Plasma total prion protein as a potential biomarker for neurodegenerative dementia: diagnostic accuracy in the spectrum of prion diseases.

AIMS: In the search for blood-based biomarkers of neurodegenerative diseases, we characterized the concentration of total prion protein (t-PrP) in the plasma of neurodegenerative dementias. We aimed to assess its accuracy in this differential diagnostic context. METHODS: Plasma t-PrP was measured in 520 individuals including healthy controls (HC) and patients diagnosed with neurological disease control (ND), Alzheimer's disease (AD), sporadic Creutzfeldt-Jakob disease (sCJD), frontotemporal dementia (FTD), Lewy body dementia (LBD) and vascular dementia (VaD). Additionally, t-PrP was quantified in genetic prion diseases and iatrogenic CJD. The accuracy of t-PrP discriminating the diagnostic groups was evaluated and correlated with demographic, genetic and clinical data in prion diseases. Markers of blood-brain barrier impairment were investigated in sCJD brains. RESULTS: Compared to HC and ND, elevated plasma t-PrP concentrations were detected in sCJD, followed by FTD, AD, VaD and LBD. In sCJD, t-PrP was associated neither with age nor sex, but with codon 129 PRNP genotype. Plasma t-PrP concentrations correlated with cerebrospinal fluid (CSF) markers of neuro-axonal damage, but not with CSF t-PrP. In genetic prion diseases, plasma t-PrP was elevated in all type of mutations investigated. In sCJD brain tissue, extravasation of immunoglobulin G and the presence of swollen astrocytic end-feet around the vessels suggested leakage of blood-brain barrier as a potential source of increased plasma t-PrP. CONCLUSIONS: Plasma t-PrP is elevated in prion diseases regardless of aetiology. This pilot study opens the possibility to consider plasma t-PrP as a promising blood-based biomarker in the diagnostic of prion disease.

Verotoxigenic Escherichia coli: costs of illness in Canada, including long-term health outcomes.

The main objective of this study was to provide cost estimates of human Escherichia coli O157 infection to facilitate future assessment of the benefits and costs of alternative preventive strategies to reduce illness. We investigated the costs of illness to Canadians from primary human infection by verotoxigenic E. coli O157 (also called Shiga toxin-producing E. coli O157) using data from the National Notifiable Diseases Registry. We used relative risk information from peer-reviewed publications to estimate the burden of illness and associated costs for eight long-term health outcomes. National estimates of the number of cases (mean and 5th and 95th percentiles), associated costs, and a rank correlation test to identify which outcomes were associated with the highest per capita costs were calculated. An estimated 22,344 cases of primary infections occur in Canada annually, costing $26.7 million. There are 37,867 additional on-going long-term health outcomes costing $377.2 million each year. Our analysis indicated that the annual cost for primary and long-term illness is $403.9 million. The analysis supports evaluation of alternative control and prevention measures and the development and implementation of policy and practices aimed at safe food production.

[Minimally invasive anterior approach]. / Der minimal-invasive anteriore Zugang.

The minimally invasive direct anterior approach for total hip arthroplasty (THA) was first published in 1985. Since then the technique has been further improved and the indications have been extended. The approach utilizes the muscle gap between the tensor fasciae latae muscle on the lateral side and the sartorius muscle on the medial side. This muscle gap allows a direct and quick approach to the hip joint with good muscle preservation. During preparation of the femur the tensor fasciae latae muscle is at risk of being damaged. The lateral cutaneous nerve of the thigh (NCFL) and its branches are also in danger of being damaged during skin incision and dissection of the subcutaneous tissue. In this article the technique, risks and current clinical results of THA using the minimally invasive direct anterior approach are described. The results from the literature, as well as own results are compared to the traditional transgluteal lateral Bauer approach and discussed. Reviewing the literature, special attention has been given to the incidence of NCFL lesions, damage of the tensor fasciae latae muscle and positioning of the cup. Especially for the latter, the general view is hindered in the minimally invasive technique.

[The German version of parents' postoperative pain measure (PPPM-D). Validation on children 2-12 years old]. / Die deutsche Version des Parents' Postoperative Pain Measure (PPPM-D). Validierung an Kindern im Alter von 2 bis 12 Jahren.

