Sarcoid optic neuropathy.

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

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.

Leprosy rash precipitated by immunotherapy for suspected inflammatory neuropathy.

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

Central Skull Base Osteomyelitis: Multimodality Imaging and Clinical Findings from a Large Indian Cohort.

Background: Central or atypical skull base osteomyelitis (CSBO) often presents with severe unrelenting headache and progressive mono or polyneuritis cranialis. MRI and CT are used as initial imaging techniques but have a poor specificity and sensitivity. Objective: To analyze our cohort of CSBO. Materials and Methods: Over a 5-year period [2015-2020], we retrospectively analyzed the records of all patients with CSBO who had undergone a 3T MRI Brain, MR angiography, regional FDG PET-CT, and skeletal scintigraphy with 99mTc MDP/SPECT-CT. Surgical biopsy specimens were sent for bacterial and fungal cultures. Results: In total, 17 patients with CSBO were identified. Typically, 88% of patients presented with severe unilateral headache. All patients had at least a cranial mono or polyneuritis. The majority of patients were diabetic [64%]. MRI was normal in 42% of patients, whereas PET-CT and with 99mTc MDP scan and SPECT-CT were abnormal in all patients. Conclusion: Our series of CSBO showed a 40% mortality rate with significant morbidity and relentless progression. Patients required repeated PET CT and bone scans to detect regression of disease activity. The average duration of IV therapy ranged from 3 weeks to 9 months and oral therapy for around 2-3 months. Cure was defined after taking into account the original diagnosis, symptom resolution, and concordant reduction of tissue uptake on PET CT and 99mTc bone scan. The combination of MRI, FDG PET CT, and 99mTc bone scan with concurrent SPECT CT was able to detect disease and disease progression in all patients.

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

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

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.

Facial neuritis in coronavirus disease 2019 associated mucormycosis: study on clinico-radiological correlates.

OBJECTIVE: To elucidate the aetiopathogenesis of facial neuritis in coronavirus disease 2019 associated mucormycosis. METHODS: A retrospective review was conducted of coronavirus disease 2019 associated mucormycosis patients who presented with peripheral facial nerve palsy from January 2021 to July 2021. The clinico-radiological details of four patients were assessed to examine the potential mechanism of facial nerve involvement. RESULTS: Serial radiological evaluation with contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging revealed infratemporal fossa involvement in all cases, with the inflammation extending along fascial planes to reach the stylomastoid foramen. Ascending neuritis with an enhancement of the facial nerve was demonstrated in all cases. CONCLUSION: The likely explanation for facial palsy in patients with coronavirus disease 2019 associated mucormycosis, backed by radiology, is the disease abutting the facial nerve at the stylomastoid foramen and causing ascending neuritis of the facial nerve.

Tibolone restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an immune-mediated and degenerating disease in which myelin sheaths are damaged as a result of chronic progressive inflammation of the central nervous system. Tibolone [(7α,17α)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-in-3-one], a synthetic estrogenic compound with tissue-specific actions and used for menopausal hormone therapy, shows neuroprotective and antioxidant properties both in vivo and in vitro. In the present study, we analyzed whether tibolone plays a therapeutic role in experimental autoimmune encephalomyelitis (EAE) mice, a commonly used model of MS. Female C57BL/6 mice were induced with the myelin oligodendrocyte glycoprotein MOG35-55 and received s.c. tibolone (0.08 mg kg-1 ) injection every other day from the day of induction until death on the acute phase of the disease. Reactive gliosis, Toll like receptor 4 (TLR4), high mobility group box protein 1 (HMGB1), inflammasome parameters, activated Akt levels and myelin were assessed by a real-time polymerase chain reaction, immunohistochemistry, and western blot analysis. Our findings indicated that, in the EAE spinal cord, tibolone reversed the astrocytic and microglial reaction, and reduced the hyperexpression of TLR4 and HMGB1, as well as NLR family pyrin domain containing 3-caspase 1-interleukin-1ß inflammasome activation. At the same time, tibolone attenuated the Akt/nuclear factor kappa B pathway and limited the white matter demyelination area. Estrogen receptor expression was unaltered with tibolone treatment. Clinically, tibolone improved neurological symptoms without uterine compromise. Overall, our data suggest that tibolone may serve as a promising agent for the attenuation of MS-related inflammation.

