pathology of the nervous system

PATHOLOGY OF THE CENTRAL

NERVOUS SYSTEM

Bernadette R. Espiritu, M.D. FPSP.Anatomic & Clinical Pathologist

NEUROPATHOLOGY Emphasizes the unique character of the

nervous system and the biological attributes that it shares with other tissues.

NS – the most complex structure in the body

Interconnected with different organs & capable of rapid communications

CENTRAL NERVOUS SYSTEM

CELLS OF THE NERVOUS SYSTEM

CONGENITAL MALFORMATION

TRAUMA

CIRCULATORY DISORDERS

CSF

INFECTIOUS DISEASE

SPONGIFORM ENCEPHALOPATHIES

DEMYELINATING DISEASE

NEURONAL STORAGE DISEASE

METABOLIC NEURONAL DISEASES

VITAMIN DEFICIENCIES

DEGENERATIVE DISEASES

NEOPLASIA

CELLS OF THE Nervous System

I. NEURONSI. Mature neurons

do not divide The human body

loses neurons – aging process

Neurons cannot regenerate axons

Not efficiently remyelinated after injury

ANATOMY OF NEURONS

Nuclei – centrally located, round, contain nucleolus

Cytoplasm - abundant and the ribosome-studded endoplastic reticulum forms prominent basophilic granules – Nissl bodies Cytoplasmic pigment

Substantia nigra Locus ceruleus

Rich in neurofilaments

CELLS OF NERVOUS SYSTEM

ANATOMY OF NEURONS Dendrites – branching projections in the cell body

Best demonstrated by Silver impregnation Axon – may or may not have myelin sheath

REACTIONS OF NEURONS Some are reversible Others forecast cell death

NEURONAL REACTIONS TO INJURY

1. CHROMATOLYSIS

Swell – Imbibe fluid

Nissl substance is displaced centrifugally and becomes marginated near the plasma membrane

Nucleus assumes eccentric position

Reversible except when the axonal transection closely approximated the body

May signal serious metabolic disturbance - poliovirus

NEURONAL REACTION TO INJURY

2. ATROPHY

Gross: reduction in brain weight or selective decrease in mass of specific region Huntington disease –

caudate nucleus

Cell shrivels & become hyperchromatic - disappear

3. NEURONOPHAGIA

Injuries that kill neurons abruptly create cellular debris which elicits phagocytosis

Process of aggregation of inflammatory cells about a dead neuron coupled with phagocytosis

NEURONAL REACTION TO INJURY

4. INTRANEURONAL INCLUSIONS

Nuclear & Cytoplasmic inclusions appear in neurons : viral encephalitides and degenerative diseases

CELLS OF THE NERVOUS SYTEM

II. ASTROCYTES

‘Star-shaped cells, also neuroectodermal in origin

ANATOMY

Fibrillary astrocytes – white matter

Protoplasmic astrocytes - the gray matter

Rounded nucleus

7-10 μm in diameter

Homogenous chromatin pattern

ASTROCYTIC REACTION TO INJURY

ATROGLIOSIS (GLIOSIS)

Multiply in and about localized sites of tissue injury

Proliferation of fibrillary astrocytes is induced over a period of several days

Glial scar – cell processes

Astrogliosis marks certain generalized disease states

Capricious Gliosis General Paresis Tertiary syphilis Pick disease

Disease that progress with little attention by astrocytes Creutzfeldt-Jakob disease Alzheimer disease

ASTROGLIOSIS

This section of a brain with Krabbe's disease shows severe This section of a brain with Krabbe's disease shows severe astrogliosis (black arrows) and globoid cells around blood vessels (blue arrows).


Fibrillary astrocytes Prone to neoplastic

transformation Responsible for

dominant family of gliomas

Protoplasmic astrocytomas uncommon

antecedents of cancer


Corpora amylacea Appear within the brains of

all aged persons with predilection for the subpial and subependymal regions

Spherical, 5-20 nm amorphous structures with basophilic and argentophilic staining affinities, which are composed of carbohydrate and protein

Light microscope: extracellular

‘E’ microscope: within glial processes of astrocytes


III. OLIGODENDROGLIA

Myelin-producing cells of the CNS and are related to astrocytes – both are neuroectodermal in origin

Have dark rounded nuclei which resembles those of lymphocytes

Thin rim of cytoplasm surrounds the nuclues

CELLS OF THE NERVOUS SYSTEM

IV. EPENDYMAL CELLS

Single layer of ependymal cells –cuboidal or flat- lines: the four ventricular

chambers Aqueducts of sylvius Central canal of the

spinal cord Filum terminale

Modulate fluid transfer between the CSF and the cells of nervous system

EPENDYMAL CELLS

During gestation, some viral infections target the ependymal cells: Aquiductal stenosis Congenital

hydrocephalus

Ependymomas – exophytic masses protruding into a ventricle (4th ) Also constitute a

common intramedullary tumor of the spinal cord and filum terminale


V. MICROGLIAL CELLS

Phagocytic elements of the CNS accounting for 5% of all glial cells

Microglia often contains lipofuscin, dense bodies, & multivesicular bodies

Gray matter: appear as isolated cells or as neuronal or vascular satellites

White matter: predominantly perivascular

MICROGLIAL CELLS

ANATOMY:

By H&E: hyperchromatic, elongated nuclei surrounded by a thin rim of cytoplasm.

