Severe Axonal Neuropathy Research Articles

Nerve ultrasound in Friedreich’s Ataxia: enlarged nerves as a biomarker of disease severity

ObjectiveIn Friedreich's ataxia research, the focus is on discovering treatments and biomarkers to assess disease severity and treatment effects. Our study examines high-resolution nerve ultrasound in these patients, seeking correlations with established clinical markers of disease severity. MethodTen patients with Friedreich’s Ataxia underwent a comprehensive clinical assessment with established scales (SARA, FARS, mFARS, INCAT, ADL 0-36, IADL). Additionally, they underwent nerve conduction studies and high-resolution nerve ultrasound. Quantitative evaluation of nerve cross-sectional area, conducted at 24 nerve sites using high-resolution nerve ultrasound, was compared with data obtained from 20 healthy volunteers. ResultsAll the patients had a severe sensory axonal neuropathy. High-resolution nerve ultrasound showed significant increase, in cross sectional area, of median and ulnar nerves at the axilla and arm. The cumulative count of affected nerve sites was directly associated with clinical disability, as determined by SARA, FARS, mFARS, ADL 0-36, and INCAT score, while displaying an inverse correlation with IADL. ConclusionsOur study shows that high-resolution ultrasound reveals notable nerve abnormalities, primarily in the upper limbs of patients diagnosed with Friedreich’s Ataxia. The observed correlation between these nerve abnormalities and clinical disability scales indicates the potential use of this technique as a biomarker for evaluating disease severity and treatment effects. SignificanceNerve Ultrasound is a potential biomarker of disease severity in Friedreich’s Ataxia.

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.

Super-resolution imaging pinpoints the periodic ultrastructure at the human node of Ranvier and its disruption in patients with polyneuropathy

The node of Ranvier is the key element in saltatory conduction along myelinated axons, but its specific protein organization remains elusive in the human species. To shed light on nanoscale anatomy of the human node of Ranvier in health and disease, we assessed human nerve biopsies of patients with polyneuropathy by super-resolution fluorescence microscopy. We applied direct stochastic optical reconstruction microscopy (dSTORM) and supported our data by high-content confocal imaging combined with deep learning-based analysis. As a result, we revealed a ∼ 190 nm periodic protein arrangement of cytoskeletal proteins and axoglial cell adhesion molecules in human peripheral nerves. In patients with polyneuropathy, periodic distances increased at the paranodal region of the node of Ranvier, both at the axonal cytoskeleton and at the axoglial junction. In-depth image analysis revealed a partial loss of proteins of the axoglial complex (Caspr-1, neurofascin-155) in combination with detachment from the cytoskeletal anchor protein ß2-spectrin. High content analysis showed that such paranodal disorganization occurred especially in acute and severe axonal neuropathy with ongoing Wallerian degeneration and related cytoskeletal damage. We provide nanoscale and protein-specific evidence for the prominent, but vulnerable role of the node of Ranvier for axonal integrity. Furthermore, we show that super-resolution imaging can identify, quantify and map elongated periodic protein distances and protein interaction in histopathological tissue samples. We thus introduce a promising tool for further translational applications of super resolution microscopy.

A Case of Acute Motor Sensory Axonal Neuropathy, a Rare Form of Guillain-Barre Syndrome, Developing After Multiple COVID-19 Infections (P13-8.009)

<h3>Objective:</h3> Guillain-Barre syndrome (GBS), an autoimmune polyneuropathy characterized by ascending weakness and characteristic cerebrospinal fluid (CSF) findings, has been identified in patients previously diagnosed with COVID-19, treated for COVID-19 infection, or vaccinated against the same. GBS is divided into axonal and demyelinating subtypes, and confirmatory testing such as electromyography and nerve conduction studies can help differentiate between subtypes. Here we present a case with recurrent COVID-19 infections, most recently treated with bebtelovimab, who developed acute motor sensory axonal neuropathy (AMSAN), a rare variant of axonal GBS. <h3>Background:</h3> A 33-year-old female presented with progressive ascending weakness and sensory loss that started two weeks after COVID-19 infection. She was fully vaccinated, however, had four episodes of COVID-19 infection within the past year and a half. Two weeks after the most recent infection, which was treated with bebtelovimab, she developed rapidly progressive weakness and sensory impairment in bilateral lower extremities quickly involving upper extremities. She received two rounds of intravenous immunoglobulin (IVIG) three and five weeks after symptoms onset. Her symptoms continued to progress requiring hospitalization. Exam showed severe weakness in all limbs with distal muscle atrophy in upper extremities. Imaging was negative. CSF demostrated albuminocytological dissociation. Nerve conduction studies concluded severe motor and sensory axonal neuropathy with active denervation which led to the suspicion of Acute Motor and Sensory Axonal Neuropathy (AMSAN), a rare variant of GBS. She underwent plasmapheresis with only minimal improvement. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> N/A <h3>Conclusions:</h3> Many cases of GBS have been reported after COVID-19 infection but only a few of them are about AMSAN. This case presents unique features including multiple COVID-19 infections despite prior vaccination, and the development of this rare variant of GBS. It raises the concern of multiple COVID-19 infections having a cumulative impact on peripheral nervous system leading to more severe forms of GBS with poor response to treatment. <b>Disclosure:</b> Dr. Narvaez Caicedo has nothing to disclose. Mr. Rao has nothing to disclose. Dr. Patel has nothing to disclose. Dr. Wu has nothing to disclose.

