Topografska anatomija moždane

kore i ovojnica, likvorskih prostora i

krvnih žila mozga

Goran Šimić

CIBR
Specijalistički poslijediplomski studij iz neurokirurgije

Kolegij „Topografska anatomija

središnjeg živčanog sustava”
 Slojevita građa moždane kore

Limbic (inner ring) and

(outer ring)

Brodmann, 1909/1914.
2016.
+Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates
PNAS vol. 113 no. 28,> Anders Eklund et al., 7900–7905, doi: 10.1073/pnas.1602413113

+fMRI clustering and false-positive rates

PNAS vol. 114 no. 17; Robert W. Cox et al., E3370–E3371, doi: 10.1073/pnas.1614961114
 5 major f-nal types of cerebral cx fields:

1. Primary sensory and motor (idiotypic) fields

2. Unimodal association fields
3. Limbic fields (“inner ring” of the limbic lobe)
4. Paralimbic fields (“outer ring” of the limbic lobe)
5. Heteromodal (transmodal) association fields

(After Broca, Wernicke, Déjérine, Brodmann, Campbell, von Economo, Koskinas, Vogt&Vogt, Liepmann,
Goldstein, Bonhöffer, Filimonoff, Yakovlev, Sarkisov, Baily, von Bonin, Sanides, Zilles,…)
 1. Primary sensory and motor
(idiotypic) fields
 Heterotypic isocx

 BA17 (visual), BA41 i 42

(auditory), BA3, 1 i 2
(somatosensory), BA4 (motor)

 Connected to sensory organs

and receptors (input), and
lower motor neurons (output)

 Are not phylogenetically

simplest and ontogenetically
earliest to develop
Cynomolgus monkey cx development with
autoradiographic labeling (E47-E88)

cingular orbitofrontal dorsal frontal visual cortex

 2. Unimodal association
fields
Homotypic isocx

BA18, 19, (visual),

BA22 (auditory), BA5 &
7 (somato-sensory),
BA6 & 8 (motor)

Respond only to
sensory stimuli in a
single modality

Receive most of the

input fibers from
respective primary
sensory fields
 3. Limbic fields (“inner ring” of
the limbic lobe)
 Made of allocx (corticoid structures, paleocx &
archicx)

 Corticoid structures (septum, basal

telencephalon, amygdala), paleo- (periamigd.,
praepirif. & piriform cx) & archicx (hipp.
formation)

 Closely reciprocally interconnected with

hypothalamus through which they control self-
preservation, sexual drive, autonomic and
endocrine systems

 Amygdala are involved in processing of fearfull

stimuli (after Sperry, Myers, Bogen, Damasio x2, LeDoux, Tranel,
Gazzaniga,…), while the hipp. formation is crucial for
formation of episodic declarative memory (after
Brown, Schäffer, Bechterew, Klüver, Bucy, Papez, Milner, Corkin,
Morris, Squire, Amaral, Zola-Morgan, Llinas, Buzsaki… )
 4. Paralimbic fields (“outer
ring” of the limbic lobe)
 Made of allocortex (mesocx)

 BA28 (entorhinal cx), BA35 & 36

(pro- & perirhinal cx), BA23-26 &
BA29-33 (cingular complex)

 Reciprocally interconnect limbic

fields with uni- and heteromodal
fields

 Coordinate and “reconciliate” inner

states of an organism with its
actions in surrounding word
(motivation – ant. cingulum,
aversive conditioning – post.
cingulum, can be blocked by central analgesics,
Bromm 2001…)
 5. Heteromodal (transmodal)
association fields
 Homotypic isocx, human-specific cx areas
 Prefront., dorsolat. & orbitofront. cx (BA9 i 10,
BA45-47, BA8, 11 & 12), dorsopariet. cx (BA39-40)
& lat. temp. cx (BA20, 21, 37, 38)

 Link sensory information with emotions, desires

and comportment, thus mediating intermediary
(integrative) processing (cognition) (After Fuster,
Goldmann-Rakic, Mesulam,…)

 Modality-specific fragments of information are

being bonded into coherent experiences and
thoughts (transcedence of instinctive behaviour,
increased depth of “hidden-layer” processing and
context-relevant behavioral repertoire)
salamander

turtle

man
lizard

monkey
oposum

hedgehog
Odvojenost
proliferativnih zona od
konačnog smještaja
neurona

Rakic (1995): Radial unit

hypothesis and sequential
ingrowth of afferents
 Razlike u duljini trajanja neurogeneze (CNV)

Mus musculus

Macaca mulatta

Homo s. sapiens
1+5 major neuronal networks of the cerebral cx:
1. Default mode network

1. Network for recognition of objects & faces

2. Network for spatial attention
3. Network of lingvistic abilities
4. Network of episodic memory and emotions
5. Network of executive f-ons and comportment
 Default mode network (DMN)
The DMN
includes:
mPFC,
PCC,
precuneus,
ACC,
parietal cortex
and in a minority
of studies also the
hippocampus

Hafkemeijer et al., Biochim. Biophys. Acta, 2012, 1822, 431-441

- DMN connectivity reflects the level of consciousness (Greicius et al., Hum. Brain Mapp., 2008;
Vanhaudenhuyse et al., Brain, 2010), generates spontaneous thoughts, and preferentially
activates when individuals engage in internal tasks such as daydreaming, envisioning the future,
and retrieving memories, while it is negatively correlated with brain systems that focus on
external visual signals
- In a subject resting quietly for 8 min during an fMRI scan, BOLD signal will fluctuate up and
down at a very low frequency (<0.1 Hz) - these low-frequency BOLD signal fluctuations are
- DMN undergoes developmental changes and coherent neuronal oscillations at a rate lower
than 0.1 Hz become more consistent in children aged 9-12 years and in older subjects
DMN FC correlates with the level of consciousness

Vanhaudenhuyse et al., Brain, 2010, 133, 161-171

 DMN fc vs DTI

fMRI • Most of baseline

activity is mediated by
neurons that are
constantly active and
participate in the
default mode network
(DMN, also known as
DTI „the resting state” or
„task-negative”
network) (Deco et al.,
TINS, 2013).

Damoiseaux et al., Brain Struct. Funct. 2009, 213, 525-533

 Mreža prepoznavanja objekata i lica
 2 epicentra: lateralna temporalna i
temporopolarna moždana kora
ALATI LICA
ŽIVOTINJE

LH čita „H”
EGO

DH čita „S”

V4
R R V3 V2
ALLO R
 BA37 i 20 (prednji i srednji V5
dio fuziformne vijuge –
percepcija objekata i lica),
granica BA19 i BA37 – 30 mil. y.
percepcija Riječi
Vidna integracija je
stupnjevit proces: (hemi)akromatopsija (clV4), anomija za boje,
nepoznata lica aktiviraju (hemi)akinetopsija (clV5)
samo unimodalne areje
vidna objektna agnozija (D), čista aleksija –
u i oko fuziformnog
girusa, dok poznata vidno prepoznavanje riječi (L)
Fregoli sy
aktiviraju i deficit vidne integracije (D) – Hooperov test
transmodalna područja, asocijativna prozopagnozija (D)
napose u prednjem diskonekcijski sindromi: vidna amnezija (L), vidna
dijelu srednjeg sljepooč. hipoemocionalnost (D), Capgras sy (D): ”ova mačka izgleda baš kao i moja”
girusa (TBI, AD, CVI) „ti si dvojnik moga prijatelja”
Mreža prostorne pozornosti
 3 epicentra: u dorzoparijetalni BA5 i 7 (stvara EGO
privremene reprezentacije lokacija u prostoru), FEF
(kontrolira konjugiranje pokrete očiju) i g. cinguli - ACC
(raspodjeljuje pozornost s obzirom na motivaciju –
prije usmjeravanja pozornosti ili posezanja rukom ALLO
treba odlučiti je li objekt uopće vrijedan pozornosti)

