Wernicke Encephalopathy: Typical and Atypical Findings in Alcoholics and Non-Alcoholics and Correlation with Clinical Symptoms.

PURPOSE: Clinical diagnosis of Wernicke encephalopathy (WE) can be challenging due to incomplete presentation of the classical triad. The aim was to provide an update on the relevance of standard MRI and to put typical and atypical imaging findings into context with clinical features. METHODS: In this two-center retrospective observational study, the local radiology information system was searched for consecutive patients with clinical or imaging suspicion of WE. Two independent raters evaluated T2-weighted imaging (WI), fluid-attenuation inversion recovery (FLAIR), diffusion WI (DWI), T2*WI and/or susceptibility WI (SWI), and contrast-enhanced (CE)-T1WI, and noted the involvement of typical (i.e., mammillary bodies (MB), periaqueductal grey (PAG), thalamus, hypothalamus, tectal plate) and atypical (all others) lesion sites. Unusual signal patterns like hemorrhages were also documented. Reported clinical features together with the diagnostic criteria of the latest guidelines of the European Federation of Neurological Societies (EFNS) were used to test for relationships with MRI biomarkers. RESULTS: 47 patients with clinically confirmed WE were included (Jan '99-Apr '23; mean age, 53 yrs; 70% males). Interrater reliability for imaging findings was substantial (κ = 0.71), with lowest agreements for T2WI (κ = 0.85) compared to all other sequences and for PAG (κ = 0.65) compared to all other typical regions. In consensus, 77% (n = 36/47) of WE cases were rated MRI positive, with FLAIR (n = 36/47, 77%) showing the strongest relation (χ2 = 47.0; P < 0.001) compared to all other sequences. Microbleeds in the MB were detected in four out of ten patients who received SWI, not visible on corresponding T2*WI. Atypical findings were observed in 23% (n = 11/47) of cases, always alongside typical findings, in both alcoholics (n = 9/44, 21%) and non-alcoholics (n = 2/3, 67%). Isolated involvement of structures, explicitly PAG (n = 4/36; 11%) or MB (n = 1/36; 3%), was present but observed less frequently than combined lesions (n = 31/36; 86%). A cut-off width of 2.5 mm for the PAG on 2D axial FLAIR was established between cases and age- and sex-matched controls. An independent association was demonstrated only between short-term memory loss and changes in the MB (OR = 2.2 [95% CI: 1.1-4.5]; P = 0.024). In retrospect, EFNS criteria were positive (≥ 2 out of 4) in every case, but its count (range, 2-4) showed no significant (P = 0.427) relationship with signal changes on standard MRI. CONCLUSION: The proposed sequence protocol (FLAIR, DWI, SWI and T1WI + CE) yielded good detection rates for neuroradiological findings in WE, with SWI showing microbleeds in the MB with superior detectability. However, false negative results in about a quarter of cases underline the importance of neurological alertness for the diagnosis. Awareness of atypical MRI findings should be raised, not only in non-alcoholics. There is limited correlation between clinical signs and standard MRI biomarkers.

[Clinical magnetic resonance imaging : Frequent incidental cerebral findings]. / Klinische Magnetresonanztomographie : Häufige zerebrale Zufallsbefunde.

The increasing use of magnetic resonance imaging (MRI) in clinical diagnostics means that patients and physicians are confronted more often with incidental findings. In the literature there are fluctuating data on the incidence of such findings and guidelines concerning the further procedure exist in only very few cases, such as incidental aneurysms and pituitary adenomas. The diagnostic and therapeutic implications which can be derived from incidental findings depend on multiple factors, such as anatomical location, patient age, comorbidity and patient wishes. For this reason it often makes sense to refer patients with incidental findings to an interdisciplinary neurological center at an early stage. In this review frequent incidental cerebral findings, epidemiological data, imaging criteria and, where possible, recommendations for the further procedure are shown.

The sclerostin-neutralizing antibody AbD09097 recognizes an epitope adjacent to sclerostin's binding site for the Wnt co-receptor LRP6.

