Updated results from MOMENTUM: Momelotinib vs. Danazol in JAK inhibitor-experienced, symptomatic, and anaemic myelofibrosis patients

The phase 3 MOMENTUM study (NCT04173494) of the ACVR1/JAK1/JAK2 inhibitor momelotinib (MMB) vs. danazol (DAN) in patients with myelofibrosis (MF) previously treated with a JAK inhibitor (JAKi) met the primary endpoint and all key secondary endpoints at week 24 (W24). We provide updated results from week 48 assessments. Eligible patients had primary or post-ET/ PV MF;DIPSS high, Int-2, or Int-1 risk;Total Symptom Score (TSS) >=10;haemoglobin (Hb) <10 g/dL;platelets >=25 x 109/L;prior JAKi for >=90 days (>=28 days if red blood cell [RBC] transfusions >=4 units in 8 weeks or grade 3/4 thrombocytopenia/anaemia/ hematoma);and palpable spleen >=5 cm. Randomisation was 2:1 to MMB 200 mg/day or DAN 600 mg/day for 24 weeks, followed by open-label (OL) MMB. Week 48 endpoints included durations of response (TSS, transfusion independence [TI], splenic) and overall and leukaemia-free survival (OS, LFS). As of 17 May 2022, 93/130 (72%) MMB -> MMB and 41/65 (63%) DAN -> MMB patients received OL MMB;mean MMB durations were 48 weeks and 24 weeks, respectively. Analyses for W24 responders showed the following: of TSS responders, 31/32 (97%) MMB -> MMB and 6/6 DAN -> MMB patients had TSS < baseline;of TI responders, 36/40 (90%) and 10/13 (77%) had no RBC transfusions or Hb <8 g/dL;and of spleen responders, all patients had splenic volume < baseline. In the OL phase, the most common grade >=3 treatment-emergent adverse events (TEAEs) were thrombocytopenia (MMB -> MMB, 9%;DAN -> MMB, 15%) and anaemia (MMB -> MMB, 9%;DAN -> MMB, 2%). Grade >=3 infections occurred in 19% of MMB -> MMB and 10% of DAN -> MMB patients, including grade >=3 (nonfatal) COVID-19. Peripheral neuropathy (PN) occurred in 2% of patients in each arm, and none discontinued MMB due to PN. TEAEs led to MMB discontinuation in 18% (MMB -> MMB) vs. 10% (DAN -> MMB). A trend towards improved OS up to W24 was previously observed with MMB vs. DAN (hazard ratio [HR], 0.506;p = 0.0719);after all patients crossed over to OL MMB, OS and LFS curves for both arms converged (HR, 0.945, 95% CI, 0.528-1.693;HR, 0.830, 95% CI, 0.473-1.4555). Sixty of 81 (74%) MMB -> MMB and 29 of 43 (67%) DAN -> MMB patients with baseline platelets <=150 x 109/L entered the OL phase. Efficacy and safety results in thrombocytopenic subgroups in the OL period were consistent with the intent-to- treat (ITT) population. OL MMB maintained symptom, TI, and spleen responses with continued good survival and safety in the ITT and low platelet populations. MMB may address an unmet need in anaemic patients with MF.

Relationship between neurological manifestations and severity of COVID-19. San Vicente de Paul Hospital. Ecuador 2021.

Introduction: SARS-CoV-2 mainly affects the respiratory system, but the damage caused by this virus also extends to other systems, including the nervous system, and the mechanisms of neurological infection can be direct or indirect. Objective(s): To determine the relationship between neurological manifestations and disease severity in symptomatic COVID-19 positive patients at San Vicente de Paul Hospital in 2021. Material(s) and Method(s): A cross-sectional observational study was conducted using medical records of patients hospitalized with COVID-19 and neurological manifestations, which were classified into manifestations of the central nervous system and manifestations of the peripheral nervous system. Result(s): The results show that 74,1 % of patients presented neurological manifestations;the highest percentage was concentrated in patients who developed severe disease (15 [60 %], CNS;91 [77,1 %], PNS;125 [65,4 %], CNS and PNS). The joint presence of central and peripheral neurological manifestations was significantly associated with critical COVID-19 (P value= 0,011;OR: 2,005). The mortality rate reached 2,69 %. Conclusion(s): Neurological manifestations in hospitalized COVID-19 patients are very common, and critical COVID-19 is more likely to have neurological manifestations.Copyright © 2022 Universidad de Ciencias Medicas de La Hab. All rights reserved.