 simultagnozija
nemogućnost percepcije vidnog polja kao cjeline(D)
 sy jednostrane nepozornosti (D),
 sy jednostranog zanemarivanja (D)
 aperceptivna prozopagnozija (deficit
prostorne integracije vidnog podražaja) (D)
 sy Balint (simultagnozija, nemogućnost fiksacije (okularna apraksija),
nemogućnost posezanja rukom prema objektima (opt. ataksija) (D)
 astatognozija (gubitak osjećaja položaja dijelova tijela u prostoru (D)
 = asomatognosia (D 7:1) SM
A
 sy Gerstmann: agnozija prstiju, dezorijentacija
G
lijevo-desno, disgrafija (uz sačuvanu mogućnost
kopiranja napisanih riječi), diskalkulija, BA39 (L)
Mreža prostorne pozornosti
 3 epicentra: u dorzoparijetalni BA5 i 7 (stvara EGO
privremene reprezentacije lokacija u prostoru), FEF
(kontrolira konjugiranje pokrete očiju) i g. cinguli - ACC
(raspodjeljuje pozornost s obzirom na motivaciju –
prije usmjeravanja pozornosti ili posezanja rukom ALLO
treba odlučiti je li objekt uopće vrijedan pozornosti)

 simultagnozija
nemogućnost percepcije vidnog polja kao cjeline(D)
 sy jednostrane nepozornosti (D),
 sy jednostranog zanemarivanja (D)
 aperceptivna prozopagnozija (deficit
prostorne integracije vidnog podražaja) (D)
 sy Balint (simultagnozija, nemogućnost fiksacije (okularna apraksija),
nemogućnost posezanja rukom prema objektima (opt. ataksija) (D)
 astatognozija (gubitak osjećaja položaja dijelova tijela u prostoru (D)
 = asomatognosia (D 7:1) SM
A
 sy Gerstmann: agnozija prstiju, dezorijentacija
G
lijevo-desno, disgrafija (uz sačuvanu mogućnost
kopiranja napisanih riječi), diskalkulija, BA39 (L)
Mreža jezičnih sposobnosti
 2 epicentra: Wernicke i Broca
područje (L)
Wernicke (BA22 & parts of BA21, 39 & 40) koordinira
interakcije između osjetnih reprezent. riječi i simboličkih
asocijacija koje im daju značenje (razumijevanje)
STRAŽNJA/ FLUENT/ TEČNA AFAZIJA
Broca područje (BA44 i dijelovi BA45-47) specijalizirano je za fa
artikulatorne (fonetičke) i gramatičke (sintaktičke) aspekte jezika
(morfosintaksu) PREDNJA/NON-FLUENT/NE-TEČNA AFAZIJA
Globalna afazija: CVI MCA (L) B
- Sve kombinacije simptoma B/W afazije
- Slabo ponavljanje rečenica
W
Anomička afazija (9-11% AD)
- Oštećenje u području temp.-parijet. Spoja (SD) i
angularnog girusa (L)
- Otežano pronalaženje riječi (naročito imenica)  osjetna disprozodija (D)
Kondukcijska (provodna) afazija  čista aleksija (L)
- Ošt. parijetalnog operkuluma u kojem se nalazi f.a.  čista gluhoća za riječi (L)
ili inzule i bijele tvari supramarg. girusa (L)  agrafestezija (somatosenzorna aleksija (L)
- Slabo ponavljanje rečenica, parafazije s  afemija
nemogućnošću pronalaženja pravih riječi
ideomotor, visual & tactile apraxia (BA6 dysconnection) (L)
Transkortikalna motorna afazija  akinetic mutism (bilateral)
- „Watershed” CVI ispred ili iznad B ili WM ispod B semantička demencija (temporoparijetalni spoj)
- Otežano započinjanje i usporen govor
- Sačuvano ponavljanje rečenica „Watershed” područja –
Transkortikalna osjetna afazija ishemija i nekroza na mjestima
- Isto „watershed” infarkt ali straga angularni g. ili iza koja su najdalje od art. opskrbe
- Slabo razumijevanje, neologizmi (sistemska hipoperfuzija)
- Sačuvano ponavljanje rečenica (moguća eholalija)
 Mreža emocija, osjećaja i raspoloženja

a) fear conditioning

b) instructed fear

c) observational fear learning

Three different ways by which humans can learn about the aversive
properties of an event. In all of them the activation of amygdala is seen.
Le Doux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 24: 155-184; Gazzaniga et al., 2002.
TLE

2
3

1
Network for executive f-ons and control of
behavior mPFC

 Epicentres in dorsolat. prefront.

(working memory - representing,
FA
maintaining and manipulating DLPFC
information, executive f-ons,
attention) (Wisconsin card-sorting,
FD
Stroop tests), medial frontal („theory OFC
of mind”) & orbitofront. cx (our
“social” brain, “learned control over
inner drives”)  frontal abulia (in general): lack of creativity, curiousity,
 Working memory provides recall of initiative, planning, decision making based on risks,
understanding of a context, mental flexibility (change of
previous experience, even in absence focus), etc. (more lateralized to the LEFT)(Tranel et al.,
of sensory stimuli (apstract thinking, 2005, Brain; signif. gender differences)
subjective reality), mediating planning  frontal dysinhibition (in general): dramatic
of actions with respect to time and impulsiveness with concurrent loss of emotional judgement,
insight, lack of empathy, capability to delay fulfillment of
space immediate wishes, personality changes etc.) (BILATERAL)
 dd FA: depression (pseudodementia)  ‘high-functioning’ autism, sy Asperger (language o.k.)
 autism (impaired social interaction, lack of empathy,
 dd FD: mania inability to change roles, lack of imagery)
Spatiotemporal dynamics of word processing in the human cortex
(MEG + fMRI + ERP)

ERP component elicited

by meaningful stimuli
(words, pictures, etc.)
 Up until 2015, it has been thought
that one of the characteristics of the
central nervous system is the lack of
a classical lymphatic drainage system.

Using monoclonal antibiodies against

Superior
sagittal LYVE-1 (lymphatic vessel endothelial
Cerebral
cortex sinus hyaluronan receptor 1), a cell surface
receptor on lymphatic endothelial
cells that is used as a lymphatic
Transverse
sinus
endothelial cell marker, a group of
Jonathan Kipnis et al. (Charlottesville,
Virginia) described functional
lympathic vessels lining the dural
Cerebellum sinuses in the mouse brain.
Jonathan Kipnis

They further showed that these lymphatic vessels are

able to carry both fluid and T lymphocytes and dendritic
cells from the cerebrospinal fluid, and are draining into
the deep cervical lymph nodes (30 min after icv
injection, Evans blue appeared in meningeal lymphatic
vessels, and had drained into the deep cervical lymph
nodes). Evans blue-filled
vessels

Lymph
node
Immediately after
intracisternal injection,
CSF tracer moved along
the along (outside) of
cerebral surface
penetrating arterioles,
but not venules. The
small–molecular weight
tracer (TR-d3, dark
blue) moved readily
into the interstitium,
whereas the large–
molecular weight tracer
(FITC-d2000, green) was
confined to the
paravascular space.
As opposed to ventricular infusion (where
there was absence of tracer in tissue remote
from the periventricular space),
intracisternal injection of tracer depended
on its size: after 30 min the smallest A594
occupied the greatest proportion of brain
tissue, TR-d3 exhibited an intermediate
distribution, whereas large FITC-d2000 was
highly restricted.

Ventricular infusion Intracisternal injection Distribution of intracisternally

injected tracers, quantified as a
percentage of total brain volume

absence of tracer in
tissue remote from the
periventricular space

759
Da

absence of tracer in 3 kDa

tissue remote from the
periventricular space
2,000
kDa
Glymphatic system
To evaluate the role of glymphatic system
in the clearance of interstitial solutes, the
elimination of intrastriate 3H-mannitol (182
Da) from the brain was measured in WT
and Aqp4-null mice. Over the first 2 h after
injection, the clearance of intrastriate 3H-
mannitol from Aqp4-null mouse brains was
significantly reduced compared to WT.
The same experiment was repeated with
intrastriate injection of 125I-amyloid 1–40
injection, and the whole-brain radiation was
measured. After 60 min in WT animals 125I-
amyloid 1–40 was cleared significantly more
rapidly than in Aqp4-null mice.
 Movement of interstitial tracer
was abolished in Aqp4-null mice.

45 kDa, intracisternal injection

To evaluate whether soluble

amyloid  within the CSF could
recycle through the brain
parenchyma, 125I-amyloid  1–40
was injected intracisternally:
compared to WT controls,
125I-amyloid 
1–40 influx was
significantly reduced in Aqp4-
null mice.
CSF enters ISF is
the brain cleared
along para- from the
arterial brain along
routes, paravenous
whereas routes.
 Cerebral microbleeds
reflect both SVD and CAA and may represent the missing link between the vascular and amyloid
pathology in AD. Also, they provide direct evidence of BBB breakdown.
GRE T2 SWI can detect
CMBs are larger than at least 67%
their actual size due more CMBs than
to „booming” effect GRE T2!
of hemosiderin (and also better
(highest in the occ. differentiate
lobe) true from
Yamada, Front. Neurol. 2012 mimicking CMBs)

with increasing age

Charidimou and Werring,

Future Neurol. 2011
Microhemorrhages were reported to preferentially occur in local regions of
concentrated amyloid indicated by PiB (Pittsburgh compound B) retention (Dierksen
et al., Ann. Neurol. 2010).

