[COVID-19 in old age-The geriatric perspective]. / COVID-19 im Alter ­ Die geriatrische Perspektive.

Predominantly the older population is affected by a severe course of COVID-19. The mortality of hospitalized patients with COVID-19 above the age of 80 years is up to 54% in international studies. These observations indicate the necessity to highlight the geriatric perspective on this disease. The diagnostics and treatment of COVID-19 do not differ between younger and older patients but atypical symptoms should be expected more frequently in old age. Older subjects show an increased need for rehabilitation after COVID-19. Paradoxically, increasing rehabilitation demands go along with a reduced availability of geriatric rehabilitation options, the latter being a consequence of closure or downsizing of rehabilitation departments during the pandemic. In general, measures of isolation and quarantine should be diligently balanced as the health and emotional consequences of such measures may be severe in older persons. In light of the poor prognosis of older COVID-19 patients, advanced care planning becomes even more relevant. Caregivers and physicians should be encouraged to compose advanced care directives that also reflect the specific circumstances of COVID-19. Fortunately, current data suggest that the effectiveness of the vaccination with the mRNA-vaccines approved in Germany may be equally high in older compared to younger persons.

[Paraneoplastic subacute degeneration of the cerebellum in non-small cell lung cancer and positive anti-Tr3 antibodies]. / Paraneoplastische subakute Degeneration des Kleinhirns bei nichtkleinzelligem Bronchialkarzinom und positiven Anti-Tr3-Antikörpern.

Neurological disorders can occur before the diagnosis of a malignoma is set. These disorders are induced by a misguided immune response with antibodies against intracellular or cell surface antigens. One of the most common paraneoplastic diseases is the subacute degeneration of the cerebellum. In most of the cases antibodies against Anti Hu, CRMP5/CV2, Amphiphysin and Ma/Ta are found and small cell bronchial carcinoma, breast cancer and lymphoma are diagnosed. We report about a 67 years old man with cerebellar symptoms and a weight loss of 10 kg who was treated in our clinic. After our diagnostic work up we found a non small cell cancer and diagnosed a subacute degeneration of the cerebellum as a paraneoplastic disorder. We found a high positive titer for Anti-Tr3 antibodies while the rest of the paraneoplastic antibodies described as typically associated with the subacute degeneration of the cerebellum were negative. The Anti-Tr3 antibodies are usually found in patients with Hodgkin and less often Non-Hodgkin disease. After initiation of a tumor specific therapy and intravenous immunoglobulin therapy the cerebellar symptoms decreased. In future follow up examinations we will see if the anti-Tr3 antibodies were associated with the non small cell bronchial carcinoma or if a lymphoma will occur in our patient.

[Altered orientation and aggressiveness in an 89-year-old woman]. / Wechselnde Vigilanz und Fremdaggressivität bei einer 89­jährigen Patientin.

An 89-year-old woman with Alzheimer's dementia was admitted because of altered orientation, aggressiveness and inability to take care of herself at home. Her patient history indicated that 14 days ago the battery of the pacemaker had be renewed. During that time the patient suffered from psychomotor alterations. Therefore, melperone had been initiated. Inspection of the urine and laboratory findings pointed towards an acute exacerbation of acute intermittent porphyria as a possible cause of the delirium. After discontinuation of melperone with additional parenteral therapy with physiological fluids, the signs of delirium significantly improved.

PEGylated human serum albumin (HSA) nanoparticles: preparation, characterization and quantification of the PEGylation extent.

Modification with poly(ethylene glycol) (PEG) is a widely used method for the prolongation of plasma half-life of colloidal carrier systems such as nanoparticles prepared from human serum albumin (HSA). However, the quantification of the PEGylation extent is still challenging. Moreover, the influence of different PEG derivatives, which are commonly used for nanoparticle conjugation, has not been investigated so far. The objective of the present study is to develop a method for the quantification of PEG and to monitor the influence of diverse PEG reagents on the amount of PEG linked to the surface of HSA nanoparticles. A size exclusion chromatography method with refractive index detection was established which enabled the quantification of unreacted PEG in the supernatant. The achieved results were confirmed using a fluorescent PEG derivative, which was detected by photometry and fluorimetry. Additionally, PEGylated HSA nanoparticles were enzymatically digested and the linked amount of fluorescently active PEG was directly determined. All the analytical methods confirmed that under optimized PEGylation conditions a PEGylation efficiency of up to 0.5 mg PEG per mg nanoparticle could be achieved. Model calculations made a 'brush' conformation of the PEG chains on the particle surface very likely. By incubating the nanoparticles with fetal bovine serum the reduced adsorption of serum proteins on PEGylated HSA nanoparticles compared to non-PEGylated HSA nanoparticles was demonstrated using sodium dodecylsulfate polyacrylamide gel electrophoresis. Finally, the positive effect of PEGylation on plasma half-life was demonstrated in an in vivo study in mice. Compared to unmodified nanoparticles the PEGylation led to a four times larger plasma half-life.

