Stephan Volk

Auguste D and Alzheimer's disease

On Nov 4, 1906, Alois Alzheimer gave a remarkable lecture, in which he described for the first time a form of dementia that subsequently, at the suggestion of Emil Kraepelin, became known as Alzheimer’s disease. In his lecture, at the 37th Conference of South-West German Psychiatrists in Tubingen, Alzheimer described a patient called Auguste D, a 51-year-old woman from Frankfurt who had shown progressive cognitive impairment, focal symptoms, hallucinations, delusions, and psychosocial incompetence. At necropsy, there were plaques, neurofibrillary tangles, and arteriosclerotic changes. The eponym Alzheimer, originally used to refer to presenile dementia, came into later use for the largest cause of primary dementia—senile dementia of the Alzheimer type (SDAT). Here, we describe the discovery and contents of the file of Auguste D, which had not been seen since 1909.

Can response to partial sleep deprivation in depressed patients be predicted by regional changes of cerebral blood flow

The possible predictive value of regional cerebral perfusion patterns with respect to the response to partial sleep deprivation (PSD) was evaluated in 15 major depressive patients (mean age = 54.9 years, mean Hamilton depression score = 21.6). Patients were studied with single photon emission computed tomography with technetium-99 m-D,L-hexamethyl-propylene amine oxime. Scans were performed on the morning before and after (at 08.00 h) PSD. Responders to PSD had significantly higher perfusion in the right orbitofrontal cortex than did non-responders before PSD. Multiple regression analysis indicated that right orbitofrontal/basal cingulate perfusion (r = -0.77, P < 0.001) before PSD, and left inferior temporal perfusion (r = 0.59, P = 0.01) after PSD, were fairly accurate predictors of change in Hamilton depression scores. Thus, it appears that the orbitofrontal cortex and the cingulate are involved in PSD and may serve as predictors of therapeutic response.

Evaluation of the effects of total sleep deprivation on cerebral blood flow using single photon emission computerized tomography

HMPAO‐single photon emission computerized tomography (SPECT) is a useful technique in studying cerebral blood flow (CBF). This method is suitable to evaluate the differences of CBF with reference to total sleep deprivation (TSD) within 24 h because of the short half‐life of the radiopharmaceutical compound. In the present study, CBF before and after TSD was analysed in patients suffering from major depression. The morning before and after TSD, Tc‐HMPAO‐SPECT was performed in 20 patients. Hamilton Rating Scale for Depression scores and subjective ratings were obtained daily. Eleven patients responded to TSD; 9 were nonresponders. The main finding was a significant left temporal and mainly right parietal increase of CBF, which was observed in the responders only. CBF values and the severity of depression correlated inversely.

Subjective sleepiness and physiological sleep tendency in healthy young morning and evening subjects

SUMMARY  The Multiple Sleep Latency Test (MSLT) was performed twice after 8h and after 4h of night sleep in 15 healthy young subjects (mean age: 23 y). Seven subjects could be regarded as morning, 8 subjects as evening types. After 8h of sleep significantly more evening types napped at 08.00 hours and at 12.00 hours. Evening types rated themselves more sleepy on an hourly administered visual analogous scale (VAS). Sleep onset latencies (SOL) decreased, and the amount of Stages 1 and 2 increased in all subjects dependent on the sleep restriction condition. No significant differences between morningness and eveningness concerning SOL and structure of nap structure could be observed. After 4 h of sleep there was a marked increase in subjectively rated sleepiness during the morning hours in both groups.

Treatment of narcolepsy-cataplexy syndrome with the new selective and reversible MAO-A inhibitor brofaromine—a pilot study

SUMMARY  Eighteen narcoleptic patients were treated in a single‐blind study with brofaromine, a new selective and reversible MAO‐A‐inhibitor. After a drug‐free period of seven days, brofaromine was administered for two weeks. Patients were treated with 75 mg brofaromine for the first week and with 150 mg brofaromine for the second week of the study. After an adaptation night nocturnal sleep EEGs were recorded under placebo before brofaromine was given, one week later under 75 mg, and another week later under 150 mg brofaromine. Excessive daytime sleepiness (EDS) was evaluated under placebo at the beginning of the study, under 75 mg at the end of the first week, and under 150 mg brofaromine at the end of the second week by means of the Multiple Sleep Latency Test (MSLT) and the Maintenance of Wakefulness Test (MWT). The number of cataplexies was protocolled by the patients. Compared to placebo the administration of 150 mg brofaromine led to a significant increase of sleep latency in the MLST as well as in the MWT. REM sleep was significantly suppressed in the nocturnal sleep EEG, in the MSLT and in the MWT. The number of cataplexies protocolled by the patient was significantly decreased under 150 mg of brofaromine compared to placebo. Improvement of vigilance and cataplexy occurred in dose‐dependent manner. No serious side effects were observed. The results of the present single‐blind study indicate that brofaromine seems to be a well‐tolerated and effective drug for the treatment of excessive daytime sleepiness and cataplexy in narcoleptic patients.

