Hydrocephalus & Cerebral Edema

Overview of CSF production

• average volume of CSF in adult ranges from 80 to 160 ml
• ventricular system holds approximately 20 to 50 ml of CSF
• 80% of CSF produced in the choroid plexuses at rate of 14-36 ml/hr
• Also by blood vessels in the sub-ependymal regions, and pia
• flows from lateral & 3 ventricles to 4 ventricle through the aqueduct
rd th

• Exit through 4 ventricle to subarachnoid space over hemispheres by

th

foramina
then absorbed into the dural venous sinusesof
viaMagendie & Luschka
the arachnoid villi.
 aqueduct

foramina of Luschka & Magendie

Central canal of spine

 Hydrocephalus
accumulation of excessive CSF within the ventricular system
caused either by CSF production Or by CSF absorption
or obstruction of the circulation
accompanied by expansion of the cerebral ventricles
enlargement of the skull and especially the forehead ( in children)

atrophy of the brain

Raised ICP
 Causes of hydrocephalus
Congenital malformations
• Aqueduct stenosis
• Chiari malformations
• Dandy‒Walker syndrome
• Benign intracranial cysts
• Congenital CNS infections
• Craniofacial anomalies
Acquired causes
• Mass lesions ( esp:posterior
fossa)
• Tumor (choroid plexus papilloma)
• Colloid cyst of 3rd ventricle
• Abscess
• Haematoma
• Absorption blockages due to
Infammation
Intracranial haemorrhage
 Types of Hydrocephalus
Communicating (nonobstructive) Hydrocephalus
ventricular system is in communication with the subarachnoid space
noncommunicating (obstructive) hydrocephalus
• ventricular system is obstructed & does not communicate with
subarachnoid space
Hydrocephalus ex vacuo
• compensatory increase in ventricular volume secondary to a loss
of brain parenchyma. Neurodegenerative Diseases
Neurodegenerative Diseases
• Normal pressure hydrocephalus
Tumors
• despite the excess fluid, CSF pressure is normal


Hydrocephalus Ex Vacuo
 Cerebral Edema

Edema of brain parenchyma
Caused by fluid leakage from blood vessels or various cells injury
• Causes
• traumatic brain injury (TBI)
• Stroke
• infection
• tumors
• high altitude
• unhealthy use of drugs
• carbon monoxide poisoning,
• Bites from poisonous animals (Snake bite)
 Cerebral Edema
1. Vasogenic edema (Extracellular swelling )
caused by blood-brain barrier disruption & increased vascular permeability
shift of fluid from intravascular area to the intercellular spaces of brain
Localized
(inflammation or Tumors) Generalized ischemic injury
2.Cytotoxic edema (intracellular swelling)
Raised intracellular fluid
Generalized
secondary to neuronal, glial, or endothelial hypoxia/ischemia
cell membrane injury
 2.Cytotoxic edema

Vasogenic edema
 Cerebral Edema
conditions associated with generalized edema ( infections & Poisoning)

often have elements of both vasogenic and cytotoxic edema.

Gyri are flattened, narrow sulci & compressed ventricular cavities

Brain expands, herniation may occur

3.Interstitial edema (hydrocephalic edema/ Trans ependymal)

Leakage of CSF from ventricles to outside

Seen in Hydrocephalous
 Signs & symptoms of cerebral edema
Headache
nausea, Projectile vomiting
seizures
drowsiness
visual disturbances
Decreased consciousness
death
 Intracranial (CSF) pressure
• Normal intracranial pressure (ICP) in an adult is
between 2-8 mmHg.
• Levels up to 16 mmHg are considered normal
• ICP higher than 40 mmHg or lower BP may combine to
cause ischemic damage
 Causes of raised ICP

• Hydrocephalus

• Brain tumors

• Encephalitis

• head injuries

• stroke
 Symptoms of raised ICP
• Headache
• nausea, vomiting
• increased blood pressure
• confusion
• double vision
• pupils don’t respond to changes in light
• shallow breathing
• seizures
• loss of consciousness & coma.
 Treatment
• Steroids
• Mannitot
• Hypertonic saline (HTS)
• Surgery
• VP shunt (ventriculo-peritonial shunt)
• A-V shunts
 NEURODEGENERATIVE DISEASES
• Group of disorders with progressive loss of neurons
• typically affecting groups of neurons with functional relationships
even if they are not immediately adjacent
• accumulation of protein aggregates (inclusions) is common in these
diseases
• imbalance between protein synthesis and clearance allows gradual
accumulation
• resistant to degradation & toxic to neurons
 Classification

