Ultrasound-based radiomic analysis of the peripheral nerves for differentiation between CIDP and POEMS syndrome.

BACKGROUND: Demyelinating peripheral neuropathy is characteristic of both polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP). We hypothesized that the different pathogeneses underlying these entities would affect the sonographic imaging features. PURPOSE: To investigate whether ultrasound (US)-based radiomic analysis could extract features to describe the differences between CIDP and POEMS syndrome. MATERIAL AND METHODS: In this retrospective study, we evaluated nerve US images from 26 with typical CIDP and 34 patients with POEMS syndrome. Cross-sectional area (CSA) and echogenicity of the median and ulnar nerves were evaluated in each US image of the wrist, forearm, elbow, and mid-arm. Radiomic analysis was performed on these US images. All radiomic features were examined using receiver operating characteristic analysis. Optimal features were selected using a three-step feature selection method and were inputted into XGBoost to build predictive machine-learning models. RESULTS: The CSAs were more enlarged in patients with CIDP than in those with POEMS syndrome without significant differences, except for that of the ulnar nerve at the wrist. Nerve echogenicity was significantly more heterogeneous in patients with CIDP than in those with POEMS syndrome. The radiomic analysis yielded four features with the highest area under the curve (AUC) value of 0.83. The machine-learning model showed an AUC of 0.90. CONCLUSION: US-based radiomic analysis has high AUC values in differentiating POEM syndrome from CIDP. Machine-learning algorithms further improved the discriminative ability.

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.

POEMS syndrome.

PURPOSE OF REVIEW: To provide an overview of polyneuropathy organomegaly endocrinopathy M-protein and skin changes (POEMS) syndrome, detailing new insights into pathogenesis, prognostic factors, treatments, and outcome scores. RECENT FINDINGS: With the development of large multicentre national cohorts of patients, POEMS syndrome is evolving into a well characterized multisystem hematoneurological syndrome. Without early diagnosis significant disability results from the neuropathy. Vascular endothelial growth factor (VEGF) is a useful and accurate biomarker supporting diagnosis and following disease activity. The past decade has seen a number of therapeutics become available to patients with POEMS, repurposed from myeloma treatment. Simple treatment algorithms are based on the extent of monoclonal proliferation and the performance status of patients. Risk factors, prognostic scores, and their impact on outcome measures have been developed from deeply phenotyped patient cohorts to predict response rate, progression-free survival and overall survival. SUMMARY: Understanding links between the monoclonal lambda plasma cell disorder and resulting proinflammatory cytokine milieu is fundamental to determining POEMS syndrome pathophysiology. Similarities to chronic inflammatory demyelinating polyradiculoneuropathy and some other monoclonal proliferative diseases makes POEMS misdiagnosis common. A range of treatments are available, and more work to identify pathogenic mechanisms and treatment targets and prognostic scores will further enable treatment stratification for optimum outcomes.

Lenalidomide-Induced Ischemic Cerebrovascular Disease in Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes Syndrome.

We describe the case of a 34-year-old woman with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. She developed transient ischemic attack after the introduction of lenalidomide plus dexamethasone (Rd) therapy despite no vascular risk factors. Magnetic resonance and computed tomography angiographies showed bilateral internal carotid artery stenosis. Rd therapy was suspended because of its thromboembolic risk. She had been neurologically stable during the suspension of Rd therapy. After Rd therapy was restarted, however, she repeated ischemic cerebrovascular disease. Rd therapy was switched to carfilzomib plus dexamethasone therapy. Thereafter, she had been neurologically stable. Multivessel stenosis is infrequently seen in POEMS syndrome. Therefore, magnetic resonance angiography should be performed before introducing Rd therapy in POEMS syndrome.

51-year old man with tingling, burning and progressive limb weakness.

Peripheral neuropathy is a common reason for referral to neurology. Chronic acquired demyelinating neuropathies are an important and varied group with overlapping presentations, and may have an immune-mediated cause. Their correct diagnosis is important as they respond to different treatments; timely intervention can prevent irreversible axonal degeneration. We present a case that highlights the approach to an adult presenting with a chronic demyelinating neuropathy.

Autologous cytokine-induced killer (CIK) cell immunotherapy combined with cyclophosphamide in five patients with POEMS syndrome.

