Walter Struhal

A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease.

To identify rare causal variants in late-onset Parkinson disease (PD), we investigated an Austrian family with 16 affected individuals by exome sequencing. We found a missense mutation, c.1858G>A (p.Asp620Asn), in the VPS35 gene in all seven affected family members who are alive. By screening additional PD cases, we saw the same variant cosegregating with the disease in an autosomal-dominant mode with high but incomplete penetrance in two further families with five and ten affected members, respectively. The mean age of onset in the affected individuals was 53 years. Genotyping showed that the shared haplotype extends across 65 kilobases around VPS35. Screening the entire VPS35 coding sequence in an additional 860 cases and 1014 controls revealed six further nonsynonymous missense variants. Three were only present in cases, two were only present in controls, and one was present in cases and controls. The familial mutation p.Asp620Asn and a further variant, c.1570C>T (p.Arg524Trp), detected in a sporadic PD case were predicted to be damaging by sequence-based and molecular-dynamics analyses. VPS35 is a component of the retromer complex and mediates retrograde transport between endosomes and the trans-Golgi network, and it has recently been found to be involved in Alzheimer disease.

Stroke and cancer: a review

Stroke is a disabling disease and can add to the burden of patients already suffering from cancer. Several major mechanisms of stroke exist in cancer patients, which can be directly tumour related, because of coagulation disorders, infections, and therapy related. Stroke can also occur as the first sign of cancer, or lead to its detection. The classical literature suggests that stroke occurs more frequently in cancer patients than in the average population. More recent studies report a very similar incidence between cancer and non‐cancer patients. However, there are several cancer‐specific types and causes of stroke in cancer patients, which need to be considered in each patient. This review classifies stroke into ischaemic, haemorrhagic, cerebral venous thrombosis and other rarer types of cerebrovascular disease. Its aim is to identify the types of stroke most frequently associated with cancer, and give a practical view on the most common and most specific types of stroke. The diagnosis of the cause of stroke in cancer patients is crucial for treatment and prevention. Management of different stroke types will be briefly discussed.

The End-of-Life Hospital Setting in Patients with Glioblastoma

Despite aggressive treatment, outcome of patients with glioblastoma is poor. Several distinct clinical problems arise in the terminal stage of this disease. The purpose of this study was to evaluate the end-of-life phase in a hospital setting in patients with glioblastoma. Twenty-nine consecutive patients with glioblastoma, who died in our department, were included in this analysis regarding symptoms, medication, diagnostics, and interventional procedures. The patients were comparable with respect to age, gender, and overall survival with data from the literature. Relevant clinical symptoms, medications, diagnostics, well as interventional procedures increased continuously toward end of life. Pain, epileptic seizures, and symptoms of brain edema were the most frequent clinical symptoms. According to this, most patients were on antiepileptic drugs (AED), steroids, and analgesics. In the last phase, symptoms from brain edema, fever, decrease of vigilance, dysphagia, and pneumonia were the prominent clinical features. Our study demonstrates that the end of life in patients with glioblastoma has several periods with different clinical aspects with respect to symptoms and treatment.

Peripheral nerve involvement in lymphoma: the meninges as the crucial barrier between meningoradicular spread and neurolymphomatosis.

Dear Editor, Peripheral nerves in lymphoma can be involved due to toxic, immunological, paraneoplastic, and rarely neoplastic causes. Neurologists are often involved in identifying the site and cause of peripheral nerve lesions and contribute to a major part in therapeutic decisions. Neoplastic involvement of the peripheral nervous system in systemic non-Hodkgin’s lymphoma (NHL) has been subject to many investigations and a recent review (Kelly and Karcher, 2005). Most frequently, meningoradicular involvement occurs, whereas other types of peripheral nerve infiltration as neurolymphomatosis, angiotrophic lymphoma (Vital et al., 1989), or local nerve infiltration are rare. Two cases of lymphoma infiltration are presented and compared, one with the classic meningoradicular type, and one with neurolymphomatosis and sparing of the cerebrospinal fluid (CSF) and spinal nerve roots.

The global perspective on neurology training: the World Federation of Neurology survey.

This World Federation of Neurology (WFN) study aimed to characterize the status quo of post-graduate neurology training throughout the world and enable a better orientation on global training in neurology. Basic data on training curricula and working conditions of neurology residents and neurologists in 39 countries worldwide were evaluated. Our data show considerable differences in manpower and training, but a continuous improvement within the last 10 years of observation. Worldwide a spread of interim evaluations and final examinations of different types are used. Online resources will undoubtedly profoundly change skill and knowledge acquisition and training practices in Neurology in the coming years.

VPS35 Parkinson's disease phenotype resembles the sporadic disease.

Recently a new autosomal dominant Parkinson’s disease mutation (p.Asp620Asn) in the VPS35 gene was discovered. The clinical features of 14 PD patients with this mutation from three Austrian families were evaluated. Age at disease-onset appears lower and depression was more common in Austrian patients compared to sporadic PD patients. However, we were unable to identify a specific clinical maker of VPS35 patients, who otherwise resemble sporadic PD patients.