The glycoprotein sclerostin has been identified as a negative regulator of bone growth. It exerts its function by interacting with the Wnt co-receptor LRP5/6, blocks the binding of Wnt factors and thereby inhibits Wnt signalling. Neutralizing anti-sclerostin antibodies are able to restore Wnt activity and enhance bone growth thereby presenting a new osteoanabolic therapy approach for diseases such as osteoporosis. We have generated various Fab antibodies against human and murine sclerostin using a phage display set-up. Biochemical analyses have identified one Fab developed against murine sclerostin, AbD09097 that efficiently neutralizes sclerostin's Wnt inhibitory activity. In vitro interaction analysis using sclerostin variants revealed that this neutralizing Fab binds to sclerostin's flexible second loop, which has been shown to harbour the LRP5/6 binding motif. Affinity maturation was then applied to AbD09097, providing a set of improved neutralizing Fab antibodies which particularly bind human sclerostin with enhanced affinity. Determining the crystal structure of AbD09097 provides first insights into how this antibody might recognize and neutralize sclerostin. Together with the structure-function relationship derived from affinity maturation these new data will foster the rational design of new and highly efficient anti-sclerostin antibodies for the therapy of bone loss diseases such as osteoporosis.

Differential Diagnosis of Acute Myelopathies: An Update.

Appropriate description may lead to adequate diagnostic and therapeutic measures, and therefore, a simple scheme to categorize and term the imaging findings of acute myelopathy is suggested based on current literature. Assigning imaging findings to five groups, that is (a) "segmental with rash," (b) "poliolike," (c) "granulomatous-nodular," (d) "longitudinally extensive transverse myelitis," (e) "short-segment ovoid or peripherally located," provides a rationale to lessen differential diagnoses. The key for understanding, proper description and differential diagnosis is the correlation of two time points: When did the first symptoms appear and when did imaging take place? Early infarction within the first 24 h will show neither swelling nor enhancement.

Differential diagnosis of white matter lesions: Nonvascular causes-Part II.

The knowledge of characteristic lesion patterns is important in daily practice imaging, as the radiologist increasingly is required to provide precise differential diagnosis despite unspecific clinical symptoms like cognitive impairment and missed elaborated neurological workup. This part II dealing with nonvascular white matter changes of proven cause and diagnostic significance aimed to assist the evaluation of diseases exhibiting lesions exclusively or predominantly located in the white matter. The etiologies commented on are classified as follows: (a) toxic-metabolic, (b) leukodystrophies and mitochondriopathies, (c) infectious, (d) neoplastic, and (e) immune mediated. The respective mode of lesion formation is characterized, and typical radiological findings are displayed. More or less symmetrical lesion patterns on the one hand as well as focal and multifocal ones on the other are to be analyzed with reference to clinical data and knowledge of predilection sites characterizing major disease categories. Complementing spinal cord imaging may be useful not only in acute and relapsing demyelinating diseases but in certain leukodystrophies as well. In neuromyelitis optica (NMO), the detection of a specific antibody and some recently published observations may lead to a new understanding of certain deep white matter lesions occasionally complicating systemic autoimmune disease.

Beyond delayed cerebral vasospasm: infarct patterns in patients with subarachnoid hemorrhage.

PURPOSE: Angiographic vasospasm (CVS) has been accused to be the main cause of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). However, treatment success including endovascular treatment remains to be improved. We performed a pattern analysis of ischemic lesions in SAH patients in the absence of angiographic cerebral vasospasm to generate further hypotheses concerning etiology and risk factors of DCI apart from vasospastic narrowing. METHODS: We retrospectively included 309 patients with cerebral infarcts after SAH. Vasospasm was assessed by means of CT or MR angiography and perfusion measurement or digital subtraction angiography. All clinical and radiological data were used to determine the most probable etiology for new infarcts. RESULTS: Twenty-seven percent of patients showed infarcts without presence of angiographic vasospasm. Seventy-three percent of these "atypical infarcts" were induced by complications of aneurysm therapy, 7 % by hypoxia, 2 % by ICP-related herniation. In 17 %, the etiology remained unclear; however, disturbances of the microcirculation for different reasons were the most likely cause in these patients. CONCLUSION: Beyond CVS and treatment complications, a not insignificant number of SAH patients suffered from infarcts of other etiology probably due to disturbance of the microcirculation. Therapeutic approaches for vasodilation of angiographic vasospasm alone should be reconsidered.

White matter lesions and vascular cognitive impairment: part 1: typical and unusual causes.

While the diagnosis of vascular dementia rests on established radiomorphological criteria, the term vascular cognitive impairment hitherto is less clear cut and hence the interpretation of white matter changes (WMC) widely held to be caused by vascular disease is pivotal. Part one of this review deals with the description of WMC and the underlying vascular etiologies. To some degree magnetic resonance (MR) imaging seems capable of differentiating these lesions by technical means and by depicting anatomical detail. Microangiopathy, notoriously causing white matter lesions, is focused in a broader sense, including inflammatory and hereditary causes of small vessel disease and corresponding to vascular diseases of the young. Accordingly, interpretation of a given lesion could fail if clinical aspects, such as age, guiding symptoms and acuteness are not taken into account.

