Severe Polyneuropathy Research Articles

AN OVERLAP OF GUILLAIN-BARRÉ SYNDROME, MILLER-FISHER SYNDROME, AND BICKERSTAFF BRAINSTEM ENCEPHALITIS PRESENTING AS CLINICAL BRAIN DEATH, A CASE SERIES

Guillain-Barré Syndrome (GBS), Miller-Fisher Syndrome (MFS), and Bickerstaff Brainstem Encephalitis (BBE) are neuroinflammatory disorders that share common immunopathogenic mechanisms. Although overlapping presentations of these conditions are rare, they pose significant diagnostic challenges, especially when mimicking clinical brain death. Objective: To present a case series of three patients who demonstrated an overlap of GBS, MFS, and BBE, with all patients exhibiting profound neurological impairments, including clinical signs of brain death. Methods: A retrospective review of three cases admitted to the ICU over the last three years was conducted. Detailed clinical profiles, cerebrospinal fluid (CSF) analysis, nerve conduction studies (NCS), and electromyography (EMG) results were reviewed. All patients were treated with intravenous immunoglobulins (IVIG) and therapeutic plasma exchange (TPE). Results: All three patients had a history of preceding infections and were presented with ophthalmoplegia, ataxia, and altered levels of consciousness, progressing to coma. CSF analysis revealed albuminocytological dissociation, and NCS/EMG indicated severe polyneuropathy. Two patients responded positively to IVIG and plasmapheresis, showing significant neurological recovery, while the third patient demonstrated a delayed but spontaneous recovery. All patients eventually achieved full or near-full neurological recovery. Conclusions: This case series highlights the clinical continuum and diagnostic complexity of overlapping GBS, MFS, and BBE, particularly in presentations mimicking brain death. Early recognition and prompt immunomodulatory therapy are crucial in improving patient outcomes, even in cases with severe neurological deficits. Further research is warranted to elucidate pathophysiology and optimize treatment strategies for overlapping neuroinflammatory syndromes.

"Voriconazole-Associated Motor Neuropathy In Acute Myeloid Leukemia: A Case Report And Literature Review"

Introduction: Voriconazole, a commonly used antifungal in immunocompromised patients is effective against various fungal pathogens. Despite its efficacy, it is associated with numerous adverse effects, including the less frequently documented motor neuropathy. Case Presentation: We report a case of a 60-year-old male with acute myeloid leukemia (AML) who developed motor neuropathy following voriconazole administration. Initially treated with standard chemotherapy and prophylactic antifungals, he developed febrile neutropenia and was subsequently administered voriconazole. Within a week, he presented with bilateral foot drop. The neurological assessment revealed severe motor weakness without sensory loss. MRI indicated lumbar disc protrusion and nerve conduction studies confirmed severe demyelinating polyneuropathy. Upon cessation of voriconazole, the patient's symptoms completely resolved, as confirmed by follow-up electromyography. Discussion: Voriconazole-associated neuropathy, though rare, can present as motor neuropathy, contrary to the more commonly reported sensory neuropathy. The exact mechanism remains unclear, and while symptoms often resolve after discontinuation, some cases may result in permanent damage. Conclusion: This case highlights the importance of recognizing voriconazole-induced motor neuropathy in AML patients. Early identification and discontinuation of the drug are crucial for symptom resolution. Further research is needed to understand the underlying mechanisms and to develop preventive and management strategies.

Low serum CTRP3 is related to more severe distal symmetric polyneuropathy in type 2 diabetes patients.

