Evidencing leprosy neuronal inflammation by 18-Fluoro-deoxy-glucose.

BACKGROUND: Leprosy is caused by multiple interactions between Mycobacterium leprae (M. leprae) and the host's peripheral nerve cells. M. leprae primarily invades Schwann cells, causing nerve damage and consequent development of disabilities. Despite its long history, the pathophysiological mechanisms of nerve damage in the lepromatous pole of leprosy remain poorly understood. This study used the findings of 18F-FDG PET/CT on the peripheral nerves of eight lepromatous patients to evaluate the degree of glucose uptake by peripheral nerves and compared them with clinical, electrophysiological, and histopathological evaluations. METHODS: Eight patients with lepromatous leprosy were included in this study. Six patients were evaluated up to three months after leprosy diagnosis using neurological examination, nerve conduction study, 18F-FDG PET/CT, and nerve biopsy. Two others were evaluated during an episode of acute neuritis, with clinical, neurophysiological, and PET-CT examinations to compare the images with the first six. RESULTS: Initially, six patients already had signs of peripheral nerve injury, regardless of symptoms; however, they did not present with signs of neuritis, and there was little or no uptake of 18F-FDG in the clinically and electrophysiologically affected nerves. Two patients with signs of acute neuritis had 18F-FDG uptake in the affected nerves. CONCLUSIONS: 18F-FDG uptake correlates with clinical neuritis in lepromatous leprosy patients but not in silent neuritis patients. 18F-FDG PET-CT could be a useful tool to confirm neuritis, especially in cases that are difficult to diagnose, such as for the differential diagnosis between a new episode of neuritis and chronic neuropathy.

Extensive neuritis ossificans of the sciatic nerve: Systematic review and illustrative case.

BACKGROUND: Neuritis ossificans is a rare disease described as heterotopic calcification that occurs in neural tissue such as nerves. METHOD: A systematic review of the literature was done in accordance with PRISMA guidelines. An illustrative case of neuritis ossificans of the sciatic nerve in an 18 year old man was also reported. RESULTS: The review yielded 17 previously reported cases of neuritis ossificans. There was a male predominance and the most common locations were the median and tibial nerves. Only 2 previous cases involved the sciatic nerve. Most were treated with excision with positive outcomes. Our case was treated initially with a biopsy, then partial excision and symptomatic management with NSAIDs and GABA inhibitors. He had a good outcome at 13 months follow-up. CONCLUSION: Neuritis ossificans is a rare disease with unclear pathophysiology that has been theorized to involve neuroinflammation. Treatment consists of excision, if deemed possible, and symptom control.

Granulomatous interstitial polymyositis and intramuscular neuritis in a dog.

BACKGROUND: Granulomatous myositis is a rare condition in both humans and dogs. In humans it is most frequently related to sarcoidosis, where a concurrent granulomatous neuritis has been reported occasionally. Simultaneous granulomatous myositis and neuritis have been diagnosed previously in dogs (unpublished observations), but have not been studied further. Additional investigations are therefore warranted to characterize this disorder. Here we present a detailed description of concurrent idiopathic granulomatous myositis and granulomatous neuritis in a dog with suspected immune-mediated aetiology. CASE PRESENTATION: The dog presented with dysphonia and paresis in the pelvic limbs and tail. In addition to muscle biopsies being taken for histopathology, magnetic resonance imaging, computed tomography and electrodiagnostics were performed. Muscle biopsies displayed granuloma formation with giant cells and epithelioid macrophages in muscle fibres and nerve branches. Microorganisms were not detected. Long-term treatment with glucocorticoids was clinically successful. Two years after the clinical signs started, the dog presented with signs of sepsis and died. Histopathologically, no granulomatous inflammation could be demonstrated in either muscles or nerves at that time. CONCLUSIONS: This case illustrates a granulomatous interstitial polymyositis and intramuscular neuritis that improved clinically and resolved histologically with glucocorticoid treatment. Idiopathic granulomatous myositis and neuritis should be considered as a differential diagnosis in dogs with clinical signs of neuromuscular disorders.