Infectious Neuropathies

Infectious diseases frequently affect the peripheral nervous system by direct infiltration or indirect inflammatory response induced by the microorganisms. Peripheral neuropathies are commonly observed in the course of HIV infection and represent the major neurological complication of the disease. The heterogeneous spectrum makes the diagnosis challenging even for the expert neurologist and includes distal symmetric neuropathies, demyelinating neuropathies, mononeuritis multiplex, progressive polyradiculopathies, and diffuse infiltrative lymphocytosis syndrome. Peripheral neuropathy (PN) is one of the most frequently reported extrahepatic complications of HCV chronic infection, occurring in about 10% of HCV-infected patients. PN usually coexists with cryoglobulinemia and may manifest as chronic "length dependent” distal symmetrical sensorimotor or mainly sensory axonal polyneuropathy, "stocking-glove” asymmetric polyneuropathy, subacute mononeuropathy multiplex, or asymmetrical neuropathy involving large or small nerve fibers. Pure motor or demyelinating neuropathies and, rarely, cranial or autonomic neuropathies, have also been reported. Among the rarest causes of infectious neuropathies, leprosy and borreliosis are an important global health concern. The differential diagnosis is often difficult and sometimes, in particular in suspected neuritic form of leprosy, requires nerve biopsy and a detailed neuropathological analysis that can help for personalized therapy. With the COVID-19 pandemic, many cases of patients with peripheral nervous system involvement have been described, in the absence of a direct role of SARS-CoV-2. © Springer Nature Switzerland AG 2022.

Neuromuscular disease: 2022 update.

This review highlights ten important advances in the neuromuscular disease field that were reported in 2021. As with prior updates in this article series, the overarching topics include (i) advances in understanding of fundamental neuromuscular biology; (ii) new / emerging diseases; (iii) advances in understanding of disease etiology and pathogenesis; (iii) diagnostic advances; and (iv) therapeutic advances. Within this general framework, the individual disease entities that are discussed in more detail include neuromuscular complications of COVID-19 (another look at the topic first covered in the 2021 review), autosomal recessive myopathy caused by MLIP mutations, autosomal recessive neuromuscular disease caused by VWA1 mutations, Leber's hereditary optic neuropathy, myopathies with autophagic defects, tRNA synthetase-associated Charcot-Marie-Tooth disease, systemic sclerosis-associated myopathy, humoral immune endoneurial microvasculopathy, and late-onset Pompe disease. In addition, the review highlights a few other advances (including new insights into mechanisms of muscle and nerve regeneration and the use of gene expression profiling to better characterize different subtypes of immune-mediated myopathies) that will be of significant interest for clinicians and researchers who specialize in neuromuscular disease.

Comment on: 'Should We Interfere with the Interleukin-6 Receptor During COVID-19: What Do We Know?'/Authors' Reply to Chia Siang Kow et al.: Comment on: 'Should We Interfere with the Interleukin-6 Receptor During COVID-19: What Do We Know So Far?'

[...]the mortality reduction has previously been reported in the prospective meta-analysis [2] conducted by The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Nonetheless, owing to relatively scarce evidence, it is still unclear whether monoclonal IL-6 antibodies reduce mortality in patients with COVID-19, similar to the IL-6 receptor inhibitors. [...]large-scale randomised trials should also be conducted to establish the role of monoclonal IL-6 antibodies in the treatment of COVID-19. [...]among hypothetical long-term complications, peripheral neuropathy would also be noticeable [10] and may contribute to the broad long COVID pattern. [...]there is a theoretical risk of altering the efficacy of immune checkpoint inhibitors during tumour disease management [11].

