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.

Incidence of Nerve Palsies During Pavlik Harness Treatment for Developmental Dysplasia of the Hip: A Retrospective Cohort Study.

BACKGROUND: The Pavlik harness has been used for approximately a century to treat developmental dysplasia of the hip (DDH). Femoral nerve palsy is a documented complication of Pavlik harness use, with an incidence ranging from 2.5% to 11.2%. Rare reports of brachial plexus palsy have also been documented. The primary purpose of the current study was to evaluate the incidence of various nerve palsies in patients undergoing Pavlik harness treatment for DDH. Secondary aims were to identify patient demographic or hip characteristics associated with nerve palsy. METHODS: We performed a retrospective review of patients diagnosed with DDH and treated with a Pavlik harness from February 1, 2016, to April 1, 2023, at a single tertiary care orthopaedic hospital. Hip laterality, use of a subsequent rigid abduction orthosis, birth order, breech positioning, weight, and family history were collected. The median (and interquartile range [IQR]) or mean (and standard deviation [SD]) were reported for all continuous variables. Independent 2-sample t tests and Mann-Whitney U tests were conducted to identify associations between the variables collected at the initiation of Pavlik harness treatment and the occurrence of nerve palsy. RESULTS: Three hundred and fifty-one patients (547 hips) were included. Twenty-two cases of femoral nerve palsy (4% of all treated hips), 1 case of inferior gluteal nerve palsy (0.18%), and 2 cases of brachial plexus palsy (0.37%) were diagnosed. Patients with nerve palsy had more severe DDH as measured by the Graf classification (p < 0.001) and more severe DDH as measured on physical examination via the Barlow and Ortolani maneuvers (p = 0.003). CONCLUSIONS: Nerve palsies were associated with more severe DDH at the initiation of Pavlik harness use. Upper and lower-extremity neurological status should be scrutinized at initiation and throughout treatment to assess for nerve palsies. The potential for femoral, gluteal, and brachial plexus palsies should be included in the discussion of risks at the beginning of treatment. Families may be reassured that nerve palsies associated with Pavlik harness can be expected to resolve with a short break from treatment. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Long-term outcome of endovascular treatment for indirect carotid-cavernous fistulas.

OBJECTIVE: Endovascular treatment (EVT) is the primary approach used to treat indirect carotid-cavernous fistulas (CCFs). In this study, the authors evaluated the immediate and long-term efficacy and safety of different endovascular techniques for indirect CCFs. METHODS: The databases of two endovascular centers were retrospectively reviewed to collect the patients with indirect CCFs treated using endovascular techniques between 2013 and 2023. Demographics, clinical presentation, CCF features, EVT characteristics, and clinical and radiological outcomes were evaluated and analyzed. The analysis was performed to compare the clinical and radiological data between different endovascular approaches and different embolic materials. RESULTS: Ninety-eight patients were included in the study. EVT was successful in 95 patients (96.9%). Immediate complete obliteration of the CCF was achieved in 93.9% of patients, with 98% undergoing embolization with liquid embolic agents (LEAs) and 95.6% undergoing coiling alone. Complete CCF obliteration was higher in the transvenous than in the transarterial approach (94.3% vs 75%, p = 0.010). At ≥ 6 months follow-up, complete CCF obliteration was achieved in all patients (100%). The rate of procedure-related complications was higher following LEAs than with coiling alone (32.0% vs 15.6%). New cranial nerve (CN) palsy was diagnosed in 26.0% and 2.2% after embolization with LEAs and coiling alone, respectively (p = 0.001), with complete CN palsy recovery in 78.6%. Procedure-related intracranial hemorrhage occurred in 3 patients (3.1%). Two patients experienced an ischemic stroke following Onyx migration into the internal carotid artery. Ocular symptoms improved in 93% (83/89) of the patients who were followed. CONCLUSIONS: In this study, complete obliteration of an indirect CCF was achieved in more than 90% of patients. Despite the occurrence of some new postprocedural ocular CN palsy, ocular symptoms improved in most patients in long-term follow-up. The transvenous approach was the most effective method for treating the indirect CCF. Coiling was safer than LEAs for the embolization of the indirect CCF.

Femoral nerve palsy as a complication due to COVID-19 coagulopathy and iliopsoas muscle hematoma - case report.

BACKGROUND: COVID-19 (Coronavirus disease 2019) pandemic is the main medical problem around the world from the end of 2019. We found until now many symptoms of this disease, but one of the most problematic was thrombosis. Wide recommendation on COVID-19 treatment was pharmacological thromboprophylaxis. In some papers we found that clinicians face the problem of bleeding in those patients. Is still unknown that coronavirus could led to the coagulopathy. CASE PRESENTATION: We described case report of patient who with COVID-19 disease present femoral nerve palsy caused by the iliopsoas hematoma. There were no deviations in coaguology parameters, patient got standard thromboprophylaxis, besides above probably COVID-19 was risk factor of hematoma formation. Non-operative treatment was applied, thrombophylaxis was discontinued. In the follow up in the radiological exam we saw reduction of the haematoma and patient report decrease of symptoms. CONCLUSIONS: We should assess individually patient with COVID-19 according to thrombosis risk factors. Probably we should be more careful in ordering thrombophylaxis medications in COVID-19 patients.

