Muscle Strength Decline Caused by Eperisone Hydrochloride: A Case Report.

A 65-year-old female with thoracic spinal stenosis and incomplete paraplegia underwent T11-T12 posterior thoracic interbody fusion. During postoperative rehabilitation, she experienced thigh pain, involuntary lower limb convulsions, and muscle fatigue. Despite being prescribed eperisone hydrochloride for relief, her muscle strength decreased after 14 doses. This adverse effect, not listed in the latest Chinese medication instructions, subsided 4 days after discontinuation. This case suggests eperisone hydrochloride potentially caused reversible muscle strength decline, highlighting its potential unsuitability for incomplete paraplegia patients due to possible further muscle strength reduction. We propose updating the medication instructions to alert clinicians to this risk.

Intranasal administration of polysulfide prevents neurodegeneration in spinal cord and rescues mice from delayed paraplegia after spinal cord ischemia.

BACKGROUND: Delayed paraplegia is a devastating complication of thoracoabdominal aortic surgery. Hydrogen sulfide (H2S) was reported to be protective in a mouse model of spinal cord ischemia and the beneficial effect of H2S has been attributed to polysulfides. The objective of this study was to investigate the effects of polysulfides on delayed paraplegia after spinal cord ischemia. METHODS AND RESULTS: Spinal cord ischemia was induced in male and female C57BL/6J mice by clamping the aortic arch and the left subclavian artery. Glutathione trisulfide (GSSSG), glutathione (GSH), glutathione disulfide (GSSG), or vehicle alone was administered intranasally at 0, 8, 23, and 32 h after surgery. All mice treated with vehicle alone developed paraplegia within 48 h after surgery. GSSSG, but not GSH or GSSG, prevented paraplegia in 8 of 11 male mice (73%) and 6 of 8 female mice (75%). Intranasal administration of 34S-labeled GSSSG rapidly increased 34S-labeled sulfane sulfur species in the lumbar spinal cord. In mice treated with intranasal GSSSG, there were increased sulfane sulfur levels, and decreased neurodegeneration, microglia activation, and caspase-3 activation in the lumbar spinal cord. In vitro studies using murine primary cortical neurons showed that GSSSG increased intracellular levels of sulfane sulfur. GSSSG, but not GSH or GSSG, dose-dependently improved cell viability after oxygen and glucose deprivation/reoxygenation (OGD/R). Pantethine trisulfide (PTN-SSS) also increased intracellular sulfane sulfur and improved cell viability after OGD/R. Intranasal administration of PTN-SSS, but not pantethine, prevented paraplegia in 6 of 9 male mice (66%). CONCLUSIONS: Intranasal administration of polysulfides rescued mice from delayed paraplegia after transient spinal cord ischemia. The neuroprotective effects of GSSSG were associated with increased levels of polysulfides and sulfane sulfur in the lumbar spinal cord. Targeted delivery of sulfane sulfur by polysulfides may prove to be a novel approach to the treatment of neurodegenerative diseases.

Neurogenic bladder in patients with paraplegia: a two-center study of the real-life experience of the patients' journey.

INTRODUCTION: Several patterns of urological dysfunctions have been described following spinal cord injury (SCI), depending on the level and the completeness of the injury. A better understanding of the natural history of neurogenic bladder in patients with SCI, and the description of their successive therapeutic lines based on their clinical and urodynamic pattern is needed to improve their management. This study aimed to describe the real-life successive therapeutic lines in patients with neurogenic lower urinary tract dysfunction (NLUTD) following SCI. METHODS: We conducted a two-center retrospective review of medical files of patients with SCI followed in two French specialized departments of Physical Medicine and Rehabilitation between January 2000 and January 2018. All patients with SCI with a level of lesion bellow T3 and older than 18 years old were eligible. The primary outcome was the description of the natural journey of neurogenic bladder in this population, from the awakening bladder contraction to the last therapeutic line. Survival curves were calculated with a 95-confidence interval using the Kaplan-Meier method. RESULTS: One hundred and five patients were included in this study. Most of the patients were young men with a complete SCI lesion. The median time of treatment introduction was 1 and 9 years for anticholinergics and intradetrusor injection of BoNT/A, respectively. Median duration of effect of treatments was 4 and 6 years post-introduction of anticholinergics and BoNT/A, respectively. CONCLUSION: This study describes NLUTD journey of patients with SCI demonstrating the mid-term efficacy of the two first therapeutic lines of NDO management. An improvement of non-surgical therapeutics is needed.