The primary objective of this study was to evaluate the safety and clinical efficacy of autologous cytokine-induced killer (CIK) cells combined with cyclophosphamide in the treatment of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome patients. We evaluated five POEMS syndrome patients treated with autologous CIK cell immunotherapy combined with cyclophosphamide from 1 May 2012 to 30 November 2014. The Overall Neuropathy Limitation Scale (ONLS), computed tomography of the chest and abdomen, ultrasound of the abdomen, serum vascular endothelial growth factor (VEGF) level and lymphocyte count findings in the five patients were recorded. The median age of the patients was 40 years (range: 25-62), and all the patients were male. CIK cells were generated routinely from peripheral blood mononuclear cells (PBMCs) of all five patients, and the numbers of CIK cells increased by approximately 105-fold after 14 days of culture. All five patients (100%) responded to their neuropathy treatment, the ONLS scores were reduced by at least 1 and a paired-sample t-test revealed a significant difference (t = 5·715, P = 0·003 < 0·01). The extravascular volume overload responses indicated partial remission (PR = 60%) or stable disease (SD = 40%), and no cases of progressive disease (PD) or complete remission (CR) were observed. During clinical treatment, the serum VEGF of patient 5 decreased after one cycle of transfusion within 1 month. The lymphocyte counts of all the patients increased significantly after CIK transfusion, and a paired-sample t-test revealed a significant difference (t = 5·101, P = 0·004 < 0·01). Autologous CIK cell infusion combined with cyclophosphamide was found to be highly safe and elicited no adverse reactions. CIK cells can improve both the symptoms and quality of life, decrease serum VEGF levels and increase lymphocyte counts in patients with POEMS syndrome.

Acutely deteriorated extravascular volume overload during peripheral blood stem cell mobilization in POEMS syndrome: A case series with cytokine analysis.

We describe two cases of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome patients with deteriorated extravascular volume overload without increased levels of vascular endothelial growth factor after the administration of cyclophosphamide + granulocyte colony-stimulating factor for stem cell mobilization. We then measured the serum levels of 27 cytokines from these cases using a multiplex suspension array system. The analysis revealed the changes of cytokine profiles before cyclophosphamide + granulocyte colony-stimulating factor and after the development of capillary leak symptoms in both cases. This may improve our current level of understanding of the pathogenesis of POEMS syndrome not driven by vascular endothelial growth factor.

CT characteristics in 24 patients with POEMS syndrome.

BACKGROUND: POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, M protein, and Skin changes) syndrome is a complicated and rare disease. Systematic research on computed tomography (CT) imaging characteristics in POEMS syndrome is scanty. The role of CT in diagnosis needs to be assessed. PURPOSE: To retrospectively analyze the CT imaging features in 24 patients with POEMS syndrome and evaluate the role of CT in diagnosis of this disease. MATERIAL AND METHODS: Twenty-four patients with confirmed POEMS syndrome were included in the study. Chest and abdominal CT images were analyzed. RESULTS: The three minor diagnostic criteria for POEMS syndrome (extravascular volume overload, organomegaly, and bone lesions) can be detected effectively by CT. Extravascular volume overload involved multiple serous cavities: hydrothorax, hydropericardium, and ascites, which were found in 79.2%, 41.7%, and 54.2% patients, respectively. The volume of effusion was small to moderate. Organomegaly involved multiorgans: hepatomegaly was found in 45.8% patients, splenomegaly in 54.2%, and lymphadenopathy in 75% patients. Hepatospleen exhibited moderate homogeneous enlargement without local enhanced signal after injection of contrast material. Bone lesions were classified into three groups: osteosclerotic, osteolytic, and mixed lesions. Osteosclerotic lesions, taking multiple, scattered, and variably sized high-density plaque-like appearance, were found in 20.8% patients. Osteolytic lesions, exhibiting punched-out low-density image, were found in 4.2% patients. Mixed ones, holding both common characteristics of them, were detected in 8.3% patients. These CT abnormalities disappeared after effective treatment. CONCLUSION: CT plays vital role in the confirmation of the three minor diagnostic criteria for POEMS syndrome: extravascular volume overload, organomegaly, and bone lesions.

POEMS syndrome associated with plasmacytoma of the clivus: "Time discovers the truth".

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome is characterized by the presence of a monoclonal plasma cell disorder, peripheral neuropathy, and one or more of the following features: Osteosclerotic myeloma, Castleman's disease (angiofollicular lymph node hyperplasia), increased levels of serum vascular endothelial growth factor (VEGF), organomegaly, endocrinopathy, edema, typical skin changes, and papilledema. [1] Solitary plasmacytomas most frequently occur in the bone but can also be found in soft tissues (extramedullary plasmacytoma). [2] We report a case that showed a rare association of POEMS syndrome with a plasmacytoma of the clivus.

Computed tomography assessment of bone lesions in patients with POEMS syndrome.

