Neurologic Pathophysiology

Cerebral Blood Flow

• Cerebral blood flow is maintained at approximately
750-900 ml/min or 15% of the cardiac output.
• It is largely controlled by auto regulatory mechanisms
that respond to metabolic needs of the brain
• Cerebral auto regulation is defined as ability of the
brain to maintain constant blood flow despite change
in systemic arterial pressure
• This mechanism is efficient with mean arterial
pressure range of 60-140 mmHg
• At least three metabolic factors affect cerebral
blood flow
CO2 – potent stimulator for vasodilation,
• 70% increase in the PaCO2 in the arterial blood results in
doubling of the cerebral blood flow
H+ - increase in [H+] increases cerebral blood flow
• Increased blood flow washes away the nurally depressive
material
• Profound ECF acidosis may result in vasomotor paralysis
O2 – decreased O2 concentration also increases cerebral
blood flow
 Cerebral Perfusion
• CPP= mean arterial pressure – ICP
• The brain achieves auto regulation by altering the
cerebral vascular resistance over a wide range of CPP
(50-100 mmHg)
• Set point of auto regulation is changed in patients
with chronic hypertension
• The initial response to raised BP is vasoconstriction to
protect the brain but this might lead to ischemic
symptoms when there is acute drop in BP even if the
BP remains in normal range
• Conditions associated with elevated ICP are
associated with decreased CPP
• If CPP is grossly elevated (>120 mmHg) there
would be breakdown of auto regulation and
development of hypertensive encephalopathy
and cerebral edema.
 Excitotoxicity
 Overstimulation of receptors for specific amino
acids such as glutamate and aspartate which
act as excitatory neurotransmitters
 Occurs in stroke, hypoglycemic encephalopathy,
chronic degenerative diseases like Huntington's
disease and Alzheimer's dementia
 Final common pathway for neuronal cell injury
and death
 Excitotoxicity- cont’d
• Glutamate is the principal excitatory
neurotransmitter in the brain
• Many actions are coupled with receptor operated ion
channels
• Glutamate-N- methyl – D- aspartate (NMDA) has
been implicated in CNS injury
• This subtype of glutamate receptor opens a large
diameter Ca++ channel that allows Na+ and Ca++ into
the cell and allows K+ to exit resulting in prolonged
action potential.
 Excitotoxicity- cont’d

• The increased intracellular Ca++ results in

release of intracellular enzymes that cause
protein breakdown, free radical formation, lipid
peroxidation, fragmentation of DNA and nuclear
breakdown
• Effects are reversible if excess glutamate is
removed or its effects blocked
 Intracranial Pressure
• Intracranial pressure is normally < 15 mmHg in adults
• The intracranial compartment is protected by the
skull – a rigid structure with fixed internal volume of
1400-1700 ml
• Under physiologic conditions intracranial contents
include (by volume)
– Brain parenchyma – 80%
– CSF – 10%
– Blood – 10%
 ICP
• Pathologic structures including mass, abscess
and hematoma may also be present
• An increase in the volume of one
compartment or the presence of a pathologic
component necessitates the
– Displacement of the other structures,
– An increase in ICP or
– Both
• An initial increase in volume results in a small increase in pressure because of intracranial
compensation (blue line). Once intracranial compensation is exhausted, additional
increases in intracranial volume result in a dramatic rise in intracranial pressure (red line)
 ICP
• Volume of the brain parenchyma is relatively
constant although it may be altered by mass
lesions or in the setting of cerebral edema

• Volume of the CSF and blood in the cranial

cavity varies to a greater degree
 CSF
• CSF is produced by the choroid plexus at a rate of
20ml/hour (500 ml/day) and resorbed into the
venous system via the arachnoid granulations
• Problems in the normal process can result in
accumulation of excess CSF resulting in
hydrocephalus
– Impaired outflow (ventricular obstruction, venous
congestion)
– Increased production (choroid plexus papilloma)
 IC Blood
• Cerebral blood flow determines the amount of
blood in the intracranial space

