BASIC PATHOLOGICAL BASIC PATHOLOGICAL ASPECTS ASPECTS

OF OF NERVOUS SYSTEM NERVOUS SYSTEM

PATHOLOGYPATHOLOGYEsti D. S. Soetrisno B.

Rino PattiataDepartement Anatomic Pathology Faculty of Medicine

University of Indonesia

BASIC PATHOLOGICAL MANIFESTATION

OF SOME DISTURBANCESDYS – NEURO EMBRYOGENESIS ABORTION / INTRA-UTERINE FETAL DEATH (IUFD) ABNORMALITIES : TERATOGENIC, MONSTER, CONGENITAL ANOMALY

AGENESIS : There is no processus (anlage) of all or partial part of NS

No formation of NS IUFDAPLASIA : There is only NS Streak Formation

abortionHYPOPLASIA : Failure to growth of all or partial part of NS

Hypotrophy (Micro Insize) Hypofunction / Fatal

e.g Microensephaly, Arnold – Chiary Syndrome

Hyperplasia : Overgrowth parts of NS e.g Macroensephaly,

Hydrocephallus, Function?

Hypertrophy: True Hypertrophy / Pseudo Hypertrophy

Defect On Enclosing of the Neural TubeThere is “Cele” Formation, or Spina Bifida Formation (Occulta/Aperta)e.g Meningocele, Encephalo -/ Myelo – Meningcocele, Syringo -Encephalo –/ Myelo – Meningcocele (Syringo Myelia)

DYS – HISTOGENESIS : incorrect migration and/or naturation – differentation

ECTOPIC :mature tissue found in abnormal places

HETEROPIC :intermingled of some mature tissues in abnormal places

HAMARTOMA :abnormal composition of mature tissues at its normal places

NEOPLASMA (GEN MUTATION) :benign and malignant

DYS – NEUROANATOMY Abnormalities of anatomy / location of NS- Dyslocation- Reverse of Several Centre

DYS - NEUROCHEMISTRY - NEUROPHYSIOLOGY

INHIBIT : Slow Conduction – Slow Movement / Analysis / etc

EXCITE : Rapid / Hyperactivity (ies)DYS – REGULATION / CONTROL : UNCONTROL

MOVEMENT – PATHOLOGICAL REFLEXES

DYSFUNCTIONAL

IMPULS CONDUCT

CNS CELLSCNS CELLS

NEURONGLIAL CELL

– ASTROCYTE– OLIGODENDROGLIA– EPENDYMA– MICROGLIA

CHOROID PLEXUS CELL

NEURONNEURON

ASTROCYTEASTROCYTE

OLIGO DENDROGLIAOLIGO DENDROGLIA

NeuronNeuron Effector cells of Nervous

System Neuron loss with progressive

aginh Neuron of CNS cannot

effectively regenerate axons over long distance → limit ability of CNS to respond to different type of injury

Infarct transects internal capsule creates permanent motor deficiti

Neuron in CNS don’t remyelinate → demyelinating disease causes permanent functional deficit (multipel sclerosis)

PIGMENTED NEURONPIGMENTED NEURON( SUBSTANTIA NIGRA )

neuromelanin

ATROPHIC NEURONATROPHIC NEURON

hyperchromatic

Loss of neurons

* global/regional reduction (atrophic)

* single neuron

ATROPHICATROPHICCEREBRAL CORTEXCEREBRAL CORTEX

CYTOPLASM FLUID ACCUMULATIONCYTOPLASM FLUID ACCUMULATION

NUCLEUSNUCLEUS NISSL SUBSTANCE

MARGINATION

CHROMATOLYSIS

Injured neuron swell → cytoplasm swell → chromatolysis: response to injury

Reversible/death

CENTRAL CHROMATOLYSIS

ANTERETROGADE DEGENERATION

AstrocyteAstrocyte

Support neuronsPromote repair

ASTROCYTEASTROCYTE

GLIOSISGLIOSIS

Reaction to injury Proliferation of astrocyte Evolves in hours to day and persists to an extent

that is usually commensurate with the severity of injury

Reactive astrocyte : gemistocytic astrocyte: exentric plump nuclei, eosinophilic cytoplam

Glial scar: composed of reactive astrocytes and their processes.

