Chapter 18: Disorders of the Central and Peripheral Nervous Systems and the Neuromuscular Junction

Traumatic Brain Injury

• Classifications

➢ Focal/diffuse

➢ Closed/open

➢ Glasgow coma scale (GCS)

    • Hallmark of severe brain injury: loss of consciousness for 6 or more hours

➢ Coup/countrecoup

Focal vs. Diffuse

• Focal TBI: Damage is localized to a specific area of the brain, often due to a direct impact (e.g., contusion, hematoma). (loss of consciousness, and the treatment is often going to be removing intracranial pressure and possibly surgery)

• Diffuse TBI: Widespread injury across multiple brain regions, often caused by rapid acceleration-deceleration forces (e.g., diffuse axonal injury). (less symptoms and less mild)

Closed vs. Open

• Closed TBI: The skull remains intact, but the brain is injured due to impact or rapid movement (e.g., concussion, contusion). (blunt trauma but doesn’t involve damaging the skull, brain tissue doesn’t become exposed to the environment)

• Open TBI: The skull is fractured or penetrated, exposing brain tissue to external elements (e.g., gunshot wounds, skull fractures). (exposes brain tissue to the environment)

Glasgow Coma Scale (GCS)

• A scoring system (3–15) used to assess consciousness after a brain injury. It evaluates:

  • Eye response (E) (1-4)

  • Verbal response (V) (1-5)

  • Motor response (M) (1-6)

Severe brain injury hallmark: Loss of consciousness for 6 or more hours, often associated with a GCS score of ≤8.

Less of a number=better, higher number=bad

Coup/Contrecoup Injuries

• Coup Injury: Occurs at the site of impact when the brain collides with the skull.

• Contrecoup Injury: Occurs on the opposite side of the impact due to the brain rebounding within the skull.

Example: A person falls and hits the front of their head—damage may occur at the front (coup) and the back of the brain (contrecoup)

primary injuries are going to be caused by the initial trauma…

it’s caused by direct impact or injury. This is what can be classified as focal or diffuse injury in the CNS.

secondary injuries which are indirect consequences of the primary injury, usually involves a cascade of ceullar and molecular events as well as the systemic response.

Expansion of the lesion bc of discharge of the neurons leads to an influx of calcium which causes further cell death. Increasing degeneration that happens after an initial injury leads to an expansion of the lesion.

most injuries are going to be focal injuries although…

any acceleration and deceleration reaction can lead to this diffuse external injury.

Traumatic Brain Injury

• Contusions can cause

➢ Epidural (extradural) hematoma

(between the dura and the skull or between the dura and the spinal cord) (can become chronic)

Traumatic Brain Injury

• Contusions can cause

➢ Subdural hematoma

(below the dura, between the dura and the pia matter)(a lot of spreading) (complaint of chronic headaches and will have tenderness, loss of consciousness is less common here)

Traumatic Brain Injury

• Contusions can cause

➢ Intracerebral hematoma

(occur in the ventricles, blood pooling in the brain tissue itself, compression of the brain tissue)

contusions

-symptoms are: loss of consciousness(especially with an epidural hematoma this is a very common symptom that happens at the time of injury followed by a lucid period that lasts for a few hours or a few days)

-headache, vomiting, drowsiness, confusion, seizures

-treatment is to relive intracranial pressure

An unconscious person is admitted to the hospital after a motorcycle accident. The person experienced a brief loss of consciousness at the scene followed by an awake, lucid period of 1 hours. You suspect this individual has a(n)

1. subdural hematoma.

2. open penetrating trauma.

3. extradural hematoma.

4. mild concussion.

extradural hematoma

explanation: Individuals with classic temporal extradural hematomas (i.e., over the temporal lobe) experience loss of consciousness at the time of injury, followed by a lucid period that lasts from a few hours to a few days in one third of individuals (if bleeding from a vein). 