Microglia in Alzheimer's Disease in the Context of Tau Pathology.

Microglia are the cells that comprise the innate immune system in the brain. First described more than a century ago, these cells were initially assigned a secondary role in the central nervous system (CNS) with respect to the protagonists, neurons. However, the latest advances have revealed the complexity and importance of microglia in neurodegenerative conditions such as Alzheimer's disease (AD), the most common form of dementia associated with aging. This pathology is characterized by the accumulation of amyloid-ß peptide (Aß), which forms senile plaques in the neocortex, as well as by the aggregation of hyperphosphorylated tau protein, a process that leads to the development of neurofibrillary tangles (NFTs). Over the past few years, efforts have been focused on studying the interaction between Aß and microglia, together with the ability of the latter to decrease the levels of this peptide. Given that most clinical trials following this strategy have failed, current endeavors focus on deciphering the molecular mechanisms that trigger the tau-induced inflammatory response of microglia. In this review, we summarize the most recent studies on the physiological and pathological functions of tau protein and microglia. In addition, we analyze the impact of microglial AD-risk genes (APOE, TREM2, and CD33) in tau pathology, and we discuss the role of extracellular soluble tau in neuroinflammation.

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.

Polyphenols from the flower of Hibiscus syriacus Linn ameliorate neuroinflammation in LPS-treated SH-SY5Y cell.

The flower of Hibiscus syriacus Linn is a well-known traditional Chinese medicine (TCM) and health food in China, which has been used to treat dysentery, vaginal discharge, and hemorrhoids. In this study, five polyphenols (compounds 1-5) and five fatty acids (compounds 6-10) were isolated from the ethanol extract of the flower of H. syriacus. The isolated compounds were characterized by spectroscopic techniques. Polyphenols, an important type of natural product, have variety of biological activities. Here, we employed LPS or H2O2-treated SH-SY5Y cell models to test the neuroprotective effect of compounds 1-10. Results found compounds 1-5 (concentration range was around 20 µM on LPS model, concentration range was around 13 µM on H2O2 model), not compounds 6-10, exhibited neuroprotective effect in LPS or H2O2-treated SH-SY5Y cell. PCR analysis showed that compounds 1-5 can effectively improve the mRNA expression of synapse-related gene and neurotrophic factors (Syp, NGF and BDNF) in LPS-treated SH-SY5Y cell. In addition, compounds 1-5 decreased the levels of ROS and MDA and increased the activities of SOD, GSH-Px and CAT in LPS-treated SH-SY5Y cell. Furthermore, compounds 1-5 inhibited neuroinflammation (TNF-α, IL-1ß and IL-6) in LPS-treated SH-SY5Y cell. In conclusion, the polyphenols in the flower of H. syriacus could be a promising candidate for preventive effect of neuroinflammation.

Proteomics-Guided Study on Buyang Huanwu Decoction for Its Neuroprotective and Neurogenic Mechanisms for Transient Ischemic Stroke: Involvements of EGFR/PI3K/Akt/Bad/14-3-3 and Jak2/Stat3/Cyclin D1 Signaling Cascades.

Buyang Huanwu Decoction (BHD), a classic traditional Chinese medicine (TCM) formula, has been used for recovering neurological dysfunctions and treating post-stroke disability in China for 200 years. In the present study, we investigated the effects of BHD on inhibiting neuronal apoptosis, promoting proliferation and differentiation of neural stem cells (NSCs) and neurite formation and enhancing learning and memory functional recovery in an experimental rat ischemic stroke model. BHD significantly reduced infarct volume and decreased cell apoptosis in the ischemic brain. BHD enhanced neuronal cell viability in vitro. BHD dose-dependently promoted the proliferation of NSCs in ischemic rat brains in vivo. Moreover, BHD promoted neuronal and astrocyte differentiation in primary cultured NSCs in vitro. Water maze test revealed that BHD promoted the recovery of learning function but not memory functions in the transient ischemic rats. We then investigated the changes of the cellular signaling molecules by using two-dimension (2D) gel electrophoresis and focused on the PI3K/Akt/Bad and Jak2/Stat3/cyclin D1signaling pathway to uncover its underlying mechanisms for its neuroprotective and neurogenetic effects. BHD significantly upregulated the expression of p-PI3K, p-Akt, and p-Bad as well as the expression of p-Jak, p-Stat3, and cyclin D1 in vitro and in vivo. In addition, BHD upregulated Hes1 and downregulated cav-1 in vitro and in vivo. Taken together, these results suggest that BHD has neuroprotective effects and neurogenesis-promoting effects via activating PI3K/Akt/Bad and Jak2/Stat3/Cyclin D1 signaling pathways. Graphical Abstract Buyang Huanwu Decoction (BHD) activates the PI3K-AKT-BAD pathway in the ischemic brain for neuroprotection. BHD also activates JAK2/STAT3/Cyclin D1 signaling cascades for promoting neurogenesis in the hippocampus of post-ischemic brains. Moreover, BHD inhibits the expression of caveolin-1 and increases the expression of HES1 for promoting neuronal differentiation. The neuroprotective and neurogenesis-promoting effects in the hippocampus of post-ischemic brains promote learning ability.

