Neurological Pathophysiology

What are the 2 main divisions of the nervous system?

\- Central Nervous System (CNS):brain and spinal cord which act as the body’s control centre

\- Peripheral Nervous System (PNS):cranial and spinal nerves

What is the purpose of a nerve?

\- To provide communication between the CNS and remote body parts

\- Delicate nerve fibres help transmit signals

What does an axon do?

Carry impulses away from the nucleus of the neutron

What do dendrites do?

\- Carry impulses towards the nucleus of the neuron

\- Most neurone have multiple dendrites but only 1 axon

\- This allows for impulses to be detected, received and transmitted along the nervous system

What is the neurological system compromised of?

The entire neurological system is comprised of a ‘highway’ of interlocking receptors and transmitters which forms a living computer which controls and regulates all of the body’s functions

What is the central nervous system protected by?

The bony structures of the skull, vertebrae, cerebral spinal fluid and by 3 membranes – dura mater, arachnoid mater and pia mater

What is the dura mater?

The outermost protective layers and is comprised of 2 tough and fibrous tissues called – endosteal dura and the meningeal dura

What is the endosteal layer?

Flows around the brain and towards the lining of the vertebrae canal

What is the meningeal layer?

Covers the brain and brain tissue to offer support and protection for the brain

What is the arachnoid mater?

Middle protective layer which is a very thin fibrous membrane that loosely covers the brain and spinal cord

What is the blood supply like to the arachnoid mater?

Avascular - few or no blood vessels present

What does the arachnoid mater contain?

This space contains CSF which makes the environment buoyant to reduce the weight of the brain from 1400g to 50g, provides a cushion to reduce impact damage and contains a gap

What is the Pia mater?

Innermost protective layer of connective tissue which extends coverage from the brain to the spinal tissue

What is the blood supply like to the Pia mater?

Very vascular

What is the space called between the dura mater and arachnoid mater?

Subdural space

What is the space called between the Pia mater and arachnoid mater?

Subarachnoid space

What does the subarachnoid space contain?

CSF which contains; water, organic materials, minerals and glucose

How do you remember the layers of the brain?

Brain has PADS

Pia, arachnoid, dura, skull

What is the cerebrum home to?

Nerve centre which controls all sensory and motor activities/functions

What are the layers of the cerebrum?

The outer layer (cerebral cortex) consists of neuron cell bodies called gray matter, the inner layer consists of axons (white matter)

What is also located in the cerebrum?

Basal ganglia is also situated here which is responsible for controlling motor co-ordination and steadiness

What does the frontal lobe control?

All voluntary movements and speech

What does the temporal lobe control?

Taste, hearing, smell and language

What does the parietal lobe control?

Coordination and interpreting sensory information

What does the occipital lobe control?

Interpretation of visual information

What does the cerebellum control?

Coordination, motor skills, posture, balance and equilibrium

Where do the motor impulses descending from the brain cross?

In the medulla at the decussation of pyramids

Where is the cerebellum located?

Under the cerebrum at the base of the brain stem

What does the brain stem contain?

Most of the cranial nerve pathways which control the main functions of our body

What does the brain stem provide?

A two way communication pathway between the spinal cord and the brain 

What do afferent nerves do?

\- Carry sensory information from receptors around the body to the CNS

\- Cell bodies are located outside of the spinal cord

What do efferent nerves do?

\- Carry motor information from brain to the PNS

\- Cell bodies are located in the ventral horn of the spinal cord

What does the autonomic division do?

Regulates involuntary body responses

What does the somatic division do?

Voluntary movement by skeletal muscles

How are spinal nerves numbered?

Based on their location on the spinal cord

What is a TIA?

\- The result of a temporary disruption/blockage within the blood supply to the brain

\- Transient (less than 24 hours) neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without evidence of acute infarction

What are symptoms of a TIA?

\- Paralysis

\- Speech abnormality

\- Vomiting

\- Vertigo

\- Confusion (GCS 14)

\- Ataxia

\- Dysphagia

Why give aspirin to a person suffering a TIA?

