Bilateral Carpal Tunnel Syndrome Research Articles

P.059 Weill-Marchesani Syndrome – a rare etiology for bilateral carpal tunnel syndrome in children

Background: Carpal tunnel syndrome (CTS) is less common in children but can be associated with significant disability. Pediatric CTS can be associated with an underlying disorder most commonly storage disorders including mucopolysaccharidoses (MPS). We report a patient with bilateral severe CTS secondary to Weill-Marchesani Syndrome (WMS). Methods: A retrospective chart review was completed. Results: A five-year-old female presented with a three-year history of bilateral thumb weakness and insensate digits two and three. Nerve conduction studies (NCS) revealed severe bilateral CTS. She underwent bilateral carpal tunnel release (CTR). Unfortunately, post-operative NCS was unchanged. Ultrasound showed significant median nerve compression with flexor tendon thickening. Metabolic investigations showed no evidence of a storage disorder. Trio whole exome sequencing showed two de novo likely pathogenic variants in ADAMTS10: c.1174delC, p.H392TfsX9 and a deletion of exons 3-8. Her exam was also noted to show bilateral camptodactyly and brachydactyly, and bilateral cataracts characteristic of WMS. Conclusions: Identifying the etiology of CTS is important for management and prognosis. WMS is a genetic connective tissue disorder that can cause brachydactyly and abnormal tendon thickening, which can have implications on surgical outcomes. Awareness of this diagnosis prior to surgery would allow for better patient counseling and management decisions.

SUTURE CHOICE IN CARPAL TUNNEL SURGERY: A RANDOMIZED CONTROLLED TRIAL

ObjectiveCarpal tunnel release surgery is a commonly performed procedure for alleviating symptoms of median nerve compression and restoring hand function. With pressure on theatre time these procedures are now commonly performed in a step-down out-patient facility under local anaesthetic. The choice of suture for skin closure in this procedure can impact the quality of wound healing, patient outcomes and the follow-up required however the question of the best type of suture remains unanswered. The purpose of this study was to compare the outcomes of absorbable and non-absorbable sutures using a randomised control trial design.MethodsEighty patients diagnosed with bilateral carpal tunnel syndrome were enrolled and underwent outpatient carpal tunnel release surgery under local anaesthetic in a staged fashion. Random number generation was used to assign each hand to receive interrupted nylon or Vicryl Rapide sutures. Pre-operative data collection included patient demographics, ASA, inflammatory conditions, smoking status as well as a Boston Carpal Tunnel Questionnaire (BCTQ) for each hand. Patients were followed up at 2 and 6 weeks after each operation and the BCTQ was repeated along with the Patient and Observer Scar Assessment Scale and the VAS score for wound discomfort. This study has approval from the DHB ethics committee, Local Iwi, HDC and ANZ Clinical Trials:ACTRN12623000100695.ResultsStatistical analysis assessed patient preference and the scores between the groups. Multi-variate analysis was performed to assess the factors that may be contributing to patient choice.ConclusionInsights into patient preference and clinical outcomes associated with absorbable sutures and non-absorbable sutures in the setting of out-patient surgery are discussed.

A case report of ATTR-amyloidosis following cardiac transplantation: thick ventricles that look alike

Abstract Background Transthyretin (ATTR-) amyloidosis is more prevalent than initially thought. As much as 13% of patients hospitalized with HFpEF may have ATTR-cardiomyopathy (CM). Conversely, heart transplant patients may manifest left ventricular hypertrophy or diastolic dysfunction, especially late after transplantation. Case Summary We present a case of a 82-year old male heart transplant patient, 31 years following orthotopic heart transplantation. While he was satisfied with his exercise capacity as an octogenarian, several years before he required pacemaker implantation due to 3rd degree AV block, had bilateral carpal tunnel syndrome treated with carpal tunnel release surgery and experienced idiopathic sudden deafness. Based on increasing left ventricular wall thickness during routine follow-up, a diagnosis of ATTR-amyloidosis was suspected. Ultimately, the diagnosis was confirmed non-invasively with a specific scintigraphic exam, while an additional physicochemical stain on an endomyocardial biopsy taken several years before provided pathological proof. We initiated tafamidis, yet stopped this treatment after one month because of gastro-intestinal intolerance. Ultimately, our patient died two years later due to heart failure. Discussion Our case shows the long delay between the onset of transthyretin deposition, the presence of clinical signs and the final diagnosis. Echocardiographic findings suggestive for ATTR-CM include left ventricular hypertrophy and diastolic dysfunction, which are both common in heart transplant patients. Yet, ATTR-CM should be considered in the differential diagnosis, especially late after transplantation, in this closely monitored population.

