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Abstract
POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare cause of demyelinating neuropathy with monoclonal plasma cell proliferation, and POEMS neuropathy is usually chronically progressive. Herein, the authors report a 34-year-old woman with POEMS syndrome presenting as acute polyneuropathy. Within 2 weeks of disease onset, she became unable to walk with electrodiagnostic features of demyelination and was initially diagnosed as having Guillan–Barré syndrome. Other systemic features (oedema and skin changes) developed later, and an elevated serum level of vascular endothelial growth factor led to the diagnosis of POEMS syndrome. She received high-dose chemotherapy with autologous peripheral blood stem cell transplantation, resulting in good recovery. The authors also reviewed patterns and speed of progression of neuropathy in the 30 patients with POEMS syndrome; 22 (73%) of them were unable to walk independently with the median period of 9.5 months from POEMS onset (range 0.5–51 months). Whereas the speed of neuropathy progression varies considerably among patients, some POEMS patients can show acute or subacute polyneuropathy. The early diagnosis and treatment could result in rapid improvement as shown in the present patient.
- POEMS syndrome
- Guillan–Barré syndrome
- polyneuropathy
- demyelination
- peripheral blood stem cell transplantation
- clinical neurology
- neuropathy
- neurophysiology
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- POEMS syndrome
- Guillan–Barré syndrome
- polyneuropathy
- demyelination
- peripheral blood stem cell transplantation
- clinical neurology
- neuropathy
- neurophysiology
POEMS (polyneuropathy, organomegaly, endocriopathy, monoclonal gammopathy and skin change) syndrome is a rare cause of mixed demyelinating-axonal polyneuropathy associated with plasma cell dyscrasia. Characteristic features other than POEMS include oedema/effusion, sclerotic bone lesions, thimbocytosis and elevated serum levels of vascular endothelial growth factor (VEGF).1 2 The pathogenesis of POEMS syndrome is not fully elucidated, but the systemic manifestations of POEMS syndrome are presumably associated with overproduction of VEGF possibly secreted by monoclonal plasma cells.3 Because the major clinical feature of the disorder is a chronic progressive polyneuropathy with demyelinating changes, it is often misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP).2 4 Previous studies have described the disease course1 4 but not sufficiently focused on patterns and progression of neuropathy in POEMS syndrome.
We herein describe a patient with acute motor-predominant polyneuropathy with Guillan–Barré syndrome (GBS)-like acute onset. Other systemic features developed later, and a diagnosis of POEMS syndrome was made. We also review the patterns of neuropathy progression in our 30 patients with POEMS syndrome.
Case report
A 34-year-old woman developed acute weakness and paraesthesias in her lower limbs 10 days after diarrhoea. Muscle weakness spread in the upper limbs over the next 3 days. Two weeks after neurological onset, she needed support to walk and was referred to our hospital. Neurological examination at week 4 showed moderate to severe limb muscle weakness (graded as 4/5 in the upper and proximal lower limbs, and as 2/5 in the distal lower limbs on the MRC scale), distal paraesthesias, decreased vibratory sensation below the knees and generalised areflexia. There was no cranial and autonomic nerve involvement. Based on the clinical course and neurological examination, she was initially diagnosed as having GBS.
Laboratory examination showed thrombocytosis and serum IgG-lambda monoclonal gammopathy. Cerebrospinal fluid (CSF) protein was elevated to 237 mg/dl with 6 cells/μl. The nerve-conduction studies on day 28 are listed in table 1. There were prominent decreases in nerve-conduction velocities with conduction block in the forearm segment of the median nerve. F-wave latencies were markedly prolonged, suggesting demyelinating polyneuropathy. The findings fulfilled electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) proposed by the European Federation of Neurological Societies/Peripheral Nerve Society.5
Nerve conduction studies before and after treatment
Because her neuropathy was still progressive at week 6, she was treated as possible CIDP with high-dose corticosteroids and intravenous immunoglobulin therapy, but her condition continued to deteriorate. She became unable to stand at week 8. Prominent foot oedema developed around this period, leading to further examination. Abdominal and pelvic CT revealed hepatosplenomegaly, ascites and multiple vertebral sclerotic bone lesions, and a serum VEGF level was markedly elevated (3990 pg/ml; normal<600 pg/ml). The diagnosis of POEMS syndrome was made.6 High-dose chemotherapy with autologous peripheral blood stem cell transplantation was indicated. Autologous peripheral blood stem cells were collected after subcutaneous injection of granulocyte colony-stimulating factor. High-dose melphalan chemotherapy (100 mg/m2/day for two consecutive days) and peripheral blood stem cells were given 1 month after blood-cell collection as previously reported.5 After treatment, her systemic and neurological symptoms/signs improved, and 4 months later, she was able to walk. The follow-up nerve-conduction studies showed a substantial improvement in nerve conduction velocities (table 1).