A SUCCESSIVE CLINICAL STORY ON GUILLAIN-BARRE SYNDROME UNDER THE LIGHT OF AYURVEDA: A CASE STUDY

Guillain-Barre syndrome (GBS) is a group of autoimmune syndromes comprising the disease's demyelinating and acute axonal degenerating forms. It is also an acute-onset, monophasic, immune-mediated polyneuropathy that often follows an antecedent infection. Here is an interesting case study where a 16-year-old girl with her parents reported to the outpatient department with the chief complaint of inability to walk without support, weakness in bilateral calf muscles, weakness in bilateral upper limbs and lower limbs and tingling sensation, pulling type of pain in the right ankle joint and also the heaviness of bilateral lower limbs, more in the morning. By examination, her sensory and motor systems showed impairment; one was hypotonic, proprioception was affected, and her gait was a high steppage gait. Her assessment was done by using Hughes GBS Disability Scale- 3/6. The patient’s nerve conduction study revealed severe motor and sensory axonal neuropathy in the upper and lower limbs. By seeing the nature of the disease and the patient's symptoms, we correlated with sarvanga vata according to our classics. Treatments were koshta shodhana (gut cleansing), abhyanga (massage of the whole body with medicated oil), Shastikashali panda sweda (Rubbing of medicated rice poultice over the body), basti (transrectal administration of medicines) and oral medicaments. Panchakarma treatments were for 30 days, followed by oral medications for the next 140 days. The intervention period of 154 days showed complete recovery of all the motor and sensory deficits; however, follow-up of the patient was maintained for 269 days, looking into the sustainability of the outcomes.

Juvenile-onset PSAT1-related neuropathy: A milder phenotype of serine deficiency disorder.

Background: Primary serine deficiency disorders have a broad range of the phenotypic spectrum. As an inborn error of metabolism, individuals with severe phenotype may be easily recognized with Neu-Laxova syndrome. However, late-onset mild phenotypes may be underdiagnosed and will lead to disastrous consequences due to treatment delays. Materials and Methods: Clinical features of patients with serine deficiency disorders were summarized in two unrelated patients. Skin and sural nerve biopsies were conducted on the patients. Whole exome sequencing (WES) was performed in the index patients. Sanger sequencing was used to analyze family cosegregation. Results: Patient 1 was a 19-year-old male presenting with infancy-onset ichthyosis and juvenile-onset neuropathy. Patient 2 was a 17-year-old male manifesting childhood-onset ichthyosis and juvenile-onset neuropathy. Except for nystagmus, no other developmental or neurodegenerative disorders were found in the patients. Electrophysiological studies indicated a severe sensorimotor axonal neuropathy with a possible demyelinating component. High-dose oral L-serine and glycine completely alleviated skin lesions and only slightly improved neuropathy symptoms. Skin biopsies showed typical features consistent with ichthyosis and severe loss of unmyelinated axons. Sural biopsies revealed a severe loss of axons and a few thinly myelinated fibers. WES found the same homozygous variant c.43G > C (p.A15P) in the PSAT1 gene, which was cosegregated in the two families. Conclusions: The skin and nervous system may be the main affected targets in serine deficiency disorders. Our patients show a more simple and mild phenotype of PSAT1-related serine deficiency disorder. The pathological changes and regenerative ability of skin and peripheral nerves determine their response to serine supplements.