Cytokine Levels in Neural Pain in Leprosy.

Pain is a frequent symptom in leprosy patients. It may be predominantly nociceptive, as in neuritis, or neuropathic, due to injury or nerve dysfunction. The differential diagnosis of these two forms of pain is a challenge in clinical practice, especially because it is quite common for a patient to suffer from both types of pain. A better understanding of cytokine profile may serve as a tool in assessing patients and also help to comprehend pathophysiology of leprosy pain. Patients with leprosy and neural pain (n = 22), neuropathic pain (n = 18), neuritis (nociceptive pain) (n = 4), or no pain (n = 17), further to those with diabetic neuropathy and neuropathic pain (n = 17) were recruited at Souza Araujo Out-Patient Unit (Fiocruz, Rio de Janeiro, RJ, Brazil). Serum levels of IL1ß, IL-6, IL-10, IL-17, TNF, CCL-2/MCP-1, IFN-γ, CXCL-10/IP-10, and TGF-ß were evaluated in the different Groups. Impairment in thermal or pain sensitivity was the most frequent clinical finding (95.5%) in leprosy neuropathy patients with and without pain, but less frequent in Diabetic Group (88.2%). Previous reactional episodes have occurred in patients in the leprosy and Pain Group (p = 0.027) more often. Analysis of cytokine levels have demonstrated that the concentrations of IL-1ß, TNF, TGF-ß, and IL-17 in serum samples of patients having leprosy neuropathy in combination with neuropathic or nociceptive pain were higher when compared to the samples of leprosy neuropathy patients without pain. In addition, these cytokine levels were significantly augmented in leprosy patients with neuropathic pain in relation to those with neuropathic pain due to diabetes. IL-1ß levels are an independent variable associated with both types of pain in patients with leprosy neuropathy. IL-6 concentration was increased in both groups with pain. Moreover, CCL-2/MCP-1 and CXCL-10/IP-10 levels were higher in patients with diabetic neuropathy over those with leprosy neuropathy. In brief, IL-1ß is an independent variable related to neuropathic and nociceptive pain in patients with leprosy, and could be an important biomarker for patient follow-up. IL-6 was higher in both groups with pain (leprosy and diabetic patients), and could be a therapeutic target in pain control.

Idiopathic third and sixth cranial nerve neuritis.

PURPOSE: To present cases with idiopathic third and sixth cranial nerve neuritis. STUDY DESIGN: Retrospective observational study METHODS: The results of high resolution pre- and post- cranial nerve magnetic resonance images (MRI) with three-dimensional sequences for visualizing cranial nerves in patients with third, fourth, and sixth cranial nerve palsies who were treated at the Neuro-ophthalmology Department of Samsung Medical Center were reviewed. Patients with cranial nerve enhancement confirmed by experienced radiologists were identified. The medical records of these patients were reviewed, and their demographics, clinical presentations, laboratory results, and clinical outcomes were analyzed. RESULTS: Of 265 patients with third, fourth, and sixth cranial nerve palsy, 60 were identified by high resolution MRI as having enhancement of the corresponding cranial nerve. Among these, 17 patients with infiltrative, granulomatous, or tumorous lesions were excluded. In addition, 28 patients with identifiable causes of cranial nerve palsy, such as Miller-fisher syndrome, virus infection, or radiation-induced neuropathy, as well as patients with vasculopathic risk factors, were also excluded. Ultimately, a total of 15 patients with idiopathic third and sixth cranial nerve neuritis were included in this study. The mean age of these patients was 43 ± 15 years. Eight patients had sixth cranial nerve palsy, six third cranial nerve palsy (two partial and four complete), and one patient with complete third and sixth cranial nerve palsy. Nine patients received steroid treatment. Eleven patients recovered fully within a period ranging from a few days to one year. Two patients were much improved up to 1 month after initial presentation, but were then ultimately lost to follow-up. Another patient was lost to follow-up after the initial work-up. The other patient lost to follow-up had partially recovered during the first 6 months. CONCLUSIONS: We present patients with idiopathic third and sixth cranial nerve neuritis. They tended to respond well to steroid treatment and to have good prognoses. In order to better understand the long-term prognosis of cranial nerve neuritis and possible association with other neurologic disorders, a larger scale and longer-term study is needed.

