[Cause analysis and clinical intervention of C 5 palsy after cervical surgery].

Objective: To review the research progress of C 5 palsy (C 5P) after cervical surgery, providing new clinical intervention ideas for the C 5P patients. Methods: The relevant literature domestically and abroad was extensively consulted and the latest developments in the incidence, risk factors, manifestations and diagnosis, prevention, and intervention measures of C 5P were systematically expounded. Results: C 5P is characterized by weakness in the C 5 nerve innervation area after cervical decompression surgery, manifested as limited shoulder abduction and elbow flexion, with an incidence rate more than 5%, often caused by segmental spinal cord injury or mechanical injury to the nerve roots. For patients with risk factors, careful operation and preventive measures can reduce the incidence of C 5P. Most of the patients can recover with conservative treatment such as drug therapy and physical therapy, while those without significant improvement after 6 months of treatment may require surgical intervention such as foraminal decompression and nerve displacement. Conclusion: Currently, there has been some advancement in the etiology and intervention of C 5P. Nevertheless, further research is imperative to assess the timing of intervention and surgical protocol.

3-Hydroxyanthranilic Acid Delays Paralysis in Caenorhabditis elegans Models of Amyloid-Beta and Polyglutamine Proteotoxicity.

Age is the primary risk factor for neurodegenerative diseases such as Alzheimer's and Huntington's disease. Alzheimer's disease is the most common form of dementia and a leading cause of death in the elderly population of the United States. No effective treatments for these diseases currently exist. Identifying effective treatments for Alzheimer's, Huntington's, and other neurodegenerative diseases is a major current focus of national scientific resources, and there is a critical need for novel therapeutic strategies. Here, we investigate the potential for targeting the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3HAA) using Caenorhabditis elegans expressing amyloid-beta or a polyglutamine peptide in body wall muscle, modeling the proteotoxicity in Alzheimer's and Huntington's disease, respectively. We show that knocking down the enzyme that degrades 3HAA, 3HAA dioxygenase (HAAO), delays the age-associated paralysis in both models. This effect on paralysis was independent of the protein aggregation in the polyglutamine model. We also show that the mechanism of protection against proteotoxicity from HAAO knockdown is mimicked by 3HAA supplementation, supporting elevated 3HAA as the mediating event linking HAAO knockdown to delayed paralysis. This work demonstrates the potential for 3HAA as a targeted therapeutic in neurodegenerative disease, though the mechanism is yet to be explored.

Venous Sinus Stent to Treat Paralysis.

Transvenous treatment of paralysis is a concept less than a decade old. The Stentrode (Synchron, Inc, New York, USA) is a novel electrode on stent device intended to be implanted in the superior sagittal sinus adjacent to the motor cortex. Initial animal studies in sheep demonstrated the safety of the implant as well as its accuracy in detecting neural signals at both short and long term. Early human trials have shown the safety of the device and demonstrated the use of the Stentrode system in facilitating patients with paralysis to carry out daily activities such as texting, email, and personal finance. This is an emerging technology with promise, although certainly more research is required to better understand the capabilities and limitations of the device.

Detection and genetic diversity of parechoviruses in children with acute flaccid paralysis in Cameroon.

Human Parechoviruses (HPeVs) have rarely been considered in the virological investigation of Acute Flacid Paralysis (AFP) cases in Africa, where enteric infections are very common. This study investigated the prevalence and genetic diversity of HPeV in 200 children aged ≤ 15 years with AFP in Cameroon from 2018 to 2019. HPeVs were detected in their faecal RNA using 5'-untranslated real-time RT-PCR. Detected HPeVs were typed by phylogenetic comparison with homologous sequences from homotypic reference strains. Overall, HPeV RNA was detected in 11.0% (22/200) of the 200 stool samples tested. Twelve HPeVs were successfully sequenced and reliably assigned to HPeV-A1, A4, A5, A10, A14, A15, A17 and A18 genotypes. Phylogenetic analyses revealed a high genetic variability among the studied HPeVs, as well as between the studied HPeVs and their previously reported counterparts from Cameroon in 2014. These findings suggest that different HPeV genotypes co-circulate in Cameroon without documented epidemics.

A guiding light for stimulating paralyzed muscles.

Improving the performance of closed-loop optogenetic nerve stimulation can reproduce desired muscle activation patterns.

