[Myelomatous meningitis: a case report].

We present the case of a 67-year-old woman with meningeal carcinomatosis who was treated with chemotherapy for refractory multiple myeloma, and was in remission. She was admitted to our hospital because of tonic seizures and disturbance of consciousness. Monoclonal CD 138-positive plasma cells were detected in her cerebrospinal fluid. Cranial MRI showed gadolinium enhancement of diffuse meninges and cranial nerves. We diagnosed the patient with systemic epilepsy due to meningeal carcinomatosis and administered antiepileptic drugs and intrathecal chemotherapy; however, she showed little improvement, and she passed away on hospital day 74 because of disease progression. Multiple myeloma is known to be associated with neurological symptoms such as peripheral neuropathy, myelopathy, and radiculopathy; however, central nervous system involvement in multiple myeloma is uncommon. We should consider central nervous system involvement in multiple myeloma, such as meningeal carcinomatosis, given the importance of early detection and therapeutic intervention.

[Nivolumab‒Induced Severe Thrombocytopenia in a Patient with Advanced Gastric Cancer].

Here, we report a case of severe thrombocytopenia induced by nivolumab. A 70‒year‒old woman with advanced gastric cancer was treated with nivolumab. After the first dose, she noticed an erythematous rash. During the second cycle, fever and purpura on the lower extremities were also noted. Laboratory examinations revealed severe thrombocytopenia of grade 4, mild hemolytic anemia, leukopenia, and coagulopathy. Immune‒related adverse events(irAE)were suspected, and we started 40 mg(0.7 mg/kg)prednisolone(PSL)per day. Her symptoms and laboratory data immediately improved. However, when we reduced the dose of PSL, she developed rash and thrombocytopenia again. We increased the dose of PSL to 40 mg, which was effective for improving these abnormalities. We then gradually reduced the PSL, paying attention to avoid a relapse of irAEs. We could not restart chemotherapy thereafter, and she died from progression of gastric cancer. As shown in this case, PSL is effective for immune‒related thrombocytopenia; however, determining how to reduce the dose of PSL and when to restart chemotherapy requires careful consideration.

Upper gastrointestinal ischemia as a rare complication of paroxysmal nocturnal hemoglobinuria.

When patients with PNH present with abdominal symptoms, thrombosis-induced gastrointestinal injury should be considered; computed tomography and esophagogastroduodenoscopy may help make the diagnosis of this potentially serious complication.

CRMP1 and CRMP4 are required for proper orientation of dendrites of cerebral pyramidal neurons in the developing mouse brain.

Neural circuit formation is a critical process in brain development. Axon guidance molecules, their receptors, and intracellular mediators are important to establish neural circuits. Collapsin response mediator proteins (CRMPs) are known intercellular mediators of a number of repulsive guidance molecules. Studies of mutant mice suggest roles of CRMPs in dendrite development. However, molecular mechanisms of CRMP-mediated dendritic development remain to elucidate. In this study, we show abnormal orientation of basal dendrites (extension to deeper side) of layer V pyramidal neurons in the cerebral cortex of CRMP4-/- mice. Moreover, we observed severe abnormality in orientation of the basal dendrites of these neurons in double knockout of CRMP1 and 4, suggesting redundant functions of these two genes. Redundant gene functions were also observed in proximal bifurcation phenotype in apical dendrites of hippocampal CA1 pyramidal neurons. These results indicate that CRMP1 and CRMP4 regulate proper orientation of the basal dendrites of layer V neurons in the cerebral cortex.

Deletion of Crmp4 attenuates CSPG-induced inhibition of axonal growth and induces nociceptive recovery after spinal cord injury.

The capacity for regeneration in the injured adult mammalian central nervous system (CNS) is largely limited by potent inhibitory barriers. Chondroitin sulfate proteoglycans (CSPGs) are major inhibitors of axonal regeneration/sprouting and accumulate at lesion sites after CNS trauma. Despite extensive research during the two decades since their discovery, the molecular mechanisms remain elusive, including intracellular phosphorylation events. Collapsin response mediator protein 4 (CRMP4) is known to directly regulate cytoskeletal dynamics and neurite extension, while phosphorylated CRMP4 loses its binding affinity for cytoskeletal proteins. We have previously found that spinal cord injury (SCI) induces CRMP4 upregulation and phosphorylation and that CRMP4 knockout (Crmp4-/-) mice show behavioral recovery of locomotor function after SCI. However, the role of CRMP4 in the recovery of other forms of physiological function such as sensation remains largely unknown. We here have demonstrated CRMP4 involvement in CSPG-induced inhibitory signaling and nociceptive recovery in Crmp4-/- mice after SCI. We cultured dorsal root ganglion (DRG) neurons on CSPG-coated dishes; Crmp4 deletion overrode CSPG-induced inhibition of axon growth in vitro. CRMP4 levels were increased in DRGs in vivo after SCI. Crmp4-/- mice exhibited axonal growth of sensory neurons and recovery of nociceptive function after spinal transection. These results support Crmp4 deletion as a therapeutic target in the treatment of SCI.