• Might be increased with hypercapnea and

hypoxemia
 Common Causes of increased ICP
• Intracranial mass lesions (tumor, hematoma)
• Cerebral edema (hypoxic ischemic injury, large
cerebral infarct, head injury)
• Increased CSF production (choroid plexus papilloma)
• Decreased CSF absorption (arachnoid granulation
adhesion after bacterial meningitis)
• Obstructed venous outflow( venous sinus
thrombosis, jugular vein compression, neck surgery)
• Idiopathic intracranial HTN (psudotumor cerebri)
 Cerebral Edema
• Two principal types
1. Vasogenic edema – Integrity of the BBB is
disrupted and there is increased vascular
permeability , it could be either localized or
generalized
2. Cytotoxic edema – Increased intracellular fluid
secondary to neuronal, glial or endothelial cell
membrane injury.
 Hydrocephalus
• Hydrocephalus refers to the accumulation of excessive CSF within
the ventricular system.
• Mechanisms of development
– Obstruction of CSF pathways,
– Impaired venous absorption, and
– Over secretion of CSF.
1) Obstructive, or noncommunicating, hydrocephalus
– The disorder that results from obstruction of the ventricular system.
Portion of the ventricular system is enlarged.
2)Communicating hydrocephalus
– Occurs when the subarachnoid pathways are blocked.
– There is enlargement of entire ventricular system
• CSF production is nearly always normal.
 Effects of Raised ICP
• Mainly related to global effects of decreased
cerebral perfusion ( CPP) and focal effects
related to mass lesions of herniation
syndromes

• A focal expansion of the brain causes it to be

displaced in relation to these partitions
resulting in herniation.
 Clinical Manifestations of Raised ICP
• Headache ( pain fibers in CN V supplying dura and
blood vessels)
• Depressed consciousness
• Projectile vomiting
• CN VI palsies
• Papilledema – decreased axonal transport and
congestion
• Bradycardia, respiratory depression and raised BP
–Cushing’s triad
 Clinical Manifestations – cont’d
• Focal symptoms of herniation syndromes
– Subfalcine,- cingulate gyrus under the falx
cerebri. May compress branches of the
anterior cerebral artery.
– Transtentorial,- contralateral pupillary
dilatation and ipsilateral hemiparesis
– Tonsillar- life threatening because of brain
stem compression
 Consciousness
• It is the state of awareness of self & external
environment and being able to become
oriented to new stimuli
• Traditionally divided into two components
– Arousal and wakefulness – Concurrent function of
both cerebral hemispheres and an intact RAS
(reticular activating system)
– Content or cognition – Determined by cerebral
cortex
 Alterations in Consciousness
• Any defect in the level of consciousness
indicates injury to either the reticular
activating system or to both cerebral
hemispheres concurrently
• Example – Head injury that affects a unilateral
hemisphere also spares the RAS usually
doesn’t impair consciousness
 Clinical Evaluation of Consciousness

• Evaluated by ability to respond appropriately

to environmental stimuli
• So it involves both evaluation of arousablity as
well as content
• Arousability – is a continum
– Consciousness, confusion, delirium, obtundation,
stupor, coma
 Arousal and wakefulness
• Confusion – Impaired ability to think clearly and difficulty
to perceive, respond to and remember current stimuli.
• Delirium – Misinterpretation of sensory stimuli causing
inappropriate excitement and arousal
• Obtundation – Decreased alertness associated
psychomotor retardation
• Stupor – Person is still conscious but there is little or no
spontaneous activity
• Coma – Unarousable and unresponsive to external
stimuli as well as internal needs
 Glasgow Coma Scale
Test score

