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Rizki Hanriko
Laboratorium Anatomi-Histo-PA
Ross MH. Nerve Tissue Histology.2011
Ross MH. Nerve Tissue Histology.2011
Parenchym otak terdiri dari:
Membentuk unit dasar dari sistem saraf
bersama dengan axon, dendrit dan

Sitoplasma mengandung endoplasmik

retikulum dengan permukaan kasar dan
roset ribosom disebut Nissl Bodies (Nissl
Keadaan/ penyakit yang dapat
menyebabkan kerusakan neuron

1. Atrophy dan Degenerasi

- Alzheimer’s disease
- Parkinson’s disease
- Huntington’s disease
- Creutzfeld-Jacob disease
2. Intra neuronal body formation
- Neurofibrillary tangles (Alzheimer’s dis)
- Lewy body (Parkinson’s dis)
- Pick bodies (Pick’s disease)
- Hirano bodies (Alzheimer’s disease)
Neurofibrillary tangles:
Kumpulan filamen pada sitoplasma
neuron yang mengelilingi nukleus
Terwarna basofil dengan HE dan
Bielschowsky (Silver stain)
Lewy bodies:
Bentuk bulat seperti elongasi, eosinofil
dalam sitoplasma
Bagian pinggir pucat.
Pick’s bodies
Inklusio filamen, bulat/ oval eosinofilik
lemah, terwarna kuat dengan silver
Hirano’s bodies
Terdapat pada proksimal dendrit,
inklusio eosinofil
3. Intraneuronal storage
Neuron dapat menjadi tempat
terkumpulnya substansi metabolisme
co/ Nieman-Pick disease (inborn errors
4. Chromatolysis (axonal
Bila axon rusak, sel neuron
membengkak menjadi bulat dan
terwarna pucat
Nissls substance hilang, nukleus akan
kebagian tepi
5. Axonal Degeneration
Disfungsi neuron mengakibatkan
neuron tidak mampu untuk memelihara
 Astrocyt
 Oligodendrocyt
 Sel ependym
Dengan HE: nukleus bulat/ oval dengan
granular chromatin halus
Dengan Cajal Gold Sublimat tampak
sitoplasma membentuk sel stelat yang
berhubungan dengan sel-sel otak lain.
Fungsi sel ini disangka menunjang
secara physiologis dan biokimia dari
neuron juga berinteraksi dengan sel
endotel kapiler untuk memelihara blood-
brain barrier
Terwarna dengan Hortega Carbonat
prosesus lebih pendek dari astrocyt.
memproduksi dan memelihara myelin
Penyakit yang mengenai sel ini akan
bermanifestasi pada myelinisasi
co/ multiple sclerosis
Sel Ependym
Membentuk lapisan epitel torak/ kuboid
pada ventrikel serebri dan canalis
sentralis medula spinalis