092 War, arsenic and A(wo)MAN

Acute motor axonal neuropathy (AMAN) is a subtype of Guillain-Barré syndrome (GBS) with predominant motor axonal changes and no sensory signs or symptoms. Recovery can vary from complete to incom- plete with residual disability1. Arsenic is a heavy metal which is poisonous at low concentrations. Acutely, it causes vomiting, colicky abdominal pain and profuse watery diarrhoea. Its poisonous effects on the nervous system include a peripheral neuropathy mimicking GBS. Arsenic is a popular choice as an incon- spicuous murder weapon. It can resemble white sugar in appearance and be tasteless and odourless2. Other uses include pest control in agriculture and as a cotton desiccant. Certain forms of arsenic have been used in chemical warfare. We present a case of a 39 year-old female refugee with a 20 year history of bilateral upper and lower limb distal weakness. Aged 17, she developed profuse vomiting followed by an acute paralytic illness whilst living on a cotton farm in Kurdistan, Iraq. Neurophysiology demonstrated a severe motor axonal neuropathy with chronic partial denervation on EMG. We believe her symptoms may be related to arsenic poisoning, used during the Iraqi-Kurdish civil war3. This case highlights the impor- tance of considering geopolitical factors to aid diagnosis in neurological presentations.tara.kozul@uhs.nhs.uk

Clinical and genetic features of a cohort of patients with MFN2-related neuropathy

Charcot–Marie–Tooth disease type 2A (CMT2A) is a rare inherited axonal neuropathy caused by mutations in MFN2 gene, which encodes Mitofusin 2, a transmembrane protein of the outer mitochondrial membrane. We performed a cross-sectional analysis on thirteen patients carrying mutations in MFN2, from ten families, describing their clinical and genetic characteristics. Evaluated patients presented a variable age of onset and a wide phenotypic spectrum, with most patients presenting a severe phenotype. A novel heterozygous missense variant was detected, p.K357E. It is located at a highly conserved position and predicted as pathogenic by in silico tools. At a clinical level, the p.K357E carrier shows a severe sensorimotor axonal neuropathy. In conclusion, our work expands the genetic spectrum of CMT2A, disclosing a novel mutation and its related clinical effect, and provides a detailed description of the clinical features of a cohort of patients with MFN2 mutations. Obtaining a precise genetic diagnosis in affected families is crucial both for family planning and prenatal diagnosis, and in a therapeutic perspective, as we are entering the era of personalized therapy for genetic diseases.

HP41: Idiopathic systemic capillary leak syndrome with severe peripheral nervous system involvement. Case report

Idiopathic systemic capillary leak syndrome (ISCLS) a rare condition characterised by repeated relapses of leaking of plasma from blood vessels into body cavities and muscles. In one third of cases the disease is associated with variable severity peripheral nervous system damage. 26 years old male was admitted to hospital after repeated fainting with complains about progressive pain and numbness in lower limbs. In the hospital symptoms were rapidly progressing and patient developed asymmetrical painful tetraparesis (muscle strength in legs 0-1, muscle strength in arms 4). Systemic manifestations included hypotension, tachycardia, hemoconcentration, hypoalbuminemia, cardiac tamponade, crush syndrome. On 5th day from symptom onset treatment with intravenous immunoglobulin (IvIg) was started. After first IVIG treatment course systemic symptoms had resolved. Patient continued to receive IvIg monthly as a prophylactic treatment. After two courses of IvIg pain ceased, muscle strength improved (arm muscles 5, leg muscles 4). Patient died 20 months after symptom onset due to repeated systemic relapses. Electrodiagnostic study (EMG/NCS) was performed 3 times (on 3rd day from symptom onset, after first and second IvIg course). First EMG/NCS showed severe axonal motor and sensory neuropathy in legs, mild motor axonal damage in arms with massive spontaneous activity in all examined muscles. After repeated IvIg courses NCS in arms become normal, in legs tibial and peroneal MUAP remained absent, sural SNAP became normal; EMG showed slight evidence of reinnervation process without signs of active denervation. Conclusion. ISCLS can be considered in patients with rapidly progressive axonal polyradiculoneuritis with autonomic signs.

