Significant Neurological Improvement Research Articles

Abstract Number ‐ 114: Deep Cerebral Venous Thrombosis requiring Venous Thrombectomy and Intra‐arterial Thrombolysis in Young Pregnant Female

Introduction Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke and mortality especially in young women and children (1). Even though, first‐line treatment remains anticoagulation, some patients deteriorate and endovascular treatment is needed. Currently there are no randomized controlled trials comparing the efficacy and safety of intracranial thrombolysis and mechanical thrombectomy to standard‐of‐care anticoagulation therapy (2). We present a case of a pregnant lady with CVST with successful clinical outcomes with venous thrombectomy and intraarterial thrombolysis. Methods Case Report Results 30 year old lady with no past medical history, 7 weeks and 4 days pregnant presented with acute progressive encephalopathy associated with nausea, vomiting and headaches. On admission, she was stuporous, had dysarthria, severe hemiparesis, and hemineglect on the right side. She had COVID‐19 infection and her fetus had subchorionic hematoma by ultrasound. Initial CT brain showed extensive cerebral venous sinus thrombosis (CVST). She was intubated and MRI showed venous infarcts. MR venography revealed acute extensive CVST of superior sagittal sinus, vein of galen, right transverse sinus, right sigmoid sinus, and right jugular vein. IV Heparin drip was initiated. Her follow‐up neurological exam deteriorated despite maximal medical therapy. The decision was made for endovascular recanalization. The cerebral angiogram confirmed the occlusion of deep venous system. Thrombectomy of bilateral internal jugular vein and sigmoid sinus was performed with retrieval of thrombi. Post‐thrombectomy runs demonstrated persistent extensive CVST and decision was made for intra‐arterial thrombolysis. A diagnostic catheter was secured in the right internal carotid artery catheter (ICA). Thombolysis was performed with 4 mg/hr recombinant tissue‐plasminogen activator (rt‐PA). Heparin drip IV was continued. Subsequently, the repeat CT brain showed significant improvement in the CVST and interval development of intraparenchymal hemorrhages and subarachnoid hemorrhages. Heparin and rt‐PA were held. The patient was found to have Factor V Leiden mutation and she was started on Enoxaparin 1mg/kg throughout her pregnancy and 6 weeks postpartum. Clinically she demonstrated significant neurologic improvement and was discharged to home from rehabilitation center. Currently, she is thirty‐ four weeks pregnant and neurologically intact without any deficits. Conclusions Pharmacological and mechanical endovascular interventions can have significantly successful clinical outcomes in deep cerebral venous thrombosis. Controlled studies are required to assess the safety and efficacy of these interventions when compared to standard systemic anticoagulation.

Multilevel ossification of the posterior longitudinal ligament causing cervical myelopathy: An observational series of North American patients.

Few studies regarding ossification of the posterior longitudinal ligament (OPLL) outside of Asia currently exist in the literature. A set of patients with multilevel cervical OPLL causing symptomatic myelopathy or radiculopathy from a North American sample is analyzed. The objective of this study was to describe the demographics, radiographic findings, and surgical outcomes of a cohort of North American patients with degenerative spondylosis presenting for operative management of multilevel (>3 segments) cervical OPLL. Forty-three patients diagnosed with multilevel cervical OPLL and degenerative spondylosis presenting with symptomatic cervical myelopathy or radiculopathy were surgically treated over a 9-year period at a single tertiary care academic medical center. Radiographic measurements were performed on preoperative computed tomography and magnetic resonance imaging images of the cervical spine. Clinical outcomes included pre- and postoperative Nurick scores, 90-day readmission, complication, and revision surgery rates. The mean age was 66.1 ± 10.9 years with a mean latest follow-up time of 32.7 ± 16.4 months. Most patients had previous diagnoses of obesity (70.7%) and hypertension (55.8%). At least one-quarter of patients were diagnosed with type 2 diabetes (34.9%), hyperlipidemia (41.9%), cardiovascular disease (25.6%), or chronic kidney disease (25.3%). The most common OPLL subtype was segmental (39.5%) and spanned a mean of 3.54 ± 1.48 segments. Myelopathic symptoms were present in 88.4% of patients. All patients experienced significant neurologic improvement at 3-week and latest follow-up (P < 0.001 for both). Obesity, diabetes, and other metabolic derangements in patients with existing cervical spondylosis may be risk factors for a particularly aggressive form of multilevel OPLL. Various operative approaches may be employed to achieve adequate neurologic recovery. Further workup for OPLL in patients with these risk factors may prove beneficial to ensure appropriate operative management.

