Upper and lower limb tremor in inflammatory neuropathies.

OBJECTIVE: The mechanisms underlying neuropathic tremor remain incompletely understood and a distinction has not been drawn between proximal and distal neuropathies. Lower limb tremor contributes to imbalance in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but this is unexplored in other neuropathies. We characterized upper and lower limb tremor in chronic immune sensory polyradiculopathy (CISP) and distal acquired demyelinating neuropathy with anti-MAG antibodies (DADS-MAG), contrasted to CIDP. METHODS: This was a cross-sectional study of 38 patients (CIDP [n = 25], CISP [n = 7], DADS-MAG [n = 6]). Clinical assessment, tremor study recordings, nerve conduction studies, and somatosensory evoked potentials were performed. Balance was measured by force platform. RESULTS: Upper limb tremor was prevalent (CIDP 66%, CISP 70%, DADS-MAG 100%). Peak frequencies followed a gradient along the upper limb, unchanged by weight-loading. Lower limb tremor was also present (CIDP 32%, CISP 29%, DADS-MAG 66%) and associated with imbalance. Nerve conduction parameters correlated with upper limb tremor in DADS-MAG and CISP, and imbalance in CISP. CONCLUSIONS: Upper limb tremor is mediated by peripheral and central mechanisms regardless of distal or proximal pathology. Lower limb tremor correlates with peripheral nerve function and contributes to imbalance. SIGNIFICANCE: This study contributes to the understanding of neuropathic tremor. Addressing lower limb tremor may be of therapeutic importance for neuropathy-associated imbalance.

Serum levels of heavy metals in patients with Bell's palsy: a case-control study.

PURPOSE: The exact etiology of Bell's palsy (BP) remains unknown, while its potential etiopathology includes neuritis and inflammation-related demyelination as in optic neuritis. It has been reported that disruption of heavy metal homeostasis may be associated with the inflammatory process of optic neuritis; therefore, heavy metals may be involved in the pathogenesis of facial nerve neuritis. In this study, we aimed to investigate serum levels of heavy metals including essential elements [iron (Fe), zinc (Zn), copper (Cu), cobalt (Co), and manganese (Mn)], and nonessential elements [lead (Pb) and cadmium (Cd)] in patients with BP. METHODS: The study included 25 patients with BP and 31 healthy volunteers. For each participant, serum levels of essential and nonessential elements were measured using the atomic absorption spectrophotometer method. RESULTS: Serum levels of essential elements were significantly lower in the patient group compared to the control group (p < 0.001, for each). Serum levels of Pb increased in the patient group compared to the control group although no significant difference was achieved (p = 0.105). In contrast, serum Cd levels increased significantly in the patient group compared to the control group (p < 0.001). CONCLUSION: Our findings suggest that decreased essential and increased nonessential elements may be associated with BP and thus, serum concentrations of these elements should be taken into account in BP. Studies are warranted to determine the role of these elements in treatment of BP.

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.

Cytokines profile in pure neural leprosy.

Introduction: Pure Neural Leprosy (PNL) is a form of this long time known disease that affects only the peripheral nervous system. Since it is a rare form of the disease, its pathophisiology is still poorly understood. Objective: Describe the cytokines profile in patients with PNL. Methods: 30 Patients diagnosed with PNL in the Souza Araujo Outpatient Clinic and with cytokines evaluated were selected. They were evaluated by neurologists and diagnosed after a nerve biopsy. Serum levels of IL-1 ß, IL-6, IL-10, IL-17, TNF, CCL-2/MCP-1, IFN-ϒ, CXCL-10/IP-10 and TGF-ß were evaluates at the moment of the diagnosis. Results: Neural thickening was a common clinical finding in this groups of patients. Small and medium sensitive fibers signs and symptoms were present in 92% of the patients and motor involvement in 53%. 43% of patients presented neuropathic pain and no one had neuritis TGF-beta, IL-17, CCl-2 and IP-10. CCL-2 levels were associated with demyelinating patters and IP-10 and IL-1o were associated with axonal patterns at NCS. Discussion: PNL patients' cytokine profile appears to be different of other clinical forms of leprosy, with the presence of cytokines described in both tuberculoid and lepromatous leprosy. High levels of CCl-2 may be related to the presence of silent neuritis as well as the presence of IL-10. PNL is unique a form of leprosy, therefore, understanding its immunological profiles essential to better understand the disease itself.

Polyneuritis cranialis as a unique initial presentation of juvenile systemic lupus erythematosus: Case report.