Charidimou and Werring, Future Neurol. 2011

 Cerebral amyloid angiopathy (CAA)
In advanced CAA, there are
Charidimou et al., J. Neurol. significant structural alterations,
Neurosurg. Psychiatry 2017 amyloid the most extreme of which is Knudsen et al., Neurology, 2001
double barrelling (detachment
deposition in and delamination of the
the vessel wall outer part of the tunica media)

amyloid deposition in the

surrounding brain
parenchima

4G8
(and not 1-40)
(with A 1-42)
A model of neurovascular unit damage in Alzheimer’s disease
(Zlokovic B., Cell, 2008)
 A model of microvascular damage in Alzheimer’s disease
(Zlokovic B., Nat. Rev. Neurosci, 2011)

Fe

- diminished amyloid-β clearance by the vascular smooth activation of MMPs

muscle cells, activation of M1 (proinflammatory) phenotype of (also Zn2+ and Ca2+ –
microglial cells, which change the phenotype of astroglia to A1 CAA and CMBs dependent), which are
degrading ECM proteins
-> foot processes become more permissive - > BBB breakdown
Some potential directions
for future therapies of AD
- To increase glymphatic system efficiency by local
application of scanning ultrasound (SUS)
Sci. Transl. Med. 2015; 278: 1-12.
iNPH is practically reversible as about 81% of
patients significantly improve after
neurosurgical enhancement of the drainage
of CSF from the lateral ventricles into the
peritoneal cavity by shunt surgery, thus
increasing the efficiency of glymphatic
paravenous efflux (Luikku et al., Acta
Neurochir. 2016; 158: 2311-2319).
 Syn-1 ir in Meissner’s and Auerbach’s plexuses in PD

S.J. Qualman, H.M. Haupt, P. Yang, S.R. Hamilton, Esophageal Lewy bodies associated with ganglion cell loss in achalasia, similarity to
Parkinson’s disease., Gastroenterology 87 (1984) 848–856.
Braak H, de Vos RA, Bohl J, Del Tredici K (2006) Gastric -synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases
staged for Parkinson’s disease-related brain pathology. Neurosci Lett 396:67–72.
Braak H, Del Tredici K (2009) Neuroanatomy and pathology of sporadic Parkinson’s disease. Adv Anat Embryol Cell Biol 201:1–119.
 Gut and Parkinson’s disease
Hypothesis: a putative
environmental pathogen
capable of passing the gastric
epithelial lining might induce
-synuclein misfolding and
aggregation in specific cell
types of the submucosal
plexus and reach the brain
via a consecutive series of
projection neurons where α-
synuclein is transported
retrogradely (and
anterogradely from cx to
spinal cord, unpublished)
S.J. Qualman, H.M. Haupt, P. Yang, S.R. Hamilton, Esophageal Lewy bodies associated with ganglion cell loss in achalasia, similarity to
Parkinson’s disease., Gastroenterology 87 (1984) 848–856.
Braak H, de Vos RA, Bohl J, Del Tredici K (2006) Gastric -synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases
staged for Parkinson’s disease-related brain pathology. Neurosci Lett 396:67–72.
Braak H, Del Tredici K (2009) Neuroanatomy and pathology of sporadic Parkinson’s disease. Adv Anat Embryol Cell Biol 201:1–119.
 Coagulation system: highly complex,
highly conserved, deficiencies are rare
 Bile acid + cholesterol (ABC transporters)

exome
seq.

GWAS

Chol. is highly important for CNS (20%

of the body cholesterol is in the brain)
Smith–Lemli–Opitz sy etc. BBB closes postnat.
7-dehydrocholesterol reductase mut.
Manolio TA et al. (2009) Finding the missing heritability of complex diseases. Nature 461: 747-753; Hardy J et al. (2014)
Pathways to Alzheimer’s disease. J Intern Med 275: 296-303; Štefulj J et al. (2013) Pathogenesis, modulation, and therapy of
Alzheimer’s disease: a perspective on roles of liver-X receptors. Transl Neurosci 4: 349-356.
 Cerebral amyloid angiopathy (CAA)
In advanced CAA, there are
Charidimou et al., J. Neurol. significant structural alterations,
Neurosurg. Psychiatry 2017 amyloid the most extreme of which is Knudsen et al., Neurology, 2001
double barrelling (detachment
deposition in and delamination of the
the vessel wall outer part of the tunica media)

amyloid deposition in the

surrounding brain
parenchima

4G8
(and not 1-40)
(with A 1-42)
 The 4 AI „hits” amend the Zlokovic’s concept of neurovascular unit
breakdown in AD (Nat. Rev. Neurosci. 2011) and converge upon the
„sealant hypothesis” of stroke and AD

- there may be no
feedback signal or
signalling pathway
through which
neurons receive
the stop signal to
cease creating A
by cleaving APP
using the
amyloidogenic
pathway, neurons
continue in AD to
generate
additional
amounts of A

Fe

- diminished Aβ clearance by the vascular smooth muscle cells, activation of MMPs

activation of M1 (proinflammatory) phenotype of microglial (also Zn2+ and Ca2+ –
cells, which change the phenotype of astroglia to A1 -> foot CAA and CMBs dependent), which are
degrading ECM proteins
processes become more permissive - > BBB breakdown
Some findings which speak in favor of a „sealant hypothesis”:

1. APP gene has been conserved for over 550 million years (so it must be
doing something important): https://www.quora.com/What-is-the-
evolutionary-history-of-amyloid-beta/answer/Jeffrey-Brender

Amyloid fibers can break with each

piece serving as a site for new growth.
Findings which speak in favor of a „sealant hypothesis”:

2. Microhemorrhages were reported to preferentially occur in local regions of

concentrated amyloid indicated by PiB (Pittsburgh compound B) retention (Dierksen et
al., Ann. Neurol. 2010) and/or, reversely, highly co-localize with amyloid plaques in
various mouse models of AD in 78-97%.
Findings which speak in favor of a „sealant hypothesis”:

3. There are three major isoforms of APP, two of which contain a domain
homologous to Kunitz-type protease inhibitors (KPI). The secreted isoforms of
APP containing the KPI domain are analogous to protease nexin-2 (PN-2). Both
APP and PN-2 strongly inhibit coagulation factor XIa and are released from
platelets and endothelial cells. They also inhibit activity of of factor IX (its role
in hemostasis is underscored by the finding that individuals with a deficiency in
this protein have spontaneous bleeding states of whom 12% have intracerebral
hemorrhage).

GRE T2
Cortical microbleeds
are larger than their
actual size due to
„booming” effect of
hemosiderin
(highest in the occ.
lobe)

Yamada, Front. Neurol. 2012

4. 2 out of five mutations in exons 16 and 17 of the
APP gene, which encode part of the APP molecule HCHWA-D
from which later proteolytic cleavage by - and -
secretase will produce A, cause fatal stroke in
adulthood: the Flemish mutation (Cys692Gly) and
the Italian mutation (Glu693Lys); however, two
other mutations in the same region of the APP gene,
are relatively less frequent and cause early AD: the
Arctic mutation (Glu693Gly) and the Osaka mutation
(Glu693Asp); the fifth mutation is protective leads
to changes in APP structure near the cleavage point
for -secretase which makes APP a weak substrate London’s mutation
for cleavage by -secretase; consequently, people
with this mutation have a lower likelihood of AD
(Jonsson et al., 2012; confirmed by Kero et al., 2013).

5. When production of A (as a

protective response) is prevented,
as has been the case with the
most ,if not all, clinical trials
(immunization, BACE and -
secretase inhibitors), there is
always an increased likelihood for
stroke to occur!
 6. Notch 3 protein is one of the many substrates for -secretase.

For over 20 years, it has been known that mutations in NOTCH3 gene cause CADASIL (Cerebral
Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy).

