CNS CONGENITAL DISORDERS, INFECTIONS, AND VASCULAR DISORDERS

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CNS CONGENITAL DISORDERS, INFECTIONS, AND
VASCULAR DISORDERS

• Prof. EEU Akang
• FMCPath, FWACP

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Canst thou not minister to a mind diseasd,
rase out the written troubles of the brain and
with some sweet oblivious antidote, purge the
memory of that perilous stuff, which weighs upon
the brain.William Shakespeare, MACBETH
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CENTRAL NERVOUS SYSTEM

• Complex- 2 TBW, 50 of genomic DNA
• Protective bony case
• Autoregulation- 25 of cardiac output
• No lymphatics
• CSF circulation
• Limited immune surveillance
• Metabolic substrate requirements

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MENINGES

• Three membranes
• Dura mater
• Arachnoid mater
• Pia mater
• Three spaces
• Epidural
• Subdural
• Subarachnoid (contains CSF)

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CELLS- NEURONS

• Topographically organised
• Differ in terms of function, metabolism,
  neurotransmitters, etc.
• ACUTE INJURY (Red neuron)
• CHRONIC INJURY (Degeneration)
• AXONAL REACTION
• INCLUSIONS (lipofuscin, viral)
• DEPOSITS (NFT, Pick bodies, Lewy bodies)

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CELLS- GLIA

• ASTROCYTES- Gliosis, Cellular swelling, Rosenthal
  fibres, corpora amylacea
• OLIGODENDROCYTES- Demyelination (Multiple
  sclerosis, PML)
• EPENDYMAL CELLS- ependymal granulations (CMV)
• MICROGLIA- rod cells, microglial nodules,
  neuronophagia

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CONGENITAL MALFORMATIONS- 1

• 1-20 of post neonatal deaths
• CAUSES
• Idiopathic (40-60)
• Multifactorial (20-25)
• Chromosomal- (10-15)
• Mendelian- (2-10)
• Maternal disease- (6-8)
• Transplacental infection- (2-3)

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CONGENITAL MALFORMATIONS- 2

• NEURULATION- wk 3 (anencephaly, spina bifida)
• TELENCEPHALISATION- wk 5-6 (arrhinencephaly,
  holoprosencephaly)
• MIGRATION- 2-5 mos (micrencephaly, lissencephaly
  (Miller-Dieker syndrome), pachygyria,
  polymicrogyria, heterotopia)
• MATURATION- 3rd trim.-post natal (megalencephaly,
  Arnold-Chiari, Dandy-Walker)

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ANENCEPHALY
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MYELOMENINGOCELE
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HOLOPROSENCEPHALY
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CNS INFECTIONS- INTRODUCTION

• Primary problem in tropical neurology
• No lymphatics
• Blood-brain barrier
• Bony casing

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ROUTES OF ACQUISITION OF CNS INFECTION

• HAEMATOGENOUS (pleuro-pulmonary, septicaemia)
• IMPLANTATION (fracture, VP shunt, craniotomy, LP)
• LOCAL EXTENSION (otitis, sinusitis, mastoiditis,
  s. bifida)
• ALONG NERVES (rabies, zoster)

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CELLULAR TROPISMS OF INFECTIVE AGENTS IN CNS

• Poliomyelitis virus (anterior horn cells)
• Rabies virus (hippocampus, Purkinje cells)
• JC virus (oligodendrocytes)
• Cytomegalovirus (ependyma)

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MENINGITIS- CLASSIFICATION TYPES

• Pachymeningitis- trauma, TB
• Leptomeningitis-
• BACTERIAL
• TUBERCULOUS
• FUNGAL
• VIRAL
• PROTOZOAN
• HELMINTHIC

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Gram-negative intracellular diplococci- N.
meningitides
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TUBERCULOUS MENINGITIS Note the basal exudate
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INDIA INK PREPARATION Cryptococcus neoformans
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MENINGITIS- COMPLICATIONS

• Subdural effusion
• Cranial nerve palsy
• Vasculitis
• Abscess
• Hydrocephalus
• Mental retardation
• Seizures
• Waterhouse-Friederichsen syndrome
• SIADH

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BRAIN ABSCESS
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TONSILLAR HERNIATION
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UNCAL HERNIATION
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CINGULATE (SUBFALCINE) HERNIATION
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DURET HAEMORRHAGE- UPPER PONS
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VIRAL ENCEPHALITIS

• Perivascular lymphocytes and plasma cells
• Neuronophagia
• Microglial nodules
• Inclusions
• 1. cytoplasmic- Negri bodies of rabies,
• 2. nuclear- HSV, VZV, measles, CMV

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SLOW VIRUS INFECTIONS

• SUBACUTE SCLEROSING PANENCEPHALITIS- Measles
• PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY- JC
  virus
• PROGRESSIVE RUBELLA ENCEPHALOPATHY- Rubella

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Prions

• Proteinaceous infectious particles
• Lack DNA and RNA
• Aggregate to form amyloid plaques
• Transmitted by intracerebral, intraperitoneal,
  intravenous, corneal and oral routes
• Hereditary and sporadic diseases
• Stanley Prusiner (1997 Nobel Prize)

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THE CENTRAL DOGMA

• DNA
• RNA
• Protein

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PRIONS

• Single 250 amino acid molecules
• Abnormal variants of normal neuronal
  sialoglycoproteins.
• Normal PrPc (protease sensitive)
• PrPres (protease resistant)
• PrPres promotes further conversion of PrPc to
  PrPres

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Spongiform encephalopathy

• Pathology

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Gliosis and kuru type amyloid plaques

• Pathology

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Human Transmissible Spongiform Encephalopathies

• Creutzfeldt-Jakob Disease (CJD)
• Gerstmann-Straussler-Scheinker disease
• Fatal familial insomnia
• Alpers disease (infants)
• PrP Cerebral amyloid angiopathy
• Kuru

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Cerebral Malaria

• Coma 6- 96 hours
• shorter in children
• 20 fatality
• Hepatosplenomegaly common
• Retinal haemorrhages
• Oedematous, slate grey brain
• Petechial haemorrhages in white matter
• Ring haemorrhages
• Dürck granulomas (microglial clusters)

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Cerebral Malaria
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Brain section - P. falciparum
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CEREBRAL VASCULAR DISORDERS

• Transient ischaemic attacks- Focal transient
  neurological deficits lasting lt1hr
• Stroke- Focal permanent neurological deficit
• HAEMORRHAGIC-
• Intracerebral haemorrhage (10)
• Subarachnoid haemorrhage (15)
• ISCHAEMIC- Thrombotic (60)
• Embolic (15)

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STROKE- Risk Factors

• Hypertension
• Atherosclerosis
• Cigarette smoking
• Alcohol
• Elderly age
• Male sex
• Black race

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ACUTE RT. SIDED CEREBRAL INFARCT
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REMOTE RT. SIDED CEREBRAL INFARCT
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HYPERTENSIVE INTRACEREBRAL HAEMORRHAGE
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ARTERIOVENOUS MALFORMATION
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TRAUMATIC INTRACRANIAL HAEMORRHAGE

• EPIDURAL- Middle meningeal artery
• SUBDURAL- Bridging veins
• SUBARACHNOID- Circle of Willis, intracerebral
  haemorrhage extension
• INTRACEBREBRAL

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EPIDURAL HAEMORRHAGE
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SUBDURAL HAEMORRHAGE
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Chance favours the prepared mind.Louis Pasteur