Neuroradiological viewpoint on the diagnostics of space-occupying brain lesions.

Conventional magnetic resonance (MR) imaging of space-occupying lesions may answer most of the questions concerning the diagnosis and subsequent treatment strategies if patient age, clinical and paraclinical findings are considered as well. However, crucial and relevant differential diagnoses require additional MR methods, such as diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and magnetic resonance spectroscopy (MRS). In necrotic ring-enhancing lesions DWI may detect inflammatory processes, whereas characteristics of the peritumoral area may help to distinguish between metastases and glioblastomas. In solid tumors DWI, PWI and MRS may also aid the differentiation between low-grade gliomas and malignant tumors, such as gliomas WHO (World Health Organization) grade III and IV and lymphomas. This review briefly explains special MR methods with respect to brain tumors and illustrates the diagnostic pathways necessary for supplying a reliable diagnosis as well as optimal pre-operative imaging of space-occupying brain lesions.

MR imaging of midbrain pathologies.

The spectrum of pathologic processes affecting the midbrain features some differences to other brain areas. The midbrain is exposed to traumatic alterations due to its position between the tentorial edges, and some neurodegenerative and metabolic-toxic diseases may typically involve the midbrain. Isolated midbrain ischemia is rare, whereas the midbrain is typically part of the "top of the basilar" syndrome. Primary midbrain tumors are also infrequent and often show a benign clinical course. Apart from multiple sclerosis other inflammatory autoimmune processes and some infectious agents predominantly affect the brainstem including the midbrain. This review discusses the different pathologic processes of the midbrain, i.e., infarction, hemorrhage and trauma, inflammation, toxic and metabolic diseases, neurodegeneration, neoplastic diseases, as well as pathologies typically involving the perimesencephalic cisterns.

[Corpus callosum. Landmark of the origin of cerebral diseases]. / Corpus callosum. Landmarke für die Genese zerebraler Erkrankungen.

Diseases of the corpus callosum include developmental disorders, immunomodulated CNS diseases, vascular malformations, disturbances of metabolism including the electrolyte homeostasis, secondary degenerations and mechanical injuries. This report provides information on the differential diagnosis of reversible and irreversible pathological changes of the corpus callosum with special focus on the localization, which often allows conclusions on the pathogenesis to be drawn.

[Perioperative lesions of the corticospinal tract. Etiology, neuroradiological features and clinical outcome]. / Perioperative Läsionen des Tractus corticospinalis. Atiologie, neuroradiologische Befunde und klinischer Verlauf.

BACKGROUND: The neurosurgical resection of mass lesions in the vicinity of the corticospinal tract (CST) may induce a postoperative impairment of motor function. The etiology and localisation of lesions causing postoperative motor deterioration were analysed by preoperative and postoperative magnetic resonance imaging (MRI). PATIENTS AND METHODS: In 32 patients with mass lesions near the CST and intraoperative deterioration of the motor-evoked potentials, preoperative and postoperative MRI was performed and evaluated for new lesions along the CST. These lesions were classified into edema, infarction and haemorrhage. All patients were examined for perioperative central motor function. RESULTS: New lesions along the CST were found in 19 of the 32 patients. Postoperatively new or deteriorated motor function was found in 13 of these 19 patients (edemas: 4 out of 6, haemorrhages: 4 out of 7; infarctions: 5 out of 6). Of the 13 patients without new MRI lesion along the CST one had a new motor deficit. CONCLUSION: The postoperative MRI in patients with mass lesions near the CST and postoperative central motor deterioration sensitively showed the etiology and localisation of the lesion. Apart from being due to infarctions and haemorrhages, a larger number of postoperative motor impairments may be caused by edema.

[Postictal MR-changes. A rare and important differential diagnosis]. / Postiktale MR-Veränderungen. Eine seltene und wichtige Differenzialdiagnose.

BACKGROUND: Postictal MR findings are analyzed in the context of MR morphological differential diagnoses. PATIENTS AND METHODS: Postictal MRI was performed in 11 patients. The patterns of MR changes and their differential diagnoses were analyzed. RESULTS: Focal accentuation of signal increase in the cortex was found on T2-weighted images in 90% of these cases, pial enhancement in 70% and signal changes of the pulvinar/thalamus in 40%. The most common differential diagnoses were encephalitis, and in tumor patients carcinomatous involvement of the meninges. CONCLUSION: Postictal MR changes vary widely and are difficult to differentiate from illnesses such as encephalitis and carcinomatosis involving the meninges. Nevertheless, knowledge of the typical pattern of postictal MR findings and the clinical course may help to avoid mistaken diagnoses.

