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.

Obesity Worsens Gulf War Illness Symptom Persistence Pathology by Linking Altered Gut Microbiome Species to Long-Term Gastrointestinal, Hepatic, and Neuronal Inflammation in a Mouse Model.

Persistence of Gulf War illness (GWI) pathology among deployed veterans is a clinical challenge even after almost three decades. Recent studies show a higher prevalence of obesity and metabolic disturbances among Gulf War veterans primarily due to the existence of post-traumatic stress disorder (PTSD), chronic fatigue, sedentary lifestyle, and consumption of a high-carbohydrate/high-fat diet. We test the hypothesis that obesity from a Western-style diet alters host gut microbial species and worsens gastrointestinal and neuroinflammatory symptom persistence. We used a 5 month Western diet feeding in mice that received prior Gulf War (GW) chemical exposure to mimic the home phase obese phenotype of the deployed GW veterans. The host microbial profile in the Western diet-fed GWI mice showed a significant decrease in butyrogenic and immune health-restoring bacteria. The altered microbiome was associated with increased levels of IL6 in the serum, Claudin-2, IL6, and IL1ß in the distal intestine with concurrent inflammatory lesions in the liver and hyperinsulinemia. Microbial dysbiosis was also associated with frontal cortex levels of increased IL6 and IL1ß, activated microglia, decreased levels of brain derived neurotrophic factor (BDNF), and higher accumulation of phosphorylated Tau, an indicator of neuroinflammation-led increased risk of cognitive deficiencies. Mechanistically, serum from Western diet-fed mice with GWI significantly increased microglial activation in transformed microglial cells, increased tyrosyl radicals, and secreted IL6. Collectively, the results suggest that an existing obese phenotype in GWI worsens persistent gastrointestinal and neuronal inflammation, which may contribute to poor outcomes in restoring cognitive function and resolving fatigue, leading to the deterioration of quality of life.

Neurosyphilis presenting as visually asymptomatic bilateral optic perineuritis.

A 39-year-old Caucasian man presented with headaches and retro-orbital pain but normal vision. Bilateral optic nerve swelling was found on funduscopy though optic nerve function and computed perimetry were normal and there was no relative afferent pupillary defect. CT venogram and MRI were unremarkable. Cerebrospinal fluid (CSF) opening pressure was normal on lumbar puncture and Treponema pallidum antibodies and T. pallidum particle agglutination test were positive on CSF analysis. He tested negative for HIV. Symptoms rapidly resolved with 2 weeks of intravenous benzylpenicillin. At 1 month follow-up, the right optic nerve swelling had reduced while the left optic nerve swelling had increased; his vision remained unaffected and he was symptom free and continued to have no objective evidence of optic nerve dysfunction.

Meningitis with cranial polyneuritis and cavernous sinus thrombosis by Borrelia crocidurae: First autochthonous case in Europe.

Borrelia crocidurae is endemic in West Africa, where it represents the leading cause of tick-borne relapsing fever (TBRF). TBRF typically presents with high fever and systemic symptoms, followed by recurrent episodes. Neurological complications may occur during febrile relapses. B. crocidurae is considered the most neurotropic agent of TBRF and is associated to severe neurological manifestations i.e. meningitis and encephalitis. To date, European cases of B. crocidurae infection have been reported in travelers returning from endemic areas. We report the first autochthonous case in Europe of B. crocidurae infection, presenting as meningitis with cranial polyneuritis and cavernous sinus thrombosis that were not preceded by classic febrile recurrences.

Lyme Neuroborreliosis is a Severe and Frequent Neurological Disease in Mexico.

