Atraumatic splenic rupture in amyloidosis

BACKGROUND: Splenic involvement in amyloidosis is rather frequent (5-10%). An atraumatic rupture of the affected spleen is however an extremely rare event. We report on a patient with undiagnosed amyloidosis who underwent emergency splenectomy for atraumatic splenic rupture. METHODS: Review of the literature and identification of 31 patients, including our own case report, with atraumatic splenic rupture in amyloidosis. Analysis of the clinical presentation, the surgical management, the nomenclature and definition of predisposing factors of splenic rupture. RESULTS: We identified 15 women and 16 men (mean age 53.3 +/- 12.4 years; median 52, range: 27-82 years) with an atraumatic splenic rupture. Easy skin bruisability and factor X deficiency were detected in four (13%) and five patients (16%), respectively. The diagnosis of splenic rupture was made either by computed tomography (n = 12), ultrasound (n = 5), exploratory laparotomy (n = 9) or autopsy (n = 4). All patients underwent surgery (n = 27) or autopsy (n = 4). Amyloidosis was previously diagnosed in nine patients (29%). In the remaining 22 patients (71%), the atraumatic splenic rupture represented the initial manifestation of amyloidosis. Twenty-five patients (81%) suffered from primary (AL) and four patients (13%) from secondary amyloidosis (AA). In two patients, the type of amyloidosis was not specified. A moderate splenomegaly was a common feature (68%) and the characteristic intraoperative finding was an extended subcapsular hematoma with a limited parenchymal laceration (65%). In five patients with known amyloidosis, the atraumatic splenic rupture was closely associated with autologous stem-cell transplantation (ASCT) (16%). Three patients were suffering from multiple myeloma (10%). A biopsy-proven amyloidotic liver involvement was present in 14 patients (45%), which lead to atraumatic liver rupture in two patients. The splenic rupture related 30-day mortality was 26% (8/31). CONCLUSIONS: Atraumatic splenic rupture in amyloidosis is associated with a high 30-day mortality. It occurs predominantly in patients with previously undiagnosed amyloidosis. A moderate splenomegaly, coagulation abnormalities (easy skin bruisability, factor X deficiency) and treatment of amyloidosis with ASCT are considered predisposing factors for an atraumatic splenic rupture.

Localized amyloid light-chain amyloidosis and extramedullary plasmacytoma of the mitral valve

An unusual case of localized amyloid light-chain (AL) amyloidosis and extramedullary plasmacytoma of the mitral valve is described. The worsening of a mitral regurgitation led to investigations and surgery. The valve presented marked distortion and thickening by type AL amyloid associated with a monotypic CD138+ immunoglobulin lambda plasma cell proliferation. Systemic staging showed a normal bone marrow and no evidence of amyloid deposition in other localizations. The patient's outcome after mitral valve replacement was excellent. To our knowledge, this is the first description of a localized AL amyloidosis as well as of a primary extramedullary plasmacytoma of the mitral valve.

Systemic light-chain amyloidosis revealed by progressive nail involvement, diffuse alopecia and sicca syndrome: report of an unusual case with a review of the literature.

Immunoglobulin light-chain (AL) amyloidosis is a form of systemic amyloidosis in which the fibrils are derived from monoclonal light chains. We report a case of a 66-year-old woman presenting with nail changes, parchment-like hand changes, progressive alopecia and sicca syndrome. Histopathological studies of biopsy specimens of the scalp, the nail, minor labial salivary glands and abdominal skin revealed deposits of AL κ-type amyloid. Urine protein electrophoresis exhibited a weak band of κ-type light chains. Based on this striking case, we here review the characteristic nail and hair manifestations associated with systemic amyloidosis. Knowledge of these signs is important for an early diagnosis of systemic amyloidosis, identification of the underlying disease and patient management.

A single-centre cohort of patients with systemic light chain AL-amyloidosis treated with conventional chemotherapy or with high-dose chemotherapy and autologous stem cell transplantation.

BACKGROUND High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) has been reported to confer better prognosis in systemic light chain AL-amyloidosis as compared with conventional chemotherapy. However, only limited data are available so far on treatment and outcome of AL-amyloidosis patients in Switzerland. METHODS Within a single-centre cohort of patients with biopsy confirmed AL-amyloidosis diagnosed between January 1995 and December 2012, we aimed to investigate treatment effects in patients treated with conventional chemotherapy versus HDCT with ASCT. RESULTS We identified 50 patients with AL-amyloidosis treated with conventional chemotherapy and 13 patients who received HDCT with ASCT. Clinical characteristics differed between the groups for the age of the patients (59 years for patients with ASCT/HDCT vs 69 years; p= 0.0006) and the troponin-T value (0.015 μg/l vs 0.08 μg/l; p = 0.0279). Patients with ASCT showed a trend towards better overall survival, with median survival not yet reached compared with 53 months in patients on conventional chemotherapy (p = 0.0651). CONCLUSION Our results suggest that light chain AL-amyloidosis patients considered fit to undergo HDCT and ASCT may have a better outcome than patients treated exclusively with conventional chemotherapy regimens; however, the better performance status of patients receiving HDCT may have added to this treatment effect.

