PATHOLOGY OF CENTRAL NERVOUS SYSTEM

PATHOLOGY OF C.N.S 

Central nervous system is

Composed mainly of brain and spinal cord

The skull and vertebrae form a rigid compartment protecting the delicate CNS

This Rigidity has serious disadvantages

When there is an expanding lesion

Pressure mounts inside the cranium

With compression of the normal brain tissue

Meninges and CSF

The CSF circulates freely in the subarachnoid space over the whole CNS

The ventricular system acts as a protective water bath

Dxs at this site e.g. infections, are usually widespread over brain & cord

Impediment to CSF flow causes hydrocephalos

Meninges & CSF cont

Extradural lesions tend to be localised bc they have to strip the dura from bone

Subdural lesions remain local but can spread more widely bc arachnoid & dura are loosely attached

Arachnoid is a delicate membrane which sends trabeculae across the subarachnoid space which contains CSF & blood vessels

Dxs in the subarachnoid space are prevented from penetrating the brain by the Pia matter

Parietal surfaces of cerebrum covered by meninges

Base of the brain

Sulci and gyri

Base of the brain

Cerebellum & brain stem

CNS CELLS

NEURONS: aggregates - nuclei, ganglia or elongated columns or layers – intermediolateral gray column or cerebral cortex

GLIA: Macroglia – astrocytes, oligodendrocytes, ependyma or microglia – fixed macrophage system

PATHOLOGY OF THE C N S  

Increased intracranial tension/herniations

    *definition: CSF pressure above 200mm of water (15mmHg) with the patient in lateral decubitus position

     *causes: The causes include increased CSF production,decreased csf drainage, haemorrhage, tumours, cerebral oedema, cerebral abscess

     *clinical features: Head ache that is worse in the mornings, mental slowness, confusion, papillaedema, focal seisures from causative lesion.

     *morphology: Flattening of the gyri and obliteration of the sulci, herniations such as tentorial, subfalcine uncinate, tonsilar. Duret haemorrhages.

CEREBRAL OEDEMA

Vasogenic oedema: Is the accumulation of oedema fluid in the interstitial space and this is the most common type of cerebral oedema. It is due to capillary damage or formation of new capillaries; eg, around tumours, abscesses infarcts, etc

Cytotoxic oedema: Is the accumulation of excess intracellular water. It predominantly affects gray matter and occurs usually due to processes such as ischaemia and water intoxication.

Interstitial oedema: This is seen in non-commumunicating hydrocephalus. The fluid accumulates around the cerebral ventricles by crossing the ependymal lining

HYDROCEPHALUS
Most cases are due to blockage to csf flow along its pathway

A-COMMUNICATING

*CSF overproduction as in choroid plexus papilloma

*Deficient reabsorption as in meningitis, sinus thrombosis, subarachnoid haemorrhage

B-NON-COMMUNICATING

Congenital malformations such as stenosis of the aquiduct of sylvius, forking of the aquiduct, gliosis of aquiduct, Dandy-Walker malform., Anold-Chiari malform., etc.

Neoplasms

          Ependymoma of IV ventricle

        Choroid plexus papilloma

        Medulloblastoma, Cyst of IV ventricle

Inflammation.

          Meningitis, cerebella abscess, CMV

Haemorrhage such intraventricular, epi and subdural and intraparenchymal.

Hydrocephalus ex-vacuo

             INFLAMMATIONS OF THE CNS

MENINGITIS

Defn. This is an inflammatory process of the CNS coverings due to infectious   

          or Chemical agents or cancer deposits ( carcinomatous meningitis)

Types: Infection, Chemical and carcinomatous

Infections:

BACTERIAL          

VIRAL              

FUNGAL

Routes of infection of the CNS:

                        Blood stream

                        Direct implantation (sharp object or skull # )

                        Local extension (ENT, Ophthal, Dental, etc)

                        Peripheral nervous system (Rabies, polio, etc)

