Production of the Cytokine VEGF-A by CD4+ T and Myeloid Cells Disrupts the Corneal Nerve Landscape and Promotes Herpes Stromal Keratitis.

Herpes simplex virus type 1 (HSV-1)-infected corneas can develop a blinding immunoinflammatory condition called herpes stromal keratitis (HSK), which involves the loss of corneal sensitivity due to retraction of sensory nerves and subsequent hyperinnervation with sympathetic nerves. Increased concentrations of the cytokine VEGF-A in the cornea are associated with HSK severity. Here, we examined the impact of VEGF-A on neurologic changes that underly HSK using a mouse model of HSV-1 corneal infection. Both CD4+ T cells and myeloid cells produced pathogenic levels of VEGF-A within HSV-1-infected corneas, and CD4+ cell depletion promoted reinnervation of HSK corneas with sensory nerves. In vitro, VEGF-A from infected corneas repressed sensory nerve growth and promoted sympathetic nerve growth. Neutralizing VEGF-A in vivo using bevacizumab inhibited sympathetic innervation, promoted sensory nerve regeneration, and alleviated disease. Thus, VEGF-A can shape the sensory and sympathetic nerve landscape within the cornea, with implications for the treatment of blinding corneal disease.

Serum levels of heavy metals in patients with Bell's palsy: a case-control study.

PURPOSE: The exact etiology of Bell's palsy (BP) remains unknown, while its potential etiopathology includes neuritis and inflammation-related demyelination as in optic neuritis. It has been reported that disruption of heavy metal homeostasis may be associated with the inflammatory process of optic neuritis; therefore, heavy metals may be involved in the pathogenesis of facial nerve neuritis. In this study, we aimed to investigate serum levels of heavy metals including essential elements [iron (Fe), zinc (Zn), copper (Cu), cobalt (Co), and manganese (Mn)], and nonessential elements [lead (Pb) and cadmium (Cd)] in patients with BP. METHODS: The study included 25 patients with BP and 31 healthy volunteers. For each participant, serum levels of essential and nonessential elements were measured using the atomic absorption spectrophotometer method. RESULTS: Serum levels of essential elements were significantly lower in the patient group compared to the control group (p < 0.001, for each). Serum levels of Pb increased in the patient group compared to the control group although no significant difference was achieved (p = 0.105). In contrast, serum Cd levels increased significantly in the patient group compared to the control group (p < 0.001). CONCLUSION: Our findings suggest that decreased essential and increased nonessential elements may be associated with BP and thus, serum concentrations of these elements should be taken into account in BP. Studies are warranted to determine the role of these elements in treatment of BP.

Sarcoid optic neuropathy.

A 45-year-old woman presented with sudden complete vision loss in her left eye and retroorbital pain worsened by eye movements. A previous milder episode of vision loss had occurred in the same eye 1 year before, with complete recovery after high-dose intravenous methylprednisolone. She had no light perception in the left eye with a swollen optic disc, but with a normal right optic disc. There were no systemic manifestations or infections. MR scan of the brain showed extensive enlargement and enhancement of the left optic nerve and optic chiasm. After excluding infections and autoimmune markers, a left optic nerve biopsy confirmed non-caseating granulomas, leading to a diagnosis of neurosarcoidosis.

Anti-myelin-associated glycoprotein neuropathy: Where do we stand?

Myelin-associated glycoprotein (MAG) is a transmembrane glycoprotein concentrated in periaxonal Schwann cell and oligodendroglial membranes of myelin sheaths that serves as an antigen for immunoglobulin M (IgM) monoclonal antibodies. Individuals who harbor anti-MAG antibodies classically develop a progressive autoimmune peripheral neuropathy characterized clinically by ataxia, distal sensory loss, and gait instability, and electrophysiologically by distally accentuated conduction velocity slowing. Although off-label immunotherapy is common, there are currently no proven effective disease-modifying therapeutics, and most patients experience slow accumulation of disability over years and decades. The typically slowly progressive nature of this neuropathy presents unique challenges when trying to find effective anti-MAG therapeutic agents. Drug development has also been hampered by the lack of validated outcome measures that can detect clinically meaningful changes in a reasonable amount of time as well as by the lack of disease activity biomarkers. In this invited review, we provide an update on the state of clinicometric outcome measures and disease activity biomarkers in anti-MAG neuropathy. We highlight the insensitivity of widely used existing clinicometric outcome measures such as the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score as well as the INCAT sensory subscore in anti-MAG neuropathy, referencing the two previous negative randomized controlled clinical trials evaluating rituximab. We then discuss newly emerging candidate therapeutic agents, including tyrosine kinase inhibitors and enhanced B-cell-depleting agents, among others. We conclude with a practical approach to the evaluation and management of anti-MAG neuropathy patients.