Although rare cases of co-occurrence of CADASIL and AD have been reported, another strong
link between AD and stroke has been discovered when
 Krvna opskrba mozga
2 izvora:
• A. carotis* interna:
opskrbljuje prednje 2/3
hemisfera velikog mozga
i međumozak
(diencephalon)
• A. vertebralis:
opskrbljuje stražnju 1/3
hemisfera velikog mozga
i dijelove diencefalona,
moždanog debla i malog
mozga

* kara grč. glava; karoun grč. utonuti u san, onesvijestiti se, budući da
pritisak na zajedničke karotide uzrokuje gubitak svijesti (Galen, 1543)
Typical cervical vertebrae (C3-C7):

- malo tijelo, a velik (veći od tijela) trokutast spinalni kanal

- rascjepljen šiljasti nastavak (C2-C6, C7 – vertebra prominens)

- rascjepljen poprečni nastavak u dvije kvržice:

- tuberculum anterius (zakržljalo vratno rebro – C7)
- tuberculum posterius (pravi poprečni nastavak)
- između kvržica je žlijeb (sulcus nn. spinalis)
- u samom poprečnom nastavku je f. transversarium
- kroz njega prolaze a. i v. vertebralis (C6-C1)
- C7 ima mali f. transversarium, jer kroz
njega prolazi samo v. vertebralis)
- gornje zglobne plohe usmjerene natrag i gore, donje naprijed i dolje
 Stephen HALES, 1726

1905
Nikolai
Korotkov 1896
 A. carotis interna, podjela i ogranci
• Terminologia Anatomica in 1998
subdivided the artery into four
parts: "cervical", "petrous",
"cavernous", and "cerebral"
• Klinički (Bouthillier, 1996) se dijeli
u: cervikalni - C1, petrozni – C2,
segment u području f. lacerum –
C3, kavernozni – C4, klinoidni – C5,
oftalmički – C6 i terminalni,
komunicirajući/moždani – C7
segment
• Cervikalni segment (C1) proteže se
od bifurkacije pa do ulaska u
karotidni kanal (canalis caroticus)
• A. carotis interna uobičajeno NEMA ogranaka u vratu
 ->n. tractus solitarii -> simpatikus, parasimpaticus (N.X), hipoth.

Heringov i Breuerov živac

kemoreceptori,
mjere pO2 u manjoj mjeri pCO2
(osjetljivi su i na pH i temp) – hipoksija
dovodi do hiperventilacije

baroreceptori
mjere RR (uz aortalne)
 Poremećaji karotidnog sinusa
Karotidni sinus često je mjesto gdje, uslijed poremećene hemodinamike,
nastaje aterosklerotski plak. Ako su ovi plakovi veliki i/ili nestabilni, oni
bolesnika predisponiraju za TIA i ishemijski moždani udar, pa je u profilaksi
ovih bolesti indicirana endarterektomija (CEA) ili stentiranje (CAS).
 Stimulacija (masaža)
karotidnog sinusa

Karotidni sinus može biti preosjetljiv na manualnu stimulaciju, zbog čega može nastati
sindrom karotidnog sinusa i sinkopa uslijed smanjenja tlaka ili frekvencije srčanog
ritma (npr. za vrijeme brijanja).

Masaža karotidnog sinusa katkad je korisna kod razlikovanja supra- od ventrikularne

tahikardije. Ona je također i terapijski postupak (kao i Valsavin manevar) u
hemodinamski stabilnog pacijenta kod SVT (iako manje učinkovit nego farmakološki,
npr. davanje verapamila).

?Smrt uslijed stimulacije karotidnog sinusa uslijed srčanog zastoja (aresta) u

slučajevima vješanja, gušenja ili autoerotske strangulacije; također postoji mogućnost
otkidanja plaka ili tromba s posljedičnim moždanim udarom
 Valsalvin* manevar
Valsalvin manevar je srednje jaki forsirani ekspirij protiv zatvorenih usta i zatvorenog nosa, čime se povećava
intratorakalni tlak i time povećava vensko vraćanje krvi, te minutni volumen srca, arterijski talk i frekvencija srca.
Valsalvin manevar može se upotrijebiti za zaustavljanje epizoda supraventrikularne tahikardije, ali također i
testiranja autonomne inervacije srca ili „ventiliranja” srednjeg uha i sinusa čime se izjednačavaju tlakovi prilikom
promjene ambijentalnog tlaka (npr. kod ronjenja, letenja avionom ili hiperbarične terapije kisikom).
Zbog Valsalva manevra, intratorakalni talk u početku postane vrlo pozitivan zbog kompresije torakalnih organa.
Povećani vanjski talk komprimira krvne žile i srčane komore smanjujući transmuralni tlak na njihove zidove. Venska
kompresija i prateće veliko povećanje tlaka u desnom atriju smanjuje venski priljev u toraks. Smanjeni venski priljev,
skupa sa kompresijom srčanih komora smanjuje srčano punjenje i preload unatoč velikom povećanju tlaka u
komorama. Smanjeno punjenje i preload vodi do pada u minutnom volumenu putem Frank-Starlingovog mehanizma. U
isto vrijeme, kompresija torakalne aorte prolazno povećava aortalni talk (faza 1); ipak, aortalni talk počinje padati (faza
2) nakon nekoliko sekundi jer pada minutni volumen. Promjene u frekvenciji srca recipročne su promjenama u
aortalnom tlaku zbog djelovanja baroreceptorskog refleksa. Effect of Valsalva Cardiac Finding

Aortic stenosis
Decreased
Pulmonic stenosis

Tricuspid regurgitation

Increased Hypertrophic cardiomyopathy,

mitral valve prolapse

Tijekom faze 1 frekvencija srca se smanjuje jer se aortalni tlak diže; tijekom faze 2, frekvencija srca se povećava jer
aortalni talk pada.Kada osoba opet počne disati normalno, aortalni talk se nakratko smanji kako se vanjska kompresija
aorte miče, i frekvencija srca se kratko refleksno poveća (faza 3). Nakon toga slijedi povećanje aortalnog tlaka (i
refleksno smanjenje frekvencije srca) kako se minutni volumen naglo povećava u odgovoru na brzo povećanje punjenja
srca (faza 4). Aortalni tlak se također diže iznad normalnog zbog baroreceptora, simpatikusom posredovanog
povećanja u sistemnom vaskularnom otporu koji se pojavio tijekom Valsalve.
Slične promjene se događaju kad god osoba provodi forsirani ekspirij ili protiv zatvorenog glotisa ili visokog otpora
pulmonalnom odtoku, ili kada se torakalni ili abdominalni mišići jako kontrahiraju. Slično se može dogoditi i kada osoba
diže teški teret.
*Antonio Maria Valsalva, 1704
 Petrozni segment (C2)
• Ogranci a. karotis
interne u C2 segmentu
su:
A. canalis pterygoidei
(Vidii)*
A. caricotympanica

C3 segment nema ogranaka

* Guido Vidius, 1500-1569

 Kavernozni segment (C4)
• Okružen kavernoznim
sinusom

• Daje:
A. (meningo)hypophysealis
inferior
 C4
daje i manje važne ogranke:
• Branches of the meningohypophyseal trunk:
– Tentorial basal branch
– Tentorial marginal branch
– Meningeal branch - helps supply blood to the meninges of the anterior cranial
fossa
– Clivus branches - tiny branches that supply the clivus
– Donja hipofizna arterija
• Capsular branches - supplies wall of cavernous sinus
• Branches of the inferolateral trunk:
– Branches to trigeminal ganglion - provide blood to trigeminal ganglion
– Artery of the foramen rotundum
– Branches to nerves
 Klinoidni segment (C5)
• A. carotis interna ovdje
izlazi iz kavernoznog
sinusa i ulazi
‘intraduralno’ u
subarahnoidalni prostor
 Oftalmički segment (C6)
• U početnom dijelu ide
paralelno s N. II
• Daje:
A. ophtalmica
A. hypophysealis superior
C7 segment

• Daje:
A. choroidea anterior
A. communicans posterior
A. cerebri anterior
(terminalni ogranak)
A. cerebri media
(terminalni ogranak)
 A. cerebri anterior