Diabetic cheiroarthropathy in uncontrolled Type 2 diabetes with positive Anti-Nuclear Antibodies: a case report from Sudan

Background: Diabetic cheiroarthropathy, also known as limited joint mobility, is one of the long-standing complications of type 2 Diabetes Mellitus (DM). It affects 8-50% of patients with type 1 diabetes and is also seen in type 2 diabetic patients. Consequently, it can mimic many rheumatological diseases and is often underdiagnosed. We present a case of a long-standing poorly controlled diabetes with diabetic cheiroarthropathy and diabetic neuropathy, along with positive ANA in the absence of any correlated autoimmune or rheumatological diseases. Case presentation: A 52-year-old female patient with poorly controlled diabetes (her last HbA1c reading was 9.5%) presented to Rheumatology clinic with flexion deformities of the fingers. The patient has impaired vibration, two-point discrimination and pinprick sensation in gloves and stock distribution, indicating peripheral neuropathy, entrapment neuropathy in the forms of bilateral carpal tunnel syndrome, and the diagnosis of diabetic cheiroarthropathy was made. Additionally, she has a positive prayer sign and tabletop sign. Despite the absence of symptoms and signs of autoimmune disorders, this patient has positive antinuclear antibodies global (ANA positive by Indirect Immuno-Fluorescence (IIF) 1\320 nucleolar pattern) with a negative: ANA profile, rheumatoid factor (RF) and Anticyclic Citrullinated Peptide Antibody (ACPA). Conclusion: Regular and careful hands examination should be part of clinical assessment for diabetic patients as it could be a very simple and useful screening tool for diabetic cheiroarthropathy. Physicians can use this condition as a mirror for microvascular complications of diabetes. This allows for early detection and appropriate interventions to prevent further progression of diabetes-related complications. It is also essential to consider the presence of positive ANA in diabetic cheiroarthropathy despite the absence of any rheumatological and autoimmune diseases.

Late Onset of Severe Demyelinating Peripheral Neuropathy in a 62-Year-Old African American Woman.

Hereditary neuropathies are typically associated with an early onset of symptoms, but same types of neuropathies may also manifest late, after the age 50 years. A 62-year-old African American woman presented with a 6-year history of gait unsteadiness and has been using a walker since the age 57 years after an unwitnessed fall. Gradual worsening of walking difficulties was later followed by decreased dexterity. The family history was negative for neuromuscular disorders, including neuropathy. On examination, the patient had both distal and proximal weakness with distal sensory loss to all modalities and hyporeflexia. Charcot Marie Tooth Examination Score was 12. Previous electrodiagnostic testing at the age 60 years showed severe sensorimotor demyelinating polyneuropathy with bilateral severe carpal tunnel syndrome. Genetic testing showed a homozygous pathogenic mutation in SH3TC2 gene (c.2860C>T; p.Arg954*), associated with CMT4C. CMT4C is the most common recessive demyelinating sensorimotor polyneuropathy and overall comprises 0.4%-1.7% of all patients with Charcot-Marie-Tooth disease. It is more common in French Canadians and Spanish Roma and in recent natural history study; only 1 of 56 patients was African American. This report demonstrates sporadic occurrence of CMT4C in other ethnic groups as well.

Relationship between Gravidity, Parity, and Neurophysiological Features in Carpal Tunnel Syndrome (CTS) Patients with a History of Pregnancy.

It is not yet clear if gravidity and parity have any relationships with the electrodiagnostic parameters of carpal tunnel syndrome (CTS). To determine whether there is a relationship between electrodiagnostic findings, gravidity, and parity number in CTS. Female patients over 18 years of age with CTS were included in this retrospective cohort study. The gravidity/parity number, median nerve compound muscle action potential (CMAP), and compound nerve action potential (CNAP) of the patients were analyzed. The two subgroups of the Boston carpal tunnel syndrome questionnaire (BCTSQ): The Symptom Severity Scale (SSS) and Functional Severity Scale (FSS) were applied to the patients. CTS patients were divided into two groups aged at first pregnancy ≤20 years and >20 years. One hundred and eight CTS extremities (seven right-sided CTS, three left-sided CTS, 49 bilateral CTS) of 59 patients were included. The median (interquartile range: 25%-75%) number of gravidity, parity, and abortion were 3 (2-5), 3 (2-4), and 0 (0-0), respectively. Right-sided CTS patients at the age of first pregnancy ≤20 years had higher BCTSQ-SSS/FSS scores and median nerve CMAP latency compared to patients at the age of first pregnancy >20 years (P = 0.029 for SSS; P = 0.042 for FSS; and P = 0.041 for CMAP latency). A negative correlation was found between the gravidity/parity numbers and median nerve CNAP/CMAP amplitudes (P = 0.028/0.031, r = -0.293/-0.289 for CNAP amplitude; and P = 0.006/0.035, r = -0.363/-0.283 for CMAP amplitude). Neurophysiological findings worsen as the number of gravidity and parity increase. Electrodiagnostic and clinical features of CTS may be worsening in females below 20 years at first pregnancy.

