The polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome is a rare multisystem disorder of obscure pathogenesis associated with osteosclerotic myeloma. Circulating levels of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha) interleukin-1 beta [IL-1 beta], IL-2, IL-6, and interferon-gamma [IFN- gamma]), anti-inflammatory cytokines (transforming growth factor beta 1 [TGF beta 1], IL-4, IL-10, and IL-13), the cytokine carrier protein alpha 2 macroglobulin, IL-1 receptor antagonist (IL-1ra), soluble TNF receptors (sTNFr) p55 and p75, and soluble IL-6 receptor (sIL-6r) were determined in 15 patients with POEMS syndrome and 15 with multiple myeloma. Patients with POEMS syndrome had higher serum levels of IL-1 beta, TNF-alpha, and IL-6 and lower serum levels of TGF beta 1 than did patients with multiple myeloma. Serum levels of IL-2, IL-4, IL-10, IL- 13, IFN-gamma, alpha 2 macroglobulin, and sIL-6r were similar in both groups. IL-1ra and sTNFrs were increased in POEMS syndrome, but out of proportion to the increase of IL-1 beta and TNF-alpha. Serial evaluations in 1 patient showed that proinflammatory cytokine serum levels paralleled disease activity assessed by platelet count and neurologic involvement. Our results suggest that the manifestations of POEMS syndrome might be regarded as the result of a marked activation of the proinflammatory cytokine network (IL-1 beta, IL-6, and TNF- alpha) associated with a weak or even decreased (TGF beta 1) antagonistic reaction insufficient to counteract the noxious effects of cytokines.

denly died from a third ventricular colloid cyst several hours after the magnetic resonance imaging (MRI) examination. Both the cyst and the downward brain shift had escaped detection on computed tomographic (CT) studies obtained over the previous several years.Our study was not about severely ill patients. Rather, it was an effort to demonstrate the frequency with which downward herniation can occur during life, the potential danger the process represents in the presence of supratentorial mass lesions, and the relative ease with which it can be identified on midsagittal MRI. Our methods section indicated that because of the remote location of our early-model MRI camera we could not safely study acutely, severely ill patients. Besides, once patients begin to show signs of lower diencephalic or mesencephalic dysfunction, one hardly needs brain images to know what's going on.Surely, the relative clinical danger of vertical versus lateral supratentorial shifts in causing upper brainstem compression is a nonissue. Both are potentially dangerous as clinicians have emphasized for several years (see {3] for review). Following upon MacEwen's early observations (1893) and reemphasized by Adolf Meyer (1921j, many early writers regarded side-to-side cerebral shifts producing uncal (lateral) herniation and subsequent mesencephalic compression as the principal, seldom reversible mechanisms causing neurological decompensation with supratentorial masses. McNealy and Plum [ 31 reemphasized the clinically important sequence of such lateral cerebral displacement but added the new clinical and pathological concept of central herniation accompanying paramedian or bilateral supratentorial masses. Others have sometimes questioned that concept, leading us to conduct the present study, which shows just how vulnerable the brain can be to such rostral-caudal shifts and how easy they are to detect by MRI.Clinically, it matters little whether signs of diencephalicmesencephalic dysfunction reflect geometric rostral-caudal compression, laterocaudal compression, or severe impaction without visible displacement, such as can occur with severe, global brain edema accompanying acute hepatic or hyperammonemic encephalopathy (personal observations). In any of these circumstances, evidence of upper brainstem dysfunction that persists for longer than a few minutes worsens the likelihood for complete recovery. The visualization in a patient with acute or subacute brain disease of severe tissue displacement about the tentorial notch, be it directed laterally or vertically, rostrally or caudally, should warn the observer of imminent danger and the need to apply appropriate preventive measures. To assist neurologists in recognizing such shifts was the goal of our report.

To evaluate a possible implication of cytokines in the pathogenesis of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome, we studied five consecutive patients with this condition, of which four had sclerotic bone lesions and four had multicentric Castleman's disease. Interleukin-1 beta (IL-1 beta) and IL- 6 serum levels were determined in these patients (13 serum samples) and in patients with multiple myeloma (5) and Waldenstrom's macroglobulinemia (5). In situ hybridization of the relevant mRNAs was performed on lymph node specimens of two patients with POEMS syndrome who had Castleman's disease. Elevated serum levels of IL-1 beta (13/13 samples), and IL-6 (7/13 samples) were found in patients with POEMS syndrome. In the other patients, serum IL-1 beta was undetectable or slightly increased and IL-6 was elevated in a single patient with Waldenstrom's macroglobulinemia. Abundant IL-1 beta mRNA-producing cells were present in interfollicular spaces in the two tested patients, while IL-6 mRNA-producing cells were rare. We conclude that IL-1 beta and IL-6 serum levels may be chronically elevated in patients with POEMS syndrome, and that lymph node may be one site of IL-1 beta overproduction. These results are in keeping with the hypothesis that cytokines mediate systemic manifestations of POEMS syndrome.