Dramatic secukinumab-mediated improvements in refractory leprosy-related neuritis via the modulation of T helper 1 (Th1) and T helper 17 (Th17) immune pathways

Abstract A 39-year-old woman was diagnosed with relapsed multibacillary leprosy and refractory neuritis. Here, we describe an evident loss of therapeutic effectiveness after the third pulse of corticosteroids, which may be attributed to tachyphylaxis and the posterior modulation of interferon- γ (IFN-γ), tumor necrosis factor- α (TNF-α,) interleukin-17A (IL-17A), and IL-12/23p40 after the induction phase of secukinumab. In this case, plasma cytokine analysis showed that secukinumab induced a reduction in IL-17 concomitant with impressive clinical improvements in the patient's neural function. Interestingly, secukinumab induced reductions in cytokines related to Th1 responses and earlier stages of the Th17 response, including IL-23/12.

Selection of optimized treatment plan of acupuncture for lateral femoral cutaneous neuritis / 中国针灸

OBJECTIVE@#To select the optimized treatment plan of acupuncture for lateral femoral cutaneous neuritis by using multiple indexes decision-making method based on the clinical evidence.@*METHODS@#The randomized control trials (RCTs) regarding acupuncture for lateral femoral cutaneous neuritis in the CNKI database, CBM database, WANFANG database, VIP database, PubMed, Cochrane Library and Embase published before December 31, 2017 were comprehensively collected. The modified Jadad scale was used to evaluate the quality of the RCTs. Then the evaluation indexes were selected and the dimensions of evaluation indexes were standardized by using extreme difference transformation method. The weight of each index was determined by using relative comparison method and the standardized matrix was weighted. Thus, the ideal solution and the negative ideal solution were obtained, and the relatively degree of each treatment plan to the ideal solution was calculated to propose the optimized plan of acupuncture for lateral femoral cutaneous neuritis.@*RESULTS@#A total of 18 RCTs were included, the optimized plan of acupuncture for lateral femoral cutaneous neuritis was using thin fire needle to rapidly prick the abnormal skin region with fast needle insertion-withdrawal technique; the fire needle was applied repeatedly; intensive pricking to form a treatment area; the treatment was given once every 5 days.@*CONCLUSION@#Based on the current clinical evidence, the optimized plan of acupuncture for lateral femoral cutaneous neuritis is using thin fire needle to prick the abnormal skin region; the multiple methods of plum-blossom needling met the characteristic of lateral femoral cutaneous neuritis and is suitable for clinical selection. The main acupoints are points in the abnormal skin area or the acupoints in the foot- meridian and foot- meridian, combined with lumbar Jiaji (EX-B2) points.

Effectiveness of the retreatment of patients with multibacillary leprosy and episodes of erythema nodosum leprosum and/or persistent neuritis: a single-center experience

Abstract: Background: Erythema nodosum leprosum may appear before, during or after treatment of leprosy and is one of the main factors for nerve damage in patients. When it occurs or continues to occur after treatment, it may indicate disease recurrence and a new treatment may be instituted again. Objective: To evaluate the retreatment of patients with multibacillary leprosy who underwent standard treatment with multidrug therapy, but developed or continued to present reactions of erythema nodosum leprosum and/or neuritis 3-5 years after its end. Method: For this objective, a new treatment was performed in 29 patients with multibacillary leprosy who maintained episodes of erythema nodosum and/or neuritis 3-5 years after conventional treatment. Results: In general, we observed that 27 (93.10%) had no more new episodes after a follow up period of eight months to five years. In five of these patients the reason for the retreatment was the occurrence of difficult-to-control neuritis, and that has ceased to occur in all of them. Study limitations: Small number of patients.. Conclusion: In the cases observed, retreatment was an effective measure to prevent the occurrence of erythema nodosum leprosum and/or persistent neuritis.