Reversible bilateral pyramidal tract lesions after hypertensive crisis and cerebral seizures.

This is a rare case of reversible high signal-intensity changes along the pyramidal tracts in a patient with reversible posterior leukoencephalopathy syndrome (RPLS). A 38-year-old man was admitted to hospital for loss of consciousness and generalized seizures. His systolic blood pressure was 220 mmHg. Neurological examination revealed bilateral pyramidal-tract signs, and paresis of the right arm. Initial MRI showed increased signal intensities on T2-weighted, FLAIR and diffusion-weighted imaging in the following regions: bilateral temporo-occipital white matter and cortex, dorsal parts of the lentiform nuclei, bilateral caudate nuclei and external capsule. High signal intensities were observed in the pyramidal tracts as well. On patient follow-up, MRI signal abnormalities and clinical symptoms were completely resolved after antihypertensive treatment.

[Cerebral lymphomatoid granulomatosis. A case report]. / Zerebrale lymphomatoide Granulomatose. Ein Fallbericht.

We present the case of a 57-year-old patient who was admitted with fever and disorientation. The cerebrospinal fluid showed a mild pleocytosis and increased protein content. MR imaging revealed multiple lesions, particularly in the subcortical white matter, with spot like central contrast enhancement. The diagnosis of lymphomatoid granulomatosis was finally made through open lung biopsy. Despite treatment with rituximab and, in the later course of the disease, additionally with cyclophosphamide, the patient died 3 months after the diagnosis was made.

[Primary central nervous system degeneration in elderly patients. Characteristic imaging features]. / Primäre Degeneration des ZNS im Alter. Bildgebung charakteristischer Atrophiemuster.

Despite further development of new magnetic resonance imaging techniques, e.g., diffusion tensor imaging and 1H magnetic resonance spectroscopy, structural imaging will continue to play a major role in the diagnosis of primary central nervous system degeneration in ageing. Characteristic imaging patterns of multisystem atrophies and primary dementias as well as differential diagnostic features are demonstrated. While such features may have high specificity, their sensitivity is low especially in cross-sectional studies. Longitudinal studies are the optimal method to characterize the dynamic neuroanatomical correlates of the disease. However, according to disease duration and progression, neuroimaging will show increased overlapping and convergence of pathological changes in multisystem atrophy as well as in dementia.

[Organ-preserving treatment in inoperable patients with primary oral and oropharyngeal carcinoma: chances and limitations]. / Organerhaltende Therapie bei inoperablen Patienten mit primären Mundhöhlen- und Oropharynxkarzinomen: Möglichkeiten und Grenzen.

INTRODUCTION: The aim of this study was to demonstrate the chances of nonoperative therapy in those patients from an unselected population suffering from primary previously untreated squamous cell carcinomas of the oral cavity and the oropharynx who did not seem to be operable. PATIENTS AND METHODS: Following interdisciplinary counseling and extensive individual discussion, 72 (21%) of 340 consecutive patients (1997-2004) did not or did not reasonably seem to be operable; three other patients with stage II disease refused surgery. Of the inoperable patients, 95%suffered from far-advanced stage IV disease, 8% had distant metastases, 14% had synchronous malignancies, 9% were aged over 85 years combined with advanced malignant disease, and nearly 50% were limited in their activity or were even bedridden. Depending on fitness and tumor extent, three therapy regimens were used: intra-arterial (i.a.) high-dose chemotherapy with systemic antagonization for palliation, induction with this i.a. high-dose chemotherapy followed by additional radiotherapy, and induction with the i.a. high-dose chemotherapy followed by additional radiochemotherapy. RESULTS: Thirty-two patients were treated with i.a. chemotherapy alone for palliation with few acute side effects. The response rate was 34%, and a further growth of the tumour could be inhibited in 49%. The 1- and 2-year survival rates were 21 and 14%, respectively. The three patients who refused surgery experienced complete clinical remission and survived 8, 6, and 2 years, respectively, to date. Twenty-three patients were fit enough to receive additional radiotherapy, and 17 an additional radiochemotherapy. Of the patients, 22% had to cut short additional radiotherapy and 47% had to discontinue concomitant chemotherapy. The 1- and 2-year survival rates were 41 and 25%, respectively; 14 of these irradiated patients experienced long-lasting complete clinical remission >2 years. CONCLUSION: About 20% of the patients classified as inoperable could achieve long-lasting remission. Viewed with caution, sex (male), performance state (ECOG) <3, and positive response to i.a. chemotherapy could be regarded as predictors for therapeutic success. The combination of i.a. chemotherapy and radiochemotherapy seemed to be most successful. Conversely, the therapies offered could not achieve a substantial improvement of survival in 80% of patients classified as inoperable; the most successful therapy combination could be offered to merely 23% of patients as classified inoperable due to reduced general condition. The i.a. high-dose chemotherapy has to be regarded as a well tolerated and effective palliation. This descriptive analysis must be followed by specific studies to establish clinical treatment recommendations.

