Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin.

Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with defined cognitive deficit (>or=1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40,000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) - perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.

A case of rapidly progressive multiple system degeneration: morphological findings and pathogenetic implications.

A 62-year-old woman was referred to our psychiatric hospital by the municipal health office, because she was in such a neglected condition that she was a danger to herself. Initially, it was suspected that she was suffering from dementia or psychosis. X-rays led to the suspicion of bronchial carcinoma. Consequently, the mental changes were interpreted as probable effects of metastases to the brain. There was not enough time, however, to check the patient thoroughly to find the actual cause of her altered personality. The patient developed a high fever (up to 42 degrees C). A few days later, she died of cardiorespiratory failure with severe abscess-forming obstructive pneumonia. An autopsy confirmed the bronchial carcinoma. However, metastases were only found in the hilar lymph nodes. No metastases were detectable in the CNS, either macroscopically or microscopically. The neuropathological examination of the brain revealed multiple system degeneration. The striking microscopic findings (a large number of typical apoptotic figures visible with the light microscope in ganglion cells, lack of cytoplasmic inclusion bodies in the oligodendroglia and an unusually strong monocytic reaction (so-called reactive satellitosis) indicated that the disease course had been very rapid. Perhaps these were early steps in the evolution of a multisystem atrophy. A kind of time-lapse effect, as it were, revealed simultaneously individual details of the pathogenetic course, which would have disappeared in the usual long course of the disease and thus could not have been observed, even with the most up-to-date molecular methods. It is very likely that this was a paraneoplastic syndrome.