Spastic paraplegia as the only manifestation in neuropsychiatric lupus: a case report.

Demyelination syndrome is one manifestation of neuropsychiatric lupus erythematosus (NPLE) and is rare in systemic lupus erythematosus (SLE). When SLE presents only neuropsychiatric symptoms without damage to other systems, its diagnosis becomes difficult. Herein, we report a 29-year-old male who suffered from lower limb stiffness with recessive onset and progressive aggravation in one year. He had paraplegia, spastic hypertonia, abnormal gait, and bilateral positive Babinski signs. His symptoms indicated spastic paraplegia. Brain MRI showed multiple small demyelinating lesions in the lateral ventricle, brainstem, and cerebellum. Anti-ds DNA, anti-Sm and anti-RNP antibodies were positive. He was diagnosed with NPLE and had a good treatment response to steroids. To the best of our knowledge, this is the first case of spastic paraplegia as the only manifestation in SLE.

[A case of surfer's myelopathy with serial imaging examination from early stage after onset].

Surfer's myelopathy is non-traumatic spinal cord injury which develops in beginner surfers. The patient was a 17-year-old female who developed severe paraplegia with bilateral sensory dysfunction below the groin and bladder/rectal dysfunctions after her first surfing lesson. A spinal-cord MRI performed six hours after onset revealed an intramedullary hyperintensity area from T8 to the conus medullaris on the T2 weighted images. Expansion of this hyperintensity area was observed on Day 3 and showed a reduction on Day 8. After providing intravenous methylpredonisolone, intravenous glycerol and intravenous edaravone, motor function and bladder/rectal functions began to improve after approximately three weeks. In this study, the expansion of the lesion in the early stages of the disease course was observed by sequential spinal MRI. Furthermore, a time lag between improvement according to imaging and improvement in symptoms was also observed.

A rare case of isolated cauda equina Nocardia farcinica infection.

Nocardia is a Gram-positive, partially acid-fast, catalase-positive, and urease-positive bacterium that grows aerobically. We present an extremely rare case of cauda equina syndrome due to isolated intramedullary Nocardia farcinica infection. A 44-year-old male presented with low backache and gradually progressive weakness in bilateral lower limbs followed by paraplegia. He was found to have a well-defined, sharply demarcated ring-enhancing lesion located from T11-T12 to L3 vertebral body. He underwent laminectomy and decompression. The histopathological examination revealed a Gram-positive filamentous organism that looks like Nocardia. The culture report was suggestive of Nocardia farcinica. He was then treated with antibiotics and had a remarkable clinical and radiological improvement.

Proactive Cortical Control in Spinal Cord Injury Subjects with Paraplegia.

Preparatory cortical activities were investigated in subjects with paraplegia attributed to spinal cord injury (SCI). Electroencephalogram (EEG) and behavioral data were recorded simultaneously in a visual-motor discrimination go/no-go task performed with the right upper limb. Eighteen SCI subjects participated to one, two, or three experimental sessions (Go/No-Go task), according to their availability and willingness to participate. To evaluate the effects of SCI on cortical activities as a function of time, we considered three SCI groups (9 individuals each), based on different time from the injury onset (acute, 1-2 months; subacute, 3-5 months; chronic, 6-9 months), and a control group of 9 healthy participants matched for age and sex. Results indicate that response time (RT) was slower and percentage of omissions was higher in SCI subjects than healthy, independently from time from lesion (TFL). Also, the proactive motor preparation, indexed by the Bereitschafts potential (BP), and the pre-frontal cognitive control, indexed by the pre-frontal negativity component, showed reduced amplitude in SCI subjects, independently from TFL. Conversely, TFL effect was observed in the BP topography, which showed a more posterior focus in subacute and chronic groups than healthies. Interestingly, despite this posteriorization, BP amplitudes maintained the well-known correlation with RTs. Overall, SCI affects cortical reorganization independently from TFL, regarding proactive activities for action inhibition and reaction time; conversely, a TFL effect was observed in the topography changes related to the cortical areas involved in proactive motor activity. Present data are in line with growing evidence of brain changes after SCI, in particular focusing on cognitive effects and evidencing possible functional mechanisms related to motor and cognitive readiness processing, relevant for SCI rehabilitation programs.