Microsurgical repair of the sural nerve after nerve biopsy to avoid associated sensory morbidity: a preliminary report

OBJECTIVE: The purpose of this article is to report our preliminary results regarding microsurgical repair of the sural nerve after nerve biopsy, in an attempt to reduce the well-described sensory morbidity and neuroma formation. METHODS: Three patients with a suspected diagnosis of peripheral neuropathy underwent sural nerve biopsies to establish definitive diagnoses. A 10-mm segment of the sural nerve was resected with local anesthesia. After harvesting of the specimen, the proximal and distal nerve stumps were carefully mobilized and united with epineural suture techniques, under a surgical microscope. Sensory evaluations (assessing the presence of hypesthesia/dysesthesia or pain) of the lateral aspect of the foot, in regions designated Areas 1, 2, and 3, were performed before and 6 and 12 months after the biopsies. A visual analog scale was used for pain estimation. RESULTS: The biopsy material was sufficient for histopathological examinations in all cases, leading to conclusive diagnoses (vasculitis in two cases and amyloidosis in one case). The early post-biopsy hypesthesia, which was present for 4 to 8 weeks, improved to preoperative levels as early as 6 months after the nerve repair. Sensory evaluations performed at 6- and 12-month follow-up times demonstrated that none of the patients complained of pain at the biopsy site or distally in the area innervated by the sural nerve. Ultrasonography performed at the 12-month follow-up examination revealed normal sural nerve morphological features, with no neuroma formation, comparable to findings for the contralateral site. CONCLUSION: Microsurgical repair of the sural nerve after biopsy can eliminate or reduce sensory disturbances such as paraesthesia, hypesthesia, and dysesthesia distal to the biopsy site, in the distribution of the sensory innervation of the sural nerve, and can prevent painful neuroma formation. To our knowledge, this article is the first in the literature to report on microsurgical repair of the sural nerve after nerve biopsy. Decreased side effects suggest that this technique can become a standard procedure after sural nerve biopsy, which is commonly required to establish the diagnosis of various diseases, such as peripheral nerve pathological conditions, vasculitis, and amyloidosis. More cases should be analyzed, however, to explore the usefulness of the technique and the reliability of sural nerve biopsy samples in attempts to obtain conclusive diagnoses.

EcPV2 DNA in equine papillomas and in situ and invasive squamous cell carcinomas supports papillomavirus etiology

Equine penile papillomas, in situ carcinomas, and invasive carcinomas are hypothesized to belong to a continuum of papillomavirus-induced diseases. The former ones clinically present as small grey papules, while the latter 2 lesions are more hyperplasic or alternatively ulcerated. To test the hypothesis that these lesions are papillomavirus-induced, samples of 24 horses with characteristic clinical and histologic findings of penile papillomas or in situ or invasive squamous cell carcinomas were collected. As controls, 11 horses with various lesions--namely, Balanoposthitis (6 cases), melanoma (3 cases), follicular cyst (1 case), and amyloidosis (1 case)--were included. DNA was extracted and polymerase chain reaction applied to amplify papillomavirus DNA. The respective primers were designed to amplify DNA of the recently discovered equine papillomavirus EcPV2. All tested papilloma and squamous cell carcinoma samples were found to contain DNA of either of 2 previously published EcPV2 variants. Among the other samples 6 of 11 were found to contain EcPV2 DNA. To further support the findings and to determine where the papillomavirus DNA was located within the lesions, an in situ hybridization for the detection of EcPV2 DNA was established. The samples tested by this technique were found to clearly contain papillomavirus nucleic acid concentrated in the nucleus of the koilocytes. The findings of this study support previous data and the hypothesis that papillomaviruses induce the described penile lesions in horses.

Non-acute myocardial infarction-related causes of elevated high-sensitive troponin T in the emergency room: a cross-sectional analysis

To systematically investigate putative causes of non-coronary high-sensitive troponin elevations in patients presenting to a tertiary care emergency department. In this cross-sectional analysis, patients who received serial measurements of high-sensitive troponin T between 1 August 2010 and 31 October 2012 at the Department of Emergency Medicine were included. The following putative causes were considered to be associated with non-acute coronary syndrome-related increases in high-sensitive troponin T: acute pulmonary embolism, renal insufficiency, aortic dissection, heart failure, peri-/myocarditis, strenuous exercise, rhabdomyolysis, cardiotoxic chemotherapy, high-frequency ablation therapy, defibrillator shocks, cardiac infiltrative disorders (e.g., amyloidosis), chest trauma, sepsis, shock, exacerbation of chronic obstructive pulmonary disease, and diabetic ketoacidosis. During the study period a total of 1,573 patients received serial measurements of high-sensitive troponin T. Of these, 175 patients were found to have acute coronary syndrome leaving 1,398 patients for inclusion in the study. In 222 (30 %) of patients, no putative cause described in the literature could be attributed to the elevation in high-sensitive troponin T observed. The most commonly encountered mechanism underlying the troponin T elevation was renal insufficiency that was present in 286 patients (57 %), followed by cerebral ischemia in 95 patients (19 %), trauma in 75 patients (15 %) and heart failure in 41 patients (8 %). Non-acute coronary syndrome-associated elevation of high-sensitive troponin T levels is commonly observed in the emergency department. Renal insufficiency and acute cerebral events are the most common conditions associated with high-sensitive troponin T elevation.

