Cefepime-Induced Neurotoxicity Can Be Confused With Neuroleptic Malignant Syndrome, Catatonia and Serotonin Syndrome: A Case Report.

Cefepime is a commonly used antibiotic. However, cefepime-induced neurotoxicity (CIN) is less commonly recognized. We describe a 75-year-old female on sertraline and risperidone who has been on cefepime for 28 days for treatment of osteomyelitis and presented with mutism, generalized rigidity, hyperreflexia, generalized stimulus-induced myoclonus, and reactive dilated pupils and found to have developed acute kidney injury. Although the diagnosis of serotonin syndrome (SS) and neuroleptic malignant syndrome (NMS) was suggested initially, the clinical picture was more compatible with CIN. Hemodialysis was suggested but gradual improvement in renal function allowed for gradual neurological recovery. This case highlights the importance of considering CIN in those who have been on Cefepime and present with altered mental status, especially in the appropriate clinical context and presence of risk factors. The overlap in clinical presentation between CIN, SS, NMS, and Catalonia may lead to a diagnostic challenge. Myoclonus seems to be characteristic of CIN and serves as a good clue to hint toward the diagnosis. This case helps to display the similarities and differences in the clinical presentation of these entities and therefore helps avoid confusion and prevents unnecessary therapeutic interventions.

Increased cognitive workload evokes greater neurovascular coupling responses in healthy young adults.

Understanding how the brain allocates resources to match the demands of active neurons under physiological conditions is critically important. Increased metabolic demands of active brain regions are matched with hemodynamic responses known as neurovascular coupling (NVC). Several methods that allow noninvasive assessment of brain activity in humans detect NVC and early detection of NVC impairment may serve as an early marker of cognitive impairment. Therefore, non-invasive NVC assessments may serve as a valuable tool to detect early signs of cognitive impairment and dementia. Working memory tasks are routinely employed in the evaluation of cognitive task-evoked NVC responses. However, recent attempts that utilized functional near-infrared spectroscopy (fNIRS) or transcranial Doppler sonography (TCD) while using a similar working memory paradigm did not provide convincing evidence for the correlation of the hemodynamic variables measured by these two methods. In the current study, we aimed to compare fNIRS and TCD in their performance of differentiating NVC responses evoked by different levels of working memory workload during the same working memory task used as cognitive stimulation. Fourteen healthy young individuals were recruited for this study and performed an n-back cognitive test during TCD and fNIRS monitoring. During TCD monitoring, the middle cerebral artery (MCA) flow was bilaterally increased during the task associated with greater cognitive effort. fNIRS also detected significantly increased activation during a more challenging task in the left dorsolateral prefrontal cortex (DLPFC), and in addition, widespread activation of the medial prefrontal cortex (mPFC) was also revealed. Robust changes in prefrontal cortex hemodynamics may explain the profound change in MCA blood flow during the same cognitive task. Overall, our data support our hypothesis that both TCD and fNIRS methods can discriminate NVC evoked by higher demand tasks compared to baseline or lower demand tasks.

Assessment of age-related decline of neurovascular coupling responses by functional near-infrared spectroscopy (fNIRS) in humans.

Preclinical studies provide strong evidence that age-related impairment of neurovascular coupling (NVC) plays a causal role in the pathogenesis of vascular cognitive impairment (VCI). NVC is a critical homeostatic mechanism in the brain, responsible for adjustment of local cerebral blood flow to the energetic needs of the active neuronal tissue. Recent progress in geroscience has led to the identification of critical cellular and molecular mechanisms involved in neurovascular aging, identifying these pathways as targets for intervention. In order to translate the preclinical findings to humans, there is a need to assess NVC in geriatric patients as an endpoint in clinical studies. Functional near-infrared spectroscopy (fNIRS) is a non-invasive neuroimaging technique that enables the investigation of local changes in cerebral blood flow, quantifying task-related changes in oxygenated and deoxygenated hemoglobin concentrations. In the present overview, the basic principles of fNIRS are introduced and the application of this technique to assess NVC in older adults with implications for the design of studies on the mechanistic underpinnings of VCI is discussed.