Recurrent motor branch neuropathy in carpal tunnel syndrome: An ultrasound study.

INTRODUCTION/AIMS: The reason for the variable rate of progression of patients with carpal tunnel syndrome (CTS) to thenar muscles impairment is not fully understood. The aim of this study was to evaluate the occurrence of ultrasound signs of recurrent motor branch (RMB) neuropathy in patients with CTS and to correlate imaging findings with clinical and electrophysiological data. METHODS: Two cohorts were recruited, one consisting of CTS patients with electrodiagnostic evidence of prolonged median distal motor latency from wrist to thenar eminence and another consisting of sex- and age-matched healthy controls. Ultrasound reliability of RMB measurement was assessed by the calculation of the interclass correlation coefficient (ICC). Patients were evaluated with electrodiagnostic tests and asked to complete the Boston Carpal Tunnel Questionnaire. The difference between the RMB diameter in patients and controls was analyzed using a t test. Correlations between RMB diameter and other parameters were assessed using linear mixed models. RESULTS: 46 hands from 32 patients with CTS and 50 hands from 50 controls were evaluated. The intra- and interobserver agreements in RMB measurement were very good (ICC = 0.84; 95% confidence interval [CI], 0.75 to 0.90) and good (ICC = 0.79; 95% CI, 0.69 to 0.87). The RMB diameter was significantly larger in patients than in controls (P < .0001). No significant correlation was found between the RMB diameter and other variables, except for BMI and median nerve cross-sectional area. DISCUSSION: Ultrasound is reliable in identifying the RMB and characterizing its abnormalities. In this patient cohort, ultrasound allowed for detection of definite signs of RMB compression neuropathy.

Polyneuritis cranialis as a unique initial presentation of juvenile systemic lupus erythematosus: Case report.

Cranial neuropathy is a rare presentation in juvenile (j) SLE and being multiple is even rarer. We describe here an adolescent girl presenting with polyneuritis cranialis (PNC) as an initial presentation of SLE which had not been reported before in literature. She presented with symptoms suggestive of bilateral abducent and hypoglossal neuropathy with nerve conduction studies showing partial axonal neuropathy of left facial and accessory nerves, 6 weeks after common cold. The condition was not associated with any other neurological or systemic manifestations nor features of Sjogren's syndrome. Her condition responded well to pulsed methylprednisolone therapy and plasma exchange. After exclusion of the common causes and owing to the initial positive ANA results and mild proteinuria, renal biopsy was taken and revealed histopathological features of class III lupus nephritis for which mycophenolate mofetil was started at 1200 mg per m2. Our case highlights the importance of considering collagen disorders including SLE in the differential diagnosis of children presenting with PNC in order to allow adequate management and proper follow-up.

Co-occurrence of polyneuritis crainials and visual impairment: a case report and literature review.

