Lithium alleviates paralysis in experimental autoimmune neuritis in Lewis rats by modulating glycogen synthase kinase-3ß activity.

IMPORTANCE: Guillain-Barré syndrome (GBS)-like neuropathy mimics the leading cause of sporadic acute nontraumatic limb paralysis in individuals from developed countries. Experimental autoimmune neuritis (EAN) is an animal model of GBS and of syndromes such as acute canine polyradiculoneuritis, seen in dogs and cats. OBJECTIVE: The involvement of glycogen synthase kinase (GSK)-3ß, a pro-inflammatory molecule, in rat EAN is not fully understood. This study evaluated the potential role of GSK-3ß in EAN through its inhibition by lithium. METHODS: Lewis rats were injected with SP26 antigen to induce EAN. Lithium was administered from 1 day before immunization to day 14 post-immunization (PI). Then the rats were euthanized and their neural tissues were prepared for histological and Western blotting analyses. RESULTS: Lithium, an inhibitor of GSK-3, significantly ameliorated EAN paralysis in rats, when administered from day 1 to day 14 PI. This corresponded with reduced inflammation in the sciatic nerves of EAN rats, where phosphorylation of GSK-3ß was also upregulated, indicating suppression of GSK-3. CONCLUSIONS AND RELEVANCE: These findings suggest that lithium, an inhibitor of GSK-3ß, plays a significant role in ameliorating rat EAN paralysis, by suppressing GSK-3ß and its related signals in EAN-affected sciatic nerves.

Rewiring movements: A single neuronal population in the spinal cord is crucial to restore walking after paralysis.

A single neuronal population in the spinal cord is crucial to restore walking after paralysis.

Exoskeletal-Assisted Walking in Veterans With Paralysis: A Randomized Clinical Trial.

Importance: Robotic exoskeletons leverage technology that assists people with spinal cord injury (SCI) to walk. The efficacy of home and community exoskeletal use has not been studied in a randomized clinical trial (RCT). Objective: To examine whether use of a wheelchair plus an exoskeleton compared with use of only a wheelchair led to clinically meaningful net improvements in patient-reported outcomes for mental and physical health. Design, Setting, and Participants: This RCT of veterans with SCI was conducted at 15 Veterans Affairs medical centers in the US from September 6, 2016, to September 27, 2021. Data analysis was performed from March 10, 2022, to June 20, 2024. Interventions: Participants were randomized (1:1) to standard of care (SOC) wheelchair use or SOC plus at-will use of a US Food and Drug Administration (FDA)-cleared exoskeletal-assisted walking (EAW) device for 4 months in the home and community. Main Outcomes and Measures: Two primary outcomes were studied: 4.0-point or greater improvement in the mental component summary score on the Veterans RAND 36-Item Health Survey (MCS/VR-36) and 10% improvement in the total T score of the Spinal Cord Injury-Quality of Life (SCI-QOL) physical and medical health domain and reported as the proportion who achieved clinically meaningful changes. The primary outcomes were measured at baseline, post randomization after advanced EAW training sessions, and at 2 months and 4 months (primary end point) in the intervention period. Device usage, reasons for not using, and adverse events were collected. Results: A total of 161 veterans with SCI were randomized to the EAW (n = 78) or SOC (n = 83) group; 151 (94%) were male, the median age was 47 (IQR, 35-56) years, and median time since SCI was 7.3 (IQR, 0.5 to 46.5) years. The difference in proportion of successes between the EAW and SOC groups on the MCS/VR-36 (12 of 78 [15.4%] vs 14 of 83 [16.9%]; relative risk, 0.91; 95% CI, 0.45-1.85) and SCI-QOL physical and medical health domain (10 of 78 [12.8%] vs 11 of 83 [13.3%]; relative risk, 0.97; 95% CI, 0.44-2.15) was not statistically different. Device use was lower than expected (mean [SD] distance, 1.53 [0.02] miles per month), primarily due to the FDA-mandated companion being unavailable 43.9% of the time (177 of 403 instances). Two EAW-related foot fractures and 9 unrelated fractures (mostly during wheelchair transfers) were reported. Conclusions and Relevance: In this RCT of veterans with SCI, the lack of improved outcomes with EAW device use may have been related to the relatively low device usage. Solutions for companion requirements and user-friendly technological adaptations should be considered for improved personal use of these devices. Trial Registration: ClinicalTrials.gov Identifier: NCT02658656.

