Efficacy and Safety of Regimens Used for the Treatment of POEMS Syndrome- A Systematic Review.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy/edema, monoclonal plasma protein [M protein], and skin changes) is a rare paraneoplastic disorder associated with underlying plasma cell neoplasia. Although limited-stage disease can be treated with radiotherapy, treatment for the more advanced disease remains unclear. The most commonly used therapies for POEMS syndrome include alkylators and steroids, high-dose chemotherapy with autologos stem cell transplantation, lenalidomide, and bortezomib. In general, patients tend to have excellent prognosis if the diagnosis is made early and appropriate therapy is used. Here we present a systematic review of the efficacy and safety of treatment regimens used to treat POEMS syndrome in the adult population. Combinations of immunomodulatory agents with corticosteroids were most frequently utilized regimens with durable hematological and neurological responses. Combinations of proteasome inhibitors and alkylating agents with corticosteroids, although less frequently utilized, appear to have reasonable safety and efficacy profiles.

Nerve ultrasound studies in POEMS syndrome.

INTRODUCTION: The aim of our study was to assess the ultrasonographic features of peripheral nerves in patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome. METHOD: 34 POEMS syndrome patients and 26 healthy control (HC) participants were recruited prospectively. Cross-sectional area (CSA) was measured in nerves of limbs, trunks of brachial plexus, and cervical nerve roots RESULTS: The CSAs were mildly enlarged at the arm segment of median nerve, elbow segment of ulnar nerve and upper trunk, moderately enlarged at the forearm segment of both median and ulnar nerve, upper trunk of brachial plexus, and C6, C7 cervical nerve roots, and markedly enlarged at the arm segment of ulnar nerve, middle and lower trunk of brachial plexus, as well as C5 cervical root. DISCUSSION: The CSAs of upper limb nerves were larger in POEMS syndrome patients than in HCs, and the enlargements were most prominent proximally.

The Wide Spectrum of Pathophysiologic Mechanisms of Paraproteinemic Neuropathy.

Monoclonal gammopathy is encountered quite frequently in the general population. This type of hematologic abnormality may be mild, referred to as monoclonal gammopathy of undetermined significance or related to different types of hematologic malignancies. The association of a peripheral neuropathy with monoclonal gammopathy is also fairly common, and hemopathy may be discovered in an investigation of peripheral neuropathy. In such a situation, it is essential to determine the exact nature of the hematologic process in order not to miss a malignant disease and thus initiate the appropriate treatment (in conjunction with hematologists and oncologists). In this respect, nerve biopsy (discussed on a case-by-case basis) is of great value in the management of such patients. We therefore propose to present the objectives and main interests of nerve biopsy in this situation.

Clinical characteristics, risk factors, and outcomes of POEMS syndrome: A longitudinal cohort study.

OBJECTIVE: POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin lesions) is a paraneoplastic disorder resulting in severe neurologic disability. Understanding the clinical, laboratory, neurophysiologic, and histopathologic features as well as treatment responses of POEMS will assist in more accurate and timely diagnosis, risk stratification, and effective management. METHODS: This was a retrospective longitudinal cohort study from 1998 to March 2019, with 7,184 person-months of follow-up time. Hospital databases were used to collate presenting features, investigations, therapies, and response. RESULTS: One hundred patients were included with a median follow-up time of 59 months (range, 1-252). Mean symptom onset to diagnosis was 15 months (range, 1-77), with 54% of patients initially misdiagnosed with chronic inflammatory demyelinating polyneuropathy. Median number of multisystem features at diagnosis was 7. Ninety-six (96%) presented with neuropathy, which was length-dependent in 93 (93%) and painful in 75 (75%). At diagnosis, 35% of patients were wheelchair or bedbound, with median Overall Neuropathy Limitation Score of 6, improving to 3 following treatment (p < 0.05). Five-year survival was 90% and 82% at 10 years, with 5- and 10-year progression-free survival of 65% and 53%. Nontreatment with autologous stem cell transplantation, nonhematologic response, and non-vascular endothelial growth factor response are significant risk factors in multivariate analysis to predict progression or death. Risk factors are incorporated to develop a risk score enabling stratification of high- and low-risk cases. CONCLUSIONS: POEMS syndrome is a rare multisystem condition with delayed diagnosis and poor neurologic function at presentation. Therapy has favorable outcomes. Patients at high risk of death or progression can be identified, which may allow for more active monitoring and influence management.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin (POEMS) changes syndrome presenting with a pseudosensory level: a case report.