BACKGROUND: Parents become increasingly more responsible for the postoperative pain management of their children. Useful and valid pain assessments for parents may improve pain measurement. The aim of this study was to evaluate a German version of the parents' postoperative pain measure (PPPM-D). METHODS: After translation of the PPPM into German 52 children between 2 and 12 years of age, undergoing orthopedic and trauma surgery, were included in a prospective study. At least one of the parents completed the PPPM-D on the preoperative day and the day of surgery until postoperative day 5. Both, the children's and infants postoperative pain scale (CHIPPS) for children between 2 and 4 years and the faces pain scale revised (FPS-R) for children between 5 and 12 years were also assessed. Moreover, the acceptance of the PPPM-D by the parents was assessed. RESULTS: The PPPM-D showed satisfactory reliability (Cronbach's α values = 0.77-0.87). Construct validity was demonstrated with strong correlations with the CHIPPS and the FPS-R. Discriminative validity was shown by both statistically and clinically significant differences between minor, medial and major surgeries on the first 3 days after surgery. The examination of sensitivity to change yielded promising results. The PPPM-D was well accepted by the participating parents. CONCLUSIONS: The results of this study provide evidence of the reliability, validity and high acceptance of the PPPM-D as an assessment tool of postoperative pain among children aged 2 through to 12 years of age after orthopedic or trauma surgery.

[Minimally invasive retrograde drilling of osteochondral lesions of the femur using an arthroscopic drill guide]. / Minimal-invasive retrograde Anbohrung der Osteochondrosis dissecans des Femurkondylus mit einem speziellen Zielinstrumentarium.

OBJECTIVE: Retrograde drilling for penetration of subchondral sclerotic bone in osteochondrosis dissecans (OCD) of the femoral condyle with preserved cartilage integrity. Hereby, revascularization of the OCD and immigration of bone marrow cells to achieve stable reintegration of the OCD into the surrounding subchondral bone. INDICATIONS: Stable juvenile and adult osteochondrosis dissecans (stage I-II of the International Cartilage Repair Society (ICRS) classification) of the medial and lateral femoral condyle with an intact articular surface and surrounding sclerosis zone, which is visible in the x-ray. CONTRAINDICATIONS: OCD stage III-IV of the ICRS grading scale. Relative contraindication: preceding retrograde drilling. SURGICAL TECHNIQUE: Arthroscopic inspection and palpation of the cartilage defect. Minimal incision over the M. vastus medialis (when the defect is located in the medial condyle) or the M. vastus lateralis (when the defect is located in the medial condyle). Preparation and dissection of the fascia of the vastus muscle. Insertion of retractors underneath the vastus muscle to expose the metaphysis of the distal femur. Intraarticular positioning of the arthroscopic drill guide, placement of the wire guide and a Kirschner(K) wire on the femur metaphysis and retrograde drilling with a 2.0-2.2 mm K wire under radiographic visualization. Length measurement of the intraosseous wire distance. Switch the guide mechanism to a multiple hole drill guide and, depending on the defect size, insertion of a further 7-10 K wires of same thickness and defined length. POSTOPERATIVE MANAGEMENT: Sterile bandage and slightly compressive dressing. Continuous active and passive knee motion. Weight bearing of 20 kg for 6 weeks, with subsequent transition to continuous weight bearing. Radiographic controls at 6 and 12 weeks postoperatively. In case of a persistent sclerosis zone in the control x-ray or clinical abnormalities, control MRI is indicated. RESULTS: A total of 55 patients with a mean age of 19.6 years were treated using the described technique: 49 patients (89.1%), and 54 knees respectively (35 juvenile OCD, 19 adult OCD), were seen with a mean follow-up of 37.9 months. An improvement was observed in 81.6% of the knees using the radiographic score, i.e., a mean improvement of 1.13 of the radiographic score published by Rodegerdts and Gleissner (preoperative 3.04 vs. postoperative 1.91). Juvenile OCD showed better radiographic results overall (88.2% healing) than adult OCD (66.7% healing).

Distress in patients with newly diagnosed brain tumours.