Colgajo glúteo mayor en reconstrucción de úlcera isquiática bilateral / Gluteal maximus flap for reconstruction of bilateral ischial ulcer

Propósito y objetivo. Demostrar una de las opciones más empleadas para la cobertura de úlceras isquiáticas en paciente parapléjico. El colgajo glúteo mayor sería de primera elección en el caso presentado de una paciente con diagnóstico de escaras isquiáticas bilateral Grado IV. Introducción. El colgajo glúteo mayor, colgajo musculocutáneo, es un procedimiento muy utilizado y de primera línea para el tratamiento de úlceras isquiáticas. Debemos tener en cuenta que para el éxito y buena evolución de la cirugía es necesario la conformación de un equipo multidisciplinario, para su seguimiento y control. Las opciones de cobertura dependen de la topografía de la lesión. Algunas de las opciones de cobertura son: colgajo glúteo inferior de rotación, colgajo glúteo inferior de avance en V-Y, colgajo de isquiotibiales en V-Y, colgajo de cara posterior de muslo y colgajo extendido de fascia lata, entre otros. Material y método. Se presenta el caso clínico de una paciente femenina con diagnóstico patológico de cavernoma intramedular D9, que padece paraplejía de un año de evolución, presentando escara isquiática bilateral grado IV acompañadas de osteomielitis. Se trató quirúrgicamente con colgajo glúteo mayor bilateral Resultados. En esta paciente se alcanzó una adecuada cobertura del defecto, que permitió su pronta rehabilitación, y un minucioso control posoperatorio que no mostró complicaciones ni recidiva, hasta la fecha. Discusión. Las úlceras isquiáticas profundas ubicadas cerca del tracto genitourinario presentan mayor dificultad para su reconstrucción. El colgajo musculocutáneo de glúteo mayor a pedículo inferior permite el cierre de cualquier úlcera isquiática y el cierre primario del sitio donador asegurando un cierre sin tensión; otras opciones quirúrgicas, como los colgajos basados en la pelvis o el tronco, son menos susceptibles a la tensión que aquellos ubicados en la porción móvil de la extremidad inferior, por lo que los colgajos de glúteo mayor, inferior y de cara posterior al muslo tienen mayor porcentaje de éxito que los colgajos de tensor de fascia lata e isquiotibiales. Conclusión. El colgajo glúteo mayor es un tratamiento de primera elección para la cobertura de úlceras isquiáticas de alta morbilidad en pacientes parapléjicos, tratado por un equipo multidisciplinario, cuya técnica quirúrgica presentó buena cobertura con un control estricto del posoperatorio con excelente evolución y sin ninguna complicación esperada

Minocycline Before Aortic Occlusion Reduces Hindlimb Motor Impairment, Attenuates Spinal Cord Damage and Spinal Astrocytosis, and Preserve Neuronal Cytoarchitecture in the Rat.