Distal symmetric polyneuropathy (DSPN) is one of the most common chronic complications in patients with type 2 diabetes mellitus (T2DM). Our previous study found that serum C1q tumor necrosis factor-related protein 3 (CTRP3) levels were decreased in type 2 diabetic patients. Thus, this study was designed to reveal the relationship between low serum CTRP3 and the prevalence and severity of DSPN. A total of 178 cases of patients with T2DM were enrolled in the study. The subjects were divided into the DSPN group (n = 89) and the non-DSPN group (n = 89). Both anthropometric parameters and neurologic symptoms were recorded. Furthermore, neurologic signs, the neuropathy symptom score (NSS), and the neuropathy disability score (NDS) were assessed. Biochemical indexes, fasting insulin, and C peptide were measured. Serum CTRP3 concentrations were assayed using the ELISA method. Serum CTRP3 levels decreased significantly in the DSPN group compared with the non-DSPN group (P < 0.05). CTRP3 was negatively associated with the number of positive signs, NSS score, and NDS score in patients with DSPN (all P < 0.05). Interestingly, the higher the NSS score or NDS score, the lower were the levels of serum CTRP3 (all P < 0.05). Moreover, patients with lower CTRP3 levels (< 7.58ng/ml) had a higher rate of neurologic signs (all P < 0.05). Binary logistic regression analysis showed that CTRP3 independently predicted the occurrence of DSPN (β = -0.316, P < 0.001). ROC curve analysis revealed that the best cut-off value of CTRP3 for the prediction of DSPN was 7.55ng/ml (sensitivity 78.7%, specificity 79.8%), the area under the curve (AUC) was 0.763 (95% CI 0.689-0.838, P < 0.001). Low serum CTRP3 could be a predictor for the occurrence and progression of DSPN in Chinese patients with T2DM.

A Rare Case of Castleman Variant of POEMS Syndrome

Abstract POEMS syndrome is a rare multisystemic disease, characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. The presence of polyneuropathy and monoclonal plasma cell proliferation is mandatory for the diagnosis of typical POEMS syndrome. However, some patients lack one of the mandatory features and are classified as the variants of POEMS syndrome. A 61-year-old male presented with the clinical picture of progressive numbness in both lower extremities and weakness in all four extremities for a 6-month duration associated with bilateral axillary lymphadenopathies, pedal edema, clubbing, and unintentional weight loss of 15 kg in 6 months. A nerve conduction study showed severe sensorimotor polyneuropathy of demyelinating type in all four extremities. A lymph node biopsy showed Castleman disease, and the computed tomography scan was suggestive of multiple osteosclerotic lesions. A diagnosis of the Castleman variant of POEMS syndrome was made, and the patient was treated with Bortezomib-based therapy with improvement in his symptoms on follow-up at 1 year. Due to the lack of definite treatment guidelines for this disease, the information provided through case reports and case series becomes very important for the treatment of such patients leading to the resolution of polyneuropathy and the maintenance of functionality in patients.

Эффективность и токсичность индукционной терапии у пациентов с впервые диагностированным системным AL-амилоидозом: результаты проспективного одноцентрового клинического исследования

Aim. To assess the outcomes of induction therapy in patients with newly diagnosed systemic AL Amyloidosis (AL-А).&#x0D; Materials &amp; Methods. The prospective single-center clinical study enrolled 60 patients (32 women and 28 men) with newly diagnosed systemic AL-A stage I/IIIA. The median age was 59 years (range 34–74 years). In 57 patients, BorСyDex (bortezomib, cyclophosphamide, dexamethasone) was used as first-line therapy. RCd regimen (lenalidomide, cyclophosphamide, dexamethasone) was administered to 3 patients. Patients with the lack of efficacy or pronounced toxicity (n = 24) received second-line induction therapy with lenalidomide or melphalan combined with dexamethasone. High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) was administered to 11 (18 %) patients.&#x0D; Results. Hematologic targeted response (complete remission [CR] and very good partial remission [VGPR]) to BorCyDex was achieved in 62 % of patients. As a result of all lines of induction therapy, including auto-HSCT, targeted response increased to 69 %, specifically in 7/51 (14 %) patients with stringent CR (sCR), 8/51 (16 %) patients with CR, and 20/51 (39 %) patients with VGPR. Renal response after BorCyDex was registered in 10/38 (26 %) patients, 6/31 (19 %) patients showed heart response, and in 4/5 (80 %) patients liver response was reported. All therapy lines with auto-HSCT led to organ response (in ≥ 1 organ) in 15/46 (32 %) patients. Clinical response was shown by all patients with achieved sCR, by 67 % of patients with CR, and 47 % with VGPR (p = 0.04). With lower hematologic response rates, no clinical improvement was observed. With follow-up duration of 36 months, the median disease-free survival (without signs of hematologic and clinical progression) was not achieved. The 3-year overall survival was 80 %. Mortality during induction therapy was 10 % (6 patients died, including 2 patients with COVID-19). The planned 6 courses of BorCyDex could be completed only in 13 (23 %) out of 55 patients. During the induction therapy using BorCyDex, 4 patients died. The treatment was discontinued in 7/55 (12 %) patients due to its inefficacy and in 22/55 (39 %) patients because of severe peripheral and autonomic polyneuropathy. Nine (16 %) out of 55 patients with the achieved hematologic response showed excessive NT-proBNP elevation, which was accompanied by cardiovascular complications and provided ground for chemotherapy withdrawal.&#x0D; Conclusion. Low organ recovery rate remains the most challenging issue for AL-A treatment. Hematologic response depth (achieved CR) is a critical factor in achieving clinical effect. The obtained data confirmed high toxicity of BorCyDex regimen in AL-A patients. Despite the advances in AL-А therapy which are associated with the use of proteasome inhibitors, treatment of this disease calls for new and more effective approaches.