[Sarcopenia and frailty in neurology]. / Sarkopenie und Frailty in der Neurologie.

Sarcopenia and frailty are common geriatric syndromes and are associated with adverse health outcome and impaired health-related quality of life. Co-occurrences of these two syndromes with age-related neurological diseases are potentially high but not well investigated. Moreover, it is not well understood how these syndromes interact with neurological diseases, such as Parkinson's disease, Alzheimer's disease and stroke. This article introduces the currently most accepted concepts of sarcopenia and frailty, discusses the potential relevance of the syndromes for geriatric patients and presents examples of studies that investigated potential interactions between these geriatric and neurological syndromes and conditions. First results indicate that (i) the co-occurrence of these geriatric syndromes and age-related neurological diseases is high, (ii) sarcopenia and frailty can influence the clinical state of neurological diseases to a relevant extent and (iii) at least some common causes and pathophysiological processes confer the geriatric and neurological conditions. In conclusion, profound knowledge about the interaction of sarcopenia, frailty and age-associated neurological conditions is currently not available. Such knowledge would have an enormous potential for improved therapy of these neurological conditions.

[Sensory aphasia during therapy with metronidazole--an important differential diagnosis of acute cerebral ischemia]. / Sensorische Aphasie unter Therapie mit Metronidazol--eine wichtige Differenzialdiagnose der akuten zerebralen Ischämie.

HISTORY AND ADMISSION FINDINGS: A 74-year old man was admitted after neurosurgical treatment of a lumbar vertebral fracture. He had a slight paresis of the right leg in combination with bladder dysfunction. INVESTIGATIONS: There were signs of a postoperative anemia (hemoglobin 10.4 mg/dl) and mildly elevated infection parameters (CRP 2 mg/dl). Routine ECG and chest X-ray were normal. TREATMENT AND COURSE: Physical training was initiated, but diarrhea occurred 2 days after admission. As the patient had received antibiotics after the operation, a treatment with metronidazole was initiated under the suspicion of diarrhoea induced by clostridium difficile. At day 6 of treatment a hypertensive crisis (blood pressure 230/120 mmHg) developed, followed by sensory aphasia. Despite treatment at the stroke unit and blood pressure regulation, the clinical signs of aphasia persisted. MRI could not detect an acute cerebral infarction. After discontinuation of metronidazole complete reconstitution occurred within 72 h. CONCLUSION: Metronidazole should be taken into account as cause of severe neurological side effects including ischemia-like syndromes like aphasia.

Reperfusion by combined thrombolysis and mechanical thrombectomy in acute stroke: effect of collateralization, mismatch, and time to and grade of recanalization on clinical and tissue outcome.

BACKGROUND AND PURPOSE: Our research focuses on interventional neuroradiology (stroke treatment including imaging methods) and general neuroimaging with an emphasis on functional MR imaging. Our aim was to determine the efficacy of revascularization (TIMI) of middle cerebral and/or carotid artery occlusion by means of mechanical recanalization techniques and to evaluate the impact of collateralization, mismatch in perfusion CT, time to revascularization, grade of revascularization on tissue, and clinical outcome in patients with acute ischemic stroke. MATERIALS AND METHODS: Thirty-one patients with MCA and/or ICA occlusion were included. Ischemic stroke was diagnosed by NECT, CTA, and volume PCT for grading collateralization and mismatch. Time to recanalization was measured from the onset of stroke to the time point of DSA-proved mechanical recanalization. Tissue outcome was calculated by segmentation of infarct size between pre- and postinterventional CT and percentage mismatch lost. Clinical outcome was determined by the mRS. RESULTS: Twenty-one of 31 patients (61.8%) presented with MCA and 10/31 patients (38.2%), with distal ICA occlusions. Sufficient recanalization (TIMI 2 and 3) was achieved in 23/31 (75%). Clinical evaluation revealed an mRS score of ≤2 in 25.5%. Age (r = 0.439, P = .038) and TIMI (r = 0.544, P = .002) showed the strongest correlation with clinical outcome. Time to recanalization, TIMI score, and mismatch were associated with a good tissue outcome in ANOVA. CONCLUSIONS: Favorable outcome after mechanical recanalization of acute MCA and ICA occlusion depends on time to and grade of recanalization, mismatch, and collateralization. These results indicate that multimodal stroke imaging is helpful to guide therapy decisions and to indicate patients amenable for mechanical recanalization.

