Cerebellar fMRI Activation Increases with Increasing Working Memory Demands.

The aim of the present study was to explore cerebellar contributions to the central executive in n-back working memory tasks using 7-T functional magnetic imaging (fMRI). We hypothesized that cerebellar activation increased with increasing working memory demands. Activations of the cerebellar cortex and dentate nuclei were compared between 0-back (serving as a motor control task), 1-back, and 2-back working memory tasks for both verbal and abstract modalities. A block design was used. Data of 27 participants (mean age 26.6 ± 3.8 years, female/male 12:15) were included in group statistical analysis. We observed that cerebellar cortical activations increased with higher central executive demands in n-back tasks independent of task modality. As confirmed by subtraction analyses, additional bilateral activations following higher executive demands were found primarily in four distinct cerebellar areas: (i) the border region of lobule VI and crus I, (ii) inferior parts of the lateral cerebellum (lobules crus II, VIIb, VIII, IX), (iii) posterior parts of the paravermal cerebellar cortex (lobules VI, crus I, crus II), and (iv) the inferior vermis (lobules VI, VIIb, VIII, IX). Dentate activations were observed for both verbal and abstract modalities. Task-related increases were less robust and detected for the verbal n-back tasks only. These results provide further evidence that the cerebellum participates in an amodal bilateral neuronal network representing the central executive during working memory n-back tasks.

Electrophysiological detection of scalar changing perimodiolar cochlear electrode arrays: a long term follow-up study.

The position of the cochlear electrode array within the scala tympani is essential for an optimal hearing benefit. An intraoperative NRT-ratio was established, which can provide information about the intraoperative intracochlear electrode array position for perimodiolar electrodes. The aims of this study were to verify the longterm reliability for the NRT-ratio in perimodiolar electrodes. In a retrospective controlled study in a Tertiary Referral Center the electrophysiological data sets of 123 patients with implanted Nucleus Contour Advance electrodes were enclosed. Intraoperative and up to 1 year follow-up Auto-NRTs were evaluated. A NRT-ratio was calculated by dividing the average Auto-NRT data from electrode 16 to 18 with the average from electrode 5 to 7. Using a flat panel tomography system, the position of the electrode array was certified radiological. 31 patients with perimodiolar electrodes with 1 year follow-up data were included in the study. Eleven patients showed regular follow-up NRT-ratio with a correlated and radiologically confirmed electrode position. 20 patients showed mismatches between the NRT-ratio and the radiological position. These patients were highly variable in terms of duration of deafness and neural spectrum disorders. The NRT-ratio can be used to determine the intracochlear position of the electrode array for perimodiolar electrodes. Intraoperatively the NRT-ratio predicts the array position within the cochlea highly reliable for perimodiolar electrodes. We showed that after 6 months and a year, the NRT-ratio remains unchanged in most of the cases and shows a good correlation to the radiological determined position of the array. Nevertheless, the condition of the neural structures is highly important for reproducible responses. Limited validity is given in patients with degenerative and structural neural disorders.

[Intraocular Tumors other than Retinoblastoma in Children]. / Intraokulare Raumforderungen im Kindesalter ohne Retinoblastom.

The diagnosis of an intraocular mass in children can be challenging as invasive procedures are not allowed, in particular if a retinoblastoma may be present. In eyes with a unilateral tumour mass and loss of function enucleation with subsequent histopathological processing might be the only option to establish a diagnosis and to exclude a malignant tumour. The present paper deals with intraocular tumours other than retinoblastoma in children, with a special focus on the correlation of modern imaging techniques and histopathological findings.

Age effects in storage and extinction of a naturally acquired conditioned eyeblink response.