The Effect of the Different Waves of COVID-19 Pandemic on the Outcome of Diabetic Foot Ulcers

Objective: Diabetic foot ulcers (DFUs) are complications of diabetes mellitus. COVID-19 pandemic has massively impacted human health. We studied effect of COVID-19 on outcome of DFUs. Method(s): We recruited 483 people with DFU from June 2020-April 2022 (pandemic group) together with a matched group of 227 people with DFU from March 2019-March 2020 (pre-pandemic group). Matching was done with respect to glycemic control (Average HbA1c in pandemic group 9.15%;pre-pandemic group 8.92%), and renal status. Primary endpoint was outcome of ulcers- healed or undergone amputation. Primary outcome was further sub analyzed in the 3 waves of COVID-19 Secondary endpoint was healing of individual types of DFUs. Basic anthropometric data with site, nature and Wegner's grading of DFUs were collected. Diagnosis of peripheral neuropathy was done by monofilament testing and peripheral arterial disease by handheld Doppler and ABI. Standardized treatment protocol including glycemic control, infection control, debridement, dressing, offloading was provided. All patients were monitored for >6 months. Result(s): In pandemic cohort of 483 patients 323(66.9%) patients had healed ulcers, 70(14.5%) had minor amputation, 11(2,2%) had major amputation, 29(6%) lost to follow up, 22(4.6%) had not healed and 28 are in follow up (5.8%). Rate of healing of DFU in pandemic group was higher (66.9%) than control group (53.5%). Similarly, rate of amputation in pandemic group was less (16.7%) than pre-pandemic group (23.4%). Among healed ulcers in pandemic group, non-infected neuropathic ulcers healed better (77.8%;199/256) than other types (54.6%;124/227) [p< 0.00001]. Similarly, rate of amputation (major/minor) in ischemic and neuroischemic ulcers in pandemic group was more (32.3%;11/34) than other types (15.6%;70/449) [p= 0.011]. Rate of healing of foot ulcers in 1st wave was 65.4% (53/81), 2nd wave 75.2% (158/210), 3rd wave 58.3% (112/192). Neuropathic ulcers though less prevalent in first two waves (49.8%;145/291) than 3rd wave (57.8%;111/192) healing rate was more in first two (79.3%;115/145 vs 75.6%;84/111). [p=0.488 (statistically not significant]. Ischemic and neuroischemic ulcers were more in 3rd wave (7.8%;15/192) than first two waves (6.5%;19/291) and undergone more amputation (46.7%;7/15 vs 15.7%;3/19). [p=0.58 (statistically not significant;due to small sample size]. Discussion/Conclusion: COVID-19 pandemic (mainly first two waves) accounted for travel restrictions contributing to better healing of neuropathic ulcers whereas ischemic and neuroischemic ulcers worsened and underwent more amputation as patients could not seek intervention. Conversely, in third wave withdrawal of COVID restrictions lead to worsening of DFUs leading to less healing and more amputation.Copyright © 2023

Post-COVID-19 vaccination Guillain-Barre syndrome with sensory ataxia, gaze-evoked nystagmus, mental-status change and positive pathological reflex

Background: Various neurological disorders have been reported after vaccination against coronavirus disease 2019, one of which is Guillain-Barre Syndrome (GBS). Case Presentation: We report a case of a 73-year-old woman who developed GBS and extra-GBS manifestations 19 days after the second dose of BNT162b2 mRNA vaccine. She presented lower limb predominant muscle weakness and loss of tendon reflexes. Nerve conduction study showed acute motor and sensory axonal neuropathy. In addition, she developed notable deep sensory ataxia, and showed positive pathological reflex, gaze-evoked nystagmus and altered consciousness, which suggested brainstem involvement. Conclusion(s): This is the first coronavirus disease 2019 vaccine-related GBS complicated with such central nervous system manifestations.Copyright © 2023 Japanese Society for Neuroimmunology.