• Povezana je s istoimenom iz
suprotne hemisfere putem a.
communicans anterior
• Kortikalni ogranci: opskrbljuju
cijelu medijalnu površinu
hemisfere velikog mozga sve do
parijetookcipitalnog sulkusa
• Središnji ogranci: opskrbljuju n.
caudatus, prednji dio
putamena i palidusa i prednji
krak kapsule interne
 A. cerebri anterior
opskrbljuje:
• Medijalnu površinu
čeonog režnja, prednje
4/5 korpusa kalozuma,
otprilike 2.5 cm lateralne
površine čeonog i
parijetalnog režnja,
prednje dijelove bazalnih
ganglija i kapsule
interne; također i
olfaktorni bulbus i trakt
 A. cerebri media
• Kortikalni ogranci:
opskrbljuju većinu
superolateralne površine
moždane kore hemisfera
velikog mozga i inzulu
• Središnji ogranci:
opskrbljuju putamen,
globus palidus i n. kaudatus,
te koljeno i stražnji krak
kapsule interne (aa.
lenticulostriatae M1
segment – naročito sklone pucanju kod
kronične hipertenzije)
Anterior limb: lenticulostriate branches of middle cerebral artery
(superior half) & recurrent artery of Heubner off of the anterior cerebral
artery (inferior half)
Genu: lenticulostriate branches of middle cerebral artery TRACTUS
CORTICOBULBARIS
Posterior limb: lenticulostriate branches of middle cerebral artery
(superior half) & anterior choroidal artery off of the internal carotid artery
(inferior half) TRACTUS CORTICOSPINALIS
 A. cerebri media
• Opskrbljuje cijelu lateralnu
površinu hemisfera osim gornjeg
dijela tjemenog režnja (a. cerebri
anterior), donjeg dijela
sljepoočnog režnja i zatiljnog
režnja (a. cerebri posterior)
• Gornji ogranci opskrbljuju
lateroinferiorni dio čeonog režnja
(uključujući Broca motoričko
područje za govor)
• Donji ogranci opskrbljuju
lateralne dijelove sljepoočnog
režnja (uključujući Wernicke
područje za razumijevanje
govora)
• Duboki ogranci opskrbljuju
bazalne ganglije i kapsulu internu
3. Mreža jezičnih sposobnosti
 2 epicentra: Wernicke i Broca
područje (L)
Wernicke (BA22 & parts of BA21, 39 & 40) koordinira interakcije fa
između osjetnih reprezentacija riječi i simboličkih asocijacija koje
im daju značenje (razumijevanje)
Broca područje (BA44 i dijelovi BA45-47) specijalizirano je za B W
artikulatorne (fonetičke) i gramatičke (sintaktičke) aspekte jezika
(morfosintaksu)

Globalna afazija: CVI MCA (L)

- Sve kombinacije simptoma B/W afazije
- Slabo ponavljanje rečenica
Anomička afazija (9-11% AD)  osjetna disprozodija (D)
- Oštećenje u području temp.-parijet. Spoja (SD) i  čista aleksija (L)
angularnog girusa (L)  čista gluhoća za riječi (L)
- Otežano pronalaženje riječi (naročito imenica)  agrafestezija (somatosenzorna aleksija (L)
Kondukcijska (provodna) afazija  afemija
- Ošt. parijetalnog operkuluma u kojem se nalazi f.a. ideomotor, visual & tactile apraxia (BA6
ili inzule i bijele tvari supramarg. girusa (L) dysconnection) (LEFT)
- Slabo ponavljanje rečenica, parafazije s
 akinetic mutism (bilateral)
nemogućnošću pronalaženja pravih riječi
Transkortikalna motorna afazija
- „Watershed” CVI ispred ili iznad B ili WM ispod B
- Otežano započinjanje i usporen govor
- Sačuvano ponavljanje rečenica „Watershed” područja –
Transkortikalna osjetna afazija ishemija i nekroza na mjestima
- Isto „watershed” infarkt ali straga angularni g. ili iza koja su najdalje od art. opskrbe
- Slabo razumijevanje, neologizmi (sistemska hipoperfuzija)
- Sačuvano ponavljanje rečenica (moguća eholalija)
Broca afazija Wernicke afazija
 Anterior choroidal artery
• passes backward, enters
inferior horn of lateral
ventricle, and ends in
choroid plexus. It supplies
lateral geniculate body,
posterior limb of internal
capsule, middle 3/5 of
crus cerebri,and globus
pallidus
 Posterior communicating artery

• runs backward to
join posterior
cerebral artery
 A. vertebralis
• Cranial branches
– Anterior and posterior spinal
arteries
– Posterior inferior cerebellar
artery
• Branches of basilar artery
– Anterior inferior cerebral artery
– Labyrinthine artery
– Pontine arteries
– Superior cerebellar artery
– Posterior cerebral artery
 Subclavian steal sy

Uzrok: ateroskleroza,
vratno rebro,
Takayasu arteritis
 Posterior cerebral artery
• Cortical branches: supply
medial and inferior
surfaces of temporal lobe
and occipital lobe
 Posterior cerebral artery

• Central branches
• postero-medial ganglionic
branches pierce the posterior
perforated substance, and
supply the medial surfaces of
the thalami and the walls of
the third ventricle.
• postero-lateral ganglionic
branches: small arteries which
arise from the posterior
cerebral artery after it has
turned around the cerebral
peduncle; they supply a
considerable portion of the
thalamus
 Cerebral arterial circle ( circle of Willis )
• Formation: formed by anterior
communicating artery, both
anterior cerebral arteries,
internal carotid arteries,
posterior communicating
arteries, and posterior
cerebral arteries
• Position: lies on sella turcica
around optic chiasma, tuber
cinereum and mamillary
bodies
• cerebral arterial circle (circle of Willis)—
in most cases prevents development of
neurological symptoms following acute
ischemic stroke
 Circle of Willis
“a potential collateral pathway for blood flow”

• Anterior cerebral artery

• Anterior communicating artery
• Internal carotid– Middle cerebral artery
• Posterior communicating artery
• Posterior cerebral artery

Nolte: pg 123
 Microaneurysm

Lenticulostriate arteries

Subarachnoid hemorrhage
Intracerebral
hemorhage

Arteriovenous
malformation
 Part VI
Deficits due to most common vascular lesions
• Spinal cord (occlusion of the ant. and post. spinal cord artery)
• Brainstem vascular lesions
- midbrain (Parinaud sy, Benedict sy, Weber sy)
- pons (Millard-Gubler, AICA, lateral mid., med.- mid., lat. sup. pontine sy)
+ acoustic neuroma (Schwannoma), internuclear ophthalmoplegia, jugular foramen sy (Vernet’s sy)

- medulla (med. medullary sy, lat. medullary sy (PICA sy, Wallenberg’s sy))
• Diencephalon
• Telencephalon
Vaskularna kompresija – najčešći uzrok neuralgije trigeminusa
Kirurška th dekompresijom (MVD)

Nakon male kraniotomije u retromastoidnom ili subokcipitalnom

području izvrši se mobilizacija k.ž. koja vrši kompresiju i uvođenje
teflonskog materijala između žile i živca u novom, odmaknutom
položaju koji se fiksira

(80-90%)

Benetto et al., BMJ 2007

 Neuralgija V:MR 3D cisternografija +
angiografija (“fusion imaging”)
Rusu et al.,
Surg Radiol
Anat 2009

Satoh et al.,
AJNR 2009
 Veins of brain
External cerebral veins
• Drain blood from cortex
and subcortical medullary
substance and empty into
adjacent sinuses of dura
mater. The external veins
are the superior cerebral
veins, inferior cerebral
veins, and middle
cerebral vein.
 Veins of brain
• Internal cerebral veins:
drain deeper parts of
hemispheres, basal nuclei,
internal capsule,
diencephalon and choroid
plexus, ultimately form
great cerebral vein which
enter straight sinus
• The venous blood from the deep
areas of the brain is collected into
channels called the venous
sinuses.
• The dural venous sinuses of the
brain are formed by layers of dura
mater lined by endothelium. The
main venous sinuses are :
• 1 superior sagittal sinus
• 1 inferior sagittal sinus
• 1 straight sinus
• 2 transverse sinus or lateral
sinuses
• 2 sigmoid sinuses
• The sigmoid sinuses situated close
to the mastoid air sinuses
continue as internal jugular veins
 Venous
Drainage
„The danger triangle” of the face
A normal
B cupping of the optic disk
due to glaucoma
C papilledema (papilla stagnans)
due to increased ICP
CT / krvarenje
EDH / SDH / SAH
 Lesions of the brainstem
• most frequently are syndromes of arterial
occlusion or circulatory insufficiency that
involve the vertebrobasilar system but also:
• acoustic neuroma (Schwannoma)
• internuclear ophtalmoplegia sy (medial
longitudinal fasciculus - MLF syndrome)
• jugular foramen (Vernet’s) syndrome
 Lesions of the midbrain
• most frequently result from vascular
occlusion of the mesencephalic branches
of the PCA (posterior cerebral artery), but
may also result from:

- aneurysms of the posterior circle of Willis

- tumors of the pineal region
- hydrocephalus
Blood Supply to the Medulla
Blood Supply to the Pons
 Blood Supply to the Pons
The paramedian branches of the Basilar artery supplies the paramedian
regions of the Pons, this includes corticospinal fibers (basis pedunculi),
the medial leminiscus, abducens nerve and nucleus (cranial nerve VI) ,
pontine reticular area, and periaquaductal gray areas
Blood Supply to the Midbrain
Blood Supply to the Midbrain
Blood Supply to the Midbrain, Pons, and Medulla
 Clinical syndromes

• Dorsal midbrain sy (Parinaud’s)

• Paramedian midbrain sy (Benedikt’s)

• Medial midbrain sy (Weber’s)

 Gowers described the sy before Parinaud.