Acquisition of conditioned eyeblink responses is known to decline with age, and age-related decline has been related to a reduction of cerebellar size and function. The aim of the present study was to investigate age-related effects on storage-related processes and extinction of visual threat eyeblink responses (VTERs), conditioned responses which are naturally acquired in early childhood. Storage and extinction of VTERs were tested in 34 healthy participants with an age range from 21 to 74 years (mean age 41.6±16.3 years). High-resolution structural magnetic resonance images (MRI) were acquired in all subjects. Conventional volumetric measures and voxel-based morphometry (VBM) were performed at the level of the cerebellum. Storage and extinction of VTERs showed a significant age-dependent decline. Likewise, cerebellar volume decreased with age. Storage, but not extinction showed a significant positive correlation with age-dependent reduction of total cerebellar volume. VBM analysis showed that gray matter volume in circumscribed areas of intermediate lobules VI, and Crus I and II bilaterally were positively correlated with VTER storage (p<0.05, FWE corrected). Considering extinction, no significant correlations with gray matter cerebellar volume were observed. The present findings show that reduction of storage of learned eyeblink responses with age is explained at least in part by age-dependent decline of cerebellar function. Future studies need to be performed to better understand which brain areas contribute to age-dependent reduction of extinction.

Humor, laughter, and the cerebellum: insights from patients with acute cerebellar stroke.

Extent of cerebellar involvement in cognition and emotion is still a topic of ongoing research. In particular, the cerebellar role in humor processing and control of laughter is not well known. A hypermetric dysregulation of affective behavior has been assumed in cerebellar damage. Thus, we aimed at investigating humor comprehension and appreciation as well as the expression of laughter in 21 patients in the acute or subacute state after stroke restricted to the cerebellum, and in the same number of matched healthy control subjects. Patients with acute and subacute cerebellar damage showed preserved comprehension and appreciation of humor using a validated humor test evaluating comprehension, funniness and aversiveness of cartoons ("3WD Humor Test"). Additionally, there was no difference when compared to healthy controls in the number and intensity of facial reactions and laughter while observing jokes, humorous cartoons, or video sketches measured by the Facial Action Coding System. However, as depression scores were significantly increased in patients with cerebellar stroke, a concealing effect of accompanying depression cannot be excluded. Current findings add to descriptions in the literature that cognitive or affective disorders in patients with lesions restricted to the cerebellum, even in the acute state after damage, are frequently mild and might only be present in more sensitive or specific tests.

[Diagnosis and treatment of retinoblastoma: current strategies for effective tumour control and preservation of vision]. / Diagnose und behandlung des retinoblastoms: aktuelle konzepte zur sicheren tumorkontrolle bei erhalt des sehvermögens.

There are approximately 40 new cases of retinoblastoma in Germany per year. Children in whom the tumour is detected when still intraocular have an excellent overall survival rate (> 95%). However, the prognosis of metastasised retinoblastoma remains poor. About 40% of retinoblastoma patients have tumours in both eyes. For these children in particular it is important to save the eye and visual function as much as possible. There are several options for conservative treatment of localised retinoblastoma including laser coagulation, thermotherapy, cryotherapy, brachytherapy and chemotherapy. In recent years, systemic chemotherapy has become the established standard for primary treatment of intraocular retinoblastoma. In case series, intra-arterial, intravitreal and periocular applications of chemotherapy were also shown to be effective in treating intraocular retinoblastoma. Genetic testing is an integral part of the routine diagnostics of all patients. Mutation analysis of tumour material is invaluable for identification of somatic mutations including mutational mosaicism. Genetic testing also identifies children with heritable retinoblastoma, which represent 50% of cases. These children also have a predisposition for the development of tumours outside of the eye (second primary neoplasm). To adequately address these and other late effects in survivors of retinoblastoma, a multidisciplinary approach is needed that optimises therapy and long-term follow-up. Upcoming multicentre clinical trials will evaluate treatment concepts for localised and metastasised retinoblastoma to improve survival rates and quality of life of children with retinoblastoma. This article was translated and modified and was primarily published in Klin Padiatr 2012; 224: 339-347.

Humor and laughter in patients with cerebellar degeneration.