Terdapat diseluruh area otak

Bila terdapat kerusakan jaringan 
proliferasi  MPS
Kelainan SSP
Intracranial herniation
 Intracranial herniation is the movement of
part of the brain from one space to another
with resultant damage.
 It usually occurs following a critical increase
in intracranial pressure caused by an
expanding lesion, e.g. tumour or haematoma.
 However, it may be inadvertently precipitated
by withdrawing CSF at lumbar puncture.
Cerebral oedema
 AbN accumulation of fluid in the cerebral parenchyma
 breakdown of the blood–brain barrier,
 Ischaemia, e.g. from infarction.
 Trauma, e.g. from head injury.
 Inflammation encephalitis or meningitis.
 Cerebral tumours (primary or secondary).
 Metabolic disturbances, e.g. hyponatraemia or
 The condition results in cerebral swelling, and it is
associated with raised intracranial pressure.
 Treatment is by minimizing the formation of oedema
by use of osmotic agents or steroids.
 increase in the volume of CSF within the
brain  expansion of the cerebral ventricles.
 It can occur by one of three mechanisms:
 Obstruction to flow of CSF (commonest form).
 Impaired absorption of CSF at arachnoid villi
 Overproduction of CSF by choroid plexus
neoplasms (very rare).
 Obstructive hydrocephalus is either
congenital or acquired.
Syringomyelia and hydromyelia
 Syringomyelia  rare, cyst (syrinx) develops within
the spinal cord, usually posterior to the central canal,
lined by gliosis (astrocytes). It is most common in the
cervical spinal cord, but it may extend into the
medulla (syringobulbia).
 Hydromyelia is dilatated central canal contains CSF,
and is lined by ependyma.
 The causes of these conditions are either: Acquired
(majority of cases)—secondary to trauma or
ischaemia, or occurring in association with tumours of
the spinal cord.
 Congenital—may be associated with
maldevelopment of the cord or other developmental
abnormalities of the craniocervical junction,
especially in Arnold–Chiari syndrome.
Perinatal injury
Cerebral palsy
 Cerebral palsy describes brain malformation or
damage affecting motor areas of the brain.
 It is the leading cause of crippling handicap in
children, affecting 2 per 1000 live births.
 Damage may occur during fetal life, may be birth
related, or may occur postnatally (Fig. 5.4)
Ischaemia and hypoxia
 Major causes of severe perinatal brain
 Perinatal hypoxia is usually due to
asphyxiation-trauma of birth,
 Perinatal ischaemia is commonly caused by
intracranial haemorrhages.
 Premature infants  disturbances in the
cerebral circulation possibly caused by in-
utero hypoxia/ischaemia.
 In full-term infants during difficult deliveries
 Mortality is high; one third of survivors may
develop cerebral palsy, epilepsy, or mental
Traumatic injuries to the central
nervous system
Skull fractures
 Skull fractures occur in approximately 80% of
fatal cases of head injuries.
 The most common are linear fractures of the
vault of the skull (62%); such fractures may
extend into the base of the skull causing
cranial nerve laceration.
Parenchymal damage
 This is an abrupt transient loss of
consciousness due to temporal neuronal
dysfunction following a relatively slight
impact. It is caused by an enormous, but
short-lived, increase in pressure within the
cranium at time of impact.
 Full recovery usually ensues, although
repeated concussion may result it permanent
brain damage.
Contusions and lacerations
 A contusion is a bruise with extravasation of blood but
with the pia-arachnoid intact.
 A laceration is where the pia-arachnoid is torn.
 Fracture contusion—occurs at the site of fracture.
 Coup contusion—occurs at point of impact in # (-)
 Contrecoup contusion—occurs diametrically opposite to
the site of impact.
 Herniation contusion—occurs when the hippocampi or
cerebellar tonsils (or both) are impacted and bruised by
the free edge of the tentorium and foramen magnum,
 Gliding contusion—occurs at the superior margins of
the cerebral hemispheres; usually caused by
interference of the dura with a rotational movement of
the brain.
Diffuse axonal injury
 result of rotational movements of the brain within the
skull during angular acceleration or deceleration.
 It often occurs in the absence of any skull fracture or
cerebral contusions.
There are two main features:
 Small haemorrhagic lesions in the corpus callosum
and the dorso-lateral quadrant of brainstem
 Widespread tearing of axons (microscopic).
 This type of injury occurs in almost 50% of patients
with a severe head injury, and in almost all fatal head
injuries. It is associated with head injuries involving
vehicular accidents.
Traumatic vascular injury
Extradural (epidural) haemorrhage
 2% of all head injuries and in 15% of fatal cases.
 Haemorrhage occurs between the skull and dura,
and gradually stripping dura from bone forming a
large, saucer-shaped haematoma
 This injury is almost always the result of skull
fracture, usually a linear fracture of the thin
squamous part of the temporal bone, which contains
the middle meningeal artery (a branch of the
 maxillary artery).
 It is associated with a post-traumatic lucid interval of
several hours followed by a rapid increase in
intracranial pressure.
Subdural haemorrhage
 Haemorrhage occurs between the dura
and the outer surface of the arachnoid
 It is usually caused by a rupture of the
small bridging veins or the venous
 The resulting haematoma is often
extensive because of the loose
attachment of the dura and arachnoid
Subarachnoid haemorrhage
 Arterial rupture is usually secondary to
superficial contusions or lacerations of the
brain. Small amounts of blood can be
disposed of by arachnoid granulations.
 Larger haemorrhages cause arachnoid
fibrosis leading to meningeal irritation and
raised intracranial pressure.
 It can also occur as a result of hypertension,
aneurysms, embolisms, or infarction.
Intracerebral haemorrhage
 This is caused by direct rupture of the intrinsic
cerebral vessels at the time of injury.
 Resulting haematomas are classified into three
 Solitary—occur in association with cortical
contusions; common in temporal and frontal
 Multiple—associated with severe contrecoup
lesions; often fatal.
 Burst lobe—intracerebral or intracerebellar
haematoma in continuity with subdural
haematoma; most common in temporal and
frontal lobes; rapidly fatal.
Cerebrovascular disease
 Stroke, a sudden event in which a neurological deficit
occurs over minutes or hours and lasts for longer
than 24 hours.
 less than 24 hours = transient ischaemic attack.
 1 or 2 per 1000 per year, but it is much higher in the
elderly, affecting males more than females.
Causes of stroke are:
 Cerebral infarction (80%).
 Intracerebral haemorrhage (10%).
 Subarachnoid haemorrhage (10%).

