Epstein-Barr virus infection or malignant lymphoma - what you see is not what you get.

Infectious mononucleosis may mimic lymphoma, both clinically and histopathologically. We present a patient with neurological symptoms and lymphadenopathy, initially diagnosed as Epstein-Barr virus (EBV)-positive angioimmunoblastic T-cell lymphoma (AITL) with cerebrospinal fluid (CSF) localisation based on lymph node pathology and a 30-fold higher EBV load in the CSF compared with serum. However, the patient fully recovered spontaneously and EBV became negative in both CSF and serum, suggestive of a dramatic presentation of EBV meningoencephalitis.

To be in pain (or not): a computer enables outpatients to inform their physician.

BACKGROUND: In the outpatient oncology clinic, pain management is often inadequate. Incorporating a systematic pain management program into visits is likely to improve this. We implemented an integrated program, including a structured pain assessment, pain treatment protocol and patient education module. In the present study, we investigated whether this intervention improved pain control. PATIENTS AND METHODS: At seven oncology outpatient clinics, patients were asked to register their pain intensity on a touch screen computer. These scores were made available into their electronic medical records. Additionally, a hospital-wide treatment protocol for cancer-related pain and a patient education module were developed. A data warehouse system enabled us to extract patient data from the electronic medical record anonymously and to use them for analysis. The primary outcome of the study was the percentage of patients with moderate to severe pain [current pain (CPI), NRS > 4] measured during 2 weeks at the start and 6 months after implementation. As secondary outcomes, we studied the percentage of pain registrations in specific patient groups and the percentage of patients treated with a curative and a palliative intention with (moderate-severe) pain. Differences were tested with the χ(2) test. RESULTS: During the first 6 months, 3407 of the 4345 patients (78%) registered their pain intensity on the touch screen computer. The percentage of patients with moderate to severe CPI decreased 32% (P = 0.021): from 12.5% at start to 8.5% after 6 months. More patients in the palliative phase than in the curative phase of their disease registered their pain intensity (82% versus 75%, respectively, P < 0.005), and more patients in the palliative phase experienced moderate to severe pain (23% versus 14%, respectively, P < 0.001). CONCLUSION: Pain registration by patients themselves is feasible, provides insight into patients' pain intensity and may improve pain control in outpatients with cancer-related pain. CLINICAL TRIAL NUMBER: Because this is an innovation project and not a primary research project, it has no clinical trial number. The protocol and all materials involved were approved by the Institutional Review Board of the Erasmus MC (MEC-2009-324).

Bortezomib-induced polyneuropathy.

BACKGROUND: Peripheral neuropathy is a frequent side effect of bortezomib chemotherapy. Relatively little is known about the clinical characteristics of this neuropathy, especially with respect to pain. Our aim was to describe the clinical characteristics and course of bortezomib-induced polyneuropathy. METHODS: This is a retrospective cohort study of 39 patients diagnosed with bortezomib-induced polyneuropathy. RESULTS: Pain is the most prominent symptom and 14 of 39 patients suffered from severe pain. More than 50% of our patients used analgesics due to moderate or severe pain. We found no correlation between severity of symptoms of bortezomib-induced polyneuropathy and cumulative dose or dose intensity of bortezomib. Nerve conduction studies did not correlate well with symptom severity. Dose reduction or discontinuation of treatment reduced severity in most cases. CONCLUSION: Painful polyneuropathy is a frequent, dose-limiting side effect of bortezomib with a relatively good prognosis. Careful neurological monitoring of symptoms and timely dose adjustment is important.

Chemotherapy-induced neurotoxicity: the value of neuroprotective strategies.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common major dose-limiting side effect of many chemotherapeutic agents, including platinum compounds, taxanes, vinca alkaloids, thalidomide and newer agents such as bortezomib. The incidence and degree of neuropathy depends on the type of cytotoxic drug, the duration of administration, cumulative dose and pre-existing peripheral neuropathy. Because of increasing survival rates of patients treated with neurotoxic agents, CIPN is accompanied by a significant decrease in the patient's quality of life among cancer survivors. Therefore, several neuroprotective strategies, including calcium/magnesium infusion, amifostine, gluthatione, glutamine, acetyl-L-carnitine and erythropoietin as most promising, have been investigated to decrease the neurotoxicity without compromising anti-tumour efficacy. However, clinical evidence for the efficacy of these drugs is sparse. In this review we will give an outline of the neurotoxic effects of chemotherapeutic agents, their clinical manifestations and potential neuroprotective strategies.

Spinal glycinergic and GABAergic neurons expressing C-fos after capsaicin stimulation are increased in rats with contralateral neuropathic pain.

