones. We suggest that γ motoneurones may be inherently more receptive to new inputs. If so, the previously discounted role of abnormal fusimotor discharges in motor disorders would be worth reconsideration.

Objective: To validate the recently proposed imaging criteria in distinguishing aquaporin-4 antibody (AQP4-ab)-seropositive neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disorder (MOG-AD) at disease onset in a Chinese population. Methods: We enrolled 241 patients in this retrospective study, including 143 AQP4-ab-seropositive NMOSD, 73 MS, and 25 MOG-AD. Cacciaguerra’s criteria were described as fulfillment of at least 2/5 conditions including the absence of the combined juxtacortical/cortical lesions, the presence of longitudinal extensive transverse myelitis (LETM) lesions, the presence of periependymal-lateral ventricles lesions, the absence of Dawson’s fingers lesions, and the absence of periventricular lesions. Results: Fulfillment of at least 3/5 conditions was able to differentiate NMOSD from MS with a good diagnostic performance (accuracy = 0.92, sensitivity = 0.91, specificity = 0.93), yet failed to differentiate NMOSD from MOG-AD. LETM lesions showed the highest accuracy (0.78), sensitivity (0.70), and specificity (0.97) for NMSOD. Conclusion: Our research suggested the utility of Cacciaguerra’s criteria in a Chinese population at disease onset. A better diagnostic performance in NMOSD could be attained with at least 3/5 conditions fulfilled. Yet their utility in distinguishing NMOSD from MOG-AD was limited.

Background and Aims Bladder dysfunction is an important cause of chronic kidney disease (CKD) due to neurogenic causes such as a spinal lesion (SL), Hinman's syndrome, or non-neurogenic neurogenic bladder (NNNB), and valve bladder syndrome (VBS). In this study, we evaluated the outcomes of neurogenic bladder caused by different etiologies. Method Single-center retrospective study of children with neurogenic bladder (NB) over 13 years (2005-2017). Results Totally, 199 children (134 boys, 67.3%) were included and divided into three groups: Group 1 (75, NNNB), Group 2 (64, SL), and Group 3 (60, VBS). Urodynamic examination revealed impaired bladder capacity in 49 children (57.6%), atonic bladder in 1 child (1.1%), and normal bladder compliance in 35 children (41.1%). Additionally, 113 children (56.8%) experienced clean intermittent catheterization (CIC). A significant improvement in the mean estimated glomerular filtration rate and CKD stages was observed among the three studied groups, but the NNNB group showed the least improvement. Children diagnosed and treated during their first year of life had better outcomes than those who presented at a later age. CIC without the need for surgical intervention was associated with improved renal function. Pyelonephritis and hydronephrosis had significant negative impacts on kidney function Conclusion Early diagnosis and management of NB in infancy are associated with better outcome and preservation of renal function. CIC is associated with better preservation of kidney function, while vesicostomy is associated with a worse outcome. Children with NB caused by SL experienced the best kidney function preservation, while those with VBS experienced the worst.

espanolIntroduccion. La rehabilitacion de las lesiones medulares (LM) busca la reinsercion social de las personas afectadas y evalua sus limitaciones segun el grado de discapacidad. Objetivo. Determinar el efecto del programa de rehabilitacion en la calidad de vida de personas con lesion medular. Metodos. Estudio analitico, observacional, prospectivo y longitudinal. Participaron personas con diagnostico de lesion medular completa e incompleta de nivel cuadriplejico y paraplejico, masculino y femenino, entre 14 y 80 anos, de etiologia traumatica y no traumatica, y tiempo evolucion menor de 10 anos. Resultados. Se seleccionaron 65 personas como muestra censal que estuvieron hospitalizados en el periodo enero-junio 2017. La caracteristica clinica mas frecuentes fueron el nivel paraplejico ASIA A con el 30,8%, de etiologia traumatica con el 72,3% y con tiempo de evolucion mayor de 3 anos en el 40%. Se encontraron diferencias entre la calidad de vida inicial y final de los componentes fisico y mental (p=0,001). Todas las escalas de los componentes fisico y mental de la calidad de vida de inicio y fin tambien fueron significativas (p=0,001).Conclusiones. La calidad de vida en los componentes fisico y mental mejoro en las personas con lesion medular al termino de la rehabilitacion. Hubo cambios positivos de la calidad de vida en el componente mental en el nivel paraplejico y de etiologia no traumatica; en las personas lesion medular incompleta ASIA C, tambien se encontro cambios de la calidad de vida en el componente fisico. EnglishIntroduction. The rehabilitation of spinal injuries (LM) seeks the social reintegration of the affected people, and assesses their limitations according to the degree of disability. Objective. To determine the effect of a rehabilitation program on quality of life of people with spinal cord injury. Methods. An analytical, observational, prospective and longitudinal study. People with a diagnosis of complete and incomplete spinal cord lesion at the quadriplegic and paraplegic level, male and female, between 14 and 80 years old, of traumatic and non-traumatic etiology and evolution time of less than 10 years were selected. Results. 65 people were selected as census sample who were hospitalized in the period january-june 2017. The most frequent clinical characteristics were the ASIA A paraplegic level with 30,8%, traumatic etiology with 72,3% and a time of evolution greater than 3 years, in 40%. Initial and final quality of life of the physical and mental components were found to be significant (p=0,001), all scales of the physical and mental components of the quality of life at the beginning and end were also significant (p=0,001). Conclusions. An improvement of quality of life, in physical and mental components, were founded in people with spinal cord injury at the end of the rehabilitation. There were positive changes in the quality of life in the mental component at the paraplegic level and in nontraumatic etiology. Changes in quality of life in the physical component were also found in people with incomplete spinal cord injury ASIA C.

