Autonomic Involvement Research Articles

Editorial: Autonomic involvement in arrhythmias: translating mechanisms to therapy

Editorial: Autonomic involvement in arrhythmias: translating mechanisms to therapy

Clinical and molecular insights into A97S variants in hereditary transthyretin amyloid polyneuropathy in South China

Objective This study aims to delineate the clinical profiles of the hereditary transthyretin amyloid polyneuropathy (ATTRv-PN) patients with A97S variant from southern China and the molecular characteristics of this mutant protein. Methods Fifteen ATTRv-PN patients with heterozygous A97S and one patient with homozygous A97S were included in the study. Serum TTR tetramer concentration was quantified through ultra-performance liquid chromatography. Stabilities of A97S-TTR were assessed through in vitro urea-mediated tryptophan fluorescence experiments, and nephelometry was employed in drug response assessment. Results All patients were late-onset (≥50 years) with a mean age of onset at 59.26 ± 5.06 years old. Patients displayed a mixed phenotype featuring sensory-motor neuropathy with autonomic dysfunction and cardiac involvement, such as palpitations and chest pain. Electrophysiological studies showed generally axonal impairment of sensory and motor nerves. Tafamidis-treated patients showed significantly higher TTR tetramer concentrations, approaching healthy controls’ levels. In vitro assessment showed that A97S-TTR was more kinetically stable than the V122I-TTR, and tetramer stabilisers inhibited A97S-TTR amyloid formation by more than 70%. Conclusion This study provides valuable insights into the clinical and molecular characteristics of ATTRv-PN patients with A97S from South China, particularly regarding the differences in disease progression and stability features.

Autonomic impairment in primary lateral sclerosis.

Prior studies reported evidence of autonomic involvement in motor neuron disease and suggested more severe dysfunction in upper motor neuron predominant syndromes. Hence, we sought to characterize autonomic impairment in primary lateral sclerosis. Neurological evaluations, thermoregulatory sweat tests, and autonomic reflex screens were analyzed retrospectively in 34 primary lateral sclerosis patients (28 definite and 6 probable). Patients with other potential causes of autonomic failure and patients with autonomic testing results compromised by artifact were excluded. A total of 17 patients reported autonomic symptoms. Orthostatic lightheadedness was most frequent (8 patients), followed by bladder (7), bowel (5), and erectile dysfunction (3). The autonomic reflex screens of 33 patients were reviewed; 20 patients had abnormal studies. The thermoregulatory sweat tests of 19 patients were reviewed; 11 patients had abnormal studies. Composite Autonomic Severity Score was calculated for 33 patients and found abnormal in 20/33 patients (60.6%): 15/20 patients (75%) had mild impairment, and 5/20 patients (25%) had moderate impairment. The frequencies of testing abnormalities were: sudomotor 18/20 (90%), cardiovagal 9/20 (45%), and adrenergic 6/20 (30%). Sweat loss pattern analysis showed global, regional, and mixed patterns to be more common than length-dependent and distal patterns. We found evidence of frequent autonomic dysfunction in primary lateral sclerosis, which is generally of modest severity akin to prior reports for amyotrophic lateral sclerosis, but more commonly in a pattern consistent with preganglionic/ganglionic localization. This suggests that primary lateral sclerosis, as with amyotrophic lateral sclerosis, is a multisystem disease that affects the autonomic nervous system.

Autonomic Dysfunction in Amyotrophic Lateral Sclerosis - A Case-Control Study.

This study aimed to explore autonomic nervous system involvement in amyotrophic lateral sclerosis (ALS) patients by evaluating sympathetic skin response (SSR). The study included 35 sporadic (ALS) patients (cases), and 35 healthy age and sex-matched participants (controls) aged <60 years. SSR was recorded in the electrophysiology lab of the Neurology Department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Patients with diseases associated with peripheral or autonomic neuropathy were excluded. Prolonged latency (delayed SSR) or an absent response was considered abnormal SSR. SSR was found to be abnormal in 17 (48.6 %) ALS cases, with an absent response in the upper limbs of six cases (17.1%). Abnormal SSR was more prevalent in the lower limbs, with 33 (94.3%) and 20 (57.1%) cases having a delayed or absent response, respectively. In comparison, SSR was normal in all control participants (P-value <0.05). Abnormal SSR was significantly more common in the lower limbs of ALS cases with bulbar palsy than those without bulbar palsy (P-value=0.04). There was no association of SSR with disease severity and duration. ALS is significantly associated with abnormal SSR, indicating autonomic nervous system involvement. There could also be an association between bulbar palsy and abnormal SSR among ALS patients. Further studies should be carried out to determine the association of abnormal SSR with disease severity, duration, and type.

