Described here is a case of accidental intrathecal administration of vincristine with pathologic findings in the central nervous system. A 3-year-old boy with acute lymphoblastic leukemia, was given his ninth course chemotherapy. Vincristine was accidentally injected intrathecally. The clinical course was rapidly progressive (6-day course) and resulted in death. An autopsy was done. The brain and spinal cord was grossly edematous and congested without any specific feature. Histologically, profound loss of neuron was noted in the spinal cord. Remaining neurons in the spinal cord, particularly anterior horn cells were markedly swollen. The spinal nerves show diffuse axonal degeneration and myelin loss. The upstream portion of the spinal cord (brain stem, cerebellum, cerebrum) showed patchy loss of neurons, especially Purkinje cells and granular cells of the cerebellar cortex. Many neurons showed axonal reaction (chromatolysis) with swelling. Several neurons show intracytoplasmic eosinophilic inclusion body. Myelin loss, axonal swelling and enlargement of perivascular spaces were seen throughout the white matter of central nervous system.
Antineoplastic Agents/therapeutic use* ; Brain/pathology ; Brain/drug effects ; Case Report ; Central Nervous System/pathology ; Central Nervous System/drug effects* ; Child, Preschool ; Fatal Outcome ; Histocytochemistry ; Human ; Injections, Spinal ; Leukemia, Lymphocytic, Acute/drug therapy* ; Male ; Medication Errors* ; Spinal Cord/pathology ; Spinal Cord/drug effects ; Spinal Nerves/pathology ; Spinal Nerves/drug effects ; Vincristine/therapeutic use* ; Vincristine/administration & dosage

Caffeine is one of the most widely consumed neuroactive drugs, coming mostly from everyday beverages such as coffee and tea. To investigate whether caffeine induces apoptosis in the central nervous system, 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay, 4,6-diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, flow cytometric analysis, DNA fragmentation assay, and caspase-3 enzyme assay were performed on SK-N-MC human neuroblastoma cells. Cells treated with caffeine at concentrations as high as 10 mM exhibited several characteristics of apoptosis. In addition, caffeine was shown to increase the caspase-3 activity. These results suggest that high-dose of caffeine induces apoptosis in human neuroblastoma cells, probably by increasing the caspase-3 enzyme activity.
Apoptosis/*drug effects ; Caffeine/*toxicity ; Caspase 3 ; Caspases/metabolism ; Cell Cycle/drug effects ; Cell Survival/drug effects ; Central Nervous System/cytology/*drug effects ; DNA Fragmentation ; Humans ; Neuroblastoma/enzymology/pathology ; Tumor Cells, Cultured

BACKGROUNDAlthough neurologic manifestations often complicate the course of patients with multiple myeloma, direct central nervous system invasion is rare. This study explored the neurologic symptoms, signs, clinical features, therapy and prognosis of Chinese patients with central nervous system myeloma invasion.

METHODSThe diagnosis, therapy and prognosis were analyzed retrospectively in 11 Chinese multiple myeloma patients with central nervous system infiltration from a total of 625 patients who have been treated at Changzheng Hospital (Shanghai, China) between January 1993 and May 2009. Survival curve was constructed with the use of Kaplan-Meier estimates.

RESULTSThere were 11 patients with central nervous system involvement from 625 multiple myeloma patients. The occurrence rate was 1.8%. Ten of the 11 patients had other extramedullary diseases. Symptoms included cerebral symptoms, cranial nerve palsies, and spinal cord or spinal nerve roots symptoms. Cerebrospinal fluid was abnormal in 7 patients, usually exhibiting pleocytosis and elevated protein content, plus positive cytologic findings. Specific magnetic resonance imaging findings suggestive of central nervous system invasion were found in 9 patients. After a median follow-up of 19 months, 3 patients were alive. The median overall survival for all patients was 23 months, while the median overall survival for patients after central nervous system invasion was merely 6 months.

CONCLUSIONSIt is exceedingly rare for there to be central nervous system infiltration in multiple myeloma patients. When it occurs, the prognosis is extremely poor despite the use of aggressive local and systemic treatment including stem cell transplantation.

Adult ; Aged ; Brain ; drug effects ; pathology ; Central Nervous System ; drug effects ; pathology ; Dexamethasone ; therapeutic use ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Methotrexate ; therapeutic use ; Middle Aged ; Multiple Myeloma ; complications ; drug therapy ; pathology ; radiotherapy ; Thalidomide ; therapeutic use

OBJECTIVETo explore the efficacy and safety of pemetrexed in the treatment of relapsed primary central nervous system lymphoma (PCNSL).

METHODSSeven cases with relapsed PCNSL admitted in our hospital between August 2012 and August 2013 were retrospectively reviewed.

RESULTSOf the 7 relapsed cases, ectopic recurrence occurred in 3, in situ recurrence in 3 and leptomeningeal metastasis in 1. Patients with relapsed PCNSL were administered with high-dose pemetrexed (900 mg/m²) once for every 3 weeks and supplemented with folic acid and vitamin B₁₂. Complete remission was obtained in 2 patients, partial remission in 3 patients and progressive disease in 2. The overall response rate was 71.4% (5/7). The main adverse reactions were myelosuppression and gastrointestinal reaction.

CONCLUSIONTreatment of relapsed PCNSL is difficult, and its prognosis is very poor. Pemetrexed therapy is a meaningful trial.

Adult ; Aged ; Central Nervous System Neoplasms ; drug therapy ; pathology ; Female ; Glutamates ; administration & dosage ; adverse effects ; therapeutic use ; Guanine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Pemetrexed ; Prognosis ; Retrospective Studies

Apoptosis is a programmed, physiologic mode of cell death that plays an important role in tissue homeostasis. As for the central nervous system, ischemic insults can induce pathophysiologic cascade of apoptosis in neurophils. Impairment of astroctye functions during brain ischemia can critically influence neuron survival by neuronglia interactions. We aimed to elucidate the protective effect of ketamine on apoptosis by energy deprivation in astrocytes. Ischemic insults was induced with iodoacetate/ carbonylcyanide mchlorophenylhydrazone (IAA/CCCP) 1.5 mM/ 20 micrometer or 150 micrometer/2 micrometer for 1 hr in the HTB-15 and CRL-1690 astrocytoma cells. Then these cells were reperfused with normal media or ketamine (0.1 mM) containing media for 1 hr or 24 hr. FITC-annexin-V staining and propidium iodide binding were determined by using flow cytometry. Cell size and granularity were measured by forward and side light scattering properties of flow cytometry system, respectively. An addition of keta-mine during reperfusion increased the proportion of viable cells. Ketamine alleviated cell shrinkage and increased granularity during the early period, and ameliorated cell swelling during the late reperfusion period. Ketamine may have a valuable effect on amelioration of early and late apoptosis in the astrocytoma cells, even though the exact mechanism remains to be verified.
Anesthetics, Dissociative/*pharmacology ; Annexin A5/pharmacology ; Apoptosis ; Astrocytes/metabolism ; Astrocytoma/*drug therapy/pathology ; Brain/pathology ; Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology ; Cell Line, Tumor ; Cell Size ; Cell Survival ; Central Nervous System/drug effects/pathology ; Enzyme Inhibitors/pharmacology ; Flow Cytometry/*methods ; Humans ; Indicators and Reagents/pharmacology ; Iodoacetates/pharmacology ; Ischemia/pathology ; Ketamine/metabolism/*pharmacology ; Light ; Neurons/metabolism/pathology ; Neutrophils/metabolism ; Perfusion ; Propidium/pharmacology ; Scattering, Radiation ; Time Factors ; Uncoupling Agents/pharmacology