Thirteen-year surveillance results of acute flaccid paralysis cases in Southeast Turkey and the effect of refugee movements on surveillance results.

OBJECTIVE: Acute flaccid paralysis (AFP) is a major neurological problem. Turkey has accepted over 4 million refugees since 2011 due to the wars in neighbouring countries. In the long term, refugees can have adverse effects on the limited resources of health, sanitation, water supply, foodstuff, and shelter services of host countries, precipitating the transmission and spread of enteroviruses causing AFP. This study examines the 13-year surveillance and incidence of AFP cases in southeast Turkey, and questions possible impact of refugee movements on these parameters, comparing the periods before (2007-2010) and after (2011-2019) 2011, when the refugee movements emerged. METHODS: The records of cases reported from southeast part of Turkey with suspected AFP between January 2007 and December 2019 were reviewed retrospectively. RESULTS: Of the patients, 121 (58.5%) were male. Mean age was 80.36 ± 46.67 months. Eighty-five (41.1%) were aged 60 months or younger. The number of patients under 60 months increased significantly after 2011. Mean incidence was calculated as 0.88 cases/100,000 person years versus 1.58 cases/100,000 person years in the period before and after 2011, respectively. Guillain-Barré syndrome (GBS) was the most common cause of AFP in both periods. As of 2011, however, the incidence of acute transverse myelitis increased approximately 4 times and GBS decreased proportionally. Non-polio enteroviruses were the most frequent isolates, detected from 9.1% of stool samples. CONCLUSION: Although refugee movements appear to may have adverse effects on AFP incidence and surveillance outcomes, larger studies involving the whole country, particularly at places where no refugees settled, are needed to achieve more conclusive evidence.

Iatrogenic botulism cases after gastric and axillary application of botulinum toxin and review of literature.

INTRODUCTION: Iatrogenic botulism is a rare, serious disease that progresses with descending paralysis and develops after cosmetic or therapeutic botulinum toxin-A (BoNT-A) application. CASE PRESENTATIONS: In this case series; six cases of iatrogenic botulism followed up in our center are presented. Four of these developed after gastric BoNT-A and two after axillary BoNT-A application. RESULTS: The most important cause for the disease was the use of unlicensed products and high-dose toxin applications. The first symptoms were blurred vision, double vision, difficulty in swallowing, and hoarseness. Symptoms appeared within 4-10 days after the application of BoNT-A. Symptoms progressed in the course of descending paralysis in the following days with fatigue, weakness in extremities and respiratory distress. Diagnosis was based on patient history and clinical findings. The main principles of foodborne botulism therapy were applied in the treatment of iatrogenic botulism. If clinical worsening continued, regardless of the time elapsed after BoNT-A application, the use of botulinum antitoxin made a significant contribution to clinical improvement and was recommended. CONCLUSIONS: Routine and new indications for BoNT-A usage are increasing and, as a result, cases of iatrogenic botulism will be encountered more frequently. Physicians should be alert for iatrogenic botulism in the follow-up after BoNT-A applications and in the differential diagnosis of neurological diseases that are presented with similar findings.

The effect of common paralytic agents used for fluorescence imaging on redox tone and ATP levels in Caenorhabditis elegans.

One aspect of Caenorhabditis elegans that makes it a highly valuable model organism is the ease of use of in vivo genetic reporters, facilitated by its transparent cuticle and highly tractable genetics. Despite the rapid advancement of these technologies, worms must be paralyzed for most imaging applications, and few investigations have characterized the impacts of common chemical anesthetic methods on the parameters measured, in particular biochemical measurements such as cellular energetics and redox tone. Using two dynamic reporters, QUEEN-2m for relative ATP levels and reduction-oxidation sensitive GFP (roGFP) for redox tone, we assess the impact of commonly used chemical paralytics. We report that no chemical anesthetic is entirely effective at doses required for full paralysis without altering redox tone or ATP levels, and that anesthetic use alters the detected outcome of rotenone exposure on relative ATP levels and redox tone. We also assess the use of cold shock, commonly used in combination with physical restraint methods, and find that cold shock does not alter either ATP levels or redox tone. In addition to informing which paralytics are most appropriate for research in these topics, we highlight the need for tailoring the use of anesthetics to different endpoints and experimental questions. Further, we reinforce the need for developing less disruptive paralytic methods for optimal imaging of dynamic in vivo reporters.