Clinicopathological Features of Amyloid Neuropathy: A Four Decade Experience

Background: Peripheral neuropathy is one of the manifestations of primary or familial amyloidosis. Published studies from India are limited. Materials and Methods: We reviewed the clinical and pathological features of amyloid neuropathy diagnosed at our Institute over the last 39 years. Results: Fifty-five cases of amyloid neuropathies were diagnosed between 1981 and 2019, constituting 0.28% of peripheral nerve biopsies (55/19,081). Age at presentation ranged from 24 to 81 years (mean—48 years) with male preponderance [M:F = 3.58:1]. Duration of symptoms at presentation varied from 3 months to 10 years (mean—2.31 years). Majority presented with small fiber neuropathy (85%). Pure sensory symptoms predominated in 23%, while 72% had sensorimotor neuropathy and 35.8% had autonomic involvement, with isolated autonomic failure in one patient. Amyloid neuropathy was clinically suspected in 22.6% of nonfamilial cases. Familial amyloid neuropathy was suspected in eight patients. Genetic testing detected ATTR and gelsolin mutation in one each of tested patients. Nerve biopsies revealed characteristic birefringent amyloid deposits stained mahogany brown by Congo red predominantly surrounding endoneurial microvessels (34.5%), also in perineurium and epineurium in 25.45% cases. Preferential loss of small diameter myelinated fibers was noted. Axonal degeneration or regeneration was conspicuously absent. Conclusion: Amyloid neuropathy is uncommon (0.28% of nerve biopsies in our series). Nerve biopsy is essential for the diagnosis. We report our experience of amyloid neuropathy and underscore the importance of making an assiduous search for amyloid deposits in the appropriate setting. Awareness of this entity is important for early diagnosis in the light of emerging therapeutic advances.

Neurogenic Bladder: A Rare Autonomic Sign in a Patient With Preserved Speech Variant (Zappella Variant) Rett Syndrome

Background: Rett syndrome is characterized by the loss of speech and purposeful hand movements, ambulation problems, and typical hand stereotypies. Preserved speech variant Rett syndrome (Zappella Variant) is a much less common form where speech is relatively preserved, from words to simple sentences. Lower urinary tract dysfunction and neurogenic bladder due to autonomic involvement have been only rarely reported in Rett syndrome. We aimed to emphasize neurogenic bladder due to autonomic dysfunction, which has very rarely been reported in the literature, in a patient with preserved speech variant Rett syndrome, a rare form of the Rett syndrome. Case presentation: A 7-year-old female patient who had been diagnosed with severe vesicoureteral reflux and neurogenic bladder when 11 months old due to the inability to urinate was suspected of suffering from Rett syndrome after intense eye contact and the stereotypic movement of hand wringing were observed. The patient could talk with phrases and walk and had purposeful hand movements. The presence of the c.961C&amp;gt;T (p.Arg321Trp) mutation in the C terminal region of the MECP2 gene was demonstrated with Sanger sequencing. The patient is currently 13 years old and is receiving special education and continues to be monitored for chronic renal disease at the pediatric nephrology department. Conclusion: The presence of hand stereotypies and intense eye pointing could indicate the Zappella variant Rett syndrome in a female patient who has developmental problems, can talk, has purposeful hand skills. Rett syndrome patients can also have lower urinary tract dysfunction although this is less common than cardiac, respiratory and gastrointestinal autonomic involvement. The development of intermittent urinary retention and vesicoureteral reflux may be associated with neurogenic bladder caused by autonomic involvement should be considered in these patients and one must be aware of the complications.

Sympathetic dysfunction as an early indicator of autonomic involvement in Parkinson's disease.

