The madness of Dionysus ? Six hypotheses on the illness of Nietzsche

Background: Friedrich Nietzsche (1844-1900) is considered as one of the most influential modern thinkers of the last two centuries. The great philosopher and poet developed a mental illness at the age of 44 and died at the age of 56. Pathological examination was not undertaken. At that time Nietzsche was diagnosed as having atypical paralysis progressiva, however recently five other probable diagnoses appeared in literature. Method: Literature search in MEDLINE and Web of Science on the illness of Nietzsche. Results: Six hypotheses were identified: 1. Paralysis progressiva (General paralysis of the insane); 2. Bipolar affective disorder followed by vascular dementia; 3. Hereditary form of frontotemporal dementia; 4. Brain tumor, 5. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoenchephalopathy (CADASIL); 6. Mitochondrial enchephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome. Conclusion: Developments in neurology and molecular genetics give new perspectives to the secret of Nietzsche’s illness and also there is a consensus on the questioning of the original paralysis progressiva concept. As there was no post-mortem, the clinical speculations on the medical problems of the great philosopher remain a challenge.