With Silver: linear form appears with fine lateral projections

MICROGLIAL REACTION TO INJURY

PATTERNS OF REACTIONS: Focal microglial nodules Diffuse microgliosis

MICROGLIAL NODULES – formed by microglia and astrocytes and characterize viral, rickettsial and protozoal infection

REACTIVE MICROGLIA – exhibit a prominent

elongated nuclues: rod cells With necrosis, they become distended by lipid

droplets and other cellular debris: gitter cells

CONGENITAL MALFORMATIONS

A congenital anomaly is the result of an interruption in the proper completion of a single developmental sequence

CONGENITAL MALFORMATIONS

I. NEURAL TUBE DEFECTS (DYSRAPHIC STATE)

-Refers to the defective closure of the dorsal aspect of the vertebral column

A. SPINA BIFIDA An NTD that is most common in the

lumbosacral region Spina Bifida occulta: restricted to the

vertebral arches; asymptomatic; dimple or small tuft of hair

Meningocoele: more extensive bony and soft tissue defect permits protrusion of the meninges as a fluid-filled sac. The lateral aspect of the sac are

characteristicaly covered by skin, whereas the apex is usually ulcerated

SPINA BIFIDA

Meningomyelocoele: refers to a more extensive defect that exposes the spinal canal and causes the nerve roots, particularly those of the cauda equina to be entrapped in subcutaneous scar tissue Characteristically, the spinal cord appears as flattened, ribbon-like

structure

Rachischisis: the spinal column is converted into a gaping canal, often without a recognizable spinal cord

SPINA BIFIDA

PATHOGENESIS: Failure of closure of the neural tube Maternal Folic acid deficiency

CLINICAL FEATURES: Absence of symptoms – occulta Lower limb paresis or paralysis Sensory loss Rectal & vesicle incontinence -

meningomyelocoele

NEURAL TUBE DEFECTS

B. ANENCEPHALY Congenital absence of all or part of the brain 0.5 – 2.0 / 1000 births with Female

predominance Stillborn or die within 1st few days of life

ANENCEPHALY

PATHOGENESIS:

Closure of the anterior neuropore

Disturbed angiogenesis

PATHOLOGY:

Absence of the cranial vault & the cerebral hemispheres are represented by a discoid mass or highly vascularized poorly differentiated neural tissue - cerebrovasculosa

MALFORMATION OF SPINAL CORD

SYRINGOMYELIA:

Pathology: A Tubular cavitation (syrinx) extends for variable distances along the entire length of the spinal cord which may or may not communicate with the central canal

damage to the spinal cord due to the formation of a fluid-filled area within the cord

Cause: Trauma, ischemia, tumors

Syringobulbia – Variant where slit-like cavities are located in the medulla

ARNOLD-CHIARI MALFORMATION

The brainstem & cerebellum are compacted into a shallow, bowl-shaped posterior fossa with a low positioned tentorium

Usually associated with lumbosacral meningomyelocoele

PATHOGENESIS:

Meningomyelocoele serves to anchor the lower end of the spinal cord and that the downward growth of the vertebral column creates traction on the medulla

ARNOLD-CHIARI MALFORMATION

PATHOLOGY:

The caudal aspect of the cerebellar vermis is herniated through an enlarged foramen magnum and protrudes as a tongue on the dorsal aspect of the cervical cord, often reaching the level of C3 to C5

The herniated tissue is bound in position by thickened meninges and shows pressure atrophy with depletion of Purkinje and granular cells

The brainstem is also displaced caudally

CONGENITAL HYDROCEPHALUS

Excessive amount of CSF in varied location and have many causes

Congenital Atresia of Aqueduct of sylvius – most c0mmon cause Midbrain – multiple atretic channels Aqueduct stenosed by periaqueductal gliosis :

transplacental transmission of viruses known to induce ependymitis

DISORDERS OF CEREBRAL GYRI

- Associated with mental retardation

Polymicrogyria –

presence of small and excessive gyri

Pachygyria – the gyri are reduced in number and unusually broad

Lissencephaly – The cortical surface of the cerebral hemispheres is smooth or only lightly furrowed Almost all patients with Lissencephaly (92%) shows

deletion in the region of LIS1 gene on chromosome 17p13.3


PATHOGENESIS

Gyral malformations arise from disturbances in neuronal migration, a highly patterned event of the trimester of embryonic development

Primitive neurons move centrifugally from the germinal mantle to populate the cortex

Number of neurons and their positions in the cortex determine factors in the redundancy of the cortical mantle which initiates the infolding that creates sulci


Heterotopia – a focal disturbance in neuronal migration that leads to nodular collections of ectopic neurons … white matter Associated with:

mental retardation seizures

Migrational disturbances is associated with: Maternal alcoholism

CONGENITAL DEFECTS

ASSOCIATED WITH

CHROMOSOMAL

ABNORMALITIES Derangements of larger

chromosomes

Incompatible with sustained intrauterine life

Affected fetuses are aborted

DOWN SYNDROME

Trisomy 21 – mental retardation, distinctive facial features, and a variety of anomalies

Weight of the brain is moderately reduced, and the organ is shortened in its anteroposterior dimension

Simple gyral pattern, with disproportionately slender superior temporal gyri

TRISOMY 13-15

1 per 5000 births; > female

Congenital deformities involve:

brain, facial features, and extremities

The complex is dominated by holoprosencephaly, arrhinencephaly, microphthalmia, cyclopia, low-set ears, harelip, and cleft palate

Extremities exhibit polydactyly and “rocker bottom” feet

TRISOMY 13-15

HOLOPROSENCEPHALY

– refers to a microcephalic brain that

features an absence of the interhemispheric fissure

Horse-shoe shaped cerebral hemispheres

Common ventricular chamber

The base of the ventricular chamber is formed by the bilobed structures of the caudate nuclei and thalami

Rarely compatible with life beyond a few weeks or months

TRISOMY 13-15

ARRHINENCEPHALY – The absence of the olfactory tracts and bulbs (rhinencephalon) is associated with holoprosencephaly or occurs as a solitary malformation

ABSENCE OF CORPUS CALLOSUM – regular feature of holoprosencephaly Associated with seizures Its absence permits the lateral ventricles to drift

outward and upward – radiographically diagnostic

Agenesis of the corpus callosum is a birth defect in which this structure in the brain is either partially or completely missing.CAUSE: disruption to development of the fetal brain which may be related to chromosome errors, genetic factors, prenatal infections, or other factors related to prenatal environment.