Traumatic Brain Injury – Clinical Presentation

• Concussions

(bruising of the brain, damage to external fibers and white matter, you’ll have some dysfunction that lasts for a short period, attention and memory deficits, but you do not see a loss of consciousness in mild concussion, in moderate concussions you can have a loss of consciousness lasting more than 30min but not accompanied by amnesia of more than 24hrs, in severe concussions loss of consciousness for more than 24 hours)

         ➢ Complications

            • Post-concussive syndrome

            • Post-traumatic seizures (epilepsy)

            • Chronic traumatic encephalopathy (repeating injuries, football or boxing)

Concussions

A concussion is a mild form of traumatic brain injury (TBI) that results from a blow to the head or rapid head movement, causing bruising of the brain, damage to external fibers, and white matter injuries. This leads to temporary neurological dysfunction affecting attention and memory.

Severity Levels of Concussions

1. Mild Concussion

   • No loss of consciousness.

   • Brief cognitive impairments (e.g., attention and memory deficits).

   • Symptoms typically resolve within minutes to hours.

2. Moderate Concussion

   • Loss of consciousness lasting more than 30 minutes but less than 24 hours.

   • Cognitive deficits, but amnesia does not last beyond 24 hours.

3. Severe Concussion

   • Loss of consciousness for more than 24 hours.

   • Greater risk of long-term neurological complications.

Complications of Concussions

1. Post-Concussive Syndrome (PCS)

   • A set of lingering symptoms that persist for weeks or months after the initial injury.

   • Symptoms include headaches, dizziness, fatigue, difficulty concentrating, and mood changes (e.g., depression, irritability).

2. Post-Traumatic Seizures (PTS)

   • Seizures that occur days to months after a head injury.

   • More common in severe TBIs and can lead to post-traumatic epilepsy if seizures become recurrent.

3. Chronic Traumatic Encephalopathy (CTE)

   • A progressive degenerative brain disease caused by repeated head injuries (common in athletes, military personnel, and individuals with multiple TBIs).

   • Symptoms develop years or decades later and include memory loss, behavioral changes, depression, aggression, and dementia-like cognitive decline.

Postconcussive Syndrome

• Clinical manifestations

-Headache

-Nervousness or anxiety

-Irritability

-Insomnia

-Depression

-Inability to concentrate, forgetfulness

-Fatigability(tired)

Postconcussive Syndrome

• Treatment

-Reassurance and symptomatic relief

-Close observation for 24 hours by a reliable individual to ensure that immediate intervention can be obtained if delayed effects become severe

Spinal Cord Injury

• Primary/secondary injury

• Clinical manifestations: spinal and neurogenic shock; autonomic dysreflexia

Spinal Cord Injury

• Spinal shock (usually affect young men)

-Complete loss of reflexes below the level of the lesion

-Manifestations: flaccid paralysis, sensory deficit, and loss of bladder and rectal control

-Few days, up to 3 months

-4 to 5 days

Spinal Cord Injury

• Neurogenic shock

-In cervical or upper thoracic injuries

-In addition to spinal shock.

-Caused by the absence of sympathetic activity and unopposed parasympathetic tone mediated by an intact vagus nerve

-symptoms: vasodilation, hypertension, slowed heart rate/ bradycardia, hypothermia

Spinal cord injuries can be classified into primary and secondary injuries:

• Primary injury: The initial mechanical trauma to the spinal cord (e.g., fracture, dislocation, or compression).

• Secondary injury: Progressive damage occurring hours to weeks after the primary injury due to inflammation, ischemia, and cell death.

Clinical Manifestations of SCI

1. Spinal Shock

   • A temporary condition following spinal cord injury where there is a complete loss of reflexes below the level of injury.

   • Key Features:

     • Flaccid paralysis (muscle weakness with no reflex activity).

     • Sensory deficits (inability to feel below the injury level).

     • Loss of bladder and rectal control (causing urinary retention and bowel dysfunction).

   • Duration: Can last from a few days up to 3 months before reflex activity begins to return.

2. Neurogenic Shock

   • Occurs in injuries to the cervical (neck) or upper thoracic spinal cord (above T6).

   • Happens in addition to spinal shock but is caused by a disruption in the autonomic nervous system.

   • Mechanism: Loss of sympathetic nervous system (SNS) activity leads to unopposed parasympathetic tone, controlled by the vagus nerve (cranial nerve X).

   • Symptoms:

     • Severe hypotension (low blood pressure due to vasodilation).

     • Bradycardia (slow heart rate).