Intrathecal Methotrexate-Induced Lumbosacral Polyradiculopathy: A Case Report

BACKGROUND: Polyradiculopathy caused by intrathecal methotrexate (IT MTX) is a rare and serious complication of chemotherapy. The pathophysiology involved is likely due to a drug-induced folate deficiency and subsequent local immune reaction in the spinal cord. CASE REPORT: The authors present a 68-year-old woman with stage I breast cancer and stage III diffuse large B-cell lymphoma who developed low back pain after IT MTX treatment. Further workup revealed diffuse rope-like thickening of the cauda equina nerve roots with subtle linear low-level leptomeningeal enhancement on magnetic resonance imaging and severe primary axonal and motor polyneuropathy affecting the upper and lower extremities on electromyography/nerve conduction studies, likely a result of IT MTX toxicity. Treatment should emphasize conservative measures. Alternatively, intravenous immunoglobulin followed by intravenous methylprednisolone can be considered. CONCLUSIONS: Polyradiculopathy caused by IT MTX is a rare finding that can be treated. It would be beneficial to further study the effects of IT MTX and create treatment protocols for its adverse effects. KEY WORDS: Intrathecal methotrexate, polyradiculopathy, cauda equina, cancer, case report

Electrophysiological grading scale for polyneuropathy severity.

To establish a simple electrophysiological scale for patients with distal symmetric axonal polyneuropathy, in order to promote standardized and informative electrodiagnostic reporting, and understand the complex relationship between electrophysiological and clinical polyneuropathy severity. We included 76 patients with distal symmetric axonal polyneuropathy, from a cohort of 151 patients with polyneuropathy prospectively recruited from November 2016 to May 2017. Patients underwent nerve conduction studies (NCS), were evaluated by the Toronto Clinical Neuropathy Score (TCNS), and additional tests. The number of abnormal NCS parameters was determined, within the range of 0-4, considering low amplitude or conduction velocity in the sural and peroneal nerve. Higher number of NCS abnormalities was associated with higher TCNS, indicating more severe polyneuropathy. Polyneuropathy severity per the TCNS was most frequently (63%-70%) mild in patients with a low (0-1) number of NCS abnormalities, and most frequently (57%-67%) severe in patients with a high number (3-4) of NCS abnormalities, while patients with an intermediate (2) number of NCS abnormalities showed mainly mild and moderate severity with equal distribution (40%). A simple NCS classification system can objectively grade polyneuropathy severity, although significant overlap exists especially at the intermediate range, underscoring the importance of clinical based scoring.

СЛОЖНОСТЬ ВЕДЕНИЯ ПАЦИЕНТА С ШЛУ ТУБЕРКУЛЕЗОМ ПРИ ЛЕЧЕНИИ КОРОТКИМ РЕЖИМОМ, ВКЛЮЧАЮЩИМ ЛИНЕЗОЛИД (BPaL)

The article describes a clinical observation illustrating a rational approach to the correction of adverse drug-induced reaction – severe toxic polyneuropathy in a patient with extensively-drug resistant (XDR) infiltrative pulmonary TB with cavities and dissemination – during administration of a new 24-week chemotherapy regimen containing bedaquiline (Bq), pretomanid (Pa) and linezolid (Lzd) (BPaL).