NEUROLOGICAL RECOVERY AFTER SURGICAL TREATMENT IN PATIENTS WITH THORACOLUMBAR TRM

ABSTRACT Objective: Evaluate the neurological recovery with a follow-up of 06 (six) months in victims of thoracic and lumbar fractures who underwent spinal decompression in less than 24 hours, between 24 and 48 hours, and more than 48 hours after the trauma. Methods: Data were collected on patients seen at a large public hospital in Belo Horizonte, between 2014 and 2018, who were victims of SCI who presented with neurological deficits at initial care, and the neurological recovery presented. Results: 41 SCI patients were evaluated, whose mean age was 34 years. There was a predominance of thoracic spine fractures (65.9% of the cases) and classified as AO Spine type C (75%). Regarding the time variable, about 68% of the patients were submitted to surgical treatment more than 48 hours after the trauma. It was observed that both the patients submitted to surgical decompression within less than 24 hours, and those operated on more than 48 hours after the trauma showed a slight neurological improvement at the 6-month follow-up. However, no statistical significance was found. It is worth noting that even when analyzing the 41 patients of the study, regardless of the surgical interval, it was impossible to observe a statistically significant neurological improvement at the 6-month follow-up. Conclusion: Our study could not demonstrate significant differences between those patients who operated early in less than 24 hours and those who operated after more than 48 hours. Level of Evidence III; Comparative retrospective study.

Timing of Recovery After Surgery for Patients With Degenerative Cervical Myelopathy: An Observational Study From the Canadian Spine Outcomes and Research Network.

The time course over which postoperative neurological recovery occurs after surgery for degenerative cervical myelopathy occurs is poorly understood. To determine the time point at which patients experience significant neurological improvement. We reviewed data from an ongoing prospective multicenter cohort study. We measured neurological function at 3 months, 1 year, and 2 years after surgery using the modified Japanese Orthopedic Association (mJOA) scale. We implemented minimal clinical important differences (MCIDs) to guide interpretation of mJOA scores, and we used 1-way analysis of variance to compare changes between follow-up intervals. Among 330 patients, the mean overall mJOA improved from 12.9 (SD 2.6) to 14.6 (SD 2.4) at 3 months, 14.7 (SD 2.4) at 1 year, and 14.8 (SD 2.5) at 2 years. The difference in means was statistically significant (P < .01) at the interval from baseline to 3 months postoperatively, but not from 3 months to 1 year or 1 year to 2 years. The MCID was reached by 161 patients at 3 months, 32 more at 1 year, and 15 more at 2 years, with a statistically significant difference only at 3 months. Patients with moderate or severe disease reached the MCID more frequently than those with mild disease. Among patients who underwent surgery for degenerative cervical myelopathy, most significant neurological improvement occurred by 3 months after surgery. These findings will facilitate valid discussions about postoperative expectations during shared clinical decision making between patients and their surgeons.

Prognostic factors and outcomes of surgical intervention for patients with spinal metastases secondary to lung cancer: an update systematic review and meta analysis.

Lung cancer is one of the most common malignant tumors. Most patients develop spinal metastases during the course of cancer and suffer skeletal-related events. Currently, no consensus has been reached on the prognostic factors in patients undergoing surgeries. This study aimed to answer two questions: (1) what are the effects of surgical intervention, and (2) what are the factors associated with postoperative survival. Searches were performed on electronic databases including PubMed, Ovid/MEDLINE, Cochrane, and Scopus for articles published before February of 2022, involving the survival factors of patients with spinal metastasis. Multiple data items were considered, such as baseline demographics, surgical details, clinical outcome, and prognostic factors. The analysis was performed in Review Manager (RevMan) 5.5. The prognostic factors of survival were analyzed with univariate and multivariate cox regression analysis. Finally, 14 studies with 813 patients were identified. Their 6, 12, and 24months survival rates ranged from 18 to 58%, 18 to 22.4%, and 0 to 58.5%, respectively. The pooled hazard ratio of preoperative ambulatory status and the number of involved vertebrae demonstrated statistical significance, while no significant prognostic effect on the overall survival was found for targeted therapy, visceral metastases, chemotherapy, radiotherapy, or postoperative ambulatory status. Overall, surgical intervention could achieve significant pain relief and neurological function improvements. For patients receiving surgery for spinal metastasis from lung cancer, preoperative ambulatory status and the number of involved vertebrae were significant prognostic factors associated with their survival.

An Unusual Cause of Cerebellitis - Case Report

In countries where tuberculosis is still very common, millions of patients are placed under Anti-tuberculous treatment, of which Isoniazid is a component. The unfortunate co-occurrence TB in end-stage renal disease patient influences the metabolism and excretion of isoniazid and increases the chances of adverse effects. We wish to present one such patient of ours on ATT who returned to our care with neurological symptoms. Both the disease of tuberculosis and its treatment are fraught with occurrence of neurological involvement and complications. Diligent neurological examination pointed towards cerebellar pathology, possibly posterior circulation stroke. Ensuing MRI brain exhibited possible features indicative of drug (Isoniazid) induced cerebellitis. Consumption of the other two drugs, metronidazole and cycloserine, was excluded. Blood and CSF examinations did not show any abnormality. INH induced cerebellitis being our most possible diagnosis, high dose pyridoxine (100mg/day) therapy was initiated. Withing a week there was significant neurological improvement, and he was eventually discharged with modified ATT. Learning from this experience we would suggest to consider cerebellitis in patients with neurological symptoms on Isoniazid therapy and institute high dose pyridoxine therapy as a preventive measure in such patients.