Miller-Fisher syndrome following by Sputnik V vaccine: Case report.

Miller-Fisher syndrome (MFS), defined as a rare variant of Guillain-Barre syndrome (GBS), is characterized by the classic triad of ataxia, areflexia, and ophthalmoplegia. It is a demyelinating polyneuropathy resulting from a deregulated autoimmune response secondary to infection by viruses and bacteria. SMF and GBS have been described during the COVID-19 pandemic. There are some reports in the literature of GBS after vaccination for COVID-19. In contrast, reports of post-vaccination FMS for SARS-CoV-2 are scarce in the literature. A 75-year-old patient is presented who consults for asthenia, adynamia, and difficulty swallowing that progresses to respiratory distress. She refers to the application of the Sputnik V vaccine as an important antecedent. During the hospital stay, the diagnosis was made by electromyography and nerve conduction study of GBS variant SMF. The objective is to expose a post-vaccination SMF to SARS-CoV-2 with the biological Sputnik V and highlight the importance of this background for surveillance in clinical practice and future research.Copyright © 2022 Asociacion Colombiana de Infectologia. All rights reserved.

Copper Deficiency Mimicking Myelodysplastic Syndrome: Zinc Supplementation in the Setting of COVID-19

While copper deficiency is rare, it can have serious consequences, including pancytopenia and neuropathy. This treatable micronutrient deficiency can present very similarly to myelodysplastic syndrome (MDS), a group of myeloid neoplasms which can carry devastating prognoses. Copper deficiency is an essential differential diagnosis in suspected MDS, as it can present with similar laboratory findings, bone marrow biopsy, and clinical picture. While copper deficiency has multiple potential causes, it typically occurs in patients with a predisposing gastrointestinal pathology. One possible cause of copper deficiency is zinc overload. Interestingly, zinc over-supplementation has been prevalent during the COVID-19 pandemic, as some believe that zinc can help prevent COVID-19 infection. Multiple case reports have illustrated the similarities between copper deficiency and MDS. They have also highlighted zinc over-supplementation as a potential cause. The following case report is unique in that our patient lacked gastrointestinal pathology. He still presented with the clinical and laboratory findings of MDS in the setting of copper deficiency. These include anemia, leukopenia, fatigue, and neuropathy. Further, this deficiency was caused by zinc over-supplementation in efforts to prevent COVID-19. The deficiency and the accompanying symptoms were treated with copper supplementation and cessation of zinc intake.

A flare of EGPA after vaccination for COVID-19, description and follow-up of a clinical case

Background: Although rarely, vaccines can stimulate the immunological mechanisms underlying immune-mediated inflammatory diseases. in patients with COVID-19 there is also evidence that high titers of autoantibodies, with variable clinical relevance, can be detected. Method(s): We describe the case of a 71-year- old lady diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) in 2010 with paraesthesia, myalgia, eosinophilia and severe asthma. After induction of remission, the patient has shown regression of the vasculitis but persistence of the uncontrolled asthma. For this reason, since February 2019 she started Mepolizumab 100 mg/month. In December 2020 she tested positive for the SARS-CoV- 2 virus, manifesting a mild form then she tested negative in January 2021. In April 2021 she was vaccinated with a single dose of BNT162b2 mRNA vaccine. After about 10 days, she started to complain arthromyalgia and after a week of gait alteration, paraesthesia, dyspnoea and worsening cough associated with chest pain. Blood tests showed an increase in creatinephosphokinase (CPK 955 U/L) and hypereosinophilia (4.3x10

Case report: Anti-CNTN1 antibody-associated nodopathies disease with asymmetric onset.

