Table Of ContentAdvances in Experimental Medicine and Biology 1394
Nima Rezaei
Sara Hanaei Editors
Human Brain
and Spinal Cord
Tumors: From Bench
to Bedside. Volume 1
Neuroimmunology and Neurogenetics
Advances in Experimental Medicine
and Biology
Volume 1394
Series Editors
Wim E. Crusio, Institut de Neurosciences Cognitives et Intégratives
d’Aquitaine, CNRS and University of Bordeaux, Pessac Cedex, France
Haidong Dong, Departments of Urology and Immunology, Mayo Clinic,
Rochester, MN, USA
HeinfriedH.Radeke,InstituteofPharmacology&Toxicology,Clinicofthe
Goethe University Frankfurt Main, Frankfurt am Main, Hessen, Germany
Nima Rezaei , Research Center for Immunodeficiencies, Children’s
Medical Center, Tehran University of Medical Sciences, Tehran, Iran
Ortrud Steinlein, Institute of Human Genetics, LMU University Hospital,
Munich, Germany
Junjie Xiao, Cardiac Regeneration and Ageing Lab, Institute of
Cardiovascular Sciences, School of Life Science, Shanghai University,
Shanghai, China
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Nima Rezaei (cid:129) Sara Hanaei
Editors
Human Brain and Spinal
Cord Tumors: From
Bench to Bedside.
Volume 1
Neuroimmunology
and Neurogenetics
123
Editors
NimaRezaei SaraHanaei
Department ofImmunology Department ofNeurosurgery
SchoolofMedicine,UniversalScientific Imam Khomeini Hospital Complex
Education andResearchNetwork Universal ScientificEducation
(USERN) andResearch Network (USERN)
Tehran University of Medical Tehran University of Medical
Sciences (TUMS) Sciences (TUMS)
Tehran,Iran Tehran,Iran
ISSN 0065-2598 ISSN 2214-8019 (electronic)
Advances in Experimental Medicine andBiology
ISBN978-3-031-14731-9 ISBN978-3-031-14732-6 (eBook)
https://doi.org/10.1007/978-3-031-14732-6
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We would like to dedicate the book to our families, whose
staunch encouragement and support made this whole work
possible.
May this book, through the joint collaboration of expert senior
and junior scientists, light the path to better understanding and
approaching the CNS tumors, leading to more favorable
survival outcomes and quality of lives of patients.
Foreword to the Book
One may ask the question Why another book on brain and spinal cord
tumors? Here, the answer lies in the question itself partially: There is no
other such timely and comprehensive overview on these two entities, which
share so many common features due to their intrinsically and ontologically
common grounds from genetics and embryology to morphology and to
diagnosis and treatment.
The two volumes of “Human Brain and Spinal Cord Tumors: From
BenchtoBedside”areproviding ajoint regardofboth brainandspinalcord
tumors. That makes sense from a merely biological point of view already.
Despitefrequentclinicallydisparatebehaviorofcertainintrinsictumors,such
as,i.e.,low-gradegliomasofthebrainvs.astrocytomasofthespinalcord,it
does not make sense to separate a scholarly view on both at the level of the
foramenmagnum.Thebrainstemisanaturalextensionfromthebraincentral
nervoustissuetothespinalcord.Whatishappeninginthistransitionalzone?
What makes some biological and oncological aspects differ between
intracranial and intraspinal CNS tumors? In addition,at this very junction, a
whole variety of extrinsic and intrinsic tumors can be found, which require
familiaritywith combined cranialandspinal surgicalapproachestothisarea
of complex anatomical relationships.
Volume 1 is dedicated to the Immunology and Genetics of tumors of the
brain and the spine. Emerging technologies in tumor treatment, such as
nanotechnology and medico-economic aspects, are equally included in
Volume 1.