PMON318 Nephrogenic syndrome of inappropriate antidiuresis in a 19 months old child with gross developmental delay

Abstract Case report 19 months old African American boy with nonsignificant past medical history presented with inability to walk, hypotonia chewing difficulties and speech delay. Initial laboratory evaluations demonstrated serum hyponatremia of 120-129 mEq/dl, low serum osmolality 261 mosm/kg (normal serum osmolality 275-295 mosm/kg) with inappropriately high urine osmolality 445 mosm/kg) (normal urine osmolality 300-1000 mosm/kg). Blood work for thyroid, adrenal, and pituitary function was unremarkable. Vasopressin level of 2.4 pg/ml (normal 0.0 - 4.7 pg/mL) did not support the diagnosis of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH). Fludrocortisone challenge test ruled out aldosterone deficiency with insufficient decrease in urine sodium and no response in serum sodium. Renal ultrasound and brain MRI were normal. Genetic testing revealed AVPR2 X-linked mutation c.409C&amp;gt;T p.R137C, consistent with nephrogenic syndrome of inappropriate antidiuresis (NSIAD). The patient was discharged on sodium chloride tablets 2g every 8 hours and remained stable, asymptomatic. One month after discharge patient showed significant neurological improvement. Discussion Sodium is known to play a significant role in growth and maturation of the whole body, especially of the nervous system. Moderate (120-129 mEq/L) to severe (&amp;lt;120 mEq/L) hyponatremia can present with nausea, malaise, headache, lethargy, motor and speech delay, seizures and even death due to brain herniation. Normal fluid and electrolyte balance is achieved by the thirst mechanism and free water excretion in kidneys. This is mediated by Vasopressin, which acts through V2R receptor in distal renal collecting duct. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatremia. Reset osmostat syndrome with a congenitally low serum osmolality threshold is one of the rare disorders on the differential. Hereditary nephrogenic syndrome of inappropriate antidiuresis is very rare mutation in vasopressin receptor, which clinically resembles SIADH except for normal/low vasopressin levels in set of hyponatremia. It causes gain of function and inappropriately high water retention. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Case Series of Spinal Epidural Hematoma: A Single Center Experience

Background and Importance: Spinal epidural hematoma (EDH) is a rare clinical condition that occurs spontaneously in patients with a spine injury. Most patients require laminectomy and evacuation of spinal EDH. Magnetic resonance imaging (MRI) of the spine with magnetic resonance angiography is the chosen radiological investigation. This study aims to review cases with spinal EDH and discuss its etiology, pathogenesis, investigations, and various management strategies. Case Presantation: This is a retrospective analysis study of five spinal EDH cases admitted at our institute from August 2020 to August 2021. Four patients underwent laminectomy and evacuation, while one was managed conservatively because of rapid clinical improvement. The patients’ functional outcomes were assessed by using American spinal cord injury association impairment scale (AIS) before and after treatment. Four of the five patients who participated in this study had significant neurological improvement. One of the patients who presented late to us had poor neurological recovery despite the surgical intervention. Conclusion: Surgical evacuation of spinal EDH within 48 hours of the onset of symptoms ensures good clinical recovery. Spontaneous resolution is possible in some cases if patients have an improvement in their neurological status early in the course of the disease. Hence, we conclude that prompt treatment in spinal EDH patients ensures maximum functional recovery. Patients with spinal EDH need close follow-up and periodical neurological examination.