\- Aspirin is an anti-platlet which reduces the bloods ability to produce clots

\- This reduction in clots reduces the risk of arterial blockages and means blood flow can continue ensuring the brain is receiving a steady supply of oxygen to avoid necrosis of brain tissue

How many TIAs lead to a major stroke?

1 in 3

Why is AF a red flag for a TIA?

\- The atria are unable to fully eject blood into the ventricle which causes blood pockets to form in the atria and this is where clots are formed

\- The clots then release into the ventricle and travel around the vascular system, potentially causing an occlusion of a cerebral artery

Explain the process of a stroke forming?

\- Clots contain plasmin (an enzyme which breaks down blood clots in the blood) which is activated by plasminogen, which freely flows through the blood stream

\- This is how clots are natural broken down within the blood and explains why most TIAs self resolve

\- However, if the blood clots does not break down on it’s own, this blockage means oxygen fails to reach all parts of the brain, resulting in necrosis of brain tissue

\- This process is commonly known as a stroke.

Using the ABCD2 tool, when would you take a patient with a TIA to hospital?

\- Under 3: refer to a TIA Clinic

\- 4 or more: take to ED

Why do ischaemic strokes occur?

Because of a reduced or lost blood supply to the brain

How does alteplase work?

\- By activating plasminogen (into plasmin) to break down fibrin and dissolve the clot

\- Alteplase works as a tissue plasminogen activator (tPA) to activate plasminogen to turn into plasma.

What is the risk with administering a tissue plasminogen activator?

Because these drugs increase plasmin activation and prevent clot formation, they also increase the risk of intracranial heamorhagge and therefore shouldn’t be given after the 4.5 hour window

How do hemorrhagic strokes occur?

Caused when weakened vessels rupture, causing blood to surround the brain

What is the difference between inter- cerebral haemorrhage and sub-arachnoid haemorrhage?

\- Inter-cerebral: bleeding within brain

\- Sub-arachnoid: bleeding on surface of brain

What are the 4 types of brain haemorrhage?

\- Epidural haematoma

\- Subdural haematoma

\- Subarachnoid haemorrhage

\- Intracerebral haemorrhage

What is an epidural haematoma?

Collection of blood which forms between the skull and dura mater – most commonly due to the fracture of the temporal bone

What are signs and symptoms of an epidural haematoma?

\- Confusion

\- Dizziness

\- Drowsiness

\- Enlarged pupil in 1 eye

\- Headache

\- Vomiting

What is a subdural haematoma?

\- Considered the deadliest type of head injury and mainly occurs following head trauma with blood filling the subdural space and compressing brain tissue

What are risk factors for a subdural haematoma?

\- Blood thinners are a big risk factor which require scans to take place to ensure no bleeding evident

\- Long term alcohol use

\- Repeated head injury

\- Very young or old

Why are blood thinners a risk factors for a subdural haematoma?

\- Anti-coagulants work in different ways but also follow the same principle of preventing the formation of clots and trying to prevent the coagulation cascade before it starts

\- For example, Warfarin is a vitamin K antagonist which blocks the enzymes that use vitamin K to produce clotting factors

What is a subarachnoid haemorrhage?

Takes place within the subarachnoid space and usually presents as severe, spontaneous headache

What are signs and symptoms of a subarachnoid haemorrhage?

\- Thunder clap headache

\- Stiff neck

\- Vomiting

\- LOC

\- Visual changes

What is an intracranial haemorrhage?

\- Second most common cause of stroke

\- Known as focal bleeding caused primarily by arterial rupture

\- Main risk factor is chronic arterial hypertension

Where do anterior strokes predominantly affect?

Frontal and parietal lobes

Where do posterior strokes predominately affect?

Brain stem, cerebellum and occipital lobe 

What tests do you do for a stroke patient?

FAST

AVVV

What do GABA receptors do and where?