Imaging of a subcutaneous abscessation in the back of a calf with hindlimb paralysis.

Background: Ultrasonography is not chosen as the common imaging modality to diagnose spinal cord diseases. The present report indicates good diagnostic efficacy of ultrasonography for identifying spinal cord compressed by subcutaneous mass when scanning through the defected vertebral laminae and spinous process. Case Description: A five-month-old female Holstein calf presented with progressive hindlimb paralysis following a surgical resection of a back mass conducted at 21 days of age. The mass was subsequently histopathologically diagnosed as a pulmonary choristoma. Alongside hindlimb paralysis, the calf developed a swollen back at the lumbar region where the mass was removed. This suggested regrowth of the resected mass, causing injury to the underlying spinal cord. Ultrasonography identified the subcutaneous involvement of the capsular mass, which had three anechoic cavities separated by the echogenic septal structures. The spinal cord could be ultrasonographically demonstrated as adjacent to the mass through the defected vertebral laminae and spinous process in the second and third lumbar vertebras. Ultrasound-guided centesis allowed the collection of purulent exudates in which Escherichia coli was isolated. Myelography and subsequent computed tomography (CT) revealed a partial blockage of the intradural flow of contrast media at the levels of the second and third lumbar vertebras, diagnosed as spina bifida on the CT images. When applying ultrasonography to the spinal cord within a saline pool soon after the subcutaneous abscess was successfully resected, the spinal cord was characterized by the interrupted and partly extended hyperechogenic line of the central canal within the echogenic parenchyma. The echotexture of the spinal cord showed damage due to compression from the subcutaneous abscess. The animal had a sub-optimal postoperative outcome, including limited improvement of the neurological signs. Conclusion: In the present case, combining ultrasonography, radiography (myelography), and CT was very effective for diagnosing spina bifida, with the subcutaneous abscess inducing spinal cord compression. Additionally, using intraoperative ultrasonographic scanning to evaluate the degree of spinal cord damage can contribute to predicting the postoperative outcome.

Shoulder Traction as a Possible Risk Factor for C5 Palsy in Anterior Cervical Surgery: A Cadaveric Study.

Background and Objectives: Many risk factors for postoperative C5 palsy (PC5P) have been reported regarding a "cord shift" after a posterior approach. However, there are few reports about shoulder traction as a possible risk factor of anterior cervical surgery. Therefore, we assessed the stretched nerve roots when shoulder traction was applied on cadavers. Materials and Methods: Eight cadavers were employed in this study, available based on age and the presence of foramen stenosis. After dissecting the sternocleidomastoid muscle of the cadaver, the shoulder joint was pulled with a force of 2, 5, 8, 10, 15, and 20 kg. Then, the stretched length of the fifth nerve root was measured in the extra-foraminal zone. In addition, the same measurement was performed after cutting the carotid artery to accurately identify the nerve root's origin. After an additional dissection was performed so that the superior trunk of the brachial plexus could be seen, the stretched length of the fifth and sixth nerve roots was measured again. Results: Throughout the entire experiment, the fifth nerve root stretched out for an average of 1.94 mm at 8 kg and an average of 5.03 mm at a maximum force of 20 kg. In three experiments, the elongated lengths of the C5 nerve root at 8 kg and 20 kg were 1.69/4.38 mm, 2.13/5.00 mm, and 0.75/5.31 mm, respectively, and in the third experiment, the elongated length of the C6 nerve root was 1.88/5.44 mm. Conclusions: Although this was a cadaveric experiment, it suggests that shoulder traction could be the risk factors for PC5P after anterior cervical surgery. In addition, for patients with foraminal stenosis and central stenosis, the risk would be higher. Therefore, the surgeon should be aware of this, and the patient would need sufficient explanation.

