- Electrophysiological and optogenetic assessment of cognition in hydrocephalic rats - Randomized multicenter trial on shunt treatment in NPH
Experimental and clinical studies on the pathophysiology of iNPH
I was lead investigator of experimental and clinical studies showing the impact of hydrocephalus on cerebral perfusion. Such studies demonstrated that hydrocephalus does not cause a cerebral blood flow impairment which is critical for the survival of neurons. Instead, my group demonstrated that a chronic “sublethal” impairment of cerebral perfusion causes permanent neuronal damage explaining the neurological deficits in hydrocephalic animals and patients.
1: Klinge PM, Samii A, Mühlendyck A, Visnyei K, Meyer GJ, Walter GF, Silverberg
GD, Brinker T. Cerebral hypoperfusion and delayed hippocampal response after
induction of adult kaolin hydrocephalus. Stroke. 2003 Jan;34(1):193-9. PubMed
2: Klinge PM, Berding G, Brinker T, Knapp WH, Samii M. A positron emission
tomography study of cerebrovascular reserve before and after shunt surgery in
patients with idiopathic chronic hydrocephalus. J Neurosurg. 1999
Samii M. PET and CBF studies of chronic hydrocephalus: a contribution to surgical
indication and prognosis. J Neuroimaging. 1998 Oct;8(4):205-9. PubMed PMID:
International guidelines for diagnosis and treatment of iNPH
I served as co-author in a group of renowned experts in the field of hydrocephalus to conduct a comprehensive review of existing literature (meta-analysis) to summarize the existing knowledge on the pathophysiology of normal pressure hydrocephalus und to provide, for the first time, guidelines for the diagnosis and treatment of NPH.
1: Marmarou A, Black P, Bergsneider M, Klinge P, Relkin N; International NPH
Consultant Group. Guidelines for management of idiopathic normal pressure
hydrocephalus: progress to date. Acta Neurochir Suppl. 2005;95:237-40. PubMed
2: Klinge P, Marmarou A, Bergsneider M, Relkin N, Black PM. Outcome of shunting
in idiopathic normal-pressure hydrocephalus and the value of outcome assessment
in shunted patients. Neurosurgery. 2005 Sep;57(3 Suppl):S40-52; discussion ii-v.
Review. PubMed PMID: 16160428.
3: Bergsneider M, Black PM, Klinge P, Marmarou A, Relkin N. Surgical management
of idiopathic normal-pressure hydrocephalus. Neurosurgery. 2005 Sep;57(3
Prospective clinical trial to improve diagnosing and monitoring of iNPH
I was lead PI of the first prospective clinical trial aiming to find standards for clinical diagnosing of normal pressure hydrocephalus. The study included 16 European centers and demonstrated the lack of diagnostic tests to predict a positive outcome following shunting. It was the major conclusion of the trial to demonstrate that it is not justified to exclude patients from surgical shunting just because of existing co-morbidity, for example Alzheimer’s disease or cerebrovascular disease.
1: Wikkelsø C, Hellström P, Klinge PM, Tans JT; European iNPH Multicentre Study
Group. The European iNPH Multicentre Study on the predictive values of resistance
to CSF outflow and the CSF Tap Test in patients with idiopathic normal pressure
Neurotechnology in nervous system disorders I had the opportunity to collaborate in a multidisciplinary project, aiming to develop an artificial structure to electrically contact severed peripheral nerves. I was responsible for the histological analysis of of nerve-implant specimens. We demonstrated, that neurons transplanted to severed nerve stumps may grow through interposed polyimide sieve implants (coated with strip conductors). Electrical stimulation via the implanted electrode results in muscle activity.
1: Klinge PM, Vafa MA, Brinker T, Brandis A, Walter GF, Stieglitz T, Samii M,
Wewetzer K. Immunohistochemical characterization of axonal sprouting and reactive
tissue changes after long-term implantation of a polyimide sieve electrode to the
transected adult rat sciatic nerve. Biomaterials. 2001 Sep;22(17):2333-43. PubMed
Samii M, Brinker T. Regeneration of a transected peripheral nerve by
transplantation of spinal cord encapsulated in a vein. Neuroreport. 2001 May
8;12(6):1271-5. PubMed PMID: 11338205.
Stem cell therapy of gliomas
I had the opportunity to collaborate in a multidisciplinary project, aiming to develop a stem cell therapy for gliomas: encapsulated mesenchymal stem cells (MSC’s) were implanted into the experimental glioma in rats. It was shown that the anti-inflammatory effects of transplanted MSC’s were effective to suppress the tumor growth in the rat model.
1: Kleinschmidt K, Klinge PM, Stopa E, Wallrapp C, Glage S, Geigle P, Brinker T.
Alginate encapsulated human mesenchymal stem cells suppress syngeneic glioma
growth in the immunocompetent rat. J Microencapsul. 2011;28(7):621-7. doi:
3: Klinge PM, Harmening K, Miller MC, Heile A, Wallrapp C, Geigle P, Brinker T.
Encapsulated native and glucagon-like peptide-1 transfected human mesenchymal
stem cells in a transgenic mouse model of Alzheimer's disease. Neurosci Lett.
2011 Jun 15;497(1):6-10. doi: 10.1016/j.neulet.2011.03.092. Epub 2011 Apr 12.
PubMed PMID: 21507341.
4: Glage S, Klinge PM, Miller MC, Wallrapp C, Geigle P, Hedrich HJ, Brinker T.
Therapeutic concentrations of glucagon-like peptide-1 in cerebrospinal fluid
following cell-based delivery into the cerebral ventricles of cats. Fluids
Barriers CNS. 2011 May 17;8:18. doi: 10.1186/2045-8118-8-18. PubMed PMID:
21575271; PubMed Central PMCID: PMC3114785.
I have an extensive research expertise in clinical and experimental neurosurgery, especially in the field of cerebrospinal fluid research. Having conducted or contributed to multiple clinical trials, I’m familiar with the organizational and legal regulatory requirements of such clinical studies.