BACKGROUND: Polyneuritis cranialis (PNC) with the disease characteristics of Guillain-Barré syndrome (GBS) in addition to both ocular and bulbar weakness in the absence of limb paralysis or ataxia is defined as an unusual variant of GBS. As evidence of central nervous system (CNS) involvement, visual impairment is an unusual finding complicating with GBS spectrum disorders and has never been reported in patients with PNC. METHODS: We describe a very rare case who clinically presented with progressive multiple cranial nerve palsy and visual impairment. Furthermore, a literature search of concurrent GBS and optic neuritis (ON) as well as PNC attributed to GBS was conducted. RESULTS: A diagnosis of PNC was considered due to the typical clinical characteristics as well as the presence of cerebrospinal fluid cytoalbumin dissociation and serum antibodies against gangliosides. The clinical manifestations and the bilateral optic nerve involvement in brain magnetic resonance imaging further suggested possible optic neuritis (ON). The patient received treatment with intravenous immunoglobulin followed by short-term use of corticosteroids and finally achieved a full recovery. Thirty-two previously reported cases (17 women, mean age 40) of concurrent GBS and ON and 20 cases of PNC (5 women, mean age 40) were analyzed. We further provided a comprehensive discussion on the potential etiologies, clinical features, therapeutic strategies, and prognosis. CONCLUSIONS: This rare case with the co-occurrence of PNC and visual impairment and the related literature review may help clinicians advance the understanding of GBS spectrum disorders and make appropriate diagnoses and treatment decisions for the rare variants and CNS complications of GBS.

Peripheral Tubercular Neuritis.

Peripheral neuropathy can affect sensory, motor, or autonomic nerves and manifest with a variety of symptoms. Tuberculosis as a major infectious disease that often affects many organs of the body. However, primary involvement of peripheral nerves is unusual. Peripheral neuropathy in patients with tuberculosis often is associated with other comorbidities, such as immunocompromised states, diabetes mellitus, malnutrition, and some antitubercular medications. This report describes the rare finding of peripheral tubercular neuritis with caseating abscesses of right median and radial nerve in a healthy 24-year man.

Immune-Mediated Neuropathies: Pathophysiology and Management.

Dysfunction of the immune system can result in damage of the peripheral nervous system. The immunological mechanisms, which include macrophage infiltration, inflammation and proliferation of Schwann cells, result in variable degrees of demyelination and axonal degeneration. Aetiology is diverse and, in some cases, may be precipitated by infection. Various animal models have contributed and helped to elucidate the pathophysiological mechanisms in acute and chronic inflammatory polyradiculoneuropathies (Guillain-Barre Syndrome and chronic inflammatory demyelinating polyradiculoneuropathy, respectively). The presence of specific anti-glycoconjugate antibodies indicates an underlying process of molecular mimicry and sometimes assists in the classification of these disorders, which often merely supports the clinical diagnosis. Now, the electrophysiological presence of conduction blocks is another important factor in characterizing another subgroup of treatable motor neuropathies (multifocal motor neuropathy with conduction block), which is distinct from Lewis-Sumner syndrome (multifocal acquired demyelinating sensory and motor neuropathy) in its response to treatment modalities as well as electrophysiological features. Furthermore, paraneoplastic neuropathies are also immune-mediated and are the result of an immune reaction to tumour cells that express onconeural antigens and mimic molecules expressed on the surface of neurons. The detection of specific paraneoplastic antibodies often assists the clinician in the investigation of an underlying, sometimes specific, malignancy. This review aims to discuss the immunological and pathophysiological mechanisms that are thought to be crucial in the aetiology of dysimmune neuropathies as well as their individual electrophysiological characteristics, their laboratory features and existing treatment options. Here, we aim to present a balance of discussion from these diverse angles that may be helpful in categorizing disease and establishing prognosis.

Inflammatory Processes in Alzheimer's Disease-Pathomechanism, Diagnosis and Treatment: A Review.

Alzheimer's disease is one of the most commonly diagnosed cases of senile dementia in the world. It is an incurable process, most often leading to death. This disease is multifactorial, and one factor of this is inflammation. Numerous mediators secreted by inflammatory cells can cause neuronal degeneration. Neuritis may coexist with other mechanisms of Alzheimer's disease, contributing to disease progression, and may also directly underlie AD. Although much has been established about the inflammatory processes in the pathogenesis of AD, many aspects remain unexplained. The work is devoted in particular to the pathomechanism of inflammation and its role in diagnosis and treatment. An in-depth and detailed understanding of the pathomechanism of neuroinflammation in Alzheimer's disease may help in the development of diagnostic methods for early diagnosis and may contribute to the development of new therapeutic strategies for the disease.