ACUTE MOTOR SENSORY AXONAL NEUROPATHY (AMSAN) VARIANT OF GUILLIAN BARRE SYNDROME (GBS) COMPLICATING PREGNANCY: A CASE REPORT

INTRODUCTION: Guillain Barre Syndrome (GBS), is an autoimmune disorder which manifests as Polyradiculoneuropathy(1,2). Several variants of GB have been identied of which Acute Motor Axonal Neuropathy (AMAN) and Acute Motor and Sensory Axonal Neuropathy (AMSAN) variants mainly occur by demyelination of neurons induced by inammation. CASE REPORT: A 20 Year old primigravida at 28 weeks of gestation, presented with history of weakness of all four limbs since 2 months. Nerve Conduction study showed evidence of Severe motor and sensory axonal neuropathy. Patient was managed with corticosteroids and showed improvement in her symptoms during her stay in the hospital. CONCLUSION: AMSAN a rare variant of GBS is uncommon in pregnancy and it can be associated with severe morbidity and complications if unrecognized and if not treated early. Such patients should be diagnosed early and should be given a multidisciplinary care and promptly treated. Prompt and early diagnosis of AMSAN variant of GBS , with a team effort involving the Physician, the Neurologist and the Obstetrician, along with an early initiation of immune-modulatory therapy, it can be ensured that good outcomes can be expected from both the mother and the fetus.

Guillain\u2013Barr\xe9 syndrome with bilateral facial diplegia secondary to severe acute respiratory syndrome coronavirus-2 infection: a\xa0case report

BackgroundThe new coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) owing to its similarity to the previous severe acute respiratory syndrome (SARS), is characterized by causing, in most patients, nonspecific symptoms similar to those of the common flu. It has been reported that many coronavirus disease 2019 (COVID-19) patients presented neurological symptoms that involve the central and peripheral nervous systems. In addition, there have been several reports of patients who presented Guillain–Barré syndrome related to COVID-19 , with sensory and motor compromise in the extremities.Case presentationIn this report, we describe a rare case of Guillain–Barré syndrome in a 50-year-old Hispanic male with bilateral facial palsy as the only neurological manifestation, following SARS-CoV-2 infection. A complete neurophysiological study showed severe axonal neuropathy of the right and left facial nerves.ConclusionRegardless of severity, clinicians must to be aware of any neurological manifestation generated by COVID-19 and start performing more neurophysiological tests to determine if the infection induces an axonal, myelin, or mixed involvement of the peripheral nervous system.

Severe Acute Motor Axonal Neuropathy associated with Influenza-A (H1N1) Infection and Prolonged Respiratory Failure - A Case Report.

Acute Motor Axonal Neuropathy (AMAN) is an immune-mediated disorder of the peripheral nervous system, part of the spectrum of the Guillain-Barre syndrome (GBS). An infectious event most often triggers it reported a few weeks before the onset. The reported case is of a 56 years-old woman who developed acute motor axonal neuropathy three weeks after respiratory infection with influenza A virus subtype H1N1. Despite early treatment with plasmapheresis and intravenous immunoglobulins, the patient remained tetraplegic, mechanically ventilated for five months, with repetitive unsuccessful weaning trails. The probable cause was considered to be phrenic nerve palsy in the context of acute motor axonal neuropathy. This case highlights that acute motor axonal neuropathy is a severe and life-threatening form of Guillain-Barre syndrome associated with significant mortality and morbidity. Neurological and physical recovery strongly depend on the inter-professional effort in an intensive care unit and neurology professionals.

The Genotype and Phenotype Features in a Large Chinese MFN2 Mutation Cohort.

Introduction: Charcot–Marie–Tooth disease type 2A (CMT2A) is a group of clinically and genetically heterogeneous disorders, which is mostly caused by mutations of the mitofusin2 (MFN2) gene. As the genotype–phenotype characteristics of CMT2A were still incompletely understood, we further explored the spectrum of CMT2A variants in China and demonstrated their phenotypic diversities.Methods: A total of 402 index patients/families with CMT throughout Mainland China were enrolled in this study. Among them, we analyzed 20 unrelated index cases with CMT2A by Sanger sequencing, next-generation sequencing, or whole-exome sequencing. Detailed clinical and genetic features of CMT2A patients were collected and analyzed. Of note, de novo mutations were not rare in MFN2 gene; we compared the clinical features of patients from the de novo group with those from the non-de novo group.Results: We identified 20 MFN2 variants, occupying 5.0% of CMT. Most patients presented with early onset and moderate phenotype with abnormal gait and foot drop as the main complaints at onset. Pyramidal signs accounts for 31.6% (6/19) in all patients, which is not uncommon. Four novel variants (p.Tyr752*, c.475-2A>G, p.Val99Met, and p.Arg275_Gln276insArg) were identified in the cohort. Besides, de novo variants occupied 35.0% (7/20) in our study with a much earlier age at onset compared with those in the non-de novo group (p = 0.021).Conclusion: Chinese CMT2A is a predominant typical pure CMT2A, with early onset and mild to moderate phenotype. Given the high frequency of de novo MFN2 mutations, genetic study should be considered for patients with early onset and severe idiopathic axonal neuropathy.

