This paper presents the case of a 50-year-old male German academic who developed neurocognitive deficits, affective symptoms, and predominant delusions for over one and a half years. The patient, as well as his family, have given their signed written informed consent for this case report, including the presented images, to be published. The patient reported a pronounced feeling of thirst, although he was drinking 10–20 liters of water a day, and he was absolutely convinced that he would die of thirst. He did not hear an imperative voice encouraging him to drink more. He said that he needed to drink less water and wondered how his body could retain all the liquid. He was delusionally convinced that he had lost the ability to urinate. In contrast, sonography repeatedly detected no residual urine. Moreover, he suffered from severe insomnia (the patient had the feeling of being completely unable to sleep), reduced cognitive performance—for example, being unable to remember dates—and reduced energy levels, as well as complete loss of interests. In the external assessment, disinhibition, flattened affect, accelerated speech and slow thinking were striking. He had suffered from recurrent depressive episodes since he was 34 years old. For the past eight years, depression had been more severe. In the period between 45 years and 48 years, he had taken high doses of Z-drugs in order to treat insomnia. At the same time, alcohol abuse had developed until two years ago (up to the age of 48 years). At the age of 48, he had suffered a single epileptic status, which was interpreted as the result of alcohol and Z-drug withdrawal in an external hospital. At that time, epileptic activity was described in EEG. Over the last two years he had not consumed any substances (). In addition, hyponatremia (i.e., 130 mmol/L; reference range: 136–145 mmol/L) had been revealed half a year prior to diagnosis. On admission to our hospital, a normal sodium concentration was measured. Additional repeated laboratory testing showed a urine osmolality of 73 and 45 mosm/kg, respectively, and a suppressed urine sodium concentration of less than 20 mmol/L. During a thirst trial, urine osmolality increased to 651 mosm/kg, which indicates psychogenic polydipsia and excludes a syndrome of inappropriate antidiuretic hormone (SIADH). Diagnostic findings: The diagnostic examinations were conducted approximately one and a half year after symptom exacerbation after admission to our special ward. In serum, anti-LGI1 antibodies were repeatedly positive in different laboratories (see ), whereas CSF antibody testing was negative. A serum titer of 1:80 (reference <1:20) was measured using cell-based assays. CSF analyses showed normal to slightly elevated white blood cell (WBC) counts (maximum 5/µL; reference <5/µL) and evidence of a blood–brain barrier dysfunction (protein concentration up to 557 mg/L; reference: <450 mg/L; albumin quotients up to 9.5, reference: <8). Oligoclonal bands were always negative. Fluid-attenuated inversion recovery (FLAIR) MRI sequences depicted hyperintensities right-mesio-temporally and on the right side of the amygdala. In the left thalamus, a small, possibly microangiopathic, lesion was detected. In addition, there was a slight grey–white matter blurring (cf. [] ). The routine EEG was normal in the visual assessment. Independent components analyses or rather automatic detection of intermittent EEG slowing remained inconspicuous (cf. []). A cerebral FDG-PET examination showed moderate hypometabolism of the bilateral mesial to medial frontal cortices, which was interpreted as being possibly due to an early manifestation of frontotemporal dementia [], whereas a sequela of substance and/or alcohol abuse was rated to be less likely. It should be noted that there was no mesial temporal or striatal hypermetabolism (), which can be present in active limbic or anti-LGI1 encephalitis. A whole-body FDG-PET/computer tomography scan detected no metabolic or structural pathologies suggestive of malignancy or inflammation. Neuropsychological testing using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test battery showed deficits in Mini Mental State Examination (25 of maximum 30 points), word-list savings, and trail-making tests B and A/B. The test for attentional performance by TAP showed deficits in working memory (missings, false alarms), set shifting (overall index) and alertness (reaction times with and without sound). All diagnostic findings are summarized in. Illness, somatic, and family histories: The patient’s past medical history was inconspicuous in terms of in-utero and birth complications. He had not suffered from febrile convulsions, inflammatory brain diseases, relevant systemic infections, or craniocerebral traumata during his childhood or adolescence. There was no evidence of neurodevelopmental or personality disorder. Seven years earlier, at the age of 43, he had developed a deep vein thrombosis by unclear coagulopathy. For several years, he had suffered from leg ulcer on the left inner ankle. He had also suffered from arterial hypertension, treated with ramipril 10 mg/day. His history of autoimmune diseases, infections, or cancer was negative. In the family history of neuropsychiatric diseases, only his father had suffered from depression. Treatment and outcome: Classic psychiatric treatment with sertraline, venlafaxine, mirtazapine, reboxetine, several tricyclic drugs, lithium, zopiclone, olanzapine, risperidone, haloperidol, quetiapine, and clozapine previously administered had no relevant positive effect on symptom relief. Under clozapine, he had developed myocarditis. After immunological findings gave evidence for chronified limbic autoimmune encephalitis, glucocorticoid pulse therapy with 500 mg of intravenous methylprednisolone daily for five days and subsequent oral tapering over two months (starting with 50 mg) led to slight improvement of mood and neurocognitive symptoms including temporal orientation, executive functions, word list savings and alertness times (with no difference between the conditions with and without sound). However, new deficits were found in fluency and word list learning with more word intrusions, while deficits in working memory and set shifting were persisting. A second steroid pulse 3 months after the first pulse with oral tapering did not lead to relevant improvement. However, the signal hyperintensities in the MRI showed a tendency to reduction. Further treatment (e.g., with plasmapheresis and/or rituximab) was refused by the patient and his legally authorized parents. Furthermore, l-thyroxine (due to hypothyroidism), vitamin B1 (prophylactic after earlier alcohol abuse), and vitamin D (due to serologically proven deficiency) were supplemented.