Peripheral Nervous System Dysfunction Research Articles

Lower vascular conductance responses to handgrip exercise are improved following acute antioxidant supplementation in young individuals with post-traumatic stress disorder.

Young individuals with post-traumatic stress disorder (PTSD) display peripheral vascular and autonomic nervous system dysfunction, two factors potentially stemming from a redox imbalance. It is currently unclear if these aforementioned factors, observed at rest, alter peripheral haemodynamic responses to exercise in this population. This study examined haemodynamic responses to handgrip exercise in young individuals with PTSD following acute antioxidant (AO) supplementation. Thirteen young individuals with PTSD (age 23±3years), and 13 age- and sex-matched controls (CTRL) participated in the study. Exercise-induced changes to arm blood flow (BF), mean arterial pressure (MAP) and vascular conductance (VC) were evaluated across two workloads of rhythmic handgrip exercise (3 and 6kg). The PTSD group participated in two visits, consuming either a placebo (PL) or AO prior to their visits. The PTSD group demonstrated significantly lower VC (P=0.04) across all exercise workloads (vs. CTRL), which was significantly improved following AO supplementation. In the PTSD group, AO supplementation improved VC in participants possessing the lowest VC responses to handgrip exercise, with AO supplementation significantly improving VC responses (3 and 6kg: P<0.01) by blunting elevated exercise-induced MAP responses (3kg: P=0.01; 6kg: P<0.01). Lower VC responses during handgrip exercise were improved following AO supplementation in young individuals with PTSD. AO supplementation was associated with a blunting of exercise-induced MAP responses in individuals with PTSD displaying elevated MAP responses. This study revealed that young individuals with PTSD exhibit abnormal, peripherally mediated exercise responses that may be linked to a redox imbalance.

Evaluation of peripheral and autonomic nervous systems dysfunctions in patients with Parkinson’s disease

BackgroundPeripheral neuropathy (PN) is increasingly recognized in Parkinson’s disease (PD). This study aimed to evaluate peripheral nerve and autonomic nervous system dysfunction in PD. Forty patients with PD (20 drug-naïve, 20 on treatment) and 20 controls underwent neurological examination, Toronto Clinical Neuropathy Score (TCNS), nerve conduction studies, autonomic function tests including (heart rate variability, Blood pressure changes with standing and sustained handgrip, and sudomotor pathways. The Ewing classification system scored each test to quantify autonomic failure severity). Laboratory tests (B12, homocysteine, methylmalonic acid).ResultsTreated patients with PD had higher MDS-UPDRS scores than drug-naïve (p = 0.001). TCNS indicated mild PN in some drug-naïve patients, and mild–moderate PN in treated patients. Nerve conduction studies showed significant sensory and motor neuropathy in treated versus drug-naïve PD and controls. Treated patients had lower B12, higher homocysteine/methylmalonic acid than other groups. Across autonomic tests, controls had the most normal results, followed by drug-naïve patients, with treated patients being most abnormal. Autonomic dysfunction correlated with disease duration, severity, L-dopa dose. Lower B12, higher homocysteine/methylmalonic acid levels were associated with greater neuropathy and disease severity.ConclusionPatients with PD show evidence of PN and autonomic dysfunction, which is milder in drug-naïve patients but worsens with disease progression and treatment. Peripheral nervous system assessments may help diagnose and monitor PD neuropathy and effects of interventions.

Chronic and acute exposure to rotenone reveals distinct Parkinson's disease-related phenotypes in human iPSC-derived peripheral neurons

Peripheral autonomic nervous system (P-ANS) dysfunction is a critical non-motor phenotype of Parkinson's disease (PD). The majority of PD cases are sporadic and lack identified PD-associated genes involved. Epidemiological and animal model studies suggest an association with pesticides and other environmental toxins. However, the cellular mechanisms underlying toxin induced P-ANS dysfunctions remain unclear. Here, we mapped the global transcriptome changes in human induced pluripotent stem cell (iPSC) derived P-ANS sympathetic neurons during inhibition of the mitochondrial respiratory chain by the PD-related pesticide, rotenone. We revealed distinct transcriptome profiles between acute and chronic exposure to rotenone. In the acute stage, there was a down regulation of specific cation channel genes, known to mediate electrophysiological activity, while in the chronic stage, the human P-ANS neurons exhibited dysregulation of anti-apoptotic and Golgi apparatus-related pathways. Moreover, we identified the sodium voltage-gated channel subunit SCN3A/Nav1.3 as a potential biomarker in human P-ANS neurons associated with PD. Our analysis of the rotenone-altered coding and non-coding transcriptome of human P-ANS neurons may thus provide insight into the pathological signaling events in the sympathetic neurons during PD progression.