Risk factors are atheroma, heart disease, hypertension,

and diabetes mellitus.
Hypoxia, ischaemia and infarction
 Cerebral infarction is the process whereby a focal
area of necrosis is produced in the brain in response
to a decreased supply of oxygen (and glucose) in the
territory of a cerebral arterial branch.
There are two main causes of infarction:
 Hypoxia—the reduction of oxygen supply to tissues
despite an adequate blood supply, e.g. following
respiratory arrest.
 Ischaemia—blood supply to tissues is absent, or
severely reduced, usually as a result of constriction
or obstruction of a blood vessel.

Ischaemia accounts for the majority of cases of cerebral

Mechanisms of ischaemia
 Vascular disease—e.g. thrombosis, embolic
occlusion or vasculitis.
 Cardiac disease—e.g. prolonged hypotension
or cardiac embolism.
 Trauma—head injury leading to vascular
occlusion, dissection, or rupture.
Infections of the central nervous
There are four possible mechanisms of meningeal
 Direct spread—from penetrating trauma (e.g.
compound skull fractures) or adjacent focus of
infection (e.g. sinusitis, middle ear or mastoid
 Blood-borne spread—from septicaemia or septic
emboli from other infections such as bacterial
 Iatrogenic infection—following the introduction of
organisms into CSF at lumbar puncture.
 Congenital abnormalities, e.g. meningomyelocoeles.
Brain abscess
 A severe focal infection of the brain and is typically
1–2 cm across. It starts as an area of cerebritis—
inflammation of the brain parenchyma— and
develops into a pus-filled cavity walled off by gliosis
and surrounded by cerebral oedema raised
intracranial pressure.
 Middle ear infection (60%)—temporal lobe and
cerebellar abscesses.
 Frontal sinusitis (20%)—frontal lobe abscess.
 Bacteraemia/septicaemia (10%)—usually frontal lobe
 Penetrating skull trauma.
 Secondary to meningitis.
 Unknown causes
Subdural empyema
 This is a collection of pus in the subdural
space and it is relatively uncommon. In adults
it usually results from frontal sinusitis,
whereas in infants it is usually secondary to
 Clinically, patients with subdural empyema
are usually very ill. The pus spreads rapidly
on the surface of a hemisphere, producing
hemiparesis, raised intracranial pressure, fits,
and meningism.
Chronic meningoencephalitis
Tuberculous meningitis
 Infection usually reaches the CNS via the
 Granulomatous inflammation affects the basal
meninges, large arteries and cranial nerves.
 Clinically with slow-onset, subacute meningitis. It may
be accompanied by isolated cranial nerve palsies.
 Hydrocephalus
 CSF shows an initial increase in polymorphs, then an
increase in lymphocytes.
 Prognosis—Untreated, the disease is usually fatal.
Intensive treatment with antituberculous drugs lowers
mortality to 15–20%.
Chronic meningitis
 Rare, middle-aged and elderly,
Neisseria meningitidis, sweating, joint
pains, and transient rash.