EPILEPSY

Paroxysmal, transient disturbances in brain function that are expressed as impairment in or loss of consciousness, abnormal motor activity or sensory or mental disturbances

Idiopathic – sporadic, hereditary

PATHOLOGY: neuronal loss & reactive gliosis

Affected areas: hippocampus, cerebellum, thalamus and cerebral neocortex

Acquired Seizures: Intracranial tumor, AV mal, Brain scar from penetrating wound

EPILEPSY

A seizure occurs when the message delivery system becomes unbalanced. Under normal circumstances, the neurotransmitter GABA does its part to make sure the system stays in synch by triggering signals in the form of charged particles (A). It causes a large concentration of negatively charged chloride particles (Cl-) to enter the receiving neuron. This tells the neuron to not pass on the message. When there is not enough GABA a person can have a seizure because receiving neurons can be flooded with signals that say "pass on this message." The "go" messages are triggered by a different type of neurotransmitter that promotes message transfer (B). The charged signals they set off are positive. This time, more positively charged sodium particles (Na+) enter the neuron, which tells the receiving neuron to pass on the message.

TRAUMA

I. EPIDURAL HEMATOMA

Accumulation of blood between the calvarium & the dura.

A result of a blow to the side of the head that fractures the temporal bone

Must be treated promptly

EPIDURAL HEMATOMA

PATHOGENESIS: Fracture of the temporo-parietal bone causing the transection of the branches of the middle meningeal artery (occupy the space between the dura & the calvarium)

Temporal bone - one of the thinnest bones of the skull

The initial 4-8 hrs : asymptomatic

The earliest volumetric adjustment – displacement of CSF through the aperture in the tentorium

Symptoms: volume of the hematoma 30-50ml.

EPIDURAL HEMATOMAPATHOLOGY

When the increased ICP exceeds the venous pressure the large venous sinuses are compressed creating cerebral ischemia & hypoxia

Clinical: confusion & disorientation

CUSHING REFLEX: Protective response that augment cerebral circulation and increased oxygenation. The heart slows down to increase ventricular filling & myocardial contraction become forceful > BP systolic is increased

EPIDURAL HEMATOMA

Continued Bleeding > Decline in the level of consciousness > hge & necrosis appear > the regional injury to the reticular formation becomes irreversible >> Death

Epidural Hematomas are invariably progressive & when not recognized early & evacuated, becomes fatal in 24-48 hrs.

SUBDURAL HEMATOMA

Accumulation of blood in the subdural space as a consequence of bleeding from torn bridging veins

Significant cause of death after head injuries from falls, assaults, vehicular accidents, and sporting mishaps

Cerebral hemispheres are immersed in CSF

Blood vessels and cranial nerves

Free to float in an anteroposterior direction

SUBDURAL HEMATOMA

Venous drainage from the cerebral hemispheres flows upward through veins in the pia

Parasagittal region

Subarachnoid space

Arachnoid

Traverse the theoretical subdural space

Dura sinus

SUBDURAL HEMATOMA

Arachnoid applied to the dura

Dural border cell (DBC)

Arachnoid barrier cell (ABC)

Intercellular junctions

SUBDURAL HEMATOMA

Hematomas and hygromas separate the meninges along the path of least resistance

Frontal or occipital portion/stationary head

Cerebral hemispheres are displaced

Soft cerebral tissues become compact and then recoil; rippled movement in the cerebral parenchyma

SUBDURAL HEMATOMA

Dura – skull

Arachnoid – cerebrum

Disparate movement of membranes produces shearing effect localized to the Dura Border Cell layer

Cortical veins are torn

Compression of severed bridging veins initiates thrombosis

SUBDURAL HEMATOMA

Bleeding from outer membrane

Vulnerable to minor trauma

Hyperosmotic state

Diaphanous arachnoid

Contiguous fibroblastic proliferation

Absence of blood in the CSF does not negate the presence of a subdural hematoma

SYMPTOMS: SUBDURAL

HEMATOMA Protean

Stretching of meninges – headaches

Pressure on motor cortex – contralateral weakness

Focal irritation of cortex – seizures

Impair cognitive function

Dementia

Enlarge mass and lethal transtentorial herniation

SUBARACHNOID HEMORRHAGE

Bleeding into the subarachnoid space of any cause

Traumatic head injuries, Cerebral contusion , Laceration

2/3 of cases reflect a pre-existing arterial aneurysm

10% AV Mal is demonstrated

CEREBRAL CONTUSION

A bruise of the cortical surface of the brain as a result of head trauma

MECHANISM OF CEREBRAL CONTUSION:

The cerebral hemispheres float in the CSF

Rapid deceleration or less commonly acceleration of the skull cause the cortex to impact forcefully into the anterior & middle fossae.

The position of a contusion is determined by the direction of the force & the intracranial anatomy

CEREBRAL CONTUSION

CEREBRAL CONTUSION

A cerebral contusion is basically a bruise of the brain.

With trauma, the tissue can become damaged and swollen and blood vessels within the tissue can break, leading to oozing of blood into the tissue.

When a traumatic brain injury occurs, the brain moves around inside the skull.

Direct impact or the sloshing of the brain and hitting the inner part of the skull can cause this type of injury to the brain. The brain tissue itself is quite fragile and easily injured. With enough force applied to the head, the brain can hit the side of the skull, leading to a cerebral contusion.

CEREBRAL CONTUSION

coup is the primary impact on the head, caused by whatever hit the head during the trauma. When this force is applied, the brain slides back and forth inside the skull, frequently hitting the bone on the other side of the head.

contra coup is opposite the side of the initial impact.

the most common location for these contusion injuries is in the area of the temporal lobes and lower frontal lobes.

