The peripheral nervous system can encounter alterations due to exposure to some of the most commonly used anticancer drugs (platinum drugs, taxanes, vinca alkaloids, proteasome inhibitors, thalidomide), the so-called chemotherapy-induced peripheral neurotoxicity (CIPN). CIPN can be long-lasting or even permanent, and it is detrimental for the quality of life of cancer survivors, being associated with persistent disturbances such as sensory loss and neuropathic pain at limb extremities due to a mostly sensory axonal polyneuropathy/neuronopathy. In the state of the art, there is no efficacious preventive/curative treatment for this condition. Among the reasons for this unmet clinical and scientific need, there is an uncomplete knowledge of the pathogenetic mechanisms. Ion channels and transporters are pivotal elements in both the central and peripheral nervous system, and there is a growing body of literature suggesting that they might play a role in CIPN development. In this review, we first describe the biophysical properties of these targets and then report existing data for the involvement of ion channels and transporters in CIPN, thus paving the way for new approaches/druggable targets to cure and/or prevent CIPN.

The use of immune checkpoint inhibitors (ICIs) for the treatment of various advanced and aggressive types of malignancy has significantly increased both survival and long-term remission rates. ICIs block crucial inhibitory pathways of the immune system, in order to trigger an aggravated immune response against the tumor. However, this enhanced immune activation leads to the development of numerous immune-related adverse events (irAEs), which may affect any system. Although severe neurological irAEs are relatively rare, they carry a high disability burden, and they can be potentially life-threatening. Therefore, clinicians must be alert and act promptly when individuals receiving ICIs present with new-onset neurological symptoms. In this narrative review, we have collected all the currently available data regarding the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of post-ICI neurological irAEs. This review aims to raise physicians\' awareness, enrich their knowledge regarding disease pathogenesis, and guide them through the diagnosis and management of post-ICI neurological irAEs.

Hereditary transthyretin amyloidosis (hATTR) with polyneuropathy (formerly known as Familial Amyloid Polyneuropathy (FAP)) is an endemic amyloidosis involving the harmful aggregation of proteins, most commonly transthyretin (TTR) but sometimes also apolipoprotein A-1 or gelsolin. hATTR appears to be transmitted as an autosomal dominant trait. Over 100 point mutations have been identified, with the Val30Met substitution being the most common. Yet, the mechanism of pathogenesis and the overall origin of hATTR remain unclear. Here, we argue that hATTR could be related to harmful metal exposure. hATTR incidence is unevenly distributed globally, and the three largest defined clusters exist in Japan, Portugal, and Sweden. All three disease regions are also ancient mining districts with associated metal contamination of the local environment. There are two main mechanisms for how harmful metals, after uptake into tissues and body fluids, could induce hATTR. First, the metals could directly influence the expression, function, and/or aggregation of the proteins involved in hATTR pathology. Such metal-protein interactions might constitute molecular targets for anti-hATTR drug design. Second, metal exposure could induce hATTR -associated genetic mutations, which may have happened several generations ago. These two mechanisms can occur in parallel. In conclusion, the possibility that hATTR could be related to metal exposure in geochemically defined regions deserves further attention.

OBJECTIVE: Chemotherapy-induced peripheral neuropathy (CIPN) continues to be a major source of chronic morbidity in patients with cancer. Current treatment options and efficacy are limited; thus, there is a need to investigate more effective therapeutic options. Spinal neuromodulation including dorsal column spinal cord stimulation (SCS) and dorsal root ganglion stimulation (DRG-S) are being explored for these patients. The purpose of this narrative review was to critically summarize and evaluate the advancements that have been made in utilizing SCS and DRG-S for CIPN.
METHODS: A thorough literature search was conducted using PubMed for any research on patients with CIPN who underwent DRG-S or SCS. Studies involving patients with general cancer-related pain were not included. Only articles that were published in English, had original, extractable data, and were available on or before August 1, 2023, were included.
RESULTS: This study evaluated twelve studies with a total of 13 patients that reported using SCS for CIPN and four studies with a total of 12 patients that reported using DRG-S for CIPN. Many of the studies demonstrated that DRG-S or SCS can assist in reducing opioid consumption, lowering pain scores, and improving sensory deficits.
CONCLUSIONS: DRG-S and SCS have the potential to improve symptoms and lower medication usage in patients suffering from CIPN. Spinal neuromodulation could be considered as an alternative therapy for patients with persistent symptoms.