OBJECTIVES: Spinal cord ischemia secondary to trauma or a vascular occlusive event is a threatening phenomenon. The neuroprotective properties of minocycline have been shown in several models of central nervous system diseases and after spinal cord ischemia; however, the benefit of using the drug requires additional confirmation in different animal models. Astrocytes are essential as regulators of neuronal functions and for providing nutrients. The authors hypothesized that astrocytes in the spinal cord may be an important target for minocycline action after ischemia and thus in the prevention of secondary spreading damage. DESIGN: A prospective, randomized animal study. SETTING: University research laboratory, single institution. PARTICIPANTS: Adult male Sprague Dawley rats, weighing between 400 and 450 g. INTERVENTIONS: A model of spinal cord ischemia in the rat was used for this study to determine whether a single, high-dose (10 mg/kg) of minocycline protects against damage to the neuronal cytoskeleton, both in the white and gray matter, and whether it reduces glial fibrillary acidic protein levels, which is an index for prevention of astrocyte activation during ischemia. Thirty minutes before thoracic aorta occlusion, minocycline was administered for 18 minutes using a 2 F Fogarty catheter. MEASUREMENTS AND MAIN RESULTS: Minocycline given prophylactically significantly mitigated severe hindlimb motor impairment and reduced glial fibrillary acidic protein plus astrocytosis in both the white and gray matter of the spinal cord, caudal to the occlusion. Neuronal histologic cytoarchitecture, which was severely and significantly compromised in control animals, was preserved in the minocycline-treated animals. CONCLUSIONS: This study's data imply that minocycline may attenuate reactive astrocytosis in response to injury with better neurologic outcome in a model of spinal cord ischemia in rats. The data suggest that future use of minocycline, clinically, might be advantageous in surgeries with a potential risk for paraplegia due to spinal cord ischemia.

[A case of local tetanus presenting spastic paraplegia mimicking myelitis].

A 35-year-old male was admitted to our hospital because of suspected myelitis. T2-weighted spinal MRI revealed a high intensity area at Th7-9. On admission, he showed mild weakness of the lower extremities and hyperreflexia of all extremities. Therefore, he was diagnosed with having spastic paraplegia. He presented no trismus or opisthotonos. There was pleocytosis in the cerebral spinal fluid. Dysuria, constipation and spasticity of the bilateral legs worsened, even though we administered methylprednisolone pulse therapy. Nonetheless, the symptoms had progressed on the 11th hospital day, opisthotonus and optic hyperesthesia were presented. On the 13th hospital day, we suspected local tetanus and administered tetanus toxoid. After one month, his symptoms had gradually improved. In the case of spastic paraplegia showing a subacute progression course and a faint abnormality on spinal MRI, the possibility of local tetanus should be considered.

First-in-Man Intrathecal Application of Neurite Growth-Promoting Anti-Nogo-A Antibodies in Acute Spinal Cord Injury.

BACKGROUND: Neutralization of central nervous system neurite growth inhibitory factors, for example, Nogo-A, is a promising approach to improving recovery following spinal cord injury (SCI). In animal SCI models, intrathecal delivery of anti-Nogo-A antibodies promoted regenerative neurite growth and functional recovery. OBJECTIVE: This first-in-man study assessed the feasibility, safety, tolerability, pharmacokinetics, and preliminary efficacy of the human anti-Nogo-A antibody ATI355 following intrathecal administration in patients with acute, complete traumatic paraplegia and tetraplegia. METHODS: Patients (N = 52) started treatment 4 to 60 days postinjury. Four consecutive dose-escalation cohorts received 5 to 30 mg/2.5 mL/day continuous intrathecal ATI355 infusion over 24 hours to 28 days. Following pharmacokinetic evaluation, 2 further cohorts received a bolus regimen (6 intrathecal injections of 22.5 and 45 mg/3 mL, respectively, over 4 weeks). RESULTS: ATI355 was well tolerated up to 1-year follow-up. All patients experienced ≥1 adverse events (AEs). The 581 reported AEs were mostly mild and to be expected following acute SCI. Fifteen patients reported 16 serious AEs, none related to ATI355; one bacterial meningitis case was considered related to intrathecal administration. ATI355 serum levels showed dose-dependency, and intersubject cerebrospinal fluid levels were highly variable after infusion and bolus injection. In 1 paraplegic patient, motor scores improved by 8 points. In tetraplegic patients, mean total motor scores increased, with 3/19 gaining >10 points, and 1/19 27 points at Week 48. Conversion from complete to incomplete SCI occurred in 7/19 patients with tetraplegia. CONCLUSIONS: ATI335 was well tolerated in humans; efficacy trials using intrathecal antibody administration may be considered in acute SCI.

A novel KIAA0196 mutation in a Chinese patient with spastic paraplegia 8: A case report.