GLIOSISGLIOSIS

GEMISTOCYTEGEMISTOCYTE

OLIGODENDROGLIAOLIGODENDROGLIA

Neuroectodermal originMyelin-producing cells during late

gestational period and early neonatal

EPENDYMAEPENDYMA

Modulate fluid transfer between the cerebrospinal fluid and CNS

During gestation some viral target the ependymal cell → aqueductus stenosis → congenital hydrocephalus

EPENDYMEPENDYM

CANALIS CENTRALISCANALIS CENTRALIS

MICROGLIAMICROGLIA

Phagocytic macrophage-derived cells Reactions: changes in areas of injury 2 pattern : focal and diffuse microgliosis Microglial nodule: responses to viral or other

infection. Rod cells: prominent elongated nucleus Gitter cells: response to necrosis: it will become

phagocytic, accumulate lipid and other material

MICROGLIA MICROGLIA (PHAGOCYTE)(PHAGOCYTE)

ACTIVATED MICROGLIAACTIVATED MICROGLIA

MYELINOLYMYELINOLYSISSIS

INTRA NUCLEAR

INCLUSION( CYTOMEGALO VIRUS )( CYTOMEGALO VIRUS )

NEGRI BODY NEGRI BODY INTRACYTOPLASM (RED)INTRACYTOPLASM (RED)(RABIES ENCEPHALITIS)(RABIES ENCEPHALITIS)

NEURONOPHAGIANEURONOPHAGIA

PMN NEUTROPHIL

VASCULAR VASCULAR DILATATIONDILATATION(HYPEREMIA)(HYPEREMIA)

HYDROCHEPALUSHYDROCHEPALUS

TYPE :1. COMMUNICANS :

obstruction occurs outside ventricle system

2. NON-COMMUNICANS3. EXVACUO

(COMPENSATED)

HYDROCEPHALUSHYDROCEPHALUSPrimary hydrocephalus

– Accompanied by increased intracranial pressure– Due to:

Obstruction– Congenital

– acquired

Impaired CSF absorption Excess CSF production

Secondary hydrocephalus– Compensatory to loss of cerebral tissue

SITES OF OBSTRUCTION OF CSF PATHWAY

1. Subarachnoid space

2. Arachnoid granulationes

3. Plexus choroid

4. Lateral ventricle

5. 3rd ventricle

6. Cerebral aqueduct

7. 4th ventricle

8. Exit foramina

OBSTRUCTED AQUADUCT SYLVIOUSOBSTRUCTED AQUADUCT SYLVIOUS( BRAIN TUMOR)( BRAIN TUMOR)

OBSTRUCTIVE OBSTRUCTIVE HYDROCEPHALUSHYDROCEPHALUS

( NEOPLASM )( NEOPLASM )

OBSTRUCTIVE HYDROCEPHAL

US( INFECTION )( INFECTION )

OBSTRUCTIVE HYDROCEPHALUS( GLIAL TISSUE POST VIRAL INFECTION)( GLIAL TISSUE POST VIRAL INFECTION)

TRAUMATRAUMAPenetrating wounds produce hemorrhage

and blast effects. Velocity contributes a blast effect to a projectile

High-velocity : it disrupts tissues by its own mass and also centrifugal blast that enlarges the diameter → immediate death

Low-velocity Seizures are threat in healed penetrating

wounds, 6-12 mo after : collagenous tissue is displaced in the brain

HIGH VELOCITY BULLET WOUND HIGH VELOCITY BULLET WOUND

LOW VELOCITY BULLET WOUNDLOW VELOCITY BULLET WOUND

HEMORRHAGIC TRACTHEMORRHAGIC TRACT (PENETRATING WOUND)

Subdural hematomaSubdural hematoma

Significant cause of death from falls, assaults, vehicular acidents, sporting mishaps

Frontal/occipital area is struck by blunt object → cerebral hemispher displaced in an anteroposterior direction → hit against inner aspect

Soft cerebral tissue becomes compact then recoil → shearing effect

Usually stop after 25-30 mL

Subdural hematomaSubdural hematoma Tissue response Formation of granulation tissue → outer

membrane Fibroblast from outer membrane moved

into the hematoma → inner membrane : 2 weeks

Evolution:– Reabsorbe leave a small amount of telltale

hemosiderophage– Remain static, with potential for calcification– Enlarge : 6 months

CHRONIC SUBDURAL HEMATOMACHRONIC SUBDURAL HEMATOMA(INNER NEOMEMBRANE)

EPIDURAL HEMATOMAEPIDURAL HEMATOMA

Middle meningeal artery branches splay across temporal-parietal area

Hemorrhage into epidural space, separating dura from calvaria

4-8 hours: asymptomatic 30-50 mL: intracranial pressure increased →

exceed venous pressure → circulatory stagnation and cerebral ischemia → global cerebral hypoxia