SARS-CoV-2 infection causes dopaminergic neuron senescence

COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.

Analysis of determinant diabetic neuropathy symptom score factors in diabetes mellitus patients

Background: Diabetes peripheral neuropathy (DPN) is a set of signs and symptoms of peripheral nervous system dysfunction in diabetes mellitus patients. Abdominal obesity is one of the main risk factors for DPN. Diabetic neuropathy symptom (DNS) is a reliable instrument with consistent results for the diagnosis of neuropathy. Objective: This study aimed to determine the correlation of abdominal obesity with scores. Methods: This research was a quantitative study with a cross-sectional approach. The sample of this study was 92 type 2 diabetes mellitus (T2DM) patients aged range 30-60 years who participated in the chronic disease management program (Prolanis) and the integrated healthcare center (Posbindu) for people in the area of three public health centers (Puskesmas) in Pekalongan Regency which purposively selected. Instruments used to measure DPN were DNS sheets, and abdominal obesity was measured by waist circumference using a midline. The bivariate analysis was performed using the Pearson correlation and linear regression tests. Results: There was a correlation between abdominal obesity and DNS scores with a p value of 0.043 with a correlation coefficient of 0.212. The DNS score was influenced by age, gender, duration of diabetes, and body mass index by 13.4%. Conclusion: There was a correlation between abdominal obesity and DNS scores. It indicated that the higher the value of abdominal obesity was, the higher DNS scores increased.

Dysfunction of peripheral somatic and autonomic nervous system in patients with severe forms of Crohn's disease on biological therapy with TNFα inhibitors-A single center study.

Crohn's disease (CD) can be associated with a wide range of extraintestinal manifestations (EIMs), including neurological ones. Published studies differ in their conclusions about the epidemiology and etiopathogenesis of neurological EIMs. The aims of this study were to demonstrate the presence and find risk factors of peripheral (somatic and autonomic) neuropathy patients with severe CD on anti-TNFα biological therapy. A clinical examination focusing on detection of peripheral sensor-motor nervous dysfunction (including Sudoscan) and examination of autonomic nervous system dysfunction (using Ewing´s battery tests and spectral analysis) together with laboratory tests and collection of demographic data followed by administration of questionnaires were performed on a total of 30 neurologically asymptomatic outpatients with severe CD on anti-TNFα biological therapy. Peripheral sensor-motor nervous function via clinical neurological examination was pathological in 36.7% and Sudoscan in 33.3% of cases. Statistically significant associations between vibration perception test and age, CD and biological therapy duration, body mass index and Crohn's Disease Activity Index were proved while statistically significant associations between temperature perception test and age and BMI were proved as well. Additionally, a decrease of total protein in a patient´s serum below the physiological cut-off in the 6 months prior to measurement was associated with a pathological result of a Sudoscan. Cardiovascular autonomic neuropathy based on Ewing´s battery tests was present in 56.7% of patients, no statistically significant risk factors were found. Our peripheral neuropathy questionnaire correlated with the results of the Sudoscan test and some tests of the clinical examination of peripheral sensor-motor nervous function (discriminatory contact perception test, temperature perception test). This study demonstrated a relatively high prevalence of peripheral (especially autonomic) neuropathy and verified some risk factors for the development of peripheral somatic neuropathy in asymptomatic patients with severe form of CD on anti-TNFα biological therapy.

Applying Lessons From Rheumatology to Better Understand Long COVID.