 Treponema pallidum, approx 25% of
cases of syphilis. mild or even
asymptomatic, but it may be severe with
transient cranial nerve palsies and
Lyme disease
 Tick-borne spirochaete Borrelia burgdorferi. It is a
systemic illness characterized by skin lesions and
neurological features.
 Viral encephalitis

Fungal infections
 Rare and occur mainly in the immunosuppressed
(e.g. associated with chemotherapy, steroid
treatment, acquired immune deficiency syndrome—
AIDS), but some organisms, e.g. Cryptococcus
neoformans, can produce disease in the absence of
Protozoal infection
 Toxoplasmosis
 Amoebae.
 Plasmodium falciparum.
 Trypanosomes.
Multiple sclerosis
 Commonest demyelinating disorder of the CNS
 50 per 100 000 in the UK. Peak incidence is between
20 and 40 years with a slight female predominance.
 MS is characterized by relapsing and remitting
episodes of immunologically mediated demyelination
within the CNS. Recovery from each episode of
demyelination is usually incomplete, leading to
progressive deterioration.
 Association with HLA antigens (A3, B7, DR2 & DQ1).
Aetiology is unknown but current theories are:
 Myelin abnormality.
 Autoimmune disorder.
 Toxin damage.
 Viral infection of the CNS, e.g. measles.
Degenerative disorders
Alzheimer’s disease
 Most common cause of dementia in Western countries. over 65
years, and 15% of people over 80 years; females more than
 Increase in incidence of sporadic cases in individuals with
ApoEe4 genotype on chromosome 19.
 The amyloid precursor protein (APP) gene on chromosome 21
has been implicated in the familial cases.
 Aetiology and pathogenesis are unknown; some cases (5%) are
familial but most (95%) are sporadic.

Current theories involve:

 Infectious agents.
 Toxins, e.g. aluminium.
 Traumatic injury.
Macroscopically, there is marked atrophy, especially of
the frontal lobes; the brain is reduced in weight to 1000
g or less (normal average 1400 g). There is a loss of
cortical grey and white matter.

Histological hallmarks are as follows:

 Senile plaques—composed of an extracellular core of
amyloid protein (10–150 nm diameter) surrounded by
dystrophic neurites; occur most frequently in the
hippocampus, cerebral cortex, and deep grey matter.
 Neurofibrillary tangles—abnormal tangles of insoluble
cytoskeletal-like proteins (paired helical filaments)
that form within the neurons of the brain.
 Neuropil threads—distorted, twisted and dilated
dendritic processes and axons of cerebral cortex
found around amyloid plaques.
 Refer to patients whose clinical presentation
is one of akinetic rigidity and resting tremor.
The causes are:
 Parkinson’s disease.
 Postencephalitic parkinsonism.
 Neuroleptic drugs.
 Cerebral anoxia.
Parkinson’s disease
 Rest tremor, slowness of voluntary movement, and
 1 per 1000 adults but 1 per 200 over the age of 65.
 The aetiology is unknown.
 The disorder shows degeneration of pigmented
dopaminergic neurons of the substantia nigra, the
locus caeruleus, and several other brainstem nuclei
 reducing the amount of dopamine in the corpus
 Surviving cells in the substantia nigra contain
eosinophilic spherical inclusions (Lewy bodies),
which contain cytoskeletal filaments.
 Drug: L-dopa, that correct neurotransmitter
imbalance, transplanted fetal tissue ?
Metabolic disorders and toxins
Vitamin B1 (thiamine) deficiency
This is common in chronic alcoholics, resulting
 Wernicke’s encephalopathy: memory
impairment, ataxia, visual disturbances, and
peripheral neuropathy.
 Korsakoff ’s psychosis: confused state,
memory loss, and confabulation.
 If both occur, it is known as Wernicke–
Korsakoff syndrome.
Vitamin B12 (cyanocobalamin) deficiency
 Weakness and paraesthesia in the lower limbs
resulting from subacute combined degeneration of
the spinal cord.
 Replacement therapy at an early stage reverses the
degenerative process, but long-standing cases show
irreversible axonal damage with reactive gliosis.