[Public health situation of CIDP patients in nine German centers-neuritis network Germany]. / Versorgungssituation von CIDP-Patienten in neun deutschen Zentren des Neuritis Netzes.

BACKGROUND: Diagnosis and treatment of patients with immune-mediated neuropathies is challenging due to the heterogeneity of the diseases. OBJECTIVES: To assess similarities and differences in the current care of patients with immune-mediated polyneuropathies in specialized centers in Germany within the German neuritis network "Neuritis Netz". MATERIAL AND METHODS: We conducted a cross-sectional survey of nine neurological departments in Germany that specialize in the care of patients with immune-mediated neuropathies. We assessed the diagnosis, the approach to diagnostic work-up and follow-up, typical symptoms at manifestation and progression of the disease, and treatment data. RESULTS: This report includes data from 1529 patients per year treated for immune-mediated neuropathies, of whom 1320 suffered from chronic inflammatory demyelinating polyneuropathy (CIDP). Diagnostic work-up almost always included nerve conduction studies, electromyography, and lumbar puncture in accordance with current guidelines. The use of ultrasound, biopsy, and MRI varied. The most important clinical parameter for therapy monitoring in all centers was motor function in the clinical follow-up examinations. A wide range of different immunosuppressants was used for maintenance therapy in about 15% of patients. CONCLUSIONS: These data provide important epidemiological insights into the care of patients with immune-mediated neuropathies in Germany. The further development of specific recommendations for treatment and follow-up examinations is necessary to ensure a uniform standard of patient care. This effort is greatly facilitated by a structured collaboration between expert centers such as Neuritis Netz.

Leprosy rash precipitated by immunotherapy for suspected inflammatory neuropathy.

Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae complex, causing skin and nerve lesions with potential for permanent disability. Leprosy can be overlooked in Western settings, as it is more prevalent in low-income and middle-income countries. We describe a 38-year-old woman with a 4-year history of progressive numbness of the left hand incorrectly diagnosed as multifocal acquired demyelinating sensory and motor neuropathy on the basis of clinical and neurophysiological findings. Treatment with empirical weekly corticosteroid followed by intravenous immunoglobulin resulted in the sudden development of a widespread rash; we then diagnosed borderline lepromatous leprosy on skin biopsy. We postulate that the immune treatments induced a temporary state of immune tolerance followed by a rebound of a T cell-mediated immune response resulting in a type 1 immunological response.

Translumbosacral Anorectal Magnetic Stimulation Test for Fecal Incontinence.