Bacterial infections

ORGANISM                  PEAK AGE INCIDENCE    GRAM STAIN

Escherichia coli/grp B strept       Neonates                      Gram negative rods

Hemophilus influenzae                  Infants and Children                 Gram negative coccobacilli

Now strept pneumon b/c of immunisation

Neisseria meningitidis                   Adolescents and Young adults    Gram negative diplococci

Streptococcus pneumoniae                   Older adults or Children     Gram positive cocci in                                                               chains

Acute pyogenic meningitis

Causative agents: E Coli, H Influenza, Neisseria meningitidis, pneumococcus

Neisseria meningitidis is the cause of epidermic meningitis among adults and adolescents.

Epidemic meningitis (CSM)

-It occurs in five-yearly epidermics with peaks of severity every 15-20 years.

-Severity of the epidermics decreases south-wards towards the costal regions of Nnigeria

-the pattern of disease is influenced by successful immunisation of the population and the use of antibiotics

-it is transmitted by droplet infection

-the infective organism has been predominantly type A until recently when types B and C were recognised. These types respond less well to sulphonamides

-the organism most frequently inhabits the nasopharinx and gets to the CNS via blood

-clinical aspects include positive Kernig’s and Brudzinki’s signs, fever, features of toxicity, peticheal haemorhhages in the skin, etc.

-shock may occur secondary to adrenal haemorrhage (Waterhouse-Fredrickson syndrome)

Pyogenic menin.

-DIC can occur

-arthritis and vasculitis secondary to immune complex deposition  may also occur

-hypocomplementaemia (C₃ particularly) is often classic

-diagnosis: csf is hasy or purulent & is under high pressure with white cell count of 900,000/mm³ and sugar content is usually low, protein content is usually high

-smear will show intracellular lanceolate diplococci.

-gross morphology; purulent exudate over the vertex; microscopically, pmn & pus cells in leptomeninges with venulitis, leptomeningeal thickening.

-Complications— cerebral abscess, adhesive arachnoiditis, hydrocephalus, cranial nerve palsies (especially in Tb meningitis), mental deficiency especially in meningoencephalitis

Acute lymphocytic meningitis (ALM)

-this is a viral meningitis presenting clinically as acute pyogenic meningitis

-csf findings are different from those of csm; lymphocytosis rather than pmn, csf sugar is normal with moderate protein elevation.

-it is self limiting

-Organisms involved include ECHO viruses, Coxsackie, EBV and HSV

Chronic meningitis (Tbc & Syphilis)

The archi-type is Tbc meningitis and is usually 2⁰ to a 1⁰ elsewhere

Other causes of chronic meningitis include cryptococcus neoformans,, brucella and treponoma pallidum

Grossly, there is gelatinous or fibrinous exudate at the base (basal meningitis), other cause of basal meningitis is H influenza meningitis

Focal granularities may be present

Tuberculoma(s) may develop in the parenchyma

Microscopy; lymphocytes, plasma cells, Macrophages, granulomata, obliterative arteritis (end arteritis obliterans)

Csf shows pleocytosis (1000 cells/mm³), normal is 100 cells/mm³ very high protein content and mildly low sugar

Cryptococcal meningitis gives a slimy exudate (microscopically as soap bubbles)

Clinically; malaise, Hd ache, mental confusion, vomiting

Neurosyphilis

Is the tertiary stage of syphilis and occurs in about 20% of untreated pts

Occurs in the form of meningovascular neurosyp, paretic neurosyp and tabes dorsalis

Meningovascular neurosyp usually involves the base of the brain and variably convexities and cord meninges

There may be associated endarteritis (Heuner arteritis)

Cerebral gummas may occur (plasma cell-rich mass lesions) and neuronal loss

Paretic type occurs due to cerebral invasion by T Pallidum terminating into sever dementia (general paresis of the insane)

Tabes dorsalis is the result of damage by spirochetes to the sensory nerves leading to locomotor ataxia and Charcot pains (loss of pain sensation to skin and and joint damage

There is loss of axons and myelin with pallor and atrophy in dorsal columns of cord. Organism are not usually demonstrable in the cord lesions

Pts with HIV infection are at a higher risk of neurosyphilis

Patients with nurosyphilis may come with incomplete or mixed pictures of the three types

Encephalitis:
This simply means inflammation of the brain

Is divided into:

                     Bacterial; Mainly Tb. & syphilis (in the form of                        neurosyphilis), brain abscess.