Primary Secondary
CVA (stroke
Global Selective Infections ( syphilis, HIV)
Neoplasms
Parkinson’s disease Drugs and toxins
Alzheimer’s disease
FTLD-TDP Huntington's disease barbiturates, digoxin, alcohol
heavy metals
Motor neuron disease hypo &Hyperthyroidism
Pick’s disease uremia
hepatic failure
Vitamin deficiencies ( B1 , B12)
 Alzheimer’s Disease
• Most common cause of dementia in elderly

• Significance cortical atrophy

• Secondary ventricular enlargement

• Neurofibrillary tangles ‒ (Intracellular (Tau)

• Neuritic plaques (Aβ amyloid) ‒ Extracellular

• Amyloid angiopathy
 Pathogenesis of Alzheimer’s Disease
Plaque Deposition of neurotoxic amyloid protein (peptide Aβ )
around blood vessels and neurons ‒ extracellular plaques

Atrophy of neurons, gliosis

Neurons have internal support structure partly made up of microtubules

Protein called tau stabilize microtubules

In AD tau changes cause microtubules to collapse & form

‘neurofibrillary intracellular tangles’

 Genetics of Alzheimer’s Disease
• Autosomal dominant genetic pattern
• 4 genes of chromosomes 1, 14, 19 and 21, influence initiation and
progression
• Chromosome 21 generates precursor protein for amyloid protein
(APP).
• Trisomy 21 produces early Alzheimer’s disease in persons with Down
syndrome
 Morphology in Alzheimer's Disease
Early
•Degeneration starts in cortex then proceed to hippocampus
•Neuronal loss leads to shrinkage
•Memory loss (first sign)
• Mild to moderate
•Involves cerebral cortex
•Memory loss, confusion, trouble handling money,
poor judgment, mood changes
anxiety, difficulty with language & thoughts
,restlessness, repetition
• Severe
•Extreme shrinkage of brain
•Patients are completely dependent on others for care
•Weight loss, seizures, skin infections, loss of bladder
and bowel control
•Death due to aspiration pneumonia or other infections
 Pick’s Disease

• 40-65 years
• Selective frontal & temporal lobe atrophy
• Progressive aphasia/ language dysfunction Behavior and
personality change
• Preserved memory
• Neurons with round intracytoplasmic Pick’s bodies (tau protein
 Huntington’s Disease
• Hereditary Neurodegenerative disease
• autosomal dominant appears mostly in late life (5 th decade )
• progressive movement disorders & dementia
• Hungtinton’s chorea
• Jerky, hyperkinetic, dystonic movements involving all parts of the
body
• Atrophy of caudate and putamen (striatum)
• Compensatory hydrocephalus of lateral ventricles
• depression, uncontrolled movement and loss of thinking ability
• Excessive CAG tandem repeats ➔ severity
 Genetics of Huntington's Disease
• All human have 2 copies of Huntingtin gene (HTT)
• which codes for protein called huntingtin (htt) (also called HD
gene and IT15)
• Huntingtin Gene:
• Located on short arm of chromosome 4
 Pathophysiology of Huntington’s Disease
Gene synthesis Abnormal Huntingtin protein (several repeats polyglutamine)

• Degeneration of GABAergic Neurons in striatum (basal ganglia)

• Loss of medium spiny striatal neurons leads to dysregulation of basal

ganglia circuitry that modulates motor output

• increased motor output, often manifested as choreoathetosis.

• involuntary jerky movements of all parts of the body

• progression to a severe dementia

Frontotemporal lobar degeneration (FTLD)
• Atrophy of frontal and temporal lobes of the brain, with
sparing of the parietal and occipital lobes
• Heterogeneous syndrome presents with decline in behavior or
language
• Leading cause of dementia < 65