Epidural Catheterization in Cardiac Surgery: A Systematic Review and Risk Assessment of Epidural Hematoma.

ABSTRACT: The potential benefits of epidural anesthesia on mortality, atrial fibrillation, and pulmonary complications must be weighed against the risk of epidural hematoma associated with intraoperative heparinization. This study aims to provide an updated assessment of the clinical risks of epidural anesthesia in cardiac surgery, focusing on the occurrence of epidural hematomas and subsequent paralysis. A systematic search of Embase, Medline, Ovid Central, Web of Science, and PubMed was conducted to identify relevant publications between 1966 and 2022. Two independent reviewers assessed the eligibility of the retrieved manuscripts. Studies reporting adult patients undergoing cardiac surgery with epidural catheterization were included. The incidence of hematomas was calculated by dividing the number of hematomas by the total number of patients in the included studies. Risk calculations utilized various denominators based on the rigor of trial designs, and the risks of hematoma and paralysis were compared to other commonly encountered risks. The analysis included a total of 33,089 patients who underwent cardiac surgery with epidural catheterization. No epidural hematomas were reported across all published RCTs, prospective, and retrospective trials. Four case reports associated epidural hematoma with epidural catheterization and perioperative heparinization. The risks of epidural hematoma and subsequent paralysis were estimated at 1:7643 (95% CI 1:3860 to 380,916) and 1:10,190 (95% CI 1:4781 to 0:1), respectively. The risk of hematoma is similar to the non-obstetric population (1:5405; 95% CI 1:4784 to 6134). The risk of hematoma in cardiac surgery patients receiving epidural anesthesia is therefore similar to that observed in some other surgical non-obstetric populations commonly exposed to epidural catheterization.

Genetic analysis of 37 cases with primary periodic paralysis in Chinese patients.

BACKGROUND: Primary periodic paralysis (PPP) is an inherited disorders of ion channel dysfunction characterized by recurrent episodes of flaccid muscle weakness, which can classified as hypokalemic (HypoPP), normokalemic (NormoPP), or hyperkalemic (HyperPP) according to the potassium level during the paralytic attacks. However, PPP is charactered by remarkable clinical and genetic heterogeneity, and the diagnosis of suspected patients is based on the characteristic clinical presentation then confirmed by genetic testing. At present, there are only limited cohort studies on PPP in the Chinese population. RESULTS: We included 37 patients with a clinical diagnosis of PPP. Eleven (29.7%) patients were tested using a specific gene panel and 26 (70.3%) by the whole-exome sequencing (WES). Twenty-two cases had a genetic variant identified, representing a diagnostic rate of 59.5% (22/37). All the identified mutations were either in the SCN4A or the CACNA1S gene. The overall detection rate was comparable between the panel (54.5%: 6/11) and WES (61.5%: 16/26). The remaining patients unresolved through panel sequencing were further analyzed by WES, without the detection of any mutation. The novel atypical splicing variant c.2020-5G > A affects the normal splicing of the SCN4A mRNA, which was confirmed by minigene splicing assay. Among 21 patients with HypoPP, 15 patients were classified as HypoPP-2 with SCN4A variants, and 6 HypoPP-1 patients had CACNA1S variants. CONCLUSIONS: Our results suggest that SCN4A alleles are the main cause in our cohort, with the remainder caused by CACNA1S alleles, which are the predominant cause in Europe and the United States. Additionally, this study identified 3 novel SCN4A and 2 novel CACNA1S variants, broadening the mutation spectrum of genes associated with PPP.

Torsion and clinical features in patients with acquired fourth cranial nerve palsy.