Fracture and migration of metal implants is a well-known issue which is especially relevant for actively loaded zones with a high amplitude of physiological movements. The authors analyzed 17 publications dedicated to Kirschner wire migration into the spinal canal after fixation of acromioclavicular joint (ACJ) injury. The present paper contains literature review and own clinical case of the authors. The authors generalize the conceptions of migration causes, surgical tactics and prevention recommendations. The key reason of fracture and migration of Kirschner wires during fixation of ACJ injury is the instability of implants, trans-articular wire insertion during fixation of reduced dislocation of acromial end of the clavicle, insufficient immobilization and untimely implants removal after removal of immobilization. Implants migration into the spinal canal is the indication for their surgical removal irrespective of clinical signs. In the majority of studied publications authors described posterior approach or lateral approach aligned with the migration direction. No grafting techniques for dura mater defects were present in the studied literature. The authors of the current paper justify a surgical procedure for removal of migrated implant using a combined posterior and lateral approach on the own clinical case. The choice of procedure algorithm results from the need for prophylaxis of secondary spinal cord lesion and liquorrhea during removal of migrated implants from spinal canal.

Despite efforts to potentiate spinal cord lesioned (SCL) patients' functional recovery with multi-targeted therapy combining pharmacological treatment and training, consistent improvements in locomotor control by descending transmission or spinal network facilitation are still eluding clinicians and researchers. Lately, United States Food and Drug Administration-approved buspirone has shown promise and promoted locomotor-like movement occurrence in SCL patients, but evidence on how and where it exerts its effects is lacking. The objective of the present study was, first, to verify buspirone effect on locomotor spinal network and to evaluate if it promoted functional recovery when combined with training. Also, we evaluated buspirone impact on locomotion in mice that had recovered from a previous hemisection before sustaining the spinal transection. This dual lesion paradigm has allowed confirmation of spinal network involvement in recovery after an incomplete SCL. Buspirone acutely increased the number of steps taken, the coupling strength between hindlimbs, angular excursion of the hip joint during locomotion, and improved paw positioning at contact and paw drag (ps 0.05). Moreover, it induced long-lasting improvements of paw positioning at contact and paw drag when combined with training in mice after a dual lesion paradigm. Altogether, the results indicate that buspirone exerts considerable acute facilitation of spinally mediated locomotion, and could be used in combination with training to promote functional recovery after SCL.

Spinal cord lesion site is mainly localised through correct performance and interpretation of a full neurological examination. Decreased or absent spinal reflexes localises the lesion within that reflex arc (low motor neuron), while intact or increased spinal reflexes indicates a lesion cranial to the reflex arc (upper motor neuron). In acute and severe spinal cord injury, lesion localisation may be compromised by the presence of spinal shock, because in individuals with spinal shock, the clinical presentation shows discrepancy between spinal reflexes and lesion localisation, with loss of segmental spinal reflexes caudally to a lesion, although the intumescence may remain intact. Lack of recognition of spinal shock in these patients could lead to erroneous clinical localisation of the lesion, inappropriate utilisation of diagnostic tests and incorrect reporting of patient prognosis to the owner.