Volume 2 is covering The Path to bedside Management. Hence, the
intrinsic logic of the present book reflects this spirit of coherence. Interna-
tionally renowned experts and with specific fields of expertise are following
thesameorderandinternalorganizationoftheirchapter,fromepidemiology
and biology to diagnostics and treatment. That includes sections on modern
adjuvant therapy and complementary and experimental therapeutic modali-
ties for each specific tumor entity and a section on neuropsychological
aspects in addition.
The inherent logic of these two volumes eludes on important steps in
pre-surgical diagnostics and surgical treatment as well: Tissue imaging is
following similar principles for cranial and spinal tumors. Both organs of
interest are surrounded by thick layers of bone, and modern MRI sequences
provide important structural and functional and metabolic information with
high spatial resolution. In addition, white matter tract imaging and
vii
viii ForewordtotheBook
spectroscopyareofgreatrelevancefortumorsaffectingeitherthebrainorthe
spinal cord.
Higher cerebral functions, as well as afferent and efferent somatosensory
functioning, are at stake frequently, due to the intricate anatomical rela-
tionship between tumor tissue and healthy CNS tissue. Meningeal and other
extrinsictumorsmaybeattachedtotheduralsheathandadjacentbones,with
subsequent encasement of peripheral cranial or spinal nerves. That may
require complex surgical approaches in order to get the best angle of attack
for surgical resection and thorough techniques for dural closure in order to
avoid CSF leakage. Similar techniques and tools are required for optimal
surgicaltreatment,bethatgentletissuehandlingormonitoringandmapping
of neural integrity and functional preservation. Hence, by treating both cra-
nial and spinal tumors together in a two-volume comprehensive book that
endeavorisservinganimportanteducationalpurposeinaddition:tomaintain
andtopromotetheexpertiseinthehandsofdedicatedteamswithinterestin
surgical neuro-oncology and related neuro-scientific fields. I am confident
thatmanyyoungandadvancedneurosurgeonsanddoctorsfromrelatedfields
will acquire this book as a reference for their practice.
The book stands for a sound intellectual and for a holistic approach to
these complexpathologies. It also showsthat brain and spine surgeonshave
common roots and interests and are one of a kind. The editors are to be
commendedforitsinternalorganizationandfortheselectionofauthors.Iam
sure that this book will serve as a reference in its field.
Karl Schaller
Professor and chairman of the Department of Neurosurgery
Geneva University Medical Center and Faculty of Medicine
Geneva, Switzerland
Co-founder of the SFITS
(Swiss Foundation for Innovation
and Training in Surgery)
Preface to the Book
EversinceIwasamedicalstudent,Iwasdeeplyconcernedandcuriousabout
CNS tumors and the lives of patients with brain tumors. Although not very
common in comparison to some other cancers, the tumors of CNS are con-
sidered as one of the most critical cancers since they influence almost every
aspectofthepatients’lives.Mostofthesepatients,whoareaffectedbybrain
or spinal cord tumors, were healthy people with active productive lives, and
sadlythediseasemayoftenresultintheirmortalityandmorbidityduetothe
irreversible sequels to the CNS. As the CNS tissue is characterized by very
lowregenerativeabilities,mostofthetumor-causedinsults,whetherdirector
indirect, are permanent, which widely affect the personal, social, and finan-
ciallivesofthepatients,inadditiontoanundeniablefinancialburdentothe
societies. Therefore, theimportance of this matter was a driving force to me
toputaneffortinthisfield,primarilyasastudent,asaresearcher,andthenas
a resident and clinician. Facing some of these patients in the final stages
of the disease and their families, it is always hard to tell how little can be
practicallydonefortheirtreatment,anddespiteallthehopetheymayexpect
tohearfromus,itisalwaysapainfulconversationtosaywehavecometoa
standstill to cure them. Although one may think there is nothing more to be
done for these kinds of diseases, or everything has already been studied, I
believethatthereisalwayssomethingtobedone,nomatterhowlittle,butit
might be a light in the darkness!
Accordingly,thecurrentbookwasplannedtogatherknowledgeaboutthe
brainandspinalcordtumorsinalmosteveryaspect.Ashighlyconcernedto
provide a comprehensive reference in the field, we invited senior expert
scientists, neurosurgeons, and clinicians to cover different chapters of this
two-volume book.