                     Viral; Rabies, CMV, HIV, Polio, Herpes simplex,              

                     Arboviruses (EEE,WEE, Venezuela, etc)

Brain abscess: This can be due to direct implantation, haematogenous (sepsis, SBE, cyanotic heart disease) or local extension. Complications include herniation, ventriculitis, sinus thrombosis, meningitis, etc.

Slow viral diseases of the CNS:
The agents that cause these diseases have a long latent period, the disease evolves very slowly and does not clinically resemble acute viral Dx.

Divided into: a) those with known viral cause (SSPE, PML, PRP

                            = progressive rubella panancephalopathy)

                             b) those with no well xrised cause  (unconventional agent= spongoform) such as  Kuru dx and Creutzfeldt-Jacob dx (also called Prion Protein-PrP diseases). This agent is now known to be both transmissible and infectious

 SSPE: -Is caused by measles virus

              -also called Dawson’s encephalitis

              -always preceded by attacks of measles in distant past or        immunisation.

       Morphology; -perivascular lymphocytic infiltrates & plasma cells

                     -neuroglial and neuronal loss

                     -dense gliosis

                     -inclusion bodies in oligodendroglia are usually present.

Slow virus infection cont.

PML (progressive multi-focal leukoencephalopathy)

Viral infection of oligodendroglia and their destruction

It causes demyelination as its principal effect

It occurs in association with advanced haematological malignancies and immunodeficiency states

It is caused by JC virus and SV40

Morphology: Sunken areas in white matter

Microscopy:

Demyelination

Inclusion bodies in oligodendroglia

Xtic giant astrocytes

Strikingly little inflammatory reaction

There is sparing of the gray matter

TUMOURS OF THE C N S
Divided into primary and secondary

CLASSIFICATION (Modified WHO)

•                                                          Tumours of neuroglia:

         a) Astrocytes    -astrocytoma: anaplastic

                                           GBM

                                           pilocytic

         b) Oligodendrocytes      -Oligodendroglioma

         c) Ependyma and its homologues       ependymoma myxopap & sub.

                                         choroid plexus papilloma

•                                                          Tumours of neurones     Neuroblastoma

                                  Ganglioneuroblastoma

                                  Ganglioneuroma

CNS tumour classification cont.

3 Tumours of neurones and neuroglia         -Ganglioglioma

4 Tumours of primitive undifferentiated cells - -Medulloblastoma

5 Tumours of pineal cells                     -Pinioloma &                                                    pineocytoa

6 Tumours of meninges          -Meningioma, meningeal haemangioma

7 Tumours of nerve sheath cells    -Schwannoma & neurofibroma

8 Lymphoma      -primary and secondary

9 Malformative tumors -Craniopharyngioma, epidermoid cyst, colloid cyst

10 Metastatic tumours.

Four major classes of brain tumours

Gliomas

Neural tumours (Gangliocytomas, gangliogliomas)

Poorly differentiated neoplasms

meningiomas

Properties of C N S tumours

A) Biological properties: Biologic malignancy/histologic malignancy

        A benign tumour at strategic location may prevent surgical removal and this is what is meant by biologic malignancy eg. Ependymoma of the floor of the IV ventricle or a meningioma around the carotid artery.

        A malignant tumour shows infiltrative margins hence complete removal without extensive removal of brain tissue is rarely possible.

        Some tumours show intraneural seeding via the CSF such as medulloblastoma and some astrocytomas leading to carcinomatous meningitis.

.      B) Clinical effects:   Local; depends on site and size.