Background Threshold values for total nucleated cell count (TNCC) and protein concentration in cerebrospinal fluid (CSF) of downer dairy cows suggestive of a spinal cord lesion were recently published. Objectives Determine short‐ and long‐term survival of downer cows that underwent CSF analysis using the reported threshold values. Evaluate the prognostic value of these threshold values to predict short‐ and long‐term survival. Animals Two hundred and fourteen downer adult dairy cows that underwent CSF analysis during hospitalization at the Centre Hospitalier Universitaire Vétérinaire (CHUV) of the Université de Montréal. Methods Retrospective study. Medical records of downer adult dairy cows presented to the hospital between January 2006 and October 2014 for which CSF analysis results were available were studied. Short‐term (discharge from hospital) and long‐term (completion of lactation) survival were determined and compared in accordance with CSF TNCC and protein concentration, using a Chi‐square test. Results Cows with CSF TNCC and/or protein concentration above the threshold values had a significantly lower short‐term survival rate (P = .02). The odds of nonsurvival of cows with one or both CSF values above the threshold values was 2.16 times higher than the odds for cows with values under the threshold values. CSF TNCC >4.5 cells/μL had sensitivity and specificity of 17.3% (95% CI: 10.7%‐25.7%) and 92.3% (95% CI: 85.4%‐96.6%), respectively, for predicting short‐term nonsurvival. CSF protein concentration >0.39 g/L had sensitivity and specificity of 20.9% (95% CI: 13.7%‐29.7%) and 91.4% (95% CI: 84.2%‐96.0%), respectively. Conclusions CSF analysis above threshold values used in this study is associated with increased odds of short‐term nonsurvival.

Charles Edward Beevor (1854–1908) was a prominent English neurologist who served in a variety of positions at the National Hospital for the Paralysed and Epileptic, Queen Square, from 1883 until his sudden death due to coronary artery disease in 1908. Staunchly committed to the meticulous study of neuroanatomy and physiology and education of his fellow physicians, Beevor was an accomplished clinician-scientist. He is most well known for describing the Beevor sign (commonly known as “Beevor's sign”), which is the upward movement of the umbilicus with truncal flexion from a supine position, used to indicate a spinal cord lesion between the levels of T10 and T12. His sign has also been reported to be suggestive of facioscapulohumeral muscular dystrophy. While the initial description of the Beevor sign has traditionally been attributed to his 1903 Croonian Lectures, he actually first described his sign in his 1898 textbook Diseases of the Nervous System: A Handbook for Students and Practitioners. In addition to his eponymous sign, Beevor also made significant contributions to the understanding of the representation of motor movements in the cerebral cortex, and, of more importance, utilized a novel method to identify cerebral vascular territory maps that are still utilized by neurologists today.

Leptomeningeal carcinomatosis (LC) diagnosis is based on cerebrospinal fluid (CSF) cytological analysis and contrast-enhanced magnetic resonance imaging (MRI); however, low sensitivity was evidenced in some cases delaying prompt and adequate treatments. Brain 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) was also employed in doubtful cases. We retrospectively described 4 suspected LC cases with uncertain or undetectable MRI and initially negative CSF cytology. Whole-body (WB) and brain 18F-FDG PET/computed tomography (CT) were used, the latter showing intracranial tracer uptakes suspected for LC in 3/4 cases. In 2 of these 3 cases, WB scan also evidenced spinal cord lesion and pulmonary tumor, respectively, while both procedures were true negative in the fourth case. CSF cytology became positive after repeated exams in the 3 PET/CT-positive cases. In 1 of these 3 patients, it was also confirmed at MRI, while it stayed negative in the remaining PET/CT-negative case with uncertain MRI. 18F-FDG PET/CT could be a useful supportive diagnostic tool in doubtful intracranial and spinal LC.

The purpose of the present study was to establish an effective robotic assistive stepping pattern of body-weight-supported treadmill training based on a rat spinal cord injury (SCI) model and assess the effect by comparing this with another frequently used assistive stepping pattern. The recorded stepping patterns of both hind limbs of trained intact rats were edited to establish a 30-sec playback normal rat stepping pattern (NRSP). Step features (step length, step height, step number and swing duration), BBB scores, latencies, and amplitudes of the transcranial electrical motor-evoked potentials (tceMEPs) and neurofilament 200 (NF200) expression in the spinal cord lesion area during and after 3 weeks of body-weight-supported treadmill training (BWSTT) were compared in rats with spinal contusion receiving NRSP assistance (NRSPA) and those that received manual assistance (MA). Hind limb stepping performance among rats receiving NRSPA during BWSTT was greater than that among rats receiving MA in terms of longer step length, taller step height, and longer swing duration. Furthermore a higher BBB score was also indicated. The rats in the NRSPA group achieved superior results in the tceMEPs assessment and greater NF200 expression in the spinal cord lesion area compared with the rats in the MA group. These findings suggest NRSPA was an effective assistive pattern of treadmill training compared with MA based on the rat SCI model and this approach could be used as a new platform for animal experiments for better understanding the mechanisms of SCI rehabilitation.

