Posts by:
Gabriella True

Neutrophil-lymphocyte ratios as inflammatory biomarkers in psychiatric patients

T Bhikram, P Sandor, Neutrophil-lymphocyte ratios as inflammatory biomarkers in psychiatric patients, Brain, Behavior, and Immunity, Volume 105, 2022, Pages 237-246, https://doi.org/10.1016/j.bbi.2022.07.006.

Conclusion: The consistent findings of elevated NLR across the reviewed psychiatric disorders suggest that abnormal NLR is not specific to any one disorder but may reflect a pathological brain process that leads to brain dysfunction. These findings support hypotheses of neuroinflammation being important to the etiology of psychiatric disorders. More research is needed to further elucidate the relationship between specific diagnostic and behavioural constructs and NLR. Future work is also needed to determine the specific neuroinflammatory mechanisms that give rise to specific disorders.

A Case of Steroid-Responsive Severe Pneumonia Following a Recent COVID-19 Infection in a Patient With Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infection

Pourshahid S, Khademolhosseini S, Giri B, et al. (July 12, 2022) A Case of Steroid-Responsive Severe Pneumonia Following a Recent COVID-19 Infection in a Patient With Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infection. Cureus 14(7): e26785. doi:10.7759/cureus.26785

“Drug-induced pneumonitis was a possibility as well; however, she was only taking rituximab and cetirizine. Rituximab is a potential agent for the treatment of pneumonitis refractory to conventional treatments [25]. Although there are a few reported cases of rituximab-induced pneumonitis [26], the three-month delay after the last injection of rituximab and rapid progression in a few days are not consistent with drug-induced pneumonitis.

It is conceivable that her recent COVID-19 infection may have activated an exaggerated inflammatory response as the immunosuppression related to rituximab was subsiding. The rapidly progressing pulmonary consolidations and worsening respiratory symptoms under these circumstances should prompt the clinician to consider steroid-responsive-pneumonia like post-COVID OP, MISA, and IRIS-like reactions. Rapid institution of high-dose steroids seems to be the key to treatment. Whether her history of PANDAS may have further impacted her immune system, making her more prone to this exaggerated response is unclear.”

Narcolepsy and pediatric acute-onset neuropsychiatric syndrome: A case report that suggests a putative link between the two disorders

Congiu, P., Puligheddu, M., Capodiferro, A. M., Falqui, S. G., Tamburrino, L., Figorilli, M., Plazzi, G., & Gagliano, A. (2024). Narcolepsy and pediatric acute-onset neuropsychiatric syndrome: A case report that suggests a putative link between the two disorders. Sleep Medicine, 121, 370–374. https://doi.org/10.1016/j.sleep.2024.06.02

  • Case report of a 13-year-old boy diagnosed with both NT1 and PANS, suggesting a shared neuroimmune mechanism.
  • Abrupt onset of vocal tics, OCD symptoms, anxiety, regression, school decline, and sleep disturbance.
  • Progressed to daytime sleepiness, spontaneous falls, confusion, and cataplexy-like episodes.
  • Elevated ASLO titer indicated prior streptococcal exposure; MRI/EEG normal; sleep study confirmed NT1.
  • HLA DQB1*06:02 negative — rare in NT1 but documented.
  • No clinical improvement with steroid immunotherapy.
  • Significant improvement with narcolepsy and psychiatric medications, including remission of cataplexy.
  • Authors propose NT1 and PANS may exist on a post-infectious autoimmune spectrum involving orexin (sleep/cataplexy) and dopamine (tics/OCD/anxiety) dysfunction.
Identification of ultra‑rare genetic variants in pediatric acute onset neuropsychiatric syndrome (PANS) by exome and whole genome sequencing

Trifiletti R, Lachman HM, Manusama O, Zheng D, Spalice A, Chiurazzi P, Schornagel A, Serban AM, van Wijck R, Cunningham JL, Swagemakers S, van der Spek PJ. Identification of ultra-rare genetic variants in pediatric acute onset neuropsychiatric syndrome (PANS) by exome and whole genome sequencing. Sci Rep. 2022 Jun 30;12(1):11106. doi: 10.1038/s41598-022-15279-3. PMID: 35773312. – Open Access

  • The pathological mechanisms are likely heterogeneous, but we hypothesize convergence on one or more biological pathways.
  • Conducted whole exome sequencing (WES) on a U.S. cohort of 386 cases, and whole genome sequencing (WGS) on ten cases from the European Union who were selected because of severe PANS.
  • Focused on identifying potentially deleterious genetic variants that were de novo or ultra‑rare (MAF) < 0.001. Candidate mutations were found in 11 genes (PPM1D, SGCE, PLCG2, NLRC4, CACNA1B, SHANK3, CHK2, GRIN2A, RAG1, GABRG2, and SYNGAP1) in 21 cases, which included two or more unrelated subjects with ultra‑rare variants in four genes.
  • These genes converge into two broad functional categories.
    • One regulates peripheral immune responses and microglia (PPM1D, CHK2, NLRC4, RAG1, PLCG2).
    • The other is expressed primarily at neuronal synapses (SHANK3, SYNGAP1, GRIN2A, GABRG2, CACNA1B, SGCE). Mutations in these neuronal genes are also described in autism spectrum disorder and myoclonus‑dystonia.
  • 12/21 cases developed PANS superimposed on a preexisting neurodevelopmental disorder. Genes in both categories are also highly expressed in the enteric nervous system and the choroid plexus.
  • Thus, genetic variation in PANS candidate genes may function by disrupting peripheral and central immune functions, neurotransmission, and/or the blood‑CSF/brain barriers following stressors such as infection