Dopamine D2 receptor occupancy measured by single photon emission computed tomography with 123I-Iodobenzamide in chronic schizophrenia.

Single photon emission computed tomography (SPECT) with 123I-iodobenzamide (123I-IBZM) was used to study 22 chronic schizophrenic patients. The patients, who were receiving maintenance therapy with typical neuroleptics, had not shown any significant improvement since their admission to the hospital. Basal ganglia/frontal cortex ratios of the uptake of 123I-IBZM did not show significant differences on the basis of neuroleptic dosage in chlorpromazine equivalents. There were, however, significant differences in 123I-IBZM uptake in the basal ganglia among patients characterized by negative, mixed and positive symptoms of schizophrenia. Although only a small number of patients had shown a positive response to treatment by the time of discharge, D2 receptor blockade was significantly higher in responders than in nonresponders. In addition, there was an inverse correlation between reduced activation as measured by the Brief Psychiatric Rating Scale and the basal ganglia/frontal cortex ratio. These findings suggest a complex pathogenetic link between the blockade of dopamine D2 receptors and psychopathology in chronic schizophrenic patients. SPECT studies with 123I-IBZM appear to have prognostic value in identifying chronic schizophrenic patients who respond poorly to neuroleptic treatment.

Eine Feldstudie zur psychosozialen Situation Wohnungsloser in Frankfurt am Main

ZusammenfassungIn einer Feldstudie wurden 71 wohnungslose Männer im mittleren Alter von 34,5 Jahren mit einem halbstandardisierten Interview untersucht. Soziodemographisch fallen niedriger Schulabschluß (47,9% erreichten den Hauptschulabschluß, 18,3% verließen die Schule ohne Abschluß), hohe Arbeitslosigkeit und geringes Einkommen auf. Haupteinnahmequelle waren regelmäßige staatliche Hilfen. Die meist unverheirateten und kinderlosen Probanden führten selten in ihrem Leben eine längerdauernde Partnerschaft. Psychosoziale Konflikte (59,2%) wurden am häufigsten als Ursache für das Hineingeraten in Wohnungslosigkeit genannt. Hier betrug das Durchschnittsalter 28,1 Jahre. Neben interpersonellen Konflikten waren Entlassung aus dem Gefängnis und Arbeitslosigkeit die erstgenannten Ursachen der aktuellen Phase der Wohnungslosigkeit. 42,3% berichteten von psychiatrischen Kliniksaufenthalten, v.a. im Zusammenhang mit Alkoholabusus. Die erhobenen Befunde weisen darauf hin, daß wohnungslose Männer frühzeitig in ihrer biographischen Entwicklung in soziale Isolation geraten und der Anteil an psychiatrischer Morbidität hoch ist.SummaryIn a current field-study a sample of 71 homeless men (mean age 35,4 years) was investigated with a semi-standardized interview. Sociodemographically, a low education level, a high unemployment rate and low income were noted. The income was gained mainly through regular social welfare support. Mostly unmarried and without children, the participants seldom lived in a stable partnership during their life. Psychosocial conflicts (59,2%) were one of the most important causes for homelessness at an average age of 28,1 years. Interpersonal conflicts, release from jail and loss of job were the most frequently reported causes of current homelessness. 42,3% had been treated in psychiatric hospitals in the past, the majority because of alcoholism. In summary the current findings indicate that homeless men experience social isolation early during their maturation and that the frequency of psychiatric disorders is high.

Can sleep deprivation response be predicted by regional changes of cerebral blood flow

Schizophrenic patients treated with seroquel (n = 4; 700-750 mg/d) and haloperidol (n = 5; 10-20 mg/d) were investigated by means of IBZM-SPECT. Two striatal ROts and two frontal ROts were each pooled together and the average counts/pixel were calculated. The S / F ratio was calculated between average count-rates in the striatum and the frontal cortex. Under treatment with haloperidol a low S / F ratio (1.08 _+ 0.04) could be shown, which suggests a high occupancy of striatal D2 receptors (88_+ 6%). Under therapy with the new antipsychotic substance seroquel, the S / F ratios were high (1.59 ± 0.10), indicating only a minor striatal D2 blockade (17 ± 10%). These results are in line with the lower incidence of EPMS in patients treated with seroquel.