PB2305: EFGARTIGIMOD: CLINICAL DEVELOPMENT OF A NOVEL FCRN ANTAGONIST IN THE TREATMENT OF AUTOIMMUNE DISEASES

Background: Immunoglobulin G (IgG) autoantibodies play a key role in the pathogenesis of various autoimmune diseases. The neonatal Fc receptor (FcRn) is the central regulator of IgG homeostasis, rescuing IgG (including pathogenic autoantibodies) and albumin from lysosomal degradation and is responsible for the long half-life of IgG. Therapeutic blocking of FcRn leads to reduction of all IgG subtypes without reducing other immunoglobulin types, making it a possible target for symptomatic treatment of autoimmune disorders, while maintaining normal immunological responses. Efgartigimod (EFG), an FcRn antagonist, is a human IgG1-derived Fc-fragment that outcompetes endogenous IgG binding, reduces IgG recycling, and increases IgG degradation. EFG is approved in the US and Japan for treatment of generalized myasthenia gravis (MG) in adult patients. Aims: This presentation provides an overview of EFG as a molecule and summarize the clinical development program to date. Methods: Studies in healthy volunteers and patients with autoimmune diseases are already completed. Phase 3 studies in immune thrombocytopenia (ITP; ADVANCE and ADVANCE SC) and phase 2/3 studies in chronic inflammatory demyelinating polyneuropathy (ADHERE), pemphigus vulgaris and foliaceus (ADDRESS), bullous pemphigoid (BALLAD), and myositis (ALKIVIA) are ongoing. Results: In a Phase 2 trial in patients with ITP, EFG (10 mg/kg given intravenously) reduced total IgG levels by 63.7% (from mean [SD] 10.6 g/L [5.1] at baseline to 4.1 g/L [2.0]) 3 days after the fourth weekly infusion. No changes in IgG levels were observed in patients treated with placebo during that time. These reductions led to clinically relevant increases in platelet counts; 46% of EFG patients vs 25% on placebo achieved a platelet count of ≥50 x109/L on ≥2 occasions. In a Phase 3 trial in MG (ADAPT), EFG rapidly reduced IgG without impacting IgM, IgA, or albumin levels while participants recorded statistically significant functional neurological improvements. In all studies to date, EFG was well tolerated, and adverse events were mainly mild to moderate. Summary/Conclusion: FcRn inhibition by EFG is a promising potential therapeutic option for several autoimmune diseases mediated by pathogenic IgG autoantibodies.

Intraspinal periosteal chondroma in upper thoracic spine causing cord compression and myelopathy: A case report.

IntroductionChondromas are slow-growing cartilage-forming benign tumors, rarely occurring in the spine. Generally, most spinal chondromas are asymptomatic; however, with slow progressive growth, these lesions may enlarge and expand and cause compressive neurological symptoms, resulting in radiculopathy or more commonly myelopathy due to direct neural compression.Presentation of caseA 15-year-old male adolescent presented to Emergency Department with history of fall (slippage) on concrete ground while playing three months back. On neurological examination, the motor power in bilateral upper limbs was 5/5 while it was 1/5 in both lower extremities. Some muscle wasting was noted in the lower limbs. The planter reflexes were upgoing; and the sensory loss was below T6 spinal level. CT scan of dorsolumbar spine demonstrated a well-defined high-density lesion in lateral aspect of spinal canal at T2-T3 vertebral level adjacent to left T2-T3 facet joint. MRI of dorsal spine revealed a 3 × 2 × 1 cm3-sized, well-defined, non-enhancing T1 low to isointense and T2/STIR heterogeneous hyperintense lesion with osseous and cartilaginous components in the left lateral aspect of spinal canal at T1-T3 level, causing compression and contralateral displacement of spinal cord. The patient was then subjected to posterior laminectomy, complete excision, followed by laminoplasty using minicranial plates and screws. Histopathology of the mass showed bony trabeculae with hematopoietic elements and attached lobules of hyaline cartilage, chondroid matrix and lobules of mature chondrocyte and myxoid changes. Postoperatively his power was improved slightly and he was able to stand up with some assistance. On six-month follow up, patient showed significant neurological improvement. He was able to walk independently with minimal assistance. He was able to control bowel and bladder functions.DiscussionChondromas occurring in the spine are rare, accounting for only about 3% of all chondromas. Spinal chondromas are commonly encountered in the thoracic spine as in our case.ConclusionComplete en bloc surgical excision is generally recommended as the treatment of choice for cases with local and/or neurological symptoms.

Endoscopy-assisted anterior cervical debridement combined with posterior fixation and fusion for the treatment of upper cervical spine tuberculosis: a retrospective feasibility study

BackgroundThis retrospective study aimed to determine the feasibility and efficacy of endoscopy-assisted anterior cervical debridement combined with posterior fixation and fusion in patients with upper cervical spine tuberculosis.MethodsBetween June 2008 and January 2016, 17 patients (10 men and 7 women) with upper cervical spine tuberculosis underwent endoscopy-assisted anterior cervical debridement combined with posterior fixation and fusion. Anti-tuberculosis treatment was administered for 2–4 weeks preoperatively and 12–18 months postoperatively. The clinical and radiographic data of the patients were analyzed.ResultsThe operation was successfully completed in all patients. Neck pain and stiffness were relieved after the surgery in all patients. The mean operation time was 210.0 ± 21.2 min, and the mean intraoperative blood loss was 364.7 ± 49.6 mL. The mean follow-up duration was 68.1 ± 6.7 months. The erythrocyte sedimentation rate returned to normal by 3 months postoperatively. Visual analog scale scores for neck pain were significantly lower postoperatively than preoperatively. All patients had significant postoperative neurological improvement. Patient-reported outcomes, as measured using the Kirkaldy-Willis criteria, were as follows: excellent, 12 patients; good, 4 patients; fair, 1 patient; and poor, 0 patients. Bone fusion was achieved at 10.9 ± 1.9 months after the surgery; no cases of instrument loosening or fracture occurred.ConclusionEndoscopy-assisted anterior cervical debridement combined with posterior fixation and fusion is a feasible and effective surgical method for the treatment of upper cervical spine tuberculosis. It can be used to restore upper cervical spine stability and facilitate spinal healing.