PENETRATING WOUNDS

Causes: Bullets / knives enter the cranium with variable velocities

Seizures – threat

Collagenous tissue

Fibroblasts

SPINAL CORD INJURIES

Morbidity – paraplegia or quadriplegia

Penetrating wounds – stab wounds, bullets

Indirect injury – vertebral fractures, fracture-dislocations, subluxation of spine

HYPEREXTENSION INJURY – tears spinal ligament

HYPERFLEXION INJURY – impact forces on vertebral body down upon the underlying one

SPINAL CORD INJURY

We can divide SCI into two categories - complete and incomplete.

A complete injury means that there is no function below the level of the injury (no sensation and no voluntary movement) and both sides of the body are equally affected.

An incomplete injury means that there is some functioning below the primary level of the injury. One limb may be able to be moved more than the other, the person may be able to feel parts of the body that cannot be moved and there may be more functioning on one side of the body than the other.


Concussion of spinal cord – mildest injury Transient and reversible disturbance of spinal

cord

Contusion of spinal cord – more severe trauma Myelomalacia Hematomyelia

Lacerations and transections of the spinal cord – penetrating wounds Irreversible; complete loss of function


The vertebral column in an adult typically consists of 33 vertebrae arranged in five regions: Seven (7) cervical

vertebra twelve (12) thoracic

vertebra five (5) lumbar vertebra five (5) fused sacral

vertebrae four (4) fused coccyx

vertebrae

In adults the vertebral column is approximately 72-75cm in length and serves to:

Protect the spinal cord and spinal nerves

Support the weight of the body

Provides a partly rigid and flexible axis for the body and a pivot point for the head

Play an important role in posture and motion (movement from one place to another)

CIRCULATORY DISORDERS

VASCULAR MALFORMATION

FOUR MAJOR CATEGORIES:

AV-MAL – most common & w/ greatest significance Evolves during embryonic dev as a result of a

focal absence of a capillary bed which direct communication between cerebral arteries an veins

Located in the cerebral cortex & the contiguous underlying white matter

Enlarges – recruitment of the tributary vessels

VASCULAR MALFORMATION CAVERNOUS ANGIOMA:

Less common Formed by large vascular spaces

compartymentalized by prominent fibrous walls

Asymptomatic Intracranial bleed, Epilepsy focal neurological disturbancesdilated, thickened blood vessels lacking elastic

lamina and without intervening brain parenchyma

VASCULAR MALFORMATION

TELANGIECTASIA : Focal aggregate of uniformly small vessels with

intervening neural parenchyma may initiate seizures but rarely ruptures

VENOUS ANGIOMA: Focus of a few enlarged veins distributed

randomly in the spinal cord or brain asymptomatic

ANEURYSMS

Weakness in arterial walls exploited by intravascular pressure

CAUSES:

Developmental Defects – gives rise to Berry Aneurysm (saccular medial defect)

Atherosclerosis

Hypertension – associated with lipohyalinosis of cerebral arterioles and induces Charcot-Bouchard aneurysm

Bacterial infection – leads to mycotic aneurysm

Trauma – causes Dissecting Aneurysm

http://emedtravel.files.wordpress.com/2011/11/information_about-brain_aneurysm.jpg

BERRY ANEURYSMPATHOGENESIS:

The consequence of arterial defects that originate during the embryonic development when the bifurcation of the artery creates a Y-shaped configuration

The muscle layer of the parent vessel & that of the 2 branches are separate and may fail to interdigitate adequately across the notch of the Y.

PATHOLOGY:

a point of muscular weakness bridged only by endothelium, the internal elastic membrane & a slender coating of adventitia

Increase Pressure > internal elastic membrane degenerates & fragments > endothelium yields >Saccular aneurysm formed by adventitia

BERRY ANEURYSM

> 90% - Carotid system: At the union of

Ant. Cerebral & ant. Communicating A

Complex of the int. carotid - post comm.- Ant. Cerebral- ant. Choroidal A

Trifurcation of the middle cerebral A

CLINICAL:

Rupture – results in life threatening subarachnoid hge with a 35% mortality during the initial hge

BERRY ANEURYSM

BERRY ANEURYSM

CLINICAL:

Rupture – results in life threatening subarachnoid hge with a 35% mortality during the initial he

Sudden severe headache – heralds the onset of subarachnoid he & maybe followed by coma

Patients who survive for 3-4 days – manifest progressive decline in consciousness – attributed to arterial spasm & consequent cerebral ischemia & infarction

Survivors – re-bleed & prognosis is worse

ATHEROSCLEROTIC ANEURYSM

Caused by atherosclerosis localized in the major cerebral vessels (vertebral, basilar,& internal carotids)

Fibrous replacement of the media & destruction of the internal elastic membrane weakens the arterial wall & permits aneurysm dilatation

Characteristically fusiform

& as they enlarge, the vessel elongates

Rarely ruptures

Major complication is Thrombosis

Pontine infarction – often sequelae of aneurysm in the basilar A

MYCOTIC ANEURYSM

Infections of arterial walls result from septic emboli with origins in an infected heart valve

Emboli - Carotid circulation - lodges in a branch of Middle Meningeal Artery at the origin of the short penetrating carotid vessel -- bacteria proliferate - inflammation - destroys the integrity of the arterial wall - aneurysm - rupture (seen as intracerebral or subarachnoid hge) - bacteria / microorganism released - cerebral abscess or suppurative meningitis

CEREBRAL HEMORRHAGE

Spontaneous – no trauma / vascular anomaly / consequence of long-standing hypertension

Strokes or apoplexy – include occlusive cerebrovascular lesions ( infarcts)

HYPERTENSIVE INTRACEREBRAL HEMORRHAGE

ORDER OF FREQUENCY: Basal ganglia-thalamus 65% Pons 15% Cerebellum 8%

CEREBRAL HEMORRHAGE

HYPERTENSIVE INTRACEREBRAL HEMORRHAGE

Charcot-Bouchard aneurysm – formed by the weakening of the wall

Small fusiform aneurysms located on the trunk of a vessel rather than at the bifurcation & are disposed to rupture & he

Onset of symptoms – abrupt & weakness dominates

When hge is progressive, Death occurs within period of hours or several days

CEREBRAL HEMORRHAGE

INTRAVENTRICULAR HEMORRHAGE

Rupture of a vessel into a ventricle rapidly distends the entire ventricular system with blood.