Background Spinal cord and brain stem lesions require a judicious approach with an optimized trajectory due to a clustering of functions on their surfaces. Intraoperative mapping helps locate function. To confidently locate such lesions, neuronavigation alone lacks the desired accuracy and is of limited use in the spinal cord. Objective To evaluate the clinical value of fluoresceins for initial delineation of such critically located lesions. Methods We evaluated fluorescein guidance in the surgical resection of lesions with blood-brain barrier disruption demonstrating contrast enhancement in magnet resonance imaging in the spinal cord and in the brain stem in 3 different patients. Two patients harbored a diffuse cervical and thoracic spinal cord lesion, respectively. Another patient suffered metastatic lesions in the brain stem and at the floor of the fourth ventricle. Low-dose fluorescein (4 mg/kg body weight) was applied after anesthesia induction and visualized using the Zeiss Pentero 900 Yellow560 filter (Carl Zeiss, Oberkochen, Germany). Results Fluorescein was helpful for locating lesions and for defining the best possible trajectory. During resection, however, we found unspecific propagation of fluorescein within the brain stem up to 6 mm within 3 h after application. As these lesions were otherwise distinguishable from surrounding tissue, monitoring resection was not an issue. Conclusion Fluorescein guidance is a feasible tool for defining surgical entry zones when aiming for surgical removal of spinal cord and brain stem lesions. Unselective fluorescein extravasation cautions against using such methodology for monitoring completeness of resection. Providing the right timing, a window of pseudoselectivity could increase fluoresceins' clinical value in these cases.

Psychometric study. The objective of this study was to examine the reliability of the Spinal Cord Independence Measure III (SCIM III) by interview and compare the findings with those of assessment by observation. This study was conducted at Loewenstein Rehabilitation Hospital, Israel. Thirty-five spinal cord lesion (SCL) patients who underwent rehabilitation at Loewenstein Rehabilitation Hospital in Israel were assessed during the last week before discharge with SCIM III by observation and by interview. Nineteen of the patients were also assessed by interview by a third rater to examine inter-rater reliability. Total agreement, kappa, Bland–Altman plots and intraclass correlation (ICC) were used for comparison between interviewers and between interviews and observations. Total agreement between the interviewers' scores and between interviews and observations was low to moderate (kappa coefficient 0.11–0.80). Bland–Altman analysis revealed good agreement, with low mean difference for almost all SCIM III subscales and total scores, between pairs of interviewers (bias −4.15, limits of agreement −22.51 to 14.19, for total score) and between interviews and observations (bias 1.62, limits of agreement −20.55 to 23.81, for total score). ICC coefficients for the SCIM III subscales and total scores were high (0.637–0.916). The findings of this study support the reliability and validity of SCIM III by interview, which appears to be useful for research of SCL patient groups. Individual scoring of SCIM III by interview, however, varied prominently between raters. Therefore, SCIM III by interview should be used with caution for clinical purposes, probably by raters whose scoring deviation, in relation to observation scores, is known.

Background. Previous studies have demonstrated the presence of intact axons across a spinal cord lesion, even in those clinically diagnosed with complete spinal cord injury (SCI). These axons may allow volitional motor signals to be transmitted through the injury, even in the absence of visible muscle contraction. Objective. To demonstrate the presence of volitional electromyographic (EMG) activity below the lesion in motor complete SCI and to characterize this activity to determine its value for potential use as a neuroprosthetic command source. Methods. Twenty-four subjects with complete (AIS A or B), chronic, cervical SCI were tested for the presence of volitional below-injury EMG activity. Surface electrodes recorded from 8 to 12 locations of each lower limb, while participants were asked to attempt specific movements of the lower extremity in response to visual and audio cues. EMG trials were ranked through visual inspection, and were scored using an amplitude threshold algorithm to identify channels of interest with volitional motor unit activity. Results. Significant below-injury muscle activity was identified through visual inspection in 16 of 24 participants, and visual inspection rankings were well correlated to the algorithm scoring. Conclusions. The surface EMG protocol utilized here is relatively simple and noninvasive, ideal for a clinical screening tool. The majority of subjects tested were able to produce a volitional EMG signal below their injury level, and the algorithm developed allows automatic identification of signals of interest. The presence of this volitional activity in the lower extremity could provide an innovative new command signal source for implanted neuroprostheses or other assistive technology.