Long COVID can sometimes be attributed to organ damage and well-characterized pathophysiology, but more often there is no evidence of organ damage or abnormal biomarkers. This is most evident in patients with mild to moderate initial SARS-CoV-2 infection who were not hospitalized. Their persistent symptoms are strikingly similar to those of fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome, including fatigue, post-exertional malaise, myalgias/arthralgias, and sleep and cognitive disturbances in 50% to 100% of cases. Analogous pathophysiologic pathways in fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and long COVID include host-microbial interactions in the absence of direct tissue invasion and absence of systemic autoimmunity, withevidence for immune dysregulation as well as autonomic, peripheral, and central nervous system dysfunction. Current treatment of long COVID has been based on multidisciplinary management recommended for FM and ME/CFS and has been formalized and made widely available by funding for nationwide long COVID clinics. Long COVID and its treatment should be distinguished by the presence or absence of organ damage. The acknowledged role of patient engagement in research and open dialogue regarding work and disability noted in long COVID may have meaningful impact on patients with FM and ME/CFS. Hopefully, advances in basic long COVID research will aid in understanding FM and ME/CFS, and rheumatologists should thus be involved in such research and patient care.

Role of Tau protein in long COVID and potential therapeutic targets.

Long COVID is an emerging public health burden and has been defined as a syndrome with common symptoms of fatigue, shortness of breath, cognitive dysfunction, and others impacting day-to-day life, fluctuating or relapsing over, occurring for at least two months in patients with a history of probable or confirmed SARS CoV-2 infection; usually three months from the onset of illness and cannot be explained by an alternate diagnosis. The actual prevalence of long-term COVID-19 is unknown, but it is believed that more than 17 million patients in Europe may have suffered from it during pandemic. Currently, there is limited understanding of the pathophysiology of this syndrome, and multiple hypotheses have been proposed. Our literature review has shown studies reporting tau deposits in tissue samples of the brain from autopsies of COVID-19 patients compared to the control group, and the in-vitro human brain organoid model has shown aberrant phosphorylation of tau protein in response to SARS-CoV-2 infection. Tauopathies, a group of neurodegenerative disorders with the salient features of tau deposits, can manifest different symptoms based on the anatomical region of brain involvement and have been shown to affect the peripheral nervous system as well and explained even in rat model studies. Long COVID has more than 203 symptoms, with predominant symptoms of fatigue, dyspnea, and cognitive dysfunction, which tauopathy-induced CNS and peripheral nervous system dysfunction can explain. There have been no studies up till now to reveal the pathophysiology of long COVID. Based on our literature review, aberrant tau phosphorylation is a promising hypothesis that can be explored in future studies. Therapeutic approaches for tauopathies have multidimensional aspects, including targeting post-translational modifications, tau aggregation, and tau clearance through the autophagy process with the help of lysosomes, which can be potential targets for developing therapeutic interventions for the long COVID. In addition, future studies can attempt to find the tau proteins in CSF and use those as biomarkers for the long COVID.

Standardization of rehabilitation medical cards for adult patients with musculoskeletal and peripheral nervous systems dysfunction

Currently, each rehabilitation institution solves the problem of registration of rehabilitation medical records empirically, based on the existing realities of a particular institution.&#x0D; The study examined the development of a medical history template for the in- and outpatient medical rehabilitation of patients with peripheral nervous system (PNS) and musculoskeletal system (MSA) dysfunction.&#x0D; The medical history template corresponded to the currently approved forms 003/y (Medical record for inpatient care) and 025/y (Medical record for outpatient care) but supplemented with chapters, allowing entry of information in accordance with the requirements of the Ministry of Health of the Russian Federation Order for medical rehabilitation of adults (No. 788n dated July 31, 2020). Additional chapters, forms, and appendices designed to include specific information about the rehabilitation process included the physical and rehabilitation medicine doctor examination list, multidisciplinary rehabilitation team members, examination lists, rehabilitation routing scale blank, list of MDRC discussions, individual patient management forms, standard rehabilitation discharge form, and list of rehabilitation quality criteria for adult patients with MSA/PNS dysfunction. Validated scales and test forms were also included.&#x0D; The unification of rehabilitation medical records for patients with MSA/PNS impairment makes it easier for the staff of the rehabilitation departments and centers to file medical records in accordance with the current legislation.