This retrospective study aimed to compare objective/subjective torsion and other clinical characteristics of patients with acquired trochlear nerve palsy. This study included 82 consecutive patients who were diagnosed with acquired fourth cranial nerve palsy between 2014 and 2021 and who were followed up for ≥ 6 months. The etiologies, ocular deviation, objective and subjective torsions were reviewed. The etiologies were classified as ischemic, traumatic, brain lesion, idiopathic, or other. The patients were classified into two groups according to the recovery state: full recovery and partial/no-recovery. We compared the torsion and clinical features based on the etiology and recovery state. The average age was 59.1 ± 11.1 years, and 58 (71.0%) of the patients were male. The most common cause was ischemic (n = 49, 59.7%) and other common causes included traumatic (n = 16, 19.5%), brain lesion (n = 8, 9.8%), idiopathic (n = 5, 6.1%) and others (n = 4, 4.9%). Of the 82 patients, 56 (68.3%) were assigned to the full recovery group, and 26 (31.7%) were assigned to the partial/no-recovery group. The average age and number of patients with ischemic causes of palsy were greater in the full recovery group (p = 0.026 and p < 0.000, respectively). The vertical deviation angle, tilted angle on the Lancaster red-green test (LRGT), proportion of patients who experienced subjective torsion on the LRGT, and head tilt were smaller in the full recovery group (p = 0.037, 0.042, 0.045, and 0.006, respectively). Ischemic trochlear nerve palsy, advanced age, a small deviation angle at the primary position, and few cases of excyclotorsion on LRGT were characteristic of the full recovery group of acquired unilateral trochlear nerve palsy patients.

Chronic bee paralysis virus exploits host antimicrobial peptides and alters gut microbiota composition to facilitate viral infection.

The significance of gut microbiota in regulating animal immune response to viral infection is increasingly recognized. However, how chronic bee paralysis virus (CBPV) exploits host immune to disturb microbiota for its proliferation remains elusive. Through histopathological examination, we discovered that the hindgut harbored the highest level of CBPV, and displayed visible signs of damages. The metagenomic analysis showed that a notable reduction in the levels of Snodgrassella alvi and Lactobacillus apis, and a significant increase in the abundance of the opportunistic pathogens such as Enterobacter hormaechei and Enterobacter cloacae following CBPV infection. Subsequent co-inoculation experiments showed that these opportunistic pathogens facilitated the CBPV proliferation, leading to accelerated mortality in bees and exacerbation of bloated abdomen symptoms after CBPV infection. The expression level of antimicrobial peptide (AMP) was found to be significantly up-regulated by over 1000 times in response to CBPV infection, as demonstrated by subsequent transcriptome and quantitative real-time PCR investigations. In particular, through correlation analysis and a bacteriostatic test revealed that the AMPs did not exhibit any inhibitory effect against the two opportunistic pathogens. However, they did demonstrate inhibitory activity against S. alvi and L. apis. Our findings provide different evidence that the virus infection may stimulate and utilize the host's AMPs to eradicate probiotic species and facilitate the proliferation of opportunistic bacteria. This process weakens the intestinal barrier and ultimately resulting in the typical bloated abdomen.

[Nerve Transfers in Children with Non-traumatic Amyoplasia] / Nerventransfers bei Kindern mit nicht traumatischer AmyoplasieNerve Transfers in Children with Non-traumatic Amyoplasia.

BACKGROUND: The treatment of obstetric brachial plexus palsy through primary reconstruction and nerve transfers has been established in the past decades. In the case of non-traumatic diseases that lead to flaccid paralysis and the inability to move the extremities, such as transverse myelitis (TM) or arthrogryposis multiplex congenita (AMC), which can have a wide variety of causes, the focus has been on rehabilitative therapy so far, while surgical interventions have been used to a lesser extent, e. g., in the form of osteotomies or muscle transfers. Our aim is to establish nerve transfers as a surgical option to improve mobility in non-traumatic amyoplasia. PATIENTS: This work presents the needs-adapted treatment of a total of 23 patients (aged 4 months to 64 months, 18 with AMC and 5 with TM) using nerve transfers on the upper extremity. RESULTS: We were able to show that early nerve transfers in the upper extremity enabled the reanimation of muscles in both AMC and TM. CONCLUSION: This work shows that the treatment of non-traumatic amyoplasia in children with selective nerve grafts is a successful method. Nerve transfers allow patients to gain or regain important functions for managing independent everyday life. The surgical methods have been established in the treatment of traumatic nerve injuries. They are well-known and can be carried out safely. We believe that this is an important treatment option for paediatric patients with paralysis associated with TM or AMC, which should also be known to the treating physicians.

Gross and histopathological findings in hindlimb paralysis syndrome in wild Carnaby's black cockatoos (Zanda laitirostris).