EPIDURAL HEMATOMAEPIDURAL HEMATOMA

Cushing reflex : protective response HR slow to increase ventricular filling Myocardial contraction is forceful Systolic pressure increased Compensatory mechanism exhausted : temporal

lobe displaced downward → transtentorial herniation

Herniation compress uncus/hyppocampus against midbrain and other structures : 3rd cranial nerve

Pupil fixed and dilated

EPIDURAL HEMATOMAEPIDURAL HEMATOMA(FRONTO PARIETAL)

SITES OF HERNIATION

1. Cingulate gyrus under falx cerebri

2. Hippocampal uncus and parahippocampal gyrus over tentorium cerebeli

3. Cerebelar tonsilar through foramen magnum

4. Any defect in the dura and skull

HERNIATION

TRANSTENTORIALTRANSTENTORIALHERNIATIONHERNIATION

(MIDBRAIN DISPLACED)(MIDBRAIN DISPLACED)

GLIOBLASTOMAGLIOBLASTOMAMULTIFORMEMULTIFORME

HEMORRHAGEHEMORRHAGEHERNIATIONHERNIATION

Head, generalized cerebral atrophy – Head, generalized cerebral atrophy – CTscanCTscan

DEGENERATIVE DISORDERSDEGENERATIVE DISORDERS

DEGENERATIVE DISORDERSDEGENERATIVE DISORDERS

Brain, cerebral cortex, Alzheimer Brain, cerebral cortex, Alzheimer disease, silver staindisease, silver stain

Brain, cerebral cortex, neuritic plaque Brain, cerebral cortex, neuritic plaque stained for tau protein and beta-amyloid stained for tau protein and beta-amyloid

DEGENERATIVE DEGENERATIVE DISORDERSDISORDERS

Brain, substantia nigra, Lewy bodiesBrain, substantia nigra, Lewy bodies

DEGENERATIVE DISORDERSDEGENERATIVE DISORDERS

ALZHEIMERALZHEIMER

AlzheimerAlzheimer

Amyloid β protein– Derived from APP– Normal degradation of APP: proteolytic middle domain– Alzheimer : proteolytic in either end

Neurofibrillary tangles– Paired of helical filaments consisted of abnormal form of MAP:

tau– Phosphorylation of tau results in a protein not associated with

microtubules → deprives cells of its microtubules effect– Impairing axonal transport & compromising neuronal function

Genetic factors Apolipoprotein E

Spinal cord, amyotrophic lateral sclerosis Spinal cord, amyotrophic lateral sclerosis (A) and normal (B)(A) and normal (B)

DEGENERATIVE DISORDERSDEGENERATIVE DISORDERS

Brain, Creutzfeldt-Jakob diseaseBrain, Creutzfeldt-Jakob disease

DEGENERATIVE DISORDERSDEGENERATIVE DISORDERS

Prion diseasePrion disease(spongiform encephalopathies)(spongiform encephalopathies)

Transmissible neurodegenerative diseaseInfectious agents is prionHuman prion gene (PRNP) express cell-

surface glycoprotein bound to plasmalemma by glycolipid anchor

PrPc and PrPsc not differ in sequence except 3 dimensional conformation an patterns of glycosylation

Prion diseasePrion disease

Kuru– Fore people– Trembling– Canibalism– Spongiform cerebral and cerebelum

Creutzfeldt-Jacob disease (CJD)– Symptoms begin insidiously– 6 months exhibits severe dementia– 1 year : death

Prion diseasePrion disease

SporadicInheritedIatrogenicNew variant CJD

SporadicSporadic

75%1: 1.000.000Polymorphisme codon 129 Classical features

– Dementia– Myoclonus– Periodic spike-wave complexes

GeneticGenetic

15%Gertsmann-Straussler-Scheiner

syndrome(GSS)– Spinocerebelar ataxia with demntia

Fatal familial insomnia– Profound disturbance of sleep-wake cycles– Sings of pyramidal and cerebellar dysfunctions– Mutation codon 178 PRNP gene

IatrogenicIatrogenic

Hormone injection– Human growth hormone (55 cases)– Human pituitary gondotropin (5 cases)

Tissue grafts– Duramater (11 cases)– Cornea (1 case)– Pericardium (1 case)

Medical devices– Depth electrode (2 cases)– Surgical instruments (not definitely proven)

New variant CJDNew variant CJD

Identified following surveillance following BSE epidemic in UK

Mean age 26 years (compared to sporadic 65) Dysesthesia, none EEG of sporadic CJD Spngioform in basal ganglia and thalamus Extensive PrP plaques in cerebrum and cerebelum More PrP than sporadic CJD BSE is likely the source of vCJD

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