The first volume, Human Brain and Spinal Cord Tumors:
Neuro-immunology and Neuro-genetics, is mainly focused on the basic
science aspects and economic impact of these tumors. Considering the
importance of the brain and spinal cord tumors, many centers organized
registriesforsurveillanceofCNStumors,whichhasbeenaninvaluableeffort
indeterminingtheepidemiologicaspectsofthesetumors.However,itshould
benotedthatdespitealloftheseadvancements,thereisstillmuchtobedone
inmanypartsoftheworldtoorganizesurveillancesystemsforCNStumors.
Therefore, the reported rates on incidence and prevalence of these tumors
may underestimate the true epidemiology of brain and spinal cord tumors.
ix
x PrefacetotheBook
The second chapter of this book discusses the epidemiology of brain and
spinal cord tumors (Chap. 2).
In brief, the occurrence of the human brain and/or spinal cord tumors
starts at molecular levels involving different genetic and immunologic
pathways. While the innate immunity has non-specific and general roles in
the occurrence and progression of these tumors, the acquired immunity acts
more specifically and therefore is considered as a more suitable target for
immunotherapy of CNS tumors. The roles of innate and acquired immunity
arediscussedindetailinChaps.3and4.Accordingly,andinadditiontothe
standard therapeutic modalities, including surgery, chemotherapy, and
radiotherapy, immune-based therapies have opened a new era in the treat-
ment of CNS cancers. The role of immunotherapy including non-specific
immunotherapy, specific active immunotherapy (cancer vaccines), and
specific passive immunotherapy (monoclonal antibodies, oncolytic virus
therapy, and CAR T cell therapy) are the main outlines in Chap. 5. Con-
sidering different types of CNS tumors, one might wonder where these
tumors come from, or which cellsmay undergo cancerous changes tocreate
each type of these tumors. Interestingly, different types of CNS tumors are
originated from different primary cells. Neural stem cells, committed pre-
cursorcells,andmaturecellsareresponsibleforthecreationofdifferentCNS
tumors.ThecelloforiginforCNStumorsisextensivelydiscussedinChap.6
.InadditiontotheroleofgeneticalterationsinthepathophysiologyofCNS
cancers, epigenetic changes such as Histon methylation and modification,
CpG island DNA methylation, and other epigenetic changes are responsible
for the occurrence of these tumors as well, which are the main discussed
outlines in Chap. 8. The tumor stem cells have been widely studied in the
creation of different cancers as well as their role in possible therapeutic
options, which have been discussed in Chap. 9. Moreover, nutritional sup-
plements and diet may be considered as either risk factors or preventive
factors for brain cancer. Also, diet may play a therapeutic role in the treat-
mentofbraintumors.Theroleofnutritioninbrainandspinalcordtumorsis
discussed in Chap. 10. Importantly, not only the scientists of biological and
medical sciences, but also the scientists of mathematical and physical sci-
ences arewidely involved inresearchfor CNScancers.Thisimportancehas
resulted in advancements in bioinformatic studies in the area to better
understand the nature of CNS tumors, as well as proposing possible thera-
peutic plans. A good example of the role of bioinformatics in CNS cancer
research is discussed in Chap. 7. Besides, the interdisciplinary combination
of physical and biological sciences has resulted in advancements in the
application of nanotechnology in the treatment of brain and spinal cord
tumors,whichareseparatelydiscussedinChaps.11and12.And,thelastbut
nottheleast,Chap.13ofthefirstvolumediscussedtheeconomicaspectsof
CNS tumors and the socioeconomic burden of these tumors.
Thesecondvolume,HumanBrainandSpinalCordTumors:ThePathto
Bedside Management, focuses on clinical aspects of brain and spinal cord
tumors and extensively discusses different types of these tumors. Purposing
onprovidingcomprehensivechaptersinadditiontohavingtheminaunified
pattern,thestructureofallchapterswasdesignedasfollows:(1)Background