Hematopoietic Stem Cell Transplantation Stabilizes Cerebral Vasculopathy in High-Risk Pediatric Sickle Cell Disease Patients: Evidence From a Referral Transplant Center.

BackgroundSevere sickle cell disease (SCD) can present with different vaso-occlusive manifestations with cerebral vasculopathy (CV) as one of the most serious complications. Hematopoietic stem cell transplant (HSCT) is the ultimate therapy for this complication. The aim of this study was to assess the outcome and impact of HSCT on severe SCD patients with CV complications.MethodsTwenty-five consecutive transplants-naive pediatric SCD patients with CV complications underwent HSCT at our institution between 1993 and 2015, using bone marrow as stem cells source from fully match related donors were included. Neurologic evaluation was done both clinically and radiologically before transplantation and regularly following the HSCT.ResultsWith a median follow-up of 52.2 ± 5.8 months, the cumulative probability of overall survival (OS) at 3 years was 92.0% and event-free survival (EFS) was 88%. Significant neurologic improvements were observed in most of the patients clinically. Different neurologic complications were assessed. The neurologic manifestations before and after HSCT were hemiparesis (11, 1), seizures (13, 8), focal neurologic deficit (4, 2), loss of conscious (2, 1) headache (6, 1), and psychological symptoms (5, 2). Post-HSCT radiological imaging was done in 15 patients, which showed stabilization of CV among all.ConclusionsAllogeneic HSCT in patients with severe SCD presenting with CV complications including moyamoya vasculopathy showed favorable outcome with significant clinical neurologic improvement and stabilization of the disease. None of the patients with severe vasculopathy underwent neurological vascular by-pass surgery prior to HSCT.

Neuroprotective Effects of the Inert Gas Argon on Experimental Traumatic Brain Injury In Vivo with the Controlled Cortical Impact Model in Mice.

Simple SummaryTraumatic brain injuries remain one of the leading causes of death in the western world and developing countries. There is an urgent need for causal therapies for such injuries. The noble gas argon has already shown promising results in in-vitro models. The influence of argon on the extent of damage after a craniocerebral trauma will be investigated in this study, in vivo, in mice. After the trauma, the animals were examined for neurological impairments and their brains were removed to detect brain edema and microscopically detectable alterations.Argon has shown neuroprotective effects after traumatic brain injury (TBI) and cerebral ischemia in vitro and in focal cerebral ischemia in vivo. The purpose of this study is to show whether argon beneficially impacts brain contusion volume (BCV) as the primary outcome parameter, as well as secondary outcome parameters, such as brain edema, intracranial pressure (ICP), neurological outcome, and cerebral blood flow (CBF) in an in-vivo model. Subjects were randomly assigned to either argon treatment or room air. After applying controlled cortical impact (CCI) onto the dura with 8 m/s (displacement 1 mm, impact duration 150 ms), treatment was administered by a recovery chamber with 25%, 50%, or 75% argon and the rest being oxygen for 4 h after trauma. Two control groups received room air for 15 min and 24 h, respectively. Neurological testing and ICP measurements were performed 24 h after trauma, and brains were removed to measure secondary brain damage. The primary outcome parameter, BCV, and the secondary outcome parameter, brain edema, were not significantly reduced by argon treatment at any concentration. There was a highly significant decrease in ICP at 50% argon (p = 0.001), and significant neurological improvement (beamwalk missteps) at 25% and 50% argon (p = 0.01; p = 0.049 respectively) compared to control.