Optic Neuritis of Korean Adult

PURPOSE: The aim of the study was to describe the clinical features and characteristics of optic neuritis patients compared with those of patients enrolled in the Optic Neuritis Treatment Trial (ONTT). METHODS: We retrospectively included consecutive patients diagnosed with optic neuritis between 2006 and 2015. The inclusion criteria were the same as those of the ONTT; an acute or subacute unilateral visual symptom ≤8 days in duration, a relative afferent pupillary defect, and a visual field defect in the affected eye. RESULTS: The 41 patients (14 females, 27 males) were of mean age 32.7 years. The incidence of papilledema was 58.5%, thus higher than that of ONTT patients (p = 0.004), and the incidence of ocular pain was 75.6%, lower than that of ONTT patients (p = 0.002). Six months after intravenous methylprednisolone therapy, 29 of 32 eyes (90.6%) recovered visual acuity of ≥1.0 or better, and only one eye exhibited poor visual acuity (≤0.5). Orbital magnetic resonance imaging (MRI) was performed on 34 patients, and most (91.2%) exhibited optic nerve enhancement. The three patients who did not exhibit enhancement reported no pain. CONCLUSIONS: The clinical features of Korean optic neuritis patients differed from those of patients of the ONTT. Most patients exhibited optic nerve MRI enhancement associated with ocular pain. If enhancement of the optic nerve is lacking, diseases other than optic neuritis should be suspected because most optic nerves with neuritis exhibit enhancement on MRI.

Perineural dexmedetomidine effects on sciatic nerve in rat / Efeitos de dexmedetomidina perineural no nervo ciático em ratos

Abstract The present study was designed to test the hypothesis that high dose dexmedetomidine would increase the duration of antinociception to a thermal stimulus in a rat model of sciatic nerve blockade without causing nerve damage. The rats were anesthetized with isoflurane. After electromyography (EMG) recordings, right sciatic nerves were explored and perineural injections were delivered: Group D (n = 7), 40 µg µg kg-1 dexmedetomidine administration, Group II (n = 6), (0.2 mL) saline administration, Group III (n = 2), only surgically exploration of the right sciatic nevre. Time to paw withdrawal latency (PAW) to a thermal stimulus for both paws and an assessment of motor function were measured every 30 min after the nerve block until a return to baseline. The compound muscle action potential (CMAP) of right and left sciatic nerves were recorded 10 times per each nerve once more after perineural injections at 14 day. After EMG recordings, right and the part of left sciatic nerve were excised at a length of at minimum 15 mm for histopathological examination. Comparison of right/left CMAP amplitude ratios before and 14 days after the procedure showed a statistically significant difference (p = 0.000). There were no differences in perineural inflammation between the Group D, Group S, and Group E at 14 days.

Resumo O presente estudo foi desenvolvido para testar a hipótese de que dexmedetomidina em dose alta aumentaria a duração da antinocicepção a um estímulo térmico em modelo de rato de bloqueio do nervo ciático sem causar danos ao nervo. Os ratos foram anestesiados com isoflurano. Após os registros da eletromiografia (EMG), os nervos ciáticos direitos foram explorados e injeções perineurais foram administradas: Grupo D (n = 7) recebeu 40 µg/kg-1 de dexmedetomidina, Grupo II (n = 6) recebeu 0,2 mL de solução salina, Grupo III (n = 2) recebeu apenas exploração cirúrgica do nervo ciático direito. O tempo de latência de retirada da pata (LRP) a um estímulo térmico para ambas as patas e uma avaliação da função motora foram avaliados a cada 30 minutos após o bloqueio do nervo até o retorno à fase basal. O potencial de ação muscular composto (PAMC) dos nervos ciático direito e esquerdo foi registrado 10 vezes para cada nervo, mais uma vez, após as injeções perineurais no 14º dia. Após os registros da EMG, o nervo ciático direito e parte do esquerdo foram excisados com um comprimento de no mínimo 15 mm para exame histopatológico. A comparação das proporções da amplitude do PAMC direito/esquerdo antes e 14 dias após o procedimento mostrou uma diferença estatisticamente significativa (p = 0,000). Não houve diferenças em inflamação perineural entre os grupos D, S e E aos 14 dias.