The specific characteristics of autonomic involvement in patients with early Parkinson's disease (PD) are unclear. This study aimed to evaluate the characteristics of autonomic dysfunction in drug-naïve patients with early-stage PD without orthostatic hypotension (OH) by analyzing Valsalva maneuver (VM) parameters. We retrospectively analyzed drug-naïve patients without orthostatic hypotension (n = 61) and controls (n = 20). The patients were subcategorized into early PD (n = 35) and mid-PD (n = 26) groups on the basis of the Hoehn and Yahr staging. VM parameters, including changes in systolic blood pressure at late phase 2 (∆SBPVM2), ∆HRVM3, Valsalva ratio (VR), pressure recovery time, adrenergic baroreflex sensitivity, and vagal baroreflex sensitivity, were assessed. In the early PD group, ∆SBPVM2, a marker of sympathetic function, was significantly lower compared with that in controls (risk ratio = 0.95, P = 0.027). Receiver operating characteristic (ROC) curve analysis showed an optimal cut-off value of -10mmHg for ∆SBPVM2 [P = 0.002, area under the curve (AUC): 0.737]. VR exhibited an inverse relationship with Unified Parkinson's Disease Rating Scale Part 3 scores in the multivariable regression analysis (VR: P = 0.038, β = -28.61), whereas age showed a positive relationship (age: P = 0.027, β = 0.35). The ∆BPVM2 parameter of the VM may help detect autonomic nervous system involvement in early-PD without OH. Our results suggest that sympathetic dysfunction is an early manifestation of autonomic dysfunction in patients with PD.

Cardiac autonomic involvement in Huntington’s disease

IntroductionHuntington’s disease (HD) is known as a neurodegenerative disease with movement disorder and cognitive impairment; autonomic involvement is also becoming common in some recent studies. The aim of this study is to demonstrate the presence of cardiac autonomic involvement in HD patients.MethodTime and frequency domain parameters obtained from the 24-h Holter ECG(hECG) were compared between 20 HD patients and 20 healthy control subjects.ResultsFourteen HD patients had tachycardia, bradycardia, and extra beats. Interval between two heartbeats, normal-to-normal (NN), standard deviation of all normal-to-normal (SDNN), square root of the mean of the sum of the squares of the differences between consecutive N-N intervals in ms (rMSSD), and the ratio of the number of consecutive pairs of N-N intervals that differ by more than 50 ms to the total number of N-N intervals (pNN50) were all significantly higher in the patient group than in the control group during 24-h hECG monitoring. However, hECG monitoring showed that the patient group had significantly higher values of the frequency-domain metrics high frequency (HF) than the control group did (P = 0.003). Very low frequency (VLF) was lower in the patient group (P = 0.009). There was no difference in low frequency (LF) in both groups. In comparison to the control group, LF/HF was much reduced in the patient group (P = 0.001).ConclusionCardiac disfunction increases, and autonomic functions change in HD, but more comprehensive studies are needed to distinguish sympathetic and parasympathetic involvement.

Characterizing Acute-Onset Small Fiber Neuropathy.

Immune-mediated small fiber neuropathy (SFN) is increasingly recognized. Acute-onset SFN (AOSFN) remains poorly described. Herein, we report a series of AOSFN cases in which immune origins are debatable. We included consecutive patients with probable or definite AOSFN. Diagnosis of SFN was based on the NEURODIAB criteria. Acute onset was considered when the maximum intensity and extension of both symptoms and signs were reached within 28 days. We performed the following investigations: clinical examination, neurophysiologic assessment encompassing a nerve conduction study to rule out large fiber neuropathy, laser-evoked potentials (LEPs), warm detection thresholds (WDTs), electrochemical skin conductance (ESC), epidermal nerve fiber density (ENF), and patient serum reactivity against mouse sciatic nerve teased fibers, mouse dorsal root ganglion (DRG) sections, and cultured DRG. The serum reactivity of healthy subjects (n = 10) and diseased controls (n = 12) was also analyzed. Data on baseline characteristics, biological investigations, and disease course were collected. Twenty patients presenting AOSFN were identified (60% women; median age: 44.2 years [interquartile range: 35.7-56.2]). SFN was definite in 18 patients (90%) and probable in 2 patients. A precipitating event was present in 16 patients (80%). The median duration of the progression phase was 14 days [5-28]. Pain was present in 17 patients (85%). Twelve patients (60%) reported autonomic involvement. The clinical pattern was predominantly non-length-dependent (85%). Diagnosis was confirmed by abnormal LEPs (60%), ENF (55%), WDT (39%), or ESC (31%). CSF analysis was normal in 5 of 5 patients. Antifibroblast growth factor 3 antibodies were positive in 4 of 18 patients (22%) and anticontactin-associated protein-2 antibodies in one patient. In vitro studies showed IgG immunoreactivity against nerve tissue in 14 patients (70%), but not in healthy subjects or diseased controls. Patient serum antibodies bound to unmyelinated fibers, Schwann cells, juxtaparanodes, paranodes, or DRG. Patients' condition improved after a short course of oral corticosteroids (3/3). Thirteen patients (65%) showed partial or complete recovery. Others displayed relapses or a chronic course. AOSFN primarily presents as an acute, non-length-dependent, symmetric painful neuropathy with a variable disease course. An immune-mediated origin has been suggested based on in vitro immunohistochemical studies.

