Manual therapeutic plasma exchange for treatment of a dog with suspected acute canine polyradiculoneuritis.

BACKGROUND: Acute canine polyradiculoneuritis is one of the most common polyneuropathies occurring in dogs. The disease is very similar to the Guillain-Barré syndrome in humans. In veterinary medicine, there is no established treatment for this disease, while in human medicine, therapeutic plasma exchange and intravenous immunoglobulin administration are two main immunotherapy treatments of this syndrome. CASE PRESENTATION: A 12-year-old male Jack Russel Terrier was presented with a history of acute weakness of the pelvic limbs progressing to flaccid tetraplegia with respiratory compromise. Complete diagnostic workup was performed including blood work, diagnostic imaging (radiographs of the thorax as well as ultrasound of the abdomen) and echocardiography. Based on the clinical course, neurological localisation and the results of electrodiagnostic examination acute canine polyradiculoneuritis was suspected. During the hospitalization, the dog deteriorated and was admitted to the intensive care unit for respiratory support via tracheostomy tube. In addition to symptomatic treatment, immunotherapy via single treatment of manual therapeutic plasma exchange was administered. This procedure was safe, and the dog showed improvement of clinical signs 3 days after therapy was initiated, as well as improvement of neurological signs (from grade 4 tetraplegia to grade 3) within 5 days. However, the dog was euthanized 3 weeks later due to complications related to the tracheostomy. CONCLUSIONS: This is the first case report of a manual therapeutic plasma exchange in a dog with suspected acute canine polyradiculoneuritis suggesting that this method is safe and well tolerated in dogs with this disease. It may be a reasonable adjunctive treatment to supportive therapy in severe cases.

Bilateral widespread segmental swelling on nerve sonography in multifocal acquired demyelinating sensory and motor neuropathy: Two case reports.

INTRODUCTION: Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) is an asymmetric immune-related neuropathy with conduction block. We report 2 MADSAM cases with detailed clinical, electrophysiological, and sonography profiles. PATIENT CONCERNS AND DIAGNOSIS: Two cases presented with patchy sensorimotor impairment in both clinical and electrophysiological findings. Notably, nerve ultrasound demonstrated multifocal nerve enlargement not only at sites of conduction blockade but also at the unaffected contralateral sites. Interestingly, in our first case, focal radial nerve enlargement was observed prior to the clinical manifestations, suggesting nerve dynamic pathogenesis with variable clinical significance. INTERVENTIONS AND OUTCOMES: The first patient was initially treated with prednisolone, however, 3 months after steroid therapy, her symptoms progressed. After treatment with intravenous immunoglobulin for 3 months, the symptoms stabilized. The second patient showed improvement after 2 months of prednisolone treatment. CONCLUSION: These observations suggest a more widespread pathomechanism underlying MADSAM, and ultrasound may detect nerve lesions earlier than clinical electrophysiology studies, and is warranted for early detection and thorough documentation of nerve pathology.

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.

[Selection of optimized treatment plan of acupuncture for lateral femoral cutaneous neuritis].

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 ashi points in the abnormal skin area or the acupoints in the foot-yangming meridian and foot-shaoyang meridian, combined with lumbar Jiaji (EX-B2) points.

Avian Ganglioneuritis in Clinical Practice.

Avian ganglioneuritis (AG) comprises one of the most intricate pathologies in avian medicine and is researched worldwide. Avian bornavirus (ABV) has been shown to be a causative agent of proventricular dilatation disease in birds. The avian Bornaviridae represent a genetically diverse group of viruses that are widely distributed in captive and wild populations around the world. ABV and other infective agents are implicated as a cause of the autoimmune pathology that leads to AG, similar to human Guillain Barrè syndrome. Management of affected birds is beneficial and currently centered at reducing neurologic inflammation, managing secondary complications, and providing nutritional support.

Pure neuritic leprosy: Current status and relevance.

Pure neuritic leprosy has always been an enigma due to its clinical and management ambiguities. Although only the Indian Association of Leprologist's classification recognizes 'pure neuritic leprosy' as a distinct sub group of leprosy, cases nonetheless are reported from various countries of Asia, Africa, South America and Europe, indicating its global relevance. It is important to maintain pure neuritic leprosy as a subgroup as it constitutes a good percentage of leprosy cases reported from India, which contributes to more than half of global leprosy numbers. Unfortunately, a high proportion of these patients present with Grade 2 disability at the time of initial reporting itself due to the early nerve involvement. Although skin lesions are absent by definition, when skin biopsies were performed from the skin along the distribution of the affected nerve, a proportion of patients demonstrated leprosy pathology, revealing sub-clinical skin involvement. In addition on follow-up, skin lesions are noted to develop in up to 20% of pure neuritic leprosy cases, indicating its progression to manifest cutaneous disease. Over the decades, the confirmation of diagnosis of pure neuritic leprosy has been subjective, however, with the arrival and use of high-resolution ultrasonography (HRUS) for nerve imaging, we have a tool not only to objectively measure and record the nerve thickening but also to assess the morphological alterations in the nerve including echo texture, fascicular pattern and vascularity. Management of pure neuritic leprosy requires multidrug therapy along with appropriate dose of systemic corticosteroids, for both acute and silent neuritis. Measures for pain relief, self-care of limbs and physiotherapy are important to prevent as well as manage disabilities in this group of patients.