     • Loss of temperature regulation (body unable to regulate heat properly).

   • Unlike spinal shock, neurogenic shock is life-threatening due to the risk of severe cardiovascular instability.

3. Autonomic Dysreflexia (Autonomic Hyperreflexia)

   • A medical emergency that occurs in SCI at or above T6, usually after spinal shock resolves.

   • Triggered by stimuli such as bladder distension, bowel impaction, or skin irritation.

   • Symptoms include:

     • Sudden, severe hypertension (can lead to stroke).

     • Bradycardia (slow heart rate).

     • Sweating and flushing above the injury level, pale and cool skin below the injury level.

     • Severe headache and blurred vision.

   • Requires immediate treatment to prevent complications like stroke or organ failure.

Spinal Cord Injury

-The most common types of spinal cord injuries are going to be contusion and bruising can be caused by bending of the vertebral column

The image illustrates different types of spinal cord injuries (SCI) and their associated mechanisms. Here’s a breakdown of the key elements:

1. Hyperextension Injury (Top Left)

• Illustration: A person with their head forcefully extended backward.

• Description:

  • Disruption of intervertebral discs.

  • Osteophytes (bony growths) contributing to spinal cord compression.

  • Ligament compression, leading to potential spinal instability.

• Common Causes: Rear-end motor vehicle accidents, falls in elderly individuals.

2. Hyperflexion Injury (Top Right)

• Illustration: A person with their head bent forward forcefully.

• Description:

  • Wedge fracture (compression fracture of the vertebral body).

  • Stretched ligaments, which can cause spinal instability.

• Common Causes: Head-on collisions, falls with forward impact.

3. Compression Injury (Bottom Left)

• Illustration: A person with an upright posture experiencing downward force.

• Description:

  • Compression fracture without cord compression (milder injury).

  • Crushed vertebral body with spinal cord compression (more severe).

• Common Causes: Falls landing on feet or buttocks, diving accidents.

4. Rotational Injury (Bottom Right)

• Illustration: A person’s upper body twisting forcefully.

• Description:

  • Twisting force can cause ligament damage and spinal misalignment.

  • Vertebrae may rotate excessively, leading to nerve or spinal cord compression.

• Common Causes: Motor vehicle accidents, sports injuries, assaults.

Spinal Cord Injury – Autonomic Dysreflexia

This image illustrates the pathophysiology of autonomic dysreflexia (AD), a medical emergency that occurs in individuals with spinal cord injury (SCI) at or above T6. It explains how a noxious stimulus (like a full bladder or bowel distension) triggers a dangerous increase in blood pressure due to unregulated autonomic nervous system activity.

Left Diagram (Normal Sensory and Autonomic Response)

1. Stimulus (e.g., bladder distension, pain, or bowel irritation)

   • Afferent sensory nerves detect the stimulus and send signals to the spinal cord.

2. Signal Travels to the Brain

   • The spinothalamic tracts carry sensory impulses to the brain for processing.

3. Brain Interpretation and Response

   • The brain determines the appropriate response (e.g., emptying the bladder or removing the painful stimulus).

4. Motor Output and Reflex Response

   • The brain sends motor impulses back down the spinal cord to eliminate the stimulus.

   • This normal feedback loop prevents excessive autonomic reactions.

Right Diagram (Autonomic Dysreflexia in SCI at or Above T6)

1. Stimulus Below the Injury Level

   • Common triggers: bladder distension, bowel impaction, skin irritation, or painful stimuli.

2. Spinal Cord Below the Injury Reacts Without Brain Control

   • The stimulus sends sensory impulses up the spinal cord but is blocked at the injury site (T6 or above), preventing brain regulation.

3. Reflex Sympathetic Overreaction

   • Below the injury, the body responds with massive vasoconstriction, leading to:

     • Severe hypertension (high blood pressure)

     • Pale, cool skin below the injury

     • Pilomotor spasms (goosebumps)

4. Baroreceptor Reflex Detects High Blood Pressure

   • The carotid sinus and aortic baroreceptors detect sudden hypertension and send signals to the brainstem.