Early Neurodevelopmental Outcome of Asphyxiated Newborns Treated with Therapeutic Hypothermia: A Non Randomised Cohort Study

Introduction: Therapeutic Hypothermia (TH) is now a proven model of treatment to prevent complications in asphyxiated newborns. Perinatal asphyxia is the leading cause of mortality and disability in India and developing countries. The TH is still not the standard treatment protocol in developing India, and data regarding early neurological outcomes after TH is lacking. Aim: To evaluate the early neurological outcome at 3, 6, and 9 months of asphyxiated newborns who received TH compared to non recipients. Materials and Methods: This was a non randomised cohort study conducted at the tertiary care teaching hospital. A total of 190 asphyxiated newborns admitted to Neonatal Intensive Care Unit (NICU) within 24 hours of life, meeting the laboratory and/ or clinical criteria of perinatal asphyxia were enrolled. Eligible newborns admitted within 6 hours of birth receiving TH were labelled as recipients, and those who received standard care were labelled as non-recipients. Neonates were assessed at 3, 6, and 9 months and compared for neurodevelopment using the Hammersmith Infant Neurological Examination (HINE) optimality score and Denver Developmental Screening Test II. Both groups were compared using t-test and chi-square test. Results: Out of the total 190 enrolled participants, 14 were excluded and 176 newborns were further divided into recipients and non recipients groups. Baseline demographic characters were similar in both groups. Seventy-five recipients were followed up till three months, 72 at six months, and 69 at nine months vs 62, 60, and 56 non recipients, respectively. Lesser number of recipients scored suboptimal scores (HINE score &lt;67) at 3 months vs non recipients (20% vs 35.4%, mean/ SD 63 [3.43] vs 57 [4.55], [p&lt;0.001]). At six months (HINE score&lt;70), the incidence was 18% vs 21% (p=0.02), mean score 67 vs 61 (p&lt;0.0001); and at 9 months (HINE score&lt;73) the incidence was 14.4% vs 30.3% (p=0.048), mean score 72 vs 65 among recipient vs non recipients (p&lt;0.0001). Recipients also had less incidence of severe disability (HINE score&lt; 40) at 6 (8.3%vs 21.6% p&lt;0.02), and 9 months (8.3% vs. 19.6%, p&lt;0.04) as compared to non recipients. More recipients had a normal developmental screening at 3,6, and 9 months on the DDST scale. Recipients required fewer anti-epileptics at 3 and 6 months (3 vs 11) as compared to non recipients (p&lt;0.05). Mortality was also less in recipients (7.8% vs 20.9%, p&lt;0.05) as compared to non recipients. Conclusion: There was a significant developmental and neurological improvement with decreased mortality, less episode of seizures, reduction in the need for antiepileptic among recipients of TH compared to non recipients at 3, 6, and 9 months of age.

The Long-Term Efficacy Study of Multiple Allogeneic Canine Adipose Tissue-Derived Mesenchymal Stem Cells Transplantations Combined With Surgery in Four Dogs With Lumbosacral Spinal Cord Injury

Severe lumbosacral pain, paraparesis or paraplegia, and urinary incontinence are common but frustrating problems in dogs with lumbosacral spinal cord injury (SCI). The surgical interventions including stabilization and decompression may not restore satisfying neurological functions in severe SCI. Adipose tissue-derived mesenchymal stem cells (Ad-MSCs) show benefits in immunomodulation, anti-inflammation, and promotion of axonal growth and remyelination, and also display efficacy in several diseases in veterinary medicine. In this report, four dogs presented with fracture of sacrum vertebrae or fracture of seventh lumbar and lumbosacral displacement after road traffic accidents. The clinical signs include lumbosacral pain (4/4), paraparesis (3/4), paraplegia (1/4), and urinary incontinence (4/4). All dogs were treated by surgical decompression with or without stabilization 1 to 7 weeks after trauma. Allogeneic canine Ad-MSCs (cAd-MSCs) were injected locally on nerve roots through the surgical region in all dogs. One dose of intravenous transplantation and 4 doses of local transplantation were also performed within 8 weeks after the surgery separately. All dogs showed significant neurological improvements with normal ambulatory ability (4/4) and urinary control (3/4) 3 months after the surgery and the first cAd-MSCs transplantation. No side effect was related to multiple cAd-MSCs transplantations during 6 months monitoring in all dogs. In conclusion, multiple cAd-MSCs transplantations could be a recommended treatment combined with surgery in dogs with lumbosacral SCI.

Surgical treatment of post-traumatic luxation of rib heads with spinal cord compression in a cat

BackgroundLuxation of the rib head with intrusion into the intervertebral foramen seems to be rare in cats. Only one report has been published describing a cat with non-ambulatory paraparesis, which was managed conservatively. Here we report a case of rib head luxation that was managed surgically.Case presentationA 4-year-old, female domestic shorthair cat with a two-week history of non-ambulatory paraparesis was presented at our clinic. Based on history and neurological examination, a diagnosis of thoracolumbar spinal cord lesion of traumatic origin was made. Computed tomography scanning revealed mild scoliosis, a luxation of the 3rd and 4th right rib heads and penetration into the spinal canal through intervertbral foramina. Surgical management using right dorsal approach to the spine was performed. The spinal cord was decompressed by cutting and removing of proximal ribs’ fragments by rotation and pulling out from the intervertebral foramina. The cat was ambulatory and paraparetic four weeks after surgery. Two years after surgery the cat regained functional gait, but ataxia remained.ConclusionsWe report the first case of a surgical treatment of rib head luxation and intrusion into the spinal canal in a cat. The applied procedure resulted in an improvement of neurological signs.