Cranial neuropathy is a rare presentation in juvenile (j) SLE and being multiple is even rarer. We describe here an adolescent girl presenting with polyneuritis cranialis (PNC) as an initial presentation of SLE which had not been reported before in literature. She presented with symptoms suggestive of bilateral abducent and hypoglossal neuropathy with nerve conduction studies showing partial axonal neuropathy of left facial and accessory nerves, 6 weeks after common cold. The condition was not associated with any other neurological or systemic manifestations nor features of Sjogren's syndrome. Her condition responded well to pulsed methylprednisolone therapy and plasma exchange. After exclusion of the common causes and owing to the initial positive ANA results and mild proteinuria, renal biopsy was taken and revealed histopathological features of class III lupus nephritis for which mycophenolate mofetil was started at 1200 mg per m2. Our case highlights the importance of considering collagen disorders including SLE in the differential diagnosis of children presenting with PNC in order to allow adequate management and proper follow-up.

Herpes Zoster Infections in Solid-Organ Transplant Recipients.

OBJECTIVES: Herpes zoster infections can be complicated and mortal in solid-organ transplant recipients. In our study, we investigated herpes zoster infections in solid-organ transplant recipients. MATERIALS AND METHODS: UntilJune 2022, our center has performed 3342 kidney, 708 liver, and 148 heart transplants.Herpes zosterinfections were investigated in 1050 adult solid-organ transplant recipients from January 1, 2011, to June 31, 2022. We studied 44 patients diagnosed with herpes zoster infections. RESULTS: Of the 44 patients with herpes zoster, 32 had kidney, 7 had heart, and 5 had liver transplant procedures. Crude incidence rate was 5.2%.,with 9.7% being heart, 5.1% being kidney, and 3.9% being liver transplant recipients; 72.7% were male patients. The median age was 47.5 years, and 61% of patients were aged >45 years. Postherpetic neuralgia was significantly higher in patients older than 45 years (P = .006). The median duration to infection posttransplant was 16.5 months. The dermatomes of patients were 43.2% thoracic. Sacral dermatome involvement was significantly higher in heart transplant patients than in other transplant recipients (P = .015). We reviewed specific findings of the Tzanck test in 36.4% of the patients. There was concomitant infection in 15.9% of the patients, and 6.8% had pneumonia. Acute neuritis was more common in kidney transplant recipients (65.6%). The mean duration of acute neuritis/neuralgia was longest in liver transplant recipients (13.5 months; P = .047). Postherpetic neuralgia was detected as high as 24%. CONCLUSIONS: Early specific and supportive treatmentis important for transplant recipients with herpes zoster infections. Appropriate antiviral prophylaxis regimens and vaccination strategies for varicella zoster (chickenpox) and herpes zoster infections should be implemented in the vaccination schedule of solidorgan transplant candidates to prevent herpes zoster infections and complications.

Anti-myelin-associated glycoprotein neuropathy: Where do we stand?

Myelin-associated glycoprotein (MAG) is a transmembrane glycoprotein concentrated in periaxonal Schwann cell and oligodendroglial membranes of myelin sheaths that serves as an antigen for immunoglobulin M (IgM) monoclonal antibodies. Individuals who harbor anti-MAG antibodies classically develop a progressive autoimmune peripheral neuropathy characterized clinically by ataxia, distal sensory loss, and gait instability, and electrophysiologically by distally accentuated conduction velocity slowing. Although off-label immunotherapy is common, there are currently no proven effective disease-modifying therapeutics, and most patients experience slow accumulation of disability over years and decades. The typically slowly progressive nature of this neuropathy presents unique challenges when trying to find effective anti-MAG therapeutic agents. Drug development has also been hampered by the lack of validated outcome measures that can detect clinically meaningful changes in a reasonable amount of time as well as by the lack of disease activity biomarkers. In this invited review, we provide an update on the state of clinicometric outcome measures and disease activity biomarkers in anti-MAG neuropathy. We highlight the insensitivity of widely used existing clinicometric outcome measures such as the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score as well as the INCAT sensory subscore in anti-MAG neuropathy, referencing the two previous negative randomized controlled clinical trials evaluating rituximab. We then discuss newly emerging candidate therapeutic agents, including tyrosine kinase inhibitors and enhanced B-cell-depleting agents, among others. We conclude with a practical approach to the evaluation and management of anti-MAG neuropathy patients.

Effectiveness of neurolysis as a treatment for complications of leprosy neuritis: a systematic review.