Diffuse Neuritis Ossificans of the Brachial Plexus: Case Report and Review of the Literature.

BACKGROUND: Neuritis ossificans (intraneural heterotopic ossification) is a rare disorder described as heterotopic ossification of a nerve. We describe the presentation and management of the first reported case of neuritis ossificans with diffuse brachial plexus involvement and review the literature. CASE DESCRIPTION: A 35-year-old man presented to our clinic for evaluation of right upper extremity weakness without history of trauma. He had significant, debilitating pain and magnetic resonance imaging demonstrated a complex contrast-enhancing mass with significant associated edema. Positron emission tomography demonstrated a 18F-fluorodeoxyglucose avid lesion within the brachial plexus that was confirmed by biopsy to be neuritis ossificans. The patient was treated with indomethacin and had clinical and radiologic improvement. CONCLUSIONS: We present the only case of diffuse, brachial plexus neuritis ossificans. Given the challenges of resecting neuritis ossificans in this region, we believe medical management for complex brachial plexus lesions should be considered first, unless the sequela of the disease is sufficiently prolonged or there is concern for permanent neurovascular compromise.

Polyneuritis cranialis and vasculopathy caused by varicella zoster virus without rash.

The neurological disorders caused by Varicella Zoster Virus (VZV) in the absence of skin rash are a challenge to the clinician. The presentation varies from acute to subacute to chronic. Reactivation of VZV usually produces zoster (shingles), meningitis or meningoencephalitis, cerebellitis, isolated or multiple cranial nerve palsies (polyneuritis cranialis), myelitis, and vasculopathy. In our case, we report a 41-year-old female presented with right oculomotor, vestibulocochlear and facial neuropathies occurred 1 year before admission and making the diagnosis. There were no skin or mucosa lesions. Magnetic Resonance Imaging revealed multiple subcortical infractions in the right temporal and occipital lobes which consist with silent vasculopathy. The diagnosis was confirmed by the existence of anti-VZV IgG in cerebrospinal fluid (CSF).

Isolated cranial neuritis of the oculomotor nerve: Expanding the MOG phenotype?

Autoantibody against myelin oligodendrocyte glycoprotein (MOG) has been reported in a range of demyelinating neurological entities. Recent studies demonstrate a wider spectrum of MOG-IgG-associated disorders with the discovery of MOG-IgG-positive brainstem encephalitis, cortical encephalitis, and cranial nerve involvement with concurrent central nervous system involvement. We present a MOG-IgG-positive pediatric patient diagnosed with isolated oculomotor neuritis without concurrent central nervous system neuroimaging lesions, in the absence of a demyelinating event. Brain MRI shows swelling and gadolinium enhancement of the left oculomotor nerve at the cisternal segment. This is the first report to demonstrate MOG-IgG seropositivity in isolated cranial nerve lesions. This case may expand the clinical phenotype of MOG-IgG-associated diseases, and clinicians should not hesitate to test for MOG-IgG in cases with neuroimaging features of cranial neuritis alone.

Adipocyte cannabinoid CB1 receptor deficiency alleviates high fat diet-induced memory deficit, depressive-like behavior, neuroinflammation and impairment in adult neurogenesis.