A clinical case of transthyretin amyloidosis with manifestations of seronegative arthritis

A clinical case of transthyretin amyloidosis with manifestations of seronegative arthritis

Abstract 12381: De Novo Multiple Myeloma in a Patient With Transthyretin Amyloid Cardiomyopathy

Background: The development of de novo multiple myeloma in a patient with transthyretin amyloid cardiomyopathy (ATTR-CM) is rare and is often associated with poor prognosis. Early and definitive diagnosis is crucial to improve survival. Case: A 63-year-old male was evaluated for heart failure. He had a history of hypertension, sick sinus syndrome status post dual chamber pacemaker, non-sustained ventricular tachycardia requiring ablation in addition to bilateral carpal tunnel syndrome, spontaneous biceps tendon rupture, and lumbar spinal stenosis. Transthoracic echocardiogram showed progressive severe left ventricular hypertrophy with a septal thickness of 2.0cm with a normal left ventricular ejection fraction. Decision-Making: Given his history, an amyloid evaluation was performed. Serum and urine assessment for light chain amyloidosis revealed elevated kappa free light chains with kappa/lambda free light chain ratio of 19.30. Bone marrow biopsy at that time showed normocellular bone marrow with less than 3% plasma cells. An abdominal fat pad biopsy was inconclusive. A cardiac MRI was unobtainable given non-compatible pacemaker leads and a technetium-99m pyrophosphate scintigraphy was deferred given his abnormal light chains. An endomyocardial biopsy was performed and revealed wild-type ATTR deposition by mass spectrometry. Serum genetic test confirmed the absence of TTR gene mutation. The patient was started on Tafamadis. Six months later, he was noted to have progressive elevation in kappa free light chains on serial evaluation and underwent a repeat bone marrow biopsy. This showed plasma cell myeloma with 25-30% marrow cellularity and flow cytometry consistent with kappa light chain multiple myeloma. He was started on Daratumumab, Lenalidomide, and Dexamethasone. This resulted in normalization of his free light chain ratio and morphologic remission on repeat bone marrow biopsy. Conclusion: In patients who are found to have monoclonal gammopathy, an endomyocardial biopsy is crucial to evaluate for amyloid cardiomyopathy. These patients should also be monitored for the progression to multiple myeloma.

Abstract 126: Bilateral Limb Shaking TIA secondary to Severe Bilateral Carotid Stenosis

Introduction A case describing bilateral limb shaking episodes in a patient with severe bilateral carotid disease ‐ a rare manifestation of limb‐shaking TIA. Methods '‐ Results CASE A 71‐year‐old male patient with a past medical history significant for type 2 diabetes mellitus and bilateral carpal tunnel syndrome is being followed for symptomatic management of known axonal sensorimotor diabetic polyneuropathy in the neuromuscular clinic. He reported on one of his follow‐up visits that he had been experiencing an eight‐month history of presyncopal to syncopal events occurring solely in the standing position, not followed by postictal state but amnesia to the syncope itself, and resulting in falls with mild injuries. He was experiencing new‐onset dry eyes and mouth but denied anhidrosis or early satiety, and cardiac event monitoring during one of these events was unremarkable for rhythmic causes. Examination was unchanged from previously and was significant for findings consistent with length‐dependent sensory loss with hyporeflexia/areflexia. The constellation of symptoms was suggestive of autonomic dysfunction, and while this may be seen with diabetic polyneuropathy, workup for alternative autonomic neuropathies (including SSA/SSB antibodies, paraneoplastic antibody panel, serum protein electrophoresis with immunofixation, serum free light chains, transthyretin amyloid) was obtained with plan for follow‐up. A few months later, he presented to the ED with intermittent upper extremity shaking (more pronounced on the right than on the left) preceding the syncopal events, which only occurred in the standing position or during physical activity and resolved with rest. There were no (transient) focal neurological deficits, including monocular vision loss or hemispheric syndrome. CTA of the head/neck was obtained and was notable for severe to critical stenoses of the bilateral internal carotid arteries (see figure 1). Duplex US revealed 80‐99% stenosis of both right and left proximal internal carotid arteries. The constellation of findings was most suggestive of bilateral limb‐shaking TIA secondary to bilateral carotid stenosis. He was started on secondary stroke prevention and referred to vascular surgery for evaluation of revascularization. The patient underwent left carotid endarterectomy briefly afterward and experienced resolution of the events – he later also underwent carotid endarterectomy of the right side and remains asymptomatic. DISCUSSION: Limb‐shaking TIA is a well‐described yet underrecognized manifestation of severe carotid disease reported by C.M. Fisher in 1962. The “limb shaking” episodes are typically unilateral, affecting the arm or leg, and are often mistaken for seizures [1]. Pathogenesis involves hemodynamic impairment related to extracranial/intracranial carotid stenosis or occlusion resulting in stereotypical recurrent contralateral limb shaking episodes precipitated by physical activity [2], [3]. The constellation of “limb shaking” spells precipitated upon standing or physical activity with resolution after activity cessation should raise suspicion for limb‐shaking TIA and warrant vascular imaging. Treatment includes medical secondary stroke prevention and revascularization procedures [4], which can alleviate or even resolve the transient symptoms [2]. Conclusion Limb‐shaking TIA is an important yet underrecognized manifestation of relative cerebral hypoperfusion related to severe cerebrovascular disease. This case describes bilateral limb shaking episodes in a patient with severe bilateral carotid disease ‐ a rare manifestation of limb‐shaking TIA.