OBJECTIVE: Patients with intracranial tumours often suffer from clinically relevant psychological distress. However, levels of distress and contributing factors have not been systematically evaluated for the early course of the disease. Using the National Comprehensive Cancer Network's Distress Thermometer (DT), we evaluated the extent and sources of distress within a population of patients with intracranial neoplasms. METHODS: One hundred and fifty-nine patients were included who underwent craniotomy for newly diagnosed intracranial tumours at our department. All patients completed the DT questionnaire, a single-item 11-point visual analogue scale measuring psychological distress. The appendant problem list (PL) consists of 40 items representing problems commonly experienced by cancer patients. Patients were asked to mark any experienced sources of distress. RESULTS: Percentage of patients suffering from relevant distress was 48.4% (cut-off ≥6). DT-scores were significantly associated with depression and anxiety as well as reported number of concerns. On average, patients reported 6.9 sources of cancer-related distress. Objective medical data (e.g. tumour stage) as well as sociodemographic data (e.g. gender, IQ) were not associated with psychological distress at this early phase. CONCLUSIONS: Prevalence of elevated distress is high shortly after primary neurosurgical treatment in patients with intracranial tumours and cannot be predicted by objective data. As a consequence, sources of distress can and should be routinely assessed and targeted in these individuals in this particular period. Further studies are needed to help to identify patients who are at risk of suffering from long-term emotional distress in order to enable targeted psychosocial intervention.

[Perioperative pain therapy in interventions for elbow stiffness]. / Perioperative Schmerztherapie bei Eingriffen wegen Ellenbogengelenksteife.

Conservative treatment and surgical release of a stiff elbow requires correct pain management which should be oriented to the individual needs of the patient. Regional anesthesia in combination with opioids is necessary postoperatively to obtain sufficient pain relief. There is a need for prospective randomized studies to develop an optimal pain therapy concept following operations for elbow stiffness.

[Elevated postoperative pain levels following orthopedic surgery. Depression as a strong predictor]. / Erhöhter postoperativer Schmerz nach orthopädischen Operationen. Depression als starker Prädiktor.

The aim of this study was to examine whether depression is a strong predictor of elevated postoperative pain levels following orthopedic surgery and whether the implementation of standardized pain management is more beneficial for patients with depression. We performed a non-randomized, prospective study with two different groups of patients who underwent orthopedic surgery. Group 1 (n=249) received non-standardized pain therapy whereas group 2 (n = 243) was treated with a standardized pain management concept. Effects of the treatment were monitored with a VAS-based pain assessment protocol. Depression was measured preoperatively with the self-reported Patient Health Questionnaire (PHQ-9). Patients with the probable diagnosis of a current episode of major depression showed significantly higher postoperative pain than patients without a depressive episode. On the other hand, patients with depression benefited from the implementation of standardized pain management. Our data suggest a predictive value of depression for severe postoperative pain. Patients with depression benefited from standardized postoperative pain therapy, but were still suffering from significantly higher postoperative pain.

[Implementation of standardized postoperative pain therapy for orthopaedic patients. Comparison between unsystematic and standardized pain therapy]. / Implementierung einer standardisierten Schmerztherapie bei postoperativen orthopädischen Patienten. Vergleich einer unsystematischen mit einer standardisierten Schmerztherapie.

BACKGROUND: The painless clinic and postoperative pain therapy are currently major issues in the management of surgical procedures. The aim of this study was to evaluate the benefit of a standardized pain therapy on the postoperative pain level after orthopaedic procedures. PATIENTS AND METHODS: We investigated two different groups of patients who underwent an orthopaedic surgical procedure. Group 1 (n = 249) received a pain therapy which was based on an individual and surgery-dependent concept whereas group 2 (n = 243) was treated with a standardized pain therapy concept. The effect of the treatment was monitored with a VAS-based protocol. RESULTS: Up to day 9 after surgery there was a significant difference between the two groups in regard to the postoperative pain. The patients of group 2 had less pain but had more unwanted side effects caused by the pain therapy during the first 3 days after surgery. Mobility and mental disposition were positively affected. CONCLUSION: The implementation of a standardized pain therapy is successful in reducing postoperative pain. Mobility and mental disposition are also influenced positively. As a consequence the incidence of unwanted side effects is rising.

Deep brain stimulation for movement disorders and its neuropsychological implications.