\- Within the central nervous system

\- GABA receptors play an essential role in signal transmission, playing a key role in; emotional regulation, cognition, pain and sleep

What happens when GABA interacts with the receptors of a neuron?

It reduces their action potential

What does GABA inhibit?

GABA inhibits nerve transmission by inhibiting neuro signalling

What else acts on GABA receptors to inhibit nerve transmissions?

- Alcohol

\- Benzodiazepines

\- Opiates

\- Entonox

These drugs give a feel good effect patients because they reduce pain by preventing action potential passing pain through the nervous system and release dopamine

What is a seizure?

\- When a group of cells lose afferent simulation (no longer able to transmit impulses from the periphery nervous system to the central nervous system), as the result of abnormal electrical discharges

\- This process may lead to patients experiencing; convulsive movements, interruption of sensations or LOC

How many epilepsy cases are idiopathic?

Half of cases

What are potential causes of epilepsy?

\- Genetic abnormalities

\- Brain tumours

\- Traumatic injury

\- Toxins

\- Strokes

\- Fever

How long do epileptic fits tend to last?

Most self resolve in 90 seconds and then followed by a long recovery period (Post Ictal)

What is convulsive status epileptics?

Seizures over 5 minutes or multiple short seizures

What are the 2 medication options for seizure management?

\- Midazolam – oral administration, takes less than 5 mins to work, sedative effect wears off after 15 minutes. Midazolam works by rapidly increasingly GABA activity in the brain which helps calm overactive Neurons. (GABA is the primary inhibitory neurotransmitter in the brain)

\- Diazepam (IV) – Second dose should be IV. Diazepam is a CNS depressant which works by – enhancing the effect of inhibitory neurons

\- Diazepam is a long acting inhibitor. Temazepam/lorazepam is medium acting. Midazolam is short acting

\- Give full dose – DO NOT TITRATE!

What are tonic, clonic and tonic clonic seizures?

Tonic – Sudden stiffening and contraction of muscles

Clonic – Rhythmic twitching or jerking

Tonic Clonic – Combination of both

What is a focal seizure?

A small part of the brain is impacted and GCS may be retained (patient may describe an AURA)

What is an aura?

\- Pungent smell

\- Nausea

\- Rising/sinking feeling in stomach

\- Dreamy feeling

\- Unusual taste

\- Visual/flashing lights

When are febrile convulsions most common?

Most common during the first day of a child’s illness due to the rapid spike in body temperature

Why do febrile convulsions occur?

\- The body temperature increases it makes neurons more excitable and meaning action potentials are more likely to happen

\- There is also thought to be a link between hyperventilation (decrease in C02) which causes an increase in blood PH – this chemical change also makes neurons more excitable

What is dementia?

An umbrella term for conditions associated with:

\- poor memory

\- difficulty processing new information

How is dementia caused?

Predominately caused by damage to neuron cells within the brain, which can be caused by a variety of diseases

How many dementia diagnoses does Alzheimers count for?

80%

What is thought to be the cause of Alzheimers?

\- Considered a neuro-degenerative disease – means loss of neurons within the cortex of the brain

\- Cause not completely known, however we do know PLAQUES and TANGLES are responsible for causing the disease

What are risk factors for Alzheimer’s?

\- Gender – females more likely due to longer life expectancy

\- Inherited genes – 50% increase if a parent has a PS1, PS2 or APP gene

\- Hypertension causes damage to blood vessels within the brain

\- Smoking/alcohol causes reduction of blood vessel diameter so less oxygen reaches the brain

•Depression/anxiety as constant stress causes persistent immune response, affecting the brain

What causes Parkinson’s disease?

Progressive rigidity of muscles and loss of movement over extended period of time

Who is most affected with Parkinson’s disease?

More males than females

What is the cause of Parkinson’s disease?

Caused by a deficiency of dopamine in the basal ganglia (located in the cerebrum). This is the dopamine-releasing pathway between the substantia nigra and the corpus striatum

What is the substantia nigra and the corpus striatum and how do they interact with each other?