There is increasing evidence that pain transmission on one side of the body is influenced by a painful state on the other side. We have investigated this phenomenon by studying the activation pattern (using C-fos labeling) of spinal glycinergic and GABAergic (Gly/GABA) neurons after capsaicin injection in the ipsilateral hind paw of rats that were preconditioned with an acute or chronic pain stimulus in the contralateral hind paw or rats that were not preconditioned (control). For this purpose, fluorescent in situ hybridization with GlyT2 and GAD67 mRNA probes was combined with fluorescent C-fos immunohistochemistry. Rats were preconditioned with acute (capsaicin, Complete Freund's Adjuvant (CFA) 1.5 h), chronic inflammatory (CFA 20 h and 4 days), neuropathic (spared nerve injury (SNI) 2 weeks), or control pain stimuli (saline 20 h and 4 days; sham-SNI 2 weeks). We found that after capsaicin injection in rats preconditioned with CFA inflammation (4 days), sham-SNI or with SNI neuropathic pain, the numbers (27 ± 3, 21 ± 2, and 21 ± 2, respectively) and percentages (55% ± 4, 43% ± 2, and 42% ± 2, respectively) of C-fos activated neurons that were Gly/GABA increased significantly as compared with control (10 ± 1 and 25% ± 2). The increase in the total number of C-fos activated Gly/GABA neurons was present primarily in the superficial dorsal horn (laminae I and II; control: 9%; CFA 4 days: 56%; SNI 2 weeks: 42%). This increase in C-fos activation of Gly/GABA neurons occurred without significant changes in the total number of C-fos activated neurons, and without any significant changes in the mechanical thresholds in the hind paws after capsaicin injection. The results showed that one-sided chronic pain, especially inflammation, significantly increases the C-fos activation pattern of spinal Gly/GABA neurons on the other side of the spinal cord. This further underlines the existence of a dynamic interaction between ipsi- and contralateral spinal neurons in the processing of nociceptive information.

Pain in Guillain-Barre syndrome: a long-term follow-up study.

BACKGROUND: Pain in Guillain-Barré syndrome (GBS) may be pronounced and is often overlooked. OBJECTIVES: To obtain detailed information about pain in GBS and its clinical variants. METHODS: This was a prospective cohort study in 156 patients with GBS (including 18 patients with Miller Fisher syndrome [MFS]). We assessed the location, type, and intensity of pain using questionnaires at standard time points during a 1-year follow-up. Pain data were compared to other clinical features and serology. RESULTS: Pain was reported in the 2 weeks preceding weakness in 36% of patients, 66% reported pain in the acute phase (first 3 weeks after inclusion), and 38% reported pain after 1 year. In the majority of patients, the intensity of pain was moderate to severe. Longitudinal analysis showed high mean pain intensity scores during the entire follow-up. Pain occurred in the whole spectrum of GBS. The mean pain intensity was predominantly high in patients with GBS (non-MFS), patients with sensory disturbances, and severely affected patients. Only during later stages of disease, severity of weakness and disability were significantly correlated with intensity of pain. CONCLUSIONS: Pain is a common and often severe symptom in the whole spectrum of GBS (including MFS, mildly affected, and pure motor patients). As it frequently occurs as the first symptom, but may even last for at least 1 year, pain in GBS requires full attention. It is likely that sensory nerve fiber involvement results in more severe pain.

Intrathecal injection of GDNF and BDNF induces immediate early gene expression in rat spinal dorsal horn.

Glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) are potent trophic factors for dorsal root ganglion cells. In addition, these factors are produced in subsets of dorsal root ganglion cells and transported anterogradely to their terminals in the superficial dorsal horn of the spinal cord, where they constitute the only source of GDNF and BDNF. We investigated the effect of 10 mug GDNF and BDNF injected by lumbar puncture on the expression of the immediate early gene (IEG) products c-Fos, c-Jun, and Krox-24 in the adult rat dorsal horn. In the dorsal horn of S1 spinal segments, GDNF and BDNF induced a strong increase in IEG expression, which was most pronounced in laminae I and II (2.9- to 4.5-fold). More distal from the injection site, in the dorsal horn of L1/L2 spinal segments, the increase in IEG expression was less pronounced, suggesting a concentration-dependent effect. In order to explain the effects of intrathecally injected GDNF, we investigated whether lumbo-sacral dorsal horn neurons expressed RET protein, the signal-transducing element of the receptor complex for GDNF. It was found that several of these neurons contained RET immunoreactivity and that some of the RET-labeled neurons had the appearance of nociceptive-specific cells, confirming their presumed role in pain transmission. Additionally, using double-labeling immunofluorescence combined with confocal microscopy, it was found that after intrathecal GDNF injection 35% of c-Fos-labeled cells were also labeled for RET. These results demonstrate that intrathecally administered GDNF and BDNF induce IEG expression in dorsal horn neurons in the adult rat, supposedly by way of their cognate receptors, which are present on these neurons. We further suggest that the endogenous release of GDNF and BDNF, triggered by nociceptive stimuli, is involved in the induction of changes in spinal nociceptive transmission as in various pain states.