Organophosphate-induced delayed neuropathy: A rare case presentation

Abstract: Organophosphate-induced delayed neuropathy (OPIDN) is a rare clinical condition. It occurs in association with ingestion of large amount of organophosphorus compound. The clinical picture is characterized by transient paraesthesia, tingling, and numbness usually confined to the distal parts of the limbs, describes as gloves and stockings pattern of sensory impairment, followed by symmetrical motor weakness, which is flaccid type, starts distally in the lower limbs first then ascends to involve upper limbs. The sensory and motor disturbances are usually mild and seen distally, but in more severe cases, it also effects proximal groups of muscles. Electrodiagnostic studies show a motor axonal neuropathy. Our case a 36-year-old female patient, who developed paraesthesia and weakness in all four limbs, 20 days after she had ingested a large amount of 50% chlorpyrifos. The electrophysiological Electromyography (EMG), Nerve conduction study (NCS), Evoked potential (EP) study was characterized by severe motor axonal polyneuropathy effecting both upper and lower limbs, considering the peripheral nerve involvement due to OP poisoning after a delay, so it can be named as OPIDN.

Morphofunctional characterisation of axonal damage in different rat models of chemotherapy-induced peripheral neurotoxicity: The role of nerve excitability testing.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common and long-lasting adverse event of several anticancer compounds, for which treatment has not yet been developed. To fill this gap, preclinical studies are warranted, exploiting highly translational outcome measure(s) to transfer data from bench to bedside. Nerve excitability testing (NET) enables to test in vivo axonal properties and can be used to monitor early changes leading to axonal damage. We tested NET use in two different CIPN rat models: oxaliplatin (OHP) and paclitaxel (PTX). Animals (female) were chronically treated with either PTX or OHP and compared to respective control animals. NET was performed as soon as the first injection was administered. At the end of the treatment, CIPN onset was verified via a multimodal and robust approach: nerve conduction studies, nerve morphometry, behavioural tests and intraepidermal nerve fibre density. NET showed the typical pattern of axonal hyperexcitability in the 72 h following the first OHP administration, whereas it showed precocious signs of axonal damage in PTX animals. At the end of the month of treatment, OHP animals showed a pattern compatible with a mild axonal sensory polyneuropathy. Instead, PTX cohort was characterised by a rather severe sensory axonal polyneuropathy with minor signs of motor involvement. NET after the first administration demonstrated the ongoing OHP-related channelopathy, whereas in PTX cohort it showed precocious signs of axonal damage. Therefore, NET could be suggested as an early surrogate marker in clinical trials, to detect precocious changes leading to axonal damage.

Severe axonal motor neuropathy after heat stroke

A 22-year-old healthy man experienced heat stroke while hiking and collapsed, resulting in multiorgan failure, cerebral edema, and prolonged intensive care unit stay. He developed flaccid tetraplegia, facial weakness, and dysphagia, and was diagnosed with severe axonal sensorimotor polyneuropathy. Rehabilitation improved dysphagia, but he remained dependent on daily activities and required assistance for transfers. The prognosis of critical illness polyneuropathy is typically good in young, healthy individuals. Peripheral neuropathy is a rare complication of heat stroke due to hyperthermia-induced neuronal injury. As global temperatures continue to rise, it is essential to recognize the potential impact of climate change on the incidence of heat stroke and to implement public health interventions to mitigate its effects.

The effect of polyneuropathy severity on nerve conduction and pain syndrome in patients with type 2 diabetes

Background. The article examines the relationship between nerve conduction indicators and polyneuropathy severity in patients with type 2 diabetes. The influence of polyneuropathy severity on nerve conduction was studied, as well as the effect of insulin therapy on these indicators. Objective: to determine the influence of polyneuropathy severity and the need for additional insulin administration in patients with type 2 diabetes on nerve conduction indicators and the development of pain syndrome. Materials and methods. Eighty patients with type 2 diabetes were examined, 49 men and 31 women. All of them underwent general clinical and biochemical laboratory tests to evaluate the hematopoietic system, li-ver, kidneys, fat and carbohydrate metabolism. The need for insulin therapy was assessed by the C-peptide level. To verify the diagnosis of diabetic polyneuropathy, complaints, clinical and instrumental examination data were evaluated. The main indicators of nerve conduction were taken into account when determining polyneuritis disorders, namely: рeroneal motor nerve conduction velocity, sensory nerve action potential of the sural nerve, sensory nerve conduction velocity of the sural nerve. Results. A dependence of nerve conduction on polyneuropathy severity was revealed, рeroneal motor nerve conduction velocity was the lowest in the group with severe polyneuropathy. A correlation was also found between the levels of sensory indicators (sensory nerve action potential and sensory nerve conduction velocity) and polyneuropathy severity, nerve conduction velocity decreases with an increase in the latter. The influence of polyneuropathy severity on the painful or painless form has been found. Among patients with severe polyneuropathy, the painful form was observed more often. No relationship was found between the need for insulin therapy and the painful or painless form of polyneuropathy. Conclusions. Indicators of nerve conduction depend on polyneuropathy severity. The presence and severity of pain syndrome directly depends on polyneuropathy severity. The need for additional insulin administration affects sensory indicators but has no effect on the development of the painful form of polyneuropathy.