OBJECTIVES: To describe the imaging findings on computed tomography (CT) and skeletal survey (SS) in patients with POEMS syndrome. METHODS: We retrospectively reviewed, with institutional review board approval, the dysproteinemia database at our institution for patients with new diagnosis of POEMS syndrome between January 1998 and December 2008. Twenty-four patients were identified with PET/CT or CT and had skeletal survey (SS) available for review. RESULTS: Twenty-four patients were included in the study group with median age of 47 years. All CTs demonstrated at least one sclerotic lesion. The most common pattern was multiple small lesions, with 18 patients (75%) having at least 5 lesions less than 1 cm. The larger lesions had a central lytic component and were FDG avid. SS had a false negative rate of 36% (8 patients). Serial CT after treatment showed a decrease in size and number of sclerotic lesions in 53% of cases (13 patients), the majority showing increased sclerosis. Two patients had complete resolution of sclerotic lesions. CONCLUSIONS: CT identified sclerotic lesions in all study patients with POEMS syndrome, the majority being less than 1 cm in size, which were not identified radiographically. CT may demonstrate increased sclerosis or even resolution of sclerotic lesions corresponding to treatment response. KEY POINTS: • CT has high sensitivity in identifying sclerotic lesions in POEMS syndrome • Most common CT patterns are multiple, less than 1 cm, sclerotic lesions • Larger lesions have lytic centres and sclerotic margins • Skeletal surveys may have a false negative rate of 36% • Treatment response includes increased sclerosis, decrease in size or resolution of lesions.

[Multiple myeloma with diffuse osteosclerosis: distinct from POEMS syndrome]. / Mieloma múltiple con osteosclerosis difusa, diferente al síndrome de POEMS.

Diffuse osteosclerotic lesions are a very uncommon radiologic presentation in multiple myeloma. These lesions affect the axial skeleton and proximal limbs; they may be accompanied by osteolytic lesions in the course of the disease. In fact, in cases of diffuse osteosclerosis, the diagnosis of multiple myeloma is reached only after ruling out other, more common diseases. We present an exceptional case of multiple myeloma with diffuse osteosclerosis and highlight the differences between this entity and POEMS syndrome.

Efficacy of lenalidomide in POEMS syndrome: a retrospective study of 20 patients.

POEMS syndrome is a rare disorder characterized by polyneuropathy, monoclonal gammopathy, multiorgan involvement, and elevated vascular endothelial growth factor levels. Localized bone lesions require irradiation, whereas young patients with disseminated disease receive intensive treatment with stem cell support. Treatment of older and non responding patients is not yet standardized. We report the use of a combination of lenalidomide and dexamethasone in 20 patients with POEMS syndrome. Four patients were newly diagnosed, and 16 had relapsed or progressed after treatment. All but one of the patients responded: clinical improvements were noted in neuropathies (16/20) organomegaly (13/13), peripheral edema (14/15), and pulmonary hypertension (5/5). At least a very good partial response was noted in 68% of patients, with partial responses in 26%. Serum VEGF levels fell markedly in all 17 patients with available values. Twelve patients had 18-FDG-PET/CT at diagnosis (11 with positive findings), and nine patients during follow-up. The number of lesions fell markedly in five cases and remained stable in two cases, while two patients became negative. During a median follow-up of 22 months, four patients relapsed. Toxicity, predominantly hematological, was mild and manageable. Lenalidomide thus appears to be effective in POEMS syndrome, inducing high rate of clinical and biological responses.

[Usefulness of (18)F-FDG PET/CT for detecting lesions in patients with POEMS syndrome].

Many patients with POEMS syndrome have osteosclerotic plasmacytoma. Radiation therapy is useful for patients who have localized lesions, although chemotherapy is necessary for patients who have widespread lesions. Thus, evaluation of these lesions is important to determine the therapeutic strategy. We evaluated the activities of lesions in two patients with POEMS syndrome by (18)F-FDG positron emission tomography (PET)/computed tomography (CT) scan. In the first patient, PET/CT scan revealed osteosclerotic lesions, which were not detected by Ga-scintigraphy or plain X-ray. It also detected residual disease activity and relapse. In the second patient, lymph node involvement was suggested by (18)F-FDG uptake, and plasmacytoma was confirmed by subsequent biopsy. In the extramedullary lesions of this case, FDG uptake was as marked as in myeloma, whereas bone lesion was only detectable by CT scan. In POEMS syndrome, the PET and CT are complementary, and the combined PET/CT scan is considered to be very useful for evaluation of involved lesions.

Nerve Ultrasound Performances in Differentiating POEMS Syndrome from CIDP.

