Seizure prevalence in neurodegenerative diseases-a study of autopsy proven cases.

BACKGROUND AND PURPOSE: Knowledge about the seizure prevalence in the whole symptomatic course, from disease onset to death, in neurodegenerative diseases (ND) is lacking. Therefore, the aim was to investigate seizure prevalence and associated clinical implications in neuropathologically diagnosed ND. METHODS: Clinical records of cases from the Neurobiobank Munich, Germany, were analyzed. Neuropathological diagnoses of the assessed cases included Alzheimer disease (AD), corticobasal degeneration (CBD), frontotemporal lobar degeneration (FTLD), Lewy body disease (LBD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Seizure prevalence during the whole symptomatic disease phase was assessed and compared amongst ND. Associations between first clinical symptom and seizure prevalence and between seizures and disease duration were examined. RESULTS: In all, 454 patients with neuropathologically diagnosed ND and with available and meaningful clinical records were investigated (AD, n = 144; LBD, n = 103; PSP, n = 93; FTLD, n = 53; MSA, n = 36; CBD, n = 25). Seizure prevalence was 31.3% for AD, 20.0% for CBD, 12.6% for LBD, 11.3% for FTLD, 8.3% for MSA and 7.5% for PSP. Seizure prevalence was significantly higher in AD compared to FTLD (p = 0.005), LBD (p = 0.001), MSA (p = 0.005) and PSP (p < 0.001). No other significant differences regarding seizure prevalence were found between the studied ND. Cognitive first symptoms in ND were associated with an increased seizure prevalence (21.1% vs. 11.0% in patients without cognitive first symptoms) and motor first symptoms with a decreased seizure prevalence (10.3% vs. 20.5% in patients without motor first symptoms). Seizures were associated with a longer disease duration in MSA (12.3 vs. 7.0 years in patients without seizures; p = 0.017). CONCLUSIONS: Seizures are a clinically relevant comorbidity in ND, particularly in AD. Knowledge of the first clinical symptom in ND may allow for estimation of seizure risk.

First symptom guides diagnosis and prognosis in neurodegenerative diseases-a retrospective study of autopsy proven cases.

BACKGROUND AND PURPOSE: Clinical diagnostic criteria for neurodegenerative diseases have been framed based on clinical phenomenology. However, systematic knowledge about the first reported clinical symptoms in neurodegenerative diseases is lacking. Therefore, the aim was to determine the prevalence and clinical implications of the first clinical symptom (FS) as assessed by medical history in neuropathologically proven neurodegenerative diseases. METHODS: Neuropathological diagnoses from the Neurobiobank Munich, Germany, were matched with clinical records for analyses of the diagnostic and prognostic values of FSs. RESULTS: In all, 301 patients with the neuropathological diagnoses Alzheimer disease (AD), progressive supranuclear palsy (PSP), frontotemporal lobar degeneration (FTLD), Lewy body disease (LBD) including the neuropathologically indistinguishable clinical phenotypes Parkinson disease and dementia with Lewy bodies, multiple system atrophy (MSA) and corticobasal degeneration (CBD) were studied. Memory disturbance was the most common FS in AD (34%), FTLD (19%) and LBD (26%), gait disturbance in PSP (35%) and MSA (27%) and aphasia and personality changes in CBD (20%, respectively). In a model adjusting for prevalence in the general population, AD was predicted by memory disturbance in 79.0%, aphasia in 97.2%, personality changes in 96.0% and by cognitive disturbance in 99.0%. Gait disturbance and tremor predicted LBD in 54.6% and 97.3%, coordination disturbance MSA in 59.4% and dysarthria FTLD in 73.0%. Cognitive FSs were associated with longer survival in AD (12.0 vs. 5.3 years; p < 0.001) and FTLD (8.2 vs. 4.1 years; p = 0.005) and motor FSs with shorter survival in PSP (7.2 vs. 9.7; p = 0.048). CONCLUSIONS: Assessing FSs in neurodegenerative diseases may be beneficial for accuracy of diagnosis and prognosis and thereby may improve clinical care and precision of study recruitment.

BrainNet Europe's Code of Conduct for brain banking.

Research utilizing human tissue and its removal at post-mortem has given rise to many controversies in the media and posed many dilemmas in the fields of law and ethics. The law often lacks clear instructions and unambiguous guidelines. The absence of a harmonized international legislation with regard to post-mortem medical procedures and donation of tissue and organs contributes to the complexity of the issue. Therefore, within the BrainNet Europe (BNE) consortium, a consortium of 19 European brain banks, we drafted an ethical Code of Conduct for brain banking that covers basic legal rules and bioethical principles involved in brain banking. Sources include laws, regulations and guidelines (Declarations, Conventions, Recommendations, Guidelines and Directives) issued by international key organizations, such as the Council of Europe, European Commission, World Medical Association and World Health Organization. The Code of Conduct addresses fundamental topics as the rights of the persons donating their tissue, the obligations of the brain bank with regard to respect and observance of such rights, informed consent, confidentiality, protection of personal data, collections of human biological material and their management, and transparency and accountability within the organization of a brain bank. The Code of Conduct for brain banking is being adopted by the BNE network prior to being enshrined in official legislation for brain banking in Europe and beyond.

Information technology for brain banking.

Implementing and maintaining the information technology (IT) infrastructure of a brain bank can be a daunting task for any brain bank coordinator, particularly when access to both funds and IT professionals is limited. Many questions arise when attempting to determine which IT products are most suitable for a brain bank. The requirements of each brain bank must be assessed carefully to ensure that the chosen IT infrastructure will be able to meet those requirements successfully and will be able to expand and adapt as the size of the brain bank increases. This chapter provides some valuable insights to be considered when implementing the IT infrastructure for a brain bank and discusses the pros and cons of various approaches and products.

Management of a twenty-first century brain bank: experience in the BrainNet Europe consortium.

Collections of human postmortem brains gathered in brain banks have underpinned many significant developments in the understanding of central nervous system (CNS) disorders and continue to support current research. Unfortunately, the worldwide decline in postmortem examinations has had an adverse effect on research tissue procurement, particularly from control cases (non-diseased brains). Recruitment to brain donor programmes partially addresses this problem and has been successful for dementing and neurodegenerative conditions. However, the collection of brains from control subjects, particularly from younger individuals, and from CNS disorders of sudden onset, remains a problem. Brain banks need to adopt additional strategies to circumvent such shortages. The establishment of brain bank networks allows data on, and access to, control cases and unusual CNS disorders to be shared, providing a larger resource for potential users. For the brain banks themselves, inclusion in a network fosters the sharing of protocols and development of best practice and quality control. One aspect of this collective experience concerns brain bank management, excellence in which is a prerequisite not only for gaining the trust of potential donors and of society in general, but also for ensuring equitable distribution to researchers of high quality tissue samples. This review addresses the legal, ethical and governance issues, tissue quality, and health and safety aspects of brain bank management and data management in a network, as well as the needs of users, brain bank staffing, donor programs, funding issues and public relations. Recent developments in research methodology present new opportunities for researchers who use brain tissue samples, but will require brain banks to adopt more complex protocols for tissue collection, preparation and storage, with inevitable cost implications for the future.