Abstract 17642: Takotsubo Cardiomyopathy After Guillian Barre Syndrome

Introduction: Guillian Barre Syndrome (GBS) has the potential to cause acute and long-term cardiac effects. Takotsubo Cardiomyopathy(TCM) is a life-threatening manifestation of dysautonomia in patients with GBS, although infrequently reported in the literature. We present a case of TCM in the setting of GBS. Case Presentation: A 54-year-old woman with no past history presented with progressive ascending bilateral lower limb weakness, numbness and paraesthesia following a recent chest infection. On exam, she had reduced motor power and absent deep tendon reflexes. MRI brain was normal. CSF analysis revealed albuminocytologic dissociation(1a). Nerve Conduction Studies(NCS) showed severe sensorimotor polyneuropathy with demyelinating features suggestive of GBS. She was treated with plasmapheresis. The next day, she developed respiratory failure and was hemodynamically unstable with persistent tachycardia and labile blood pressure. ECG showed sinus tachycardia with ST-segment depression(1b). Chest CT was normal. Echocardiogram showed moderate anterolateral hypokinesia with an ejection fraction(EF) of 30%. Coronary angiography showed no significant arterial stenosis, suggesting TCM with a diagnostic TCM score of 59 (1c,1d). She received steroids, furosemide and norepinephrine. Repeat ECG and echocardiogram on day 11 were normal with improved EF (52%).This was followed by a Cardiac MRI which was normal (1e). Discussion: The precise etiology of TCM in GBS is unknown and is believed to be related to a complex interplay of autonomic dysfunction, catecholamine release and inflammation. Although rare, TCM is a fatal complication of GBS, warranting urgent evaluation and management. Sudden onset hemodynamic instability and new onset ECG changes may raise the suspicion of TCM in GBS and must be ruled out. Early diagnosis and treatment can improve the patient’s prognosis.

OA18 Small vessel and large vessel vasculitis due to rheumatoid vasculitis: a case of mononeuritis multiplex with pulseless foot leading to amputation

