Long term outcomes in patients with anti-DPPX autoimmunity.

DDPX antibody-associated encephalitis is characterized by cognitive dysfunction, neuropsychiatric symptoms, and CNS hyperexcitability, preceded by prodromal weight loss and diarrhea. Data regarding long-term outcomes is scarce. We retrospectively identified six anti-DPPX encephalitis patients across all three Mayo Clinic sites with inclusion criteria: 1) positive DPPX cell-based assay and mouse tissue-based immunofluorescence samples in both serum and CSF; 2) duration of follow up of at least 36 months from symptom onset to last follow up. Only one patient had a paraneoplastic process in the setting of chronic lymphocytic leukemia. At last follow up, all patients had resolution of GI symptoms. Residual cognitive impairment was seen in 4/6 (67%). Clinical stability was reached in 3/6 (50%) while on immunotherapy. Immunotherapy was discontinued in 2/6 (33%) and they remained stable without relapse at last follow up. One patient died of unclear etiology. Overall long-term outcomes are good in anti-DPPX encephalitis. Symptoms can improve on immunotherapy, but full resolution and return to premorbid baseline is unlikely.

Acute Herpes Zoster Radiculopathy of the Lower Extremity With Dermatomal Rash and Lumbar Nerve Enhancement on MRI.

Herpes zoster is a frequent cause of neuralgia and dermatomal vesicular rash secondary to reactivation of latent varicella zoster virus. However, it rarely presents with acute lumbar radiculopathy and the diagnosis can be quite challenging in such cases. Nerve signal abnormalities on magnetic resonance imaging are well recognized in herpes zoster neuropathy or plexopathy affecting the extremities, although gadolinium enhancement is characteristically absent. In this article, we describe a case of acute herpes zoster lumbosacral radiculopathy with characteristic vesicular dermatomal rash and second ever reported finding of gadolinium enhancement of the lumbar nerve on magnetic resonance imaging.

Ruptured Distal Superior Cerebellar Artery Aneurysm After Gamma Knife Radiosurgery for Trigeminal Neuralgia: A Case Report and Review of the Literature.

BACKGROUND: Intracranial aneurysm formation after Gamma Knife radiosurgery (GKRS) is a rare complication that has only recently been reported in the literature. We report the case of a fatal distal superior cerebellar artery (SCA) aneurysm rupture in a woman treated twice with GKRS for trigeminal neuralgia along with a review of the literature regarding radiation-induced aneurysms. CASE DESCRIPTION: A 77-year-old white woman with a history of refractory right-sided trigeminal neuralgia treated with GKRS in 2001, and again in 2006 after a relapse, presented to our emergency department with complaints of a sudden-onset severe headache associated with vomiting, right eye vision loss, left-sided facial droop, and left-sided weakness with no history of hypertension or smoking prior to presentation. Initial head computed tomography scan without contrast demonstrated an intraparenchymal hemorrhage centered in the right middle cerebellar peduncle with subarachnoid hemorrhage in the basal cisterns and extension into the fourth ventricle causing early hydrocephalus. Head computed tomography angiography (CTA) demonstrated a distal right SCA aneurysm adjacent to the hemorrhage. The patient's mental status deteriorated into coma after suspected rerupture during the CTA requiring immediate intubation, external ventricular drain placement, and emergent cerebral angiogram with coil embolization. Ultimately, the patient never recovered despite medical and surgical management; therefore, care was withdrawn in accordance with her known wishes. CONCLUSIONS: The pathophysiologic association of aneurysm formation after GKRS remains to be elucidated, but given the potentially fatal consequences of aneurysm rupture, we advocate for further research and propose serial vascular imaging during the postradiosurgery follow-up period for iatrogenic aneurysm formation surveillance.

Megestrol Acetate Induced Paradoxical Embolism in a Sickle Cell Disease Patient.

We report a case of a 43-year-old African American female patient with otherwise stable sickle cell disease (SCD) in which use of megestrol acetate for appetite stimulation quickly potentiated her prothrombotic state within just a few days. This resulted in infarcts involving the bilateral cerebral hemispheres suggestive of embolic infarcts and the patient was subsequently confirmed to have a patent foramen ovale (PFO). A widespread literature search in PubMed revealed that this is a rare case in the literature and that the effects of megestrol acetate use in patients with SCD have not been well studied. Future research should focus on the risks of initiating megestrol acetate therapy to develop an advanced risk assessment algorithm in patients with SCD as the risk of thromboembolism may far outweigh the potential benefits.

Constitutively active Akt1 cooperates with KRas(G12D) to accelerate in vivo pancreatic tumor onset and progression.

BACKGROUND AND AIMS: Pancreatic adenocarcinoma is a deadly disease characterized by metastatic progression and resistance to conventional therapeutics. Mutation of KRAS is the most frequent early event in pancreatic tumor progression. AKT isoforms are frequently activated in pancreatic cancer, and reports have implicated hyperactivation of AKT1, as well as AKT2, in pancreatic tumor formation. The objective here is to delineate the role of AKT in facilitating in vivo pancreatic tumor progression in the context of KRAS mutation and predisposition to pancreatic cancer. METHODS: Mice with Akt1 and KRas mutant alleles expressed using the pancreas Pdx promoter were mated to characterize the incidence and frequency of histologic and genetic alterations known to occur commonly in human pancreatic ductal adenocarcinoma. RESULTS: Active Akt1 (Akt1(Myr), containing a myristoylation sequence) cooperated with active mutant KRas(G12D) to accelerate pancreatic carcinoma onset and progression and increase phosphorylation of downstream effectors in the Akt pathway. Mucin and smooth muscle actin expression was found in and around pancreatic intraepithelial neoplasms (PanINs), and accelerated time to metastasis was found in Akt1(Myr)/KRas(G12D) mice. CONCLUSIONS: In contrast to prior reports of pancreatic KRas mutant mice mated with mice deficient for various tumor suppressor genes, which resulted in aggressive disease within a few months of age, Akt1(Myr)/KRas(G12D) mice enabled the study of PanINs and spontaneous pancreatic transformation more characteristic of human pancreatic progression in elderly individuals. The Akt1(Myr)/KRas(G12D) model holds promise for delineating the tumor biology and biomarkers critical for understanding their cooperation in cancer oncogenesis and future targeting in therapeutic strategies.