Anti-contactin-1 (CNTN1) IgG4 antibody-associated nodopathies is an autoimmune antibody-mediated peripheral neuropathy with a unique clinical presentation, pathophysiology, electrophysiology, and therapeutic response. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. Here, a 62-year-old male patient presented with subacute unilateral limb onset, progressive exacerbation, marked weakness of the extremities, cranial, and autonomic nerve involvement. Neurophysiology showed slowed motor nerve conduction velocity (MCV), prolonged distal motor delay (DML), slowed sensory nerve conduction velocity (SCV), decreased sensory nerve activity potential (SNAP) amplitude, decreased amplitude of bilateral neuromotor conduction, abnormal cutaneous sympathetic response (SSR) in both lower extremities, axonal damage, prolonged F-wave latency, and discrete waves. In the initial phase, there was a response to intravenous immunoglobulin (IVIG), and corticosteroids and rituximab were also effective. After 1 year follow-up, the patient improved significantly. This article reports on a patient with nodular disease with anti-contactin-1 (CNTN1) IgG4 antibodies and reviews the literature to improve clinicians' understanding of the disease.

It Takes Two to Make a Thing Go Wrong

Seventy-three-year-old diabetic male was a high-risk transfer from Alaska for respiratory decompensation in the setting of progressive bulbar and proximal weakness. He was diagnosed with COVID-19 two months prior and viral mononucleosis 1 month prior to presentation. While the patient had a fall 3 months prior to presentation, and decreased mobility at home, there was abrupt onset of progressive upper/lower extremity weakness, dysphagia, and difficulties managing secretions 2 weeks prior to presentation. Initial exam was notable for MRC 3-4/5 proximal upper/lower extremity weakness, areflexia, and negative inspiratory force of 224 to 230 cm H20. A subtle periorbital heliotrope rash was documented. Lumbar puncture demonstrated albumino-cytologic dissociation (protein 142 mg/dL, 6 WBCs) and CK remained elevated (1930 U/L) despite intravenous hydration. Outside electrodiagnostic testing demonstrated a sensorimotor axonal neuropathy with questionable myopathic features on needle electromyography. Given concern for an inflammatory neuropathy and concomitant inflammatory myopathy, intravenous immunoglobulin 2G/kg and IV methylprednisolone 1G/day over 5 days was started. He was transferred for further diagnostic workup and supportive care 6 days after presentation and required intubation within 24 hours of admission. Exam showed progressive proximal and distal weakness of the extremities and general areflexia/hyporeflexia. Repeat electromyography confirmed a severe sensorimotor axonal polyneuropathy without acquired demyelinating features and normal repetitive nerve stimulation. While the patient could no longer activate muscles voluntarily, proximal muscles had increased spontaneous activity with predominant myotonia. Neuroaxis imaging was notable only for enhancement of the lumbar nerve roots. Combined vastus lateralis muscle biopsy and serologic testing confirmed a second pathologic process contributing to the patient's weakness. This case highlights the cooccurrence of 2 distinct neuropathological entities, with potential relation to a prior viral infection, and the importance of ancillary testing to guide treatment for acute causes of neuromuscular respiratory failure.

Underused Physical Therapy Services in Primary Care Settings: An Overview

The combined effects of longer life, noncommunicable diseases, and injuries increase the need for rehabilitation services. Although physical therapists' unique skill set on movement-related dysfunction allows for broad contributions to health care, physical therapy (PT) remains underutilized. This article situates the problem within the broader primary care context, focusing on PT's ability to mitigate disability and dysfunction in complex syndromes including pelvic floor incontinence, vertigo, cancer, chronic neuromusculoskeletal pain, and long coronavirus disease (ie, lingering effects after acute coronavirus disease infection passes). The path from PT research to clinical implementation remains dependent on factors beyond research evidence. This overview underscores the need to address this evidence to practice gap.