Median nerve neuropathy

The median nerve is the most important nerve in the upper extremity, as it is responsible for most of the sensation of the hand, the fine motor functions of the thumb, and finger grasping. Median neuropathies most commonly occur as compressive neuropathy or entrapment neuropathy, but sometimes as neuritis without any compressive lesion. Carpal tunnel syndrome (CTS), anterior interosseous nerve syndrome, and pronator teres syndrome are the subtypes of median nerve neuropathies, of which CTS is the most common. Median neuropathies can be diagnosed clinically by careful history-taking and a physical examination. Typical symptoms of CTS include night pain (crying), a tingling sensation of the radial digits, numbness or paresthesia, clumsiness, and atrophy of the thenar muscles. Electrophysiologic testing can be used for confirmation of the diagnosis and for documentation before surgical treatment. Imaging modalities including ultrasonography or magnetic resonance imaging can be used to ensure diagnostic accuracy and to detect unusual causes of compression. Conservative treatments include rest, bracing, nerve stretching, non-steroidal anti-inflammatory drugs, and steroid injections. If nonsurgical approaches are unsatisfactory or the nerve damage is severe, surgical treatment should be considered. Carpal tunnel release for CTS is a relatively simple procedure that involves division of the transverse carpal ligament and decompression of the median nerve. Early diagnosis and proper management are important, as muscle atrophy and sensory loss may persist when surgical release is delayed in patients with advanced disease.

The Fate of Anterior Interosseous Nerve Syndrome

PURPOSE: We report the causes and prognosis of anterior interosseous nerve syndrome (AIN) according to the treatment. METHODS: From March 2009 to December 2015, the 20 patients with the clinical symptom of AIN syndrome were enrolled in the study and electromyography (EMG) of AIN was performed. We retrospectively reviewed hand function test, active range of motion, the disabilities of the arm, shoulder and hand (DASH) score and EMG during the recovery from disease. We further surveyed the time of recovery and residual symptoms. RESULTS: The patients with unknown cause of the disease (12 cases), heavy work or trauma (6 cases) and infection (2 cases) were investigated in the study. Thirteen out of 15 cases with conservative treatment and 2 out of 5 cases with a surgical treatment at an average of 8 months from disease were recovered. In addition, 8 cases with fine motor disturbance and 3 cases with tingling residual symptom were observed. CONCLUSION: Due to the low possibility of entrapment neuropathy, conservative treatment for 7 months is the first choice rather than surgical treatment. If there is no improvement from the conservative treatment, surgical exploration of AIN is the indication of treatment. After recovery, patients may have the symptoms of fine motor disturbance and tingling.

Dermal and neural toxicity caused by acrylamide exposure in two Korean grouting workers: a case report

BACKGROUND: Peripheral neuritis caused by acrylamide is well-known, and many Korean grouting workers are frequently exposed to acrylamide in grouting agents that are injected into cracked concrete. We recently encountered two cases of dermal and neural toxicity in Korean grouting workers with exposure to grouting agents that contained a high concentration of acrylamide. CASE PRESENTATION: The first case involved a 44-year-old man with 8 years of waterproofing experience. The patient developed peeling skin on both hands while grouting, which progressed to systemic neurological symptoms, such as reduced sensory function and strength. The patient was diagnosed with peripheral neuropathy caused by acrylamide exposure, and fully recovered after conservative treatment and withdrawal of exposure to the grouting agent. The second case involved a 34-year-old man with 10 years of grouting experience. The patient initially experienced weakness in both legs, which progressed to weakness in his arms and uncontrolled phonation. After being hospitalized, he was diagnosed with cerebellar ataxia and peripheral neuropathy caused by acrylamide exposure, and was discharged after conservative treatment. Our follow-up investigation revealed that both workers were recently exposed to grouting agents that contained higher concentrations of acrylamide, compared to the agents that they had previously been using. CONCLUSIONS: Both workers had workplace acrylamide exposure through dermal contact plus inhalation of dust and vapor, which led to the neural toxicity and dermatitis. Therefore, government studies are needed to investigate the current status of workplace acrylamide use, and to protect workers from the hazardous effects of using acrylamide-containing grouting agents.

Vestibular Paroxysmia Mimicking Benign Parxysmal Positional Vertigo / 대한평형의학회지

Vestibular paroxysmia is the name given to the syndrome caused by vascular compression of the vestibulocochlear nerve. The main symptoms of vestibular paroxysmia are recurrent, spontaneous, brief attacks of spinning, non-spinning vertigo or positional vertigo that generally last less than one minute, with or without ear symptoms (tinnitus and hypoacusis). Prior to attributing a patient's symptoms to vestibular paroxysmia, however, clinicians must exclude common conditions like benign paroxysmal positional vertigo, Menière's disease, vestibular neuritis and vestibular migraine. This is usually possible with a thorough history and bedside vestibular/ocular motor examination. Herein, we describe a patient with vestibular paroxysmia that mimicked resolved BPPV with a literature review.