INTRODUCTION: Polyneuropathy is a key feature of polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome, which is a paraneoplastic manifestation of an underlying lymphoproliferative neoplasm. We report the first case of polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome presenting with a pseudosensory level. CASE PRESENTATION: A 59-year-old Tamil woman with long-standing diabetes mellitus and hypertension developed painless, progressive inguinal lymphadenopathy. A contrast-enhanced computed tomography scan showed mild hepatomegaly and intra-abdominal lymphadenopathy. A histological examination of an enlarged inguinal lymph node showed features of a plasma cell-type Castleman disease. She was treated with rituximab. Six months later, she developed gradually ascending numbness and weakness of both lower limbs. On examination, she had flaccid paraparesis (power 3/5) with a sensory level to pinprick at thoracic level 9. Joint position sense was preserved. Her cranial nerves and upper limbs were neurologically normal. Nerve conduction studies confirmed peripheral neuropathy with conduction slowing and a magnetic resonance imaging of her spine did not show cord or root compression. Serum protein electrophoresis showed a monoclonal band. A bone marrow biopsy showed a hypercellular marrow with 30% plasma cells. A repeat contrast-enhanced computed tomography scan showed sclerotic bony lesions involving multiple vertebrae in addition to mild hepatomegaly and intra-abdominal lymphadenopathy. Polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome was diagnosed and she was treated with intravenously administered pulse therapy of dexamethasone and cyclophosphamide. After three cycles of treatment, she regained normal muscle power and sensation. CONCLUSIONS: Polyneuropathy in polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome can present as a pseudosensory level.

Evaluating heart function in patients with POEMS syndrome.

AIMS: Our aim is to investigate the characterized echocardiographic cardiac measurements of POEMS syndrome and determine its relationship with clinical manifestations. METHODS AND RESULTS: The cross-sectional study included 27 treatment-naïve patients with newly diagnosed POEMS syndrome and 26 age- and sex-matched healthy volunteers. Information of clinical manifestations, serological tests, pulmonary function tests, and both conventional echocardiograph and tissue Doppler imaging (TDI) were collected and analyzed. Pearson's correlation coefficient was used for determining the related clinical and echocardiographic parameters. Compared to healthy people, left ventricular (LV) mass index (LVMI) was elevated in patients with POEMS syndrome (41.3 ± 11.0 g/m2.7 , P < .05). LV systolic dysfunction was found by decreased mitral S' (9.0 ± 2.2 m/sec, P < .01), and diastolic dysfunction by mitral E'/A' (1.10 ± 0.42, P < .05), E/E' (8.69 ± 4.06, P < .001) on lateral, and E/E' (7.90 ± 3.28, P = .133) on septal mitral annulus. The presence of decreased tricuspid annular plane systolic excursion (TAPSE) (22.2 ± 3.5 mm, P < .01) and lateral tricuspid S' (11.1 ± 1.8 m/sec, P < .05) suggested deterioration of right ventricular (RV) systolic function. Parameters obtained from standard echocardiograph (tricuspid E/A ratio and DT) and TDI ((lateral tricuspid annulus E'/A' and E/E') indicated reduced RV diastolic function. Pulmonary hypertension (PH) was presented in six patients. Correlation analysis suggested that PH was related to total lung capacity (TLC) and diffusion capacity of carbon monoxide (DLCO). CONCLUSION: Echocardiographic measurements found that there was elevation of LVMI, pulmonary artery hypertension, and subclinical impairment of systolic and diastolic functions of both the right and left heart in patients with POEMS syndrome.

A relapse of POEMS syndrome presenting as acute kidney injury.

Peripheral neuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (POEMS) syndrome is a rare disease, and only in a minority of cases, causes an impairment of kidney function. Here, we describe a case of a 55-year-old man with a history of POEMS syndrome who presented with acute kidney injury following a routine blood test. On further investigation, a relapse in POEMS syndrome was diagnosed, uniquely isolated to renal involvement.