5. Brain Attempts to Fix the Issue

   • The brainstem (via the vagus nerve - CN X) tries to lower blood pressure by slowing heart rate (bradycardia) and dilating blood vessels above the injury level.

   • This results in:

     • Flushed skin above the injury

     • Sweating

     • Severe headache

6. Loss of Descending Inhibition Below T6

   • The brain’s corrective signals cannot travel below the spinal injury, leaving the vasoconstriction below T6 unchecked, worsening hypertension.

-increase in heart rate and blood pressure→ lead to autonomic dyregulation→overaction of the sympathetic division of the nervous system

You know that spinal shock results in

1. bradycardia.

2. moderate hypertension.

3. fever.

4. poor venous circulation.

poor venous circulation

explanation: In spinal shock there is a disruption of central communication with sympathetic spinal nerves which causes a transient drop in blood pressure, poor venous circulation, and disturbed thermal regulation.

Degenerative Disorders of the Spine (all of these cause back pain, specifically lower back pain→ lower lumber to the sacral spinal cord)

• Degenerative disk disease (DDD)

➢ Spondylolysis (degenerative process of the vertebral column that is associated with soft tissue damage that is usually hereditary)

➢ Spondylolisthesis (when the vertebrae slide forward in relation to the vertebrae below it sets actual movement of vertebrae in relation to each other)

➢ Spinal stenosis (narrowing of the spinal cord, causes compression)

Degenerative Disorders of the Spine (all of these cause back pain, specifically lower back pain→ lower lumber to the sacral spinal cord)

• Herniated intervertebral disk (sciatica)

Degenerative Disorders of the Spine

Degenerative spine disorders involve progressive wear and tear on the spinal structures, particularly the intervertebral discs and vertebrae. These conditions can lead to pain, nerve compression, and reduced mobility.

1. Degenerative Disk Disease (DDD)

• A gradual deterioration of the intervertebral discs, which act as cushions between the vertebrae.

• Causes include aging, repeated stress, poor posture, and genetic factors.

• Leads to disc thinning, reduced shock absorption, and increased pressure on spinal nerves.

• Symptoms: Chronic back pain, stiffness, and nerve compression symptoms like numbness and tingling.

2. Spondylolysis

• A stress fracture or defect in the pars interarticularis (a part of the vertebra).

• Common in athletes who engage in repetitive spinal extension (e.g., gymnasts, football players).

• Often occurs in the lumbar spine (L5 most commonly affected).

• Symptoms: Lower back pain that worsens with activity.

3. Spondylolisthesis

• Forward displacement (slipping) of a vertebra over the one below it, often due to spondylolysis or disc degeneration.

• Types:

  • Congenital (present at birth).

  • Isthmic (caused by a fracture in the pars interarticularis).

  • Degenerative (due to aging and DDD).

• Symptoms: Lower back pain, leg pain, stiffness, and nerve compression (sciatica-like symptoms).

4. Spinal Stenosis

• Narrowing of the spinal canal, leading to compression of the spinal cord or nerve roots.

• Can be caused by bone spurs, thickened ligaments, herniated discs, or degenerative arthritis.

• Most common in the cervical and lumbar spine.

• Symptoms:

  • Neurogenic claudication (pain and weakness in the legs while walking, relieved by sitting).

  • Back pain, numbness, and tingling in extremities.

5. Herniated Intervertebral Disk

• Occurs when the soft nucleus pulposus (inner gel-like part of the disc) pushes through a tear in the outer annulus fibrosus.

• Common in the lumbar spine (L4-L5, L5-S1) and cervical spine (C5-C6, C6-C7).

• Symptoms:

  • Severe back pain and radiculopathy (pain radiating down the legs or arms, depending on location).

  • Muscle weakness, numbness, tingling in the affected nerve distribution.

Clinical Management

• Conservative treatment: Physical therapy, pain management (NSAIDs, corticosteroid injections), and lifestyle modifications.

• Surgical interventions:

  • Laminectomy (for spinal stenosis).

  • Spinal fusion (for severe spondylolisthesis).

  • Discectomy (for herniated discs causing nerve compression).

Cerebrovascular Disorders

• Most frequently occurring neurologic disorder.