Review of neuropathy progression in our 30 POEMS patients
Medical records were reviewed in consecutive 30 patients with POEMS syndrome (20 men and 10 women) seen at Chiba University Hospital between 1992 and 2009. At entry (before treatment), their mean age was 54 years (range 31–76 years), and the mean duration of disease was 37 months (range 10–79 months). Twenty-two (73%) of the patients (15 men and seven women) were unable to walk independently at first visit, with the median duration from disease onset of 9.5 months (range 2 weeks (in the case presented above) to 51 months). Figure 1A shows the Kaplan–Meier curves of probabilities of reaching inability to walk independently in 30 patients with POEMS syndrome; the probability of an inability to walk after 3 years from onset was 65%, and a half of patients were unable to walk independently 12 months after onset. Figure 1B shows the period for reaching inability to walk in 22 patients; 50% of them were categorised into between 6 and 12 months. These findings indicate that the presented case had an unusual rapid progression of neuropathy.
(A) Histogram showing periods for reaching inability to walk from disease onset (n=22). Eleven (50%) of the patients were unable to walk within 12 months of onset. (B) Kaplan–Meier curve showing the probability of the ability to walk independently in 30 patients with POEMS syndrome. Fifty per cent of the patients were unable to walk independently 12 months after onset.
The initial symptom was polyneuropathy in 15 patients, oedema/effusion in seven and skin changes in four. Factors associated with rapid progression of neuropathy were analysed (table 2; supplementary file). Rapid progression (unable to walk within 6 months from the onset) were associated with the presence of ascites/pleural effusion at the time of neuropathy onset (75% vs 25%; p=0.04) and higher serum VEGF levels (mean (SE), 5123 (649) pg/ml vs 1893 (195) pg/ml; P=0.02).
Discussion
Our patient case is characterised by acute polyneuropathy with electrophysiological features of demyelination. In particular, the speed of neuropathy progression was exceptionally rapid as POEMS syndrome and the patient was treated initially as GBS, and then CIDP. Other systemic features of POEMS syndrome developed later. Eventually, the patient had skin changes, M-protein, hepato-splenomegary, oedema/effusion, osteosclerotic lesions and an elevated serum VEGF level, and therefore was diagnosed as suffering from POEMS syndrome. The review of consecutive 30 patients with POEMS syndrome shows that neuropathy progression in POEMS syndrome is usually chronic but varies considerably among patients. We suggest that in unusual acute demyelinating neuropathy resembling GBS with paraprotein, other differential diagnoses including POEMS syndrome should be considered.
Previous studies have shown that electrodiagnostic features of POEMS syndrome are somewhat different from those of CIDP; patients with POEMS syndrome have a slowing of nerve conduction more predominant in the intermediate than in the distal nerve segments, rare conduction block and more severe attenuation of compound muscle action potentials in the lower- than in upper-limb nerves.7 8 The precise mechanisms for neuropathy in POEMS syndrome remain unknown. However, VEGF would increase nerve microvascular permeability inducing endoneural oedema, and could allow some neurotoxic serum components toxic to access the nerve parenchyma, leading to demyelination and secondary axonal degeneration.7 Our patient had disproportional nerve conduction slowing in median nerve studies (distal latency, 5.7 ms; forearm nerve conduction velocity, 26 m/s) and severe axonal loss in tibial motor axons (non-recordable compound muscle action potential), consistent with the hypothesis. However, there was prominent conduction block in the forearm segment of the median nerve that is rarely seen in POEMS syndrome. We speculate that the nerve trunks were involved by multifocal demyelination more prominently than usual, and this might explain the rapid progression of muscle weakness in this patient.
From the neurological aspect, our results showed that POEMS syndrome is a serious disorder; 22 (73%) of them were unable to walk independently with the median periods of 9.5 months from onset. Moreover, it is a potentially fatal systemic disease. Therefore, early diagnosis and treatment are necessary to improve the prognosis of the disorder. We suggest that careful electrodiagnositic examination, as well as screening of systemic POEMS features and measurement of serum VEGF levels, is useful for an early diagnosis of POEMS syndrome.
Footnotes
Funding This work was supported in part by the Health and Labour Sciences Research Grant on Intractable Diseases (Neuroimmunological Diseases) (SK) and the Research Grant 16B-1 for Nervous and Mental Disorders (SK) from the Ministry of Health, Labour and Welfare of Japan.
Competing interest None.
Ethics approval Ethics approval was provided by the Ethics Committee, Chiba University School of Medicine.
Provenance and peer review Not commissioned; externally peer reviewed.