Multiple myeloma-associated amyloidoma of the sacrum: case report and review of the literature.

Study Design Case report. Objectives With only two previously reported cases, localized amyloidosis of the sacrum is extremely rare. Here we report a 64-year-old woman with a large osteolytic lesion accompanied by weakness and paresthesia of the right leg and difficulties in bladder control. Methods Fine needle biopsy and standard staging procedures revealed a primary solitary amyloidoma that was treated with intralesional resection, lumbopelvic stabilization, and consolidation radiotherapy. Results Clinical follow-up revealed the diagnosis of multiple myeloma 9 months after initial treatment. At 12 months, no local recurrence has occurred, the neurologic symptoms have resolved, and the systemic disease is in remission. Conclusions Intralesional resection with adjuvant radiotherapy of the amyloidoma achieved good local tumor control with limited morbidity.

Sleep-Wake Cycle Dysfunction in the TgCRND8 Mouse Model of Alzheimer's Disease: From Early to Advanced Pathological Stages.

In addition to cognitive decline, individuals affected by Alzheimer's disease (AD) can experience important neuropsychiatric symptoms including sleep disturbances. We characterized the sleep-wake cycle in the TgCRND8 mouse model of AD, which overexpresses a mutant human form of amyloid precursor protein resulting in high levels of β-amyloid and plaque formation by 3 months of age. Polysomnographic recordings in freely-moving mice were conducted to study sleep-wake cycle architecture at 3, 7 and 11 months of age and corresponding levels of β-amyloid in brain regions regulating sleep-wake states were measured. At all ages, TgCRND8 mice showed increased wakefulness and reduced non-rapid eye movement (NREM) sleep during the resting and active phases. Increased wakefulness in TgCRND8 mice was accompanied by a shift in the waking power spectrum towards fast frequency oscillations in the beta (14-20 Hz) and low gamma range (20-50 Hz). Given the phenotype of hyperarousal observed in TgCRND8 mice, the role of noradrenergic transmission in the promotion of arousal, and previous work reporting an early disruption of the noradrenergic system in TgCRND8, we tested the effects of the alpha-1-adrenoreceptor antagonist, prazosin, on sleep-wake patterns in TgCRND8 and non-transgenic (NTg) mice. We found that a lower dose (2 mg/kg) of prazosin increased NREM sleep in NTg but not in TgCRND8 mice, whereas a higher dose (5 mg/kg) increased NREM sleep in both genotypes, suggesting altered sensitivity to noradrenergic blockade in TgCRND8 mice. Collectively our results demonstrate that amyloidosis in TgCRND8 mice is associated with sleep-wake cycle dysfunction, characterized by hyperarousal, validating this model as a tool towards understanding the relationship between β-amyloid overproduction and disrupted sleep-wake patterns in AD.

Electrophysiologic assessment of conduction abnormalities and atrial arrhythmias associated with amyloid cardiomyopathy.

BACKGROUND Arrhythmias in cardiac amyloidosis (CA) result in significant comorbidity and mortality but have not been well characterized. OBJECTIVE The purpose of this study was to define intracardiac conduction, atrial arrhythmia substrate, and ablation outcomes in a group of advanced CA patients referred for electrophysiologic study. METHODS Electrophysiologic study with or without catheter ablation was performed in 18 CA patients. Findings and catheter ablation outcomes were compared to age- and gender-matched non-CA patients undergoing catheter ablation of persistent atrial fibrillation (AF). RESULTS Supraventricular tachycardias were seen in all 18 CA patients (1 AV nodal reentrant tachycardia, 17 persistent atrial tachycardia [AT]/AF). The HV interval was prolonged (>55 ms) in all CA patients, including 6 with normal QRS duration (≤100 ms). Thirteen supraventricular tachycardia ablations were performed in 11 patients. Of these, 7 underwent left atrial (LA) mapping and ablation for persistent AT/AF. Compared to non-CA age-matched comparator AF patients, CA patients had more extensive areas of low-voltage areas LA (63% ± 22% vs 34% ± 22%, P = .009) and a greater number of inducible ATs (3.3 ± 1.9 ATs vs 0.2 ± 0.4 ATs, P <.001). The recurrence rate for AT/AF 1 year after ablation was greater in CA patients (83% vs 25%), and the hazard ratio for postablation AT/AF recurrence in CA patients was 5.4 (95% confidence interval 1.9-35.5, P = .007). CONCLUSION In this group of patients with advanced CA and atrial arrhythmias, there was extensive conduction system disease and LA endocardial voltage abnormality. Catheter ablation persistent AT/AF in advanced CA was associated with a high recurrence rate and appears to have a limited role in control of these arrhythmias.