Synthesis and Biological Evaluation of a Depsipeptidic Histone Deacetylase Inhibitor via a Generalizable Approach Using an Optimized Latent Thioester Solid-Phase Linker.

We describe the synthesis of Xyzidepsin, a depsipeptidic analogue of HDAC inhibitor Romidepsin (FK228), using a solid-phase strategy. Our latent thioester solid-phase linker was synthesized in 92% yield (three steps). Chemoselective conditions unmasked the thioester functionality and cyclized the depsipeptidic macrocycle. An IC50 value of 0.50 µM ± 0.05 was obtained for U937 cells. This synthetic route, well-suited to SAR, represents a generalizable route toward all manner of analogues, including structures with acidic and basic amino acids.

Acute and chronic ischemia in the bilateral cerebellar border zones in patient with migraine with associated diffusion weighted imaging findings.

We present a case of acute and chronic ischemia in the bilateral cerebellar border zones in a patient with migraine with aura. To our knowledge, this imaging presentation has not been published. The patient presented with 20 years of migraines that had worsened with developing aura prior to MRI, which showed restricted diffusion in the bilateral cerebellar border zones, consistent with acute ischemia. Additional ADC hyperintensities were demonstrated in the border zones, consistent with chronic infarcts. Follow-up CT angiogram showed no occlusion, stenosis, vasospasm, or significant atherosclerosis in the posterior circulation. Additionally, follow-up MRI performed 56 days after initial MRI showed that post-migraine ischemia can be associated with signs of microscopic damage on DWI/ADC map that are not visible with T2 weighted or FLAIR sequences. Cerebellar border zone hypoperfusion from cortical spreading depression and/or transient vasospasm is the most likely etiology due to poor collateral circulation and thus a lower ischemic threshold. Changes in physiologic response to 5-HT during migraine with aura may be responsible for these perfusional abnormalities. Some patients may be more prone due to anatomic variability of the superior cerebellar arteries (SCA) and posterior inferior cerebellar arteries (PICA). Radiologist should be aware of subtle small cerebellar zone infarcts with migraine patients when scrutinizing the posterior fossa.

Perfusion Imaging in Autoimmune Encephalitis.

Encephalitis is characterized by inflammation of brain tissue and has various infectious and noninfectious causes. CSF analysis and MRI usually reveal inflammatory changes although sometimes brain imaging may be normal. Autoimmune encephalitis is caused by antibodies against neuronal synaptic receptors, surface proteins, or intracellular proteins. In this case report, we present a 65-year-old female who presented with a fall and altered mental status. Workup for infectious etiologies was negative and MRI of the brain displayed focal restricted diffusion with corresponding T2-FLAIR hyperintensity involving gray matter structures, making the diagnosis unclear. CT perfusion of the brain demonstrated increased cerebral blood volume and cerebral blood flow in the left parietooccipital gray matter, with corresponding normal mean transit time. Following treatment failure with acyclovir, antibiotics, and steroids, the patient was found to be positive for GAD65 antibodies and diagnosed with autoimmune encephalitis. Symptoms markedly improved with plasmapheresis. Autoimmune encephalitis rarely causes restricted diffusion and this is the first case report to describe corresponding hyperperfusion on CT perfusion study.

Enhancing Mass Lesion of the Sphenoid: Atypical Presentation of Ongoing Pneumatization.

Sinus pneumatization is a complex variable process that begins in early life and continues for many years. We present a case of a 6-year-old boy with progressive headaches and neurologic symptoms suggestive of intracranial pathology. The presence of enhancing tissue within the sphenoid sinus created a diagnostic dilemma which leads to a transsphenoidal biopsy. Knowledge of imaging characteristics associated with incomplete pneumatization can help differentiate it from more ominous skull base pathology and prevent unnecessary testing. We describe four-year imaging follow-up in a patient with incomplete pneumatization of the sphenoid sinus presenting as an enhancing mass lesion with subsequent follow-up imaging demonstrating gradual regression and increased aeration of the sphenoid sinus.