An Unusual Case of Limbic Encephalitis Caused by Whipple Disease.

Whipple disease (WD), a multisystemic infectious disorder caused by Tropheryma whipplei (T. whipplei), typically presents with gastrointestinal (GI) symptoms such as abdominal pain, diarrhea, GI bleeding, and weight loss. Uncommonly, it can also involve the central nervous system (CNS) and may present with a range of symptoms, including personality changes, dementia, and rhombencephalitis. Prompt antibiotic treatment and careful follow-up are crucial for favorable patient outcomes and a reduction in morbidity and mortality. In this case, we describe a 46-year-old male with primary CNS-WD and discuss the symptomatic manifestations, diagnostic findings, differential diagnosis, and management. This patient initially presented with arthritic complaints and, over a five-year period, developed progressive neurocognitive symptoms, including anxiety, panic attacks, retrograde amnesia, personality changes, aphasia, anhedonia, dysarthria, and rapidly progressive dementia. Magnetic resonance imaging (MRI) revealed symmetric T2 fluid-attenuated inversion recovery (FLAIR) hyperintensities in the bilateral medial temporal lobes, hippocampi, and hypothalamus. A lumbar puncture (LP) showed mild pleocytosis and elevated protein, with no autoimmune or paraneoplastic causes. Temporal lobe biopsy revealed rod-like structures, and T. whipplei DNA was confirmed by polymerase chain reaction (PCR). This case underscores the importance of maintaining a high index of suspicion for WD in patients presenting with atypical symptoms with rapidly progressive dementia, as early detection and management are key to circumventing irreversible neurological damage and death.

Stroke Secondary to Air Embolism Following Laparoscopic Nissen Fundoplication.

An air embolism is characterized by the entry of gas bubbles into the circulatory system, which can lead to the possible occlusion of blood vessels, posing a potentially life-threatening risk. While commonly associated with lung trauma or decompression sickness, it can also result from medical procedures such as central venous catheter insertion or, in our case, gas insufflation for laparoscopic surgery. We present the case of a 65-year-old female who suffered from a stroke secondary to an air embolism after undergoing a laparoscopic Nissen fundoplication in which carbon dioxide insufflation of the abdominal cavity was utilized. We also will discuss the elusive etiology of this complication as well as diagnosis, treatment, and proposed preventative measures.  A 65-year-old female with gastroesophageal reflux disease and a hiatal hernia elected to undergo a laparoscopic Nissen fundoplication for hernia repair. After a successful surgery, the patient was found with significant neurological deficits, including left-sided hemiplegia, numbness in the left hand, hemianopsia, dysarthria, and a National Institutes of Health Stroke Scale score of 20. CT head imaging revealed several low-density foci in the right frontal lobe, while CT neck and chest imaging revealed subcutaneous emphysema and pneumomediastinum. Subsequent labs were significant for an elevated lactate at 7.6 mmol/L. MRI of the brain depicted evidence of an acute infarct in the right frontal lobe with diffusion-weighted imaging (DWI) sequences. The imaging results were correlated with the patient's clinical presentation to establish the diagnosis of a nondominant hemisphere stroke, localized to an anterior branch of the right middle cerebral artery (MCA). After intubation and supportive treatment for three days, the patient was extubated and able to follow commands but had left facial weakness and diminished strength in the left upper and lower extremities. At the two-month follow-up visit, the patient no longer had any focal neurological deficits. Air emboli, though very rare, can occur as a complication in laparoscopic surgeries that utilize CO2 for body cavity insufflation. Patients may be asymptomatic with small, self-limiting emboli, while others may exhibit pulmonary symptoms, cardiac arrest, or focal neurologic changes, depending on the emoji's size and location. Given the wide range of patient presentations, the elevated mortality of laparoscopic procedures complicated by air emboli, and the rare occurrence of focal neurological symptoms as depicted in this case, rapid diagnosis and close postoperative observation and treatment are vital for both short-term and long-term patient outcomes.

EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain.

Recent studies by us and others have shown that enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, in glial cells regulates the genesis of neuropathic pain by modulating the production of proinflammatory cytokines and chemokines. In this review, we summarize recent advances in this research area. EZH2 is a subunit of polycomb repressive complex 2 (PRC2), which primarily serves as a histone methyltransferase to catalyze methylation of histone 3 on lysine 27 (H3K27), ultimately resulting in transcriptional repression. Animals with neuropathic pain exhibit increased EZH2 activity and neuroinflammation of the injured nerve, spinal cord, and anterior cingulate cortex. Inhibition of EZH2 with DZNep or GSK-126 ameliorates neuroinflammation and neuropathic pain. EZH2 protein expression increases upon activation of Toll-like receptor 4 and calcitonin gene-related peptide receptors, downregulation of miR-124-3p and miR-378 microRNAs, or upregulation of Lncenc1 and MALAT1 long noncoding RNAs. Genes suppressed by EZH2 include suppressor of cytokine signaling 3 (SOCS3), nuclear factor (erythroid-derived 2)-like-2 factor (NrF2), miR-29b-3p, miR-146a-5p, and brain-specific angiogenesis inhibitor 1 (BAI1). Pro-inflammatory mediators facilitate neuronal activation along pain-signaling pathways by sensitizing nociceptors in the periphery, as well as enhancing excitatory synaptic activities and suppressing inhibitory synaptic activities in the CNS. These studies collectively reveal that EZH2 is implicated in signaling pathways known to be key players in the process of neuroinflammation and genesis of neuropathic pain. Therefore, targeting the EZH2 signaling pathway may open a new avenue to mitigate neuroinflammation and neuropathic pain.

Aged gastric mucosa: Mechanisms of vulnerability.

The incidence, frequency of complications and mortality of gastric ulcer disease are increased four-fold in the elderly taking non-steroidal anti-inflammatory drugs (NSAID). There is controversy as to whether this reflects increased usage of NSAID or specific vulnerability associated with age. We have investigated two possible mechanisms for this increase in gastrointestinal effects in the elderly: (i) increased susceptibility to acute gastrotoxicity; and (ii) reduced adaptation to NSAID, in a model of young (2 month), mature (12 month) and aged (24 month) rats. Aspirin damaged 7.7% of the volume of gastric mucosa in the young rat. In mature and aged rats, this increased to 11.3% (P < 0.002 compared to control) and 21.9% (P < 0.005 compared to control), respectively. Thus, aspirin caused a three-fold increase in the severity of acute gastric mucosal injury in aged animals. However, indomethacin, ibuprofen and L745 337 did not produce any significant acute gastric mucosal damage in 2-, 12- or 24-month-old rats. Significant gastric adaptation to diclofenac treatment occurred in both aged and young rats as measured by gastric mucosal damage. The aged gastric mucosa adapted equally as well as the young gastric mucosa to diclofenac. The findings of this study provide only modest support to the hypothesis of increased vulnerability of the stomach in the aged. Aspirin was associated with greater damage in the aged. Adaptation to diclofenac-induced damage was not reduced in the aged and there was not an increased susceptibility to damage by the non-aspirin NSAID tested. The selective cyclo-oxygenase-2 inhibitor, L745 337, was the least toxic agent and may represent a group of NSAID which cause fewer gastrointestinal complications in the elderly.