Genetic screening for hereditary transthyretin amyloidosis with polyneuropathy in western Sicily: Two years of experience in a neurological clinic.

Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils. A prospective systematic genetic screening for ATTRv-PN was proposed in patients presenting with a sensory-motor idiopathic polyneuropathy and two or more "red flags" among the following: family history of polyneuropathy or cardiopathy, bilateral carpal tunnel syndrome, cardiac insufficiency, renal amyloidosis, lumbar tract stenosis, autonomic dysfunction, idiopathic gastrointestinal disease, amyloid deposits on biopsy, and vitreous opacities. The detection rate was calculated, and nonparametric analyses were carried out to underline differences among screened positive versus negative patients. In the first step, 145 suspected patients underwent genetic testing, revealing a diagnosis of ATTRv-PN in 14 patients (10%). Then, cascade screening allowed early recognition of 33 additional individuals (seven symptomatic ATTRv-PN patients and 26 presymptomatic carriers) among 84 first-degree relatives. Patients with a positive genetic test presented a higher frequency of unexplained weight loss, gastrointestinal symptoms, and family history of cardiopathy. A systematic screening for ATTRv-PN yielded an increased recognition of the disease in our neurological clinic. Unexplained weight loss associated with axonal polyneuropathy had the highest predictive value in the guidance of clinical suspicion. A focused approach for the screening of ATTRv-PN could lead to an earlier diagnosis and identification of asymptomatic carriers, who will be promptly treated after a strict follow-up at the clinical onset.

Prevalence, Predictors and Diagnosis of Cardiac Amyloidosis in Patients with Aortic Stenosis

Cardiac amyloidosis and aortic stenosis often share a common clinical phenotype, and are associated with morbidity and mortality if untreated. Cardiac amyloidosis is present in ~15% of patients with aortic stenosis. Clinical suspicion for cardiac amyloidosis in aortic stenosis is often raised based on history (bilateral carpal tunnel syndrome, severe lumbar spinal stenosis, spontaneous biceps rupture), chronic troponin elevation, electrocardiographic features (low-voltage criteria, pseudoinfarct pattern), echocardiogram (bilateral ventricular hypertrophy, abnormal longitudinal strain) and magnetic resonance imaging (late gadolinium enhancement, elevated T1 and T2). Eventual diagnosis of cardiac amyloidosis is based either on pyrophosphate nuclear scintigraphy or tissue biopsy depending on which subtype of cardiac amyloidosis is suspected.

Wide-awake local anesthesia no tourniquet and dexamethasone (WALANT-D) for modified Camitz opponens plasty in severe carpal tunnel syndrome-a retrospective study of 30 cases