Deep brain stimulation (DBS) has gained increasing attention as a therapy for movement disorders. Neuropsychological alterations can accompany the disease evolution and medical therapy of PD. Also, interfering abruptly with the biological balance by means of a surgical intervention into complex circuits with motor but also cognitive and limbic functions, could potentially cause severe problems. Because cognitive or emotional impairments may have an even stronger impact on quality of life, than motor symptoms, care must be taken to perform surgery in the safest possible way to exclude adverse effects in these domains. Detailed neuropsychological evaluations may become helpful to further understand the mechanisms underlying some aspects of the clinical pictures both pre- and postoperatively and to define risk populations, that should be excluded from this intervention.

Investigations of the potential risk factors associated with cases of bovine spongiform encephalopathy in Bavaria, Germany.

In order to identify the management and feeding practices that might have contributed to the occurrence of bovine spongiform encephalopathy (BSE) in Bavaria, Germany, information from 110 dairy farms on which a case of BSE had been reported was compared with information derived from a questionnaire sent to approximately 10,000 Bavarian farms on which no case of BSE had been reported up to February 2003. Representative information was obtained from 4006 dairy farms. The results indicated that in comparison with these control farms a higher proportion of the BSE farms had also kept pigs or poultry, although the difference was not significant, and that a significantly higher proportion of the BSE farms had fed proprietary concentrates and/or milk replacers to their calves.

Dynorphin A (1-17) induces apoptosis in striatal neurons in vitro through alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor-mediated cytochrome c release and caspase-3 activation.

Dynorphin A (1-17), an endogenous opioid neuropeptide, can have pathophysiological consequences at high concentrations through actions involving glutamate receptors. Despite evidence of excitotoxicity, the basic mechanisms underlying dynorphin-induced cell death have not been explored. To address this question, we examined the role of caspase-dependent apoptotic events in mediating dynorphin A (1-17) toxicity in embryonic mouse striatal neuron cultures. In addition, the role of opioid and/or glutamate receptors were assessed pharmacologically using dizocilpine maleate (MK(+)801), a non-equilibrium N-methyl-D-aspartate (NMDA) antagonist; 6-cyano-7-nitroquinoxaline-2,3-dione, a competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate antagonist; or (-)-naloxone, a general opioid antagonist. The results show that dynorphin A (1-17) (>or=10 nM) caused concentration-dependent increases in caspase-3 activity that were accompanied by mitochondrial release of cytochrome c and the subsequent death of cultured mouse striatal neurons. Moreover, dynorphin A-induced neurotoxicity and caspase-3 activation were significantly attenuated by the cell permeable caspase inhibitor, caspase-3 inhibitor-II (z-DEVD-FMK), further suggesting an apoptotic cascade involving caspase-3. AMPA/kainate receptor blockade significantly attenuated dynorphin A-induced cytochrome c release and/or caspase-3 activity, while NMDA or opioid receptor blockade typically failed to prevent the apoptotic response. Last, dynorphin-induced caspase-3 activation was mimicked by the ampakine CX546 [1-(1,4-benzodioxan-6-ylcarbonyl)piperidine], which suggests that the activation of AMPA receptor subunits may be sufficient to mediate toxicity in striatal neurons. These findings provide novel evidence that dynorphin-induced striatal neurotoxicity is mediated by a caspase-dependent apoptotic mechanism that largely involves AMPA/kainate receptors.

Co-existence of hyperparathyroidism, hypergastrinaemia and multiple gastric carcinoids is not always due to incomplete expression of the MEN-1 syndrome.

Until recently, the association of primary hyperparathyroidism and gastric carcinoid, with or without hypergastrinaemia, had been considered an incomplete form of multiple endocrine neoplasia type 1. This is because it seemed unlikely that the rare joint appearance of these diseases could occur only by chance. It is now possible to evaluate the pathogenetic involvement of the multiple endocrine neoplasia type 1 gene in many, apparently sporadic, clinical conditions. This is a case report of a female mimicking multiple endocrine neoplasia type 1 due to the presence of hyperparathyroidism, gastric carcinoid, and hypergastrinaemia. However, involvement of the MEN-1 gene (exons 2-10) was not detected, whereas hypergastrinaemia was attributed to a chronic atrophic gastritis.

In situ analysis of coronary terminal arteriole diameter responses: technical report of a new experimental model.

