PurposeHematologic toxicities, including neutropenia, thrombocytopenia, and anemia, are major adverse effects of PARP inhibitors (PARPis), but the incidence rate and overall risk has not been systematically studied. Therefore, we conducted a meta-analysis of published clinical trials to investigate the incidence and relative risks (RRs) of severe (high-grade) hematologic events in cancer patients treated with PARPis.MethodsPubMed, Embase, and oncology conference proceedings were searched for relevant studies. Eligible studies were Phase II and III randomized controlled trials (RCTs) of PARPis in cancer patients with adequate safety data on hematologic toxicities. The summary incidence, RRs, and 95% confidence intervals (CIs) were calculated.ResultsA total of 2,479 patients from 12 RCTs revealed that the incidence of PARPi-associated severe hematologic toxicities was, respectively: neutropenia: 32.9% (95% CI, 20.5%–48.3%); thrombocytopenia: 15.9% (95% CI, 9.5%–25.4%), and anemia: 9.1% (95% CI, 5.1%–15.7%). Olaparib was associated with an increased risk of severe neutropenia. Veliparib was associated with an increased risk of severe neutropenia and thrombocytopenia. Niraparib was associated with an increased risk of severe thrombocytopenia, anemia, and neutropenia. When stratified by combination therapy, significantly increased risk of hematologic toxicities was observed for patients treated with PARPis monotherapy and PARPis combined with single-agent chemotherapy.ConclusionTreatment with PARPis olaparib, veliparib, and niraparib is associated with a significant increase in the risk of hematologic toxicities in cancer patients, and frequent clinical monitoring should be emphasized when managing these PARPis.

Focal cortical dysplasia type IIB (FCDIIB) is a developmental malformation of the cerebral cortex that is associated with pharmacoresistant epilepsy. Overexpression of adenosine kinase (ADK) has been regarded as a pathologic hallmark of epilepsy. We hypothesized that the epileptogenic mechanisms underlying FCDIIB are related to abnormal ADK expression. We used immunohistochemistry to examine the expression of ADK and of heterogeneous cell population markers of astrocytes (glial fibrillary acidic protein), immature glia (vimentin), immature neurons (neuronal class III beta-tubulin, TUJ1), multipotential progenitor cells (nestin), mature neurons (microtubule-associated protein 2), and antiapoptotic gene products (Bcl-2) in surgically resected human epileptic cortical specimens from FCDIIB patients (n = 20). Expression patterns were compared with those in normal autopsy (n = 6) and surgical control (n = 6) brain samples. Balloon cells in FCDII lesions were immunoreactive for ADK (77%) and balloon cells expressing the different cell markers expressing different degrees of ADK. Adenosine kinase expression assessed by Western blot and enzymatic activity were also greater in FCD versus control samples. These results suggest that upregulation of ADK is a common pathologic component of FCDIIB. Adenosine kinase might, therefore, be a target in the treatment of epilepsy associated with FCD.

Rasmussen encephalitis (RE) is a rare neurologic disorder of childhood characterized by unihemispheric inflammation, progressive neurologic deficits, and intractable focal epilepsy. The pathogenesis of RE is still enigmatic. Adenosine is a key endogenous signaling molecule with anticonvulsive and anti-inflammatory effects, and our previous work demonstrated that dysfunction of the adenosine kinase (ADK)–adenosine system and astrogliosis are the hallmarks of epilepsy. We hypothesized that the epileptogenic mechanisms underlying RE are related to changes in ADK expression and that those changes might be associated with the development of epilepsy in RE patients. Immunohistochemistry was used to examine the expression of ADK and glial fibrillary acidic protein in surgically resected human epileptic cortical specimens from RE patients (n = 12) and compared with control cortical tissues (n = 6). Adenosine kinase expression using Western blot and enzymatic activity for ADK were assessed in RE versus control samples. Focal astrogliosis and marked expression of ADK were observed in the lesions of RE. Significantly greater ADK expression in RE versus controls was demonstrated by Western blot, and greater enzymatic activity for ADK was demonstrated using an enzyme-coupled bioluminescent assay. These results suggest that upregulation of ADK is a common pathologic hallmark of RE and that ADK might be a target in the treatment of epilepsy associated with RE.