                                        General; insiduous frontal lobe tumour may grow                         large before coming to clinical attention

.      C) Incidence and distribution:

                -CNS tumours are one of the commonest tumours in infants and children.

                -CNS tumours are unusual above the age of 70 years

                -Some of them have predisposition to some sites such medulloblastoma which is    -usually confined to cerebellum and pilocytic astrocyto. to hypothal. and cerebel.

                -70% are infratentorial in children; reverse is the case with adults

                -age specificity; medulloblastoma is seen in the 1^st  2 decades of life.

NEUROGLIAL TUMOURS

Astrocytoma and GBM.

-they form 80% of adult primary brain tumours

-three grades of increasing anaplasia   -asrocytoma; fibrillary,                                 protoplasmic & gemistiocytic

                                    -anaplastic

                                    -Glioblastoma multiforme

-they tend to be more anaplastic with time

-misleading diagnosis can arise from small biopsies of anaplastic tumours

-they are poorly defined

-they can be solid, soft, gelatinous or firm depending on fibrillary content

-xtic fibrillary background of astrocytic processes of varying density and calibre.

Astrocytomas cont.

       -GBM almost never arise from the cerebellum

-anaplastic variants have in addition hypercellularity, pleomorphism, nuclear hyperchromasia and irregularity.

-GBM has a variegated appearance, necrosis, cyst & endothelial cell prolif. are common

       -microscopically shows necrosis and pseudopallisading in addition to other features of anaplasia.

       -bizarre giant cells may be present

       -prognosis is very poor.

      - GLIOMATOSIS CEREBRI – infil of brain by neoplastic astrocytes

Pilocytic astrocytoma:

-almost invariably benign

-occurs typically in children and young adults

-usually located in the cerebellum

-is composed of hypercelluar bipolar cells with long hair-like processes

-Rosenthal fibres and microcysts are present

CNS tumours cont.

Oligodendroglioma:

-forms about 5% of gliomas

-mostly cerebellar in location

-most common in middle life

-circumscribed gelatinous gray masses often with cysts, calcification, etc.

-microscopically sheets of regular cells with spherical nuclei surrounded by cytoplasmic halo

-xtic fried egg appearance

-calcification is present in 90% of cases.

-etc

Meningioma

Predominantly benign tumours of adults

Arise from meningothelial cells

Usually attached to the dura matter

May be found along any of the external surfaces of the brain

Usually round to oval well defined encapsulated masses with compressive effects on the underlying brain

Variant called meningioma en plaque has a flat growth patter

Has up to four grades (I-IV) with varying degrees of risk of recurrence

Varying histological pattern with no prog. Significance; fibroblastic, syncytial, transitional, etc.

Psammoma bodies are common in a variant called psammomatous meningioma

Atypical (WHO II/IV) also called aggressive  and Anaplastic (malignant) meningiomas have varying grades of histology that change with degree of aggression.

Medulloblastoma

This tumour occurs predominantly in children and exclusively in the cerebellum

One of the small blue cell tumours of childhood

The tumour is largely undifferentiated

Morphologically located mainly in the midline of the cerebellum

Rapid growth may lead to hydrocephalus

Often well circumscribed, gray and friable

Microscopically shows extreme cellularity with sheets of anaplastic cells with scanty cytoplasm

Mitoses are abundant

Direct dissemination through CSF (‘drop metastasis’) occurs

The tumour is highly malignant and prognosis is dismal

It is highly radiosensitive

Primary CNS lymphoma (PCNSL)

Accounts for 2% of extranodal lymphomas and 1% of intracranial tumours

Commonest intracranial neoplasm in the immunosuppressed

Often multiple sites in the brain at presentation

Extracranial involvement is a rare and late complication

Majority are of B-cell origin

Relatively aggressive disease with poor response to chemo.

Morphologically, the lesions are often multiple and involve deep gray matter and white matter

Nearly always high grade and cells accumulate around blood vessels giving typical hooping which is xtic of PCNSL

CNS MALFORMATIONS AND DEVELOPMENTAL DISEASE

Aetiology and pathogenesis, not clear however genetic and environmental factors clearly play significant role.