Asymmetrical cortical surface area decrease in epilepsy patients with postictal generalized electroencephalography suppression.

Postictal generalized electroencephalographic suppression is a possible electroencephalographic marker for sudden unexpected death in epilepsy. We aimed to investigate the cortical surface area abnormalities in epilepsy patients with postictal generalized electroencephalographic suppression. We retrospectively included 30 epilepsy patients with postictal generalized electroencephalographic suppression (PGES+), 21 epilepsy patients without postictal generalized electroencephalographic suppression (PGES-), and 30 healthy controls. Surface-based analysis on high-resolution T1-weighted images was conducted and cortical surface areas were compared among the three groups, alongside correlation analyses with seizure-related clinical variables. Compared with PGES- group, we identified reduced surface area in the bilateral insula with more extensive distribution in the right hemisphere in PGES+ group. The reduced right insular surface area was associated with younger seizure-onset age. When compared with healthy controls, PGES- group presented reduced surface area in the left caudal middle frontal gyrus; PGES+ group presented more widespread surface area reductions in the right posterior cingulate gyrus, left postcentral gyrus, middle frontal gyrus, and middle temporal gyrus. Our results suggested cortical microstructural impairment in patients with postictal generalized electroencephalographic suppression. The significant surface area reductions in the insular cortex supported the autonomic network involvement in the pathology of postictal generalized electroencephalographic suppression, and its right-sided predominance suggested the potential shared abnormal brain network for postictal generalized electroencephalographic suppression and sudden unexpected death in epilepsy.

High-voltage electrocution myelopathy: A case report and review of the literature

Abstract High-voltage electrocution-induced neurological complications are often associated with dire consequences. The low-resistance neural pathway provides an easy gateway for the current propagation and subsequent injuries. We present a case of electrocution-induced high-cervical myelopathy resulting in quadriparesis with sensorimotor and autonomic involvement with a slow recovery course along with the subsequent imaging and electrophysiological finding suggestive of long-term degeneration of the central corticospinal tracts. On review of prior works of literature, few similar cases are seen with varied postulations of the pathophysiology of the injury. More frequent reporting of such cases, which often go undetected, should be done to increase awareness.

Characterizing systemic physiological effects on the blood oxygen level dependent signal of resting-state fMRI in time-frequency space using wavelets.

Systemic physiological dynamics, such as heart rate variability (HRV) and respiration volume per time (RVT), are known to account for significant variance in the blood oxygen level dependent (BOLD) signal of resting-state functional magnetic resonance imaging (rsfMRI). However, synchrony between these cardiorespiratory changes and the BOLD signal could be due to neuronal (i.e., autonomic activity inducing changes in heart rate and respiration) or vascular (i.e., cardiorespiratory activity facilitating hemodynamic changes and thus the BOLD signal) effects and the contributions of these effects may differ spatially, temporally, and spectrally. In this study, we characterize these brain-body dynamics using a wavelet analysis in rapidly sampled rsfMRI data with simultaneous pulse oximetry and respiratory monitoring of the Human Connectome Project. Our time-frequency analysis across resting-state networks (RSNs) revealed differences in the coherence of the BOLD signal and heartbeat interval (HBI)/RVT dynamics across frequencies, with unique profiles per network. Somatomotor (SMN), visual (VN), and salience (VAN) networks demonstrated the greatest synchrony with both systemic physiological signals when compared to other networks; however, significant coherence was observed in all RSNs regardless of direct autonomic involvement. Our phase analysis revealed distinct frequency profiles of percentage of time with significant coherence between BOLD and systemic physiological signals for different phase offsets across RSNs, suggesting that the phase offset and temporal order of signals varies by frequency. Lastly, our analysis of temporal variability of coherence provides insight on potential influence of autonomic state on brain-body communication. Overall, the novel wavelet analysis enables an efficient characterization of the dynamic relationship between cardiorespiratory activity and the BOLD signal in spatial, temporal, and spectral dimensions to inform our understanding of autonomic states and improve our interpretation of the BOLD signal.