Anti-Tr/DNER Antibody–Associated Cerebellar Ataxia: a Systematic Review

Rapidly progressive cerebellar ataxia is a classical paraneoplastic neurological syndrome associated with different autoantibodies and typical demographic characteristics, extracerebellar signs, tumor association, and prognosis. Anti-Tr/anti-Delta/Notch-like epidermal growth factor-related receptor (DNER) antibody is one of the associated antibodies. Given the rarity of this condition, our current knowledge is based on case reports and small case series. In order to improve our understanding of these conditions, we conducted a systematic review of the literature. Our study followed the PRISMA reporting guidelines. Studies of patients with the presence of anti-Tr/DNER antibodies in serum or cerebrospinal fluid (CSF) were included. We extract data information related to study characteristics, demographics, clinical symptoms, tumor association, neuroimaging, and cerebrospinal fluid analysis. Out of 131 records, we analyzed 17 papers, including a total of 85 patients with anti-Tr/DNER antibody-associated cerebellar ataxia. We confirmed that this disease occurred mostly in middle-aged males. Isolated cerebellar ataxia was the most common presentation. Extracerebellar features were rare (8%). Ninety-one percent of the patients presented an associated tumor, being Hodgkin lymphoma the most common. Abnormal neuroimaging patterns included cerebellar atrophy (19%) and cerebellar hypersignal (6%). Cerebrospinal fluid was inflammatory in 64% of the patients. Oncological response was complete in 88%, but neurological prognosis was poor with only 41% of the patients presenting significant neurological improvement at the last follow up. Anti-Tr/DNER antibodies should be tested in rapid progressive cerebellar ataxia. Oncological response is excellent; however, many patients do not improve from their cerebellar ataxia.

Intrathecal Chemotherapy As a Potential Alternative Treatment for Steroid-Refractory Immune Effector Cell-Associated Neurotoxicity Syndrome

IntroductionChimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment paradigm for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and other hematologic malignancies. However, its use is associated with serious adverse effects including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Severe ICANS can present with aphasia, mutism, somnolence, seizures, signs of increased intracranial pressure and rarely cerebral edema. Corticosteroids (CS) and IL-6 inhibitors are first line treatment for CRS and ICANS. Prolonged CS use has been associated with decreased over-all survival in CAR T-cell treated patients. Data on effective treatments for CART T-cell induced neurotoxicity is limited, especially in steroid-refractory ICANS. Blood-brain barrier (BBB) disruption and infiltration of myeloid and immune effector cells into the central nervous system are implicated in the pathogenesis of ICANS. This likely explains the role of intrathecal chemotherapy, which has been described in literature for treatment of steroid-refractory ICANS. Here, we report the outcomes of two patients with refractory DLBCL who developed severe ICANS after receiving axicabtagene ciloleucel (axi cel) and treated with intrathecal (IT) chemotherapy.Case PresentationOur first case is of a 66 year old male with diagnosis of R/R DLBCL, who was treated with R-CHOP, followed by R-GemOx, with no response then received axi cel. Patient developed grade 2 CRS and grade 1 ICANS (National Cancer Institute Common Terminology Criteria for Adverse Effects v4.03) on day +2 post infusion, treated with tocilizumab and dexamethasone with good response initially. While tapering dexamethasone on day +5, he developed grade 3 CRS and grade 3 ICANS. Brain MRI did not show any intracranial abnormality and EEG showed no seizure activity. Lumbar puncture (LP) was done on day +7 and showed opening pressure of 32 cm H2O, and 12 lymphocytes. He was started on IV solumedrol and tocilizumab was resumed. CRS improved while neurotoxicity progressed to grade 4 prompting intubation and mechanical ventilation on day +8. On day +9, patient received intrathecal methotrexate 12 mg and hydrocortisone 50 mg. On day +12, neurotoxicity improved to grade 1 and patient was extubated on day +13. Steroid taper stopped on +17. Despite disease response, patient remained hospitalized at day +45 for deconditioning and vocal cord paralysis related to a lengthy hospital stay and intubation. He was eventually discharged, however passed away on day +49 from complications of prolonged hospitalization.Our second case is of a 69 year old female with a diagnosis of R/R DLBCL with CNS involvement, treated with RCHOP x6 followed by salvage chemotherapy with refractory disease, She then received axi cel. Patient developed grade 1 CRS on day +4, treated with tocilizumab and dexamethasone, and patient responded well. On day +9, she developed grade 2 CRS and grade 3 ICANS. At that time, dexamethasone was switched to pulse dose solumedrol and tocilizumab was continued. CT head showed no acute intracranial abnormality and EEG did not show any epileptiform activity. LP showed opening pressure of 21, and 84 lymphocytes. On day +11, patient's CRS resolved, however ICANS developed to grade 4 and patient received 12 mg intrathecal methotrexate and hydrocortisone 50 mg for steroid-refractory ICANS. The very next day, patient showed significant neurological improvement. Steroid taper was initiated and patient's ICANS resolved on day +16. MRI brain showed decrease in size of nodular enhancement along periventricular white matter and left occipital area corresponding to treatment response. She was discharged on day +28 and continues to do well one year out of axi cel infusionConclusionOur abstract adds to the sparse literature about the use IT chemotherapy in cases with severe ICANS. It also highlights its importance as an alternative potential therapy to high doses and prolonged courses of corticosteroids which is associated with increased morbidity and mortality. Steroid-refractory ICANS has limited treatment options and further evaluation of the use of IT chemotherapy in large scale studies is warranted. DisclosuresKahn: Abbvie: Research Funding, Speakers Bureau; Astrazeneca: Research Funding, Speakers Bureau; Beigene: Research Funding, Speakers Bureau; Epizyme: Research Funding, Speakers Bureau; Genetech: Research Funding, Speakers Bureau; GSK: Speakers Bureau; Karyopharm: Speakers Bureau; Kite: Speakers Bureau; Morphosys: Speakers Bureau; Sanofi: Speakers Bureau; SeaGen: Speakers Bureau. Fazal: Agios: Consultancy, Honoraria, Speakers Bureau; AMGEN: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; Glaxo Smith Kline: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Janssen Oncology: Consultancy, Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Karyopharm Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Sanofi Genzyme: Consultancy, Honoraria, Speakers Bureau; Stemline Therapeutics: Consultancy, Honoraria, Speakers Bureau; Taiho Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau. Lister: Oncology Analytics: Other: Academic Board.