NCMP-23. PEMBROLIZUMAB-ASSOCIATED CD8+ VASCULITIC MONONEURITIS MULTIPLEX IN A PATIENT WITH MESOTHELIOMA: FIRST CASE REPORT

Abstract INTRODUCTION Immunotherapy, especially with immune checkpoint inhibitors (ICPI), has increasingly become an attractive treatment modality for various types of cancers. However, many patients develop ICPI-associated autoimmune adverse events such as pneumonitis, colitis or rarely neurological syndromes. Large and medium vessel vasculitis haS only occasionally been reported. Here we report the first case of ICPI-associated mononeuritis multiplex in a patient with malignant mesothelioma, caused by a histological proven small vessel vasculitis. CASE REPORT A 61-year old female developed subacute progressive painful and asymmetric sensorimotor deficits on distal extremities. Electrophysiologically, signs of a severe axonal neuropathy of both legs and the right arm were found, and swellings of the corresponding nerves were seen upon nerve ultrasound exam. The clinical and electrophysiological findings were reminiscent of mononeuritis multiplex. Laboratory work up including CSF examination was normal. More than two years prior to developing peripheral nerve deficits, the patient had been diagnosed with malignant pleural mesothelioma and treated with the anti-PD1 monoclonal antibody pembrolizumab on progression after chemotherapy. Biopsy of the right sural nerve revealed a small vessel vasculitis with a lymphocyte predominance of CD8+ T cells over CD4+ T as well as B lymphocytes. Despite discontinuation of pembrolizumab and immunosuppressive treatment (high dose methylprednisone, cyclophosphamide) complemented by opioid therapy, painful allodynia persisted. CONCLUSION ICPI-associated autoimmune disorders also include small vessel vasculitis with rare phenotypes such as mononeuritis multiplex. Further studies are required to improve our understanding of the link between ICPIs, and the pathogenic process leading to vasculitis, as well as to optimize treatment options for those rare diseases.

EP35 Cryoglobulinaemic vasculitis: an uncommon complication of Sjögren’s syndrome

EP35 Cryoglobulinaemic vasculitis: an uncommon complication of Sjögren’s syndrome

MIOPATI KONGENITAL PADA BAYI: SEBUAH LAPORAN KASUS

Background: The congenital myopathies are group of genetic muscle disorders with a prevalence estimated between 1:22,480 in Sweden and 1:135,000 in Northern England. The most severe forms of congenital myopathy present In infant is the floppy infant with hypotonia and generalized musle weakness, and a frog leg posture, with facial, bulbar and respiratory weakness. We will provide an approach to the diagnosis of congenital myopathies with clinical examination, muscle imaging (MRI), muscle biopsy and identifying the genetic basis. Management of congenital myopathy are treatment of symptoms and complication caused by myopathies.&#x0D; Aim: To report a case of congenital myopathy in infant&#x0D; Case Description: A boy, a month, consulted from pediatric department to neurology department with chief complains the mouth is held in a open position, difficulty in feeding and generalized muscle weakness. From physical examintaion shows hypotonus in the masseter muscle, bulbar, respiration and all of extremities. In the chest cavity show pectus excavatum. Reflexes decrease in all of extremities with phatological reflexes in both lower extremities. We found pneumonia bilateral from thorax X-ray. ENMG shows moderate to severe axonal neuropathy and demyelination on all of extremities with normal EMG results. He received paracetamol 30 mg iv, ampicilin 150 mg iv, gentamicin 12 mg iv. He received exercise and chest fisiotherapy. After 22 days of treatment, he was discharge with clinical improvement. &#x0D; Conclusion: Patient has pneumonia bilateral caused by respiratory weakness congenital myopathy. Follow up and histological features is essential in guiding management for prediction of prognosis.