BACKGROUND: Neuropathy may cause fecal incontinence and mixed fecal incontinence/constipation, but its prevalence is unclear, partly due to the lack of comprehensive testing of spino-anorectal innervation. OBJECTIVE: This study aimed to develop and determine the clinical usefulness of a novel test, translumbosacral anorectal magnetic stimulation for fecal incontinence. DESIGN: This observational cohort study was conducted from 2012 to 2018. SETTINGS: This study was performed at a tertiary referral center. PATIENTS: Patients with fecal incontinence, patients with mixed fecal incontinence/constipation, and healthy controls were included. INTERVENTIONS: A translumbosacral anorectal magnetic stimulation test was performed by using an anorectal probe with 4 ring electrodes and magnetic coil, and by stimulating bilateral lumbar and sacral plexuses, uses and recording 8 motor-evoked potentials at anal and rectal sites. MAIN OUTCOME MEASURES: The prevalence of lumbar and/or sacral neuropathy was examined. Secondary outcomes were correlation of neuropathy with anorectal sensorimotor function(s) and morphological changes. RESULTS: We evaluated 220 patients: 144 with fecal incontinence, 76 with mixed fecal incontinence/constipation, and 31 healthy controls. All 8 lumbar and sacral motor-evoked potential latencies were significantly prolonged (p < 0.01) in fecal incontinence and mixed fecal incontinence/constipation groups compared with controls. Neuropathy was patchy and involved 4.0 (3.0) (median (interquartile range)) sites. Lumbar neuropathy was seen in 29% to 65% of the patients in the fecal incontinence group and 22% to 61% of the patients in the mixed fecal incontinence/constipation group, and sacral neuropathy was seen in 24% to 64% and 29% to 61% of these patients. Anal neuropathy was significantly more (p < 0.001) prevalent than rectal neuropathy in both groups. There was no correlation between motor-evoked potential latencies and anal sphincter pressures, rectal sensation, or anal sphincter defects. LIMITATIONS: No comparative analysis with electromyography was performed. CONCLUSION: Lumbar or sacral plexus neuropathy was detected in 40% to 75% of patients with fecal incontinence with a 2-fold greater prevalence at the anal region than the rectum. Lumbosacral neuropathy appears to be an independent mechanism in the pathogenesis of fecal incontinence, unassociated with other sensorimotor dysfunctions. Translumbosacral anorectal magnetic stimulation has a high yield and is a safe and clinically useful neurophysiological test. See Video Abstract at http://links.lww.com/DCR/B728. PRUEBA DE ESTIMULACIN MAGNTICA TRANSLUMBOSACRAL ANORECTAL PARA LA INCONTINENCIA FECAL: ANTECEDENTES:La neuropatía puede causar incontinencia fecal y una combinación de incontinencia fe-cal/estreñimiento, pero su prevalencia no está clara, en parte debido a la falta de pruebas comple-tas de inervación espino-anorrectal.OBJETIVO:Desarrollar y determinar la utilidad clínica de una nueva prueba, estimulación magnética trans-lumbosacral anorrectal para la incontinencia fecal.DISEÑO:Estudio de cohorte observacional del 2012 al 2018.ENTORNO CLINICO:Centro de referencia terciario.PACIENTES:Pacientes con incontinencia fecal, combinación de incontinencia fecal/estreñimiento y controles sanos.INTERVENCIONES:Se realizó una prueba de estimulación magnética translumbosacral anorrectal utilizando una sonda anorrectal con 4 electrodos anulares y bobina magnética, y estimulando los plexos lumbares y sacros bilaterales y registrando ocho potenciales evocados motores las regiones anal y rectal.PRINCIPALES MEDIDAS DE RESULTADO:Se examinó la prevalencia de neuropatía lumbar y/o sacra. Los resultados secundarios fueron la correlación de la neuropatía con las funciones sensitivomotoras anorrectales y cambios morfológi-cos.RESULTADOS:Evaluamos 220 pacientes, 144 con incontinencia fecal, 76 con combinación de incontinencia fe-cal/estreñimiento y 31 sujetos sanos. Las ocho latencias de los potenciales evocadas motoras lum-bares y sacras se prolongaron significativamente (p <0,01) en la incontinencia fecal y el grupo mixto en comparación con los controles. La neuropatía fue irregular y afectaba 4,0 (3,0) (mediana (rango intercuartílico) sitios. Se observó neuropatía lumbar en 29-65% en la incontinencia fecal y 22-61% en el grupo mixto, y neuropatía sacra en 24-64% y 29-61 % de pacientes respectivamen-te. La neuropatía anal fue significativamente más prevalente (p <0,001) que la rectal en ambos grupos. No hubo correlación entre las latencias de los potenciales evocadas motoras y las presio-nes del esfínter anal, la sensación rectal o los defectos del esfínter anal.LIMITACIONES:Sin análisis comparativo con electromiografía.CONCLUSIÓNES:Se detectó neuropatía del plexo lumbar o sacro en el 40-75% de los pacientes con incontinencia fecal con una prevalencia dos veces mayor en la región anal que en el recto. La neuropatía lumbo-sacra parece ser un mecanismo independiente en la patogenia de la incontinencia fecal, no asocia-do con otras disfunciones sensitivomotoras. La estimulación magnética translumbosacral anorrec-tal tiene un alto rendimiento, es una prueba neurofisiológica segura y clínicamente útil. Consulte Video Resumen en http://links.lww.com/DCR/B728.

