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.

Cerebral large artery stenosis and occlusion in POEMS syndrome.

BACKGROUND: This study aimed to investigate the frequency and risk factors for cerebral artery stenosis and occlusion in patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome. METHODS: We reviewed results of magnetic resonance angiography (MRA) or computed tomography angiography (CTA) in 61 patients with POEMS syndrome seen between 2010 and 2017. Stenosis or occlusion was assessed in the initial MRA/CTA. Multivariate analysis was used to identify risk factors for artery stenosis/occlusion. In an autopsy case, pathologic examination was conducted of the occluded middle cerebral arteries. RESULTS: Stenosis (> 50 %) or occlusion of the major cerebral arteries was found in 29 (47.5 %) patients on the initial MRA/CTA. The internal carotid artery was involved most frequently (32.8 %), followed by the anterior (21.3 %) and middle (16.4 %) cerebral arteries. The basilar (1.3 %) and vertebral (3.6 %) arteries were rarely affected. Cerebral infarction developed in eight (13.1 %) patients. The serum vascular endothelial growth factor (VEGF) level was an independent predictor for stenosis/occlusion (odds ratio, 1.228; 95 % confidence interval, 1.042-1.447; P = 0.014). An autopsy study showed occluded middle cerebral arteries by fibrous and myxomatous thickening of intima with splitting of the internal elastic lamina. Follow-up MRA in 23 patients showed improved, worsened, and unchanged stenosis in 20.7 %, 8.7 %, and 69.6 %, respectively. CONCLUSIONS: Cerebral large-vessel stenosis or occlusion is frequently seen in approximately half of patients with POEMS syndrome. Vasculopathy was related to serum VEGF levels and thereby disease activity. Assessment of cerebral vessels is recommended in these patients to improve management.

Membrane property changes in most distal motor axons in chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: Distal nerve terminals, where the blood-nerve barrier is anatomically deficient, are preferentially affected in immune-mediated neuropathies. Excitability alterations near the motor nerve terminals may be more prominent than the nerve trunk in typical chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: In 20 patients with typical CIDP, motor nerve excitability testing was performed at the motor point and wrist of the ulnar nerve, and results were compared with those in 20 healthy persons. RESULTS: Chronic inflammatory demyelinating polyneuropathy patients showed greater threshold changes in hyperpolarizing threshold electrotonus at the motor point (P < .05) but not at the wrist. Strength-duration time constant did not show significant differences between CIDP and controls at both sites. DISCUSSION: Axonal property changes in CIDP are more prominent in distal portions of axons compared with the nerve trunk, presumably due to salient demyelination near the distal nerve terminals. Motor point excitability measurements could elucidate underlying pathophysiology in immune-mediated neuropathies.

Electrodiagnostic accuracy in polyneuropathies: supervised learning algorithms as a tool for practitioners.

OBJECTIVE: The interpretation of electrophysiological findings may lead to misdiagnosis in polyneuropathies. We investigated the electrodiagnostic accuracy of three supervised learning algorithms (SLAs): shrinkage discriminant analysis, multinomial logistic regression, and support vector machine (SVM), and three expert and three trainee neurophysiologists. METHODS: We enrolled 434 subjects with the following diagnoses: chronic inflammatory demyelinating polyneuropathy (99), Charcot-Marie-Tooth disease type 1A (124), hereditary neuropathy with liability to pressure palsy (46), diabetic polyneuropathy (67), and controls (98). In each diagnostic class, 90% of subjects were used as training set for SLAs to establish the best performing SLA by tenfold cross validation procedure and 10% of subjects were employed as test set. Performance indicators were accuracy, precision, sensitivity, and specificity. RESULTS: SVM showed the highest overall diagnostic accuracy both in training and test sets (90.5 and 93.2%) and ranked first in a multidimensional comparison analysis. Overall accuracy of neurophysiologists ranged from 54.5 to 81.8%. CONCLUSIONS: This proof of principle study shows that SVM provides a high electrodiagnostic accuracy in polyneuropathies. We suggest that the use of SLAs in electrodiagnosis should be exploited to possibly provide a diagnostic support system especially helpful for the less experienced practitioners.

Proposal of new clinical diagnostic criteria for POEMS syndrome.

OBJECTIVE: To propose the optimal diagnostic criteria for polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome using appropriate statistical methods and disease controls. METHODS: This retrospective cohort study included 104 consecutive patients with suspected POEMS syndrome, among whom a gold standard group of 60 patients with definitive POEMS syndrome diagnosis were followed for at least 12 months to strictly exclude other disorders mimicking POEMS syndrome and to confirm response to POEMS syndrome-specific treatment. Thirty patients with chronic inflammatory demyelinating polyradiculoneuropathy (demyelinating polyradiculoneuropathy controls) and 30 with multiple myeloma or immunoglobulin light chain amyloidosis (monoclonal plasma cell proliferation controls) were also included. Logistic regression analyses were performed to determine optimal combination of clinical and laboratory abnormalities, characteristic of POEMS syndrome. RESULTS: The diagnostic criteria were statistically defined as the presence of the three major criteria (polyneuropathy (typically demyelinating), monoclonal plasma cell proliferative disorder and elevated vascular endothelial growth factor) and at least two of the four minor criteria (oedema/effusion, skin changes, organomegaly and sclerotic bone lesions), based on best performance by area under the receiver operating characteristic curve analyses. The sensitivity and specificity were 100% and 100%, respectively; the diagnostic accuracy of the proposed criteria was equivalent to somewhat complicated previous criteria. CONCLUSIONS: The statistically defined, simple diagnostic criteria for POEMS syndrome could accelerate early diagnosis and treatment, thereby contribute to better outcome in patients with this serious disease. Prospective larger studies are required to confirm the validity.