Spinal adhesive arachnoiditis (SAA) is a rare, but often devastating, cause of compressive myelopathy. We report a patient with SAA resulting in a longitudinally extensive T2-hyperintense spinal cord lesion with initial nodular pial and dural enhancement mimicking neurosarcoidosis. Neurologists should be aware of this entity, especially in patients who have pertinent risk factors, such as prior meningitis, spinal cord trauma, or surgery.

Title Case Study of Physiotherapy Treatment of a Patient with Paraparesis Aim of the thesis The theoretical part brings general outlook and detailed information about diagnose of spinal cord injury. Practical part overviews a study case of a patient with traumatic spinal cord injury resulting in paraparesis. The study includes outcome and effect of the applied therapy. Method The protocol is based on two weeks therapeutical plan that was based on initial kinesiological examination. Therapy included maximal number of most appropriate techniques to reach maximal result of improvement. Result After two weeks of intensive rehabilitation patient showed a signs of improvement. Nevertheless, patient is 10 months after injury with slow progress of improvement. Two weeks is short time for significant improvement. The results were recorded not quantitatively according to standard testing, but the quality of the movement, fluency, comfort and the dexterity which patient obtained in this two weeks, are the main positive results. Keywords Paraparesis, Paraplegia, Spinal Cord Injury, Spinal Cord Lesion

In this study, we evaluated the ability of stretch-grown tissue-engineered nerve grafts (TENGs) to perform as a living scaffold for axonal regeneration across a severed spinal cord lesion. TENGs, consisting of stretch-grown axons spanning two populations of dorsal root ganglia neurons, have proven to be effective in bridging gaps in peripheral nerve injury. A complete transection was performed at the thoracic level in a rodent model and 5 mm of cord was completely removed. TENGs encapsulated in a collagen hydrogel were placed within the cavity and compared against a collagen only transplant. Through hematoxylin and eosin (HE) staining and immunohistochemistry, we found that TENGs survived up to 6 weeks post-transplant, extending neuronal processes into and through host tissue early on in both the rostral and caudal direction. In several cases, TENG axons penetrated into and through glial scar tissue, appearing to overcome a common obstacle for axonal regeneration in spinal cord injuries (SCIs). HE staining also provided evidence that animals treated with TENGs resulted in lesion sites with greater tissue infiltration and less compression than animals treated with a collagen hydrogel only, an encouraging finding given the severity of the injury model. We also observed effects the TENGs had on glial scar formation, cyst formation, and immune response at multiple time points as these are common difficulties faced in tissue engineering methods to treat or repair SCI. If able to address these universal challenges associated with SCI, TENGs may offer an alternative option in neural transplantation and may represent a viable tool in the multifaceted treatment of SCI. Impact statement In complete spinal cord injury (SCI), a significant gap forms in the injury sites replacing the neural connections and limiting the link between healthy spinal cord distal to the injury and cerebral cortex. This study aims to demonstrate the potential benefit of hydrogel collagen constructs bearing stretch-grown dorsal root ganglion axons to bridge a complete injury gap, to restore the lost connections and forming a basic infrastructure to support the regrowth of new connection. This application of stretch-grown axons in neural implants offers hope to achieve a highly modifiable and resilient bridging strategy to treat SCI.

Spinal cord lesion is one of major causes of neurological disability due to trauma and non trauma. Thisdisability can cause damage and loss of function below the level of lesion and also has adversed effects onseveral body systems. Traumatic spinal cord lesion is the most widely reported incidence compared to nontraumatic spinal cord lesion. The most leading cause of traumatic spinal cord lesion is motor vehicle crash in children, whereas in old age, falls become the main cause. The mechanism of injury influences the type of spinal cord lesion and the degree of neurological deficit. Spinal cord lesions can be classified into completeand incomplete based on the presence or absence of a function that is maintained below the level of lesion.Complete spinal cord lesion shows absence of voluntary movement or sensation below the level of the lesionon both sides, whereas incomplete lesion shows the persistence of the variation of some functions below the level of lesion. Knowledge on the anatomy of the spinal cord plays an important role in the clinicaldiagnosis. The level of lesion at the different segments of the spinal cord determines different signs andsymptoms, caused by destruction of segmental tissue and disconnection of ascending and descending tracts above and below the level of lesion. The level of lesion is helpful in predicting deficits of body functions thatmay occur, in determining the next treatment and in predicting the prognosis of the disease. Incompletespinal cord lesion tends to have a better prognosis. Death usually occurs in lesion with multiple trauma. Theleading cause of death is complications due to neurological disability, i.e. pneumonia, pulmonary embolism,septicemia, and renal failure.