Death : Distension of the 4th ventricle & compression of the vital centers of the medulla

PONTINE HEMORRHAGE

Loss of consciousness reflects damage to the reticular formation – overshadows all other specific cranial nerve deficits

Patients rarely survives

CEREBRAL HEMORRHAGE

CEREBELLAR HEMORRHAGE

Abrupt ataxia, accompanied by severe occipital headache and vomiting

Compression of medulla – herniation of cerebellar tonsils into the foramen magnum

OTHER CAUSES:

Leakage from AV-Mal

Erosion of vessels by a 1o or 2o neoplasm

Bleeding diathesis – thrombocytopenic purpura

Endothelial injury by microorganism: rickettsia

Embolic infarction

ISCHEMIA & INFARCTION

Inadequate perfusion of the brain

STROKE

cerebrovascular accident (CVA), a stroke is a potentially fatal event in which part of the brain does not get enough oxygen.

It may be due to either a prolonged lack of oxygen-rich blood (cerebral ischemia or cerebral infarction) or bleeding into or around the brain (cerebral hemorrhage).

CEREBRAL ISCHEMIA

(INFARCTION) The most common type of stroke occurs when a blood vessel

becomes plugged, and it accounts for about 80% of all strokes.

The plug can originate in an artery of the brain or it can originate somewhere else in the body, often the heart, where it breaks off and travels up the arterial tree to the brain, until it lodges in a blood vessel.

"traveling clots" - emboli

Strokes caused by emboli from the heart are often seen in:

people with an irregular heartbeat -atrial fibrillation

after a heart attack or heart surgery

Ischemic strokes are largely preventable if risk factors are recognized early and managed.

CEREBRAL HEMORRHAGE

Rupture of a blood vessel can produce a bleeding type of a stroke. This is when an aneurysm, or an out-pouching, of a blood vessel in the brain ruptures.

Account for about 15-20% of all strokes, but they are the most deadly.

The main thing you can do to prevent a cerebral hemorrhage is to control high blood pressure.

PART II

INFECTIOUS DISEASES

MENINGITIS

Leptomeningitis – denotes an inflammatory process that is localized to the interfacing surfaces of the pia and arachnoid CSF – excellent culture medium for most

microorganisms

Pachymeningitis – Inflammation of the dura, a consequence of contiguous infection: Chronic sinusitis / Mastoiditis Dura – substantial barrier to infection & inflammation

is usually restricted to the outer surface

meningitis

BACTERIAL MENINGITIS

1. SUPPURATIVE MENINGITIS

Purulent meningitis (suppurative meningitis) is a type of meningitis characterized by a purulent exudate within the subarachnoid space

Most definitive index of meningitis - PMNs

SUPPURATIVE MENINGITIS


E. coli – prime cause in NBs Cross-placental transfer: requires IgM

H. influenza – maximal in 3mos – 3 yrs

Strep pneumoniae Pts w/ basilar skull fracture; the 2nd most frequent

cause of purulent meningitis.

Neisseria meningitides – frequents the nasopharynx Airborne – transmission Initial phase – bacteremia: fever, malaise, petechial rash Maybe associated with lethal adrenal hges (Waterhouse-

Friderichsen syndrome

ACUTE SUPPURATIVE MENINGITIS

Severe infection, almost always caused by bacterial infection

Highest peak in Children ; 2nd peak in elderly Neonate & Children

Group B Strep, E. coli, Listeria Older infants, Children, Young Adults

Strep. Pneumonia, N. meningitidis Older Adults

S. pneumoniae, gm – rods

Very ill, with fever, headache, prostration, neck stiffness & photophobia


PATHOGENESIS:

Hematogenous dissemination (Most Common) From bacteremia

Near organ infected Sinusitis, Otitis media, Mastoiditis, Brain Trauma

From Congenital Developmental Malformation Spinal Meningocoele, Paranasal Sinuses Leak,

Sinus Tract

Cerebral surgery & lumbar puncture Iatrogenic

GROSS:

Subarachnoid space contains cream colored purulent exudate

Secondary thrombosis of the superficial vessels & cerebral ischemic damage, hydrocephalus (impaired CSF Flow)

Brain abscess

MICROSCOPIC

TUBERCULOUS MENINGITIS

TB MENINGITIS

POTT DISEASE – TB OF SPINAL COLUMN

Inclusion bodies in viral encephalitides

Herpes simplex(Cowdry Type A)

Neuron

Cytomegalovirus Neuron or astrocyte

RabiesNegri bodies Neuron

Progressive multifocal leukoencephalopathy

Oligodendroglia

Subacute sclerosing panencephalitis

Neuron

CRYPTOCOCCAL MENINGITIS

Cryptococcus neoformans (Fungal)

Inhalation of contaminated particulates

Birds excreta – inhaled- pneumonitis

– bloodstream – intracranial compartment

Gelatinous cysts – brain parenchyma

Amoebic Meningoencephalitis

Naegleria & Acanthamoeba – olfactory nerves to cribriform plate – intracranial compartment after swimming

SYPHILITIC MENINGITIS

Treponema pallidum - enters the bloodstream from the primary chancre

CSF PROFILEPROFILE COMMON CAUSES

PURULENT PMNs LOW GLUCOSE INCREASED CHON

BACTERIAL

LYMPHOCYTIC LOW GLUCOSE

TB, FUNGAL, SPIROCHETAL, SARCOIDOSIS; CA

LYMPHOCYTIC NORMAL GLUCOSE MOD. INCREASED CHON

VIRAL (ASEPTIC)

NEOPLASIA

Nueroectoderm – Gliomas

Mesenchymal Structures – Meningiomas &

Schwannomas

Ectopic Tissues – Craniopharyngiomas, Dermoid & Epidermoid cysts, Lipomas, Dysgerminomas

