## 5 Summary and Conclusions  
The current case report presents the case of a patient diagnosed with CFS over 10 years ago who was longitudinally followed for response to treatment. We highlight the lack of a positive response to classical approaches to treating CFS, reflecting the limitations of CFS diagnosis and available treatments to alleviate patients' symptoms. Additionally, we show the lack of adherence of this CFS patient to medication (a common trend among CFS patients possibly, a consequence of improvement failure). The current case supports the implication of stress factors on the etiology of CFS as well as the role of catecholamines on the symptoms described. The data obtained revealed biochemical indicators of an altered HPA axis as well as a genetic predisposition or vulnerability to stress, which, in other cases, could be of epigenetic nature. The current pathomechanism hypothesis highlights monoamine alterations (hyperadrenergic state) in the DA/adrenergic system and a dysfunctional autonomic nervous system resulting from sympathetic overactivity. In the context of a hyperadrenergic state, dysfunctional autonomic nervous system (ANS) activity could arise primarily from excessive sympathetic overactivity. This condition would disrupt the delicate balance between the sympathetic and parasympathetic branches of the ANS, leading to a range of physiological disturbances. The patient presents excessive catecholamine activity, which could implicate heightened sympathetic tone, which, in this case, is manifested clinically as altered temperature regulation and respiratory irregularities in response to limited physical exercise (reported by the patient). These symptoms reflect maladaptive responses in ANS regulation, potentially stemming from CNS dysregulation and abnormalities in neurotransmitter pathways such as DA and NE. The patient has been diagnosed with conditions associated with sympathetic overactivity-induced ANS dysfunction, such as POTS and stress-related disorders, which underscore the significant impact of hyperadrenergic states on overall autonomic function and health outcomes. After years of a series of trial-and-error treatments, the patient highlights his unexpected positive response to AMPT. AMPT inhibits TH (converts tyrosine to DA) (Figure 5D). The patient had presented decreased levels of tyrosine and increased levels of DA andNA, as well as other downstream metabolites such as vanillyImandelic acid (VMA) and B1/B2 adrenergic autoantibody receptors (Table 1). Additionally, the tryptophan pathway showed elevated levels of quinolinic acid, a toxic product of activated microglia in the brain (Figure 5D). Due to the previous hyperadrenergic alteration history of the patient, it does not seem surprising that the patient showed reduced stress and fatigue levels after AMPT treatment (low-intermediate doses 80-300 mg bid). A limitation is not counting with post-AMPT treatment analytics. AMPT treatment also attenuates oxidative stress and inflammation [28], aspects possibly altered in the patient according to his genotype. AMPT has been tested in clinical trials of 22q11.2 deletion syndrome (which is characteristic of COMT polymorphism) [27; 29]. Other disorders have given AMPT a chance (obsessive-compulsive disorder [30], schizophrenia [31; 32], and mood disorders [33], with some positive results). Currently, a metryrosine derivative is being tested for autism spectrum disorder (ClinicalTrials.gov Identifier: NCT05067582). We are not aware of previous studies that have reported the use of AMPT for the treatment of CFS patients. Our data support the relevance of personalized treatment, focused on the patient's specific symptoms, biochemical findings (including circulating levels of relevant neurotransmitters), and genotype towards tailored improvement in the patient's quality of life. CFS is a devastating heterogenic disorder with a lack of effective treatments. The response to AMPT treatment highlights the relevance of pacing with regard to stressful situations and increased activity.