Clinical criteria and diagnostic assessment of fibromyalgia: position statement of the Italian Society of Neurology-Neuropathic Pain Study Group

BackgroundThe role of central and/or peripheral nervous system dysfunction is basically fundamental in fibromyalgia.AimThe aim of this position statement on behalf of the Neuropathic Pain Study Group of the Italian Society of Neurology is to give practical guidelines for the clinical and instrumental assessment of fibromyalgia (FM) in the neurological clinical practice, taking into consideration recent studies.MethodsCriteria for study selection and consideration were original studies, case-controls design, use of standardized methodologies for clinical practice, and FM diagnosis with ACR criteria (2010, 2011, 2016).ResultsACR criteria were revised. For diagnostic procedure of small-fiber pathology, 47 studies were totally considered.Recent diagnostic criteria should be applied (ACR, 2016). A rheumatologic visit seems mandatory. The involvement of small fibers should request at least 2 among HRV + SSR and/or laser-evoked responses and/or skin biopsy and/or corneal confocal microscopy, eventually followed by monitoring of metabolic and/or immunological/ and or/paraneoplastic basis, to be repeated at 1-year follow-up.ConclusionsThe correct diagnostic approach to FM could promote the exclusion of the known causes of small-fiber impairment. The research toward common genetic factors would be useful to promote a more specific therapeutic approach.

Autonomic dysfunction and exercise intolerance in concussion: a scoping review.

Concussion commonly results in exercise intolerance, often limiting return to activities. Improved understanding of the underlying mechanisms of post-concussive exercise intolerance could help guide mechanism-directed rehabilitation approaches. Signs of altered cardiovascular autonomic regulation-a potential contributor to exercise intolerance-have been reported following concussion, although it is not clear how these findings inform underlying mechanisms of post-concussive symptoms. Systematic summarization and synthesis of prior work is needed to best understand current evidence, allowing identification of common themes and gaps requiring further study. The purpose of this review was to (1) summarize published data linking exercise intolerance to autonomic dysfunction, and (2) summarize key findings, highlighting opportunities for future investigation. The protocol was developed a priori, and conducted in five stages; results were collated, summarized, and reported according to PRISMA guidelines. Studies including injuries classified as mild traumatic brain injury (mTBI)/concussion, regardless of mechanism of injury, were included. Studies were required to include both autonomic and exercise intolerance testing. Exclusion criteria included confounding central or peripheral nervous system dysfunction beyond those stemming from the concussion, animal model studies, and case reports. A total of 3116 publications were screened; 17 were included in the final review. There was wide variability in approach to autonomic/exercise tolerance testing, as well as inclusion criteria/testing timelines, which limited comparisons across studies. The reviewed studies support current clinical suspicion of autonomic dysfunction as an important component of exercise intolerance. However, the specific mechanisms of impairment and relationship to symptoms and recovery require additional investigation.

A Budget Impact Model of Maintenance Treatment of Chronic Inflammatory Demyelinating Polyneuropathy with IgPro20 (Hizentra) Relative to Intravenous Immunoglobulin in the United States.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare, progressive autoimmune disease causing peripheral nervous system dysfunction. Guidelines recommend immunoglobulin (IG) therapy as an immunomodulatory agent in CIDP. Drawbacks and unmet needs with intravenous immunoglobulin (IVIG) include adverse effects and wear-off effects, along with the burden of administration based on site of care. Subcutaneous administration of Hizentra, a subcutaneous immunoglobulin (SCIG) reduces patient burden by allowing self-administration outside the hospital setting and has fewer adverse events (AEs). We aimed to compare the expected cost of treatment and the budget impact of Hizentra compared with IVIG for maintenance treatment of CIDP in the United States. A decision tree model was developed to estimate the expected budget impact of maintenance treatment with Hizentra for US stakeholders. The model adopts primarily a US integrated delivery network perspective and, secondarily, a commercial perspective over a 1-year time horizon. Pharmacy costs were based on a payment mix of average sales price (73%), wholesale acquisition cost (2%), and average wholesale price (25%). Costs in the model reflect 2022 US dollars. In accordance with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines and recommendations for budget impact modeling, no discounting was performed. The PATH clinical study of Hizentra maintenance in CIDP was used to determine clinical inputs for relapse rates at initial assessment (24 weeks) and at 52 weeks for Hizentra. The ICE clinical study of Gamunex maintenance in CIDP was the basis of relapse rates for Gamunex (and other IVIGs). Literature-based estimates were obtained for infusion costs by site of care, costs of IVIG infusion-related complications, and significant IVIG AE rates. Hizentra AE rates from the US Hizentra prescribing information were assessed but were not included in the model as the AEs in CIDP were mild, easily treated, and self-limited. Sensitivity analyses and scenario analyses were conducted to evaluate variations from the base case. The model showed that a Hizentra starting dose of 0.2 g/kg is expected to result in annual cost savings of US$32,447 per patient compared with IVIG. For a hypothetical 25-million-member plan, the budget impact of a 10% market share shift from IVIG to Hizentra is expected to result in savings of US$2,296,235. This analysis projects that Hizentra is likely associated with favorable economic benefit compared with IVIG in managing CIDP.