Uncommon cause of trigeminal neuritis and central nervous system involvement by herpes labialis: a case report.

BACKGROUND: Trigeminal neuropathy is characterized by numbness in the region innervated by the trigeminal nerves, with or without neuropathic weakness in the muscles of mastication. Trigeminal neuritis is a form of trigeminal neuropathy in which the lesion is caused by an inflammation. Herein, we report a patient with trigeminal neuritis due to central nervous system (CNS) involvement of herpes labialis (HL) infection, which was successfully treated with anti-viral and anti-inflammatory agents. CASE PRESENTATION: A young healthy female presented with numbness in the left hemiface for two weeks. She had a preceding typical HL infection on left facial lip one week before the sensory symptom onset. Brain magnetic resonance imaging revealed high signal intensities and asymmetrical thickening with enhancement along the cisternal segment of the left trigeminal nerve. Additionally, brain MR angiography showed multifocal stenoses in the M1 segment of the middle cerebral artery and the cavernous portion of the internal carotid artery. Cerebrospinal fluid (CSF) examination showed mild pleocytosis with normal protein level, glucose ratio, but CSF polymerase chain reaction assay for specific anti-viral antibodies including herpes simplex virus was negative, and CSF culture also did not identify a specific pathogen. The results of serologic testing including tumor markers and autoimmune markers were all unremarkable. A tentative diagnosis of trigeminal neuritis as a complication of HL involving the CNS was made considering the clinical, neuroradiological, and laboratory findings of the patient. Therefore, the patient was treated with intravenous methylprednisolone and acyclovir for 10 days. After the treatments, her sensory disturbance was markedly improved. Brain MRI at the 3-month follow-up also demonstrated improvement of previously identified high signal intensity lesions and multifocal intracerebral artery stenoses. CONCLUSION: HL is usually a self-limiting, benign disease without complications, but rarely presents as trigeminal neuritis due to CNS involvement. Therefore, meticulous evaluation may be necessary if trigeminal neuritis or CNS involving symptoms occur after HL.

Acute myelitis with multicranial neuritis caused by Varicella zoster virus: a case report.

BACKGROUND: Varicella zoster virus (VZV) can remain lifelong in the latent state in ganglionic neurons and adrenal glands after the initial infection. However, it can be reactivated anytime and can trigger several severe neurological manifestations such as encephalitis, meningitis, Ramsay-Hunt syndrome, cerebellitis, myelitis, and stroke. In addition, due to the diversity of clinical manifestations, clinical diagnosis of VZV can be difficult, especially in the absence of varicella. Here, we describe the case of a 52-year-old male who presented with symptoms of acute myelitis as well as polycranial neuritis, and was finally diagnosed with VZV infection through metagenomic next-generation sequencing (mNGS). CASE PRESENTATION: A 52-year-old male came to our hospital with complaint of headache, fever, weakness of right lower limb, abdominal distension, and hearing loss. T2-weighted MRI revealed a hyperintense lesion in the spinal cord extending from T8 to T11. In addition, enhanced MRI showed small patches and strips hyperintensities in both the spinal cord and meninges. Plain abdominal radiographs and abdominal computed tomography (CT) scan displayed air-fluid levels and incomplete bowel obstruction. Moreover, electrophysiological evaluation of the peripheral neuropathy in the extremities was found to be normal. Finally, by using metagenomic next-generation sequencing (mNGS) we found that the copy number of VZV DNA in cerebrospinal fluid (CSF) was significantly increased and IgG antibody against VZV in CSF was also noted to be positive. Hence, VZV infection was identified in patient's central neuron system. Finally, after a few days of low dose steroid treatment, the patient's symptoms were found to be significantly improved. CONCLUSIONS: The findings indicate that we should pay proper attention to the various symptoms caused by VZV infection due to the clinical heterogeneity, especially in the absence of cutaneous lesions.

Zoster neuritis of lumbar nerves: A clinical, magnetic resonance imaging, and electrodiagnostic evaluation.