INTRODUCTION: To date, investigation of coronary arteriole vasomotor activity has been limited to arterioles >30- 40 microm. Here, we introduce a new experimental model to allow for in situ microscopy of terminal coronary arterioles. METHODS: Rat hearts were perfused in a closed loop system (priming volume 20 ml) which was placed on a computer-controlled microscope stage. FITC-dextran and tetrodotoxin (TTX, 50 microM) were added. Tilting of the microscope by 90 degrees allowed for visual access to the ventricular surface. Arterioles were identified by the flow direction of fluorescent beads (1 microm). Images were recorded on video tape, and arteriole diameters were measured offline. Stability of the preparation and maintenance of coronary flow reserve were analyzed. Responses of coronary flow and arteriole diameters to the vasodilators papaverine and Na-nitroprusside were recorded. RESULTS: In TTX-arrested control hearts coronary flow and terminal arteriole diameters were stable for 2 h. Administration of papaverine and Na-nitroprusside increased coronary flow from 6.4 +/- 0.7 to 13.3 +/- 1.3 ml/min, decreasing coronary resistance by 52 +/- 3%. Terminal coronary arteriole diameters increased from 12.0 +/- 0.9 to 13.6 +/- 1.0 microm, decreasing hindrance of this vessel segment by 45 +/- 11%. CONCLUSION: Preservation of coronary terminal arteriolar tone and adequate responsiveness to vasodilators in the TTX-arrested isolated heart were demonstrated. Thus, this model may serve to complement our understanding of coronary microvascular control mechanisms by extending observations to the terminal arteriolar bed.

Relapse in the skull after myeloablative therapy for high-risk neuroblastoma.

Patterns of relapse were determined for 20 high-risk neuroblastoma patients treated with chemotherapy, surgery, primary and metastatic site radiation (21 Gray), myeloablative chemotherapy, peripheral blood stem cell rescue, and 13-cis-retinoic acid. The median follow-up duration after transplant is 21 months (range, 8-34 months). The event-free survival and overall survival at 2 years were 45 and 75%, respectively. There were 2 primary site recurrences. Metastatic sites that became MIBG-scan negative on induction chemotherapy were not irradiated. Four patients relapsed in irradiated metastatic sites, 3 in the skull, 1 in the liver. Failure also occurred at 2 skull sites treated with chemotherapy only, and at 5 new sites: 1 skull, 2 distant lymph nodes, and 2 bones other than skull. Eight of 20 patients had skull metastasis at presentation; 6 were irradiated and 3 were controlled. Skull metastasis warrants more aggressive evaluation and treatment.

Dynorphin A toxicity in striatal neurons via an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor mechanism.

Dynorphin A (1-17) is an endogenous opioid peptide that is antinociceptive at physiological concentrations, but in excess can elicit a number of pathological effects. Both kappa-opioid and N-methyl-D-aspartate receptor antagonists modulate dynorphin toxicity, suggesting that dynorphin is acting directly or indirectly through these receptor types. We found in spinal cord neurons that the neurotoxic effects of dynorphin A and several dynorphin-derived peptide fragments are largely mediated by N-methyl-D-aspartate receptors. Despite these findings, aspects of dynorphin A toxicity could not be accounted for by opioid or N-methyl-D-aspartate receptor mechanisms. To address this issue, neurons enriched in kappa-opioid, N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors were isolated from embryonic day-15 mouse striata and the effects of extracellularly administered dynorphin A (1-17) and (13-17) on neuronal survival were examined in vitro. Unlike spinal cord neurons, N-methyl-D-aspartate receptors mature later than alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptors in striatal neurons, thus providing a strategy to elucidate non-N-methyl-D-aspartate receptor-mediated mechanisms of toxicity. Time-lapse photography was used to repeatedly follow the same neurons before and during experimental treatments. Dynorphin A (1-17 or 13-17; 10 microM) caused significant neuronal losses after 48 to 72 hours versus untreated controls. Dynorphin A or A (13-17) toxicity was unaffected by the opioid receptor antagonist naloxone (10 microM) or by dizocilpine (10 microM). In contrast, the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline- 2,3-dione (10 microM) significantly attenuated only dynorphin A (1-17)-induced neuronal losses and not that induced by dynorphin A (13-17). Dynorphin A (1-17) toxicity was accompanied by a proportional loss of R2 and R3 subunits of the AMPA receptor complex, but not non-N-methyl-D-aspartateR1, expressing neurons and was mimicked by the ampakine 1-(1,4-benzodioxan-6-ylcarbonyl)piperidine. Although it is unclear whether dynorphin A activates alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptors directly or indirectly via glutamate release, our culture conditions do not support glutamate retention or accumulation. Our findings suggest that dynorphin A (1-17) can exert toxic effects on striatal neurons via an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor mechanism.