Rare manifestation of familial vitreous amyloidosis caused by Gly103Arg transthyretin.

To identify and analyze the genotype of the patients with special ocular manifestations of familial vitreous amyloidosis (FVA) in a Chinese Han family. Pars plana vitrectomy (PPV) surgery was performed on a 52-year-old Chinese woman presented with vitreous amyloidosis and progressive visual impairment, without evidence of cardiac, renal, gastrointestinal, central nervous system or peripheral nervous system dysfunction. During the surgery, the patient presented with a gray-white dense and thick cotton wool-like change in the vitreous body, accompanied by complete retinal detachment. Additionally, hard, free and movable yellow-white deposits were observed in the posterior pole and surrounding retina, the vitreous and subretinal deposits were examined by Congo red staining and immunohistochemical pathological examination, and whole exome sequencing was performed on blood samples from the patient and her cousin. During the operation, it was discovered that there was a complete detachment of the retina and a significant amount of hard, free-floating yellow-white deposits were observed beneath the posterior pole and surrounding retina. This is an exceedingly rare ocular manifestation. Pathological examination of the vitreous and subretinal deposit specimens revealed positive Congo red staining, as well as elevated vascular endothelial growth factor (VEGF) expression in vascular endothelial cells within the sediment specimens upon immunohistochemical examination. The patient and her cousin both exhibited a heterozygous mutation in Glyl03Arg within the transthyretin (TTR) gene, resulting in a substitution of glycine (Gly) at position 103 with arginine (Arg). FVA may present with various ocular manifestations, but panretinal detachment is a rare occurrence. In cases where retinal detachment persists for an extended period of time, amyloid deposits may form under the retina through retinal tears, leading to subretinal deposits that can impede retinal reattachment and negatively impact visual prognosis. Elevated levels of VEGF in the eyes of FVA patients may indicate an overexpression state, necessitating careful postoperative follow-up. The heterozygous mutation Gly103Arg may represent a unique pathogenic site in Chinese individuals.

Assessment of Hearing and Vestibular Functions in a Post-COVID-19 Patient: A Clinical Case Study

SARS-CoV-2 infection may cause such complications as post-COVID-19 syndrome, which includes chronic fatigue, myalgia, arthralgia, as well as a variety of neurological manifestations, e.g., neuropathy of small fibers, hearing and vestibular dysfunction, and cognitive impairment. This clinical case describes a 41-year-old patient suffering from post-COVID-19 syndrome and chronic fatigue syndrome. A detailed examination was performed, including an in-depth study of peripheral and central hearing and vestibular functions, as well as small nerve fibers length and density in the skin and cornea of the eye. Contrary to expectations, no peripheral nervous system dysfunction was detected, despite the presence of dizziness and gait instability in the patient. Hearing tests (gap detection test and dichotic test) showed central auditory processing disorders. The evaluated lesion in the processing of temporal and verbal auditory information can be a significant factor contributing to additional overload of the neural activity and leading to chronic fatigue when performing daily activities in patients with CFS and post-COVID-19 complications.

