K Chu and SK Lee reviewed previous studies and organized experimental plans

K Chu and SK Lee reviewed previous studies and organized experimental plans. Conflict of Interest No conflicting relationship exists for the authors. Acknowledgements This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (2016R1C1B2011815, 2016M3C7A1914002 by the Brain Research Program). dysfunction, pneumonia, hypoventilation, rhabdomyolysis, or status epilepticus.5, 6, 7 Hypersalivation is one of the main autonomic dysfunctions in anti\NMDAR encephalitis where its prevalence was estimated between 4 and 18%.1, 3 Patients with anti\NMDAR encephalitis can show excessive production of saliva, the inability to retain saliva within the mouth, and profound drooling, thus sometimes requiring constant suction of saliva. It may complicate aspiration pneumonia and volume depletion in severe cases. 8 While anticholinergic medications partially improve the hypersalivation, they can aggravate the autonomic dysfunctions, including paralytic ileus, orthostatic hypotension, and heart rate variability.9 Accordingly, effective and safe therapeutics to control the hypersalivation are critically necessary. Botulinum toxin type A 2,4-Pyridinedicarboxylic Acid (BTXA) is a neurotoxin that can reduce saliva secretion by blocking the release of acetylcholine at the neuroglandular junction of salivary gland.10 Evidence indicates that BTXA is an effective 2,4-Pyridinedicarboxylic Acid and safe treatment for hypersalivation related to several neurological disorders including Parkinson’s disease,11 amyotrophic lateral sclersois,12 and cerebral palsy.13 If this works without remarkable adverse effects in anti\NMDAR encephalitis setting, it could be a great option to replace anticholinergic drugs and would prevent aspiration events. Thus, we evaluated the efficacy and safety of BTXA injection on hypersalivation due to anti\NMDAR encephalitis. Methods Patients We have operated a prospective cohort for anti\NMDAR encephalitis since June 1, 2012, and the current study is an analysis of the data\set. The patients with anti\NMDAR encephalitis were included who were treated with BTXA injection due to disabling hypersalivation from Sep 30, 2016, when the first injection of BTXA was performed, until Mar 1, 2017. Anti\NMDAR encephalitis was diagnosed according to clinical presentation and the detection of NMDAR autoantibodies in the serum or cerebrospinal fluid using rat brain section and cell\based immunocytochemistry kit (Euroimmune Ag, Germany), as described previously.6, 14 The study protocol was approved by the Seoul National University Hospital Institutional Review Board and followed to the principles of the Declaration of Helsinki. BTXA injection and outcome evaluation For each patient, 2?mL of normal saline was used to dilute 100 units of BTXA (Botox?, Allergan, Irvine, CA).11 Using a 25\gauge needle under ultrasonography guidance, 30 units was injected into each parotid gland and 20 units into each submandibular gland, totaling 100 units per patient. The effect of BTXA on hypersalivation 2,4-Pyridinedicarboxylic Acid was measured using Drooling Severity and Frequency Scale before injection and at 1, 4, 8, 12, and 16?weeks after injection. Adverse effects following BTXA injection were evaluated using a review of medical records. The patients were reinjected on week 12 if the Drooling Severity and Frequency Scale had deteriorated. Drooling severity and frequency scale The Drooling Severity and Frequency Scale was used to evaluate the severity and frequency of hypersalivation. The severity and frequency scales were categorized into 5\level domains (1?=?never drools; 2?=?only lips wet; 3?=?lips and chin wet; 4?=?clothing soiled; and 5?=?clothing, hands and tray moist wet) and 4\level domains (1?=?never drools; 2?=?occasional drooling\not every day; 3?=?frequent drooling\every day; and 4?=?constant drooling), respectively. Results Clinical features and demographics Among 36 patients with anti\NMDAR encephalitis enrolled in our cohort registry, 12 (33.3%) experienced hypersalivation. However, the treatment of BTXA was initiated since Sep 2016, and thus, six patients were included in this study. Table?1 shows the result of clinical features and 2,4-Pyridinedicarboxylic Acid demographics of the patients. The median age was 24.5?years (range, 17C58?years), and five were women. All patients had semi\comatose mentality with tracheostomy and feeding tube. Table 1 Clinical features of the patients with anti\NMDA receptor encephalitis thead valign=”top” th align=”left” valign=”top” rowspan=”1″ colspan=”1″ COL11A1 Patient /th th align=”left” valign=”top” rowspan=”1″ colspan=”1″ 1 /th th align=”left” valign=”top” rowspan=”1″ colspan=”1″ 2 /th th align=”left” valign=”top” rowspan=”1″ colspan=”1″ 3 /th th align=”left” valign=”top” rowspan=”1″ colspan=”1″ 4 /th th align=”left” valign=”top” rowspan=”1″ colspan=”1″ 5 /th th align=”left” valign=”top” rowspan=”1″ colspan=”1″ 6 /th /thead Age172028242558GenderFFFFFMClinical manifestationsPsychiatric symptoms Seizure 2,4-Pyridinedicarboxylic Acid Dyskinesia Memory disturbance Speech problem Central hypoventilation Decreased mentality .