The First Case of Vestibulocochlear Neuritis in a Patient with Acquired Immunodeficiency Syndrome in Korea

The incidence of human immunodeficiency virus (HIV) infections continue to increase throughout the world. Although neurologic complications are frequent in individuals with HIV infection or acquired immunodeficiency syndrome (AIDS), vestibulocochlear neuritis is still a relatively rare manifestation. We report the first case of vestibulocochlear neuritis occurring in an AIDS patient in Korea.

Surgical treatment of type I neuritis in a teenage boy with borderline tuberculoid leprosy

Exacerbation of the immune response against Mycobacterium leprae can lead to neuritis, which is commonly treated via immunosuppression with corticosteroids. Early neurolysis may be performed concurrently, especially in young patients with a risk of functional sequelae. We report the case of a young patient experienced intense pain in the left elbow one year after the treatment of tuberculoid-tuberculoid leprosy. The pain was associated with paresthesias in the ulnar edge and left ulnar claw. After evaluation, the diagnosis was changed to borderline tuberculoid leprosy accompanied with neuritis of the left ulnar nerve. Early neurolysis resulted in rapid reduction of the pain and recovery of motor function.

Management of traumatic neuralgia in a patient with the extracted teeth and alveoloplasty: a case report

A majority of patients who sustain injuries to the peripheral sensory nerves of the face and jaws experience a slow but gradual return of sensation that is functional and tolerable, if not the same as before the injuries. However, long-term effects of such injuries are aggravating for many patients, and a few patients experience significant suffering. In some of these patients, posttraumatic symptoms become pathological and are painful. The predominant painful components are (1) numbing anesthesia dolorosa pain, (2) triggered neuralgiaform pain, (3) burning and aching causalgiaform pain, and (4) phantom pain. This is a case report of conservative management of traumatic neuralgia and neuritis as part of posttraumatic pain syndromes in geriatric patients who have undergone the teeth extraction and alveoloplasty.

Herbicide paraquat induces sex-specific variation of neuroinflammation and neurodegeneration in Drosophila melanogaster.

There are several reports on herbicide paraquat (PQ)-induced Parkinsonian-like pathology in different animal models, including Drosophila melanogaster. Also, the role of some inflammatory factors, such as nitric oxide is reported in PQ-induced neuroinflammation of Drosophila. Although invertebrate model is valuable to study the conserved inflammatory pathway at the time of neurodegeneration, but neuroinflammation during PQ-mediated neurodegeneration has not been studied explicitly in Drosophila. In this study, the inflammatory response was examined in Drosophila model during PQ-induced neurodegeneration. We found that after exposure to PQ, survivability and locomotion ability were affected in both sexes of Drosophila. Behavioural symptoms indicated similar physiological features of Parkinson’s disease (PD) in different animal models, as well as in humans. Our study revealed alteration in proinflamatory factor, TNF-α and Eiger (the Drosophila homologue in TNF superfamily) was changed in PQ-treated Drosophila both at protein and mRNA level during neurodegeneration. To ensure the occurrence of neurodegeneration, tyrosine hydroxylase (TH) positive neuronal cell loss was considered as a hallmark of PD in the fly brain. Thus, our result revealed the conserved inflammatory events in terms of expression of TNF-α and Eiger present during a sublethal dose of PQ-administered neurodegeneration in male and female Drosophila with significant variation in proinflamatory factor level among both the sexes.