Humor is a complex behavior which includes cognitive, affective and motor responses. Based on observations of affective changes in patients with cerebellar lesions, the cerebellum may support cerebral and brainstem areas involved in understanding and appreciation of humorous stimuli and expression of laughter. The aim of the present study was to examine if humor appreciation, perception of humorous stimuli, and the succeeding facial reaction differ between patients with cerebellar degeneration and healthy controls. Twenty-three adults with pure cerebellar degeneration were compared with 23 age-, gender-, and education-matched healthy control subjects. No significant difference in humor appreciation and perception of humorous stimuli could be found between groups using the 3 Witz-Dimensionen Test, a validated test asking for funniness and aversiveness of jokes and cartoons. Furthermore, while observing jokes, humorous cartoons, and video sketches, facial expressions of subjects were videotaped and afterwards analysed using the Facial Action Coding System. Using depression as a covariate, the number, and to a lesser degree, the duration of facial expressions during laughter were reduced in cerebellar patients compared to healthy controls. In sum, appreciation of humor appears to be largely preserved in patients with chronic cerebellar degeneration. Cerebellar circuits may contribute to the expression of laughter. Findings add to the literature that non-motor disorders in patients with chronic cerebellar disease are generally mild, but do not exclude that more marked disorders may show up in acute cerebellar disease and/or in more specific tests of humor appreciation.

[New developments in molecular genetics and treatment of retinoblastoma]. / Neue Entwicklungen zur Genetik und Therapie des Retinoblastoms.

Retinoblastomas are the most frequent primary malignant intraocular tumours worldwide. Conventional and new treatment modalities have significantly improved the chance for survival and preservation of vision. The armamentarium of treatment modalities has been broadened recently by new techniques like intraarterial chemotherapy, which still has to be considered as experimental since long-term follow-up results are not yet available. The excellent prognosis for retinoblastomas in countries with a well developed health system is contrasted by the miserable prognosis for retinoblastomas in developing countries, which must be changed by a joint effort of all centres.

Magnet dislocation following magnetic resonance imaging in cochlear implant users: Diagnostic pathways and managment.

OBJECTIVES: Although modern cochlear implants (CIs) are approved for magnetic resonance imaging (MRIs) adverse events still occur with unacceptable frequency. Methods: In this retrospective study, magnet displacement due to MRIs was analysed. Relevant factors e.g. symptoms during MRI, diagnostics, surgical intervention following the diagnosis and possible subsequent damage were assessed. RESULTS: 16 patients were enclosed. All patients complained about pain while the scan was conducted. Computed tomography (CT) scans of the temporal bone or X-rays of the skull were performed to confirm diagnosis. Artefacts on CT scans delayed immediate diagnosis in some cases. DISCUSSION: Despite various studies demonstrating the range of adverse events related to CIs following MRI, little information is available on diagnosis and radiologic recognition of magnet dislocation. In patients complaining about pain following an MRI scan an X-ray of the head should be performed immediately. Most adverse events occur in radiological centres without expertise in cochlear implants. CONCLUSION: Comprehensive training of patients, surgeons and radiologists is the most efficient tool to prevent damage to the CI and the patient. X-ray of the skull is suggested to be used as the method of choice in imaging.

Myocardial scars are an underestimated cardiovascular burden in patients with internal carotid artery stenosis.