OBJECTIVE: To describe clinical cases with neurological manifestations associated with Borrelia burgdorferi infection in a large cohort of children and adults from Mexico. MATERIAL AND METHODS: Patients with neurological manifestation (cranial neuritis, radiculoneuritis, meningitis and encephalomyelitis) were recruited in one pediatric and two general hospitals, during January 2006-December 2015. Blood and cerebrospinal fluid (CSF) samples were drawn from each patient at inclusion. IgM and IgG antibodies against B. burgdorferi were detected using a commercial ELISA test, and confirmed by Western-Blot test (WB) using three different antigens from Borrelia burgdorferi complex. Following CDC criteria were considered true cases with both positive tests. RESULTS: Of 606 patients recruited, 403 (66.5%) were adults and 203 (33.4%) children, 50.5% were male. B. burgdorferi infection was diagnosed in 168 patients (27.7%), 97 adults, mean age 42 ± 14.7 years and 71 children, mean age 9.6 ± 5 years; early disseminated disease occurred in 130 cases (77.4 %) and chronic stage in 38 (22.6 %). A previous tick bite was reported by 21% cases, and 5% recalled an erythema migrans lesion. Polyradiculoneuropathy and encephalomyelitis were the most common manifestations, whereas 14.8% presented an initial Guillain-Barré Syndrome. B. burgdorferi sensu stricto was identified in 142 (84%) cases, B. garinii in 14 (8%), B. afzelii in three, and nine cases presented coinfection with two species. CONCLUSION: Lyme neuroborreliosis is a frequent condition in patients with neurological diseases in Mexico.

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

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.

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.

Minocycline in leprosy patients with recent onset clinical nerve function impairment.

Nerve function impairment (NFI) in leprosy may occur and progress despite multidrug therapy alone or in combination with corticosteroids. We observed improvement in neuritis when minocycline was administered in patients with type 2 lepra reaction. This prompted us to investigate the role of minocycline in recent onset NFI, especially in corticosteroid unresponsive leprosy patients. Leprosy patients with recent onset clinical NFI (<6 months), as determined by Monofilament Test (MFT) and Voluntary Muscle Test (VMT), were recruited. Minocycline 100mg/day was given for 3 months to these patients. The primary outcome was the proportion of patients with 'restored,' 'improved,' 'stabilized,' or 'deteriorated' NFI. Secondary outcomes included any improvement in nerve tenderness and pain. In this pilot study, 11 patients were recruited. The progression of NFI was halted in all; with 9 out of 11 patients (81.82%) showing ?restored? or ?improved? sensory or motor nerve functions, on assessment with MFT and VMT. No serious adverse effects due to minocycline were observed. Our pilot study demonstrates the efficacy and safety of minocycline in recent onset NFI in leprosy patients. However, larger and long term comparative trials are needed to validate the efficacy of minocycline in leprosy neuropathy.

A critical appraisal on pure neuritic leprosy from India after achieving WHO global target of leprosy elimination.

Background: Clinical data on pure-neuritic leprosy (PNL) is limited. Objective: To study the clinical and epidemiological features of PNL in the leprosy post-elimination era. Methods: This was a retrospective analysis of the clinic records of leprosy patients from January 2006 to June 2013. Data regarding age, sex, disease duration, presenting complaints, nerves affected, complications and treatment received were extracted from PNL cases. Results: Among 906 registered leprosy cases, 48 (5·3%) were found to have PNL. The mean age was 36·9 ± 16·2 years and predominantly males were affected (85·4%). The mean delay between onset of symptoms and diagnosis was 2·1 ± 2·2 years. Multiple nerves were affected in 36 patients (75%) and 12 (25%) had only one nerve involved. Visible deformities at presentation were noted in 32 (66·7%) patients. Forty patients (83·3%) were treated with multi drug therapy-multibacillary (MDTMB) regimen and three (6·25%) were treated with MDT-paucibacillary regimen. Twenty-one patients (43·8%) were considered positive responders to treatment. There was no correlation between the duration of NFI and treatment outcome. Conclusion: PNL continues to occur in the post-elimination era. Grade 2 deformities are common in PNL compared to other leprosy patients because of delayed diagnosis and treatment. Distinct diagnosis and treatment guidelines and sensitisation of health care workers and physicians to the occurrence of PNL is the need of the day.

Leprosy profiles in post-elimination stage: a tertiary care hospital experience.

BACKGROUND: Most countries that were previously highly endemic for leprosy have achieved elimination at the national level. OBJECTIVES: To find out the pattern, prevalence, and trends of leprosy in the post-elimination stage. METHODS: A descriptive retrospective cross-sectional study was carried out using the registered records of patients attending the leprosy clinic in Chittagong Medical College Hospital between the periods 2001 and 2011. RESULTS: The new case detection rate was declining. The prevalence rate was 0.75 at the end of 2011. Of a total of 789 patients, males (74%) outnumbered the females (26%). The age of the patients in the study group ranged from 6 years to 87 years with mean age 35.58 years ± 0.05 SEM. Paucibacillary (PB) and multibacillary (MB) cases were 314 (39.80%) and 475 (60.20%), respectively. MB percentage was increasing more among new cases in the study period, and 119 (15.08%) patients presented with grade 2 deformities. Smear positive cases were 141 (17.87%). Leprosy reaction comprised of 193 (24.46%) type 1, 68 (8.62%) type 2, and 97 (12.29%) neuritis cases. LIMITATIONS: This is a retrospective study from a single tertiary health center. CONCLUSION: MB cases with grade 2 deformities are in an upward trend, and rates of children are declining. Developing reinforced new therapies to curb reactions, deformities are very important and contact tracing, especially of children, is essential. Domiciliary treatment needs to be made available to ensure early diagnosis.