Abstract Introduction Rheumatoid vasculitis occurs in patients with longstanding severe seropositive rheumatoid arthritis. The incidence has reduced drastically with availability of more effective medication. Rheumatoid vasculitis primarily affects small and medium vessels, and rarely large vessels as well. Case description This 77-year-old lady with deforming seropositive rheumatoid arthritis was stable on methotrexate under the care of multiple Trusts for the last 30 years. Methotrexate had been stopped a year ago due to pancytopenia and she was started on prednisolone and hydroxychloroquine. While on these medications she flared with arthralgia and had difficulty in walking attributed to ankle synovitis. She was started on adalimumab, after 3 doses of which she developed widespread skin psoriasis leading to discontinuation. Subsequently, she was admitted to our Trust with left foot gangrene and was referred to rheumatology. Further questioning revealed that numbness in both lower limbs, inability to walk and frequent falls had started following the cessation of methotrexate. On examination, there was bilateral foot drop, worse on the right side. The left foot was gangrenous with diminished pulses in dorsalis pedis and posterior tibial arteries with preserved all other pulses. There was no vasculitic rash or nail fold infarcts. Psoriatic rash had resolved and there was no active synovitis in the joints. Nerve conduction test revealed severe ongoing axonal degenerative type sensory and motor polyneuropathy in the lower limbs without any upper limb involvement. CT angiogram showed multifocal stenoses, more so in the left common iliac, external iliac and superficial femoral artery. There were no conventional vascular risk factors such as hypertension, diabetes, dyslipidaemia or smoking, and there was no past history of cardiovascular disease. PET-CT scan did not reveal any features of vasculitis or aortitis. The vasculitis screening was negative including cryoglobulins. Initially she was on IV antibiotics for left foot cellulitis, hence she was managed with steroids without any potent immunosuppressive agents. Subsequently, she underwent left sided below knee amputation. After the wound had healed, she was started on IV rituximab with low-dose methotrexate and steroid taper. Discussion Although rare, rheumatoid vasculitis can cause significant morbidity and complications. Rheumatoid vasculitis tends to occur in patients with so-called ‘burnt-out’ RA and strongly associated with seropositivity. While it can affect many organ systems, skin and the peripheral nervous system are most frequently affected. Cutaneous vasculitis occurs in around 90% of patients and is the most common clinical manifestation. This includes parable purpura, leg ulcers and nailfold infarcts. It may lead to digital ischaemia, necrosis and gangrene if large vessels are involved. Another common manifestation is a vasculitic neuropathy due to involvement of the vaso nervorum. Around 40% have a sensory neuropathy and 20% have a mixed sensory motor neuropathy like the index patient. Ocular manifestations such as scleritis have been described and may be the first indication of rheumatoid vasculitis. Aortitis in rheumatoid vasculitis may present with aortic insufficiency and aneurysm formation. Pericarditis has also been described as a possible disease manifestation in patients with rheumatoid vasculitis. Our patient did not have any of these clinical features and the PET-CT scan was unremarkable, which could have been due to the steroids she was on prior to the scan. Clinically, there was pulseless gangrene of the left foot with CT angiogram showing multiple stenosis suggesting large vessel involvement in the absence of conventional vascular risk factors. Renal involvement in rheumatoid vasculitis is very rare. PAN like renal involvement and glomerulonephritis has been described. Our patient did not have any haematuria or any significant proteinuria, and imaging did not reveal any renovascular aneurysms. Isolated nailfold infarcts do not require any systemic treatment. Systemic involvement with rheumatoid vasculitis requires aggressive treatment with high-dose steroids with cyclophosphamide or rituximab. Our patient had neuropathy and gangrene of the left foot, hence she was started on rituximab accordingly. Key learning points Rheumatoid vasculitis is a rare but serious complication which can present with a vasculitic neuropathy/mononeuritis multiplex. Rarely, it can cause ischemia and gangrene. If there is systemic involvement, aggressive therapy with steroids, cyclophosphamide or rituximab is needed.

Cytomegalovirus-related Guillain-Barre syndrome in an adult liver transplant recipient: a case report

Guillain-Barré syndrome (GBS) is an immune-mediated condition affecting both the motor and sensory spinal roots and peripheric nerves. GBS is a rare entity, with its global incidence being as low as 0.81 to 1.89 cases per 100.000 person-year. Despite its low incidence, GBS have an important morbidity and lethal potential. This syndrome is usually triggered by infections. Due to its clinical presentation heterogeneity and its disease natural history, there is scarse availability of international clinical practice guidelines for the management of this entity. In this report, we present the case of a 67 years-old man on his fifth month after liver transplant (LT), who developed acute non-inflammatory diarrhea followed by sudden ascending symmetric paresia and soles paresthesias. Electrophysiologic studies reported a demyelinating inflammatory polyradiculoneuropathy compatible with GBS, acute severe inflammatory demyelinating polyneuropathy (AIDP) subtype. His neurolo¬gy deficit was associated with a simultaneous primary Cytomegalovirus (CMV) infection, one of the most common GBS-related infectious agents.

