Hydrocephalus and other cerebrospinal fluid dynamic disturbances
Short description
Normal pressure hydrocephalus (NPH), an important treatable cause of dementia and gait impairment, affects up to 3% of people aged 65 or above. The condition is severely under-diagnosed, partly due to lack of good methods for diagnosis and prediction of the effect of treatment, a neurosurgical operation.
Our research aims to develop better diagnostic and predictive methods, improve assessment of clinical symtoms and explore underlying pathogenesis and involve advanced MR-methodology and CSF biomarkers in collaboration with scientists in Sweden and internationally.
The project can lead to major improvements in the care of patients with NPH with humanitarian and socio-economic benefits, but also to a better understanding of other neurodegenerative diseases.
Background
Idiopathic normal pressure hydrocephalus (iNPH), one of few reversible neurodegenerative disorders, is common in the elderly. However, only around 30% of patients are treated. The major reason for this is a current lack of precise methods for diagnosis and prediction of outcome after shunt surgery, a very effective treatment leading to improvement in up to 80% of the patients.
There is a need for better diagnostic methods and for better prediction of treatment outcomes. A better understanding of pathophysiological mechanisms, risk factors affecting long-term prognosis and the typical clinical picture may lead to a better and more individual treatment.
Aim
The main aim of the hydrocephalus research project is to develop better methods for diagnosing iNPH and for prediction of outcome after shunt surgery. Further, to develop better treatment methods, establish a better assessment of patients’ symptoms and signs and radiological changes with the use of clinical scales, and to explore the pathophysiology of the disease.
Ongoing research projects
Around 20% of the patient fail to show improvement after shunt surgery. In a large ongoing project, we study the predictive level of new biomarkers using advanced MR techniques and cerebrospinal fluid (CSF) biochemical markers.
Patients with iNPH and subcortical vascular ischemic disease show similar white matter changes and there is a bulk of evidence showing that the disorders can coexist. Using CSF biomarkers, we study pathophysiological differences between the disorders.
The underlying pathogenesis in iNPH is largely unknown. In earlier studies, we have shown that increasing age and vascular mechanisms are important factors. We are planning a population based study investigating the association between development of symptoms, enlargement of the ventricular system and appearance of white matter changes.
One factor that could possibly explain the age-related increase in NPH is a decrease in cilia / flagella function’s control of the flow of the CSF through the brain and the brain cavities. Together with researchers in Trondheim, we plan to measure the levels of cilia-related changes in the CSF. This project may lead to development of new, non-surgical treatment methods.
A major problem is that the diagnosis of NPH and the grading of the symptoms do not have internationally accepted criteria. Our research group has taken the initiative for a group of international researchers to develop new evidence-based criteria. The work has been successful for more than a year. We have also taken the initiative to propose a new scale for grading the severity of the symptoms and the outcome of the shunt operation. The project is executed in collaboration with researchers in Uppsala, Kuopio, Bologna and Porto Alegre (Brazil). We have just begun data collection and validation of the scale.
We also have ongoing projects in which we study patients' quality of life, life satisfaction and prevalence of depressive symptoms before and after shunt surgery and evaluate patients' and relatives' own estimate of the effect of treatment. The purpose of these projects is, among other things, to deepen the understanding of how the patients are affected by the disease.
It has been shown several times that the symptoms of NPH are generated in central parts of the brain. Our group has previously, and now recently with more advanced technology, shown that the brain stem can be a crucial structure for the generation of symptoms. We could also point to changes in the structure of the brain stem that may play a role in the assessment of treatment outcomes and help us understand important pathophysiological mechanisms.
The treatment of patients with NPH can be further improved. In collaboration with researchers in Linköping, we have conducted a randomized study in which we investigate whether intensive training can increase the degree of improvement after shunt surgery.
The hydrocephalus research project can have major positive impact on future care of patients with iNPH with favorable humanitarian and socio-economic effects. Results can be implemented in clinical routine with short delay. The project can also lead to a better understanding of other neurodegenerative disorders.
We collaborate with other research groups nationally and internationally and lead several multicenter studies. We participate in the international work of developing research and healthcare within the Hydrocephalus Society. In September 2021, the research group will host the annual Hydrocephalus World Yearly Meeting in Gothenburg, Hydrocephalus 2021.
Group members
Mats Tullberg, Adjuct Professor, Principal Investigator
Simon Agerskov, PhD, Consultant in Radiology
Gunilla Ahl-Börjesson, Administrator
Johanna Andersson, PhD, Resident Physician in Rehabilitation Medicin
Kerstin Andrén, PhD, Consultant in Neurology
Jonathan Arvidsson, PhD, Physicist, Medical physics and technology
Isabella Björkman-Burtscher, Professor in Neuroradiology
Clara Constantinescu, Doctoral Student, Medical Intern
Mia Emgard, Associate Professor, Resident Physician in Radiology
Dan Farahmand, Associate Professor, Consultant in Neurosurgery
Rebecca Grönning, Doctoral Student, Medical Intern
Per Hellström, PhD, Neuropsychologist
Daniel Jaraj, PhD, Resident Physician in Neurology
Anna Jeppsson, PhD, Resident Physician in Neurology
Oscar Jelnefjord, Associate Professor, Physicist, Medical physics and technology
Gökce Kilincalp, Doctoral Student, Consultant in Neurology
Judith Klecki, Administrator
Lena Kollén, PhD, Physiotherapist
Kerstin Lagerstrand, Associate Professor, Physicist, Medical physics and technology
Sanna Pääaho, Reseach Student, Psychologist
Majd Saadaldeen, Reseach Student, Resident Physician in Neurology
Carsten Wikkelsö, Professor Emeritus in Neurology
Doerthe Ziegelitz, PhD, Senior Consultant in Radiology
Research partners
The research group collaborates with Professors Kaj Blennow and Henrik Zetterberg, Neurochemistry Lab in, Mölndal.
We have a developed national and international collaboration with research groups in e.g. Linköping, Uppsala, Umeå, Östersund, Kuopio, Copenhagen, Bologna.
The research group leads several ongoing multicenter studies.