Ischemic monomelic neuropathy: A rare complication after brachiocephalic arteriovenous fistula

Ischemic monomelic neuropathy (IMN) is a rare neuropathy of the distal nerves due to ischemia secondary to acute loss of proximal arterial supply as a result of shunting or non-compressive occlusion. The main features of IMN are multiple distal focal mononeuropathies with axonal injury. A 71 years old female patient with history of end stage renal disease on hemodialysis and type 2 diabetes. Presented with right hand persistent pain and reduced hand function that started 24 h after formation of right brachiocephalic arteriovenous (AV) fistula. Doppler scan was done suggesting of steal syndrome. Patient then underwent MILLER banding procedure for the fistula. Despite good vascular supply, the right hand pain did not improve and was partially responding to gabapentin and codeine+ paracetamol. On examination: The right hand was warm and the capillary refill was satisfactory, palpable radial pulse with no signs of tissue ischemia. She was unable to flex the wrist and fingers of the right hand and she had clawing of right hand. She had allodynia and hyperalgesia in the distribution of right median, ulnar nerves. Nerve conduction study showed absent sensory responses from the right median, ulnar and radial nerves. The right median and ulnar motor responses were significantly attenuated suggestive of a severe axonal neuropathy and peripheral neuropathy secondary to diabetes. She was referred to vascular surgery for fistula ligation. IMN is a potentially rare devastating complication of arteriovenous access for hemodialysis which can result in permanent disability.

W1-4. Severe lower limb axonal neuropathy that developed after diabetic ketoacidosis presenting with gadolinium enhancement of cauda equina

W1-4. Severe lower limb axonal neuropathy that developed after diabetic ketoacidosis presenting with gadolinium enhancement of cauda equina

Severe Guillain-Barr\xe9 syndrome associated with chronic active hepatitis C and mixed cryoglobulinemia: a case report

BackgroundWe describe a case of severe Guillain-Barre syndrome (GBS) associated with chronic active hepatitis C and mixed cryoglobulinemia (MC). To our knowledge, this association between GBS and hepatitis C virus (HCV) infection has been rarely reported.Case presentationA 56-year-old man developed symmetrical muscle weakness in all extremities, areflexia and sensorial disorder followed by acute respiratory failure associated with chronic active hepatitis C, which was confirmed by the presence of anti-HCV antibodies in the serum and persistence of HCV RNA viral load for more than 6 months. Chronic hepatitis C was further complicated by type 3 MC. Electromyography showed peripheral nerve injury (mainly in axon). A severe acute motor sensory axonal neuropathy (AMSAN) was diagnosed. After treatment with intravenous immunoglobulin and plasma exchange followed by antiviral therapy by direct-acting antiviral agent, patient showed progressive recovery and was transferred 3 months after his first admission to a rehabilitation center.ConclusionsOur case reported a severe GBS associated with HCV infection and MC. EMG classified for the first time the subtype of GBS (severe AMSAN) correlated with severe clinical form. HCV infection should be screened in high-risk patients to prevent silent progression of the chronic hepatitis C and its potentially severe extra-hepatic manifestations.

051 Overlapping syndrome of giant cell arteritis and ANCA-associated vasculitis complicated by severe axonal neuropathy: a case report

CaseA 61-year- old woman presented with what was thought to be a refractory, temporal artery biopsy-proven giant cell arteritis (GCA). After 4 months of therapy she was unable to get the prednisolone dose below 40 mg/day, so weekly subcutaneous Tocilizumab was introduced but with minimal response after 8 weeks. She was then admitted to hospital with a severe rapidly progressive length dependent sensorimotor peripheral neuropathy. Nerve conduction studies showed predominantly an axonal neuropathy with multiple pseudo-conduction blocks.Sural nerve and gastrocnemius biopsies revealed a necrotising vasculitis with numerous giant cells and active axonal degeneration. She proved to be ANCA-PR3 positive, without other systemic manifestations. ANCA-associated vasculitic neuropathy was diagnosed and she was treated with two 1g Rituximab infusions, 2 weeks apart.On follow-up after a month, she had regained some strength but still required a wheelchair for mobility. Further Rituximab infusion after 6 months is planned; prednisolone had been successfully weaned to 10 mg/day.ConclusionPeripheral nerve involvement, which is relatively common in ANCA-associated vasculitis, has also been reported in 14% of GCA cases. But ANCA-PR3 positivity is rare in biopsy-proven GGA, with only a handful of well-documented cases.Heightened suspicion of an alternative diagnosis in the face of an unusual clinical course (lack of steroid response and appearance of small vessel vasculitic symptoms for what is accepted to be a large vessel vasculitis) is critical and our experience highlights the important fact that a diagnosis of one of these disorders does not preclude the subsequent diagnosis of the other.