POEMS syndrome complicated by ischaemic stroke and cerebral vasculitis.

We present a case of ischaemic stroke in the context of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome associated with cerebral vasculitis as confirmed by imaging. There is little information on the prevalence of cerebral vasculitis in POEMS patients, and we found only one previous report of such case in the literature.

[An unusual case of POEMS syndrome: in absence of clinical sign of polineuropathy.] / Un raro caso di sindrome di POEMS: in assenza di sintomi di polineuropatia.

POEMS syndrome (P polyradiculoneuropathy, O organomegaly, E endocrinopathy, M clonal plasma cell disorder, and S skin changes) is a rare syndrome due to a plasma cell dyscrasia. It is characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes. Increased serum VEGF, sclerotic bone lesions, Castleman's disease, oedema, ascites, papilledema and thrombocytosis are other important clinical features. We report a case of POEMS syndrome in a 34-years old man with an unusual clinical presentation. Dyspnoea, organomegaly, and skin changes preceded the clinical manifestations of polyneuropathy. The variability of presentation of the POEMS should suggest to consider the diagnosis even in the lack of the signs of polyneuropathy.

POEMS Syndrome Showing Left Ventricular Dysfunction and Extracellular Edema Assessed by Cardiac Magnetic Resonance Imaging.

Although cardiac involvement is rare in polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome, the clinical course becomes considerably worse on complication with cardiac lesions. The increased release of various cytokines has been observed in the pathogenesis of POEMS syndrome, and serum vascular endothelial growth factor (VEGF) levels are known to be associated with the disease activity. We herein report a patient with POEMS syndrome who showed left ventricular systolic dysfunction and was treated with lenalidmide therapy. Of note, the reduction in extracellular edema in the left ventricular wall was clearly visualized by changes in the native T1 values and extracellular volumes on cardiac magnetic resonance imaging.

An update on the diagnosis and management of the polyneuropathy of POEMS syndrome.

POEMS syndrome is a rare, chronic, disabling paraneoplastic disorder characterized by peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cells disorder and skin changes. Diagnosis relies on the fulfillment of a set of clinical criteria of which polyneuropathy and a monoclonal plasma cell dyscrasia are early and essential features. Treatment may be either local or systemic and is aimed at the monoclonal plasma cell disorder. Our knowledge of the pathogenesis underlying the POEMS syndrome has advanced greatly over the past years, favoring an important progression in the recognition and management of this disorder. Here, we discuss the recent literature that has advanced our knowledge of the pathogenesis and clinical management of the polyneuropathy in POEMS syndrome.

Transthyretin amyloid polyneuropathies mimicking a demyelinating polyneuropathy.

OBJECTIVE: To clearly define transthyretin familial amyloid polyneuropathies (TTR-FAPs) fulfilling definite clinical and electrophysiologic European Federation of Neurological Societies/Peripheral Nerve Society criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: From a cohort of 194 patients with FAP, 13 of 84 patients (15%) of French ancestry had late-onset demyelinating TTR-FAP. We compared clinical presentation and electrophysiology to a cohort with CIDP and POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome. We assessed nerve histology and the correlation between motor/sensory amplitudes/velocities. Predictors of demyelinating TTR-FAP were identified from clinical and electrophysiologic data. RESULTS: Pain, dysautonomia, small fiber sensory loss above the wrists, upper limb weakness, and absence of ataxia were predictors of demyelinating TTR-FAP (p < 0.01). The most frequent demyelinating features were prolonged distal motor latency of the median nerve and reduced sensory conduction velocity of the median and ulnar nerves. Motor axonal loss was severe and frequent in the median, ulnar, and tibial nerves (p < 0.05) in demyelinating FAP. Ulnar nerve motor amplitude <5.4 mV and sural nerve amplitude <3.95 µV were distinguishing characteristics of demyelinating TTR-FAP. Nerve biopsy showed severe axonal loss and occasional segmental demyelination-remyelination. CONCLUSION: Misleading features of TTR-FAP fulfilling criteria for CIDP are not uncommon in sporadic late-onset TTR-FAP, which highlights the limits of European Federation of Neurological Societies/Peripheral Nerve Society criteria. Specific clinical aspects and marked electrophysiologic axonal loss are red flag symptoms that should alert to this diagnosis and prompt TTR gene sequencing.