BackgroundTo analyze the outcome of modified Camitz opponens plasty using the wide-awake local anesthesia no tourniquet with dexamethasone (WALANT-D) technique in severe carpal tunnel syndrome (CTS). MethodsA retrospective review was performed in 30 hands of 27 patients who underwent Camitz opponens plasty for severe CTS between 2019 and 2021. All patients had 8 mg of dexamethasone mixed with WALANT. Preoperative active palmar abduction, grip strength, side, and pulp pinch strength, Kapandji score, and electrophysiological assessment of compound muscle action potential (CMAP) for abductor pollicis brevis (APB) were compared with the postoperative values. The palmaris longus had dual insertion into the abductor pollicis brevis and extensor expansion. The time interval of post-operative pain-free was noted. The Disabilities of the Arm, Shoulder, and Hand (DASH) and Carpal Tunnel Syndrome instrument (CTSI) also assessed the functional outcome. ResultsThe mean age of patients was 35 years (range 32–58 years). There were five male and 22 female patients. Of the female patients, three females had severe bilateral CTS. Twenty right and ten left hands were affected. The mean follow-up of our study was 12.5 months (range 10–14 months). The patients were pain-free for an average of 19.5 h postoperatively. There was a significant improvement in the thumb palmar abduction, grip strength, side, and pulp pinch strength, DASH score, CTSI, and APB-CMAP (p < 0.05) at the final follow-up. ConclusionsModified Camitz opponens plasty with a dual insertion into APB and extensor expansion effectively improves thumb opposition and daily activities. The tendon tensioning, checking the pulley impingement, appreciation of active movements, and a comfortable patient operative experience are advantages of the WALANT. Adding dexamethasone as an adjuvant to WALANT prolongs the analgesia and duration of the nerve block. Level of evidenceIV, Retrospective case study.

Idiopathic carpal tunnel syndrome in male patients

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Introduction. &amp;lt;/strong&amp;gt;The carpal tunnel syndrome (CTS) in male patients, due to anatomical characteristics and the perception of CTS-related symptoms, remains undetected for a long time. Men respond less well to CTS treatment, and early detection enables conservative treatment of mild and moderate CTS. The aim of this paper was to examine the average age, the frequency of bilateral CTS and its correlation with the age, and to determine the grade of electrophysiological damage of the median nerve in male patients with idiopathic CTS diagnosed by electromyoneurography. &amp;lt;strong&amp;gt;Methods.&amp;lt;/strong&amp;gt; The retrospective study included 83 male patients, aged from 32 to 81 years, with complaints of unilateral CTS on the right, dominant hand. All patients underwent EMNG for confirmation of CTS and the degree of median nerve damage. Statistical analysis was performed by methods of descriptive statistics, t-test, Wilcoxon signed rank test, and Pearson&amp;amp;rsquo;s correlation coefficient. The value of p &amp;amp;lt; 0.05 was considered statistically significant.&amp;lt;strong&amp;gt; Results.&amp;lt;/strong&amp;gt; The average age of patients was 55.84 years. The bilateral CTS was confirmed in 88.4%, most often of a moderate degree and more pronounced on the right, dominant hand (p=0.001). In cases of bilateral CTS, age did not correlate with the grade of CTS changes in both hands. The changes in the dominant hand were more pronounced in patients older than 51 years.&amp;lt;strong&amp;gt; Conclusion.&amp;lt;/strong&amp;gt; Male patients with idiopathic CTS usually have bilateral CTS, with more pronounced changes on dominant hand. Bilaterality of CTS and the degree of median nerve damage are not connected with age.&amp;lt;/p&amp;gt;

Occult Amyloid Deposition in Older Patients Presenting With Bilateral Carpal Tunnel Syndrome or Multiple Trigger Digits

The diagnosis of amyloidosis is important for early intervention, disease monitoring, and prevention of complications and progression. Carpal tunnel syndrome (CTS) and trigger digit (TD) are two common conditions associated with early disease. The purpose of this study was to define disease prevalence among patients with bilateral CTS and multiple TDs and assess for an increased rate of diagnosis in the presence of both. Men older than 50 years and women older than 60 years of age diagnosed with bilateral CTS, multiple TDs, or a combination of the 2 were prospectively enrolled in our study. Tenosynovial biopsy samples taken at the time of surgery were tested for the presence of amyloid using Congo red staining. Demographic and medical covariates were also collected and analyzed for differences between amyloid-positive and -negative patients. Fifty-six patients were enrolled in the study, and nine patients tested positive for amyloid deposition. The demographics and medical comorbidities were similar between amyloid-positive and -negative patients. Thirty patients with bilateral CTS were enrolled, and four tested positive for amyloid. For patients with multiple TDs, a total of 17 patients were enrolled, and 4 tested positive for amyloid. Among patients with multiple TDs, only men tested positive for amyloid and were, on average, younger than those who tested negative (61 and 73 years, respectively). Patients presenting with a combination of CTS and TD did not exhibit increased amyloid discovery. Hand surgeons should consider tenosynovial biopsy in men older than 50 years and women older than 60 years presenting with either bilateral CTS or multiple TDs. Prognostic IV.