Bilateral tympanokeratomas (cholesteatomas) with bilateral otitis media, unilateral otitis interna and acoustic neuritis in a dog.

BACKGROUND: An aural cholesteatoma, more appropriately named tympanokeratoma, is an epidermoid cyst of the middle ear described in several species, including dogs, humans and Mongolian gerbils. The cyst lining consists of stratified, keratinizing squamous epithelium with central accumulation of a keratin debris. This case report describes vestibular ganglioneuritis and perineuritis in a dog with chronic otitis, bilateral tympanokeratomas and presumed extension of otic infection to the central nervous system. CASE PRESENTATION: An 11-year-old intact male Dalmatian dog with chronic bilateral otitis externa and sudden development of symptoms of vestibular disease was examined. Due to the dog's old age the owner opted for euthanasia without any further examination or treatment and the dog was submitted for necropsy. Transection of the ears revealed grey soft material in the external ear canals and pearly white, dry material consistent with keratin in the tympanic bullae bilaterally. The brain and meninges were grossly unremarkable. Microscopical findings included bilateral otitis externa and media, unilateral otitis interna, ganglioneuritis and perineuritis of the spiral ganglion of the vestibulocochlear nerve and multifocal to coalescing, purulent meningitis. A keratinizing squamous epithelial layer continuous with the external acoustic meatus lined the middle ear compartments, consistent with bilateral tympanokeratomas. Focal bony erosion of the petrous portion of the temporal bone and squamous epithelium and Gram-positive bacterial cocci were evident in the left cochlea. The findings suggest that meningitis developed secondary to erosion of the temporal bone and ganglioneuritis and/or perineuritis of the vestibulocochlear nerve. CONCLUSIONS: Middle ear tympanokeratoma is an important and potentially life-threatening otic condition in the dog. Once a tympanokeratoma has developed expansion of the cyst can lead to erosion of bone and extension of otic infection to the inner ear, vestibulocochlear ganglion and nerve potentially leading to bacterial infection of the central nervous system.

Autoimmune Granulomatous Inflammation of Lacrimal Glands and Axonal Neuritis Following Treatment With Ipilimumab and Radiation Therapy.

Immune checkpoint inhibitors such as anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), anti PD-1 (programmed cell death protein 1) and PD-L1 (programmed cell death protein-ligand 1) monoclonal antibodies are emerging as standard oncology treatments in various tumor types. The indications will expand as immunotherapies are being investigated in various tumors with promising results. Currently, there is inadequate identification of predictive biomarkers of response or toxicity. Unique response patterns include pseudoprogression and delayed response. The use of immune checkpoint inhibitors exhibit an unique toxicity profile, the immune-related adverse events (irAEs). The most notable immune reactions are noted in skin (rash), gastrointestinal track (colitis, hepatitis, pancreatitis), lung (pneumonitis), heart (myocarditis), and endocrine system (thyroiditis, hypophysitis). We present a patient with metastatic adenoid cystic carcinoma of the left submandibular gland with granulomatous inflammation of the lacrimal glands and axonal neuritis of the cervical and paraspinal nerves following treatment with ipilimumab and radiation therapy.

Nontraumatic "isolated" posterior interosseous nerve palsy: Reinterpretation of electrodiagnostic studies and MRIs.