Inhibition of host cell apoptosis by Toxoplasma gondii is accompanied by reduced activation of the caspase cascade and alterations of poly(ADP-ribose) polymerase expression.

The obligate intracellular protozoan parasite Toxoplasma gondii has been shown to protect different cell types from apoptosis induced by a variety of pro-apoptotic treatments. However, the precise cell biological mechanisms of this inhibition remained unknown. As shown in this study, apoptosis in human-derived HL-60 and U937 cells induced by treatment with actinomycin D or TNF-alpha in combination with cycloheximide, respectively, was indeed dose-dependently downregulated by prior infection with T. gondii, as determined by DNA fragmentation assays. Cleavage of caspase 3 and caspase 9 after treatment with pro-apoptotic stimuli was considerably diminished by T. gondii. Furthermore, release of mitochondrial cytochrome c during apoptosis in HL-60 cells was prevented by intracellular parasites and this was correlated with the absence of DNA strand breaks on the single cell level. Inhibition of cytochrome c release coincided with a twofold upregulation of Mcl-1 protein levels in HL-60 and U937 cells, while Bcl-2 expression did not increase after infection. Parasitic interference with the caspase cascade led to a reduced proteolytic cleavage of the nuclear target molecule protein kinase C delta. In parallel, poly(ADP-ribose) polymerase protein levels were prominently downregulated by T. gondii, irrespective of whether HL-60 and U937 cells had been treated with pro-apototic stimuli or left untreated. However, poly(ADP-ribose) polymerase mRNA levels remained unchanged after infection as determined by RT-PCR analyses. These observations suggest that T. gondii has evolved different mechanisms that may contribute to downregulation of host cell apoptosis, namely inhibition of cytochrome c release and subsequent caspase activation as well as downregulation of poly(ADP-ribose) polymerase protein levels.

Gluten sensitivity in sporadic and hereditary cerebellar ataxia.

Gluten sensitivity, with or without classical celiac disease symptoms and intestinal pathology, has been suggested as a potentially treatable cause of sporadic cerebellar ataxia. Here, we investigated the prevalence of abnormally high serum immunoglobulin A (IgA) and IgG anti-gliadin antibody titers and typical human lymphocyte antigen (HLA) genotypes in 50 patients presenting with cerebellar ataxia who were tested for molecularly characterized hereditary ataxias. A high prevalence of gluten sensitivity was found in patients with sporadic (7/26; 27%) and autosomal dominant (9/24; 37%) ataxias, including patients with known ataxia genotypes indicating a hitherto unrecognized association between hereditary ataxias and gluten sensitivity. Further studies are needed to determine whether gluten sensitivity contributes to cerebellar degeneration in patients with hereditary cerebellar ataxia. Patients with hereditary ataxia (including asymptomatic patients with known ataxia genotype) should be considered for screening for gluten sensitivity and gluten-free diet trials.

Are some memory deficits unique to lesions of the mammillary bodies?

The role of the mammillary bodies in human memory is still in debate. A recent model of human amnesia proposes similar functions for the mammillary bodies and the hippocampus. But the main evidence for this model comes from animal studies using the delayed non-matching to sample paradigm. We describe a patient who developed a severe memory impairment after surgical removal of a germinoma. Postsurgical high resolution MRI revealed bilaterally shrunken mammillary bodies and an infarct of the left mammillary body. There were no other relevant lesions. Neuropsychological testing showed mildly impaired frontal lobe functions (executive functions, working memory and word fluency), almost intact learning and recognition, but severely impaired free and delayed recall. Experimental investigations revealed a reduced but preserved release of proactive interference and a pronounced impairment of recency and source judgments. We conclude that the mammillary bodies do play a prominent role in human memory, although the role differs slightly from that of the hippocampus.