Orientaciones para la búsqueda activa de casos de parálisis flácida aguda, sarampión y rubéola / Guidelines for active case finding of acute flaccid paralysis, measles and rubella

La presente publicación describe las orientaciones técnicas e instrumentos de recolección de datos para realizar la búsqueda activa integral de parálisis flácida aguda, sarampión y rubéola a nivel institucional (establecimientos de salud) y comunitario. La implementación conjunta de la búsqueda activa para estas tres enfermedades pretende lograr una sinergia de los recursos humanos y financieros, tomando en cuenta las consideraciones específicas de cada enfermedad. Asimismo, presenta, en los anexos, los diagnósticos diferenciales e instrumentos de recolección de datos para otras enfermedades prevenibles por vacunación como difteria, tétanos, tétanos neonatal y tos ferina, en caso de que el país tenga interés en incluir alguna de estas enfermedades durante la implementación de la búsqueda activa

Comparison between Air-Q Self Pressurized Airway Device with Blocker and Proseal Laryngeal Mask Airway in anesthetized paralyzed adult female patients undergoing elective gynecological operations.

INTRODUCTION: The Air-Q Self Pressurized Airway Device with Blocker (SP Blocker) was compared to the Proseal Laryngeal Mask Airway (PLMA) during positive pressure ventilation regarding the primary outcome (oropharyngeal leak pressure [OLP]), secondary outcomes (peak inspiratory pressure [PIP], inspired tidal volume [ITV], expired tidal volume [ETV], leak volume [LV] and leak fraction [LF]), insertion time, ventilation score, fiber-optic glottis view score, and postoperative laryngopharyngeal parameters (LPM). MATERIAL AND METHODS: Adult healthy female patients scheduled for elective gynecological laparotomies under general anesthesia using controlled mechanical ventilation were recruited to a prospective randomized comparative clinical trial. Exclusion criteria were body mass index (BMI) ≥ 35 kg m -2 , El-Ganzouri score ≥ 5, upper airway problems, hiatus hernia or pregnancy. Patients were classified into an SP Blocker group ( n = 75) and a PLMA group ( n = 75). Primary and secondary outcomes were assessed initially and at fixed time points after successful insertion of devices. RESULTS: Initially after successful device insertion: the SP Blocker group showed statistically significant higher mean OLP (cmH 2 O) (29.46 ± 2.11 vs. 28.06 ± 1.83 respectively; 95% CI: -2.037 to -0.76, P < 0.0001), lower mean PIP (cmH 2 O) (15.49 ± 0.61 vs. 17.78 ± 1.04 respectively; 95% CI: 2.02 to 2.56, P < 0.0001), higher mean ITV (mL) (411 ± 30 vs. 403 ± 15 respectively; 95% CI: -15.65 to -0.347, P = 0.041), higher mean ETV (mL) (389 ± 12 vs. 354 ± 11 respectively; 95% CI: -38.72 to -31.29, P < 0.0001), lower mean LV (mL) (22 ± 18 vs. 49 ± 10 respectively; 95% CI: 22.3 to 31.7, P < 0.0001) and lower mean LF (%) (5 ± 2.04 vs. 12 ± 6.8 respectively; 95% CI: 5.38 to 8.62, P < 0.0001) than the PLMA group. Mean insertion time (seconds) was shorter in the SP Blocker group than the PLMA group (16.39 ± 2.81 vs. 18.63 ± 3.44 respectively; 95% CI: 1.23 to 3.25, P < 0.0001). The SP Blocker group offered a better fiber-optic glottis view score than the PLMA group without differences concerning ventilation score and LPM. CONCLUSIONS: SP Blocker provided as safe anesthesia during controlled mechanical ventilation as PLMA.

Lacticaseibacillus rhamnosus HA-114 and Bacillus subtilis R0179 Prolong Lifespan and Mitigate Amyloid-ß Toxicity in C. elegans via Distinct Mechanisms.