BACKGROUND: Patients with internal carotid artery (ICA) stenosis have an increased incidence of coronary heart disease. Evidence about the incidence of clinically silent myocardial infarction (MI) in these patients is limited. Contrast-enhanced cardiac magnetic resonance (CMR) imaging allows for the detection of minor myocardial damage. OBJECTIVE: We tested whether patients with ICA stenosis exhibit a relevant incidence of silent MI when assessed by CMR. METHODS: In a single-center study, 77 consecutive patients (age 68 +/- 7 years) with suspected ICA stenosis were imaged prospectively with a combined MRI protocol including T(1), T(2), diffusion-weighted imaging, fluid-attenuated inversion recovery, and contrast-enhanced MR angiography (CEMRA) imaging of the brain and a short (11 min) CMR protocol with left ventricular function and late gadolinium enhancement imaging. Blinded to any clinical information, two readers evaluated the cardiac and neuroradiologic examinations. RESULTS: Of 154 imaged ICA, 85 presented with stenosis and 17 were occluded. In 7 patients, the suspected ICA stenosis could not be confirmed by CEMRA. In the remaining 70 patients with ICA stenosis, 34.3% had cerebral lesions (15.7% with a homodynamic pattern,18.6% with territorial infarction). CMR detected MI in 29 (41%) patients, whereas ECG and medical history enabled diagnosis in only 7 (10%) patients. CONCLUSIONS: ICA stenosis patients have a higher incidence of myocardial scars proving silent MI when detected by contrast-enhanced CMR than clinically expected. Whether the presence and extent of silent MIs detected by CMR affect peri-interventional risk and prognosis of ICA stenosis patients remains to be evaluated in a large patient cohort with long-term follow-up.

Pronounced reduction of acquisition of conditioned eyeblink responses in young adults with focal cerebellar lesions impedes conclusions on the role of the cerebellum in extinction and savings.

Human cerebellar lesion studies provide good evidence that the cerebellum contributes to the acquisition of classically conditioned eyeblink responses (CRs). As yet, only one study used more advanced methods of lesion-symptom (or lesion-behavior) mapping to investigate which cerebellar areas are involved in CR acquisition in humans. Likewise, comparatively few studies investigated the contribution of the human cerebellum to CR extinction and savings. In this present study, young adults with focal cerebellar disease were tested. A subset of participants was expected to acquire enough conditioned responses to allow the investigation of extinction and saving effects. 19 participants with chronic surgical lesions of the cerebellum and 19 matched control subjects were tested. In all cerebellar subjects benign tumors of the cerebellum had been surgically removed. Eyeblink conditioning was performed using a standard short delay protocol. An initial unpaired control phase was followed by an acquisition phase, an extinction phase and a subsequent reacquisition phase. Structural 3T magnetic resonance images of the brain were acquired on the day of testing. Cerebellar lesions were normalized using methods optimized for the cerebellum. Subtraction analysis and Liebermeister tests were used to perform lesion-symptom mapping. As expected, CR acquisition was significantly reduced in cerebellar subjects compared to controls. Reduced CR acquisition was significantly more likely in participants with lesions of lobule VI and Crus I extending into Crus II (p<0.05, Liebermeister test). Cerebellar subjects could be subdivided into two groups: a smaller group (n=5) which showed acquisition, extinction and savings within the normal range; and a larger group (n=14) which did not show acquisition. In the latter, no conclusions on extinction or savings could be drawn. Previous findings were confirmed that circumscribed areas in lobule VI and Crus I are of major importance in CR acquisition. In addition, the present data suggest that if the critical regions of the cerebellar cortex are lesioned, the ability to acquire CRs is not only reduced but abolished. Subjects with lesions outside these critical areas, on the other hand show preserved acquisition, extinction and saving effects. As a consequence, studies in human subjects with cerebellar lesions do not allow drawing conclusions on CR extinction and savings. In light of the present findings, previous reports of reduced extinction in humans with circumscribed cerebellar disease need to be critically reevaluated.

Association of aneurysms and variation of the A1 segment.