The aim of this study was to describe the gross and histopathological features of a neurological syndrome in endangered Western Australian Carnaby's black cockatoos (Zanda laitirostris) that was first observed in 2012. The syndrome, named hindlimb paralysis syndrome in Carnaby's cockatoos (CHiPS), is characterized by annual outbreaks of hindlimb paralysis with occasional loss of deep pain and cloacal tone, typically occurring between January and March. Previous limited investigations suggested a possible toxic aetiology. Full gross necropsy and histopathology examinations were performed on 17 CHiPS cases and on 11 control birds for reference. Histopathological examination was carried out on all major organs including brain, spinal cord, brachial plexus, sciatic nerve and wing and hindlimb muscles. Gross and histopathological examinations did not elucidate a definitive cause of the clinical signs seen in CHiPS cases. There were no substantial gross or histopathological changes within the brain, spinal cord, sciatic nerve or brachial plexus that could explain the hindlimb paralysis. The most noteworthy changes were seen in the hindlimb and wing muscles, with a monophasic to polyphasic myopathy present in the hindlimb muscles of 15 of the 17 CHiPS cases and in the wing muscles in 11 of those cases. The cause and significance of the myopathy is unclear and requires further investigation. Based on the above findings, the most likely differential diagnoses include neurotoxicoses (eg, organophosphate, organochlorine and carbamate) and, less likely, myotoxicosis (eg, ionophore toxicosis), nutritional myopathy (eg, vitamin E/selenium deficiency) or botulism.

Influence of musculoskeletal pain during gait on kinematics and selective motor control in individuals with spastic cerebral palsy: A pilot study.

BACKGROUND: Individuals with cerebral-palsy commonly present with altered kinematics and selective-motor-control during gait, and may also experience musculoskeletal pain. This pilot study aims to investigate if the immediate experience of musculoskeletal pain during gait influences kinematics and selective-motor-control in individuals with spastic cerebral-palsy. METHODS: Retrospective treadmill-based gait-analysis data for 145 individuals with spastic cerebral-palsy were screened. Participants were asked about experiencing lower-extremity musculoskeletal pain immediately during gait, with 26 individuals (18%) reporting this was the case (pain-group; mean 11.55 ± 3.15 years, Gross-Motor-Function-Classification-System levels I/II/III n = 5/13/8, Uni/bilateral involvement n = 11/15). Of the 77 individuals who did not report any pain, a no-pain group (n = 26) was individually matched. Kinematics were evaluated using the Gait-Profile-Score and spatiotemporal parameters (dimensionless-walking-speed, single-leg-support percentage and step-time). Selective-motor-control was assessed using the Walking-Dynamic-Motor-Control index. FINDINGS: In the pain-group, 58% reported experiencing pain in their more-involved leg, 8% in the less-involved leg and 34% in both legs. Regarding the pain location, 38% of the pain-group reported experiencing pain in multiple locations. On a more specific level, 35%, 46% and 54% reported pain around the hip/thigh, knee/calf and ankle/ft, respectively. No significant differences were observed between the pain and no-pain groups for any of the outcome measures, in each leg or bilaterally. INTERPRETATION: No significant differences in kinematics and selective-motor-control during gait were found between individuals with spastic cerebral-palsy, with and without musculoskeletal pain. This suggests that the individuals in this study may not present with obvious antalgic gait patterns, which may relate to the pre-existing altered kinematics and selective-motor-control.

Applying the IEEE BRAIN neuroethics framework to intra-cortical brain-computer interfaces.

Objective. Brain-computer interfaces (BCIs) are neuroprosthetic devices that allow for direct interaction between brains and machines. These types of neurotechnologies have recently experienced a strong drive in research and development, given, in part, that they promise to restore motor and communication abilities in individuals experiencing severe paralysis. While a rich literature analyzes the ethical, legal, and sociocultural implications (ELSCI) of these novel neurotechnologies, engineers, clinicians and BCI practitioners often do not have enough exposure to these topics.Approach. Here, we present the IEEE Neuroethics Framework, an international, multiyear, iterative initiative aimed at developing a robust, accessible set of considerations for diverse stakeholders.Main results. Using the framework, we provide practical examples of ELSCI considerations for BCI neurotechnologies. We focus on invasive technologies, and in particular, devices that are implanted intra-cortically for medical research applications.Significance. We demonstrate the utility of our framework in exposing a wide range of implications across different intra-cortical BCI technology modalities and conclude with recommendations on how to utilize this knowledge in the development and application of ethical guidelines for BCI neurotechnologies.