Acute motor and sensory axonal neuropathy in a patient with undiagnosed mixed connective tissue disease

Case Report: Acute motor and sensory axonal neuropathy (AMSAN) syndrome is a rare subtype of Guillain-Barre syndrome (GBS) with poor recovery [1]. While respiratory and gastrointestinal infections may precipitate AMSAN, an underlying autoimmune disorder is seldom reported in literature. We herein report the complex case of a patient with undiagnosed, asymptomatic mixed connective tissue disease (MCTD) who developed AMSAN syndrome. Case: A 44-year-old Asian male without medical history presented with progressively worsening weakness of both upper and lower extremities and inability to perform daily activities. His symptoms started 12 weeks prior with difficulty standing from a seated position. He felt subjectively better for some time until a week prior, when he became bedbound. He had diarrhea 6 months ago, with 5-6 loose bowel movements a day for a few weeks. Vital signs on admission was normal. On neurological examination, he was alert and oriented, with bilateral upper and lower extremity flaccid paralysis, diffuse muscle atrophy, bilateral hand and foot drop, negative Hoover sign, diffuse areflexia, and intact sensation. Cerebrospinal fluid (CSF) analysis showed WBC 0 and protein level 136. MRI cervical, thoracic, and lumbar spine were normal. EMG revealed sensory involvement with positive sharp waves in proximal muscles along with fibrillations. Intravenous immunoglobulin (IVIG) was initiated at 0.4 mg/kg for 5 days. Infectious workup for COVID-19, stool culture, HIV, TB, RPR and campylobacter jejuni antibody (Ab), was negative. ANA was positive in a speckled pattern with titres 1:1280, with a positive RNP Ab, SS-A, and RF IgM, IgG and IgA. Rest of the autoimmune workup (anti-dsDNA, anti-CCP, SS-B, aldolase, anti-Jo-1, anti-Scl-70, p-ANCA, c-ANCA, anti-GM1, anti-GQ1b, and anti-GD1a ganglioside Ab) was negative. The myositis specific 11 Ab panel was negative. Despite IVIG therapy, he developed dysphagia, respiratory distress, with a negative inspiratory force of -0, requiring intubation. He had a tracheostomy and PEG tube placed and remains quadraplegic nearly 120 days later. Discussion(s): The authors report a unique case of a patient who became progressively weak over 3 months, leading to complete quadriplegia. Interestingly, this is more consistent with chronic inflammatory demyelinating poly-neuropathy (CIDP), as AMSAN typically develops over a short period of 2 to 4 weeks [2]. Despite having negative anti-GM1 and anti-GD1a Ab (in which positive Ab are pathognomonic but not always present in AMSAN syndrome), the patient had weakness that began in the lower extremities, progressing to paralysis, along with albuminocytological dissociation on CSF analysis, pointing to a GBS diagnosis [3]. He had sensory involvement in the EMG, thus making the diagnosis as AMSAN. He had an undiagnosed, asymptomatic autoimmune process most consistent with MCTD. Whether the two disease processes are related to each other is a concept that has not yet been investigated. Pediatric Clinical Case Reports Concurrent Session Saturday February 4, 2023 1:00 PM Copyright © 2023 Southern Society for Clinical Investigation.