Iodine deficiency
 Hypothyroidism; >> affect the CNS in children.
 In the fetus, severe iodine deficiency causes
cretinism characterized by dwarfism, mental defect,
and spastic diplegia.
 This can be prevented by iodine supplements during
Carbon monoxide
 CO binds irreversibly to Hb rendering
erythrocytes incapable of oxygen transport.
 CO poisoning, therefore, results in brain
damage due to hypoxia.
 >20%—Dyspnoea and slight headache.
 30%—Severe headache, fatigue, and
 judgement.
 60–70%—Loss of consciousness.
 >70%—Rapidly fata
 Highly toxic to the CNS, lipid soluble, so it
readily diffuses into the CSF and aqueous
humour in concentrations higher than in
 Methanol is metabolized into formic acid and
 Acute—sudden death with multiple
haemorrhagic lesions in the cerebral
 Chronic—atrophy of retinal ganglion cells with
secondary degeneration of the optic nerve.
Tumor dari neuroglia
 Astrosit => Astrocytoma
Anaplastic astrocytoma
Glioblastoma multiforme
Pilocytic astrocytoma
 Oligodendrocytes => Oligodendroglioma
 Ependyma and its homologues => Ependymoma

Tumor dari neuron
 Neuroblastoma
 Ganglioneuroblastoma
 Ganglioneuroma

Tumor dari neuron dan neuroglia

 Ganglioglioma
Tumor dari sel-sel primitif dan tidak
 Meduloblastoma

Tumor dari sel pineal

 Pineoblastoma

Tumor dari meningen

 Meningioma
 Meningeal hemangiopericytoma
 Meningeal sarcoma
Tumor dari selubung saraf
 Schwannoma
 Neurofibroma

 Primer
 Sekunder

Tumor malformasi
 Craniopharyngioma
 Epidermoid cyst
 Dermoid Cyst
 Colloid cyst
Tumor metastase
Sebanyak 25-30% tumor di dalam otak
adalah tumor metastase yang berasal dari
organ lainnya. Terbanyak adalah dari jenis
Tumor yang sering bermetastase ke otak
 Paru-paru
 Payudara
 Kulit
 Ginjal
 usia pertengahan
 60 thn => anaplastic
 70 thn => glioblastoma multiforme
 masa putih abu-abu
 infiltratif
 padat, lunak, gelatinous
  bbrp cm
 lokalisasi: hemispher cerebri
Sel-sel uniform

Bentuk anaplastic:
 hypercelluler
 nukleus pleomorf, ireguler, hyperchromatis
 proliferasi dan hyperplasia dari endotel
Glioblastoma Multiforme
Terdapat bermcm2x: kdg2x tdpt area putih
padat, kuning lunak nekrosis, kista,
Mikros:  anaplastic
- kapiler mbtk “cluster”
Lokasi tersering astrositoma:
 Pd dewasa di hemisphere, kdg2x di med.
 tidak pernah di cerebellum
Prognosis: jelek
Pilocytic Astrocytoma
 Khas tjd pd anak-anak dan dewasa muda
 Lokasi: cerebellum, dasar dan dinding
ventrikel III, N. Optikus, hemisphere cerebri
Makros: kistik kdg2x padat
 Bipolar sel dengan prosesus panjang dan
 Prolif. Vasculer.
Tumor tumbuh lebih lambat.
 5% dr seluruh glioma
 Umur pertengahan
 laki-laki = perempuan
 Berbatas tegas
 Gelatinous, keabuan, dgn bgn2x kistik,
hemoragis fokal, kalsifikasi
 Penyebaran ke ruang subarach.
 Tdd sel-sel yg berkelompok dengan inti
spheris bergranul
 Sytoplasma ber-halo
 Kapiler-kapiler yang bersambungan
memisahkan sel-sel tumor mjd
 Type anaplastik: - progresif
- nukleus pleomorf
Penderita dpt hidup ± 5 thn.
 Berasal dari sel-sel epitel yg melapisi
ventrikel & canalis spinalis
 Mengenai usia 10-20 thn.
 Seringkali pd ventrikel IV
 Pd usia pertengahan sering di medula
 Di ventrikel IV, bentuk padat atau papillary
=> reseksi sulit
 Intraspinal - berbatas tegas => dpt
 Sel-sel oval-bulat atau “carrot shaped” nuclei,
granular chrom.
 Membentuk gambaran ependymal
 Pathognomonis: blepharoplast basal bodies
of cilia ( w: PTAH )