NEURAL TUBE DEFECTS

Failure of a portion of neural tube to close may lead to several malformations involving combination of neural tissue, meninges or overlying bone or soft tissues.

ANENCEPHALY

Is a malformation of the anterior end of the neural tube with absence of brain and calvarium

It occurs in 1 to 5 per 1000 live births forebrain devt. Is disrupted and what remains is only area cerebrovasculosa

ENCEPHALOCELE

Is a diverticulum of malformed CNS tissue extending through a cranial defect

Is mostly occipital in location

SPINAL DYSRAPHISM OR BIFIDA. From asymptomatic bony defect to severe malformation with flattened and disorganised segment of spinal cord associated with outpouching of meningeal covering

MENIGOCELE/MENINGOMYELOCELE-  Meningeal/neural tissue extrusion

Miningomyelocoele

FOREBRAIN ABNORMALITIES

Polymicrogyria

Is characterised by loss of neural external contour of the cerebral convolusions

The gyri appear small, numerous and poorly formed

Meganencephaly/microencephaly. These refer to the abnormality in volume of the brain. Alcoholism (fetal alcohol syndrome), genetic defects and HIV infection acquired in utero may lead to micoencephaly.

Agenesis of corpus callosum

Relatively common malformation is the absence of the white matter bundles that carry cortical projections btw the two cerebral hemispheres

POSTERIOR FOSSA ABNORMALITIES

Anold-Chiari malformation consist of small posterior fossa, a misshapen midline cerebellum with downward extension of the vermis through foramen magnum with consequent hydrocephalus, etc.

Dandy-Walker malformation is characterised by an enlarged posterior fossa. The cerebellar vermis is either absent or rudimentary. A midline cyst may replace it.

SYRINGOMYELIA AND HYROMYELIA.

Hydromyelia. Characterised by discontinuous multisegmental or confluent expansion of the central canal of the spinal cord

Syringomyelia. Fluid-filled cleft-like cavity in the inner portion of the cord

Flattened cerebellum, elongation of brain stem, herniation into a conical shaped foramen magnum

Hypertensive vascular diseases of the CNS

Binswanger’s dx; also called multi-infarct dementia (mainly involving white matter), characterised by dementia, gait abnormalities, and pseudobulba signs. It is usually due to cerebral athreosclerosis, vessel thrombosis or embolism, or cerebral arteriolar sclerosis from HPTN

Lacunae/lacunar infarcts; single or multiple small infarcts due to cerebral arteriolar sclerosis in HPTN leading to development of small cavities or lakes (etat lacunaire). Most commonly seen in basal ganglia and hemispheric white matter

Hypertensive encephalopathy- Is due to failure of autoregulation of blood flow with break down of BBB. Is Xrised by head ache, drowsiness, vomiting, convulsions, stupor, coma. Pathologically, there is cerebral oedema, peticheal haemorhages, fibrinoid necrosis of arterioles. These changes are also seen in eclampsia, hypertension of acute nephritis, and malignant hypertension.

Primary demyelinating diseases of the CNS

These are acquired conditions characterised by preferential damage to myelin with relative preservation of axons. These include:

Multiple sclerosis

Acute disseminated encephalomyelitis (measles, chickenpox, rubella, etc)

Central pontine myelinosis (demyelination in the basis pontis and is associated with many factors such as alcolism, rapid correction of hyponatraemia, etc)

Leukodystrophies .represent a group of dxs in which there is an intrinsic defect that interferes with generation and/or maintenance of myelin

Multiple sclerosis

Is the commonest demyelinating dx of the CNS

Is commoner in temperate climates and people of European extraction

It affects young adults (peak btw 18-40 years)

Prevalence is approximately 1 per 1000 persons in the US and Europe

Xrised by waxing and waning neurological abnormalities involving different regions of the CNS over a number of years

Aetiology: it is an autoimmune disorder characterised by destruction of myelin through highly sensitized T-cells. The lesion contains CD-4 and CD-8 lymphocytes as well as macrophages and are reactive to MBP

Current evidence suggests that infections and hereditary factors contribute to the autoimmunity of the dx.