INTRODUCTION: Different hypotheses have been proposed for the pathophysiology of posterior interosseous nerve (PIN) palsy, namely compression, nerve inflammation, and fascicular constriction. We hypothesized that critical reinterpretation of electrodiagnostic (EDX) studies and MRIs of patients with a diagnosis of PIN palsy could provide insight into the pathophysiology and treatment. MATERIALS AND METHODS: We retrospectively reviewed patients with a diagnosis of nontraumatic PIN palsy and an upper extremity EDX and MRI. The original EDX studies and MRIs were reinterpreted by a neuromuscular neurologist and musculoskeletal radiologist, respectively, both blinded to our hypothesis. RESULTS: Fifteen patients met the inclusion criteria, i.e., having an "isolated" PIN palsy. Four patients (27%) had a defined mass compressing the PIN. The remaining 11 patients (73%) presented with at least one finding incompatible with the compression hypothesis: physical examination revealed that weakness in muscles was not innervated by the PIN in 4 patients (36%); EDX abnormalities not related to the PIN were found in 4 patients (36%); and reinterpretation of the MRIs showed muscle atrophy or nerve enlargement beyond the territory of the PIN in 9 patients (82%), without any evidence of compression of the PIN in the proximal forearm. CONCLUSION: The eleven patients in our series with presumed isolated and idiopathic PIN palsy had evidence of a more diffuse nerve-muscle involvement pattern, without any radiologic signs of nerve compression of the PIN itself. These data would favor an inflammatory pathophysiology when a structural lesion compressing the nerve is ruled out with imaging.

Ventriculoatrial Shunts in Adults, Incidence of Infection, and Significant Risk Factors: A Single-Center Experience.

BACKGROUND: In recent years, the number of ventriculoatrial (VA) shunt insertions has decreased worldwide, the major cause being the risk of shunt infection. VA shunts remain as an alternative option to ventriculoperitoneal shunts. We describe our 10-year experience with VA shunts by analyzing the incidence of shunt infections and predisposing cofactors. METHODS: During a median follow-up of 15.3 months, 259 shunt insertions, performed on 255 patients, were analyzed. The infection rate was calculated and the predisposing cofactors age, gender, cause of the hydrocephalus, previous external ventricle drainage, antibiotic-impregnated catheters, the number of revisions, the educational level of the surgeons, and the duration of the operations were analyzed. Two observation times were stratified. RESULTS: We found overall infections in 18 patients (7.1%), 16 deep infections (6.3%) including 1 shunt nephritis (0.4%) and 2 superficial infections (0.8%). Wound dehiscence occurred in 17 patients (6. 6%). Analyzing follow-up time, the infection rate was 3.65% (95% confidence interval, 0.9%-5.9%) at survival time 1, 3.38% (95% confidence interval, 1.1%-6.2%) at survival time 2. In the first 6 months, 95% of patients were free of infection. Only the number of revision procedures was associated with the number of infections (P value < 0.0005). CONCLUSIONS: In our patient cohort, the infection rate related to VA shunt insertion is low; the only statistically significant risk factor was the number of revisions. If the VA shunt is applied following a standardized protocol, the infection risk does not represent an argument for reluctance towards the VA draining concept.

Magnetic resonance neurography in the diagnosis of neuropathies of the lumbosacral plexus: a pictorial review.

Magnetic resonance neurography (MRN) is an important tool to detect abnormalities of peripheral nerves. This pictorial review demonstrates the MRN features of a variety of neuropathies affecting the lumbosacral plexus (LSP) and lower extremity nerves, drawn from over 1200 MRNs from our institution and supplemented by the literature. Abnormalities can be due to spinal compression, extraspinal compression, malignancy, musculoskeletal disease, iatrogenesis, inflammation, infection, and idiopathic disorders. We discuss indications and limitations of MRN in diagnosing LSP neuropathies. As MRN becomes more widely used, physicians must become familiar with the differential diagnosis of abnormalities detectable with MRN of the LSP.

Reinterpretation of Electrodiagnostic Studies and Magnetic Resonance Imaging Scans in Patients with Nontraumatic "Isolated" Anterior Interosseous Nerve Palsy.