Dysautonomia in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, characterized in its typical presentation by a combination of lower and upper motor neuron symptoms, with a progressive course and fatal outcome. Due to increased recognition of the non-motor symptoms, it is currently considered a multisystem disorder with great heterogeneity, regarding genetical, clinical, and neuropathological features. Often underestimated, autonomic signs and symptoms have been described in patients with ALS, and various method analyses have been used to assess autonomic nervous system involvement. The aim of this paper is to offer a narrative literature review on autonomic disturbances in ALS, based on the scarce data available to date.

Postprandial hypotension as a predictor of respiratory failure in patients with foodborne botulinum intoxication – a case-control study in outbreak investigation

ObjectivesBotulism is a rare syndrome characterized by acute, flaccid paralysis with possible involvement of respiratory muscle-producing pump failure requiring mechanical ventilation. A predominance of autonomic involvement can occur. MethodsWe enrolled patients affected by foodborne botulism during an outbreak. All patients underwent the detection of the toxin in stool specimens, and 24-hour ambulatory blood pressure monitoring (ABPM). A blinded expert operator analyzed ABPM data for the diagnosis of hypertension and postprandial hypotension (PPH). ResultsTwenty male patients met the inclusion and exclusion criteria. Thirty-four healthy subjects matched for sex and age were enrolled as a control group. PPH was significantly more frequent in the botulin group than in healthy subjects (40% vs 2.9%, P <0.0001). At the logistic regression, the probability that patients affected by botulinum could require ventilation was increased by 733% (adjusted odds ratio: 8.33) when PPH is encountered. ConclusionsThe likelihood of resorting to ventilation in subjects with botulinum intoxication was seven times greater in patients presenting PPH. These results could allow the prompt identification of patients at high risk for requiring ventilation.

Algorithm for multimodal medication therapy in patients with complex regional pain syndrome.

Complex regional pain syndrome (CRPS), previously known as reflex sympathetic dystrophy and causalgia, is a clinical entity characterized by classic neuropathic pain, autonomic involvement, motor symptoms, and trophic changes in the skin, nails, and hair. Although various therapeutic modalities are used to control CRPS-related pain, severe pain due to CRPS often persists and progresses to the chronic phase. In this study, we constructed an algorithm for multimodal medication therapy for CRPS based on the established pathology of CRPS. Oral steroid pulse therapy is recommended for initial pain management in patients with CRPS. Oral steroid therapy can reduce peripheral and central neuroinflammation, contributing to the development of neuropathic pain during the acute and chronic phases. If steroid pulse therapy offers poor relief or is ineffective, treatment to control central sensitization in the chronic phase should be initiated. If pain persists despite all drug adjustments, ketamine with midazolam 2 mg before and after ketamine injection can be administered intravenously to inhibit the N-methyl D-aspartate receptor. If this treatment fails to achieve sufficient efficacy, intravenous lidocaine can be administered for 2 weeks. We hope that our proposed drug treatment algorithm to control CRPS pain will help clinicians appropriately treat patients with CRPS. Further clinical studies assessing patients with CRPS are warranted to establish this treatment algorithm in clinical practice.

