The assessment of treatment response in glioblastoma is difficult with MRI because reactive blood-brain barrier alterations with contrast enhancement can mimic tumor progression. In this study, we investigated the predictive value of PET using O-(2-18 F-fluoroethyl)-L-tyrosine ( 18 F-FET PET) during treatment. Methods: In a prospective study, 25 patients with glioblastoma were investigated by MRI and 18 F-FET PET after surgery (MRI-/FET-1), early (7-10 d) after completion of radiochemotherapy with temozolomide (RCX) (MRI-/FET-2), and 6-8 wk later (MRI-/FET-3). Maximum and mean tumor-to-brain ratios (TBR max and TBR mean , respectively) were determined by region-of-interest analyses. Furthermore, gadolinium contrastenhancement volumes on MRI (Gd-volume) and tumor volumes in 18 F-FET PET images with a tumor-to-brain ratio greater than 1.6 (T vol 1.6 ) were calculated using threshold-based volume-ofinterest analyses. The patients were grouped into responders and nonresponders according to the changes of these parameters at different cutoffs, and the influence on progression-free survival and overall survival was tested using univariate and multivariate survival analyses and by receiver-operating-characteristic analyses. Results: Early after completion of RCX, a decrease of both TBR max and TBR mean was a highly significant and independent statistical predictor for progression-free survival and overall survival. Receiver-operating-characteristic analysis showed that a decrease of the TBR max between FET-1 and FET-2 of more than 20% predicted poor survival, with a sensitivity of 83% and a specificity of 67% (area under the curve, 0.75). Six to eight weeks later, the predictive value of TBR max and TBR mean was less significant, but an association between a decrease of T vol 1.6 and PFS was noted. In contrast, Gd-volume changes had no significant predictive value for survival. Conclusion: In contrast to Gd-volumes on MRI, changes in 18 F-FET PET may be a valuable parameter to assess treatment response in glioblastoma and to predict survival time.

Abducens palsy occasionally has been observed after diagnostic lumbar puncture (DLP). 1-3 Its risk is not exactly known. We are aware of only one report, which mentions not a single case among 1,341 DLPs when using 22-gauge needles. 4 At our clinic, an average of 800 inpatients a year undergo DLP. We usually use 22gauge needles, and occasionally (in less than 5%), 20-gauge needles. Over a 14.5-year period, we saw two patients with abducens palsy-one unilateral, one bilateral-after DLP. This translates to a risk of less than 1 out of 5,800 DLPs.Patient reports. Patient 1. A 61-year-old man with type 2 diabetes noticed progressive weakness of the legs. Neurologic examination revealed proximal paraparesis, loss of deep tendon reflexes of the legs, diminished sensation to touch and pain in a stocking-like pattern, and diminished vibration sense. Nerve conduction studies documented sensorimotor demyelinating neuropathy of the legs and, less pronounced, of the arms. DLP was done with a 22-gauge needle and was not followed by postlumbar puncture headache. After 7 days, he noticed horizontal diplopia when looking to the right. There was a right-sided abducens palsy. MRI documented small bifrontal and parietal hygromas and diffuse meningeal gadolinium enhancement (figure). Abducens palsy recovered completely within 4 months.Patient 2. A 33-year-old man with type 2 diabetes noticed exercise-related pain in the calf and thigh muscles (finally attributed to a myoadenylate deaminase deficiency). Neurologic examination revealed bilateral loss of ankle jerks and diminished sensation to touch and pain in a stocking-like pattern. Nerve conduction studies documented sensory demyelinating neuropathy of the legs and, less pronounced, of the arms. After DLP with a 22-gauge needle, he developed mild postlumbar puncture headache recovering within 7 days. Two days later (9 days after DLP), he noticed horizontal diplopia when looking to the left and right. There was a bilateral abducens palsy. MRI documented diffuse meningeal gadolinium enhancement. Abducens palsies completely recovered within 7 months.Discussion. Sixth nerve palsy after DLP is attributed to continuous CSF leakage through the dural hole. 2,5 This results in intracranial hypotension with MRI-documented descent of the brain even in the supine position, causing traction of the VIth nerve and pain-sensitive structures (dura, blood vessels, nerves). 5 This also explains orthostatic headache, which is usually associated with post-DLP abducens palsies. 1,2,5 The needle size seems to be crucial for both post-DLP abducens From the Departments of Neurology (Drs. Thömke, Mika-Grü ttner, and Visbeck) and Neuroradiology (Dr. Brü hl),

Objective: To analyze antisynthetase syndrome-associated myositis by modern myopathologic methods and to define its place in the spectrum of idiopathic inflammatory myopathies (IIMs). Methods: Skeletal muscle biopsies from antisynthetase syndrome-associated myositis and other IIMs from different institutions worldwide were analyzed by histopathology, quantitative PCR, and electron microscopy. Results: Myonuclear actin filament inclusions were identified as a unique morphologic hallmark of antisynthetase syndrome-associated myositis. Nuclear actin inclusions were never found in dermatomyositis, polymyositis, sporadic inclusion body myositis, autoimmune necrotizing myopathy associated with signal recognition particle or 3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies, or nonspecific myositis associated with other systemic diseases, harboring myositis-associated autoantibodies, and presenting myofiber necrosis. We show that molecules involved in actin filament formation and actin shuttling mechanisms are altered in antisynthetase syndrome, and may thus be involved in pathologic myonuclear actin aggregation. In addition, we have identified a typical topographic distribution of necrotic myofibers predominantly located at the periphery of muscle fascicles accompanied by inflammation and destruction of the perimysial connective tissue. Conclusion: Antisynthetase syndrome-associated myositis is characterized by distinctive myonuclear actin filament inclusions, including rod formations and a typical necrotizing perimysial myositis. This supports the hypothesis that antisynthetase syndrome-associated myositis is unique and should not be grouped among dermatomyositis, polymyositis, sporadic inclusion body myositis, necrotizing autoimmune myositis, or nonspecific myositis. Classification of evidence: This study provides Class II evidence that for patients with IIMs, the presence of myonuclear actin filament inclusions accurately identifies patients with antisynthetase syndrome-associated myositis (sensitivity 81%, specificity 100%). Methods: Skeletal muscle biopsies from antisynthetase syndrome-associated myositis and otherIIMs from different institutions worldwide were analyzed by histopathology, quantitative PCR, and electron microscopy.Results: Myonuclear actin filament inclusions were identified as a unique morphologic hallmark of antisynthetase syndrome-associated myositis. Nuclear actin inclusions were never found in dermatomyositis, polymyositis, sporadic inclusion body myositis, autoimmune necrotizing myopathy associated with signal recognition particle or 3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies, or nonspecific myositis associated with other systemic diseases, harboring myositis-associated autoantibodies, and presenting myofiber necrosis. We show that molecules involved in actin filament formation and actin shuttling mechanisms are altered in antisynthetase syndrome, and may thus be involved in pathologic myonuclear actin aggregation. In addition, we have identified a ...