BACKGROUND: Different hypotheses have been proposed for the pathophysiology of anterior interosseous nerve palsy: compression, fascicular constriction, or nerve inflammation (Parsonage-Turner syndrome). The authors hypothesized that critical reinterpretation of electrodiagnostic studies and magnetic resonance imaging scans of patients with a diagnosis of anterior interosseous nerve palsy could provide insight into the pathophysiology and treatment. METHODS: A retrospective review was performed of all patients with a diagnosis of nontraumatic anterior interosseous nerve palsy and an upper extremity magnetic resonance imaging scan. The original electrodiagnostic study and magnetic resonance imaging scan reports were reinterpreted by a neuromuscular neurologist and musculoskeletal radiologist, respectively, both blinded to the authors' hypothesis. RESULTS: Sixteen patients met the inclusion criteria as having "isolated" anterior interosseous nerve palsy. Physical examination revealed weakness in muscles not innervated by the anterior interosseous nerve in five cases (31 percent), and electrodiagnostic studies showed abnormalities not related to the anterior interosseous nerve in nine of 15 cases (60 percent). In all cases, reinterpretation of the magnetic resonance imaging scans demonstrated atrophy in at least one muscle not innervated by the anterior interosseous nerve and did not reveal any evidence of compression of the anterior interosseous nerve. CONCLUSIONS: All patients in the authors' series with presumed isolated anterior interosseous nerve palsy had magnetic resonance imaging evidence of a more diffuse muscle involvement pattern, without any radiologic signs of nerve compression of the anterior interosseous nerve branch itself. These data strongly support an inflammatory pathophysiology.

Myenteric plexitis is a risk factor for endoscopic and clinical postoperative recurrence after ileocolonic resection in Crohn's disease.

BACKGROUND: As surgical resection is not curative in Crohn's disease, postoperative recurrence remains a crucial issue. The selection of patients, according to available risk factors, remains disappointing in clinical practice highlighting the need for better criteria, such as histologic features. AIMS: To investigate whether submucosal and myenteric plexitis increase the risk of endoscopic, clinical and surgical postoperative recurrence in Crohn's disease. METHODS: From the pathology department database, we retrospectively retrieved the data of all the patients who have undergone ileocolonic resection for Crohn's disease. Two pathologists, blinded from clinical data, reviewed all specimens to evaluate the presence of plexitis at the proximal resection margin. RESULTS: Of the 75 included CD patients, 19 (25.3%) had histological involvement of resection margin. Inflammatory cells count for myenteric and submucosal plexus were performed in 56 patients. In multivariate analysis, the myenteric plexitis was a risk factor for endoscopic postoperative recurrence (HR 8.83 CI95% [1.6-48.6], p=0.012), and the presence of at least one myenteric lymphocyte (HR 4.02 CI95% [1.4-11.2], p=0.008) was predictive of clinical postoperative recurrence. We observed no histologic predictor for surgical postoperative recurrence. CONCLUSION: Myenteric plexitis in proximal margins of ileocolonic resection specimens is independently associated with endoscopic and clinical postoperative recurrence in Crohn's disease.

[Amyothropic neuralgy of lumbosacral plexus - case report]. / Neuralgia amiotroficzna splotu ledzwiowo-krzyzowego - opis przypadku.

Amyothropic neuralgy is a rare disease witch unknown etiopathogenesis. The main popular theory says that inflammatory and immunomodulatory process is connected with that disease. Diagnosis is made after exclusion of other causes of plexus lumbosacralis damage. The main symptom is neuropathic pain after which there is observed muscle weakness and atrophy. ENG/EMG study and MRI are made to confirm the diagnosis. In this study we described a case of 52 years old female with lower limbs paresis, who was diagnosed few years after first symptoms. Limb paresis was preluded by lumbar pain. MRI study revealed central spinal disc herniations on L1-2, L2-3, L3-4 levels with dura matter compression, L4-5 spinal disc right lateral herniation and synovial cyst. MRI of both lumbar plexuses was also normal. EMG study revealed features of bilateral, chronic damage of lower legs nerves on lumbar plexus level. Patient was treated with physiotherapy and gabapentin with dose of 2x600mg per day.

A Rare Combination of Pure Neuritic Leprosy with Morphea Leading to Diagnostic Confusion.

