Assessment of disease severity and patient prognosis in anti-GABABR encephalitis with and without comorbid tumors.

Purpose: This study aimed to analyze the severity of the condition and prognosis of patients with anti-gamma-aminobutyric-acid type B receptor (anti-GABABR) encephalitis with tumors. Methods: Patients with anti-GABABR encephalitis admitted to one of two hospitals from 2020 to 2022 were enrolled and divided into tumor and non-tumor groups. The clinical characteristics, condition severity, treatment options, and prognosis of the two groups of patients were compared and analyzed. Results: Eighteen patients with anti-GABABR encephalitis were included, ten of whom had tumors. The comparison of clinical characteristics showed that rates of status epilepticus and coma were significantly higher in the group with tumors (P = 0.013 and P = 0.025, respectively); the incidences of pulmonary infection, respiratory failure, hyponatremia, and hypoproteinemia were also substantially more frequent in the tumor group (P = 0.054, P = 0.036, P = 0.015, and P = 0.025, respectively). The laboratory test result comparison showed that serum neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) were present only in the group with tumors (P = 0.036 and P = 0.092, respectively), but there was no significant difference in the occurrence of elevated CEA between the two groups. Conversely, the percentage of serum systemic autoimmune antibodies was higher in the group without tumors than in the group with tumors (P = 0.043). Patients with tumors tended to have poor outcomes (P = 0.152, OR: 7.000). Conclusion: Severe brain damage and complications occur in patients with anti-GABABR encephalitis and comorbid tumors. Early screening for serum NSE and CEA helps in the early diagnosis and treatment of tumors. The prognosis is much worse for anti-GABABR encephalitis with tumors.

Status dystonicus in adult patients with anti-N-methyl-D-aspartate-acid receptor encephalitis.

OBJECTIVE: Status dystonicus (SD) is a severe movement disorder (MD) and has rarely been recognized in anti-N-methyl-D-aspartate-acid receptor (NMDAR) encephalitis, particularly in adult patients. We aim to explore the clinical characteristics and outcome of SD in anti-NMDAR encephalitis. METHODS: Patients with anti-NMDAR encephalitis admitted to Xuanwu Hospital from July 2013 to December 2019 were prospectively enrolled. SD was diagnosed based on the patients' clinical manifestations and video EEG monitoring. Outcome was evaluated 6 and 12 months after enrollment using the modified Ranking Scale (mRS). RESULTS: A total of 172 patients with anti-NMDAR encephalitis, including 95 males (55.2%) and 77 females (44.8%) with a median age of 26 years (interquartile range 19 to 34) were enrolled. Eighty patients (46.5%) presented with movement disorder (MD), 14 of whom suffered from SD, which manifested as chorea (14/14, 100%), orofacial dyskinesia (12/14, 85.7%), generalized dystonia (8/14, 57.1%), tremor (8/14, 57.1%), stereotypies (5/14, 35.7%), and catatonia (1/14, 7.1%) of the trunk and limbs. All SD patients exhibited disturbed consciousness and central hypoventilation, requiring intensive care. SD patients also had high cerebrospinal fluid NMDAR antibody titers, a higher proportion of ovarian teratoma, higher mRS scores upon enrollment, longer duration to recover, and poorer outcomes at 6 (P < 0.05) but not at 12 months as compared to non-SD patients. CONCLUSION: SD is not uncommon in anti-NMDAR encephalitis patients and relates to the severity and worse short-term outcome of the anti-NMDAR encephalitis. Early recognition of SD and timely treatment is important to shorten the time needed for recuperation.

Ion channel P2X7 receptor in the progression of cancer.

P2X7 receptor (P2X7) is a non-selective and ATP-sensitive ligand-gated cation channel. Studies have confirmed that it is expressed in a variety of cells and correlates with their function, frequently in immune cells and tumor cells. We found increased expression of this receptor in many tumor cells, and it has a role in tumor survival and progression. In immune cells, upregulation of the receptor has a double effect on tumor suppression as well as tumor promotion. This review describes the structure of P2X7 and its role in the tumor microenvironment and presents possible mechanisms of P2X7 in tumor invasion and metastasis. Understanding the potential of P2X7 for tumor treatment, we also present several therapeutic agents targeting P2X7 and their mechanisms of action. In conclusion, the study of P2X7 is an important guideline for the use of clinical tumor therapy and may be able to provide a new idea for tumor treatment, but considering the complexity of the biological effects of P2X7, the drugs should be used with caution in clinical practice.

Characteristics and Outcomes of Paroxysmal Sympathetic Hyperactivity in Anti-NMDAR Encephalitis.

Background: To explore the clinical characteristics and prognosis of autonomic dysfunction and paroxysmal sympathetic hyperactivity (PSH), and evaluate the efficacy of drugs used to suppress PSH episode in anti-NMDAR encephalitis patients. Methods: Patients who met the diagnostic criteria of anti-NMDAR encephalitis were enrolled from January 2012 to August 2018 and followed up for 2 years. PSH was diagnosed according to the PSH-Assessment Measure. The demographics data, clinical features, auxiliary tests results, treatments, and outcomes were prospective collected and analyzed. Results: A total of 132 anti-NMDAR encephalitis patients were enrolled, of which 27.3% and 9.1% experienced autonomic dysfunction and probable PSH respectively. Cardiac autonomic dysfunction was the most common subtype (77.8%). Patients with a higher incidence of ovarian teratoma, mechanical ventilation, neurological intensive care unit admission, and elevated glucose and NMDAR antibody titer in the CSF were more likely to exhibit autonomic dysfunction or PSH. Episodes of PSH can be suppressed by monotherapy in patients without prior sedative drug use with an efficacy of 90%. No significant difference was observed between the prognosis of patients with or without autonomic dysfunction, or between the PSH versus non-PSH groups after 6 months and even during long-term follow-up. However, patients with cardiac autonomic dysfunction had poor prognosis at 6 months. Conclusion: PSH is a common clinical condition in patients with anti-NMDAR encephalitis, especially in severe cases, and can be effectively managed by several drug monotherapies. Despite necessitating longer hospital stay, autonomic dysfunction or PSH do not seem to compromise the neurological recovery of patients.