Human herpesviruses, particularly the varicella-zoster virus, are notorious for affecting the central nervous system, especially when secondarily reactivated from a latent state. We present one such case of zoster radiculitis with an ensemble of typical dermatological and neurological features diagnosed on imaging and cerebrospinal fluid (CSF) studies and encourage the consideration of viral (zoster) neuritis as a differential in patients presenting with radicular pain.

Triceps tongue versus olecranon osteotomy for intra-articular distal humeral fractures: a matched-cohort study.

BACKGROUND: There are various approaches to the distal humerus when managing a distal humeral fracture, and controversy exists regarding which approach is optimal. The purpose of this study was to report the outcomes of the triceps tongue (TT) approach when used for osteosynthesis of AO type 13-A, B, and C distal humeral fractures. Secondarily, we aimed to compare the outcomes of the TT approach vs. olecranon osteotomy (OO) when used for osteosynthesis of AO type 13-C distal humeral fractures. METHODS: We performed a retrospective review of patients with distal humeral fractures treated with open reduction-internal fixation by either a TT or OO approach between 2007 and 2019 at 2 separate institutions. TT patients with AO type 13-C fractures were matched to OO patients at a 1:1 ratio based on age, sex, and fracture characteristics. Surgical time, intraoperative blood loss, elbow motion, fracture union, complications, and Disabilities of the Arm, Shoulder and Hand scores were compared. RESULTS: A total of 28 patients treated with the TT approach were assessed, and the matched TT and OO cohorts each comprised 15 patients. The TT group showed less blood loss (119.3 mL vs. 268.5 mL, P = .03), had greater maximal flexion (126° vs. 116°, P = .03), and achieved a larger flexion-extension arc (108° vs. 93°, P = .05) than the OO group. In the OO cohort, 27% of patients had complications directly related to the OO, and OO patients had a higher rate of postoperative ulnar nerve neuritis (33% vs. 0%, P = .04). There was no difference in Disabilities of the Arm, Shoulder and Hand score (P = .08), procedure time (P = .2), total number of patients with ≥1 complication (P = .5), difficulty with union (P = .7), or number of patients requiring revision surgery (P = .7). CONCLUSIONS: The TT approach is a safe and effective approach for the treatment of distal humeral fractures. When compared with the OO approach for AO type 13-C fractures, the TT approach did not differ regarding functional outcomes but showed increased range of motion, decreased intraoperative blood loss, and a lower rate of postoperative ulnar nerve neuritis. The TT approach should be considered as a safe and reliable first-line approach for intra-articular distal humeral fractures because it allows adequate visualization of the articular surface, eliminates complications related to osteotomy including delayed union or nonunion and hardware failure or irritation, and allows for easy conversion to total elbow arthroplasty.

Donor site morbidity of calcaneal, distal tibial, and proximal tibial cancellous bone autografts in foot and ankle surgery. A systematic review and meta-analysis of 2296 bone grafts.