Results of acute cerebral infarction treatment with hyperbaric oxygen therapy, 2020-2022.

BACKGROUND: Cerebral stroke is the third leading cause of death after cardiovascular disease, cancer and the leading cause of disability for patients. Hyperbaric oxygen is a non-drug treatment that has the potential to improve brain function for patients with ischaemic stroke. The objective of this study was to evaluate the results of treatment of acute cerebral infarction with hyperbaric oxygen therapy (HBOT). MATERIALS AND METHODS: This was a case-control study. One hundred ninety-five patients diagnosed with cerebral infarction, with signs of onset within 24 hours, were treated at the Centre for Underwater Medicine and Hyperbaric Oxygen of Vietnam National Institute of Maritime Medicine during the period from January 2020 to December 2022. Study group included 100 patients with acute cerebral infarction treated with a combination of HBOT and medication and reference group included 95 patients treated by medication only (antiplatelets drugs, statins, control of associated risks factors) RESULTS: After 7 days of treatment with hyperbaric oxygen (HBO), symptoms such as headache, dizziness, nausea, sensory disturbances, and Glasgow score of the study group improved better than that of the reference group (p < 0.01). Movement recovery in the study group was better than the reference group: the percentage of patients with mild and moderate paralysis in the study group increased higher than that of the reference group (86.0% and 68.4%), the degree of complete paralysis of the study group decreased more than that of the reference group (14.0% and 31.6%). The degree of independence in daily activities in the study group was better than the reference group. In the study group, the percentage of patients with complete independence in daily life increased from 27.0% to 84.0%. In the reference group, the rate of patients who were independent in their daily activities increased from 37.9% to 51.6%. The average number of treatment days of the study group was 10.32 ± 2.41 days and it the reference group 14.51 ± 3.24 days. CONCLUSIONS: Hyperbaric oxygen therapy is a non-drug treatment with many good effects in the treatment of cerebral infarction, especially acute cerebral infarction. HBOT reduces and improves functional symptoms, improves mobility, and reduces treatment time for patients.

Paralysis under pressure.

Treating cardiovascular paralysis with epidural electrical neuromodulation.

Botulism mimicking Guillain-Barre syndrome: The question of plasma exchange in an unusual case of acute paralysis.

Guillain-Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy and the most common cause of acute flaccid paralysis worldwide. GBS classically presents with acute, progressive, ascending weakness, reduced to absent reflexes, and albuminocytological dissociation on cerebrospinal fluid (CSF) analysis. Botulism is a neurotoxin-mediated acute descending flaccid paralysis with cranial nerve palsies and dysautonomia. Botulism in adults is caused by ingestion/inhalation of botulinum toxin or wound infection with Clostridium botulinum. Both GBS and botulism can rapidly precipitate respiratory failure; thus, prompt diagnosis and treatment are crucial to mitigate poor outcomes. Herein, we describe a case of botulism initially diagnosed as GBS given classic laboratory features, and describe the importance of careful consideration of the most appropriate therapeutic modalities in cases of acute flaccid paralysis, particularly regarding empiric administration of botulinum antitoxin and use of intravenous immune globulin in lieu of plasma exchange for potential GBS to prevent removal of antitoxin.

Immediate effects of electroacupuncture in oculomotor nerve palsy following brainstem infarction: A case report.

INTRODUCTION: Research has demonstrated that electroacupuncture (EA) stimulation of paralyzed muscles significantly improves nerve regeneration and functional recovery. DESCRIPTION: An 81-year-old man with no history of diabetes mellitus or hypertension presented with a history of brainstem infarction. Initially, the patient had medial rectus palsy in the left eye and diplopia to the right in both eyes, which almost returned to normal after six sessions of EA. METHODS: The CARE guidelines informed the case study report. The patient was diagnosed with oculomotor nerve palsy (ONP) and photographed to document ONP recovery after treatment. The selected acupuncture points and surgical methods are listed in the table. DISCUSSION: Pharmacological treatment of oculomotor palsy is not ideal, and its long-term use has side effects. Although acupuncture is a promising treatment for ONP, existing treatments involve many acupuncture points and long cycles, resulting in poor patient compliance. We chose an innovative modality, electrical stimulation of paralyzed muscles, which may be an effective and safe complementary alternative therapy for ONP.

Invisible consequences of paralysis.

Neuroprosthetic technologies can control blood pressure and restore walking.