• Examples

➢ Cerebrovascular accidents (CVAs) or strokes

➢ Transient ischemic attacks (mini-strokes, occur in localized areas of the brain and they are transient, twitches in the eye) (you do not end up with permanent neurologic deficits)

➢ Aneurysms or malformations

Cerebrovascular Disorders – Cerebrovascular Accident

• Fifth-leading cause of death in the US

• Can range from minimal effects to death

• Greatest risk factor: hypertension

• Types

➢ Ischemic

➢ Hemorrhagic

➢ Crytogenic

(most strokes are ischemic and hemorrhagic)

(infarction=death of tissue due to lack of oxygen)

Cerebrovascular Accident(CVA) aka stroke

A Cerebrovascular Accident (CVA), commonly known as a stroke, occurs when there is an interruption of blood flow to the brain, leading to brain cell death due to lack of oxygen. It is the fifth-leading cause of death in the U.S. and can cause long-term disability.

Key Risk Factor: Hypertension

• High blood pressure is the greatest risk factor for strokes because it damages blood vessels over time, making them more likely to rupture (hemorrhagic stroke) or become blocked (ischemic stroke).

• Other risk factors include diabetes, smoking, heart disease, obesity, and high cholesterol.

Types of Stroke1. Ischemic Stroke (Most Common)

• Caused by a blockage in a blood vessel supplying the brain.

• About 87% of all strokes are ischemic.

• Can be due to:

  • Thrombosis: A clot forms inside a cerebral artery, usually due to atherosclerosis.

  • Embolism: A clot or debris travels to the brain from another part of the body (e.g., atrial fibrillation).

• Symptoms: Sudden weakness, numbness, speech difficulty, vision problems, confusion, or loss of coordination.

• Treatment: Clot-busting drugs like tPA (tissue plasminogen activator) if given within 3-4.5 hours, or mechanical thrombectomy to remove the clot.

2. Hemorrhagic Stroke (More Severe, Less Common)

• Caused by bleeding into the brain due to a ruptured blood vessel.

• Two main causes:

  • Hypertension-induced rupture of weakened arteries.

  • Aneurysm or arteriovenous malformation (AVM) rupture.

• Symptoms: Sudden severe headache ("thunderclap headache"), nausea, vomiting, weakness, vision changes, and loss of consciousness.

• Treatment:

  • Blood pressure control to prevent further bleeding.

  • Surgery (clipping an aneurysm, draining excess blood).

3. Cryptogenic Stroke (Unknown Cause)

• No obvious source of embolism or thrombosis.

• Possible causes:

  • Undetected atrial fibrillation (irregular heart rhythm).

  • Small-vessel disease that is not easily seen on imaging.

  • Hypercoagulable states (blood clotting disorders).

• Patients may need long-term heart monitoring and blood thinners.

Cerebrovascular Disorders – Cerebrovascular Accident

• Ischemic stroke

(going to occur when there is blood vessel occulusion of the artery that prevents the blood getting to the brain tissue) (treatment: systemic anticoagulant therapies, thrombolysis anti inflammatory therapy like using aspirin)

Cerebrovascular Disorders – Cerebrovascular Accident

• Lacunar stroke

(smaller areas, most likely a gyrus is going to be affected, smaller than a centimeter,) (same type of treatments as ischemic stroke) (less dysfunctional)

Cerebrovascular Disorders – Cerebrovascular Accident

• Hemorrhagic stroke

(more aggressive treatments because you need to limit hematoma)

• Ischemic Stroke

• Caused by a blood clot or blockage in an artery supplying the brain.

• The CT scan on the right (labeled "ischemic") shows an area of darker tissue, indicating reduced blood supply leading to infarction (brain tissue death).

• This is the most common type of stroke (about 87% of strokes).

• Lacunar Stroke

• A small vessel stroke that occurs deep in the brain, affecting small penetrating arteries.

• Often related to hypertension or diabetes.

• The MRI image (bottom left) highlights small infarcts (white arrows) characteristic of lacunar strokes.

• Hemorrhagic Stroke

• Caused by rupture of a blood vessel, leading to bleeding into the brain tissue.

• The CT scan on the right (labeled "hemorrhagic") shows a bright white area, indicating active bleeding.