Appropriate end-points for right results in the age of antiangiogenic agents: future options for phase II trials in patients with recurrent glioblastoma.

The progression-free survival rate at 6 months (PFS-6) has long been considered the best end-point for assessing the efficacy of new agents in phase II trials in patients with recurrent glioblastoma. However, due to the introduction of antiangiogenic agents in this setting, and their intrinsic propensity to alter neuroradiological disease assessment by producing pseudoregression, any end-point based on neuroradiological modifications should be reconsidered. Further, statistically significant effects on progression-free survival (PFS) only should not automatically be considered reliable evidence of meaningful clinical benefit. In this context, because of its direct and unquestionable clinical relevance, overall survival (OS) represents the gold standard end-point for measuring clinical efficacy, despite the disadvantage that it is influenced by subsequent therapies and usually takes longer time to be evaluated. Therefore, while awaiting novel imaging criteria for response evaluation and/or new imaging tools to distinguish between 'true' and 'pseudo'-responses to antiangiogenic agents, the measurement of OS or OS rates should be considered primary end-points, also in phase II trials with these agents.

Response assessment in neuro-oncology (a report of the RANO group): assessment of outcome in trials of diffuse low-grade gliomas.

Although low-grade gliomas (LGG) have a less aggressive course than do high-grade gliomas, the outcome of these tumours is ultimately fatal in most patients. Both the tumour and its treatment can cause disabling morbidity, particularly of cognitive functions. Because many patients present with seizures only, with no other signs and symptoms, maintenance of quality of life and function constitutes a particular challenge in LGG. The slow growth pattern of most LGG, and the rare radiological true responses despite a favourable clinical response to treatment, interferes with the use of progression-free survival as the primary endpoint in trials. Overall survival as an endpoint brings logistical challenges, and is sensitive to other non-investigational salvage therapies. Clinical trials for LGG need to consider other measures of patient benefit such as cognition, symptom burden, and seizure activity, to establish whether improved survival is reflected in prolonged wellbeing. This Review investigates clinical and imaging endpoints in trials of LGG, and provides response assessment in neuro-oncology (RANO) criteria for non-enhancing tumours. Additionally, other measures for patients with brain tumours that assess outcome are described. Similar considerations are relevant for trials of high-grade gliomas, although for these tumours survival is shorter and survival endpoints generally have more value than they do for LGG.

Specific biomarkers of receptors, pathways of inhibition and targeted therapies: clinical applications.

A deeper understanding of the role of specific genes, proteins, pathways and networks in health and disease, coupled with the development of technologies to assay these molecules and pathways in patients, promises to revolutionise the practice of clinical medicine. In particular, the discovery and development of novel drugs targeted to disease-specific alterations could benefit significantly from non-invasive imaging techniques assessing the dynamics of specific disease-related parameters. Here we review the application of imaging biomarkers in the management of patients with brain tumours, especially malignant glioma. This first part of the review focuses on imaging biomarkers of general biochemical and physiological processes related to tumour growth such as energy, protein, DNA and membrane metabolism, vascular function, hypoxia and cell death. These imaging biomarkers are an integral part of current clinical practice in the management of primary brain tumours. The second article of the review discusses the use of imaging biomarkers of specific disease-related molecular genetic alterations such as apoptosis, angiogenesis, cell membrane receptors and signalling pathways. Current applications of these biomarkers are mostly confined to experimental small animal research to develop and validate these novel imaging strategies with future extrapolation in the clinical setting as the primary objective.

[Primary brain tumors and brain metastases. Symptomatic epilepsy and driving ability - systematic review and expert opinion]. / Primäre Hirntumoren und Hirnmetastasen. Symptomatische Epilepsie und Fahreignung - Expertenumfrage und systematisches Review.