Leprosy, caused by the bacterium Mycobacterium leprae, is known to primarily affect the skin and peripheral nerves. We present a rare case of leprosy initially manifesting as demyelinating polyneuropathy. A 46-year-old female presented with progressive weakness, tingling, and numbness in her extremities. Nerve conduction studies revealed evidence of demyelination, prompting further investigations. Skin slit-skin smears confirmed the diagnosis of leprosy, with the presence of acid-fast bacilli. The patient was subsequently started on multidrug therapy, leading to significant clinical improvement. This case highlights the importance of considering leprosy as a differential diagnosis in patients presenting with demyelinating polyneuropathy, especially in endemic regions.

Recreational use of nitrous oxide (N2O), commonly known as laughing gas, has increased in the last few years, bringing an increase in the number of reported cases of toxicity due to this gas. Subacute combined degeneration (SCD) of the spinal cord is the most frequently reported neurological disorder due to the use of N2O, as well as polyneuropathy and even psychiatric symptoms. All of these disorders are consequences of a functional deficit of vitamin B12. We are reporting the cases of two patients with a history of N2O abusive use presenting to the emergency department with progressive symptoms of paresthesia, ascending symmetric paraparesis, and gait ataxia, emulating the clinical characteristics of Guillain-Barré Syndrome (GBS). In both cases, magnetic resonance imaging (MRI) showed findings compatible with transverse myelitis of the cervical spinal cord, and electrodiagnosis studies reported the presence of polyneuropathy with a mixed mechanism. All these findings together pointed to the presence of myeloneuropathy due to a vitamin B12 deficit induced by the prolonged use of N2O. Symptoms improved gradually with vitamin B12 supplementation and abstinence from N2O. It is important to acknowledge the clinical characteristics of complications due to neurotoxicity induced by N2O. Such complications are potentially reversible if they are treated appropriately and quickly. Considering the increase in N2O abuse, it should be considered a probable cause when treating patients with myelopathy and/or neuropathy of an unusual etiology.

Bilateral facial palsy with paresthesia (FDP) is a rare variant of GBS, characterized by simultaneous bilateral facial palsy and paresthesia of the distal limbs. Mounting evidence indicates that the presence of anti-GT1a IgG has a pathogenic role as an effector molecule in the development of cranial nerve palsies in certain patients with GBS, whereas anti-GT1a antibody is rarely presented positive in FDP. Here, we report the case of a 33-year-old male diagnosed with FDP presented with acute onset of bilateral facial palsy and slight paresthesias at the feet as the only neurological manifestation. An antecedent infection with no identifiable reason for the fever or skin eruptions was noted in the patient. He also exhibited cerebrospinal fluid albuminocytologic dissociation and abnormal nerve conduction studies. Notably, the testing of specific serum anti-gangliosides showed positive anti-GT1a IgG/IgM Ab. The patient responded well to intravenous immunoglobulin therapy. This case brings awareness to a rare variant of GBS, and provides the first indication that anti-GT1a antibodies play a causative role in the development of FDP. The case also suggests that prompt management with IVIG should be implemented if FDP is diagnosed.