The European association of young neurologists and trainees: advocating young neurologists in Europe

The European Association of Young Neurologists and Trainees was founded 10 years ago to advocate the interests of young neurologists in Europe. Key objectives could be achieved like representing young neurologists within major European bodies and supporting European exchange. In addition, interconnecting young neurologists and informing on important subjects including grant possibilities are a major field of activity. Neurology is an expanding field, which motivates many young doctors to enter neurology training programmes. Training quality has developed into a key issue in neurology. However, organizations working in the field of improving training quality are often lead by colleagues who have completed their training several years ago. In order to organize a training curriculum closer to the interests of today s trainees, a group of young residents formed what is now known as European Association of Young Neurologists and Trainees (EAYNT). This organization is in place to provide opinions and independent feedback for young neurologists, it also aims at arriving at minimal requirement definitions, training curricula or assessments in order to improve training.

The phoenix from the ashes: cardiovascular autonomic dysfunction in behavioral variant of frontotemporal dementia.

BACKGROUND Patients with autonomic failure may experience postural dizziness, syncope, and falls. Identifying symptomatic dysautonomia in dementia is of importance to ensure appropriate management and reduce risk of falls. OBJECTIVE The aim of this prospective study is to identify cardiovascular autonomic dysfunction in patients suffering from behavioral variant of frontotemporal dementia (bvFTD), compared to Alzheimers disease (AD). METHODS Patients were prospectively recruited from 2009 until 2013. Clinical autonomic function tests were carried out in an Autonomic Unit according to Ewings cardiovascular battery. Parasympathetic tests included resting heart rate variability, deep breathing, and Valsalva. Sympathetic function tests compromised blood pressure regulation on valsalva, cutaneous cold stimulation, and 70° head up tilt including of plasma noradrenaline. RESULTS 26 patients (17 female) with bvFTD and 18 patients (10 female) with AD were examined. Mean age of bvFTD was 69 ± 11 years, AD 74 ± 9 years. History taking was often not conclusive and did not correlate with autonomic signs. In 42% bvFTD patients and 44% AD patients, autonomic dysfunction was demonstrated. Manifest orthostatic hypotension (OH) was present in 19% of bvFTD and 33% AD patients. Frequency of autonomic dysfunction and orthostatic hypotension did not differ between bvFTD and AD, but were significantly higher than in healthy controls. Autonomic dysfunction was associated with an increased risk of falling (assessed with Tinetti Score). CONCLUSION This is the first prospective study to elucidate autonomic dysfunction in bvFTD patients. There is a considerable higher frequency of cardiovascular dysfunction and OH in bvFTD. History taking may be not conclusive thus cannot exclude cardiovascular dysautonomia.

Autonomic Dysfunction in Patients with Mild to Moderate Alzheimer’s Disease

BACKGROUND Autonomic function has received little attention in Alzheimers disease (AD). AD pathology has an impact on brain regions which are important for central autonomic control, but it is unclear if AD is associated with disturbance of autonomic function. OBJECTIVE To investigate autonomic function using standardized techniques in patients with AD and healthy age-matched controls. METHOD Thirty-three patients with mild to moderate AD and 30 age- and gender-matched healthy controls, without symptoms of autonomic dysfunction, underwent standardized autonomic testing with deep breathing, Valsalva maneuver, head-up tilt, and isometric handgrip test. Brachial pressure curve and electrocardiogram were recorded for off-line analysis of blood pressure and beat-to-beat heart rate (HR). RESULTS AD patients had impaired blood pressure responses to Vasalva maneuver (p < 0.0001) and HR response to isometric contraction (p = 0.0001). A modified composite autonomic scoring scale showed greater degree of autonomic impairment in patients compared to controls (patient: 2.1 ± 1.6; controls: 0.9 ± 1.1, p = 0.001). HR response to deep breathing and Valsalva ratio were similar in the two groups. CONCLUSION We identified autonomic impairment ranging from mild to severe in patients with mild to moderate AD, who did not report autonomic symptoms. Autonomic impairment was mainly related to impairment of sympathetic function and evident by impaired blood pressure response to the Vasalva maneuver. The clinical implications of this finding are that AD may be associated with autonomic disturbances, but patients with AD may rarely report symptoms of autonomic dysfunction. Future research should systematically evaluate symptoms of autonomic function and characterize risk factors associated with autonomic dysfunction.

Parkinson Patients’ Initial Trust in Avatars: Theory and Evidence

Parkinson’s disease (PD) is a neurodegenerative disease that affects the motor system and cognitive and behavioral functions. Due to these impairments, PD patients also have problems in using the computer. However, using computers and the Internet could help these patients to overcome social isolation and enhance information search. Specifically, avatars (defined as virtual representations of humans) are increasingly used in online environments to enhance human-computer interaction by simulating face-to-face interaction. Our laboratory experiment investigated how PD patients behave in a trust game played with human and avatar counterparts, and we compared this behavior to the behavior of age, income, education and gender matched healthy controls. The results of our study show that PD patients trust avatar faces significantly more than human faces. Moreover, there was no significant difference between initial trust of PD patients and healthy controls in avatar faces, while PD patients trusted human faces significantly less than healthy controls. Our data suggests that PD patients’ interaction with avatars may constitute an effective way of communication in situations in which trust is required (e.g., a physician recommends intake of medication). We discuss the implications of these results for several areas of human-computer interaction and neurological research.