Subjective and Objective Differences in Patients with Unilateral and Bilateral Carpal Tunnel Syndrome and the Role of Obesity in Syndrome Severity.

It remains unclear whether physiologic differences exist in musculoskeletal ultrasound nerve measurements when comparing bilateral and unilateral carpal tunnel syndrome (CTS) patients. Similarly, the influence of body mass index on CTS severity is not well characterized. Unilateral and bilateral CTS patients were seen from October of 2014 to February of 2021. Obese and nonobese CTS patients were compared. Median nerve cross-sectional area (CSA), Boston Carpal Tunnel Syndrome Questionnaire (BCTSQ), and six-item Carpal Tunnel Symptom Score (CTS-6) measures were obtained. Nerve conduction studies recorded distal motor latency (DML) and distal sensory latency (DSL). Statistical analysis used Wilcoxon signed rank testing for paired continuous variables, Mann-Whitney U testing for nonpaired continuous variables, and chi-square testing for continuous variables, with a significance level of P < 0.05. A total of 109 (218 nerves) bilateral and 112 (112 nerves) unilateral CTS patients were reviewed. Bilateral patients had larger median nerve CSAs on their more symptomatic side, when defined by BCTSQ score ( P < 0.0001), CTS-6 score ( P < 0.0001), DML ( P < 0.0001), and DSL ( P < 0.01). Bilateral patients also had higher symptom severity scale ( P < 0.01) and DSL ( P < 0.001) outcomes compared with unilateral patients. Obese patients had higher median nerve CSA ( P < 0.01), prolonged DML, and prolonged DSL ( P < 0.0001) values despite similar CTS severity (BCTSQ and CTS-6). Ultrasound identifies the more symptomatic side in bilateral patients, which correlates with increasing severity (NCS and BCTSQ). Obesity increases median nerve CSA and prolongs nerve conduction studies without influencing CTS severity. This information can be used when considering which diagnostic test to order for CTS.

P339 LIGHT–CHAIN CARDIAC AMYLOIDOSIS WITH FULMINANT EVOLUTION, A NOT–SO–RARE CONDITION: THE IMPORTANCE OF EARLY DIAGNOSIS

Abstract Introduction Amyloid AL results from misfolding of immunoglobulin light chain (kappa or lambda) secreted by abnormal plasma cells such as in multiple myeloma. It is a rare, multisystemic disease with an estimated annual incidence rate of 6 to 10 cases per million inhabitans in Western countries. The prognosis of this hematologic neoplasm is guided by the extent of cardiac involvement; if untreated, survival rate is less than 6 months; with early initiation of chemotherapy treatment, median survival can range from 4 to 10 years, except for high–risk cases. Case report: 58–year–old patient presented to emergency department in May 2022 with the first syncopal episode and sphincter release. The patient had no cardiovascular risk factors. Echocardiografy showed markedly hypertrophic left ventricle with hyper–reflective walls with a granular–sparkling appearance. Electromyography revealed sensory–motor polyneuropathy, early–stage autonomic neuropathy and bilateral carpal tunnel syndrome. Implantation of a loop recorder was performed to investigate the cause of syncope. In suspected amyloidosis, the patient underwent electrophoresis, which showed no monoclonal peaks, serum and urine kappa and lambda light chains were negative. Bone scintigraphy showed no osteotropic radiopharmaceutical uptake in the heart. Cardiac magnetic resonance imaging (MRI) revealed biventricular hypertrophic phenocopy (concentric hypertrophy) with diffuse edema–like tissue alterations. The patient was asymptomatic. In August 2022, hematologic evaluation revealed a monoclonal band for lambda light chains in repeated immunofixation and bone marrow biopsy showed 9–10% monoclonal lambda plasma cells. The patient was referred to a specialized center for amyloidosis, where a biopsy of peri–umbilical fat was performed to confirm the diagnosis and initiate therapy. In October 2022, due to recurrent syncope, advanced atrioventricular block and extreme bradycardia at loop recorder, a dual–chamber pacemaker was implanted. A few days after discharge, the patient suffered cardiac arrest at home due to electromechanical dissociation and died, only 5 months after the first symptom. Conclusion AL amyloidosis is an aggressive hematological neoplasm, with cardiac involvement. Early diagnosis is crucial for timely initiation of therapy, which is the only means available to increase patient survival. It is important to maintain a high level of awareness and diagnostic suspicion for this condition.