Electrical stimulation to promote muscle and motor unit force and endurance after spinal cord injury.

Fatigue is a common feature of paralysed skeletal muscle, hindering performance when subjected to functional electrical stimulation (ES) for movement. We asked whether (1) 20 Hz ES for 5% of each day (2.5 s on and 2.5 s off for 3 h) increases tibialis anterior and medial gastrocnemius muscle and motor unit (MU) endurance after paralysis by hemisection and deafferentation (HSDA), and (2) muscle length or loading affects their isometric contractile properties. The daily 5% ES increased muscle endurance, largely independent of muscle length or loading, but to a lesser extent than the daily 50% ES (2.5 s on and 2.5 s off for 24 h). The former was effective in counteracting the decline and slowing of muscle force promoted by the 50% ES. The altered muscle properties were confirmed at the MU level in final experiments once the properties had plateaued. Fast-fatigable MUs were converted to fatigue-intermediate and -resistant MUs that finally comprised ∼80% as compared to ∼10% of the total MU number in the daily 5% ES and the control normal groups, respectively. We conclude that the daily 5% ES regimen counteracts the fatigue of paralysed muscle without compromising contractile force, and thereby, is effective in conditioning muscle for effective movement. KEY POINTS: We asked whether 20 Hz electrical stimulation (ES) for 5% of each day (2.5 s on and 2.5 s off for 3 h; 5% ES) preserves medial gastrocnemius and tibialis anterior muscle and MU isometric contractile forces and increases their endurance after paralysis. Daily 5% ES promoted increased muscle endurance irrespective of the muscle length or loading but to a lesser extent than daily 50% ES (20 Hz ES 2.5 s on and 2.5 s off for 24 h). 5% ES was effective in counteracting decline and slowing of muscle force that resulted from 50% ES. Motor units (MUs) were converted from fast fatigable to fatigue intermediate and resistant MUs, comprising ∼80% as compared to ∼10% in the control normal groups. We conclude that the 5% ES regimen counteracts the fatigue of paralysed muscle without compromising contractile force, and thereby is effective in conditioning the muscle for effective movement.

Persistent facial nerve palsy after middle meningeal artery embolization for subdural hematoma: a case report.

OBJECTIVE: To describe a case of persistent facial nerve palsy after middle meningeal artery (MMA) embolization for chronic subdural hematoma (cSDH). METHODS: A literature search was conducted for publications within the last 10 years of facial nerve palsy following cerebral circulation embolization procedures. RESULTS: With inconsistencies between previously believed pathophysiology and clinical features, other mechanisms causing cSDH such as angiogenesis and capillary formation have been proposed. MMA embolization has evolved as a therapeutic approach to reduce recurrence of subdural hematoma; however, postoperative neural complications such as cranial nerve palsies are poorly described in the literature. CONCLUSIONS: cSDH is increasingly more common and is on trajectory to become the most prevalent cranial neurosurgical condition. MMA embolization is described as a safe and minimally invasive procedure; however, as a relatively new procedure further research is needed to elucidate associated complications.

Repetitive facilitative exercise under continuous electrical stimulation for recovery of pure motor isolated hand palsy after infarction of the "hand knob" area: A case report.

PURPOSE: Pure motor isolated hand palsy (PMIHP) following infarction of the "hand knob" area is a rare entity in stroke. PMIHP usually recovers within the first few days, but there are rare cases where patients do not recover rapidly. Herein, we report a case of residual PMIHP in which repetitive facilitative exercise under concurrent low-amplitude continuous neuromuscular electrical stimulation ("RFE-under-cNMES") was introduced to improve hand function. CASE DESCRIPTION: A 65-year-old man with PMIHP (30 days after onset) participated in a rehabilitation program involving RFE-under-cNMES. This protocol followed an A1-B1-A2-B2 schedule, where the "A"-period consisted of RFE-under-cNMES ("A1," 2 weeks; "A2," 1 week), and the "B"-period consisted of 1-week conventional rehabilitation. OUTCOMES: The 5-week intervention promoted not only recovery from paralysis (8 points by the Fugl-Meyer Assessment), but also the ability to manipulate objects (13 points by the Action Research Arm test) and increased the subjective use of the affected upper limb during activities of daily living (2.88 points by the Motor Activity Log). Changes that exceeded the minimal clinically important difference occurred only in the RFE-under-cNMES period. CONCLUSIONS: The patient had improved outcomes. Further studies are required to determine the possibility of RFE-under-cNMES relieving motor paralysis in patients with PMIHP who do not recover rapidly.

Time Course and Risk Factors for Repeat Procedures After Ureteroscopy or Shockwave Lithotripsy.