Background: Recent advances linking gut dysbiosis with neurocognitive disorders such as Alzheimer's disease (AD) suggest that the microbiota-gut-brain axis could be targeted for AD prevention, management, or treatment. Objective: We sought to identify probiotics that can delay Aß-induced paralysis. Methods: Using C. elegans expressing human amyloid-ß (Aß)1-42 in body wall muscles (GMC101), we assessed the effects of several probiotic strains on paralysis. Results: We found that Lacticaseibacillus rhamnosus HA-114 and Bacillus subtilis R0179, but not their supernatants or heat-treated forms, delayed paralysis and prolonged lifespan without affecting the levels of amyloid-ß aggregates. To uncover the mechanism involved, we explored the role of two known pathways involved in neurogenerative diseases, namely mitophagy, via deletion of the mitophagy factor PINK-1, and fatty acid desaturation, via deletion of the Δ9 desaturase FAT-5. Pink-1 deletion in GMC101 worms did not modify the life-prolonging and anti-paralysis effects of HA-114 but reduced the protective effect of R0179 against paralysis without affecting its life-prolonging effect. Upon fat5 deletion in GMC101 worms, the monounsaturated C14:1 and C16:1 FAs conserved their beneficial effect while the saturated C14:0 and C16:0 FAs did not. The beneficial effects of R0179 on both lifespan and paralysis remained unaffected by fat-5 deletion, while the beneficial effect of HA-114 on paralysis and lifespan was significantly reduced. Conclusions: Collectively with clinical and preclinical evidence in other models, our results suggest that HA-114 or R0179 could be studied as potential therapeutical adjuncts in neurodegenerative diseases such as AD.

Idiopathic cervical cord infarction in a young girl presenting with acute neck pain and flaccid paralysis: a case report.

INTRODUCTION: Spinal cord infarction (SCI) is a rare disease representing nearly 1% of all strokes with a wide variety of symptoms at presentation. SCI diagnosis is very challenging owing to its low incidence and the variety of symptoms, and could be misdiagnosed with neuromyelitis optica spectrum disorders (NMOSD). CASE PRESENTATION: We describe the case of an 18-year-old girl who presented to the emergency department with acute neck pain and flaccid paralysis of the left upper and lower extremities. Few hours later, she developed apnea and was endotracheally intubated. Brain MRI was normal but spinal cord MRI revealed non-enhancing longitudinal abnormal high T2 signal intensity extending from C1 to C5. The patient underwent steroid therapy with methylprednisolone (1 g daily for 7 consecutive days) combined with physiotherapy. She was extubated after 3 weeks and discharged after 30 days of hospitalization with a muscle force of 4/5 in her left extremities. DISCUSSION: Idiopathic SCI in adolescence is a rare but often devastating disorder with unknown pathophysiology, however, some specific conditions in adolescent such as mechanical stresses on the immature spine can be considered as risk factors for SCI development. Early diagnosis and treatment can improve outcomes in SCI.

NMR-based metabolomic investigation of dogs with acute flaccid paralysis due to tick paralysis.

BACKGROUND: Acute flaccid paralysis (AFP) is a complex clinical syndrome with various aetiologies. If untreated, AFP may lead to death due to failure of respiratory muscles. Tick paralysis, which is a noninfectious neurologic syndrome of AFP, occurs following tick attachment, engorgement, and injection of tick saliva toxins. There is no specific diagnostic test for tick paralysis, and mortality increases as definitive diagnosis is delayed. Although metabolomic investigation of tick saliva was conducted, there is a lack of research on metabolomic evaluation of hosts affected by tick paralysis. OBJECTIVES: Thus, the aim of this study is to investigate metabolomic changes in serum samples of dogs with tick paralysis due to Rhipicephalus sanguineus using NMR-based metabolomics and to identify potential diagnostic/prognostic markers. MATERIALS AND METHODS: Forty dogs infested with R. sanguineus, with clinical findings compatible with AFP and with a confirmed tick paralysis diagnosis ex juvantibus, constituted the Paralysis Group. Ten healthy dogs, which were admitted either for vaccination and/or check-up purposes, constituted the Control Group. After the confirmation tick paralysis, medical history, vaccination and nutritional status, body surface area and estimated tick numbers of all the dogs were noted. Physical examination included body temperature, heart and respiratory rate, capillary refill time evaluation and Modified Glasgow Coma Scale calculation. Serum samples were extracted from venous blood samples of all the dogs and were prepared for NMR analysis, and NMR-based metabolomics identification and quantification were performed. RESULTS: NMR-based serum metabolomics of the present study revealed distinct up/down-regulated expressions, presenting a promising avenue. Moreover, it was observed that energy metabolism and especially liver functions were impaired in dogs with tick paralysis, and not only the respiratory system but also the kidneys were affected. CONCLUSION: It was concluded that the present approach may help to better understand the pathological mechanisms developing in cases of AFP due to tick paralysis.