RATIONALE: We report a case of Spastic paraplegia 8 (SPG8) with a novel mutation of KIAA0196 gene. PATIENTS CONCERNS: A 12-year-old boy presented as ankle sprained, lower limb stiffness, abnormal gait since he was 5 years old. DIAGNOSES: The next generation sequence showed a novel c.1128delG (p.L376fs) mutation in KIAA0196 gene, the electromyography showed the pyramidal tract conduction dysfunction and deep sensory conduction abnormalities of lower limbs without motor neuron damage. The diagnose was SPG8. INTERVENTIONS: Patient was gaven Baclofen treatment (30 mg/day, orally). OUTCOMES: At one year follow up, his symptoms didn't improved. LESSONS: We describe a novel KIAA0196 c.1128del.G (p.L376fs) mutation in a Chinese patient with SPG8. To our knowledge, it's the first frame delete mutation causing shift mutation of KIAA0196 gene, resulting in the earliest onset of SPG8 in the world. Gene sequencing is a powerful diagnostic tool to identify a causal mutation in genetically heterogeneous HSP.

A novel paraplegia model in awake behaving macaques.

Lower limb paralysis from spinal cord injury (SCI) or neurological disease carries a poor prognosis for recovery and remains a large societal burden. Neurophysiological and neuroprosthetic research have the potential to improve quality of life for these patients; however, the lack of an ethical and sustainable nonhuman primate model for paraplegia hinders their advancement. Therefore, our multidisciplinary team developed a way to induce temporary paralysis in awake behaving macaques by creating a fully implantable lumbar epidural catheter-subcutaneous port system that enables easy and reliable targeted drug delivery for sensorimotor blockade. During treadmill walking, aliquots of 1.5% lidocaine with 1:200,000 epinephrine were percutaneously injected into the ports of three rhesus macaques while surface electromyography (EMG) recorded muscle activity from their quadriceps and gastrocnemii. Diminution of EMG amplitude, loss of voluntary leg movement, and inability to bear weight were achieved for 60-90 min in each animal, followed by a complete recovery of function. The monkeys remained alert and cooperative during the paralysis trials and continued to take food rewards, and the ports remained functional after several months. This technique will enable recording from the cortex and/or spinal cord in awake behaving nonhuman primates during the onset, maintenance, and resolution of paraplegia for the first time, thus opening the door to answering basic neurophysiological questions about the acute neurological response to spinal cord injury and recovery. It will also negate the need to permanently injure otherwise high-value research animals for certain experimental paradigms aimed at developing and testing neural interface decoding algorithms for patients with lower extremity dysfunction.NEW & NOTEWORTHY A novel implantable lumbar epidural catheter-subcutaneous port system enables targeted drug delivery and induction of temporary paraplegia in awake, behaving nonhuman primates. Three macaques displayed loss of voluntary leg movement for 60-90 min after injection of lidocaine with epinephrine, followed by a full recovery. This technique for the first time will enable ethical live recording from the proximal central nervous system during the acute onset, maintenance, and resolution of paraplegia.

Heroin-induced acute myelopathy with extreme high levels of CSF glial fibrillar acidic protein indicating a toxic effect on astrocytes.

A man aged 33 years with previous heroin substance abuse was found unconscious lying in a bush. The patient had been without heroin for some time but had just started to use intravenous heroin again, 0.5-2 g daily. The patient had almost complete paraplegia and a sensory loss for all modalities below the mamillary level and a urine retention of 1.5 L. Acute MRI of the spine revealed an expanded spinal cord with increased intramedullary signal intensity, extending from C7-T9. The cerebrospinal fluid showed extremely high levels of nerve injury markers particularly glial fibrillar acidic protein (GFAP): 2 610 000/ng/L (ref. <750). The patient was empirically treated with intravenous 1 g methylprednisolone daily for 5 days and improved markedly. Very few diseases are known to produce such high levels of GFAP, indicating a toxic effect on astrocytes. Measuring GFAP could possibly aid in the diagnosis of heroin-induced myelopathy.

Longitudinal Outcomes in the 2014 Acute Flaccid Paralysis Cluster in Canada.