A circumscribed sclerotic plaque of morphea can sometimes be mistaken for tuberculoid leprosy and vice versa can also happen. However, the co-existence of a patch of morphea mimicking as Leprosy patch in an underlying case of neuriticleprosy, can be very misleading. We present a case with glove and stocking anaesthesia and peripheral nerve enlargement with a single large hypopigmented, non-anaesthetic macule on trunk, clinically diagnosed as Hansen's disease (Borderline Tuberculoid - BT). Slit skin smears proved to be negative for AFB and histopathology of the skin lesion was consistent with morphea, which lead us to do a nerve biopsy. Sural nerve biopsy proved it to be Hansen's neuritis with occasional bacilli. The patient was started on MDT-MB and followed up. This is a rare case of co-existing morphea with Hansen's disease. It would have been easily misclassified if we had presumed the cutaneous lesion to be a case of Hansen's (BT) patch and not done a cutaneous nerve biopsy which led to diagnosis of multibacillary leprosy.

In vivo imaging of radial keratoneuritis in patients with Acanthamoeba keratitis by anterior-segment optical coherence tomography.

PURPOSE: To investigate in vivo corneal changes of radial keratoneuritis in early-stage Acanthamoeba keratitis (AK) using anterior-segment optical coherence tomography (AS-OCT). DESIGN: Single-center, prospective clinical study. PARTICIPANTS: Four eyes (4 patients with a mean age of 28.5 years) with early-stage AK showing radial keratoneuritis were included in this study. Definitive diagnosis was made by confirmation of AK cysts using in vivo confocal microscopy and culture. METHODS: Anterior-segment OCT examination was performed on the initial visit and at follow-up visits paying special attention to radial keratoneuritis. MAIN OUTCOME MEASURES: Selected AS-OCT images of the cornea were evaluated qualitatively for the shape and degree of light reflection of abnormal neurons. RESULTS: With the use of AS-OCT, we successfully obtained high-resolution images of putative radial keratoneuritis in all patients as highly reflective bands or lines in the corneal stroma. The depth and width of the highly reflective bands/lines varied from case to case (anterior stroma to mid-stroma, from 20 to 200 µm). Some lines ran obliquely from the deep peripheral stroma toward the anterior stroma, and some were located at different depths (subepithelial and mid-stroma) and ran relatively parallel to the corneal layers. After appropriate treatment, radial keratoneuritis was resolved by both slit-lamp biomicroscopy and AS-OCT in all patients. CONCLUSIONS: High-resolution Fourier-domain AS-OCT provides novel and detailed visual information of radial keratoneuritis in patients with early-stage AK. Visualization of radial keratoneuritis by AS-OCT may be a useful adjunct to the diagnosis and follow-up of early-stage AK.

Latency of multifocal visual evoked potentials in nonoptic neuritis eyes of multiple sclerosis patients associated with optic radiation lesions.

PURPOSE: The aim of the study was to test the hypothesis that latency delay of multifocal visual evoked potentials (mfVEP) in nonoptic neuritis (NON) eyes of multiple sclerosis (MS) patients is related to retrochiasmal demyelinating lesions. METHODS: A total of 57 MS patients with no history of optic neuritis at least in one eye, and 25 age- and sex-matched healthy controls was enrolled. Probabilistic tractography was used to reconstruct optic radiation (OR) fibers. The MS lesion volume within and outside of OR was calculated. Diffusion tensor imaging (DTI) indices were measured along OR fibers. The relationship of the mfVEP latency with OR lesions and DTI indices was examined. RESULTS: Average mfVEP latency in the MS cohort was significantly delayed compared to controls (P < 0.0001). Of the patients, 77% demonstrated OR lesions. Axial, radial, and mean diffusivity were significantly abnormal in MS patients (P < 0.001). Partial correlation demonstrated significant association between mfVEP latency delay and OR lesion load. There was also significant correlation between MfVEP latency and OR DTI. Subgroup analysis revealed significantly higher correlations in patients without a history of ON in either eye compared to the fellow eye of patients with previous ON. CONCLUSIONS: The findings of this study support our hypothesis that latency delay of the mfVEP in eyes of MS patients without previous ON is related to retrogenicular demyelinating lesions. Additionally, this study demonstrated that a previous episode of ON in the fellow eye may be a significant confounding factor, masking the relationship between the latency and OR lesions.