BACKGROUND: Complications of leprosy neuritis are considered serious and apparent, with the potential to disable and/or limit individuals. These complications affect not only a patient's physical functioning, but also their family and social lives, while directly impacting the ability to work and/or maintain financial independence, subsequently interfering with their overall quality of life. The present review, therefore, aimed to analyze the effectiveness of neurolysis as an alternative treatment for the complications associated with leprosy neuritis. METHODS: The present review was performed based on the Joanna Briggs Institute methodology, in an effort to answer the following research question: what is the effectiveness of neurolysis as a treatment for leprosy neuritis complications? This research question was defined using the patient-intervention-outcome (PIO) framework, where leprosy represents 'P', neurolysis for 'I', and neuropathic pain/motor function/sensorial function/physical disability/quality of life for 'O'. Randomized and non-randomized clinical trials and prospective observational cohort studies were included in the present review, with no time or date restrictions. RESULTS: The present review included 1 randomized clinical trial and 10 prospective studies, published between 1976 and 2020. All of the outcomes showed improvement, with relief from neuropathic pain being the primary finding. CONCLUSIONS: The evidence obtained in the present review suggested that neurolysis is an effective alternative for the treatment of physical disabilities, the recovery of sensory and motor function, the restoration of quality of life, and neuropathic pain relief.

2,4-Dinitrophenol does not exert neuro-regenerative potential in experimental autoimmune neuritis.

OBJECTIVE: We evaluated the potential neuro-regenerative effects of the mitochondrial uncoupler 2,4-Dinitrophenol in experimental autoimmune neuritis, an animal model for an acute autoimmune neuropathy. METHODS: Experimental autoimmune neuritis was induced in Lewis rats. Different concentrations of 2,4-Dinitrophenol (1 mg/kg, 0.1 mg/kg and 0.01 mg/kg) were applied during the recovery phase of the neuritis (at days 18, 22 and 26) and compared to the vehicle. Any effects were assessed through functional, electrophysiological, and morphological analysis via electron microscopy of all groups at day 30. Additional immune-histochemical analysis of inflammation markers and remyelination of the sciatic nerves were performed for the dosage of 1 mg/kg and control. RESULTS: No enhancement of functional or electrophysiological recovery was observed in all 2,4-Dinitrophenol-treated groups. Cellular inflammation markers of T cells (CD3+) were comparable to control, and an increase of macrophages (IbA1+) invasion in the sciatic nerves was observed. Treatment with 2,4-Dinitrophenol reduced axonal swelling in myelinated and unmyelinated fibers with an increased production of brain-derived neurotrophic factor. CONCLUSION: Our findings do not support the hypothesis that repurposing of the mitochondrial uncoupler 2,4-Dinitrophenol exerts functionally relevant neuro-regenerative effects in autoimmune neuritis.

Outcomes of Surgical Treatment for Sural Neuritis: A Retrospective Case Series.

BACKGROUND: Somatic nerve pain is one of the most common complications following surgery of the foot and ankle but may also arise following traumatic injury or chronic nerve compression. The sural nerve is a commonly affected nerve in the foot and ankle; it is at risk given the proximity to frequently used surgical approaches, exposure to crush injuries, and traction from severe ankle inversion injuries. The purpose of this study is to investigate the outcomes of sural nerve neurectomy with proximal implantation for sural neuromas (SN) and chronic sural neuritis (CSN). METHODS: Patients that underwent neurectomy with proximal implantation (20 muscle, 1 adipose tissue) by 2 foot and ankle specialists for isolated SN- and CSN-related pain at a single tertiary institution were included. Demographic data, baseline outcomes including 36-Item Short Form Health Survey (SF-36), Foot and Ankle Ability Measure (FAAM), and visual analog scale (VAS) were recorded. Final follow-up questionnaires using Patient Reported Outcomes Measurement Information System (PROMIS) lower extremity function, pain interference (PI), and neuropathic pain quality, FAAM, and VAS were administered using REDCap. Perioperative factors including neuropathic medications, diagnostic injections, the use of collagen wraps, and perioperative ketamine were collected from the medical record. Descriptive statistics were performed and potential changes in patient-reported outcome measure scores were evaluated using Wilcoxon signed-rank tests. RESULTS: The 21 patients meeting inclusion criteria for this study had a median age of 47 years (interquartile range [IQR], 43-49) and had median follow-up duration of 33.7 months (IQR, 4.5-47.6). Median FAAM activities of daily living score improved from 40.6 (38.7-50.7) preoperatively to 66.1 (53.6-83.3) postoperatively, P = .032. FAAM sports scores improved from 14.1 (7.8-21.9) to 41.1 (25.0-60.9) postoperatively, P = .002. VAS scores improved from a median of 9.0 (8.0-9.0) to 3.0 (3.0-6.0), P < .001. At final follow-up, patients reported PROMIS lower extremity function score median of 43.8 (35.6-54.9), PROMIS neuropathic pain quality score of 54.1 (43.6-61.6), and PROMIS PI of 57.7 (41.1-63.8). Patients with both anxiety and depression reported less improvement in pain and physical. Other perioperative factors lacked sufficient numbers for statistical analysis. CONCLUSION: Sural nerve neurectomy and proximal implantation (20 muscle, 1 adipose) provided significant improvement in pain and function for patients with sural neuromas and chronic sural neuritis at median follow-up of 33.7 months. Anxiety and depression were associated with significantly poorer outcomes following surgery. Patients with CRPS as well as recent nicotine use tended to report less improvement in pain and worse function after surgery, although this sample size was too limited for statistical analysis of these variables. Further research is needed to identify the ideal surgical candidates and perioperative factors to optimize patient outcomes. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Vestibular Nucleus Involvement in Patients With Acute Vertigo Due to Herpes Zoster Oticus or Vestibular Neuritis.