Visual search in patients with subcortical vascular dementia: short fixations but long reaction times.

Visual search is a cognitive function of high ecological relevance. It involves rapid alternations between allocating and shifting attention. In patients with Alzheimer's disease, the duration of fixations during visual search increases already in the early stage of the illness. Subcortical vascular dementia (SVD), a newly defined subgroup of vascular dementia, has not yet been examined in this respect. SVD affects patients with a history of lacunar infarctions and/or transient ischemic attacks, focal neurological signs and evidence of subcortical white matter lesions as well as lacunes in the deep grey matter. Here, we report our findings from tracking eye movements during a visual search task with different array sizes in 9 patients with SVD and compare the number and duration of eye fixations they made with the values obtained in 9 healthy elderly control subjects. While patients with SVD were significantly slower in the tasks with longer center to target distances (mean reaction time), the number and duration of fixations they made did not differ from those in controls. Impairment of visual search in patients with SVD seems to be an effect of general cognitive slowing in more demanding arrays of visual search rather than a specific deficit in parameters of eye fixation.

Importance of diffusion-weighted imaging in the diagnosis of cystic brain tumors and intracerebral abscesses.

OBJECTIVE: It is often difficult to decide whether a cystic brain lesion is a tumor or an abscess by means of conventional MRI techniques. The immediate diagnosis of a brain abscess is important for the patient's outcome. Our goal was to study the ability of diffusion-weighted imaging and calculation of the apparent diffusion coefficient (ADC) to differentiate between these two pathologies. PATIENTS AND METHODS: Ten patients (five men, five women) with cystic brain lesions were examined with MRI. The ADC maps were calculated for each subject and the ADC value of each lesion was measured. Histology revealed glioblastoma multiforme in six patients and abscess in four patients. RESULTS: All brain abscesses showed markedly hyperintense signal changes on diffusion-weighted imaging, whereas the appearance of glioblastoma varied from slightly hyperintense to hypointense signal conversion. The mean ADC value calculated in the six patients with cystic brain tumor was: 2.05 x 10 (-3) mm(2)/s (1.38-2.88 x 10 (-3) mm(2)/s). The mean ADC value of the four patients with brain abscess was: 0.57 x 10 (-3) mm(2)/s (0.38-0.77 x 10 (-3) mm(2)/s). CONCLUSION: Diffusion-weighted imaging and calculation of ADC maps constitute a helpful tool to differentiate between cystic brain tumors and brain abscesses.

Effects of arousing emotional scenes on the distribution of visuospatial attention: changes with aging and early subcortical vascular dementia.

BACKGROUND: The modulation of attention by emotionally arousing stimuli is highly important for each individual's social function. Disturbances of emotional processing are a supportive feature for the diagnosis of subcortical vascular dementia (SVD). We address here whether these disturbances might be useful as an early disease marker. METHODS: In order to examine the modulation of visual attention by emotionally arousing stimuli of different valence, 12 elderly patients with early SVD, 12 age-comparable healthy adults and 12 young healthy subjects were studied while looking at pairs of pictures from the International Affective Picture Battery that were either neutral-neutral, neutral-positive or neutral-negative in terms of emotional content. Eye movements were recorded with an infrared eye-tracking system. The direction of the first saccade and the dwell time during the 10 s of presentation were measured and compared among groups with parametric tests. RESULTS: All subjects showed a modulation of initial attentional orienting as well as a higher percentage of dwell time towards the pictures containing emotional material. Patients with SVD and old controls did not differ in either experimental measure. Young patients showed a stronger bias towards emotionally negative material than both groups of older individuals. CONCLUSIONS: Modulation of visuospatial attention is preserved in early SVD. This might have implications for therapeutic interventional approaches. A weakened sustained attention towards negative but not positive emotional pictures in the elderly is in accordance with the socioemotional selectivity theory, describing a relative selection of positive stimuli with aging.