Chapter 7 : The Nervous System Central Nervous System , Physiology & Pathology
Pathology of the Nervous System
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Transcript of 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).
ASTROCYTIC REACTION TO INJURY
Fibrillary astrocytes Prone to neoplastic
transformation Responsible for
dominant family of gliomas
Protoplasmic astrocytomas uncommon
antecedents of cancer
ASTROCYTIC REACTION TO INJURY
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
CELLS OF NERVOUS SYSTEM
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
CELLS OF NERVOUS SYSTEM
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
DISORDERS OF CEREBRAL GYRI
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
DISORDERS OF CEREBRAL GYRI
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.
SPINAL CORD INJURIES
SPINAL CORD INJURIES
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
SPINAL CORD INJURIES
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
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
SUPPURATIVE MENINGITIS
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.