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 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.

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.

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.

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.

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.

Frequent central nervous system, pachymeningeal and plexus MRI changes in POEMS syndrome.

OBJECTIVE: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome is a rare multisystem disease associated with a plasma-cell dyscrasia. Although pachymeningeal involvement has occasionally been described, MRI of the central nervous system (CNS) has not yet been extensively investigated. METHODS: We retrospectively evaluated CNS MRI in Europe's largest single-center cohort of POEMS syndrome. Of 77 patients who have been formally diagnosed with POEMS, 41 had MRI brain and 29 had MRI spine. A control group of 33 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) was used as this is the major differential diagnosis. Of these CIDP patients, 12 underwent both MRI brain and spine, 7 had solely MRI brain and 14 had MRI spine. RESULTS: In 41 POEMS patients with MRI brain, we identified frequent smooth, diffuse meningeal thickening of the cerebral convexities and falx (n = 29, 71%), of which 4 had meningeal collections. 17 (41%) had vascular abnormalities including white-matter disease, of which 4 had established infarcts. Of 29 patients with MRI spine, 17 (59%) had thickening of the brachial and lumbosacral plexus. Conversely in 19 CIDP patients with MRI brain, none had meningeal thickening (p < 0.0001); however, 8 (42%) had vascular abnormalities (p = 0.85). Of 26 patients with MRI spine, 9 (35%) had brachial or lumbosacral plexus thickening (p = 0.06). CONCLUSIONS: In contrast to CIDP, POEMS patients frequently have pachymeningeal thickening. Vascular abnormalities and plexus thickening were also common but not statistically different to CIDP.

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.

Two patients with TAFRO syndrome exhibiting strikingly similar anterior mediastinal lesions with predominantly fat attenuation on chest computed tomography.

We herein report on two middle-aged men with TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis or renal failure, and organomegaly) syndrome, a unique clinicopathological variant of multicentric Castleman׳s disease recently proposed in Japan. Strikingly similar anterior mediastinal fat swellings with soft tissue density were observed in the patients on chest computed tomography. In TAFRO syndrome, bilateral pleural effusion and slight lymph node swelling are common in the thoracic region; however, anterior mediastinal lesions have not been previously observed. Although the mechanisms of anterior mediastinal lesions have not been defined, these lesions seem to have a close relationship with TAFRO syndrome.

Cranial Pachymeningeal Involvement in POEMS Syndrome: Evaluation by Pre- and Post-contrast FLAIR and T1-weighted Imaging.

PURPOSE: To evaluate the cranial pachymeningeal involvement of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome using pre- and post-contrast fluid-attenuated inversion recovery (FLAIR) and T1-weighted imaging (T1WI). METHODS: The appearance of pachymeningeal involvement in nine cases of POEMS syndrome was evaluated using pre- and post-contrast FLAIR and T1WI. The degree of pachymeningeal thickening was graded as normal or abnormal using pre-contrast FLAIR. The degrees of contrast enhancement effect were evaluated based on pre- and post-contrast images, and recorded in each of three separate anatomical areas, i.e., the falx cerebri, cerebral convexity, and tentorium cerebelli. The degrees of contrast enhancement of pachymeninges were graded as not detected (ND), positive, or prominent on post-contrast FLAIR, and normal range (NR), positive, and prominent on post-contrast T1WI. RESULTS: Pre-contrast FLAIR demonstrated 41% of pachymeningeal anatomical regions as areas of thickening. Post-contrast FLAIR did not detect any contrast enhancement on 26% of the regions but showed positive enhancement on 30% and prominent enhancement on 44%. Post-contrast T1WI showed normal range enhancement on 48%, positive enhancement on 11%, and prominent enhancement on 41% of the regions. Post-contrast FLAIR showed the highest percentage for detection of pachymeningeal abnormalities (74%). CONCLUSION: Post-contrast FLAIR may contribute to objective judgment in the evaluation of pachymeningeal involvement in 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.

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.

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.

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.