BACKGROUND AND PURPOSE: Previous studies have described a correlation between variants of the circle of Willis and pathological findings, such as cerebrovascular diseases. Moreover, anatomic variations of the anterior cerebral artery (ACA) seem to correspond to the prevalence of aneurysms in the anterior communicating artery (ACoA). The aim of this study was to assess the prevalence of aneurysms in patients with anatomical/morphological variations of the circle of Willis. METHODS: We retrospectively analyzed 223 patients who underwent cerebral angiography between January 2002 and December 2010 for aneurysm of the ACoA. Diagnostic imaging was reviewed and statistically evaluated to detect circle of Willis anomalies, aneurysm size, and rupture. 204 patients with an unrelated diagnosis served as the control group. RESULTS: Variations of the A1 segment occurred significantly more frequently in the aneurysm group than in the control group. Mean aneurysm size in patients with grades I and III hypoplasia or aplasia was 6.58 mm whereas in patients with grade II hypoplasia it was 7.76 mm. CONCLUSIONS: We found that variations in the A1 segment of the ACAs are correlated with a higher prevalence of ACoA aneurysms compared with patients with a symmetric circle of Willis.

Complete endovascular occlusion of a cranial dural fistula using a venous "to the point" approach.

BACKGROUND AND OBJECT: Cranial dural arteriovenous fistulas are commonly treated using an endovascular method. In comparison to intracerebral arteriovenous malformations, it is important to reach the venous part of these malformations to maintain a complete occlusion. Therefore, often the venous side is totally occluded using coils and∕or glue. PATIENT AND METHODS: We describe a patient with an initially Type IIab (Cognard classification) left occipital cranial fistula. The patient suffered from an intense pulsate tinnitus. Therefore, the first embolization was performed using an approach via the dilated left middle meningeal artery using Onyx. The shunt of the fistula was reduced significantly but total occlusion was impossible. Therefore, the venous approach was used. Over a guiding catheter in the sigmoid sinus, the venous side of the fistula could be reached with a microcatheter. This part of the fistula was then completely occluded using coated and bare coils, without occluding the adjacent sinus. Control angiography of all previous feeders showed a complete occlusion of the fistula (used classification: Cognard). RESULTS: The fistula was entirely occluded. The patient's outcome was excellent. The patient did not develop any symptoms and no complication occurred due to the treatment. CONCLUSIONS: Direct occlusion of the venous part of an arteriovenous cranial fistula can be an option before an occlusion of the sinus has to be performed. This approach can lead to reduction of risk during the endovascular procedure and risk reduction in long-term follow-up.

Endovascular treatment of intracranial aneurysms in patients 65 years or older: clinical outcomes.

BACKGROUND AND PURPOSE: A controversial discussion concerning treatment of aneurysms in elderly patients exists. The aim of this study was to analyze clinical outcome in patients older than 65 years harboring intracranial aneurysms after endovascular treatment. MATERIALS AND METHODS: A total of 108 patients aged 65 years or older (mean age, 72 years, range, 65-87 years) were selected for endovascular treatment between 1997 and 2005. A total of 85 (78.7%) patients had an acute subarachnoid hemorrhage (SAH). SAH was classified according to Hunt and Hess (HH) grade: I (n = 16), II (n = 11), III (n = 33), IV (n = 19), and V (n = 6). There were 69 aneurysms that were small; 46, medium; 8, large; and 5, giant. Occlusion rate was categorized as complete (100%), subtotal (95% to 99%), and incomplete (<95%) obliteration according to the Raymond scale. RESULTS: Endovascular treatment was technically feasible in 108 of 113 aneurysms. Complete occlusion could be achieved in 80 patients; basal remnant was seen in 26 patients and a dog ear in 2 patients. Procedural complications included thrombotic vessel occlusion (n = 9), aneurysmal rupture (n = 4), and stenosis of the parent vessel (n = 2). The Glasgow Outcome Scale (GOS) for the patients with SAH after 6 months was good recovery (n = 43), moderate disability (n = 12), severe disability (n = 28), persistent vegetative state (n = 5), and death (n = 18). Outcome for the patients with unruptured aneurysms was good recovery in all 23 patients. On follow-up digital subtraction angiography (DSA) in 69 patients, complete aneurysmal occlusion was confirmed in 81% after 6 months. Five patients with recanalization were re-treated with coiling. CONCLUSION: Endovascular treatment of ruptured and unruptured intracranial aneurysms in this subgroup was safe and effective.