A Virtual Reality-Based Protocol to Determine the Preferred Control Strategy for Hand Neuroprostheses in People With Paralysis.

Hand neuroprostheses restore voluntary movement in people with paralysis through neuromodulation protocols. There are a variety of strategies to control hand neuroprostheses, which can be based on residual body movements or brain activity. There is no universally superior solution, rather the best approach may vary from patient to patient. Here, we propose a protocol based on an immersive virtual reality (VR) environment that simulates the use of a hand neuroprosthesis to allow patients to experience and familiarize themselves with various control schemes in clinically relevant tasks and choose the preferred one. We used our VR environment to compare two alternative control strategies over 5 days of training in four patients with C6 spinal cord injury: (a) control via the ipsilateral wrist, (b) control via the contralateral shoulder. We did not find a one-fits-all solution but rather a subject-specific preference that could not be predicted based only on a general clinical assessment. The main results were that the VR simulation allowed participants to experience the pros and cons of the proposed strategies and make an educated choice, and that there was a longitudinal improvement. This shows that our VR-based protocol is a useful tool for personalization and training of the control strategy of hand neuroprostheses, which could help to promote user comfort and thus acceptance.

Palsy of Both the Tibial Nerve and Common Peroneal Nerve Caused by a Ganglion Cyst in the Popliteal Area.

A ganglion cyst is a benign mass consisting of high-viscosity mucinous fluid. It can originate from the sheath of a tendon, peripheral nerve, or joint capsule. Compressive neuropathy caused by a ganglion cyst is rarely reported, with the majority of documented cases involving peroneal nerve palsy. To date, cases demonstrating both peroneal and tibial nerve palsies resulting from a ganglion cyst forming on a branch of the sciatic nerve have not been reported. In this paper, we present the case of a 74-year-old man visiting an outpatient clinic complaining of left-sided foot drop and sensory loss in the lower extremity, a lack of strength in his left leg, and a decrease in sensation in the leg for the past month without any history of trauma. Ankle dorsiflexion and great toe extension strength on the left side were Grade I. Ankle plantar flexion and great toe flexion were Grade II. We suspected peroneal and tibial nerve palsy and performed a screening ultrasound, which is inexpensive and rapid. In the operative field, several cysts were discovered, originating at the site where the sciatic nerve splits into peroneal and tibial nerves. After successful surgical decompression and a series of rehabilitation procedures, the patient's neurological symptoms improved. There was no recurrence.

Risk factors for preoperative neurological impairment in patients with spinal meningioma: A retrospective multicenter study.