Botulinum neurotoxin (BoNT) can counteract the highly frequent involuntary muscle contractions and the uncontrolled micturition events that characterize the neurogenic detrusor overactivity (NDO) due to supra-sacral spinal cord lesions. The ability of the toxin to block the neurotransmitter vesicular release causes the reduction of contractions and improves the compliance of the muscle and the bladder filling. BoNT is the second-choice treatment for NDO once the anti-muscarinic drugs have lost their effects. However, the toxin shows a time-dependent efficacy reduction up to a complete loss of activity. The cellular mechanisms responsible for BoNT effects exhaustion are not yet completely defined. Similarly, also the sites of its action are still under identification. A growing amount of data suggest that BoNT, beyond the effects on the efferent terminals, would act on the sensory system recently described in the bladder mucosa. The specimens from NDO patients no longer responding to BoNT treatment displayed a significant increase of the afferent terminals, likely excitatory, and signs of a chronic neurogenic inflammation in the mucosa. In summary, beyond the undoubted benefits in ameliorating the NDO symptomatology, BoNT treatment might bring to alterations in the bladder sensory system able to shorten its own effectiveness.

Spinal cord injury results in locomotor impairment attributable to the formation of an inhibitory fibrous scar, which prevents axonal regeneration after trauma. The scarcity of knowledge about the molecular and cellular mechanisms involved in scar formation after spinal cord lesion impede the design of effective therapies. Recent studies, by using state-of-the-art technologies, including genetic tracking and blockage of pericytes in combination with optogenetics, reveal that pericyte blockage facilitates axonal regeneration and neuronal integration into the local neural circuitry. Strikingly, a pericyte subset is essential during scarring after spinal cord injury, and its arrest results in motor performance improvement. The arising knowledge from current research will contribute to novel approaches to develop therapies for spinal cord injury. We review novel advances in our understanding of pericyte biology in the spinal cord.

Central Horner syndrome is a rare condition, comprising a unique pathophysiological phenomenon. It results from vascular lesions, head or thoracic trauma. We describe a case of Horner syndrome associated to cervical disc herniation, and first-order neuron compression. To our knowledge, this is the second case reported to date in the literature.

Over the last ten years, we have published various manuscripts on the recovery of assisted voluntary walking in people with chronic spinal chord injuries (SCI), following laparoscopic implantation of stimulation electrodes on the pelvic somatic nerves - the LION procedure. Although at the beginning of this research the objective was to allow "robotic" walking by stimulating the muscles, we realized relatively quickly that continuous low frequency stimulation of the pelvic nerves might allow the recovery of voluntary functions of the lower limbs and of the trunk necessary for walking: Seventeen out of a total of twenty-five complete motor chronic SCI-patients (68%) developed enough recovery of supra-spinal control of leg movements, that voluntary walking became feasible, even though a minimal amount of stimulation may be required. All current theories for recovery these voluntary functions below the spinal cord lesion are based on the induced regrowth or reconnection of nerves or at least the recovery of functional anatomical pathways. In this manuscript we formulate the hypothesis that electrical stimulation could be responsible for inducing the formation of "electrical pathways" within the body, which under conditions of electrical stimulation might enable the transport of necessary information from the brain to below the spinal cord lesion allowing voluntary movements of the lower limbs.

We report the case of a 35-year-old male patient suffering from a clinical and radiological manifestation of a transverse myelitis associated with antiphospholipid antibodies. After a challenging diagnosis the patient improved substantially due to immunosuppressive treatment. The demyelinating spinal cord lesion and the impressive therapeutic outcome may support the possibility of a direct binding of antiphospholipid antibodies to CNS antigens and consequently leading to a neuroimmunological pathomechanism distinct from the well-known pro-thrombotic effect of antiphospholipid antibodies. In terms of clinical routine diagnostic this case report highlights a rare but notable differential diagnosis of Multiple Sclerosis-like syndromes.