OBJECTIVES: Herpes zoster oticus (HZO) typically provokes vestibular symptoms and is traditionally viewed as a cranial nerve equivalent of shingles, but in contrast to vestibular neuritis (VN), it is unclear whether the pathology of HZO is limited to the vestibular nerve (neuritis) or can also involve the brainstem (nucleitis). METHODS: We retrospectively compared brain MRIs of patients with HZO with those of patients with VN to study radiologic changes in the brainstem. RESULTS: Five of 10 patients with HZO showed signal abnormalities in the vestibular nuclei, which lie in multiple vascular territories, whereas no patients with VN exhibited such findings. DISCUSSION: HZO may at least in part reflect vestibular nucleitis, as opposed to a pure neuritis.

Unexpected Ocular Manifestations Due to Exposure to Highly Concentrated Peracetic Acid: A Case Report.

BACKGROUND Peracetic acid is among the disinfectants that irritate the upper respiratory tract, skin, and conjunctiva. It can cause symptoms of eye irritation, secondary to an inflammatory process that can lead to various manifestations. Irritation happens due to the high reduction potential of the acid, which causes the consequent release of reactive oxygen species. This fact serves to reinforce the importance of personal protective equipment when handling peracetic acid. CASE REPORT During an accident at work, a 21-year-old patient received a strong jet of disinfectant solution directly into both eyes. The composition of the disinfectant solution was 15% peracetic acid, 15-16% hydrogen peroxide, 22-23% acetic acid, and 16-17% horticultural sanitizers. Twenty-four hours after the incident, eye damage (punctate keratitis and low visual acuity) had occurred, and was treated by washing the eye with ice water and frequently applying lubricating eye drops. The next day, the patient returned with an improvement of irritative symptoms, but with a major complaint of low visual acuity in left eye, secondary to optic neuritis, detected by fundoscopy and confirmed by optical coherence tomography. In the following week, fluorescent angiography indicated the persistence of neuritis in the left eye. This was treated with prednisone, 40 mg/day, which brought about gradual improvement. Two months later, the patient returned with test results showing normal magnetic resonance imaging and negative serologies (for syphilis, HIV, and herpes virus), visual acuity 20/20 in both eyes, and normalization of angiography and optical coherence tomography parameters. CONCLUSIONS Until now, there have been no published studies demonstrating neuritis caused by direct contact of peracetic acid into the eyes. Therefore, this is the first report in the world literature of this manifestation of ocular exposure to peracetic acid. This is a chemical formulation that is widely useful and prevents the growth of various pathogens. Further investigation and studies on the subject should be encouraged to improve its management and use.

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.

Recurrent motor branch neuropathy in carpal tunnel syndrome: An ultrasound study.

INTRODUCTION/AIMS: The reason for the variable rate of progression of patients with carpal tunnel syndrome (CTS) to thenar muscles impairment is not fully understood. The aim of this study was to evaluate the occurrence of ultrasound signs of recurrent motor branch (RMB) neuropathy in patients with CTS and to correlate imaging findings with clinical and electrophysiological data. METHODS: Two cohorts were recruited, one consisting of CTS patients with electrodiagnostic evidence of prolonged median distal motor latency from wrist to thenar eminence and another consisting of sex- and age-matched healthy controls. Ultrasound reliability of RMB measurement was assessed by the calculation of the interclass correlation coefficient (ICC). Patients were evaluated with electrodiagnostic tests and asked to complete the Boston Carpal Tunnel Questionnaire. The difference between the RMB diameter in patients and controls was analyzed using a t test. Correlations between RMB diameter and other parameters were assessed using linear mixed models. RESULTS: 46 hands from 32 patients with CTS and 50 hands from 50 controls were evaluated. The intra- and interobserver agreements in RMB measurement were very good (ICC = 0.84; 95% confidence interval [CI], 0.75 to 0.90) and good (ICC = 0.79; 95% CI, 0.69 to 0.87). The RMB diameter was significantly larger in patients than in controls (P < .0001). No significant correlation was found between the RMB diameter and other variables, except for BMI and median nerve cross-sectional area. DISCUSSION: Ultrasound is reliable in identifying the RMB and characterizing its abnormalities. In this patient cohort, ultrasound allowed for detection of definite signs of RMB compression neuropathy.