Infections and immune dysregulation in ataxia-telangiectasia children with hyper-IgM and non-hyper-IgM phenotypes: A single-center experience

Ataxia-telangiectasia (A-T) is a severe syndromic neurodegenerative inborn error of immunity characterized by DNA reparation defect, chromosomal instability, and hypersensitivity to ionizing radiation, thereby predisposing affected individuals to malignant transformation. While the leading disease symptomatology is associated with progressively debilitating cerebellar ataxia accompanied by central and peripheral nervous system dysfunctions, A-T is a multisystemic disorder manifesting with the heterogeneity of phenotypic features. These include airway and interstitial lung disease, chronic liver disease, endocrine abnormalities, and cutaneous and deep-organ granulomatosis. The impaired thymic T cell production, defective B cell development and antibody production, as well as bone marrow failure, contribute to a combined immunodeficiency predisposing to infectious complications, immune dysregulation, and organ-specific immunopathology, with the A-T hyper-IgM (HIGM) phenotype determining the more severe disease course. This study aimed to clarify the immunodeficiency and associated immune dysregulation as well as organ-specific immunopathology in children with A-T. We also sought to determine whether the hyper-IgM and non-hyper-IgM phenotypes play a discriminatory role and have prognostic significance in anticipating the clinical course and outcome of the disease. We retrospectively reviewed the medical records of twelve A-T patients, aged from two to eighteen years. The patients' infectious history, organ-specific symptomatology, and immunological workup including serum alpha-fetoprotein, immunoglobulin isotypes, IgG subclasses, and lymphocyte compartments were examined. For further comparative analysis, all the subjects were divided into two groups, HIGM A-T and non-HIGM A-T. The clinical evaluation of the study group showed that recurrent respiratory tract infections due to viral and bacterial pathogens and a chronic obstructive airway disease along with impaired humoral immunity, in particular complete IgA deficiency, were noted in all the A-T patients, with both HIGM and non-HIGM phenotypes. The most important features with the discriminatory role between groups, were autoimmune disorders, observable four times more frequently in HIGM than in non-HIGM A-T. Two patients with the HIGM A-T phenotype were deceased due to liver failure and chronic Epstein-Barr virus (EBV) infection. It may therefore be assumed that the HIGM form of A-T is associated with more profound T cell dysfunction, defective immunoglobulin class switching, chronic EBV expansion, and poorer prognosis.

Clinical features of olfactory dysfunction in elderly patients

ObjectiveThis study aimed to investigate the causes of olfactory dysfunction (OD) and to discuss the benefits of understanding the characteristics of OD in elderly patients. MethodsA total of 4300 patients with OD who were treated at our hospital between January 1996 and December 2020 were retrospectively analyzed. There were 1833 men and 2467 women, with ages ranging from 4 to 95 years. The patients were divided into two groups: younger (less than 65 years old, n = 2947) and elderly (65 years old or more, n = 1353) groups. Causative diseases were chronic rhinosinusitis (CRS), post-viral (PV), post-traumatic (PT), central nervous system dysfunction (CNS), peripheral nervous system dysfunction (PNS), congenital, psychogenic, and unknown. Visual analogue scale (VAS) and olfactory detection and recognition thresholds using the T&T olfaction test were used to evaluate olfaction. The mean detection and recognition thresholds, as well as the deviation difference (the difference between the mean detection and recognition thresholds) were compared by causative disease. ResultsThe causative diseases in elderly group were CRS (32%), PV (28%), PT (3%), CNS (2%), and PNS (4%). OD of unknown cause was significantly more in elderly (30%) than in younger patients (12%). Olfactory detection and recognition thresholds in elderly group were significantly worse than in younger group (p < 0.05). The olfactory detection and recognition thresholds were not any significant differences between patients with OD of unknown cause and those with CNS. ConclusionOD of unknown cause was predominantly observed in elderly group. The olfactory acuity of OD of unknown cause was similar to CNS OD. These findings suggest the importance of continuous follow-up due to the potential of neurodegenerative diseases in elderly OD patients.