Enhanced effect of guizhi plus Gegen Decoction on learning and memory disorder in LPS induced neuroinflammatory mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the potential effect of Guizhi plus Gegen Decoction (GGD) in improving learning and memory of lipopolysaccharides (LPS) induced neuroinflammatory mice and its possible mechanisms.</p><p><b>METHODS</b>Totally 63 male ICR mice were randomly divided into 5 groups, i.e., the normal control (n = 13), the model group (n = 13), the low dose GGD group (n = 10), the high dose GGD group (n = 14), and the positive control group (n = 13). Mice were intraperitoneally injected with LPS (0.33 mg/kg) to induce Alzheimer's disease (AD) model. Mice in the high and the low dose GGD groups were administered with 12 g/kg or 6 g/kg by gastrogavage for 4 successive weeks. Mice in the control group were intraperitoneally injected with minocycline (50 mg/kg) for 3 days. By the end of treatment LPS were injected 4 h before behavior test each day, and then behavior test was conducted in mice of each group. Effect of GGD on learning and memory of AD mice was observed by using open field test, novel object recognition task, and Morris water maze.</p><p><b>RESULTS</b>Open field test showed there was no statistical difference in the movement time and the movement distance among all groups (P > 0.05), suggesting that LPS and GGD had no effect on locomotor activities of mice. In novel object recognition test, AD mice spent significantly shorter time to explore novel object after they were induced by LPS (P < 0.05), while for AD mice in the low and high dose GGD groups, their capacities for exploration and memory were significantly improved (P < 0. 05, P < 0.01). Results of Morris water maze showed that AD mice exhibited increased escape latency (P < 0.05) and spent much less time in swimming across the original platform (both P < 0.05). However, AD mice in the low and high dose GGD groups had obvious shortened latency and increased time percentage for swimming (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>GGD possessed certain improvement in learning and memory disorder of LPS induced AD mice.</p>

Scavenger receptor on astrocytes and its relationship with neuroinflammation / 中国医学科学院学报

Neuroinflammation in central nervous system, featured by glial cells activation, can always be found during the development of neurodegenerative diseases. Astrocytes, the most abundant glial cells in the brain, can release both pro-inflammatory and anti-inflammatory factors, thus playing a crucial role in the neuroinflammation. A variety of pattern-recognition receptors on astrocytes are involve d in the inflammatory response, particularly the scavenger receptor. Scavenger receptor is a cell surface glycoprotein and can identify diverse ligands. With a variety of biological functions, it may activate many signal pathways related to neuroinflammation, regulate the host defense and the development of neuroinflammation, and eventually regulate the process of neuroinflammation. Thus, it play a key role in the development of neurodegenerative diseases and many other conditions. This review summarizes the scavenger receptor expressed on astrocytes and how it regulates signal transduction pathways associated with neuroinflammation and thus participates in regulating neuroinflammation.

A Case of Pseudo-Vestibular Neuritis with Contralesional Canal Paresis due to Spontaneous Bilateral Vertebral Artery Dissection / 대한이비인후과학회지

Pseudo-vestibular neuritis is a central pathology of acute vestibular syndrome, characterized by unidirectional nystagmus mimicking acute peripheral vestibulophaty. We report a 39-year-old female patient who developed cerebellar infarction with isolated vertigo, spontaneous nystagmus, a positive head thrust test, and unilateral canal paresis in the contralesional side. The patient had no vascular risk factors. A diffusion-weighted image of the brain showed infarction of medial branch of posterior inferior and superior cerebellar artery on the left side. A magnetic resonance angiography of neck disclosed a wide range of diffused severe stenosis and narrowing of right and left vertebral arteries, respectively. This case suggests the possibility of vestibular ischemia masking the central pathology in isolated vertigo.

Olfaction and Neurodegenerative Disease / 한양의대학술지

Olfactory dysfunction is an early and common symptom of many neurodegenerative diseases, particularly of Parkinson's disease, Alzheimer's disease, and mild cognitive impairment that heralds progression to dementia. Olfactory impairment is known to be related to several pathologic changes including the deposition of alpha-synuclein, hyperphosphorylated tau protein, neurofilament protein, Lewy bodies and neuritis inducing a complex cascade of molecular processes such as oxidative stress, neuroinflammation, and cytosolic disruption of cellular processes leading to cell death. The areas mainly showing these pathologic changes are the olfactory epithelium, olfactory bulb and tract, primary olfactory cortices, and their secondary target areas. Since early loss of olfactory function is common among several common neurodegenerative disorders, recent investigations have focused on its utility as a biomarker for early diagnosis and progression. Olfactory impairment appears to be an important sign for early detection, a useful biomarker for disease progression and a useful differentiator between neurological disorders.