Presence of Anti-Thyroid Antibodies Correlate to Worse Outcome of Anti-NMDAR Encephalitis.

Objective: To investigate the characteristics and prognosis of anti-NMDAR encephalitis with the prevalence of anti-thyroid antibodies (ATAbs). Methods: The clinical data of anti-NMDAR encephalitis patients admitted to Xuanwu Hospital from January 2012 to August 2018 was prospectively analyzed, and the patients were followed up for 24 months. Results: A total of 120 patients were enrolled, of which 34.2% (41/120) were positive for ATAbs. The antibodies were more frequent in patients with severe disease compared to the non-severe group (51.4% vs. 25.6%, P=0.008). In addition, prevalence of ATAbs correlated with a higher incidence of disturbed consciousness, autonomic dysfunction, central hypoventilation and mechanical ventilation. The ATAbs-positive patients were also more likely to receive intravenous gamma immunoglobulin and immunosuppressor compared to the ATAbs-negative cases (P=0.006; P=0.035). Although the presence of ATAbs was associated with longer hospital stays and worse prognosis at 6 months (P=0.006; P=0.038), it had no impact on long-term patient prognosis. Positive status of anti-thyroglobulin antibody was an independent risk factor for worse prognosis at 6 months [odds ratio (OR)= 3.907, 95% CI: 1.178-12.958, P=0.026]. Conclusion: ATAbs are prevalent in patients with anti-NMDAR encephalitis, especially in severe cases, and correlate with poor prognosis and impaired short-term neurological recovery.

Clinical efficacy of plasma exchange in patients with autoimmune encephalitis.

OBJECTIVE: To determine the clinical and antibody response after therapeutic plasma exchange (TPE) in patients with severe refractory antibody-associated autoimmune encephalitis (AE). METHODS: This single-center prospective cohort included all patients consecutively admitted to our hospital because of severe refractory AE over the period from July 2014 to June 2019. All patients received immunotherapy (steroids, intravenous immunoglobulin (IVIG), and/or TPE). The primary outcome was evaluated at 1- and 2-month postenrollment, and the long-term outcome was followed up at 6 and 12 months. AE antibody titers in the cerebrospinal fluid and plasma were evaluated before and after TPE/IVIG. RESULTS: This study enrolled 57 patients with severe refractory AE, including anti-NMDA receptor encephalitis (n = 51), anti-GABAb receptor encephalitis (n = 3), anti-LGI 1 encephalitis (n = 2), and anti-AMPA receptor encephalitis (n = 1). Of all 57 patients, 33 patients received TPE for a total of 193 procedures, and 24 patients with contraindications or refusal of TPE were in the non-TPE group. Compared with the non-TPE group, the TPE group exhibited greater clinical improvement: 21 (37%) versus 8 (14%) after 1 month (P = 0.03) and 31 (54%) versus 16 (28%) after 2 months (P = 0.01), respectively. Complications and adverse events associated with TPE occurred in 91 procedures (47%) without serious adverse events associated with the use of TPE. INTERPRETATION: TPE might be an effective rescue therapy associated with rapid functional improvement in patients with severe steroid/IVIG refractory antibody-associated AE from this nonrandomized control trial.

[Self-control study of dynamic multiple pelvic angiography and pelvic four-contrast defecography in the diagnosis of functional defecation disorder].

OBJECTIVE: To evaluate and compare the value of dynamic multiple pelvic angiography and pelvic four-contrast defecography in the diagnosis of functional defecation disorder. METHODS: From September 2014 to July 2015, a prospective controlled trial was carried out in Chengdu Anorectal Hospital. A total of 32 patients met the inclusion criteria of functional defecation disorder simultaneously underwent pelvic four-contrast defecography and dynamic multiple pelvic angiography. The diagnostic results of these two methods were compared. RESULTS: The absolute values of anorectal angle and level of perineum, peritoneum and bladder from rest to defecation were (29.6±13.6)°, (26.2±14.2) mm, (55.5±25.6) mm and (28.9±16.5) mm in dynamic multiple pelvic angiography, and (24.6±5.8)° (18.7±10.6) mm, (34.5±18.4) mm and (19.2±11.8) mm in pelvic four-contrast defecography respectively, whose differences were statistically significant (P = 0.026, 0.022, 0.000, 0.011 respectively). The diagnostic rate of pelvic peritoneal hernia was 93.8%(30/32) and 68.8%(22/32) in dynamic multiple pelvic angiography and pelvic four-contrast defecography respectively with significant difference(P=0.011). CONCLUSION: Dynamic multiple pelvic angiography has significant advantage in the diagnosis of pelvic peritoneal hernia, and can provide a more objective basis for the diagnosis of functional defecation disorder.