Eye opening
Spontaneous 4
To call 3
To pain 2
None 1
Motor response
Obeys command 6
Localizes pain 5
Normal flexion (withdrawal) 4
Abnormal flexion (decorticate) 3
Abnormal extension (decerebrate) 2
None 1
Verbal response
Oriented 5
Confused conversation 4
Inappropriate words 3
Incomprehensible sounds 2
none 1
The GCS is scored between 3 and 15, 3 being the worst,
and 15 the best. It is composed of three parameters:
best eye response (E), best verbal response (V), and
best motor response (M).
The components of the GCS should be recorded
individually; for example, E2V3M4 results in a GCS
score of 9.
≥13 correlates with mild brain injury;
9-12 with moderate injury; and
≤8 represents severe brain injury.
 Causes of Altered Consciousness
• Structural-Brain lesion that destroy
tissue/occupy space that is normally occupied
by brain. Example: Epilepsy, tumor & trauma
• Cardiovascular – Permanent/temporary
interruption of blood supply to brain.
Example: Stroke, TIA, shock, hypertensive
encephalopathy, dysrrythemia
• Metabolic-Abnormally high/ low level of
circulating metabolites
 Example: Hypoxia, hypoglycemia,
hyperglycemia, renal failure, liver failure,
infection
• Environmental–External factors that cause
deterioration of nervous system function.
Example: overdose, toxin
• Behavioral- Abnormal mental status that results
from internal factors.
Example: psychiatric disorders
 Care for a Comatose Patient
• * Reading assignment!!!
 Seizure Disorders
• Seizure ( Latin Sacire “to take possession of”)
• It is a paroxysmal event due to abnormal,
excessive , hyper synchronous discharge from
an aggregate of CNS neurons.
• Epilepsy – A condition in which a person has
recurrent seizure due to chronic underlying
process
 Classification of Seizures
1. Partial seizures (focal)- seizure activity restricted
to discrete areas of the cerebral cortex.
• A. Simple partial seizure
• B. Complex partial seizure
• C. Partial seizure with secondary generalization
2. Primarily Generalized seizures
• A. Absence seizure (petit mal) seizure
• B. Generalized tonic-clonic seizure (grand mal)
• C. Atonic seizure
• D. Myoclonic seizure
 Simple Partial Seizure
• Cause motor, sensory, autonomic or psychic symptoms
without alteration of consciousness
• Tod’s paralysis – Localized weakness for minutes to hours
following seizure
• Motor symptoms – Clonic involuntary movement of an
extremity
• Somatic sensation – Parasthesia
• Vision – Flashing lights or formed hallucination
• Autonomic – Flashing, sweating, piloerection
• Temporal or frontal cortex – Psychic symptoms, olfaction,
higher cortical functions
 Complex Partial seizure
• Focal seizure activity accompanied by transient
impairment of consciousness
• Seizure usually begins with an aura (simple partial seizure)
• Start of ictal phase is often sudden behavioral arrest or
motionless stare which marks the onset of amnesia
• Automatism - Involuntary automatic behavior that has a
wide range of manifestations
– Chewing, lip smacking, swallowing, ‘picking’ movement of the
hands or running
• Patient usually confused following the seizure
 Partial Seizure with Secondary
Generalization
• Partial seizure can spread to involve both
hemispheres and produce generalized seizure
• Often the onset may be overlooked and
therefore thought to be a primarily
generalized seizure
 Absence Seizure/ petit mal
• Characterized by sudden brief lapse of
consciousness without loss of postural control
• Usually lasts for few seconds and no post ictal
confusion
• Usually begin in childhood
• Can occur hundreds of time per day,
• Unexplained day dreaming and declining
school performance
Generalized Tonic- Clonic Seizure/Grand mal

• Most common form of seizure resulting from metabolic

disturbance and 10% of epilepsy
• Starts abruptly without warning
• Initial phase of seizure is usually tonic contraction of
muscles throughout the body
• Respiratory muscles – loud moan ‘ictal cry’
• Jaw muscles – biting of tongue
• Increased HR, BP papillary size
• After 10-20 seconds tonic phase evolves into clonic phase
caused by superimposition of periods of relaxation on the
tonic muscle contraction
Generalzed Tonic-Clonic Seizure Cont’d