Modeling leukocyte trafficking at the human blood-nerve barrier in vitro and in vivo geared towards targeted molecular therapies for peripheral neuroinflammation.

Peripheral neuroinflammation is characterized by hematogenous mononuclear leukocyte infiltration into peripheral nerves. Despite significant clinical knowledge, advancements in molecular biology and progress in developing specific drugs for inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis, there are currently no specific therapies that modulate pathogenic peripheral nerve inflammation. Modeling leukocyte trafficking at the blood-nerve barrier using a reliable human in vitro model and potential intravital microscopy techniques in representative animal models guided by human observational data should facilitate the targeted modulation of the complex inflammatory cascade needed to develop safe and efficacious therapeutics for immune-mediated neuropathies and chronic neuropathic pain.

Prospective, Multicenter, Randomized, Double-Blinded, Partial Crossover Study to Assess the Safety and Efficacy of the Novel Neuromodulation System in the Treatment of Patients With Chronic Pain of Peripheral Nerve Origin.

INTRODUCTION: Currently available central nervous system treatment strategies are often insufficient in management of peripheral neuropathic pain, prompting a resurgence of neuromodulation focused on peripheral pain. A new peripheral nerve stimulation device was investigated in a prospective, randomized, double blind, crossover study, looking specifically at efficacy and safety, with Food and Drug Administration oversight. METHODS: Prospective, multicenter, randomized, double-blind, partial crossover study to assess safety and efficacy. After IRB approval, patients were enrolled, implanted, and then followed for three months to assess efficacy and one year for safety based on Food and Drug Administration guidance. RESULTS: One hundred forty-seven patients were consented and screened for the study. Thirty-five did not meet inclusion or exclusion criteria. Ninety-four patients were implanted and then randomized to the treatment (45) or the Control group (49). The primary efficacy endpoint, three months after randomization to treatment, demonstrated that patients receiving active stimulation achieved a statistically significantly higher response rate of 38% vs. the 10% rate found in the Control group (p = 0.0048). Improvement in pain was statistically significant between the randomized groups, with the Treatment group achieving a mean pain reduction of 27.2% from Baseline to Month 3 compared to a 2.3% reduction in the Control group (p < 0.0001). During the partial crossover period, patients again demonstrated statistically significant improvement in pain relief with active stimulation compared to baseline. Further, the Treatment group had significantly better improvement than the Control group in secondary measures including but not limited to quality of life and satisfaction. Safety, assessed throughout the trial and with follow-up to one year, demonstrated no serious adverse events related to the device. All device-related adverse events were minor and self-limiting. CONCLUSION: The novel peripheral nerve stimulation device is a safe and effective treatment strategy to address neuropathic pain of peripheral nerve origin.

Transplantation of cerebellar neural stem cells improves motor coordination and neuropathology in Machado-Joseph disease mice.

Machado-Joseph disease is a neurodegenerative disease without effective treatment. Patients with Machado-Joseph disease exhibit significant motor impairments such as gait ataxia, associated with multiple neuropathological changes including mutant ATXN3 inclusions, marked neuronal loss and atrophy of the cerebellum. Thus, an effective treatment of symptomatic patients with Machado-Joseph disease may require cell replacement, which we investigated in this study. For this purpose, we injected cerebellar neural stem cells into the cerebellum of adult Machado-Joseph disease transgenic mice and assessed the effect on the neuropathology, neuroinflammation mediators and neurotrophic factor levels and motor coordination. We found that upon transplantation into the cerebellum of adult Machado-Joseph disease mice, cerebellar neural stem cells differentiate into neurons, astrocytes and oligodendrocytes. Importantly, cerebellar neural stem cell transplantation mediated a significant and robust alleviation of the motor behaviour impairments, which correlated with preservation from Machado-Joseph disease-associated neuropathology, namely reduction of Purkinje cell loss, reduction of cellular layer shrinkage and mutant ATXN3 aggregates. Additionally, a significant reduction of neuroinflammation and an increase of neurotrophic factors levels was observed, indicating that transplantation of cerebellar neural stem cells also triggers important neuroprotective effects. Thus, cerebellar neural stem cells have the potential to be used as a cell replacement and neuroprotective approach for Machado-Joseph disease therapy.

[Case of ataxic sensory neuronopathy associated with Sjögren's syndrome].