We describe the presenting features and long-term outcome of an unusual cluster of pediatric acute flaccid paralysis cases that occurred in Canada during the 2014 enterovirus D68 outbreak. Children (n = 25; median age 7.8 years) presenting to Canadian centers between July 1 and October 31, 2014, and who met diagnostic criteria for acute flaccid paralysis were evaluated retrospectively. The predominant presenting features included prodromal respiratory illness (n = 22), cerebrospinal fluid lymphocytic pleocytosis (n = 18), pain in neck/back (n = 14) and extremities (n = 10), bowel/bladder dysfunction (n = 9), focal central gray matter lesions found in all regions of the spinal cord within the cohort (n = 16), brain stem lesions (n = 8), and bulbar symptoms (n = 5). Enterovirus D68 was detectable in nasopharyngeal specimens (n = 7) but not in cerebrospinal fluid. Acute therapies (corticosteroids, intravenous immunoglobulins, plasmapheresis) were well tolerated with few side effects. Fourteen of 16 patients who were followed beyond 12 months post onset had neurologic deficits but showed ongoing clinical improvement and motor recovery.

Mean platelet volume to platelet count ratio predicts in-hospital complications and long-term mortality in type A acute aortic dissection.

Type A acute aortic dissection is a life-threatening vascular emergency because of its high morbidity and mortality. Platelet is a pivotal ingredient involved in the development of acute aortic dissection. In this study, we aimed to investigate whether mean platelet volume (MPV)/platelet count ratio predicts in-hospital complications and long-term mortality in type A acute aortic dissection. In this single-center and prospective cohort study, 106 consecutive patients with Stanford type A acute aortic dissection admitted to the hospital within 12 h after onset were recruited. The best cut-off value of MPV/platelet count ratio predicting all-cause mortality was determined by the receiver operator characteristic analysis. Patients were divided into high (H-MPV/platelet count) and low (L-MPV/platelet count) groups based on the cut-off value of 7.49 (10 fl/10/l). Patients were followed up for 3.5 years. Of the 106 acute aortic dissection patients, 71 (67.0%) died during the study period, with a median follow-up duration of 570 days. Compared to the L-MPV/platelet count group, patients with H-MPV/platelet count had a higher risk of in-hospital complications including hypotension, hypoxemia, myocardial ischemia/infarction, conscious disturbance, pericardial tamponade, paraplegia, and poor survival (all P < 0.05). In multivariable Cox regression models adjusted for potential confounders, MPV/platelet count ratio was positively associated with the hazard of all-cause mortality, irrespective of interventions either with medication only or urgent surgery, and the hazard ratios were 2.81 (95% confidence interval 1.28-4.48) for the H-MPV/platelet count group when taking L-MPV/platelet count group as the reference (P = 0.005). The MPV/platelet count ratio was a strong independent predictor for in-hospital complications and long-term mortality in patients with type A acute aortic dissection.

Isotopic scintigraphy combined with computed tomography: a useful method for investigating inefficiency of intrathecal baclofen.

BACKGROUND: Intrathecal baclofen infusion is an established method for the treatment of generalized and disabling spasticity. The most frequent technical problems are due to catheter /pump disconnections, but diagnosis of dysfunction may be difficult. CASE REPORT: We report here the case of a 53-year-old woman with spastic paraplegia treated with intrathecal baclofen. Spasticity remained uncontrolled despite a gradual increase in baclofen dosage. On plain radiographs the distal end of the catheter was found to be pointing downwards with the catheter tip at level L5 and no apparent disconnection or failure. Indium111 diethylenetriamine penta-acetic acid (DTPA) scintigraphy combined with computed tomography revealed that the activity of the radioisotope was highest next to the first sacral vertebra and that there was no leakage. Radioisotope activity above the lumbar level was very low. The catheter tip was therefore repositioned to level T7. One month later, spasticity was well controlled and a second scintigraphy confirmed high activity of intrathecal radioisotope up to the basal cisterns. DISCUSSION: The combination of Indium111 DTPA scinti-graphy with computed tomography allows anatomical and functional investigation of intrathecal drug administration. In this case report this approach showed that the inefficiency of intrathecal baclofen was due to the caudal orientation of the catheter.