Dorsal midbrain sy (Parinaud’s)

• result from a vascular
occlusion/hemorrhage of the
dorsal midbrain branches of
PCA or pinealoma
• affected structures and resultant
deficits are:
- superior colliculus and pretectal
area: paralysis of upward (and
downward) gaze, pupillary disturbances,
absence of convergence
- cerebral aqueduct: non-
communicating hydrocephalus due to
compression from a pineal tumor Aqueductus cerebri

1. Colliculus superior, 9. Substantia grisea centralis (PAG)

Patient lose
the ability to
look upward,
but my
develop lid
retraction
when trying
to do so
(Collier’s
sign) (Parsons,
1993)
CT MRI
 Basic aspects of pineal tumors
• 1% of all brain tumors; 45% pineoblastoma (males),
0.3% germinoma (2:1 males); peak age 0-20 y, except
pineocytoma 20-40y

• Benign: pineal cyst, pineocytoma, teratoma, dermoid

• Malignant: germinoma, pineoblastoma,

choriocarcinoma

• Imaging modality of choice: MRI (CT if MRI not

available)
 Clinical aspects of pineal tumors
• Typical presentation: obstructed CSF flow: headache, nausea,
vomiting, impaired vision with papilledema

• Treatment options: shunt, ventriculostomy, irradiation

• Course and prognosis: pineocytoma 5y survival rate - 86%,

pineoblastoma 5y- 58%, germinoma/teratoma 5y- 65-95%

• What does the clinician want to know: is CSF slow obstructed,

extent of tumor, metastases?

• Differential diagnosis
- Metastasis (often history of primary tumor, but may be difficult to
distinguish from pineal tumor)
- Arachnoid cyst (does not enhance, homogenous isointense structure)
- Pylocytic astrocytoma (peripineal location, cystic component enhances
asymmetrically)
 Paramedian midbrain sy
(Benedikt’s)
• is result of occlusion or
hemorrhage of the paramedian
midbrain branches of the PCA
• affected structures and
resultant deficits are: G

- CN III roots (intra-axial fibers):

C

complete ipsilateral paralysis of CN III,

eye abduction and depression (due to
unopposed action of CN VI and IV,
ptosis (paralysis of the levator
palpebrae muscle), ipsilateral fixed and
dilated pupil (“complete internal Lemniscus
ophtalmoplegia”) medialis

- red nucleus and

dentatorubrothalamic tract: 4. n. ruber
contralateral cerebellar ataxia with 5. CN III roots
intention tremor 6. CN III motor nucleus
- medial lemniscus: contralateral
loss of proprioception, discriminative
tactile sensation and vibration from
trunk and extremities
 Medial midbrain sy (Weber’s)
• is result of occlusion or
hemorrhage of the midbrain
branches of the PCA and
aneurisms of the circle of Willis
• affected structures and resultant
deficits are:
- CN III roots (intra-axial fibers):
complete ipsilateral paralysis of CN III,
eye abduction and depression (due to
unopposed action of CN VI and IV,
ptosis (paralysis of the levator palpebrae
muscle), ipsilateral fixed and dilated Aqueductus cerebri
pupil (“complete internal
ophtalmoplegia”)
- corticobulbar tracts: contralateral 4. n. ruber
weakness of the lower face (CN VII), 5. CN III roots Cxpontine tract
tongue (CN XII) and palate (CN X) 6. CN III motor nucleus
7. n. niger
- corticospinal tracts: contralateral 8. crus cerebri Cxspinal tract
hemiparesis of the trunk and extremities
Cxpontine and cxbulbar tracts
 Acoustic neuroma (Schwannoma)
• benign tumor of the Schwann
cells affecting CN VIII
• frequently compresses CN VII
• may affect the spinal trigeminal
tract (CN V)
• affected structures and
resultant deficits are:
- cochlear nerve: unilateral nerve
hearing impairment or deafness
and tinnitus (ear ringing)
- vestibular nerve: vertigo,
nystagmus, nausea, vomiting,
unsteadiness of gait
- facial nerve: facial weakness or
paresis and loss of corneal reflex
(efferent limb)
- spinal trigeminal tract:
paresthesias and anesthesia of MRI
ipsilateral face, loss of corneal
reflex (afferent limb)
- if impinged on CN IX: difficulty 8% of all intracranial tumors! Metastases are rare,
swallowing
M:F=1:2, peak age 30-60 y, modality of choice: MRI
 The MLF carries information about the direction that the eyes should move.
It yokes the cranial nerve nuclei III, IV and VI together, as well as the gaze centers and information about head movement (from cranial nerve VIII).
It also carries the decending tract and tracts into the cervical spinal cord, and innervates some muscles of the neck and upper extremities.

Internuclear ophtalmoplegia
• also known as medial
longitudinal fasciculus (MLF)
syndrome
• lesions occur in the dorsomedial
pontine tegmentum and may
affect one or both MLFs
• is a frequent sign of multiple
sclerosis
• results in medial rectus palsy on
attempted lateral gaze and
mononuclear nystagmus in the
abducting eye (with normal
convergence)
• if lesion extends to the motor
nucleus of CN VI (D) it causes
MLF signs + lateral rectus 3. n. gracilis, 4. n. cuneatus, 5. n. olivaris inf.
paralysis and internal strabismus 6. lemniscus med., 7. pyramis, 8. n. oliv. access. med.
(“one-and-one-half” sy)
 Jugular foramen sy (Vernet’s sy)
• Affects CN IX, X and XI

CN IX: - loss of the gag reflex (afferent limb)

- loss of taste sensation in the
posterior third of the tongue
- unilateral loss of the carotid sinus
reflex
CN X: - laryngeal (with dysarthria, dysphagia
and dysphonia) and palatal paralysis
(with loss of the efferent limb of the gag
reflex)
CN XI: - weakness of the SCM and upper trapezoid
muscles (the shoulder droops and the
scapula is winged)
 Vascular lesions of the pons
• most frequently result from occlusion of the
basilar artery or its branches (the anterior
inferior cerebellar artery (AICA), transverse
pontine arteries and superior cerebellar artery:

- Medial inferior pontine sy (Millard-Gubler sy)