Case Report: Vagal Nerve Neuritis Associated with Pulmonary Melioidosis Provides Potential Insights into the Pathophysiology of Neuromelioidosis.

Encephalomyelitis is the most frequent manifestation of neuromelioidosis in Australia. It is hypothesized that Burkholderia pseudomallei causes encephalomyelitis after entering the brain directly, if complicating a scalp infection, or after traveling to the brain within peripheral or cranial nerves. A 76-year-old man presented with fever, dysphonia, and hiccups. Chest imaging demonstrated extensive bilateral pneumonia with mediastinal lymphadenopathy, blood cultures isolated B. pseudomallei, and nasendoscopy confirmed a left vocal cord palsy. Magnetic resonance imaging identified no intracranial abnormality but demonstrated an enlarged, enhancing left vagus nerve, consistent with neuritis. We hypothesize that B. pseudomallei invaded the vagus nerve in the thorax, was traveling proximally-involving the left recurrent laryngeal nerve and causing the left vocal cord palsy, but had not yet reached the brainstem. Given the frequency of pneumonia in cases of melioidosis, the vagus nerve may represent an alternative, and indeed common, route for B. pseudomallei to enter the brainstem in cases of melioidosis-related encephalomyelitis.

Inflammatory Processes in Alzheimer's Disease-Pathomechanism, Diagnosis and Treatment: A Review.

Alzheimer's disease is one of the most commonly diagnosed cases of senile dementia in the world. It is an incurable process, most often leading to death. This disease is multifactorial, and one factor of this is inflammation. Numerous mediators secreted by inflammatory cells can cause neuronal degeneration. Neuritis may coexist with other mechanisms of Alzheimer's disease, contributing to disease progression, and may also directly underlie AD. Although much has been established about the inflammatory processes in the pathogenesis of AD, many aspects remain unexplained. The work is devoted in particular to the pathomechanism of inflammation and its role in diagnosis and treatment. An in-depth and detailed understanding of the pathomechanism of neuroinflammation in Alzheimer's disease may help in the development of diagnostic methods for early diagnosis and may contribute to the development of new therapeutic strategies for the disease.

Incidence of Underlying Abnormal Findings on Routine Magnetic Resonance Imaging for Bell Palsy.

Importance: There is no consensus on the benefits of routine magnetic resonance imaging (MRI) of the facial nerve in patients with suspected idiopathic peripheral facial palsy (PFP) (ie, Bell palsy [BP]). Objectives: To estimate the proportion of adult patients in whom MRI led to correction of an initial clinical diagnosis of BP; to determine the proportion of patients with confirmed BP who had MRI evidence of facial nerve neuritis without secondary lesions; and to identify factors associated with secondary (nonidiopathic) PFP at initial presentation and 1 month later. Design, Setting, and Participants: This retrospective multicenter cohort study analyzed the clinical and radiological data of 120 patients initially diagnosed with suspected BP from January 1, 2018, to April 30, 2022, at the emergency department of 3 tertiary referral centers in France. Interventions: All patients screened for clinically suspected BP underwent an MRI of the entire facial nerve with a double-blind reading of all images. Main Outcomes and Measures: The proportion of patients in whom MRI led to a correction of the initial diagnosis of BP (any condition other than BP, including potentially life-threating conditions) and results of contrast enhancement of the facial nerve were described. Results: Among the 120 patients initially diagnosed with suspected BP, 64 (53.3%) were men, and the mean (SD) age was 51 (18) years. Magnetic resonance imaging of the facial nerve led to a correction of the diagnosis in 8 patients (6.7%); among them, potentially life-threatening conditions that required changes in treatment were identified in 3 (37.5%). The MRI confirmed the diagnosis of BP in 112 patients (93.3%), among whom 106 (94.6%) showed evidence of facial nerve neuritis on the affected side (hypersignal on gadolinium-enhanced T1-weighted images). This was the only objective sign confirming the idiopathic nature of PFP. Conclusions and Relevance: These preliminary results suggest the added value of the routine use of facial nerve MRI in suspected cases of BP. Multicentered international prospective studies should be organized to confirm these results.