"Hirnsymptome bei Carcinomatose" - Hermann Oppenheim and an Early Description of a Paraneoplastic Neurological Syndrome

Abstract

Paraneoplastic neurological syndromes belong to the most enigmatic and fascinating disorders. Their remarkable clinical spectrum ranges from sensory neuronopathy to cerebellar degeneration or limbic encephalitis. We retrace the clinical and pathological description of a forgotten case published by Hermann Oppenheim in 1888, which to our knowledge represents the first report of a paraneoplastic neurological syndrome. The young Oppenheim used thorough observation and good clinical judgment to suggest a causal link between the seemingly mere association of an underlying malignancy and a neurological syndrome, decades before Denny-Brown's identification of sensory neuronopathy in 1948 and a century before the discovery of "anti-Hu" antibodies. Oppenheim anticipated that scientific progress was required to prove this link, and he indicated his finding as "a pointer for future observers." In this way, he leaves the reader with the fascinating question of which observations during our current neurology practice could be the next "pointers" in medical research.

Keywords: Hermann Oppenheim; cancer; encephalitis; paraneoplastic neurological syndrome.

Figure 1.

Hermann Oppenheim, the famous neurologist of the late-nineteenth and early-twentieth centuries, published his remarkable case “On Brain Symptoms Associated with Carcinomatosis without Detectable Changes in the Brain” in the 1888 issue of the Charité Annalen, at that time a renowned annual collection of clinical cases and observations at the Charité Hospital in Berlin.

Figure 2.

Pathomechanistic hypotheses for fatal diseases of the nervous system in the absence of anatomical changes, suspecting infectious or toxic causes.

Figure 3.

Description of the initial clinical presentation of the index case, the 54-year-old housemaid Ernestine Maetschke.

Figure 4.

Microscopic analysis of the brain did not reveal abnormalities.

Figure 5.

Oppenheim states that he has not found similar cases of ‘carcinomatosis’ patients in the literature in whom brain symptoms occurred in the absence of macroscopical and microscopical changes.

Figure 6.

Most likely, the toxic focal neurological symptoms of the brain are in fact caused by the presence of a carcinoma.

Figure 7.

The case was not seen as definite proof, but rather as a valuable pointer, indicating the right direction for future observers.