P.043 Plasmapheresis for treatment of light chain amyloidosis related myopathy

Background: Light chain (AL) amyloidosis is a plasma cell disorder characterized by abnormal fibrillary light chain deposition causing cardiac, renal, hepatic, gastrointestinal and peripheral nervous system dysfunction. Muscle disease occurs in 1.5% of individuals causing progressive proximal weakness thus far considered untreatable. Methods: We reviewed two cases of AL amyloidosis associated myopathy at our institution who had robust response to plasmapheresis. Both were at stringent clinical response following CyBorME therapy during peak severity of their myopathy. Results: In case 1, a 70-year-old male with recently diagnosed kappa light chain multiple myeloma and cardiac/renal amyloidosis developed severe subacute proximal weakness preventing ambulation. CK was normal and electromyography was consistent with irritable myopathy. Deltoid biopsy showed perimysial and endomysial amyloidosis. A trial of plasmapheresis in a tapering schedule resulted in robust recovery of strength. In case 2, a 67-year-old female with recently diagnosed kappa light chain multiple myeloma with amyloidosis on fat pad aspirate developed severe subacute proximal weakness requiring prolonged hospital admission. CK was normal and electromyography demonstrated non-irritable myopathy. Bicep biopsy showed perivascular amyloidosis. A trial of plasmapheresis in a tapering schedule resulted in robust recovery of strength. Conclusions: Plasmapheresis is a novel and potentially effective treatment for patients with AL amyloidosis associated myopathy.

Comparative study on visual evoked potential (VEP) wave P100 latency in hypothyroid and euthyroid individuals

Hypothyroidism is classified as congenital and acquired according to the time of onset. Consequences of thyroid gland dysfunction also depend on the life stage at which they occur. Peripheral and central nervous system dysfunction are important clinical features of congenital as well as acquired hypothyroidism. Although thyroid hormone effects on the brain are most prominent in development, also in adult-acquired hypothyroidism symptoms such as sensory impairments, disagreeable smells and taste, slowness of thought and action, changes of speech, irritability, headaches ,sleep disturbances, confusion up to delusions and Hallucinations, impairments of memory, of vision as well as of hearing frequently occur. The most prominent and first significant clinical symptom to develop in hypothyroidism is a slowing of speech and of visual perception. These findings indicate CNS involvement in hypothyroidism. VEP may be a useful test to detect these changes in early stage of disease.

Breast Implant Illness: A Case Series

Since the advent of breast implants, there has been unprecedented controversy and FDA bands regarding their safety. There has been a demonstrated link with certain types of lymphoma, autoimmune disorders, and systemic illness associated with breast implants. A significant population of women currently pursue bilateral breast implant removal in hopes to alleviate a constellation of symptoms anecdotally known as “breast implant illness”. This is not yet an accepted clinical entity due to the lack of sound literature on the subject. Common presenting symptoms include fatigue, anxiety, chronic pain, endocrine, autonomic, and peripheral nervous system dysfunction. Currently, there is no standard of care or guideline for treating women experiencing such symptoms. The current literature regarding breast implant illness has been widely observational and descriptive. With over four million women across the globe with augmented breasts, the potential impact of this research is great. This paper presents three patients believed to be suffering from breast implant illness, who after en-bloc resection, experienced resolution of their symptoms.

Reactive Balance Responses After Mild Traumatic Brain Injury: A Scoping Review.

Balance testing after concussion or mild traumatic brain injury (mTBI) can be useful in determining acute and chronic neuromuscular deficits that are unapparent from symptom scores or cognitive testing alone. Current assessments of balance do not comprehensively evaluate all 3 classes of balance: maintaining a posture; voluntary movement; and reactive postural response. Despite the utility of reactive postural responses in predicting fall risk in other balance-impaired populations, the effect of mTBI on reactive postural responses remains unclear. This review sought to (1) examine the extent and range of available research on reactive postural responses in people post-mTBI and (2) determine whether reactive postural responses (balance recovery) are affected by mTBI. Scoping review. Studies were identified using MEDLINE, EMBASE, CINAHL, Cochrane Library, Dissertations and Theses Global, PsycINFO, SportDiscus, and Web of Science. Inclusion criteria were injury classified as mTBI with no confounding central or peripheral nervous system dysfunction beyond those stemming from the mTBI, quantitative measure of reactive postural response, and a discrete, externally driven perturbation was used to test reactive postural response. A total of 4747 publications were identified, and a total of 3 studies (5 publications) were included in the review. The limited number of studies available on this topic highlights the lack of investigation on reactive postural responses after mTBI. This review provides a new direction for balance assessments after mTBI and recommends incorporating all 3 classes of postural control in future research.