#6086 NEUTRAL LIPID STORAGE DISEASE WITH RENAL INVOLVEMENT: A CASE REPORT

Abstract Background and Aims Neutral lipid storage diseases (NLSD) are rare conditions caused by an inborn error of neutral lipid metabolism that results in a deficit in the degradation of cytoplasmic triglycerides and a consequent abnormal storage of the neutral lipids. Their accumulation in cytoplasmic lipid droplets in most tissues of the body results in a very heterogeneous phenotype: myopathic syndrome, intellectual deficit, cataract, neuropathy, cardiomyopathy, hepatomegaly are the main clinical manifestations. Less frequent conditions are diabetes, chronic pancreatitis and renal involvement. Method A 27-year-old woman visited our hospital on November 2022 because of progressive onset of edema, dyspnea, nausea and loss of appetite. The medical history showed that 4 years before she was diagnosed with diabetes mellitus and she has been suffering from severe muscle weakness (she was helping herself with the wheelchair) for two years. In 2017 a proctological evaluation showed an anal hypotonia from likely neuropathy. Blood chemistry tests revealed a metabolic acidosis, a decreased renal function, anaemia and nephrotic range proteinuria at the urinalysis. A bilateral pleural effusion was described at the chest radiograph and a circumferential pericardial effusion at a first echocardiogram. The ultrasound of the abdomen described a small size of the right kidney (90 mm) and an angiomyolipoma on the left kidney. Neurological examination showed a mild intellectual disability, facies with dysmorphic appearance and hypotonia of proximal and distal muscular masses of the upper limbs. Lower limbs showed a more pronounced strength deficit on the left and a hypotonia to proximal muscle masses. Electromyography showed a condition of severe sensitivity polyneuropathy: signs of chronic denervation and morphological alterations of the motor unit especially in the proximal districts of the lower limbs. Ophthalmological examination showed an advanced cataract. Cardiological evaluation through heart echo scanshowed a dilated heart disease with ventricular function and dilation of the pulmonary artery. A quadriceps muscle biopsy finally revealed myogenic features consistent with neutral lipid storage disease. Fabry test came back negative. Despite several drug treatments, the patient continued to be asthenic, inappetent and the oxygen therapy could not be removed because frequent episodes of desaturation. The deterioration of the patient's clinical conditions required the onset of dialysis immediately. Unfortunately, despite adequate information on the risks of possible refusal, the patient denied consent for central venous catheter placement and hence the beginning of renal replacement therapy. Sadly, the patient was lost to follow up and it was not possible to carry out other diagnostic investigations. Results Our patient developed an end-stage renal disease in the framework of a neutral lipid storage disease. Since cytoplasmic lipid droplets are ubiquitous organelles, we can assume that in this case, kidney involvement is due to a pathogenetic mechanism similar to that of other storage diseases such as Fabry disease (Table 1). Conclusion Here we describe a 27-year-old NLSD female patient showing late onset myopathy and difficulties in mobilization in association with severe cardiac and ocular involvement, mild intellectual disability, diabetes mellitus type 2 and end stage renal disease. Our data expand the clinical manifestations of NLSD, providing further evidence for clinical NLSD heterogeneity and mainly, further evidence for storage diseases with renal involvement.

Description of a Rare Compound Heterozygous Transthyretin Mutation Val30Met/Val122Ile Conferring Early Onset Hereditary Amyloidosis with Severe Features (P14-8.009)

<h3>Objective:</h3> To describe a case of hereditary amyloidosis with a rare compound heterozygous mutation that is not described in the literature. <h3>Background:</h3> Hereditary amyloidosis is a rare disease characterized by accumulation of amyloid deposits in tissue, causing end-organ failure. Most common manifestations include cardiomyopathy, nephropathy, and neuropathy. The transthyretin (TTR) is encoded on chromosome 18 and functions to transport thyroxine and retinol through blood and CSF. Mutations in TTR increase the amyloidogenic potential of the protein. TTR is inherited in an autosomal dominant fashion, and thus mutagenic carriers often have a strong family history of the associated diseases. There are over 100 characterized mutations of this gene. The vast majority of genetically proven cases are associated with missense mutations in a single codon. Compound heterozygotes are rarely reported in the literature. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 40-year-old male with history of chronic diarrhea and anemia presents with two years of pedal edema, weight loss, dyspnea on exertion, and progressive limb weakness resulting in multiple falls. On cardiac evaluation he was found to have severe cardiomyopathy with increase LV thickness and evidence of amyloidosis on cardiac MRI. EMG demonstrated a severe sensorimotor polyneuropathy. Exam was notable for absent joint position sense resulting in gait dysfunction necessitating use of a cane. Subsequent endomyocardial biopsy revealed ATTR type amyloid deposition. Genetic evaluation demonstrated two separate pathogenic variants in TTR (Val30Met/Val122Ile). He was started on therapy with tafamidis and later transitioned to patisiran infusions with some symptomatic improvement. Genetic testing of family members was suggested however not yet completed. <h3>Conclusions:</h3> Compound heterozygous mutations in TTR are exceedingly rare, and this report presents a perhaps never before described case of an individual with both Val30Met and Val122Ile mutations resulting in early onset severe hereditary amyloidosis with multisystem involvement. <b>Disclosure:</b> Dr. Nardin has nothing to disclose. Dr. Traub has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. Traub has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. The institution of Dr. Traub has received research support from Alnylam Pharmaceuticals. The institution of Dr. Traub has received research support from Alexion. The institution of Dr. Traub has received research support from Muscular Dystrophy Association (MDA). The institution of Dr. Traub has received research support from Ionis.