Altered cerebral blood flow in the anterior cingulate cortex is associated with neuropathic pain.

OBJECTIVE: To assess the cerebral blood flow (CBF) in patients with diabetic neuropathic pain, and its changes after duloxetine therapy. METHODS: Using iodine-123-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography (IMP-SPECT), we performed a cross-sectional study of 44 patients with diabetes, and compared CBF in those with (n = 24) and without neuropathic pain (n = 20). In patients with neuropathic pain, we also longitudinally assessed changes in CBF 3 months after treatment with duloxetine. RESULTS: IMP-SPECT with voxel-based analyses showed a significant increase in cerebral blood flow in the right anterior cingulate cortex and a decrease in the left ventral striatum in patients with neuropathic pain, compared with those without pain. After duloxetine treatment, volume of interest analyses revealed a decrease in cerebral blood flow in the anterior cingulate cortex in patients with significant pain relief but not in non-responders. Furthermore, voxel-based whole brain correlation analyses demonstrated that greater baseline CBF in the anterior cingulate cortex was associated with better pain relief on the numerical rating scale. CONCLUSIONS: Our results suggest that the development of neuropathic pain is associated with increased activity in the anterior cingulate cortex, and greater baseline activation of this region may predict treatment responsiveness to pharmacological intervention. TRIAL REGISTRATION NUMBER: UMIN000017130;Results.

Reconstruction magnetic resonance neurography in chronic inflammatory demyelinating polyneuropathy.

To study distribution and patterns of nerve hypertrophy in chronic inflammatory demyelinating polyneuropathy (CIDP), magnetic resonance neurography with 3-dimensional reconstruction of short tau inversion recovery images was performed in 33 patients. This technique clearly showed longitudinal morphological changes from the cervical roots to the nerve trunks in the proximal arm. Nerve enlargement was detected in 88% of the patients. According to the clinical subtype of CIDP, typical CIDP patients showed symmetric and root-dominant hypertrophy, whereas Lewis-Sumner syndrome patients had multifocal fusiform hypertrophy in the nerve trunks. The patterns of nerve hypertrophy presumably reflect the different pathophysiology of each CIDP subtype.

Different electrophysiological profiles and treatment response in 'typical' and 'atypical' chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is currently classified into 'typical' CIDP and 'atypical' subtypes such as multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). OBJECTIVES: To assess the frequency of CIDP subtypes, and to elucidate clinical and electrophysiological features, and treatment response in each subtype. METHODS: We reviewed data from 100 consecutive patients fulfilling criteria for CIDP proposed by the European Federation of Neurological Societies and the Peripheral Nerve Society. The Kaplan-Meier curve was used to estimate long-term outcome. RESULTS: Patients were classified as having typical CIDP (60%), MADSAM (34%), demyelinating acquired distal symmetric neuropathy (8%) or pure sensory CIDP (1%). Compared with patients with MADSAM, patients with typical CIDP showed more rapid progression and severe disability, and demyelination predominant in the distal nerve segments. MADSAM was characterised by multifocal demyelination in the nerve trunks. Abnormal median-normal sural sensory responses were more frequently found for typical CIDP (53% vs 13%). Patients with typical CIDP invariably responded to corticosteroids, immunoglobulin or plasmapheresis, whereas patients with MADSAM were more refractory to these treatments. The Kaplan-Meier analyses showed that 64% of patients with typical CIDP and 41% of patients with MADSAM had a clinical remission 5 years later (p=0.02). CONCLUSIONS: Among the CIDP spectrum, typical CIDP and MADSAM are the major subtypes, and their pathophysiology appears to be distinct. In typical CIDP, the distal nerve terminals and possibly the nerve roots, where the blood-nerve barrier is anatomically deficient, are preferentially affected, raising the possibility of antibody-mediated demyelination, whereas cellular immunity with breakdown of the barrier may be important in MADSAM neuropathy.

Delayed facial weakness in Guillain-Barré and Miller Fisher syndromes.

INTRODUCTION: Dr. C. Miller Fisher described the appearance of unilateral facial palsy after resolution of ataxia in a patient with the eponymic Miller Fisher syndrome (MFS). However, there have been very few reports of delayed appearance of facial weakness in Guillain-Barré syndrome (GBS) and MFS when the other neurological signs reached nadir or started improving. METHODS: In this study we reviewed the clinical and laboratory findings of consecutive patients with GBS (n=195) and MFS (n=68). RESULTS: Delayed facial weakness occurred in 12 (6%) GBS and 4 (6%) MFS patients and was unilateral in 5 (42%) GBS and 2 (50%) MFS patients. In those patients with delayed facial weakness, neither limb weakness nor ataxia progressed, and facial weakness disappeared without immunotherapy. CONCLUSIONS: Because facial weakness can lead to further morbidity, it would be prudent for clinicians to warn patients of this possibility, although additional immunotherapy is usually not required.