Specific structuro‐metabolic pattern of thalamic subnuclei in fatal familial insomnia: A PET/MRI imaging study

AbstractBackgroundDysfunction of the thalamus has been proposed as a core mechanism of fatal familial insomnia. However, detailed metabolic and structural alterations in thalamic subnuclei are not well documented. We aimed to address the multimodal structuro‐metabolic pattern at the level of the thalamic nuclei in fatal familial insomnia patients, and investigated the clinical presentation of primary thalamic alterations.MethodFive fatal familial insomnia patients and 10 healthy controls were enrolled in this study. All participants underwent neuropsychological assessments, polysomnography, electroencephalogram, and cerebrospinal fluid tests. MRI and fluorodeoxyglucose PET were acquired on a hybrid PET/MRI system. Structural and metabolic changes were compared using voxel‐based morphometry analyses and standardized uptake value ratio analyses, focusing on thalamic subnuclei region of interest analyses. Correlation analysis was conducted between gray matter volume and metabolic decrease ratios, and clinical features.ResultThe whole‐brain analysis showed that gray matter volume decline was confined to the bilateral thalamus and right middle temporal pole in fatal familial insomnia patients, whereas hypometabolism was observed in the bilateral thalamus, basal ganglia, and widespread cortices, mainly in the forebrain. In the regions of interest analysis, gray matter volume and metabolism decreases were prominent in bilateral medial dorsal nuclei, anterior nuclei, and the pulvinar, which is consistent with neuropathological and clinical findings. A positive correlation was found between gray matter volume and metabolic decrease ratios.ConclusionOur study revealed specific structuro‐metabolic pattern of fatal familial insomnia that demonstrated the essential roles of medial dorsal nuclei, anterior nuclei, and pulvinar, which may be a potential biomarker in diagnosis. Also, primary thalamic subnuclei alterations may be correlated with insomnia, neuropsychiatric, and autonomic symptoms sparing primary cortical involvement.

Pattern of Autonomic Involvement in Adult Patients with Guillain Barre Syndrome in a Tertiary Hospital

Background: Guillain Barre Syndrome (GBS) is an acute post infectious immune mediated peripheral neuropathy with a marked variation in pathology, clinical presentation and prognosis. Autonomic dysfunction is one of the important manifestations of GBS which may lead to significant morbidity and mortality. Objective: The aim of the study is to assess the autonomic involvement, to determine its frequency and pattern of involvement in adult patients with GBS Methods: An observational, descriptive, cross sectional study was carried out in the Department of Neurology, BSMMU, Dhaka from March, 2015 to September, 2017. Total 43 patients of GBS and 35 apparently healthy controls were recruited as the study population. On the basis of nerve conduction study patients were classified into different groups: acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN) and acute motor sensory axonal neuropathy (AMSAN) and other variants. Disability status at the time of autonomic testing was measured by Hughes functional grading scale. The following tests of autonomic nervous system were performed in both patients and controls 1) resting heart rate and heart rate on changing posture (30: 15 ratio) 2) supine blood pressure and blood pressure on changing posture 3) heart rate response to valsalva maneuver 4) heart rate response to deep breathing and E: I ratio 5) sphincter disturbance by symptoms questionnaire. Results: The mean age of patients was 35±12 years (range18 to 65 years) and 58.1% were male. Around 88.4 % of patients showed some sort of autonomic dysfunction. Variation of heart rate by different maneuver like posture change, deep breathing and valsalva maneuver was found commonly. Among them 30:15 ratio was abnormal in majority of the patients (82.4%) followed by abnormal max-min HR/min (58.1%) and abnormal valsalva ratio (37.2%). Other abnormalities were postural hypotension (38.2%), sinus tachycardia (25.6%), hypertension (16.3%), hypotension (2.7%), sinus arrhythmia (4.7%), constipation (30%), urinary retention (7%) and urinary incontinence (4.7%). Conclusion: In this study different patterns of autonomic dysfunction was found in 88.4% of patients with GBS involving both sympathetic and parasympathetic components. The present study found no significant association between autonomic dysfunction and motor disability scores. Thus autonomic function assessment is essential in every patient with GBS in addition to motor &amp; sensory function. Bangladesh Medical Res Counc Bull 2022; 48(3): 174-179

A Case of Mononeuopathy Multiplex in the Setting of Durvalumab Therapy (P13-8.002)