Cross-Sectional Study of Assessment of Predominance of Prakrutiamong Patients with Diabetic Neuropathy in Wardha City

India is a developing country, so much of the Indian subcontinent are converting into urban areas, which lead to changes in lifestyle involving major tourist in battery plateau physical activities and increasing mental stress, which leads to insulin inertia. Approximately 246 million people worldwide have diabetes mellitus. It is estimated that 20 to 30 million people globally suffer from symptomatic diabetic neuropathy. The prevalence of diabetic neuropathy also rises over time. If type 1 diabetes is not well controlled, severe diabetic polyneuropathy and poor glycemic control can appear in young adults just a few months after the disease manifests. Ayurveda can be correlated with MajjaDhatuDushti (Structural and functional defects of neurons). Identification of the predominance of a specific type of Prakrutiin patients with diabetic neuropathy in Wardha City. The prime objectives of the present study are to find out the predominance of specific Prakriti in patients with diabetic neuropathy in Wardhacity&amp;create awareness in them regarding complications of Diabetes mellitus, especially diabetic neuropathy and its relation with Prakruti. The current study was a cross-sectional study based on a personal interview of patients and Prakrutiquestionnaires. It occurred at Salod(H), Wardha, Maharashtra's Mahatma Gandhi Ayurved College, Hospital &amp; Research Center. It was found that the prevalence of diabetic neuropathy is high in PittajPradhanVataPrakruti. In this present study, most of the affected patients were male. The present study concludes that diabetic neuropathy was found more prevalently in patients with Pitta PradhanVataPrakruti. Specific lifestyle modifications can be recommended for patients with Prakriti, as mentioned earlier, to prevent diabetic neuropathy in the future. Keywords: , , , ,

Severe Polyneuropathy in Hereditary Transthyretin Amyloidosis Caused by H90D Variant.

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EFFECT OF NON-ALCOHOLIC FATTY LIVER DISEASE ON THE COURSE OF DIABETIC POLYNEUROPATHY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS.

The aim: To study the peculiarities of diabetic polyneuropathy in patients with type 2 diabetes mellitus and concomitant NAFLD. Materials and methods: We examined 75 patients with type 2 diabetes mellitus, including 31 (41.3%) women and 44 (58.7%) men. The main group included 35 patients with NAFLD (46.7%), and the control group included 40 patients without NAFLD (53.3%). The severity of polyneuropathy was assessed using the Toronto clinical neuropathy score. The presence of neuropathic pain syndrome in patients allowed us to divide patients into groups with painful or painless forms of diabetic polyneuropathy. The electroneuromyographic examination was used to study nerve conduction parameters, namely peroneal motor nerve conduction velocity (PMNCV), sensory nerve action potential (SNAP), and sensory nerve conduction velocity (SNCV). Results: The proportion of patients who did not have diabetic polyneuropathy in the NAFLD group was 12.5%, and in the group without NAFLD - 87.2%. The frequency of diabetic polyneuropathy was higher in the main group, namely: mild, moderate, and severe polyneuropathy was 80%, 56% and 59.3%, respectively, compared to the control group - 20%, 44%, 40.7% (p=0.02). The painful form of DPN was more common in patients of the main group than in the control group, respectively 69.8% and 30.2% (p=0.01). The degree of liver fibrosis did not affect the course of DPN. The study of nerve conduction by PMNCV, SNAP, and SNCV parameters showed that PMNCV was higher in the NAFLD group, and SNAP and SNCV - in the control group, but without statistical significance (p>0.05). Conclusions: In patients with type 2 diabetes mellitus, the presence of NAFLD affects the severity of diabetic polyneuropathy and increases the risk of painful DPN. The degree of liver fibrosis did not show an effect on the development of diabetic polyneuropathy. ENMG parameters did not demonstrate a statistically significant difference in the study groups.