• Periods of relaxation progressively increases

until the end of seizure which lasts less than
one minute.
• Post ictal phase – unresponsiveness, muscular
flaccidity, excessive salivation, bladder and
bowel incontinence
• Atonic seizure
– Sudden loss of postural muscle tone lasting 1 -2
seconds
– Consciousness is usually impaired but no post ictal
confusion
• Myoclonic Seizure
– Is a sudden and brief muscle contraction that may
involve one part of the body or the entire body
 Causes of Seizure
• Result of shift in the normal balance of excitation and
inhibition within the CNS
• Normal brain is capable of having a seizure under
appropriate circumstances
• There is difference between individuals in the
susceptibility or threshold for seizure
• Some conditions have high likelihood of resulting in
chronic seizure disorders
– Ex. Penetrating head injury (50%)
• Precipitating factors- like sleep deprivation
 Cause – cont’d
• Seizure and epilepsy results from dynamic
interplay of:
– Endogenous factors
– Epileptogenic factors
– Precipitating factors
 Causes of Seizure
• Neonates (<1 month)
– Perinatal hypoxia and ischemia
– Intracranial hemorrhage and trauma
– Acute CNS infection
– Metabolic disturbances (hypoglycemia, hypocalcemia,
hypomagnesemia, pyridoxine deficiency)
– Drug withdrawal
– Developmental disorders
– Genetic disorders
 Causes of Seizure – cont’d
• Infants and children (>1 mo and <12 years)
– Febrile seizures
– Genetic disorders (metabolic, degenerative,
primary epilepsy syndromes)
– CNS infection
– Developmental disorders
– Trauma
– Idiopathic
 Causes of Seizure – cont’d
• Adolescents (12–18 years)
– Trauma
– Genetic disorders
– Infection
– Brain tumor
– Illicit drug use
– Idiopathic
 Causes of Seizure – cont’d
• Young adults (18–35 years)
– Trauma
– Alcohol withdrawal
– Illicit drug use
– Brain tumor
– Idiopathic
 Causes of Seizure – cont’d
• Older adults (>35 years)
– Cerebrovascular disease
– Brain tumor
– Alcohol withdrawal
– Metabolic disorders (uremia, hepatic failure,
electrolyte abnormalities, hypoglycemia)
– Alzheimer's disease and other degenerative CNS
diseases
– Idiopathic
 Febrile seizure
• Common cause of convulsion in young children
• Criteria for febrile seizure:
– Convulsion associated with elevated temperature
>38 degree Celsius
– Child less than 6years
– No CNS infection or inflammation
– No systemic metabolic abnormalities which could
result in convulsion
– No history of previous afebrile seizure
 Febrile seizure
• Divided into two categories:
– Simple (benign) –
– lasts less than 15 minutes
– No focal nature
– If they occur in series total duration less than 30
minutes
– Complex febrile seizure
– Episodes that last more than 15 minutes
– Has focal nature and post ictal paresis
– Occurs in series with total duration >30minutes
• Simple febrile seizures are the most commonly
encountered type in children
• Majority have their febrile seizures on their
first day of illness
• Meningitis and encephalitis are the major
concerns in children who present with febrile
seizure
 Lumbar Puncture/ LP
• In the past for all febrile seizures LP and CSF analysis
• Recommendation/Indication:
– When there are meningial signs or other clinical features
that suggest a possible meningitis or intracranial infection
– 6-12 month old not immunized for H.Influenza type b
and strept pneumonia
– Patients on antibiotic treatment which can mask sign&
symptoms of meningitis
– Febrile status epilepticus
 Febrile Seizure Treatment
• Febrile seizure that continues for more than 5
minutes should be treated with anticonvulsants
• Fever should be treated as well as the underlying
cause
• Prognosis is favorable
• Overall recurrence rate is 30-35%
• Neurologic sequelae - rare
• Subsequent epilepsy –occurs more frequently than
general population