PURPOSE: Primary brain tumors and metastases are common causes of symptomatic epilepsy. Seizures, neurological and neuropsychological deficits can interfere with driving ability. The present paper aims to systematically review the incidence of epileptic seizures in brain tumor patients and to discuss driving ability in the context of the current German guidelines and expert opinions. METHODS: To evaluate the incidence of epileptic seizures which occur at the beginning and in the course of the disease, we performed a systematic literature research in PubMed from 1960 to 2007. Additionally on the basis of this data we performed a survey collecting expert opinions regarding the driving ability of brain tumor patients from members of the German working groups "Arbeitsgemeinschaft für prächirurgische Epilepsiediagnostik und operative Epilepsietherapie" (Working Group for Presurgical Epilepsy Diagnostics and Operative Epileptic Therapy) and "Neuroonkologische Arbeitsgemeinschaft" (Neuro-oncological Working Group). RESULTS: The incidence of epileptic seizures depends on the entity, dignity and localization of the tumor. The driving ability of brain tumor patients is not explicitly regulated in Germany. Of the interviewed experts 72% judged the guidelines to be precise enough and 44% did not want to deprive the patients of their driving ability without a first seizure, independent of the individual risk. DISCUSSION: The available studies are methodologically insufficient and show that a further evaluation is necessary to assess the driving ability. Possible restrictions of the driving ability in patients with a high risk of seizures in the course of the disease have to take into account the balance between individual rights and the interests of the general public.

Imaging noradrenergic influence on amyloid pathology in mouse models of Alzheimer's disease.

INTRODUCTION: Molecular imaging aims towards the non-invasive characterization of disease-specific molecular alterations in the living organism in vivo. In that, molecular imaging opens a new dimension in our understanding of disease pathogenesis, as it allows the non-invasive determination of the dynamics of changes on the molecular level. IMAGING OF AD CHARACTERISTIC CHANGES BY microPET: The imaging technology being employed includes magnetic resonance imaging (MRI) and nuclear imaging as well as optical-based imaging technologies. These imaging modalities are employed together or alone for disease phenotyping, development of imaging-guided therapeutic strategies and in basic and translational research. In this study, we review recent investigations employing positron emission tomography and MRI for phenotyping mouse models of Alzheimer's disease by imaging. We demonstrate that imaging has an important role in the characterization of mouse models of neurodegenerative diseases.

In vivo evaluation of the uptake of [(123)I]FIAU, [(123)I]IVFRU and [(123)I]IVFAU by normal mouse brain: potential for noninvasive assessment of HSV-1 thymidine kinase gene expression in gliomas.

Radioiodinated 5-iodo-1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)uracil (F *IAU) is most commonly used for noninvasive assessment of herpes simplex virus type 1 thymidine kinase (HSV-1-tk) gene expression. However, it does not permeate the intact blood-brain barrier (BBB) because of its moderate lipophilicity. In this work, three iodo-nucleosides, FIAU, IVFRU, and IVFAU, were radiolabeled with iodine-123 and tested for permeation of the BBB in mice and for potential measurement of HSV-1-tk gene expression in gliomas. The results demonstrate that brain uptake and retention of these nucleosides is not directly related to their lipophilicity. The low brain uptake of IVFAU, in conjunction with its higher and constant brain/blood ratio, may reflect greater stability against hydrolysis of the N-glycosidic bond. In vivo PET evaluations of [(124)I]IVFRU and [(124)I]IVFAU in tumor-bearing mice are warranted.

Immediate CEA for symptomatic carotid disease preferably performed under local anaesthesia is safe.

BACKGROUND: Previous general reservations against carotid endarterectomy (CEA) early after stroke, which were primarily based on concerns of postoperative intracerebral hemorrhage, are resolved. Moreover, a delay of surgery is proofed to be associated with a risk of recurrent cerebral ischemia. However, the complication rate of CEA seems to increase with less time interval to the onset of symptoms. The main purpose of this study was to assess the safety of very early CEA. PATIENTS AND METHODS: Patients having a symptomatic high-grade (> 70%) internal carotid artery (ICA) stenosis were referred by neurologists for CEA within different timeframes, so that they were later differentiated depending on whether surgery was performed within 2 days (immediate CEA = iCEA) or 2 weeks (urgent CEA = uCEA) after neurological deficits have occurred primarily. The perioperative complication rate in these groups was than evaluated and compared. RESULTS: From January 2000 until August 2006 130 consecutive patients (median age 68 years, range: 42-90; 66% male, 34%female)presenting with an ipsilateral TIA (n = 80), stroke (n = 50) underwent iCEA (n = 40) or uCEA (n = 90). Demographic and clinical characteristics were equally distributed between treatment groups. Mostly (121/130), CEA was performed under local anaesthesia with selective shunt use which became necessary in 26%. Besides postoperative hemorrhage (n = 4), cardiac complications (n = 2) and temporary cranial nerve lesions (n = 2), new perioperative neurological deficits occurred in total in 8 patients of which 6 were temporary. The other 2 patients developed strokes of which one patient died. Therefore, the combined stroke- and mortality rate was 1.5% (2/130) for the whole study population. With regard to the timing of surgery, a single incident was observed after iCEA (1/40) which also was the only intracerebral hemorrhage. CONCLUSIONS: It seems that patients with a symptomatic high-grade ICA stenosis can undergo CEA particularly under local anaesthesia as soon as possible without anticipating an increased complication rate.