P5 DISCOVERY OF A NEW HATTR GENETIC VARIANT: A CASE REPORT OF A PATIENT WITH CARDIAC UPTAKE AT 99–MTC–DIPHOSPHONATES SCINTIGRAPHY AND ABNORMAL MONOCLONAL PROTEINS TESTS

Abstract Introduction Cardiac amyloidosis is an infiltrative disease that remains an under–diagnosticated cause of heart failure. Diagnostic algorithms focus on identifying the two most frequent forms of the disease, light chains amyloidosis (AL) and transthyretin amyloidosis (ATTR), by the initial use of 99mTc–DPD scintigraphy coupled to assessment of monoclonal proteins. Etiological distinction is and of pivotal importance since the availability of specific disease modifying treatments. Case Description We report the case of a 61–year–old man hospitalized for new onset of heart failure. Past medical history highlights bilateral carpal tunnel syndrome and monoclonal gammopathy of undetermined significance (MGUS). Cardiovascular examination reveals clinical signs of pulmonary and peripheric congestion. ECG shows conduction disturbances and low QRS voltage. Transthoracic echocardiography reveals left ventricular hypertrophy, normal systolic function (LVEF 58%), 3rd degree LV diastolic disfunction and mild pericardial effusion. Laboratory tests shows abnormal levels of TnT and pro–BNP. A diagnosis of cardiac amyloidosis is considered, and further exams are executed: cardiac magnetic resonance, haematological laboratory tests and 99mTc–DPD scintigraphy (tab. 1). Since both bone scintigraphy and monoclonal proteins tests are positive, diagnosis of cardiac amyloidosis cannot be made without non–invasive modalities (fig.1) and the patient is referred to an Amyloidosis Centre. Haematological evaluation and abdominal fat pad biopsy show stability of haematological disease and confirms the deposition of amyloidogenic TTR both in wild–type and mutated Ile88Arg variants. The results of genetic analysis confirms the presence of a heterozygous mutation of TTR gene (p.Ile88Arg – c.263T&amp;gt;G) (fig. 2). This mutation is not reported in database ClinVar nor in gnomAD, but according to the ACMG criteria it can be considered likely pathogenic. Considering the final diagnosis of cardiac hATTR the patient is considered eligible for treatment with Tafamidis. Discussion and Conclusion Despite clinical history with cardiac conduction system abnormalities and bilateral carpal tunnel syndrome, some gene TTR variants can bring false negative results at 99mTc–DPD scintigraphy, so ATTR form should not be excluded basing on non–invasive modalities. Performing a compete diagnostic workup led us to discover a new TTR pathogenic variant and confirm ATTR form without performing endomyocardial biopsy.

P326 FALSE POSITIVE BONE–SCINTIGRAPHY IN ELDERLY HYPERTROPHIC CARDIOMYOPATHY

Abstract Differential diagnosis of cardiomyopathies with hypertrophic phenotype is crucial because some secondary forms of cardiac hypertrophy can be susceptible of specific treatment aimed to revert and/or stabilize the increase in wall thickness.A positive nuclear scintigraphy with hydroxy bisphosphonate bone tracer (99mTc–HPD)is believed to have high sensitivity and specificity for the diagnosis of transthyretin (TTR) amyloid cardiomyopathy. An 85–year–old man with systemic arterial hypertension was admitted because of pre–syncope associated to evidence at Holter monitoring of both bradiarrhythmias(1st degree AV block with PR interval of 300 ms and several episodes of 2nd degree Mobitz type 1 AV block with electrical pause &amp;gt;3 s) and tachyarrhythmias.He suffered from a bilateral carpal tunnel syndrome that underwent surgery 2 years earlier.Routine laboratory tests were normal except for elevated cardiac troponin HS(0.295 mcg/L,nv &amp;lt; 0.014 mcg/L) and N–terminal pro–BNP (384.3 pg/mL,nv = 0–254 pg/mL).Because of clinical suspicion of senile amyloidosis,nuclear scintigraphy with hydroxy bisphosphonate bone tracer(99mTc–HPD)was performed,that revealed a grade 3 myocardial uptake.Serum–urine immunofixation and immunoglobulin free light–chain was negative for monoclonal gammopathy.Neurological examination was unremarkable Genetic test did not show TTR mutation.Thus,a diagnosis of wild–type TTR cardiac amyloidosis was suggested.The patient,in view of Tafamidis treatment,underwent a LV endomyocardial biopsy.Six specimens were drawn from the LV,cut and processed for histology,immunohistochemistry,and transmission electron microscopy. Unexpectedly,histology failed to confirm amyloid deposition but revealed the presence of severely hypertrophied disarrayed cardiomyocytes fragmented in short runs by interstitial and replacement fibrosis,denoting a sarcomeric hypertrophic cardiomyopathy.Congo red staining at polarized light scored negative for areas of apple–green florescence.Immunohistochemistry form transthyretin,kappa/lambda light chain and SAA was negative.Transmission electron microscopy failed to demonstrate the presence of rigid unbranched amyloid fibrils.Thus,a final diagnosis of hypertrophic cardiomyopathy was reached. Coclusion:A positive cardiac signal of bone scintigraphy can occur in other pathologic settings.Future studies are needed to investigate the incidence of false–positive TTR cardiac amyloidosis to bone scintigraphy compared with endomyocardial biopsy.