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Patients suffering different intervals of facial nerve injury were investigated by functional magnetic resonance imaging to study changes in activation within cortex.Forty-five patients were divided into 3 groups based on intervals of facial nerve injury. Another 16 age and sex-matched healthy participants were included as a control group. Patients and healthy participants underwent task functional magnetic resonance imaging (eye blinking and lip pursing) examination.Functional reorganization after facial nerve injury is dynamic and time-dependent. Correlation between activation in sensorimotor area and intervals of facial nerve injury was significant, with a Pearson correlation coefficient of −0.951 (P < 0.001) in the left sensorimotor area and a Pearson correlation coefficient of 0.333 (P = 0.025) in the right sensorimotor area.Increased activation in integration areas, such as supramarginal gyrus and precunes lobe, could be detected in the early-middle stage of facial dysfunction compared with normal individuals. Decreased activation in sensorimotor area contralateral to facial nerve injury could be found in late stage of facial dysfunction compared with normal individuals. Dysfunction in the facial nerve has devastating effects on the activity of sensorimotor areas, whereas enhanced intensity in the sensorimotor area ipsilateral to the facial nerve injury in middle stage of facial dysfunction suggests the possible involvement of interhemispheric reorganization. Behavioral or brain stimulation technique treatment in this stage could be applied to alter reorganization within sensorimotor area in the rehabilitation of facial function, monitoring of therapeutic efficacy, and improvement in therapeutic intervention along the course of recovery.

The aim of this research is to apply an approach based on phase transfer entropy (PTE) and graph theory to study the interactions between the stereo-electroencephalography (SEEG) activities recorded in multilobar origin, in order to evaluate their ability to detect the epileptogenic zone (EZ) of temporal lobe epilepsies (TLE). Forty-three patients were included in this retrospective study. Five to sixteen (median = 12) multilead electrodes were implanted per patient, and, for each patient, a sub-set of between 10 and 32 (median = 22) bipolar derivations was selected for analysis. The leads were classified into the onset leads (OLs), the early propagation leads (EPLs), and the rest of the leads (RLs). The results showed that a significantly different dynamic trend of the out/in ratio (more obvious in the gamma band) distinguishes the OLs from RLs in the 23 patients who were seizure-free not only during the ictal event (significant elevation), but also during the inter-,pre-, late-ictal periods, and especially in the post-ictal (sharp decline) state. However, in the 20 patients who were not-seizure-free, the differences between the OLs and RLs during the post-ictal period were not found in any frequency band. The dynamic trend was used to predict surgical outcome, and the results showed that the sensitivity was 91% and the specificity was 70%. In brief, this study indicates that our approach may add new and valuable information, providing efficient quantitative measures useful for localizing the EZ.

Rasmussen encephalitis (RE) is a severe pediatric inflammatory brain disease characterized by unilateral inflammation and atrophy of the cerebral cortex, drug‐resistant focal epilepsy and progressive neurological and cognitive deterioration. The etiology and pathogenesis of RE remain unclear. Our previous results demonstrated that the adenosine A1 receptor (A1R) and the major adenosine‐removing enzyme adenosine kinase play an important role in the etiology of RE. Because the downstream pathways of inhibitory A1R signaling are modulated by stimulatory A2AR signaling, which by itself controls neuro‐inflammation, glial activation and glial glutamate homeostasis through interaction with glutamate transporter GLT‐1, we hypothesized that maladaptive changes in adenosine A2A receptor (A2AR) expression are associated with RE. We used immunohistochemistry and Western blot analysis to examine the expression of A2ARs, glutamate transporter‐I (GLT‐1) and the apoptotic marker Bcl‐2 in surgically resected cortical specimens from RE patients (n = 18) in comparison with control cortical tissue. In lesions of the RE specimen we found upregulation of A2ARs, downregulation of GLT‐1 and increased apoptosis of both neurons and astroglia. Double staining revealed colocalization of A2ARs and Bcl‐2 in RE lesions. These results suggest that maladaptive changes in A2AR expression are associated with a decrease in GLT‐I expression as a possible precipitator for apoptotic cell loss in RE. Because A2AR antagonists are already under clinical evaluation for Parkinson's disease, the A2AR might likewise be a tractable target for the treatment of RE.

Background: Rasmussen encephalitis (RE) is a rare progressive encephalitis that results in intractable seizures, cognitive decline and hemiparesis. Surgery seems to be the only effective way to control seizures in RE patients. Objective: To describe the clinical, electrophysiological, neuroradiological and histological findings of our patients with RE and to evaluate the outcome of their surgical treatment. Methods: A total of 20 patients were identified by the criteria of RE. Surgery was conducted in the left hemisphere in 6 patients and in the right hemisphere in 14. The surgical methods included anatomical hemispherectomy, functional hemispherectomy, hemispherotomy, lesion resection, multilobar resection, selective resection and bipolar electrocoagulation of functional cortexes. Results: The mean follow-up period was 5.45 years (range 3-8). After surgery, 16 patients (80%) were evaluated as being Engel class I. All of the patients had increases in cognitive abilities after surgery except 1 patient with bilateral RE. After surgery, most patients could walk independently, but the fine movement of the hands was lost. Postoperative hydrocephalus was observed in 1 patient after functional hemispherectomy, and there was no death in this series. Conclusion: Hemispherectomy and hemispherotomy were both confirmed as beneficial procedures in controlling seizures and improving quality of the life in RE cases.