HSV-1 amplicon-mediated post-transcriptional inhibition of Rad51 sensitizes human glioma cells to ionizing radiation.

Standard treatment for glioblastoma multiforme and other brain tumors consists of surgical resection followed by combined radio-/chemotherapy. However, radiation resistance of tumor cells limits the success of this treatment, and the tumors invariably recur. Therefore, the selective inhibition of molecular mediators of radiation resistance may provide therapeutic benefit to the patient. One of these targets is the Rad51 protein, which is a key component of the homologous recombinational repair of DNA double-strand breaks. Here, we investigated whether post-transcriptional silencing of Rad51 by herpes simplex virus-type 1 (HSV-1) amplicon vector-mediated short interfering RNA expression can enhance the antitumor effect of radiation therapy. We demonstrate that these vectors specifically and efficiently inhibited the radiation-induced recruitment of Rad51 into nuclear foci in human glioma cells. The combination of vector-mediated silencing of Rad51 expression and treatment with ionizing radiation resulted in a pronounced reduction of the survival of human glioma cells in culture. In athymyc mice, a single intratumoral injection of Rad51-specific HSV-1 amplicon vector followed by a single radiation treatment resulted in a significant decrease in tumor size. In control animals, including mice that received an intratumoral injection of Rad51-specific amplicon vector but no radiation treatment, the tumor sizes increased.

Role of in vivo imaging of the central nervous system for developing novel drugs.

Over the past decade imaging technologies employed in clinical neurosciences have significantly advanced. Imaging is not only used for the diagnostic work-up of neurological disorders but also crucial to follow up on therapeutic efforts. Using disease-specific imaging parameters, as read-outs for the efficiency of individual therapies, has facilitated the development of various novel treatments for neurological disease. Here, we review various imaging technologies, such as cranial computed tomography (CT), magnetic resonance imaging (MRI) and spectroscopy (MRS), positron emission tomography (PET) and single-photon emission computed tomography (SPECT), with respect to their current applications in non-invasive disease phenotyping and the measurement of therapeutic outcomes in neurology. In particular, applications in neuro-oncology, Parkinson's disease, Alzheimer's disease, and cerebral ischemia are discussed. Non-invasive imaging provides further insights into the molecular pathophysiology of human diseases and facilitates the design and implementation of improved therapies.

Primary stroke unit treatment followed by very early carotid endarterectomy for carotid artery stenosis after acute stroke.

BACKGROUND: Although it is recognized that carotid endarterectomy (CEA) is the treatment of choice in symptomatic internal carotid artery (ICA) stenosis, in the past, very early CEA has been shown to carry substantial risks. We assessed an interdisciplinary concept of very early CEA in patients with high-grade (>70%) symptomatic ICA stenosis at a single center. PATIENTS AND METHODS: The course of treatment and outcomes of patients who underwent CEA as early as possible after being referred to the stroke unit for symptoms of transient ischemic attack and stroke were prospectively evaluated, including the following parameters: age, severity of ischemia-related symptoms according to the modified Rankin scale, duration of symptoms until admission, multimodal imaging findings (color-coded duplex, cranial computed tomography, magnetic resonance imaging, positron emission tomography), duration until CEA, perioperative course and complications, as well as duration of in-hospital care. RESULTS: Fifty consecutive patients (median age 68 years, range 44-90) with clinical and imaging signs of transient ischemic attack (n = 19) or stroke (n = 31) were included from January 2000 until December 2004. All except 1 patient showed a preoperative Rankin < 4. There was a median time period of 6 h between the onset of symptoms and admission (range 1 h to 15 days) and a median duration of 4 days after admission until operation (range 1-21 days). Seven patients underwent CEA of the contralateral, severely stenosed ICA after symptomatic ipsilateral ICA occlusion. Four out of 5 patients who primarily underwent systemic thrombolysis recovered almost completely. Three patients (6%) experienced a clinical deterioration before surgery. In the majority of patients (43/50), CEA was performed under local anesthesia with selective shunt use which became necessary in 26%. Three patients (6%) had postoperative worsening due to new infarcts. In 2 cases, an intracerebral hemorrhage occurred, of which 1 remained asymptomatic. In 1 case, surgical revision was necessary because of an ICA thrombosis without permanent neurological decline. Patients were discharged after a median time of 14.5 days (range 4-44). CONCLUSIONS: After careful selection and preparation in a stroke unit, patients with acute stroke due to carotid stenosis can undergo very early CEA under local anesthesia with a perioperative risk comparable with the risk of later endarterectomy, therefore preventing very early stroke recurrences.