Mechanisms of nerve injury in leprosy.

All patients with leprosy have some degree of nerve involvement. Perineural inflammation is the histopathologic hallmark of leprosy, and this localization may reflect a vascular route of entry of Mycobacterium leprae into nerves. Once inside nerves, M. leprae are ingested by Schwann cells, with a wide array of consequences. Axonal atrophy may occur early in this process; ultimately, affected nerves undergo segmental demyelination. Knowledge of the mechanisms of nerve injury in leprosy has been greatly limited by the minimal opportunities to study affected nerves in man. The nine-banded armadillo provides the only animal model of the pathogenesis of M. leprae infection. New tools available for this model enable the study and correlation of events occurring in epidermal nerve fibers, dermal nerves, and nerve trunks, including neurophysiologic parameters, bacterial load, and changes in gene transcription in both neural and inflammatory cells. The armadillo model is likely to enhance understanding of the mechanisms of nerve injury in leprosy and offers a means of testing proposed interventions.

Mechanisms of nerve injury in leprosy

All patients with leprosy have some degree of nerve involvement. Perineural inflammation is the histopathologic hallmark of leprosy, and this localization may reflect a vascular route of entry of Mycobacterium leprae into nerves. Once inside nerves, M leprae are ingested by Schwann cells, with a wide array of consequences. Axonal atrophy may occur early in this process; ultimately, affected nerves undergo segmental demyelination. Knowledge of the mechanisms of nerve injury in leprosy has been greatly limited by the minimal opportunities to study affected nerves in man. The nine-banded armadillo provides the only animal model of the pathogenesis of M leprae infection. New tools available for this model enable the study and correlation of events occurring in epidermal nerve fibers, dermal nerves, and nerve trunks, including neurophysiologic parameters, bacterial load, and changes in gene transcription in both neural and inflammatory cells. The armadillo model is likely to enhance understanding of the mechanisms of nerve injury in leprosy and offers a means of testing proposed interventions.

Tuberculous neuritis: a rare sequel of a common disease.

Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis is an infectious disease that continues to be a significant health problem in a developing country like India. The cause of peripheral neuropathy associated with tuberculosis is controversial. Possibilities include the toxic effects of anti-tuberculous chemotherapy (especially, rifampicin, streptomycin & ethambutol), immune mediated neuropathy, direct invasion of nerves, vasculitic neuropathy, compressive neuropathy, and meningitic reaction. This report describes an unusual finding of tuberculous granulomas in the peripheral nerve (Greater auricular nerve) of a patient ,who presented with a painful neck swelling. Granulomas were present in Greater auricular nerve (C2,C3) biopsy specimen associated with tuberculous peri-neuritis, but with no more specific indications of the mechanism of the neuropathy.

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.

[Acute cranial multineuritis caused by a fungus]. / Multineuritis craneal aguda de causa fúngica.

TITLE: Multineuritis craneal aguda de causa fungica.

Nerve abscess in primary neuritic leprosy.

Nerve abscess is an infrequently reported complication of leprosy. We describe a patient with a pure neuritic type of leprosy with multiple nerve abscesses, who presented with tingling and numbness in the medial aspect of his right forearm and hand. Subsequently he developed pain, redness and swelling over the medial side of his right elbow and the flexor aspect of his right wrist. High-resolution ultrasound showed diffuse thickening of the right ulnar nerve with hypoechoic texture housing a cystic lesion with internal debris suggesting an abscess, at the cubital tunnel. Histopathological examination of the pus and tissue obtained from the abscess revealed presence of granulomas with lepra bacilli. The patient responded to surgery and multidrug therapy. In conclusion, the nerve abscess as the first manifestation of leprosy is uncommon and a high index of suspicion is required to make a correct diagnosis.