<h3>Objective:</h3> NA <h3>Background:</h3> As immune checkpoint inhibitors (ICIs) become a mainstay of treatment for several malignancies, neurological complications associated with their use have been increasingly recognized. We present a case of mononeuropathy multiplex (MM) in the setting of durvalumab (PD-L1 inhibitor) use. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 68-year-old man with stage III non-small cell lung cancer (NSCLC) was seen for the evaluation of asymmetric, painful bilateral upper extremity weakness of 2 months’ duration. He had pre-existing painless glove-and-stocking sensory loss, attributed to cisplatin-induced peripheral neuropathy. Following 4 cycles of cisplatin-based chemotherapy, the patient was started on durvalumab 4 months prior to presentation. Key exam findings included weakness affecting right digit I flexion, wrist and finger extension as well as left interphalangeal joint flexion affecting digits II–V, glove-and-stocking sensory loss, and diffuse areflexia. Upper extremity EMG findings were notable for active denervation changes restricted to multiple bilateral radial- and median-innervated muscles. Following initial assessment, the right wrist drop continued to progress, and a decision was taken to discontinue durvalumab given the concern for peripheral neurotoxicity. The left arm weakness resolved over 3–4 weeks, while the right wrist drop had improved only partially at last assessment 5 months later. The patient had declined a trial of steroids or IVIG. <h3>Conclusions:</h3> The clinical and EMG findings were consistent with MM and bore a temporal relation to durvalumab use. No alternate etiology was identified. ICI-mediated toxicity can result in sensory, motor and autonomic peripheral nerve involvement with a myriad of clinical presentations. In the existing literature, MM has been described with both ipilimumab and nivolumab, but to our knowledge, this is the first reported case of MM with durvalumab use. Early identification of often severe neurological adverse events is crucial due to implications for treatment and decisions regarding continued immune checkpoint therapy. <b>Disclosure:</b> Miss Scurfield has nothing to disclose. Miss Kelly has nothing to disclose. Dr. Desai has nothing to disclose. Dr. Dhanjal has nothing to disclose.

Amyloidosis: a case series and review of the literature

BackgroundSystemic amyloidosis is group of disorders characterized by the accumulation of insoluble proteins in tissues. The most common form of systemic amyloidosis is light chain amyloidosis, which results from the accumulation of misfolded immunoglobulins. The disease is progressive, with treatment targeted at the underlying plasma cell dyscrasia. Since essentially any organ system can be affected, the presentation is variable and delays in diagnosis are common. Given this diagnostic difficulty, we discuss four different manifestations of light chain amyloidosis.Case presentationsIn this case series, we discuss four cases of light chain amyloidosis. These include cardiac, hepatic, and gastrointestinal as well as autonomic and peripheral nerve involvement with amyloidosis. The patients in our series are of Caucasian background and include a 69-year-old female, a 29-year-old female, a 68-year-old male, and a 70-year-old male, respectively. The case discussions highlight variability in presentation and diagnostic challenges.ConclusionsAmyloidosis is a rare but serious disease that is often complicated by long delays in diagnosis. Morbidity and mortality can sometimes be limited if diagnosed earlier. We hope our real life cases will contribute to understanding and to early suspicion that can lead to early diagnosis and management.

Autonomic nervous system involvement in chronic inflammatory demyelinating polyradiculoneuropathy: a literature review.

Although dysautonomia is a well-recognized complication of acute demyelinating polyradiculoneuropathy, it is rarely reported and evaluated in chronic demyelinating neuropathies. The purpose of this review is to search and synthesize the current literature on the prevalence and type of autonomic dysfunction (AD) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). PubMed and Web of Science were searched for studies reporting AD in CIDP. Twelve studies, including 346 patients with CIDP, were found eligible for the review. Seven studies used autonomic tests only as an additional component of the comprehensive clinical evaluation, and found that dysautonomia in CIDP may indicate the presence of a comorbid disease (e.g., diabetes) and facilitate the differentiation of CIDP from other neuropathies (e.g., amyloid neuropathy). Five studies performed quantitative assessment of autonomic function in CIDP as a primary goal. Two studies have used the Composite Autonomic Severity Score (CASS) to assess severity and distribution of dysautonomia. The reported prevalence of dysautonomia in CIDP during quantitative assessment of autonomic function ranged from 25 to 89%, depending on the battery of tests used, with CASS not exceeding 4 points. The abnormalities in autonomic tests indicated both sympathetic and parasympathetic dysfunction and did not correlate with the duration, severity and variant of CIDP. Clinical or subclinical involvement of the ANS has been shown to be common and relatively mild in CIDP. The impact of autonomic impairment on disability and of its possible response to therapy in CIDP needs to be further investigated.