Peripheral neuropathy and amputation are common complications of diabetes mellitus (DM) that significantly impact the quality of life of the affected individuals. This study aims to investigate the prevalence of peripheral neuropathy, the level of amputation, and the quality of life in patients with DM. This cross-sectional study was conducted after approval of the synopsis involving 225 diagnosed patients with DM on pre-defined eligibility criteria, selected from public sector OPDs, specialized diabetes centres, and centres manufacturing orthotics and prosthetics. Data were collected through interviews, observations, and the administration of the Michigan Neuropathy Screening Instrument and the Asian Diabetes Quality of Life Questionnaire. The level of amputation was recorded for each participant. Data was entered into SPSS, and results were synthesized. Pearson correlation is applied to find an association between gender and the quality of life of the participants, while P ≤ 0.05 will be considered significant. The prevalence of peripheral neuropathy in a sample of 225, based on a self-administered questionnaire, was (44.4%), and in terms of foot examination was (51.1%). As people progressed in age, the prevalence increased to 20.0% in patients above 60 years and 8.9% in ≤ 35 years of age. The majority of participants (56.0%) have had DM for less than five years. Females were 57.8% of the study population, while 97.8% of participants had type II DM. Below-knee amputation of the right limb was observed in 22(9.8%) of the participants. The QoL was poor in the majority of the participants (96.9%) patients with DM (P = 0.638 and T = -0.471). This cross-sectional study highlights a high prevalence of peripheral neuropathy and amputation and poor QoL in patients with diabetic mellitus.

The incidence of peripheral facial palsy is on the rise, with psychological issues influencing quality of life due to visible symptoms. Consequently, patient-reported outcome measures are critical in assessing the disease burden and the treatment efficacy of peripheral facial palsy from patients\' perspective. This study examines factors influencing patients\' global impression of change (PGIC) scores, a type of patient-reported outcome measure, in hospitalized patients with peripheral facial palsy. This retrospective study analyzed the electronic medical records of 200 patients with peripheral facial palsy who were admitted to the Korean Medicine Hospital, Kyung Hee University Medical Center from May 1, 2022 to April 30, 2023. Impact of demographic, electrophysiological, intervention, and clinical factors on PGIC scores were evaluated. Descriptive statistics showed that the length of hospitalization (P = .020), time from disease onset to hospitalization (P = .022), lacrimal disorders (P = .002), House-Brackmann (HB) grade evaluated at admission (P = .016) and at discharge (P < .001), improvement in HB-grade from admission to discharge (P = .002), and total facial disability index (FDI) score at discharge (P < .001) were significantly associated with PGIC scores. In multivariate logistic regression analysis, HB-grade at admission (OR: 13.89, 95% CI: 2.18-113.60), length of stay (OR: 0.27, 95% CI: 0.07-0.92), time from disease onset to hospitalization (OR: 5.55, 95% CI: 1.36-24. 77), tear-related symptoms (OR: 0.41, 95% CI: 0.17-0.96), total FDI score (OR: 0.45, 95% CI: 0.20-0.98), and greater improvement in HB-grade at discharge compared to admission (OR: 0.08, 95% CI: 0.02-0.31) were significantly associated with PGIC scores. Patients with milder initial disease severity, hospitalization period exceeding 7 days, shorter time from disease onset to hospitalization, improvement of lacrimal symptoms, total FDI score, and HB-grade between admission and discharge experienced more significant subjective improvement in peripheral facial palsy.

UNASSIGNED: Guillain-Barré syndrome (GBS) is an autoimmune disease associated with significant morbidity. A wide variety of infectious and non-infectious triggers have been identified to be associated with GBS. COVID-19 has gained attention in recent years for its role in GBS pathogenesis. Our study aims to review the literature on GBS and its epidemiological and pathophysiological association with COVID-19.
UNASSIGNED: Recent literature on GBS associated with COVID-19 infections, such as case reports, case series, systematic reviews, and large-scale epidemiological studies, were reviewed. We also reviewed studies that included vaccines against COVID-19 in association with GBS. Studies that focused on understanding the pathobiology of GBS and its association with infectious agents including COVID-19 were reviewed.
UNASSIGNED: Despite a lack of consensus, GBS is strongly associated with COVID-19 infection. The exact pathophysiological mechanism regarding COVID-19 as a causative agent of GBS is unknown. Mechanisms, such as the proinflammatory state, triggering of autoimmunity, and direct viral invasion, are postulated and remain to be investigated. Adenovirus vector vaccines are most likely associated with GBS, and the consensual reports clearly suggest mRNA vaccines are associated with low risk and may be protective against GBS by reducing the risk of COVID-19 infection.