Functional neurological disorder: A common reason for a neurology inpatient referral.

BACKGROUND AND PURPOSE: In 2021, the European Academy of Neurology's training requirements were updated to include functional neurological disorder (FND) as a core topic for the first time. To reinforce these changes, we aimed to understand the proportion of inpatients (in non-neurology settings) who are diagnosed with FND. METHODS: We prospectively collected data on diagnoses made after inpatient ward reviews from neurology trainees at three tertiary neurology centres in Scotland from April to September 2021. We assessed healthcare utilization data for patients with a diagnosis of FND, epilepsy and epileptic seizures, or a neuroinflammatory disorder over the preceding 12 months. RESULTS: There were 437 inpatient reviews for 424 patients by 13 trainees. The largest single diagnosis was FND (n = 80, 18%), followed by epilepsy (n = 64, 14%), primary headache disorder (n = 40, 9%) and neuroinflammatory disorders (n = 28, 6%). There was an uncertain diagnosis for 48 reviews (11%). Compared to patients with epilepsy or neuroinflammatory disorders, patients with FND had a similar number of admissions (2 vs. 2 vs. 1) and brain/spine imaging studies (2 vs. 1 vs. 2). CONCLUSIONS: In Scotland, FND was the most common diagnosis made after a request for an inpatient review by a neurologist from another department in the hospital. Patients with FND have similar health resource needs to those with other common neurological disorders when they present to hospitals with tertiary neurology centres. This data supports the inclusion of FND as a core curriculum topic in neurology training.

Elevated levels of oncogenic protein kinase Pim-1 induce the p53 pathway in cultured cells and correlate with increased Mdm2 in mantle cell lymphoma.

Mutation of the p53 gene is a common event during tumor pathogenesis. Other mechanisms, such as mdm2 amplification, provide alternative routes through which dysfunction of the p53 pathway is promoted. Here, we address the hypothesis that elevated expression of pim oncogenes might suppress p53 by regulating Mdm2. At a physiological level, we show that endogenous Pim-1 and Pim-2 interact with endogenous Mdm2. Additionally, the Pim kinases phosphorylate Mdm2 in vitro and in cultured cells at Ser(166) and Ser(186), two previously identified targets of other signaling pathways, including Akt. Surprisingly, at high levels of Pim expression, as would occur in tumors, active, but not inactive, Pim-1 or Pim-2 blocks the degradation of both p53 and Mdm2 in a manner that is independent of Mdm2 phosphorylation, leading to increased p53 levels and, proportionately, p53-dependent transactivation. Additionally, Pim-1 induces endogenous ARF, p53, Mdm2, and p21 in primary murine embryo fibroblasts and stimulates senescence-associated beta-galactosidase levels, consistent with the induction of senescence. Immunohistochemical analysis of a cohort of 33 human mantle cell lymphomas shows that elevated expression of Pim-1 occurs in 42% of cases, with elevated Pim-2 occurring in 9% of cases, all of which also express Pim-1. Notably, elevated Pim-1 correlates with elevated Mdm2 in MCL with a p value of 0.003. Taken together, our data are consistent with the idea that Pim normally interacts with the p53 pathway but, when expressed at pathological levels, behaves as a classic dominant oncogene that stimulates a protective response through induction of the p53 pathway.