\- The substantia nigra – part of the brain which controls movement (black substance is the translation because it is darker than other areas of the brain when examining)

\- The corpus striatum – controls skeletal movements, oculomotor and decision-making

\- They connect to the motor cortex!

\- The substantia nigra transmits signals to the striatum (in the cerebral cortex – responsible for movement) through the nigrostriatal pathway – dopamine is the key neurotransmitter in this pathway.

What causes Parkinson’s symptoms?

Dopamine transmission becomes decreased due to neuron degeneration/death 

What is multiple sclerosis?

Progressive demyelinating disease of the central nervous system (brain and spinal cord) – usually impacting structuring such as; optic and ocular motor neurons and spinal nerve tract

What are thought to be the 2 main factors of multiple sclerosis?

Genetic

\- More likely to impact females

\- Not directly inherited but having a close relative with the disease increases chance of developing the condition

Environmental

\- Northern urban areas – farthest from the equator

\- Vitamin D deficiency

\- Smoking – Increases quantity of relapses and causes bigger lesions

\- Obesity – increases quantity of relapses

What is meningitis?

Inflammation of the central nervous system

What can cause meningitis?

Bacterial, fungal or viral infection

What does meningitis result in?

\- Reduced blood flow

\- Swelling of brain tissues

\- Increase in intra-cranial pressure

What is in the sub-arachnoid space?

CSF

How is CSF replenished each day?

Through the blood-brain barrier

What is the blood-brain barrier made of?

Tightly knitted endothelial cells which only allow certain molecules to pass through

What may inflammation be caused by?

\- Auto-immune diseases

\- Adverse reaction to medication

\- Infection

\- Can be caused by pathogens directly entering through the meninges layer from the skull or spine (think of trauma as an access point) or through the blood stream and transfers across the endothelial cells of the blood brain barrier. Eventually, the WBC in the spinal fluid recognise this threat and increase WBC count. This increase means more CSF is generated which causes increased intra-cranial pressure

What does the increased ICP cause?

\- Severe headache

\- Fever

\- Neck stiffness

What are the 2 tests for meningitis?

\- Put the knee at a 90 degree, when lift upwards, if back pain then this would be Kernigs positive

\- Life the patient’s neck and if this causes the patient to automatically bend their knees then this would be Brudinski positive

\- This is because of irritation of the motor nerve roots which pass through the inflamed meninges.

What is temporal arthritis?

Form of vasculitis whereby the temporal arteries at the side of the head (temples) become inflamed,causing blood vessel constriction and potentially serious implications for patients

What are signs and symptoms of temporal arthritis?

\- Fatigue

\- Fever

\- Tenderness of the scalp

\- Visual disturbances (potentially blindness)

\- Aneurysm

\- Stroke (due to damaged blood vessels)

What are risk factors of temporal arthritis?

\- Female

\- Over 50 years of age

\- Most common amongst the white north European demographic or Scandinavian decent 

How does temporal arthritis form?

\- Antibodies mistakenly attack the blood vessel wall which causes damage and encourages immune proteins to develop. These immune proteins travel along the blood vessel and can reach anywhere in the body. This causes a global immune response with symptoms such as fever/fatigue etc.

\- With the blood vessel damaged, the immune proteins and antibodies join together to form immune complex molecules – these travel around the body. They become lodged in joints and cause general arthritis symptoms – causing misdiagnoses of other types of arthritis

\- Now we can see the external carotid leads into the temporal artery (near the ear and the eye – behind the mandible) which means chewing or mouth movement or palpation can cause pain

\- The reason we get visual disturbances is because damage to the ophthalmic artery (which supplies blood to the eyes)

What is the best cause of treatment for temporal arthritis?

\- Steroids are best course of treatment – Corticosteroid as they are anti-inflammatory and reduce the inflammation which is causing the symptoms

\- Inflammation, pain and fever is caused by prostaglandins. NSAIDs decrease the production of these prostaglandins which reduces pain, inflammation and fever