Spotting the Needle Amongst the Haystack - When Asthma Isn't Asthma

Introduction/Background: Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss Syndrome, is a rare, small to medium vessel ANCA associated vasculitis. Hallmarks of EGPA include asthma, chronic rhinosinusitis, and peripheral neuropathy. EGPA is characterized by a prodrome of asthma and allergic rhinitis, followed by peripheral blood hyper-eosinophilia and accumulation of extravascular eosinophils, and finally systemic vasculitis. Extrapulmonary involvement is common, sometimes with fatal outcomes. The onset of EPGA is typically between 25-50 years;however, EGPA also occurs during childhood and has a significant morbidity and mortality. Description/Method: Our patient presented to the emergency department with a 2-week history of lethargy, wheeze and left sided neck swelling. After testing COVID-19 positive eight months prior to this, she developed wheezy episodes and was subsequently diagnosed with asthma which was managed with bronchodilators as required. She was reviewed by an allergist who confirmed a dust mite allergy and prescribed Montelukast. She remained well during the summer months however during winter she had 3 distinctive episodes of wheeze and cough which were managed by antibiotics and prednisolone. In the emergency department, an echocardiogram was performed which showed a cardiac tamponade. She was transferred to CICU where she had a pericardial drain inserted. The fluid was abundant with inflammatory cells. Multiple investigations were performed as follows: Hb: 135g/L, wbc: 20.30 x 10 9/L, Eosinophils: 12.77 x 10 9/L, CRP: 51 mg/L, ESR: 75 mm/hr, LDH: 1188 IU/L, IgE: 8000 UI/ml, ANA, ANCA: negative. CT chest showed mediastinal lymphadenopathy and patchy bilateral infiltrate and cardiac MRI showed myopericarditis and LV fibrosis. BMA showed no malignant cells and sinusitis was confirmed by CT. On examination, she was underweight. Her nasal mucosa looked inflamed. Otherwise systemic examination was unremarkable. In the context of poor ejection fraction (20%) with LV fibrosis, urgent MDT was arranged and concluded that our working diagnosis was EGPA. The decision was made to start IV methylprednisolone 10mg/kg/day for 3 days and Ivermectin. That night our patient had a VF arrest which required a single shock conversion 4J/kg. There was 7-minute downtime. Treatment was escalated to include cyclophosphamide, rituximab and plasmapheresis. The patient made a remarkable recovery, extubated and transferred to a normal ward. Her eosinophils count and inflammatory markers improved dramatically following treatment. However, she developed severe neuropathic left leg pain and NCS confirmed peripheral neuropathy Discussion/Results: EGPA is a very rare disease and diagnosis can be challenging especially with the absence of histopathology diagnosis. Early empirical treatment especially in a very ill child in intensive care unit can save lives and divert the progress of the disease. This patient has fulfilled the American College of Rheumatology criteria to diagnose EGPA including asthma, eosinophil count > 10% of upper normal, peripheral neuropathy, pulmonary infiltrates on CT thorax and paranasal sinuses abnormalities. Cardiac biopsy of the fibrotic mass may be a useful tool for diagnosis;however, this invasive procedure may expose this patient with high risk of fatal arrhythmias. Since other causes of eosinophilia were ruled out including parasitic infections, lymphoproliferative disorders, and rare primary immunodeficiency syndromes (hyper-IgE syndrome due to STAT3 or DOCK8 deficiency and Omenn syndrome) and the patient responded well to treatment, the diagnosis of EGPA was supported. Key learning points/Conclusion: Asthma not responding to bronchodilator could be another diagnosis Eosinophilia should be interpreted with caution. Defer the need for histopathology diagnosis in critically ill children Cardiac involvement is a life-threatening marker Early diagnosis prevents life threatening complications.