Chronic inflammatory demyelinating polyneuropathy (CIDP) and polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome are both acquired demyelinating polyneuropathies. We aim to explore the different features of ultrasonographic changes between CIDP and POEMS syndrome. Nerve ultrasonographic studies were performed in 120 patients with CIDP and 34 patients with POEMS syndrome. Cross-sectional areas (CSAs) were measured on the bilateral median nerve, ulnar nerve, and brachial plexus. Nerve conduction studies were performed on median and ulnar nerves to detect motor conduction blocks (CBs). CSAs at all sites were larger in patients with CIDP and POEMS syndrome than in healthy controls. Maximal CSA (median (min to max)) was 14 (6-194) mm2 for median nerve, 9 (4-92) mm2 for ulnar nerve, and 14 (7-199) mm2 for brachial plexus in CIDP and 11 (8-16) mm2 for median nerve, 8.5 (6-13) mm2 for ulnar nerve, and 14 (10-20) mm2 for brachial plexus in POEMS syndrome. The ratio of maximum/minimum CSA of the median nerve was significantly larger in CIDP (2.8 ± 2.8) than in POEMS syndrome (1.7 ± 0.3). CBs or probable CBs were detected in 60 out of 120 CIDP patients but in none of the POEMS syndromes. For distinguishing CIDP and POEMS syndrome, a two-step protocol using CB and maximum/minimum CSA of the median nerve yields a sensitivity of 93% and a specificity of 79%. In conclusion, compared with CIDP, nerve CSA enlargement was more homogeneous along the same nerve in individual POEMS patients, as well as among different POEMS patients. The addition of nerve ultrasound to nerve conduction studies significantly improves the differential diagnosis between the two diseases.

Ultrasound evaluation of peripheral neuropathy in POEMS syndrome.

INTRODUCTION: Polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome is a rare multisystem disorder associated with plasma cell dyscrasia whose main neurological feature is a demyelinating polyneuropathy. The aim of our study was to assess the pattern of ultrasound (US) nerve abnormalities in POEMS syndrome patients. METHODS: Eight POEMS syndrome patients underwent neurological examination and US evaluation of the median, ulnar, fibular, tibial, and sural nerves. Nerve cross-sectional area and echogenicity abnormalities were analyzed. RESULTS: US abnormalities were mostly localized at entrapment sites. Enlargements outside the entrapment sites were uncommon. No correlation was found between muscle weakness and focal US findings. CONCLUSIONS: No specific pattern of US abnormalities was identified in this cohort of patients with POEMS syndrome. The lack of correlation between US and clinical findings may be secondary to the chronic nerve damage that is common in POEMS syndrome, where the diagnosis is often delayed.

Sonographic findings in a case of polyneuropathy associated with POEMS syndrome.

Polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndrome is a rare multi-system disease. We describe the ultrasonography (US) and color Doppler ultrasonography (CDUS) findings of peripheral neuropathy in a patient with POEMS syndrome. In US examination, peripheral nerves were found to be diffusely thickned in both upper limbs. CDUS imaging showed arterial blood flow with low systolic peaks on the nerves.

Posttreated POEMS Syndrome With Concurrent Follicular Lymphoma Revealed by 18F-FDG and 68Ga-Pentixafor PET/CT.

A 59-year-old man with history of POEMS syndrome was found with a painless mass in the right neck for 9 months. In F-FDG and Ga-pentixafor PET/CT, there were multiple neck nodes and left inguinal nodes that showed intense F-FDG and Ga-pentixafor uptake. In addition, osteoblastic bone lesions with mild F-FDG and Ga-pentixafor uptake were noted in the pelvis, which was consistent with posttreated osseous involvement of POEMS syndrome. However, considering lymphoadenopathy with such intense F-FDG uptake is not usually seen in POEMS syndrome, the patient underwent biopsy of the right cervical nodes. The histopathology with immunohistochemistry confirmed follicular lymphoma.

Neurological recovery from pentaplegia after resection for sacral plasmacytoma presenting with POEMS syndrome.

The authors describe a case of a 52-year-old woman in whom tetraplegia developed with neurological respiratory failure due to POEMS syndrome associated with a solitary sacral plasmacytoma. Resection was finally performed after her condition proved resistant to radiation and chemotherapy. The patient showed a dramatic recovery and was ambulatory without tumor recurrence after 5 years and 6 months of follow-up. To the authors' knowledge, there are only 3 reported cases in the literature of bilateral phrenic nerve palsy leading to respiratory failure treated by chemotherapy. This is the first report describing neurological recovery after surgery for pentaplegia due to POEMS syndrome associated with solitary sacral plasmacytoma.