 Fossa posterior ependymoma disertai:
hidrocephalus, obstruksi V. IV, invasi ke pons
& medulla
 Tumbuh lambat, prognosa buruk.
 Padat, kalsifikasi
 Bentuk nodule yg melekat pd ddg
 Kadang2x: - asymptomatic
- hidrocephalus
 Tdpt pd V. lateral dan V. IV
Choroid Plexus Papilloma
 Tjd pd tempat plexus choroideus
 Srg pd anak-anak
 Ventrikel lateral
 Dws - pd ventrikel IV
Makr:  plexus choroid normal
tumbuh papilifer
Mikr: jaringan ikat dilapisi epitel kuboid,
columner + cilia
Klinis: - disertai hidrocephalus
- obstruksi ventrikel oleh tumor
 Tjd pd hemispher cerebri
 Anak-anak
 Mikr: rossete
dan Gangliocytoma
 Ganglioneuroma berupa massa berbatas
tegas + kalsifikasi
 Pd ventr. III, hipotalamus atau lobus
Sel-sel ganglion dipisah oleh stroma yang
tidak terlalu seluler.
 Tjd di cerebellum
 Dekade 2 kehidupan (25%)
 Kdg2x pd usia lebih tua
 Menimbulkan disfungsi cerebellar atau
 10 ysr  50%
 Masa putih keabuan
 Pd anak tdpt di vermis cerebell. Pd dws:
hemisphere lateral
 Penyebaran mll CSF ke ependym & suarachnoid
 Kelompokan sel-sel padat dg inti kecil, pleomorf,
sitoplasma sedikit.
 Kdg2x membentuk Homer Wright rossete
(diferensiasi neuronal).
 Gambaran utama adalah adanya diferensiasi
neuronal dan glial.
 Tumor yg tumbuh pd atap arachnoid
 20% dr slrh tumor primer intra cranial
 Lokasi tersering: ½ bgn depan kepala
tmsk lengkung hemisphere, falx cerebri,
tulang sphenoid, foramen olfactorius.
 Jarang: - ventrikel
- cerebellopontine angel
- foramen magnum
- med. spinalis.
 iregular
 melekat pd dura
 kdg2x mbtk “plate like form” dsbt meningioma
 tumor solid, dg permukaan kasar
 WHO Grade I: Meningothelial, Fibrous, Transitional,
Psamomatous, Microcystic, Secretory,
Limphoplasmacytic-rich, Metaplasia.
 WHO Grade II: Atypical, Clear cell, Chordoid
 WHO Grade III: Papillary, Rhabdoid, Anaplastic
Colloid Cyst of Third Ventricel
 dws muda
 2% dr tumor primer intracran.
 Ø 1-4 cm di anterior ventrikel III
 tdd kapsel fibrosa dilapisi epitel kuboid /
kolumnar kdg bersilia / goblet sel
 dpt menyebabkan: - obstruksi for.
- blok aliran CSF
- hidrocephalus
Metastatic Tumors
 25-30% tumor intracran.
 terutama carcinoma (80%): - paru
- mamma
- melanoma
- ginjal
 membentuk massa yg berbatas pd
cortico-white matler junction
 dikelilingi daerah udema
Saraf Tepi