Morphology of multiple sclerosis

The external appearance of the brain and spinal cord is usually normal.

Cut sections are xrised by plaques (areas of demyelination)

The plaques may appear anywhere in the brain and this may explain the wide variety of the clinical features.

Common sites include periventricular white matter, the optic nerves and spinal cord.

The plaques are well demarcated with acute lesions appearing slightly pink and soft while older lesions tend to be firm and pearly gray to pink

Microscopically the lesions are xrised by demyelination initially as perivenous distribution accompanied by variable perivascular lymphocytic inflammatory infiltrate.

Evidence of myelin breakdown is present in active lesions manifested by lipid laden macrophages

The peripheral nervous system is spared.

Clinical features of MS

Onset may be acute or insiduous

The clinical manifestations are protean

Common manifestations include visual disturbances (blurred vision, diplopia, scotomata), paraesthesias, spasticity of one or more extrimities, speech disturbances and gait abnormalities.

Various emotional disturbances may be seen but intelectual function is typically preserved.

The course of MS is unpredictable with some pts dying within weeks to months of onset and others experiencing a normal life span.

However in most cases the dx is xrised by multiple exacerbations and remissions with cumulative neurological deficits developing over the course of years.

DEGENARATIVE DISEASES

These are diseases of gray matter principally characterised by progressive loss of neurons with associated secondary changes in white matter tracts

The pattern of neuronal loss is selective with some areas affected more than others and in fact some remain unaffected

The diseases arise without any clear inciting event in pts without previous neurologic deficits

The diseases are selective in areas of affectation, eg; some are cortical while others may simply be subcortical

They also have many shared features

A common theme among them is the development of protein aggregates that are resistant to normal cellular degredation systems

Some examples of these diseases include:

1    Alzheimer disease (cortical)

2    Pakinsonism/Pakinson disease (Basal ganglia & Brain stem)

3    Huntington disease (Basal ganglia & Brain stem), etc.

ALZHEIMER DISEASE

Is the most common cause of dementia in the elderly

Is a degenerative disaese of the CNS

Most cases occur after the age of 50 years with increasing incidence as age advances

Most cases are sporadic but about 10% have family history of dementia

Clinical features include progressive impairment of memory and other cognitive functions independent of the state of attention, and death is usually as a result of bronchopneumonia or other infections

The so-called "early onset" cases of AD in persons in their 30's, 40's, and 50's may have a genetic basis. Less than 1% of early onset AD cases are linked to a genetic defect on chromosome 21 (which may explain the appearance of Alzheimer's disease in persons with Down syndrome surviving to middle age) which affects amyloid precursor protein, resulting in fibrillar aggregates of beta-amyloid that is toxic to neurons. About half of early onset AD cases are linked to mutations in the presenilin 1 gene on chromosome 14. A presenilin 2 gene has been discovered on chromosome 1, but this defect accounts for less than 1% of cases.

Alz cont….

The more typical "late onset" cases of AD occurring after age 60 may have underlying genetic defects. A genetic locus on chromosome 19 encodes for a cholesterol transporter called apolipoprotein E (apoE). The E4 variant of apoE, which increases deposition of fibrillar beta-amyloid, can be found in 40% of AD cases. A genetic locus on chromosome 12 that encodes for alpha-2-macroglobulin may be found in 30% of AD cases.

Alz cont…

The definitive diagnosis is made pathologically by examination of the brain at autopsy. Grossly, there is cerebral atrophy, mainly in frontal, temporal, and parietal regions. As a consequence, there is ex vacuo ventricular dilation.

Microscopically, there are neurofibriallary tangles, neuritic plaques, amyloid (congophilic) angiopathy, hirano bodies and granulovacuolar degeneration

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Posted by : Unknown July 11, 2015 Tags : NEWS

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