P349 EARLY DIAGNOSIS OF HEREDITARY CARDIAC AMYLOIDOSIS(ATTRV) IN A CARRIER: WHEN IS ENDOMYOCARDIAL BIOPSY INDICATED?

Abstract Background Hereditary transthyretin amyloidosis (ATTRv) is a rare, adult–onset, autosomal dominant genetic disorder caused by mutations in the TTR gene. The growing availability of effective therapies determining a greater benefit the earlier they start, highlights the importance of identifying cardiac involvement even in the absence of left ventricular hypertrophy. Clinical Case A 58–year–old man came to our observation for exertional dyspnea and received a diagnosis of hereditary transthyretin amyloidosis (Val142Leu). Family screening led to the identification of the 56–year–old brother who was carrier of the same mutation. This patient was symptomatic for palpitations. Blood tests, including cardiac Troponin and NTproBNP, were normal. The ECG showed sinus rhythm, with normal atrioventricular and intraventricular conduction but frequent premature ventricular contractions. Transthoracic echocardiogram was normal, including strain rate evaluation. In order to identify early cardiac involvement, the patient underwent cardiac magnetic resonance imaging and biphosphonate scintigraphy that were negative for cardiac involvement. Neurological examination showed initial bilateral carpal tunnel syndrome. Due to the presence of premature ventricular contractions, the patient underwent to an endomyocardial biopsy which unpredictably showed a slight focal positivity to Congo Red staining, and immunohistochemistry confirmed a slight focal positivity for transthyretin. Therefore, the patient started therapy with Tafamidis. At 12–month follow up cardiac scintigraphy was still negative as well as ventricular thickness resulted within normal limits. Conclusion This case shows that in ATTR mutation carriers, an initial cardiac involvement can be present even in the absence of left ventricular hypertrophy and positive bisphosphonate scintigraphy. In the presence of clinical symptoms and/or suspicious signs of disease, such as arrhythmias, an endomyocardial biopsy may be indicated in order to start disease modifying therapy earlier.

C67 ATRIOVENTRICULAR BLOCK DUE TO CARDIAC CONDUCTION TISSUE INFILTRATION: A CLINICAL PRESENTATION OF TRANSTHYRETIN CARDIAC AMYLOIDOSIS

Abstract Background In cardiac amyloidosis, the deposition of insoluble amyloid fibrils can affect the cardiac conduction tissue, causing bradyarrhythmic clinical manifestations, often in the advanced stages of the disease. In this clinical case, atrioventricular block represented the clinical onset of transthyretin cardiac amyloidosis. Clinical case A 68–year–old man was admitted to our ward for recurrent syncopal episodes. He had in his medical history bilateral carpal tunnel syndrome. The electrocardiogram documented sinus rhythm with preserved QRS voltages, right bundle branch block, left anterior hemiblock, and first and second degree atrioventricular block with mean ventricular rate of 38 beats/min. A color–Doppler echocardiogram revealed increased left and right ventricular thickness (maximum thickness 16 and 10 mm, respectively), diastolic dysfunction, and preserved ejection fraction (60%). The patient underwent a coronary angiography, which was normal, and an endomyocardial biopsy of the left ventricle, which revealed the presence of hypotrophic and degenerated cardiomyocytes surrounded by large areas of amorphous substance that exhibited apple–green birefringence in polarized light after staining with Congo red, suggesting the diagnosis of cardiac amyloidosis. Sections of conduction tissue were included in the specimens, which appeared on histology as small myocytes positive by immunohistochemistry for HCN4, suggestive of conduction tissue cardiomyocytes. The conducting tissue was almost completely replaced by amyloid deposits positive by immunohistochemistry for transthyretin. The affected patient underwent a genetic test which revealed the mutation of the TTR gene (p.Thr79Lys). The patient subsequently underwent pacemaker implantation and started treatment with Tafamidis due to the absence of neurological involvement. Conclusion In patients presenting clinically with syncope and conduction abnormalities, the diagnosis of cardiac amyloidosis should always be considered, because they may represent the clinical onset of the disease.