A 71-year-old woman developed advanced thermal hypoalgesia, bathyesthesia, and significant sensory ataxia 1 year ago. She also had difficulty maintaining a sitting posture. Patchy and reduced thermal nociception corresponding to a dermatome was found in her four extremities and trunk. On the basis of several tests, she was diagnosed with ataxic sensory neuronopathy due to dorsal root ganglionitis associated with Sjögren's syndrome. Generally, dorsal root ganglionitis associated with Sjögren's syndrome is refractory. After treatment with simple plasmapheresis, she was able to maintain a sitting posture. Finally, her symptoms stabilized after the inclusion of oral D-penicillamine to her treatment regimen. Although the clinical course was observed for about one year, we report this case because of its valuable finding, i.e., her symptoms improved after simple plasmapheresis and oral administration of D-penicillamine.

Fungal keratitis presenting as radial keratoneuritis.

A 44-year-old man presented with severe pain, redness, watering and photophobia for 10 days in the right eye without any history of trauma. Diagnosis of herpes simplex disciform keratitis was made and he was prescribed topical steroids. The patient showed clinical worsening and presented with ring infiltrate, diffuse stromal oedema and radial keratoneuritis, a finding pathognomic of acanthamoeba keratitis. With two inconclusive corneal scrapings and the patient showing clinical worsening, an urgent therapeutic penetrating keratoplasty was carried out. Histopathological and microbiological examination of the excised corneal button revealed the presence of fungus. At 5 weeks follow-up, the patient has best-corrected visual acuity 20/40 with no recurrence of infection.

[Diagnosis and treatment of upper arm radial neuritis by ultrasonography].

OBJECTIVE: To evaluate the application of ultrasonography in diagnosis and treatment of the upper arm radial neuritis. METHODS: 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. RESULTS: 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. CONCLUSION: Ultrasonography examination provide morphological evidence for the diagnosis and treatment of the upper arm radial neuritis.

Placenta-derived adherent cells attenuate hyperalgesia and neuroinflammatory response associated with perineural inflammation in rats.

Neuropathic pain is a debilitating condition of the somatosensory system caused by pathology of the nervous system. Current drugs treat symptoms but largely fail to target the underlying mechanisms responsible for the pathological changes seen in the central or peripheral nervous system. We investigated the therapeutic effects of PDA-001, a culture expanded placenta-derived adherent cell, in the rat neuritis model. Pain is induced in the model by applying carrageenan to the sciatic nerve trunk, causing perineural inflammation of the sciatic nerve. PDA-001, at doses ranging from 0.4×10(6) to 4×10(6) cells/animal, or vehicle control was intravenously administrated to assess the biological activity of the cells. A dose-dependent effect of PDA-001 on pain relief was demonstrated. PDA-001 at doses of 1×10(6) and 4×10(6), but not 0.4×10(6), reduced mechanical hyperalgesia within 24h following treatment and through day 8 after induction of neuritis. The mechanism underlying PDA-001-mediated reduction of neuroinflammatory pain was also explored. Ex vivo tissue analyses demonstrated that PDA-001 suppressed homing, maturation and differentiation of dendritic cells, thus inhibiting T-cell priming and activation in draining lymph nodes. PDA-001 also reduced interferon gamma and IL-17 in draining lymph nodes and in the ispilateral sciatic nerve, and increased the levels of IL-10 in draining lymph nodes and plasma, pointing to T-cell modulation as a possible mechanism mediating the observed anti-hyperalgesic effects. Furthermore, in the ipsilateral sciatic nerve, significantly less leukocyte infiltration was observed in PDA-001-treated animals. The results suggest that PDA-001may provide a novel therapeutic approach in the management of inflammatory neuropathic pain and similar conditions.

Reversal of inflammatory pain by HSV-1-mediated overexpression of enkephalin in the caudal ventrolateral medulla.

Targeting supraspinal pain control centers by gene transfer is known to induce sustained analgesia. In this study, we evaluated the effects of injecting a Herpes Simplex Virus type 1 vector which expresses enkephalin (HSV-ENK vector) in the lateralmost part of the caudal ventrolateral medulla (VLMlat), a pain control center that exerts mainly descending inhibitory effects on pain modulation. Overexpression of enkephalin at the VLMlat reduced the number of flinches during the early and delayed phases of the formalin test and decreased c-fos expression in the spinal cord. These antinociceptive effects were detected at 2 and 10days after injection of HSV-ENK in the VLMlat and were completely reversed by local administration of naloxone. Virally driven-enkephalin was expressed from transduced neurons located in the VLMlat and, at lower extent, in the rostral ventromedial medulla. Our results show that HSV-mediated expression of enkephalin in the VLMlat induced antinociceptive effects, likely due to an enhancement of the opioidergic input to the VLMlat which accounted for descending inhibition of the nociceptive transmission at the spinal cord. This study also demonstrates the value of HSV-1 derived vectors to manipulate, in a sustained and directed manner, pain modulatory pathways in the brain, which is important in the study of supraspinal pain control circuits.