- Lateral inferior pontine sy (AICA sy)
- Lateral midpontine syndrome
- Lateral superior pontine syndrome
 Medial inferior pontine syndrome
(Millard-Gubler sy)
• results from occlusion of
the paramedian branches
of the basilar artery
• affected structures and
resultant deficits are:
- CN VI nerve roots (intra-
axial fibers): ipsilateral lat.
rectus paralysis
- cxbulbar and cxspinal
tracts: contralat.
hemiparesis of the trunk
and extremities and
contralat weakness of the
lower face
- base of the pons (nn.
pontis): ipsilateral limb and
gait ataxia 1. n. CN VI, 4. lemniscus medialis, 5. tractus cxspinalis,
6. nn. pontis, 7. corpus trapezoideum, 9. n. CN VII
- medial lemniscus: contralat.
loss of proprioception,
discriminative tactile
sensation and vibration
from the trunk and
extremities
 Lateral inferior pontine sy (AICA)
• results from occlusion of a long
circumferential branch of the basilar
artery (AICA)
• affected structures and resultant
deficits are:
- CN VII nucleus and its intra-axial nerve
roots: ipsilateral facial nerve paralysis,
loss of taste from the ant. 2/3 of the
tongue, loss of corneal and stapedial
reflexes
- cochlear nuclei and its intra-axial nerve
fibers: unilateral central nerve deafness
- vestibular nuclei and its intra-axial nerve
fibers: nystagmus, nausea, vomiting,
vertigo
1. n. CN VI, 3. fila
- spinal trigeminal nucleus and tract: radicularia CN VII, 5.
ipsilat. loss of pain and temp. sensation tractus cxspinalis,
from the face 6. nn. pontis, 7. corpus
- middle and inferior cerebellar trapezoideum, 8. tractus
peduncles: ipsilat. limb and gait tegmentalis
dystaxia centralis, 9. n. CN VII
- spinothalamic tracts: contralat. loss of
pain and temp. sensation from the trunk
and extremities
In 85% of cases
- descending sympathetic tract: ipsilat. AICA gives rise to
Horner’s sy (ptosis, miosis, the labyrinthine a.
hemianhydrosis, enophtalmos)
 Lateral midpontine sy
• Results from occlusion of a short
circumferential branch of the
basilary artery
• affected structures and
resultant deficits are:
- trigeminal nuclei and nerve root
(motor and principal sensory
nuclei): complete ipsilat. CN V
paralysis (paralysis of the
masticatory muscles, jaw
deviation to the paretic side due
to the unopposed action of the
intact lateral pterygoid muscle,
facial hemianesthesia (pain,
temp., touch and proprioception),
loss of afferent limb of corneal 2. pedunculi cerebellares sup., 3. medii, 4. corpus trapezoideum,
5. tractus cxspin., 6. fibrae pontis profundae, 7. RF, 8. n. motorius CN V,
reflex) 9. n. sensibilis principalis CN VI
- middle cerebellar peduncle:
ipsilat. limb and gait dystaxia
Medial midpontine sy

MLF

LL
LM

2. pedunculi cerebellares sup., 3. medii, 4. corpus trapezoideum,

5. tractus cxspin., 6. fibrae pontis profundae, 7. RF, 8. n. motorius CN V,
9. n. sensibilis principalis CN VI
Locked-in syndrome - lesion of
corticobulbar fibers (A) due to infarction in
the ventral midbrain (basilar artery). MRI
shows that area in front of aqueduct is
preserved (B)

Locked-in syndrome – 38-year-old

Locked-in syndrome – 53-year-old

 Glasgow coma scale

Rohkamm R, Color atlas of Neurology, Thieme, 2004

Respiratory signs in coma

Rohkamm R, Color atlas of Neurology, Thieme, 2004

Rohkamm R, Color atlas of Neurology, Thieme, 2004
 Lateral superior pontine syndrome
• Results from occlusion of a
superior cerebellar artery
• affected structures and
resultant deficits are:
- superior and middle cerebellar
peduncles: ipsilat. limb an trund
dystaxia
- dentate nucleus: dystaxia,
dysmetria, intention tremor
- spinothalamic and
trigeminothalamic tracts:
contralat. loss of pain and temp.
from the trunk, extremities and
face
- descending sympathetic tract LL
(interruption of its pathway to the
ciliospinal center of Budge in Th1- LM
Th2) : ipsilateral Horner’s sy 2. pedunculi cerebellares sup., 3. medii, 4. corpus trapezoideum,
(ptosis, miosis, hemianhydrosis,
enophtalmos) 5. tractus cxspin., 6. fibrae pontis profundae, 7. RF, 8. n. motorius CN V,
9. n. sensibilis principalis CN VI
- medial lemniscus: contralat. loss
of proprioception, discriminative
tactile sensation and vibration
from the trunk and lower extremity
Asking the patient to close her/his eyes and smile.
a) Peripheral facial paralysis demonstrating compromise of
the entire affected hemiface
b) Central facial paralysis, demonstrating compromise of
only the lower portion of the face

Bell’s palsy
Vascular lesions of the medulla
• result from occlusion of the vertebral artery
or its branches (the anterior and posterior
spinal arteries and the posterior cerebellar
artery, PICA), so that two main clinical
syndromes can be distinguished:

- medial medullary syndrome

- lateral medullary syndrome (PICA sy,
Wallenberg’s sy)
 Medial medullary syndrome
• results from occlusion of the
anterior spinal artery
• affected structures and
resultant deficits are:
- cxspinal tract: contralat.
Hemiparesis of the trunk and
extremities
- medial lemniscus: contralat.
loss of proprioception,
discriminative tactile
sensation and vibration
sensation from the trunk and
extremities
- hypoglossal nerve roots
(intra-axial fibers): ipsilat.
flaccid paralysis of the
tongue
 Lateral medullary syndrome (Wallenberg’s sy)
• results from occlusion of the vertebral
artery or one of its medullary branches,
e.g. PICA
• affected structures and resultant deficits
are:
- vestibular nuclei: nystagmus, nausea,
vomiting, vertigo
- inferior cerebellar peduncle: ipsilat.
dystaxia, dysmetria, dysdiadochokinesia
- 3. nucleus ambiguus of CN IX, X and XI
(SVE fibers): ipsilat. laryngeal, pharyngeal
and palatal paralysis (loss of the gag
reflex – efferent limb), dysarthria,
dysphagia and dysphonia (voice
hoarseness)
- CN IX nerve roots (intra-axial fibers): loss
of the gag reflex – afferent limb
- CN X nerve roots (intra-axial fibers):
same as in 3.
- spinothalamic tracts: contralat. loss of
pain and temp. sensation from the trunk
and extremities
- spinal trigeminal nucleus and tract: ipsilat.
loss of pain and temp. sensation from the
face
- descending sympathetic tract: ipsilat.
Horner’s syndrome
PICA sy

Rohkamm R, Color atlas of Neurology, Thieme, 2004

 Branches of the Vertebral Artery
1. Posterior Inferior Cerebellar Artery
(PICA), the largest branch of the
vertebral, arises at the caudal end of
the medulla on each side.

Runs a course winding between the

medulla and cerebellum

Distribution:
a. posterior part of cerebellar
hemisphere
b. inferior vermis
c. central nuclei of cerebellum
d. choroid plexus of 4th ventricle
e. medullary branches to
dorsolateral medulla
Brainstem syndromes summary (1)

Rohkamm R, Color atlas of Neurology, Thieme, 2004

Brainstem syndromes summary (2)

Rohkamm R, Color atlas of Neurology, Thieme, 2004

Brainstem syndromes summary (3)

Rohkamm R, Color atlas of Neurology, Thieme, 2004

 Lesions of the spinal cord
• May be classified according to the area of origin or
the area affected:

- LMN lesions
- UMN lesions
- sensory pathway lesions
- peripheral nervous system lesions
- combined UMN and LMN lesions
- combined motor and sensory lesions
- herniations of the intervertebral disk
 Neurological deficits resulting from
LMN lesions
Examples of diseases of LMN:
- poliomyelitis: an acute inflammatory
viral infection caused by enterovirus
- spinal muscular atrophy (SMA): type I –
• flaccid paralysis Werdnig-Hoffmann disease, II – juvenile,
• muscle atrophy III – Kugelberg-Welander disease (all are
(amyotrophy) caused by mutations of the exon 7 in the
SMN1 gene on chr. 5)
• hypotonia
• areflexia (loss of muscle stretch reflexes –
e.g. knee and ankle jerks, and loss of superficial
reflexes – e.g. abdominal and cremasteric reflexes)

• fasciculations (visible
muscle twitches)
• fibrillations (seen only on
an EMG)
MRI scan of 72 years old man.
What happened?
72 years old man
Infarction of the central part of the
left precentral gyrus – paralysis of
the right hand.
CT scan of 48 years old
man.
What happened?
48 years old man.
Infarction of the medial part
of the right precentral gyrus
– paralysis of the left leg.
Infarction of of the short
circumferent a. of pons.
Paralysis of contralateral arm
and hand.
 Neurological deficits resulting from
UMN lesions
• when rostral to the pyramidal decussation of the caudal
medulla, they result in deficits below the lesion and on
the contralateral side
• when caudal to the pyramidal decussation, they result in
deficits below the lesion and on the ipsilateral side

3 types of cxspinal tract lesions:

- lateral corticospinal tract lesion

- ventral corticospinal tract lesion
- hereditary spastic paraplegia or diplegia
 Lateral corticospinal tract lesion
- results in the following ipsilat. motor
deficits found below the lesion:
• spastic hemiparesis with muscle
weakness
• hyperreflexia (exaggerated muscle
stretch reflexes)
• clasp-knife spasticity (when a joint is
moved briskly, resistance is felt
initially and then fades like the
opening of a pocketknife blade)
• loss of superficial reflexes
(abdominal and cremasteric)
• clonus (rhythmic contractions of
muscles in response to sudden,
passive movements (wrist, patellar
or ankle clonus)
• Babinski’s sign (plantar reflex
response is extension i.e.
dorsiflexion of big toe)
Ventral corticospinal tract lesion
• results in mild contralateral motor deficit
• ventral cxspinal tract fibers decussate at
spinal levels in the ventral white
commissure
Hereditary spastic paraplegia or diplegia
• bilateral degeneration of the cxspinal tracts
• gradual development of spastic weakness of
the legs with increased difficulty in walking
 Combined UMN and LMN lesions
• are characterized
by muscle ALS:
weakness and
wasting without - Usually occurs in persons 50-70
sensory deficits years of age, 2:1 men
• prototypic - Either component may dominate the
disease:
amyotrophic clinical picture:
lateral sclerosis -
ALS (also Lou Progressive spinal muscular atrophy
Gehrig’s disease)
or progressive bulbar palsy refers to
a LMN component
Pseudobulbar palsy or primary lateral
sclerosis refers to an UMN
component
 Bilateral glossal atrophy in ALS

Rohkamm R, Color atlas of Neurology, Thieme, 2004

Spinal Cord Blood Supply

Ventral Dorsal
 Spinal Cord Blood Supply
Anterior Spinal
Artery, provides
sulcal branches
which penetrate
the ventral
median fissure
and supply the
ventral 2/3 of the
spinal cord.

Posterior Spinal
Arteries, each
descends along the
dorsolateral
surface of the
spinal cord and
supplies the dorsal
1/3.
 Spinal Cord Blood Supply

Radicular arteries,
originating from
segmental arteries at
various levels, which
divide into anterior and
posterior radicular
arteries as they move
along ventral and dorsal
roots to reach the spinal
cord. Here they
reinforce spinal arteries
and anastomose with
their branches.

From these varied sources of blood supply, a series of circumferential anastomot

channels are formed around the spinal cord, called the arterial vasocorona, from
which short branches penetrate and supply the lateral parts of the cord
 CSF is obtained by inserting a
Needle into the lumbar cistern
between the 3rd and 4th or 4th
and 5th lumbar spinal
processes.

Schematic drawings showing the relationship between

the spinal cord and the vertebral column at various stages
of development.
 Sensory pathways lesions
• Dorsal columns Results in the following ipsilat. sensory deficits
syndrome: found below the lesion (because these are the
first order neurons, the pathway has NOT yet
- includes the fasciculi crossed. If the pathway hasn’t crossed, the
gracilis (Th6-S5) and lesion is ipsilateral):
cuneatus (C2-Th6)
and the dorsal roots - loss of tactile discrimination, proprioception
- is seen in subacute (joint position) and vibratory sensation
degeneration due to
vitamin B12 - astereognosis
neuropathy
- is seen as tabes - paresthesias and pain (dorsal root irritation)
dorsalis in
neurosyphilis - hyporeflexia or areflexia (dorsal root
- is seen in deafferentation)
nonsyphilitic sensory
neuropathies - urinary incontinence, constipation, and
impotence (dorsal root deafferentation)
- Romberg’s sign (sensory dystaxia – standing
patient is more unsteady with eyes closed
 Lateral spinothalamic tract lesion
• results in contralat. loss of pain and
temperature sensation one segment below
the level of the lesion
 Ventral spinothalamic tract lesion
• results in contralat. loss of light (crude) touch sensation 3
or 4 segment below the level of the lesion
• does not appreciably reduce touch sensation if the
dorsal columns are intact
 Dorsal spinocerebellar tract lesion
• results in ipsilat. leg dystaxia: patient has
difficulty performing heel-to-shin test
Ventral spinocerebellar tract lesion
• results in contralat. leg dystaxia: patient
has difficulty performing the heel-to-shin
test
 Combined motor and sensory
lesions
• spinal cord hemisection (Brown-Séquard sy)
• complete transection
• anterior spinal artery occlusion
• conus medullaris and epiconus syndromes
• cauda equina sy
• filum terminale (tethered cord) syndrome
• subacute combined degeneration (vit. B12
neuropathy)
• syringomyelia
 Spinal cord hemisection (Brown-
Séquard sy)
• affected structures and resultant deficits
are:

- dorsal columns: ipsilat. loss of tactile

discrimination, proprioception and
vibration sensation below the lesion
- lat. spinoth. tract: contralat. loss of pain
and temp. sensation, starting one
segment below the lesion
- ventral spinoth. tract: contralat. loss of
crude touch sensation, starting 3 or 4
segments below the lesion
- dorsal spinocerebellar tract: ipsilat. leg
dystaxia
- ventral spinocerebellar tract: contralat.
leg dystaxia
- hypothalamospinal transection rostral to
Th2: Horner’s sy
- lateral cxspinal tract: ipsilat. spastic
paresis below the UMN lesion with
Babinski’s sign
Spinal cord hemisection
(Brown-Séquard sy)
Anesthesia at site of lesion

Loss of tactile discrimination,

proprioception and vibration
sensation
+ spastic paresis with pyramid signs

Loss of pain and temperature

sensation

Hemisection at Th10
Complete transection of the spinal
cord
• results in the following conditions:

• exitus letalis between C1 and C3

• quadriplegia between C4 and C5
• paraplegia below Th1
• spastic paralysis of all voluntary
movements below the lesion
• complete anesthesia below the
lesion
• Urinary and fecal incontinence,
although reflex emptying may occur
• anhidrosis and loss of vasomotor
tone
• paralysis of volitional and automatic
breathing, if the transection is
above C5 (the phrenic nucleus is
found at C3-C5)
 Anterior spinal artery occlusion
• causes infarction of the ventral 2/3 of the
spinal cord
• usually spares the dorsal columns and
dorsal horns
 almost always are bilateral

Conus medullaris and epiconus sy

• Conus medullaris sy • Epiconus sy involves
involves segments S3-Co segments L4-S2
and is usually caused by
small intramedullary tumor
metastases or hemorrhagic - results in:
infarcts
- reflex functioning of the
- results in: bladder and rectum but loss
of voluntary control
- destruction of sacral
parasympathetic nucleus
(paralytic bladder, fecal - considerable motor
incontinence, impotence) disability (external rotation
and extension of the thigh
are most affected)
- peroanogenital sensory
loss (saddle anesthesia)
- is associated with absent
Achilles tendon reflex
(in absence of motor deficits
in the lower limbs)
 Cauda equina sy
• Involves spinal roots L3-Co
• Neurol. deficits are similar to conus or
epiconus lesions
• Signs frequently predominate on one side
• May result from intervertebral disk
herniation
• Severe spontaneous radicular pain is
common
Rohkamm R, Color atlas of Neurology, Thieme, 2004
 Filum terminale (tethered cord) sy
• Results from a thickened and shortened
filum terminale that adheres to the sacrum
and causes traction of the conus
medullaris
• Results in sphincter dysfunction, gait
disorders, and deformities of the feet
 Subacute combined degeneration
(B12 neuropathy)
• Is a spinal cord disease associated with
pernicious anemia
• Consists of demyelination of dorsal
columns and corticospinal and
spinocerebellar tracts
 Syringomyelia
• Is a central cavitation of
the cervical spinal cord
of unknown etiology
• Results in destruction of
the ventral white matter
commissure and
interruption of
decussating
spinothalamic fibers,
causing bilateral loss of
pain and temperature
sensation
Putative pg mechanisms of
syringomyelia

Rohkamm R, Color atlas of Neurology, Thieme, 2004

 Intervertebral disk herniation
• consists of prolapse or
herniation of the nucleus
pulposus trough the
defective anulus fibrosus into
the vertebral canal: the
nucleus pulposus impinges
on spinal roots, resulting in
root pain (radiculopathy) or
muscle weakness
• in 90% of cases appears at
the L4-L5 or L5-S1 (cauda
equina sy) interspaces
• in 10% appears in the
cervical region, usually at the
C5-C6 or C6-C7 interspaces
• spinal root symtoms include:
paresthesias, pain, sensory
loss, hyporeflexia and
muscle weakness
Iz Schmachmann-a
Diencephalon
Schmahmann JD, Pandya DN, Cortex 2008
 Hvala na pozornosti

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