BACKGROUND: Obesity is a low-grade inflammation condition that facilitates the development of numerous comorbidities and the dysregulation of brain homeostasis. Additionally, obesity also causes distinct behavioral alterations both in humans and rodents. Here, we investigated the effect of inducible genetic deletion of the cannabinoid type 1 receptor (CB1) in adipocytes (Ati-CB1-KO mice) on obesity-induced memory deficits, depressive-like behavior, neuroinflammation and adult neurogenesis. METHODS: Behavioral, mRNA expression and immunohistochemical studies were performed in Ati-CB1-KO mice and corresponding wild-type controls under standard and high-fat diet. RESULTS: Adipocyte-specific CB1 deletion reversed metabolic disturbances associated with an obese condition confirming previous studies. As compared to obese mice, the metabolic amelioration in Ati-CB1-KO mice was associated with an improvement of mood-related behavior and recognition memory, concomitantly with an increase in cell proliferation in metabolic relevant neurogenic niches in hippocampus and hypothalamus. In mutant mice, these changes were related to an increased neuronal maturation/survival in the hippocampus. Furthermore, CB1 deletion in adipocytes was sufficient to reduce obesity-induced inflammation, gliosis and apoptosis in a brain region-specific manner. CONCLUSIONS: Overall our data provide compelling evidence of the physiological relevance of the adipocyte-brain crosstalk where adipocyte-specific CB1 influences obesity-related cognitive deficits and depression-like behavior, concomitantly with brain remodeling, such as adult neurogenesis and neuroinflammation in the hippocampus and hypothalamus.

Concurrent leukoencephalomyelitis and polyneuritis in a Maltese terrier: resembling combined central and peripheral demyelination in humans.

A one-year-old male Maltese terrier presented with mild ataxia and disorientation for 4 months. Over time, clinical signs progressed from paraparesis to non-ambulatory tetraparesis, voice change and dysphagia. Histological examination revealed concurrent leukoencephalomyelitis and polyneuritis. Infectious etiologies, including dengue, Japanese encephalitis, Zika, canine distemper, pseudorabies, rabies, toxoplasmosis, neosporosis, leishmaniasis, and encephalitozoonosis, were ruled out by PCR and/or immunohistochemical (IHC) staining. IHC tested on neurological tissues highlighted a heterogeneous population of infiltrating T and B lymphocytes admixed macrophages. Therefore, this case was diagnosed with current leukoencephalomyelitis and polyneuritis, resembling combined central and peripheral demyelination (CCPD), an autoimmune inflammatory demyelinating disease affecting both the CNS and PNS in humans.

Spontaneous peripheral neuritis in two electric eels (Electrophorus electricus).

This study represents cases with spontaneous neuritis of peripheral nerves in electric eels. Two electric eels were presented with abnormal swimming behavior and loss of appetite. Electric eels had extensive histopathologic lesions in the splenic and cardiac nerves. The lesions were characterized by swelling of neuronal cells, central chromatolysis and marked inflammatory cell infiltration consisting mainly of lymphocytes around the affected nerves. To the best of our knowledge, this is the first case report of spontaneous neuritis of peripheral nerves in electric eels.

Isoniazid-induced neuropathy in a pre-pubertal child.

Isoniazid (INH)-induced peripheral neuritis is not uncommonly reported in adults, especially those with malnutrition and alcoholism, but it is very rare in children. INH leads to peripheral neuritis by causing a deficiency in the serum level of pyridoxine which depends on the dose of INH, duration of treatment and the patient's nutritional and acetylator status. A 12-year-old girl developed tingling and numbness of the lower limbs after commencing anti-tuberculous therapy which included INH 10 mg/kg/day. The symptoms continued despite the dose being reduced to 5 mg/kg/day. Nerve conduction velocity was normal. Her diet was poor: she consumed little or no fruit and vegetables and ate mostly dal and rice. Discontinuation of INH was advised and her therapy was changed to ofloxacin, rifampicin, ethambutol and pyrazinamide along with a high dose of pyridoxine and multi-vitamins. The tingling and numbness subsided within 15 days, after which INH was prescribed at the dose of 10 mg/kg/day. Although INH-induced neuropathy is rare in children, the World Health Organization recommends pyridoxine prophylaxis for children on INH who are malnourished or have HIV infection.