Diagnosis and treatment of upper arm radial neuritis by ultrasonography / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the application of ultrasonography in diagnosis and treatment of the upper arm radial neuritis.</p><p><b>METHODS</b>From 2005.12 to 2011.7, 10 patients of the upper arm radial neuritis were selected and included 6 males and 4 females with an average age of 32 years old ranging from 20 to 40 years. The course of disease ranged from 4 months to 2 years. All patients feel pain on the outside of upper arm. Medical examination showed Tinel's sign masculine, and the muscle force included extension of wrist and fingers were reduced. Upper arm radial neuritis were diagnosed by clinical sign and medical examination. All patients underwent ultrasonography examination, electrophysiology examination and operation. The ultrasonography were compared to the results of electrophysiology examination,and ultrasonography were compared to intra-operative findings and pathology examination.</p><p><b>RESULTS</b>The ultrasound images showed average diameter of affected limb radial nerve were (0.29+/-0.04) cm, average area were (0.23+/-0.05) cm2, and all of these were greater than uninjured side. Ultrasonograghic findings and orientation of radial neuritis were consistent with intra-operative findings,and the results of ultrasonography were consistent with the results of pathology examination.</p><p><b>CONCLUSION</b>Ultrasonography examination provide morphological evidence for the diagnosis and treatment of the upper arm radial neuritis.</p>

The role of TLR4-mediated MyD88-dependent pathway in neuroinflammation in hippocampal neurons of rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate weather there is a toll-like receptor 4 (TLR4)-mediated myeloid differentiation factor 88 (MyD88)-dependent pathway in hippocampal neurons of rats and the probable role of the pathway in neuroinflammation.</p><p><b>METHODS</b>To establish the proper model, primarily cultured hippocampal neurons were treated with lipopolysaccharides (LPS), or pretreated with TLR4 antibody then co-treated with LPS. The expression of mRNA of MyD88 and TNF-alpha receptor associated factor 6 (TRAF6) were tested by RT-qPCR. The content of MyD88 and TRAF6 were tested by Western blot. The nuclear translocation of nuclear factor-kappaB/P65 (NF-kappaB/p65) was tested by immunofluorescence. The content of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and nitric oxide (NO) were tested by ELISA.</p><p><b>RESULTS</b>LPS could increase MyD88 and TRAF6 mRNA, upregulate protein level of MyD88 and TRAF6 and increase the level of TNF-alpha, IL-1beta and NO in cell culture supernatant. LPS also could promote NF-kappa B/p65 translation to the nucleus. The pretreatment with TLR4 antibody reduced the translocation to nucleus for NF-kappaB/P65 and the contents of TNF-alpha, IL-1beta and NO in the culture supernatant.</p><p><b>CONCLUSION</b>There is a TLR4-mediated MyD88-dependent pathway in hippocampal neurons. The activation of this pathway can increase the level of TNF-alpha, IL-1beta and NO in cell culture supernatant. TLR4-mediated MyD88-dependent pathway in hippocampal neurons participate in neuroinflammation, that means neurons are not passive in inflammation.</p>

Activation of small Rho GTPases by blebbistatin in PC12 cells / 동물의과학연구지

Neuronal differentiation is a complex biological process accompanying cytoskeletal reorganization, including neurite outgrowth and growth cone formation. Therefore, neuronal differentiation is critically regulated by actin-related signaling proteins, such as small Rho GTPases, guanine nucleotide exchange factors (GEFs), and myosins. This study will demonstrate the change in activity of three small Rho GTPases, Rac, Cdc42, and Rho A, by treatment with blebbistatin (BBS), a specific inhibitor for myosin, during bFGF-induced neurite outgrowth in PC12 cells. Treatment with BBS induced morphological changes in growth cones and neurites during differentiation. A marked increase in protrusion and filopodia structures in growth cones, the shaft of neuritis, and cell membranes was observed in the cells treated with BBS. Activity of Rho GTPases showed the alterations in response to BBS. Activities of both Rac and Rho A were inhibited by BBS in a time-dependent manner. By contrast, Cdc42 activity was not changed by BBS. These results suggest that inactivation of myosin II by BBS induced morphological changes in neurites and growth cones and distinct regulation of three Rho GTPases during differentiation of PC12 cells.