P.005 Ovarian resection in anti-NMDAr encephalitis

Background: Anti-N-methyl-D-aspartate receptor encephalitis (NMDArE) is commonly associated with ovarian teratomas, surgical resection of which can lead to significant neurologic improvement. However, the necessity of aggressive resection at the time of diagnosis is unknown; specifically, whether unilateral or bilateral oophorectomy, versus lesionectomy and partial oophorectomy (ovariotomy), is required. Methods: Eleven patients with NMDArE who underwent ovarian resection between January 1st 2012 and December 31st 2020 were retrospectively identified. Primary outcome was good one-year functional status, defined as modified Rankin Scale (mRS) score of 0-1. Results: Median age at encephalitis onset was 24 years (19–38); median delay from symptom onset to surgery was 39 days (16–129). Six patients (54.5%) had good mRS scores, unrelated to surgical resection type. Conclusions: Added clinical benefit of aggressive ovarian resection techniques at one-year follow-up was not identified in our data. Further longitudinal studies are needed to determine the indications for different surgical techniques in patients with NMDArE. Ovarian resection approaches and associated functional outcomes in patients with NMDArE

Treatment of Chronic Spinal Cord Injury in Dogs Using Amniotic Membrane-Derived Stem Cells: Preliminary Results.

IntroductionIntervertebral disc diseases (IVDD) represent the majority of neurological attendance and responsible for the most cases of paralysis in dogs. Treatments currently used do not show satisfactory results in patients with more severe and chronic neurological manifestations.MethodsTo promote nerve and muscular recovery, as well as improve quality of life, we aimed to create a double-blind test method, associating spinal decompression surgery and allogeneic transplantation of amniotic membrane-derived stem cells (AMSCs) in dogs with chronic IVDD. Cells were characterized as fetal mesenchymal cells and safe for application. Eight animals completed the experiment: stem cell applications were made in four animals that had previously undergone an unsuccessful surgical procedure (“SC group”, n = 4); two animals were submitted to surgery, followed by applications of stem cells (“Surgery + SC”, n = 2); two other animals were submitted to surgery, followed by the application of saline solution (“Surgery + placebo”, n = 2). During the surgical procedure, a topical application was performed on the lesion and after fifteen and forty-five days another two applications were made via epidural. Animals were monitored biweekly and reassessed three months after surgery, by functional tests and magnetic resonance exams.ResultsSome animals presented significant neurological improvement, such as the recovery of nociception and ability to remain on station. Despite the need further studies, until the present moment, cell therapy has been feasible and has no harmful effects on animals.ConclusionThe protocol of preclinical trial showed the association with decompressive surgery and cell transplantation in dogs with thoracolumbar IVDD proved feasible, and it was possible to observe neurological improvement after treatment. No tissue improvement through MRI was found. The double-blind test guaranteed reliability of the evaluations and results obtained that, even with a small sample size, generated satisfactory results for the animals and owners.