BACKGROUND: Patients with spinal meningioma may present preoperatively with paralysis and sensory deficits. However, there is a paucity of detailed evaluations and a lack of consensus regarding imaging findings that are predictive of neurological symptoms in patients with spinal meningioma. METHODS: Herein, a total of 55 patients who underwent surgical resection of spinal meningiomas in eight hospitals between 2011 and 2021 were enrolled. Patient characteristics, degree of muscle weakness, sensory disturbances, and the presence of bowel/bladder dysfunction (BBD) before surgical treatment were evaluated using medical records. Patients with American Spinal Injury Impairment Scale grades A-C and the presence of BBD were classified into the paralysis (+) group. Patients with sensory disturbances were assigned to the sensory disturbance (+) group. Based on magnetic resonance (MR) and computed tomography images, the tumor location was classified according to the spinal level and its attachment to the dura mater. To evaluate tumor size, the tumor occupation ratio (OR) was calculated using the area and distance measurement method in horizontal MR images, and the maximum length and area of the tumor in the sagittal plane were measured. RESULTS: Of all patients, 85 % were women. The mean age of patients at surgery was 69.7 years. Twenty-eight (51 %) and 41 (75 %) patients were classified into the paralysis (+) and sensory disturbance (+) groups, respectively. The average tumor length and area in the sagittal plane were 19.6 mm and 203 mm2, respectively; OR-area and diameters were 70.3 % and 72.3 %, respectively. In univariate analyses, tumor length and area in the sagittal plane were significant risk factors for paralysis. OR-diameter, symptom duration, and a low MIB-1 index correlated with sensory disturbances. Multivariate logistic regression analysis demonstrated that the area and length of the tumor in the sagittal plane were significantly correlated with paralysis, whereas the OR-diameter and symptom duration significantly correlated with sensory disturbances. The cut-off values for the area and length of the tumor in the sagittal plane to predict paralysis were 243 mm2 and 20.1 mm, respectively. CONCLUSIONS: Preoperative paralysis in patients with spinal meningiomas was significantly associated with sagittal tumor size than with high tumor occupancy in the horizontal plane. Sensory disturbances were associated with high occupancy in the horizontal plane. Patients with spinal meningiomas > 20 mm in length or 243 mm2 in area in the sagittal plane are at risk of developing paralysis and could be considered for surgery even in the absence of paralysis.

Local Tetanus Begins with a Neuromuscular Junction Paralysis around the Site of Tetanus Neurotoxin Release due to Cleavage of the Vesicle-Associated Membrane Protein.

Local tetanus develops when limited amounts of tetanus neurotoxin (TeNT) are released by Clostridium tetani generated from spores inside a necrotic wound. Within days, a spastic paralysis restricted to the muscles of the affected anatomical area develops. This paralysis follows the retrograde transport of TeNT inside the axons of motoneurons and its uptake by inhibitory interneurons with cleavage of a vesicle-associated membrane protein required for neurotransmitter release. Consequently, incontrollable excitation of motoneurons causes contractures of innervated muscles and leads to local spastic paralysis. Here, the initial events occurring close to the site of TeNT release were investigated in a mouse model of local tetanus. A peripheral flaccid paralysis was found to occur, before or concurrent to the spastic paralysis. At variance from the confined TeNT proteolytic activity taking place within motor neuron terminals, central protein cleavage was detected within inhibitory interneurons controlling motor neuron efferents innervating muscle groups distant from the site of TeNT release. These results indicate peripheral activity of TeNT in tetanus and explains why the spastic paralysis observed in local tetanus, although confined to single limbs, generally affects multiple muscles. The initial TeNT neuroparalytic activity can be detected by measuring the compound muscle action potential, providing a very early diagnosis and therapy, thus preventing the ensuing life-threatening generalized tetanus.

Single-cell and spatial atlases of spinal cord injury in the Tabulae Paralytica.

Here, we introduce the Tabulae Paralytica-a compilation of four atlases of spinal cord injury (SCI) comprising a single-nucleus transcriptome atlas of half a million cells, a multiome atlas pairing transcriptomic and epigenomic measurements within the same nuclei, and two spatial transcriptomic atlases of the injured spinal cord spanning four spatial and temporal dimensions. We integrated these atlases into a common framework to dissect the molecular logic that governs the responses to injury within the spinal cord1. The Tabulae Paralytica uncovered new biological principles that dictate the consequences of SCI, including conserved and divergent neuronal responses to injury; the priming of specific neuronal subpopulations to upregulate circuit-reorganizing programs after injury; an inverse relationship between neuronal stress responses and the activation of circuit reorganization programs; the necessity of re-establishing a tripartite neuroprotective barrier between immune-privileged and extra-neural environments after SCI and a failure to form this barrier in old mice. We leveraged the Tabulae Paralytica to develop a rejuvenative gene therapy that re-established this tripartite barrier, and restored the natural recovery of walking after paralysis in old mice. The Tabulae Paralytica provides a window into the pathobiology of SCI, while establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.

The evolution, facilitators, barriers, and additional activities of acute flaccid paralysis surveillance platform in polio eradication programme Bangladesh: a mixed-method study.