• This type of stroke is less common but more severe than ischemic strokes.

Often caused by high blood pressure, aneurysms, or head trauma.

Key Differences in Imaging for strokes:

• Ischemic strokes appear darker (hypodense) on CT scans because of the lack of blood flow and oxygen.

• Hemorrhagic strokes appear brighter (hyperdense) due to the presence of fresh blood.

• Lacunar strokes are often small and deep, best seen on MRI.

-clinically what you are going to see is death of neurons in that ischemic area or infarct area if the tissue has died, edema too→further dysfunction

-artery thats most commonly affected in CVAs is going to be the middle cerebral artery(supplies areas of the frontal, temporal and paritetal lobe) → sensory and motor dysfunction

-the dysfunction you see is going to depend exactly on where the stroke occurs

-common stroke symptoms are going to include loss of motor control, problems with speaking, working their jaw(problems swallowing and working their throat)

Cerebrovascular Disorders – Intracranial Aneurysm (aneurysms are outpocketing or dilation of blood vessels) (they are silent) (symptoms show up when the aneurysm bursts and when it does burst the most common presentation is going to be excruciating headache and projectile vomiting) (they are acquired and formed, and often because of atherosclerotic disease)

• Saccular (berry) (we see these associated with congenital abnormalities or degenerative changes in the blood vessels)

• Fusiform (giant) (commonly seen with diffuse arterial sclerotic changes)

• Mycotic (caused by infections)

• Traumatic (dissecting) (trauma to the brain)

Cerebrovascular disorders, including intracranial aneurysms, involve abnormalities in the blood vessels of the brain that can lead to life-threatening conditions such as hemorrhagic strokes. An aneurysm is an outpouching or dilation of a blood vessel due to weakness in the vessel wall. There are different types of intracranial aneurysms:

1. Saccular (Berry) Aneurysm

• The most common type of intracranial aneurysm.

• It has a sac-like outpouching with a narrow neck connected to the blood vessel.

• Usually occurs at arterial bifurcations in the Circle of Willis.

• Associated with conditions like hypertension, smoking, and genetic predisposition.

• At risk of rupture, leading to subarachnoid hemorrhage.

Fusiform (Giant) Aneurysm

• Characterized by dilation of the entire circumference of a segment of a blood vessel.

• Often affects larger arteries, such as the basilar artery.

• Can be caused by atherosclerosis.

• Less likely to rupture than saccular aneurysms but may cause neurological symptoms by compressing surrounding structures.

Mycotic Aneurysm

• Caused by an infection that weakens the arterial wall, leading to an aneurysm.

• Often linked to bacterial endocarditis or systemic infections.

• Can lead to septic embolism, which can cause rupture and hemorrhage.

Traumatic (Dissecting) Aneurysm

• Results from head trauma or penetrating injury to the blood vessel.

• Can occur due to dissection (tearing) of the vessel wall, leading to an aneurysm.

• May cause stroke-like symptoms or hemorrhage if it ruptures.

You recall that fusiform aneurysms are:

1. congenital.

2. common in children.

3. due to arteriosclerotic changes.

4. from arteritis caused by bacterial emboli.

due to arteriosclerotic changes

explanation: Arteriosclerotic changes in the basilar and internal carotid arteries produce fusiform aneurysms.

Cerebrovascular Disorders – Vascular Malformations (they are rare, often going to be asymptomatic unless there is an issue with the blood supply)

• Cavernous angiomas (collections of blood vessels in the sinuses, withpit the blood vessels being dispered into the brain tissue)

• Capillary telangiectasis (dilated capillaries that are interspersed within the normal brain tissue)

• Venous angioma (most common malformation and that is going to be the embryological veins are radiating out from a central vein)

• Arteriovenous malformation (symptoms are usually nondescript headache and taht would be indicative of the vascular issues that are presented with the direct transfer of the oxygenared blood to a vein)

Vascular malformations are rare abnormalities of the blood vessels in the brain. They are often asymptomatic and may go undetected unless they disrupt blood flow, cause hemorrhages, or lead to neurological symptoms. There are different types of vascular malformations, each with unique characteristics:

1. Cavernous Angiomas (Cavernous Malformations)

• Clusters of abnormal, thin-walled blood vessels that resemble small "caverns."