Retained Embryonal Structures – Paraphyseal cysts

Metastasis

NEOPLASIA

2 % of all aggressive tumors

Frequent in childhood Gliomas – 60%

Astrocytes - Astrocytomas Oligodendroglia- oligodendrogliomas Ependyma - ependymomas

Meningiomas – 20% All the others – 20%

Difficulty: Well-diff – Normal Tissue

Anaplastic tumors – Not resemble nervous

tissue

NEOPLASIA: REMINDERS

Benign Vs. Malignant

Requires Qualification when used in reference to gliomas

Age of the Patient & Location

Predictable geographic location Astrocytic tumors :

Cerebral hemispheres, middle life & old age Cerebellum & pons – Childhood Spinal cord – in young adults

NEOPLASIA

Oligodendrogliomas Predominantly involve the cerebrum – Adults

Ependymomas Highest incidence in the 4th ventricle Intramedullary lesion derived from the lining

of the spinal canal & filum terminale Lowest incidence – Lateral ventricle

Meningiomas – Arise from widely distributed arachnoid villi but with preferred sites of origin

NEOPLASIA: SYMPTOMS:

Neurological deficit – sensory or motor

Cognitive functions

Seizures Meningiomas Well-diff Gliomas:

Astrocytomas Oligodedrogliomas Gangliomas

Increase intracranial pressure – Edema + Mass Headache Vomiting

TRANSTENTORIAL HERNIATION

Medial aspect of the hippocampus (uncus) herniates into the aperture of the tentorium

Interferes with the circultory dynamics of the midbrain & causes a decline in the level of consciousness – result of the impaired function of the reticular formation

Compresses the 3rd nerve against the edge of the tentorium – 3rd nerve palsy – FIXED DILATED PUPIL

Irreversible Midbrain necrosis & hemorrhage – permanent loss of consciousness then DEATH

FORAMEN MAGNUM HERNIATION

Cerebellar tonsils herniate into the Foramen magnum due to increase pressure in the posterior fossa

Compresses the cardiac & respiratory centers

Death

SUBFALCINE HERNIATION

The cingulate gyrus herniates beneath the falx – results in infarction of areas supplied by the pericallosal vessels >> Weakness or sensory loss in the legs

TUMORS FROM ASTROCYTES

1. ASTROCYTOMA

A glioma composed of well-differentiated astrocytes

20% of primary intracranial tumors

Frequent location: Cerebral hemispheres in adults Optic nerve, walls of the 3rd ventricle, midbrain,

pons & cerebellum – 1st 2 decades of life Spinal cord – pred in the thoracic & cervical

regions – young Adults

FIBRILLARY ATROCYTOMA

Cerebral hemispheres in adults

Intermediate dense glial processes

The pivotal event in the transformation of normal to neoplastic astrocytes is mutation of the tumor supressor gene p53 on 17p.

GFAP immunostain -The protein of these filaments, glial fibrillary acidic protein

ASTROCYTOMA

The fibrillary astrocytoma is the most common histologic subtype of diffuse astrocytoma.

Gemistocytic is the other common subtype, and it has a higher and more rapid rate of progression to glioblastoma

GEMISTOCYTIC ASTROCYTOMA

Abundant eosinophilic cytoplasm

the tumor cells can be stellate, spindle-shaped with fiber like processes, or plump with a large eosinophilic cytoplasmic mass (gemistocytic astrocytomas). They spread in a diffuse fashion but may also form microcysts and other tissue patterns.

PILOCYTIC ASTROCYTOMA

Cerebellum

Pons

Hypothalamus

GROSS: Circumscribed & Cystic

JUVENILE PILOCYTIC

ASTROCYTOMA Occurs in children

Characterized by abundant hair-like glial processes & typically contains the Rosenthal fibers and eosinophilic granular bodies.

Sparsely cellular , without anaplasia or mitoses. - biphasic pattern, consisting of cellular and fibrillary perivascular areas, alternating with loose microcystic zones.

GLIOBLASTOMA MULTIFORME-WHO GRADE

IV

Necrosis & hemorrhageVarriegated appearance

GBM

anaplsia Necrosis and pseudopalisading

GBM Vascular endothelial

proliferation

Densely cellular arrays of tumor cells are often arranged in a perpendicular (pseudopalisading) fashion around serpiginous necrotic areas. It has been proposed that these tumor cells are migrating away from a central hypoxic area.

GBM is one of the most highly vascular solid tumors.

WHO GRADING SYSTEM

Grade I-Pilocytic astrocytoma Benign cytological features

Grade II-Low-grade astrocytoma Moderate cellularity-no anaplasia or mitotic

activity

Grade III- Anaplastic astrocytoma Cellularity, anaplasia, mitoses

Grade IV-Glioblastoma Same as Grade III plus microvascular

proliferation and necrosis

OLIGODENDROGLIOMA

Arise in the cerebral hemispheres of middle-aged adults.

They are insidious, slow-growing tumors and have a mean survival of five years.

Oligodendrogliomas are more circumscribed than astrocytomas.

the tumor cells are uniform and have round central nuclei surrounded by a clear space or halo (unstained cytoplasm) which is an artifact of processing.

OLIGODENDROGLIOMAS

Infiltrate the cortex diffusely

Traversed by delicate capillaries and have a tendency to calcify, which is helpful in radiological and histological diagnosis

EM examination, the tumor cells produce abundant plasma membrane that tends to form concentric layers mimicking myelin

Some oligodendrogliomas have an astrocytic component. Such mixed tumors are called oligoastrocytomas.

Can be classified: as low-grade or high-grade based on cellularity, mitotic activity, vascular endothelial proliferation, and necrosis.

OLIGODENDROGLIOMAS

Oligodendrogliomas are among the most chemosensitive solid tumors.

They show losses of chromosomes 1p and 19q which correlate with increased sensitivity to PVC and temozolomide chemotherapy and longer survival

EPENDYMOMA

EPENDYMOMAS

Predominantly tumors of children and adolescents.