BACKGROUND: The Global Polio Eradication Initiative (GPEI) helped develop the standard acute flaccid paralysis surveillance (AFP) system worldwide, including, knowledge, expertise, technical assistance, and trained personnel. AFP surveillance can complement any disease surveillance system. OBJECTIVE: This study outlines AFP surveillance evolution in Bangladesh, its success and challenging factors, and its potential to facilitate other health goals. METHODS: This mixed-method study includes a grey literature review, survey, and key informant interviews (KIIs). We collected grey literature from online websites and paper documentation from GPEI stakeholders. Online and in-person surveys were conducted in six divisions of Bangladesh, including Dhaka, Rajshahi, Rangpur, Chittagong, Sylhet, and Khulna, to map tacit knowledge ideas, approaches, and experiences. We also conducted KIIs, and Data were then combined on focused emerging themes, including the history, challenges, and successes of AFP surveillance programme. RESULTS: According to the grey literature review, survey, and KII, AFP surveillance successfully contributed to decreasing polio in Bangladesh. The major facilitating factors were multi-sectoral collaboration, Surveillance Immunization Medical Officer (SIMO) network activities, social environment, community-based surveillance, and promising political commitment. On the other hand, high population growth, hard-to-reach areas, people residing in risky zones, and polio transition planning were significant challenges. Bangladesh is also utilizing these polio surveillance assets for other vaccine-preventable diseases. CONCLUSION: As the world is so close to eradicating polio, the knowledge, and other assets of the AFP surveillance, could be used for other health programmes. In addition, its strengths can be leveraged for combating new and emerging diseases.

Main findings: The research found that Bangladesh has achieved a world-standard surveillance system, with facilitating factors including multi-sectoral collaboration, GPEI partners, and political and community support. However, high population growth, hard-to-reach areas and people, and polio transition planning were found to be challenges.Added knowledge: In addition, Bangladesh is now utilizing these polio surveillance assets to monitor other vaccine-preventable diseases.Global health impact for policy and action: Since polio is still a threat to some LMICs, the knowledge gained from AFP surveillance of Bangladesh could assist those countries in eradicating the cases of polio from the earth and serve VPDs and other health programmes as well.

VP1 is the primary determinant of neuropathogenesis in a mouse model of enterovirus D68 acute flaccid myelitis.

Enterovirus D68 (EV-D68) is an emerging pathogen that can cause severe respiratory and neurologic disease [acute flaccid myelitis (AFM)]. Intramuscular (IM) injection of neonatal Swiss Webster (SW) mice with US/IL/14-18952 (IL52), a clinical isolate from the 2014 EV-D68 epidemic, results in many of the pathogenic features of human AFM, including viral infection of the spinal cord, death of motor neurons, and resultant progressive paralysis. In distinction, CA/14-4231 (CA4231), another clinical isolate from the 2014 EV-D68 outbreak, does not cause paralysis in mice, does not grow in the spinal cord, and does not cause motor neuron loss following IM injection. A panel of chimeric viruses containing sequences from IL52 and CA4231 was used to demonstrate that VP1 is the main determinant of EV-D68 neurovirulence following IM injection of neonatal SW mice. VP1 contains four amino acid differences between IL52 and CA4231. Mutations resulting in substituting these four amino acids (CA4231 residues into the IL52 polyprotein) completely abolished neurovirulence. Conversely, mutations resulting in substituting VP1 IL52 amino acid residues into the CA4231 polyprotein created a virus that induced paralysis to the same degree as IL52. Neurovirulence following infection of neonatal SW mice with parental and chimeric viruses was associated with viral growth in the spinal cord. IMPORTANCE: Emerging viruses allow us to investigate mutations leading to increased disease severity. Enterovirus D68 (EV-D68), once the cause of rare cases of respiratory illness, recently acquired the ability to cause severe respiratory and neurologic disease. Chimeric viruses were used to demonstrate that viral structural protein VP1 determines growth in the spinal cord, motor neuron loss, and paralysis following intramuscular (IM) injection of neonatal Swiss Webster (SW) mice with EV-D68. These results have relevance for predicting the clinical outcome of future EV-D68 epidemics as well as targeting retrograde transport as a potential strategy for treating virus-induced neurologic disease.