PURPOSE: This study aims to report on the safety and donor site morbidity of the distal lower extremity (calcaneal, proximal, and distal tibial) cancellous bone autografts. We summarized the findings in a comprehensive infographic illustration. We are unaware of any similar meta-analyses to date. METHODS: Following the PRISMA guidelines, two independent investigators searched MEDLINE (PubMed), EMBASE, SCOPUS, Google Scholar, and Cochrane databases in December 2020 using the following keywords and their synonyms: ("bone graft", "donor site morbidity", "calcaneal graft", "proximal tibia graft", and "distal tibia graft"). Besides, the reference lists from previous review articles were searched manually for eligible studies. The primary outcomes of interest were (1) chronic pain, (2) fracture, and (3) infection, whereas the secondary outcomes were (1) neurological complications, (2) sensory disturbance and hypertrophic scars, (3) other complications such as shoe-wear difficulties and gait disturbance. Inclusion criteria were: studies on complications and adverse events of lower extremity bone autografts (calcaneal, proximal tibial, and distal tibial bone autografts) reporting at least one of the desired outcomes. Studies not reporting any of the outcomes of interest or if the full text is not available in English were excluded. Studies reporting on bone marrow aspirate or autografts for non-orthopedic indications were also excluded. RESULTS: After the removal of duplicates, a total of 5981 studies were identified. After screening those records, 85 studies remained for full-text assessment. Out of those, 15 studies qualified for the meta-analysis with a total of 2296 bone grafts. Out of those grafts, 1557(67.8%) were calcaneal grafts, 625 (27.2%) were proximal tibial grafts, and 114 (5%) were distal tibial grafts. In calcaneal bone grafts, there were 28 cases of chronic pain [1.97%, CI:1.10-2.50%, I2 = 66%], 5 fractures [0.32%, CI: 0.10-0.60%,I2 = 0%], 20 sural neuritis [1.28%, CI:0.70-1.80%, I2 = 0%), and no wound infections. In proximal tibial grafts there were 13 cases of chronic pain [2.08%, CI: 1.01-3.2%, I2 = 34.5%], 1 fracture [0.16%, CI:0.10-0.50%, I2 = 0%], and 3 superficial wound infections [0.48%, CI: 0.10-1.01, I2 = 0%]. In the distal tibial grafts there were no cases of chronic pain or wound infections, 1 fracture [0.90%, CI: 0.80-2.6%, I2 = 0%], and 5 saphenous neuritis [4.5%, CI: 0.70-8.40%, I2 = 65%]. CONCLUSION: Calcaneal, distal tibial, and proximal tibial bone autografts are safe with a low rate of overall and major complications. We report an overall complication rate of 6.8%, which is less than half of that previously reported for iliac crest grafts. The authors recommend using distal lower extremity grafts for foot and ankle primary surgeries instead of iliac crest grafts when indicated. Clinical trials with a large sample size are required.

Clinical neurophysiology and cerebrospinal liquor analysis to detect Guillain-Barré syndrome and polyneuritis cranialis in COVID-19 patients: A case series.

We report a case series of five patients affected by SARS-CoV-2 who developed neurological symptoms, mainly expressing as polyradiculoneuritis and cranial polyneuritis in the 2 months of COVID-19 pandemic in a city in the northeast of Italy. A diagnosis of Guillain-Barré syndrome was made on the basis of clinical presentation, cerebrospinal fluid analysis, and electroneurography. In four of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 g/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases a significant decrease in amplitude of compound motor action potential compound muscle action potential (cMAP). Four patients presented a mild facial nerve involvement limited to the muscles of the lower face, with sparing of the forehead muscles associated to ageusia. In one patient, taste assessment showed right-sided ageusia of the tongue, ipsilateral to the mild facial palsy. In three patients we observed albuminocytological dissociation in the cerebrospinal fluid, and notably, we found an increase of inflammatory mediators such as the interleukin-8. Peripheral nervous system involvement after infection with COVID-19 is possible and may include several signs that may be successfully treated with immunoglobulin therapy.

Oxytocin reverses ethanol consumption and neuroinflammation induced by social defeat in male mice.

Oxytocin (OXT) modulates social interactions, attenuates stressful responses and can decrease drug-seeking and taking behaviors. In previous studies, we observed that social defeat (SD) induced a long-lasting increase in ethanol intake and neuroinflammation in male mice. We also know that OXT blocks the increase in cocaine reward induced by SD. Therefore, in the present study we aimed to evaluate the effect of 1 mg/kg of OXT administered 30 min before each episode of SD on ethanol consumption and the neuroinflammatory response in adult male mice. Three weeks after the last SD, mice underwent oral ethanol self-administration (SA) procedure, and striatal levels of the two chemokines CX3CL1 and CXCL12 were measured after the last SD and at the end of the ethanol SA. OXT administration blocked the increase in voluntary ethanol consumption observed in defeated mice, although it did not affect motivation for ethanol. An increase in the striatal levels of CX3CL1 and CXCL12 was observed in defeated animals immediately after the last defeat and after the ethanol SA. However, defeated mice treated with OXT did not show this increase in the neuroinflammatory response. In conclusion, OXT treatment can be a powerful therapeutic target to reduce the negative effects of social stress on ethanol consumption and the neuroinflammatory process.