Autologous blood stem cell transplantation in refractory systemic lupus erythematodes with recurrent longitudinal myelitis and cerebral infarction.

Autologous hematopoietic stem cell transplantation (ASCT) has the potential to eliminate autoreactive lymphocytes and may represent a therapeutic option for patients with refractory autoimmune diseases. We describe a 19-year old woman with neuropsychiatric systemic lupus erythematodes (NPSLE) presenting with acute longitudinal myelitis and aseptic meningitis. Despite therapy with methylprednisolone and cyclophosphamide (CYC), recurrence of longitudinal myelitis and a disabling stroke-like relapse occurred. Hematopoietic stem cells were mobilized by CYC at 2 g/m2 and G-CSF. The patient was conditioned by CYC at 200 mg/kg and anti-thymocyte globulin and 3.6 x 10(6) CD34+ cells/kg were infused. Hematopoietic regeneration was observed on day 12 after ASCT. Currently, 18 months after ASCT, the patient is in clinical remission with no evidence for residual serological or neuroradiological activity of SLE. Although a longer follow-up will be needed to reliably assess the efficacy of ASCT in this patient, the present case demonstrates that ASCT may represent a therapeutic option for patients with severe NPSLE.

Stroke after initiation of interferon-beta treatment for relapsing-remitting disseminated white matter disease.

BACKGROUND: Interferon-beta (INF-beta) is effective and used in reducing exacerbation frequency and disease progression in multiple sclerosis. In certain circumstances, INF-beta can lead to rare side effects. AIMS OF THE STUDY: We report the case of a 34-year-old female patient satisfying the McDonald criteria of multiple sclerosis without showing typical pathologic changes in cerebrospinal fluid (CSF). After introduction of INF-beta treatment, she quickly developed further progression of her disseminated neurological symptoms and finally an ischemic cerebral infarction. METHODS: Evaluation of the patient included arterial angiography, magnetic resonance and positron emission tomography, histopathological assessment as well as a broad spectrum of serum and CSF analysis. RESULTS: All diagnostic evaluations and the clinical course revealed evidences for a primary angiitis of the CNS. We discuss the possible worsening due to inappropriate INF-beta treatment in cerebral angiitis promoting severe cerebrovascular insufficiency. CONCLUSION: The authors suggest that all diagnostic multiple sclerosis criteria including typical CSF findings should be ascertained before INF-beta treatment is initiated.

[Fatal familial insomnia: case presentation and discussion of typical clinical and imaging findings]. / Fatale familiäre Insomnie: Kasuistik zur Darstellung der klinischen und bildgebenden Befunde.

Fatal familial insomnia (FFI) is a hereditary prion disease caused by a mutation in codon 178 of the prion protein gene PRNP on chromosome 20. It is characterized by disturbed night sleep, resulting in daily vigilance perturbations and a variety of other neurological symptoms. We present the case of a 46-year-old woman deteriorating despite immunosuppressive treatment which was initiated suspecting cerebral vasculitis as the cause of her progressive neurological symptoms. The correct diagnosis was established only post mortem. Based on the case presented here, we discuss typical clinical symptoms and imaging findings. In particular, we outline how modern diagnostic methods such as positron emission tomography with [(15)O]H(2)O and [(18)F]FDG and single photon emission computed tomography can add valuable information to results from conventionally performed imaging techniques and genetic testing.