Arise most frequently in the 4th ventricle and cause hydrocephalus by blocking CSF flow.

Occur anywhere in relation to the ventricular system or central canal

The most common primary intra-axial tumors in the spinal cord and filum terminale.

Well demarcated from the surrounding brain and spinal cord

Grow in an exophytic fashion, protruding into and out of the fourth ventricle.

Spinal ependymomas are circumscribed intra-axial masses.

EPENDYMOMAS

Perivascular pseudorosettes Tubular formation – true rosettes

EPENDYMOMA

Microscopically:

The tumor cells resemble normal ependymal cells and are arranged in: perivascular

formations tubular structures

like the central canal of the spinal cord

papillary formations

An anaplastic version of ependymoma, called ependymoblastoma, is seen infrequently in young children.

Most ependymomas are histologically and biologically low-grade, but surgical resection of fourth-ventricle ependymomas is difficult.

MEDULLOBLASTOMA Medulloblastoma is a highly

malignant primary brain tumor that originates in the cerebellum (infratentoria) or posterior fossa in the external granular layer of the neurons

Another term for medulloblastoma is infratentorial PNET.

Medulloblastoma is the most common PNET originating in the brain.

All PNET tumors of the brain are invasive and rapidly growing tumors that, unlike most brain tumors, spread through the CSF & freq metastasize to different locations in the brain & spine

10-yr survival rate = 50%

MEDULLOBLASTOMA

medulloblastoma

External granular layerDesmoplastic

MEDULLOBLASTOMA

Second most frequent BT in children after pilocytic astrocytoma.

Most medulloblastomas occur in the 1st decade of life. There is a second peak in the early 20s.

Its embryonal nature is underlined by its high incidence in infants and children and by its undifferentiated, immature appearance, which resembles developing neural tissue.

The term primitive neuroectodermal tumor (PNET), which has been applied to medulloblastoma and other "small blue cell tumors" of the brain, reflects the embryonal nature and undifferentiated appearance of these tumors and their potential for neuronal and glial diffferentiation

MEDULLOBLASTOMA

Gross :

medulloblastomas are soft, pink-red, and well demarcated.

They can block the fourth ventricle and the aqueduct, causing hydrocephalus.

MEDULLOBLASTOMA

Microscopically:

classical medulloblastoma is a highly cellular tumor composed of diffuse masses of small, undifferentiated oval or round cells.

Some medulloblastomas show neuronal, glial and other differentiation.

Neuronal differentiation is manifested by neuropil and rosette formation.

Rosettes are groups of tumor cells arranged in a circle around a fibrillary center.

Infrequent mature neurons may also be found in medulloblastomas.

Glial differentiation in some tumors is reflected by GFAP-positive cells.

MEDULLOBLASTOMATreatment :

begins with maximal resection of the tumor

The addition of Radiation to the entire neuraxis and chemotherapy may increase the disease-free survival This combination: 5-

yr survival > 90%

Gamma knife radiosurgery – for recurrent

Prognosis:

Presence of desmoplastic featres – better prognosis

Prognosis is worse

< 3 yrs. Old

Inadequate resection

CSF, Spinal, Supratentorial or systemic spread

Intracranial pressure may be controlled with corticosteroid or VP shunt

NEOPLASM OF MESENCHYMAL

ORIGINMENINGIOMA

Intracranial tumor that arise from the arachnoid villi and produce symptoms by compressing adjacent brain tissue

MENINGIOMA A meningioma is benign neoplasm that

arises from the meninges. The tumor can arise within the intracranial cavity, spinal cord or orbit.

PATHOGENESIS:

Arise in one of the 3 settings:1. Sporadic cases (most common)

2. Iatrogenic cases caused by prior radiation therapy to the cranium

3. In association with a genetic disorder esp neurofibromatosis type 2

MENINGIOMA

Sporadic: loss, partial deletion or mutation of chromosome 22 involving the NF2 locus (22q12)

Suggests that inactivation of the putative NF2 tumor-suppressor gene is involved in the genesis of many meningiomas and schwannomas arising sporadically

Seizures – parasagittal & over the convexity

Post-Radiation – dose related

GROSS: MENINGIOMA

Meningiomas are circumscribed;

They may be attached to the dura, though they do not arise from the dura per se.

Usually, they displace brain tissue without invading it.

Some meningiomas grow flat on the surface of the brain.

Meningioma: HISTOLOGIC

the most common histological subtypes of meningiomas - have no prognostic significance.

Meningothelial meningiomas are composed of diffuse masses of arachnoidal-like cells.

Transitional meningiomas, tumor cells are arranged in whorls with hyalinized and calcified centers that are called psammoma (sand) bodies because they resemble tiny grains of sand.

Fibroblastic meningiomas are composed of fascicles of fiber-like cells with abundant interstitial collagen.

MENINGIOMA

Fibroblastic meningiomasTransitional meningiomas w/ whorls

MENINGIOMA

Malignant meningiomas are relatively infrequent. They display overt histological anaplasia and increased mitoses and invade the brain.

These atypical meningiomas grow more rapidly and are more prone to recur after surgical resection.

Some histological types, such as papillary, chordoid, rhabdoid, and clear cell meningioma, also have a more aggressive behavior and are associated with a higher rate of recurrence.

Meningiomas of the optic nerve typically affect middle-aged women (female: male ratio = 5: 1).

This tumor either arises from the meningeal coverings of the optic nerve or from direction extension from the cranial vault.

Manifestations include slowly progressive vision loss, mild proptosis, optic atrophy & optociliary shunt vessels.

SCHWANNOMA

Arise most often in cranial and spinal nerve roots and peripheral nerves but can occur anywhere, including in the brain and in the ventricles.

90% arise in the 8th nerve root (acoustic Schwannoma, cerebellopontine angle tumor)

The preferential involvement of the 8th nerve may have to do with chronic exposure to loud noise (acoustic trauma)

Most Schwannomas are solitary.

