Einfluss von Vitamin B1 auf den klinischen Verlauf kritisch kranker Kinder mit V.a. Meningoenzephalitis unklarer Genese in Bhutan

Funk, Christoph (2024): Einfluss von Vitamin B1 auf den klinischen Verlauf kritisch kranker Kinder mit V.a. Meningoenzephalitis unklarer Genese in Bhutan. Dissertation, LMU München: Medizinische Fakultät

Abstract

Since 2008, the opening year of the PICU at JDWNRH in Thimphu, there where a lot of patients with the assumed diagnosis „meningoencephalitis“. A common cause for the disease or an infectious organism was however not yet detected. Patients presented with minor symptoms of upper respiratory tract infection which resulted in severe neurological impairment such as seizures and/or apathy. They quickly developed respiratory failure, kidney failure and other „shock-like“ clinical signs. Neurological imaging like cCT showed hypodense basal ganglia regions. Most of this patients did not survive the following week. In July 2018 one patient with „meningoencephalitis“ also had metabolic acidosis and pulmonary hypertension. As an inborn error of metabolism was suspected, the patient was treated with several amino acids, vitamins, enzymes and coenzymes including a high dose of thiamin. That resulted in dramatic clinical improvement. This was the first patient for the subsequent clinical investigation. We collected all the data from patients admitted in 2018 which had the diagnosis „meningoencephalitis“. Patients from the first seven month where enrolled retrospectively and made up the group which did not receive thiamin. From august 2018 onwards every patient with the diagnosis „meningoencephalitis“ was given thiamin after protocol. We compared the clinical presentation on admission and during hospital stay by vital signs, blood samples, urinary output, cerebral spinal fluid, respiration (including mandatory ventilation), echocardiography, cCT and cMRI if done. In total fifty-one patients were enrolled in the study out of which 32 received thiamin and 19 did not receive thiamin. Mean age was 3 months (2-7 months), 51% where females and 74,5% where fully breastfed. On admission most common neurologic signs where irritability (56,9%), seizures (43,1%) and signs of decortication (41,2%). Lumbar puncture was performed in 70,6% and always came back negative. 64,7% of all patients received cCT of which 84,8% showed basal ganglia hypo intensities. During the course of hospital stay 49,0% showed signs of shock, 58,8% respiratory failure and 29,6% acute kidney failure. In 25,5% metabolic acidosis was seen (not every patient did get tested due to lack of availability), 35,3% showed anemia and 13,7% showed signs of liver involvement. 27,5% where diagnosed with pulmonary hypertension. Overall mortality was 27,5%. The mortality in the non-treated group was 73,7% and 0% in the Thiamin group. 57,9% in the non-treated group underwent cCT-Scan and 90,9% of them showed pathological findings in the area of the basal ganglia. Mortality of these patients was 54,5%. We could demonstrate a direct correlation with positive outcome for patients with „meningoencephalitis“ and thiamin administration, which makes thiamin deficiency the most likely cause of this disease despite missing blood level concentrations. The infantile form of severe thiamin deficiency presented here as Wernicke Encephalopathy and multiorgan failure. Unfortunately the evaluation of the thiamin concentrations before, during and after treatment was not possible because of low income settings and high costs to do so. Also, a formal ethical committee statement was not obtained, the change in management was initiated by the pediatric ICU team and implicated by the hospital representatives. More clinical investigation towards this etiology should be done including measurements of thiamin status of sick patients on admission, after administration of thiamin and even broad testing of the healthy population. Also, a long term follow-up of patients after discharge seems to be necessary to monitor any neurological sequalae in patients with Wernicke Encephalopathy. Broad Thiamine supplementation of the population at risk as well as broad education concerning this problem should decrease the number of cases on the PICU if not completely vanish the disease in the population of interest.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Thiamin, Meningoenzephalitis, Beriberi, Bhutan, Wernicke Enzephalopathie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Deutsch
• Datum der mündlichen Prüfung: 19. Januar 2024
• 1. Bericht­erstatter:in: Haas, Nikolaus