Problems in Comparing Jitter Values Obtained with Voluntary Activation and Electrical Stimulation.

Comparing results from jitter studies performed with voluntary and electrical activation is difficult to perform quantitatively, particularly in complex signals as seen in reinnervation. High jitter values in individual spikes in these multispike signals can be missed with both activation methods, which introduces a bias towards more normal values.With voluntary activation, triggering on a spike from an abnormal end-plate in multispike potentials will overestimate individual jitter values and the number of abnormal jitter values.With electrical stimulation, artefactually-increased jitter may be caused by subliminal stimulation, which causes uncertainty at the stimulation point. Electrical stimulation also may activate many axons, causing signal summation, with erroneous or impossible jitter estimation.Awareness of such pitfalls can improve the correct performance and interpretation of jitter recordings. Quantitative comparisons of results can be made between studies in reinnervated muscle performed with the same activation method, but not between results obtained with different activation methods.

Temporal and Spatial Correlation Between Choroidal Thickness and Visual Function in a Case of POEMS Syndrome.

PURPOSE: To report the correlation between visual function and subfoveal choroidal thickness (SChT) in a case of POEMS syndrome. CASE REPORT: A 53 year old man diagnosed with POEMS syndrome was referred due to blurred vision. Best corrected visual acuity (BCVA) was 0.5 in his right eye (RE) and 0.7 in his left eye (LE), with a mild perimetric defect in the RE. SChT was 356 and 263 µm in his RE and LE. After an autologous peripheral blood stem-cell transplantation, both visual and systemic symptoms improved. At the most recent visit, SChT was 284 and 222 µm in his RE and LE, BCVA was 1.2 in both eyes and the perimetric defects had improved. CONCLUSIONS: SChT was inversely correlated with visual function in space and time. Due to the high sensitivity of choroidal tissue to vascular endothelial growth factor, SChT might be useful to monitor disease activity in POEMS.

Blink R1 latency utility in diagnosis and treatment assessment of polyradiculoneuropathy-organomegaly-endocrinopathy-monoclonal protein-skin changes and chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION: In polyradiculoneuropathy-organomegaly-endocrinopathy-monoclonal protein-skin changes (POEMS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), limb nerve conduction studies (NCSs) are limited in identifying demyelination and in detecting treatment effects in severely affected patients. Blink R1 latency may improve these assessments. METHODS: POEMS and CIDP patients who had undergone NCS and blink reflex were identified. Correlations among R1 latency, limb NCS, and neuropathy impairment scores (NIS) were compared. RESULTS: Among 182 patients (124 POEMS, 58 CIDP) who were identified, R1 prolongation (>13 ms) occurred in 64.3% (65.3% POEMS, 62.1% CIDP). R1 prolongation correlated with more severely affected NCS in both POEMS (ulnar CMAP 2.6 mV vs. 4.5 mV, P = 0.001) and CIDP (2.0 mV vs. 6.1 mV, P < 0.001). In severely affected patients (ulnar CMAP ≤0.5 mV [10%:18/182]), R1 (>13 ms) helped establish demyelination. In 31 patients (16 POEMS, 15 CIDP), the R1 latency changes were concordant with NIS changes in 94% of patients with POEMS and 60% of patients with CIDP. DISCUSSION: Blink R1 latencies are valuable in defining demyelination and detecting improvement in severely affected POEMS and CIDP patients. Muscle Nerve 57: E8-E13, 2018.

The Peripheral Neuropathies of POEMS Syndrome and Castleman Disease.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS) syndrome is a rare paraneoplastic disorder. The polyneuropathy can be the presenting symptom and is typically a painful, motor-predominant polyradiculoneuropathy often mimicking chronic inflammatory demyelinating polyradiculoneuropathy. The presence of a lambda monoclonal protein, elevated vascular endothelial growth factor, systemic features, and treatment resistance are clues to the diagnosis. Castleman disease (CD) is seen in a subset of these patients, and when present the neuropathy is similar but less severe. In contrast, in those patients with purely CD, the neuropathy is often a mild, painless distal sensory neuropathy.