OBJECTIVE: To determine risk factors and time course for repeat procedures after ureteroscopy (URS) or shockwave lithotripsy (SWL) procedure using a large employer-based claims database. METHODS: We identified all patients who underwent treatment for ureteral or renal stone with URS or SWL from January 1, 2007 to December 31, 2014 using the IBM MarketScan Commercial Database. Repeat stone procedure was evaluated after a 90-day grace period from the index procedure. Patients were followed until December 31, 2017. We performed multivariate analyses using Cox proportional hazards to determine independent risk factors for repeat procedure after the initial stone removal. RESULTS: A total of 189,739 patients underwent a SWL or URS and were included in the study. The incidence of repeat procedure per 100 person years was 6.8, and 4.4 after SWL and URS, respectively. The median time to reoperation was 12.5 months for SWL and 14.6 months for URS. On multivariable analysis, SWL was associated with an increased risk of repeat procedure compared to URS. (HR = 1.63). Paralysis, neurogenic bladder and inflammatory bowel disease were also associated with an increased risk of repeat procedure (HR = 1.66, 1.40, and 1.36 respectively) CONCLUSION: In a large national cohort, patients with paralysis and neurogenic bladder had a significantly higher risk of repeat stone procedure. SWL was associated with higher risk of repeat procedure than URS. Urologists can use these data to identify and counsel patients at high risk for need for recurrent procedure.

The neurons that restore walking after paralysis.

A spinal cord injury interrupts pathways from the brain and brainstem that project to the lumbar spinal cord, leading to paralysis. Here we show that spatiotemporal epidural electrical stimulation (EES) of the lumbar spinal cord1-3 applied during neurorehabilitation4,5 (EESREHAB) restored walking in nine individuals with chronic spinal cord injury. This recovery involved a reduction in neuronal activity in the lumbar spinal cord of humans during walking. We hypothesized that this unexpected reduction reflects activity-dependent selection of specific neuronal subpopulations that become essential for a patient to walk after spinal cord injury. To identify these putative neurons, we modelled the technological and therapeutic features underlying EESREHAB in mice. We applied single-nucleus RNA sequencing6-9 and spatial transcriptomics10,11 to the spinal cords of these mice to chart a spatially resolved molecular atlas of recovery from paralysis. We then employed cell type12,13 and spatial prioritization to identify the neurons involved in the recovery of walking. A single population of excitatory interneurons nested within intermediate laminae emerged. Although these neurons are not required for walking before spinal cord injury, we demonstrate that they are essential for the recovery of walking with EES following spinal cord injury. Augmenting the activity of these neurons phenocopied the recovery of walking enabled by EESREHAB, whereas ablating them prevented the recovery of walking that occurs spontaneously after moderate spinal cord injury. We thus identified a recovery-organizing neuronal subpopulation that is necessary and sufficient to regain walking after paralysis. Moreover, our methodology establishes a framework for using molecular cartography to identify the neurons that produce complex behaviours.

Neonatal brachial plexus palsy - early diagnosis and treatment.

Background and purpose: The incidence of brachial plexus palsy (BPP) has decreased recently, but the indivi-d-ual's quality of life is endangered. To provide better chan-ces to BPP neonates and infants, the Department of Developmental Neurology worked out, introduced, and applied a complex early therapy, including nerve point stimulation. Methods: After diagnosing the severity of BPP, early intensive and complex therapy should be started. Appro-x-imately after a week or ten days following birth, the slightest form (neurapraxia) normalizes without any intervention, and signs of recovery can be detected around this period. The therapy includes the unipolar nerve point electro-stimulation and the regular application of those elemen-tary sensorimotor patterns, which activate both extremities simultaneously. Results: With the guideline worked out and applied in the Department of Developmental Neurology, full recovery can be achieved in 50% of the patients, and even in the most severe cases (nerve root lesion), functional upper limb usage can be detected with typically developing body-scheme. Conclusion: Immediately starting complex treatment based on early diagnosis alters the outcome of BPP, providing recovery in the majority of cases and enhancing the everyday arm function of those who only partially benefit from the early treatment.

Epidural electrical stimulation of the cervical dorsal roots restores voluntary upper limb control in paralyzed monkeys.

Regaining arm control is a top priority for people with paralysis. Unfortunately, the complexity of the neural mechanisms underlying arm control has limited the effectiveness of neurotechnology approaches. Here, we exploited the neural function of surviving spinal circuits to restore voluntary arm and hand control in three monkeys with spinal cord injury, using spinal cord stimulation. Our neural interface leverages the functional organization of the dorsal roots to convey artificial excitation via electrical stimulation to relevant spinal segments at appropriate movement phases. Stimulation bursts targeting specific spinal segments produced sustained arm movements, enabling monkeys with arm paralysis to perform an unconstrained reach-and-grasp task. Stimulation specifically improved strength, task performances and movement quality. Electrophysiology suggested that residual descending inputs were necessary to produce coordinated movements. The efficacy and reliability of our approach hold realistic promises of clinical translation.