Bilateral acoustic or multiple Schwannomas are the hallmark of NF2.

schwannoma

Pons is deformed & pushed laterally

Palisading tissue pattern

SCHWANNOMA

Microscopically

they consist of fascicles of spindle cells that are arranged in palisades. Less frequently they form a loose reticular pattern.

They are benign, slow-growing tumors, and cause symptoms by compression.

Gross:

Schwannomas are extra-axial, circumscribed and encapsulated and range from small and solid to large, irregular, cystic, and hemorrhagic masses.

They do not invade, but rather displace the brainstem and spinal cord as they grow

NEUROFIBROMA

Peripheral nerve tumors composed of a mixture of Schwann cells and fibroblasts.

They cause a fusiform enlargement of the nerve in which they arise.

Microscopically, their cells are loosely arranged in a wavy pattern.

Multiple neurofibromas that involve long segments of peripheral nerves (plexiform-from a Greek word that means braid- neurofibromas) are characteristic of NF1

NEOPLASM DERIVED FROM ECTOPIC

TISSUES CRANIOPHARYNGIO

MA

Grossly, they show a mixture of solid and cystic areas.

CRANIOPHARYNGIOMA

Microscopically

composed of sheets of squamous epithelial cells and keratin, set in a loose connective tissue stroma.

Islands of keratin often calcify.

Water accumulating in the central portion of the epithelial islands causes them to loosen, creating an appearance that resembles adamantinoma.

FNA – CHOLESTEROL CRYSTALS

TUMORS OF GERM CELL ORIGIN

HEMANGIOBLASTOMAS

are sporadic or familial.

The latter are associated with the von Hippel Lindau disease.

Young & middle aged group

Found in the cerebellum as a mural nodule within a cyst

Benign Tumor which consists of numerous delicate capillaries set in a background of clear foamy cells.

CEREBRAL LYMPHOMA

Spreading across the corpus callosum

Large cell lymphoma with perivascular infiltration

LYMPHOMAS

Primary cerebral lymphomas are thought to arise from indigenous brain histiocytes (microglia) or from rare lymphocytes that are normally present in the meninges and around vessels.

affect immunosuppressed individuals such as patients with AIDS

Microscopically, most of them are large, B-cell lymphomas.

The tumor cells form dense perivascular sheaths or diffuse masses.

Meningeal spread is very common, and some cerebral lymphomas arise in the subarachnoid space.

Cerebral lymphomas, like their extracerebral high-grade counterparts, are highly malignant.

METASTATIC TUMORS

Metastatic tumors account probably for the majority of BT.

Brain metastases are found at autopsy in 14% to 37% of malignant tumors.

In men, the most common primary is carcinoma of the lung, which shows brain metastases in 35% of the cases

in women, it carcinoma of the breast, which metestasizes in 21% of the cases.

METASTATIC TUMORS

The tumor with the highest rate of metastasis is melanoma.

Meningeal carcinomatosis (diffuse spread of tumor in the subarachnoid space) is seen in 4% to 8% of metastatic BT and is more common with carcinoma of the lung, carcinoma of the breast, and acute lymphoblastic leukemia.

The CSF in meningeal carcinomatosis shows:

high protein, low glucose, and a few lymphocytes.

The often insidious onset of symptoms and the CSF findings suggest mycobacterial meningitis, especially if the primary tumor is too small to be detected.

Cytological examination of CSF reveals tumor cells.

THE EFFECTS OF BRAIN TUMORS

The local effects of BT are loss of function (focal deficits) and seizures.

The general effects of tumors have to do mainly with increased intracranial pressure.

Increased intracranial pressure is caused by:

a) the mass of tumor added to the brain

b) hydrocephalus due to obstruction of CSF circulation and

c) cerebral edema, i.e., accumulation of fluid in the interstitial space around the tumor.

A T & TUMORS ????

1. Which of the following(s) is(are) true about childhood meningiomas?

1. They are more likely to behave more aggressive and recur more

frequently.

2. They are associated with neurofibromatosis 2 (NF2).

3. They are more likely to be found at infratentorial, intraventricular, or

intraparenchymal locations.

4. Meningioms are common tumors in infants and children.

A. 1, 2, and 3 are true. D. Only 4 is true

B. 1 and 3 are true. E. All of the Above

C. 2 and 4 are true.

2. This primary cerebral tumor was removed from an 18 month-old boy. The most likely diagnosis is:

A. Ependymoma.

B. Choroid plexus papilloma.

C. Pilomyxomoid astrocytoma.

D. Medulloepithelioma.

E. Medulloblastoma.

3. Which type of meningioma is most likely to be found in patients under 20 years of age?

A. Fibrous meningioma.

B. Transitional meningioma.

C. Secretory meningioma.

D. Chordoid meningioma.

E. Psammomatous meningioma.

4. Which of the followings is not true about optic nerve glioma?

A. Optic nerve gliomas in children tend to behave in a indolent, slowing growing fashion.

B. Optic nerve gliomas are associated with neurofibromatosis 1 (NF1).

C. Optic nerve gliomas in adults tend to be non-familial and behave in a benign fashion.

D. Spontaneous regression has been described in childhood cases of optic nerve gliomas.

E. Optic nerve gliomas tend to grow outside the optic nerve and expand the subarachnoid and subdual space.

5. This primary tumor is removed from the cerebellum of a 2 year-old boy. The most likely molecular changes that would associate with this tumor is:

A. Isochromosome 17.

B. Deletion of chromosome 22q.

C. t(11;22)(q24;q12) translocation.

D. Human homologue of the Drosophilia segment polarity gene (PTCH gene) on chromosome 9q22.3.

E. None of the above.

pathology of the nervous system

Documents

external granular layer

optic nerve gliomas

increased intracranial pressure

spinal cord injuries

middle meningeal artery

optic nerve

central canal

cerebral hemorrhage