Acute renal infarction presenting as hypertensive urgency

Case Report: A 46-year-old lady with medical history of hypertension, diabetes mellitus, and peripheral neuropathy was admitted to the hospital with the diagnosis of sepsis without septic shock secondary to a right foot pressure ulcer. Her presentation was non-specific as she was complaining of fatigue, myalgia, fever, and chills. Routine COVID-19 test was done on admission and it came back positive despite her denying having any respiratory symptoms. She was being treated with fluids and antibiotics until her third night of admission. According to the patient, she got up to use the restroom when she suddenly noticed weakness in her lower extremities. She thought it may be due to a muscle spasm;hence, she did not notify the medical team. Later, her nurse was routinely checking the patient's blood pressure when she noted a blood pressure of 220/105 mmHg. She then received a total of 3 doses of intravenous labetalol over three hours;however, her blood pressure continued to be elevated. Patient did endorse right flank pain but it was responding to intravenous fentanyl. The on-call physician then proceeded to perform a full physical examination and noted paleness, weakness, and absent pulses in bilateral lower extremities. A STAT computed tomography (CT) angiogram of the abdominal aorta and iliofemoral arteries was performed and it revealed low-density defects in the right kidney compatible with infarcts, occlusive thrombus in the infrarenal abdominal aorta and extensive bilateral arterial thrombosis. Vascular surgery was immediately consulted and they kept the patient on heparin drip and took her to the operation room within few hours for thrombectomies. Her blood pressure improved following the removal of the thrombus and there were no other documented occurrence of uncontrolled hypertension during her hospitalization. Discussion(s): Acute renal infarction is an arterial vascular event that leads to sudden disruption of blood flow in the renal artery. It can often be diagnosed late due to its rare incidence. In addition, it has a nonspecific clinical presentation that can mimic many common causes. The most common causes of renal infarction include atrial fibrillation, endocarditis, ischemic heart disease, hypercoagulable disorders, and spontaneous renal artery dissection. A case report published by Bourgault M, et al. on renal infarction suggested that around 97% had abdominal/flank pain and 48% of patients had marked uncontrolled hypertension at initial presentation of renal infarction. Our patient did not have any of the afore mentioned risk factors except for a possible hypercoagulable state from her COVID-19 infection and she did present with the two most common presentations. In conclusion, clinicians should have a low threshold for the suspicion of renal ischemia in patients with severe hypertension and flank pain. Copyright © 2023 Southern Society for Clinical Investigation.

Electrophysiological assessment in patients with COVID-19-related peripheral neuropathies and myopathies: a systematic review.

Neurological manifestations associated with Coronavirus Disease-2019 (COVID-19) are commonly reported, but patients were not referred to perform the electrophysiological assessment. We aimed to review the existing literature on clinical studies on COVID-19 peripheral neuropathy to correlate patients' symptoms and characteristics with nerve conduction studies/electromyography (NCS/EMG) outcomes. This protocol is registered in the Open Science Framework (https://www.doi.org/10.17605/OSF.IO/ZF4PK). The systematic search included PubMed, ScienceDirect, and Google Scholar, for articles published from December 2019 to March 2022. A total of 727 articles were collected, and according to our inclusion and exclusion criteria, only 6 articles were included. Of 195 participants, only 175 underwent NCS/EMG assessment. Of these, 44 participants (25.1%) had abnormal EMG, 54 participants (30.8%) had abnormal motor NCS, and only 7 participants (4%) had abnormal sensory NCS. All cases presented with myopathy, while a limited number of cases presented with polyneuropathy. According to motor NCS and EMG, the most affected nerves were the tibial and peroneal in the lower extremities and the ulnar nerve in the upper extremities. Interestingly, the median nerve was reported to be associated with the severity and the rate of motor recovery of patients with COVID-19. COVID-19 generates a demyelinating motor neuropathy and myopathy. Clinicians are encouraged to refer patients with COVID-19 presenting with neurological symptoms to be assessed by electrophysiological methods to objectively determine the nature of their symptoms, follow their prognosis, and plan their rehabilitation.

Effects of COVID-19 on Synaptic and Neuronal Degeneration.

Neurons are the basic building blocks of the human body's neurological system. Atrophy is defined by the disintegration of the connections between cells that enable them to communicate. Peripheral neuropathy and demyelinating disorders, as well as cerebrovascular illnesses and central nervous system (CNS) inflammatory diseases, have all been linked to brain damage, including Parkinson's disease (PD). It turns out that these diseases have a direct impact on brain atrophy. However, it may take some time after the onset of one of these diseases for this atrophy to be clearly diagnosed. With the emergence of the Coronavirus disease 2019 (COVID-19) pandemic, there were several clinical observations of COVID-19 patients. Among those observations is that the virus can cause any of the diseases that can lead to brain atrophy. Here we shed light on the research that tracked the relationship of these diseases to the COVID-19 virus. The importance of this review is that it is the first to link the relationship between the Coronavirus and diseases that cause brain atrophy. It also indicates the indirect role of the virus in dystrophy.