• These vessels lack normal capillary connections, meaning blood slowly pools inside them.

• They are not dispersed into normal brain tissue but instead form in clusters.

• Often asymptomatic, but can cause seizures, headaches, or hemorrhages if they leak.

• Diagnosed through MRI and may require surgical removal if symptomatic.

Capillary Telangiectasia

• Made up of dilated capillaries interspersed within normal brain tissue.

• Usually benign and asymptomatic, found incidentally on imaging.

• Blood flow remains slow and low pressure, reducing the risk of rupture.

• Rarely requires treatment unless associated with other vascular abnormalities.

Venous Angioma (Developmental Venous Anomaly - DVA)

• Most common vascular malformation.

• Characterized by embryological veins radiating from a central draining vein, creating a "caput medusae" (medusa head) appearance.

• Usually asymptomatic and considered a normal variant rather than a disease.

• Rarely causes problems unless it leads to venous congestion or hemorrhage.

Arteriovenous Malformation (AVM)

• The most dangerous type of vascular malformation due to the direct connection between arteries and veins, bypassing capillaries.

• This abnormal shunting leads to high-pressure blood flow, increasing the risk of rupture and hemorrhage.

• Symptoms can include:

  • Nondescript headaches (which may be a warning sign of vascular stress).

  • Seizures.

  • Neurological deficits if it compresses brain tissue.

  • AVMs are often diagnosed via MRI or angiography and may require surgical removal, embolization, or radiosurgery to prevent rupture.

Headache Syndromes (headaches are most commonly associated with increased pressure in the blood vessels in the brain/changes in the vasculature)

 Migraine

 Cluster

 Tension

Headache Syndromes (headchaes are most commonly associated with increased pressure in the blood vessels in the brain/chnages in the vasculature)

• Migraine

(throbbing or pulsing pain on ONE SIDE of your head) (last 40-72 hours)(triggered by some external factor and they may or not have an aura)(trigeminal nerve)(associated with increased blood vessel contriction and blood flow through the brain at high pressure)(unilateral head pains or pulsating pain)(nausea,vominting, phonophobia or photophibia)

Headache Syndromes (headchaes are most commonly associated with increased pressure in the blood vessels in the brain/chnages in the vasculature)

• Cluster

(severe pain concentrated around ONE EYE) (several attacks occurring during the day for days on end and they are how long periods of spontaneous remission) (pain being referred to the face or teeth)

Headache Syndromes (headchaes are most commonly associated with increased pressure in the blood vessels in the brain/chnages in the vasculature)

• Tension

(most common type of headache)(tight band of squeezing pressure AROUND your head)(bilateral)

Headaches are commonly caused by changes in blood vessel pressure or alterations in the vasculature of the brain. Different types of headaches have distinct symptoms, causes, and durations.

1. Migraine Headaches

• Description: Throbbing or pulsating pain that typically affects one side of the head.

• Duration: Lasts 4 to 72 hours.

• Triggers: Can be caused by external factors like stress, lack of sleep, certain foods, hormonal changes, or environmental stimuli.

• Aura: Some migraines are preceded by an aura, which includes visual disturbances (flashes of light, blind spots), sensory changes, or speech difficulties.

• Cause: Related to trigeminal nerve activation and abnormal blood vessel constriction followed by high-pressure blood flow.

• Symptoms:

  • Unilateral (one-sided) throbbing pain

  • Nausea and vomiting

  • Photophobia (light sensitivity)

  • Phonophobia (sound sensitivity)

Treatment: Includes pain relievers, triptans, preventive medications, and lifestyle modifications.

Cluster Headaches

• Description: Severe, stabbing, or burning pain localized around one eye.

• Pattern:

  • Occurs in clusters, meaning multiple attacks per day for several days or weeks.

  • Followed by long periods of remission where no headaches occur.

• Referred Pain: Pain can spread to the face, teeth, or jaw.

• Symptoms:

  • Tearing, redness in the affected eye

  • Runny or congested nose on the same side as the headache

  • Restlessness due to intense pain

Treatment: Oxygen therapy, triptans, nerve block injections, and preventive medications.

Tension Headaches

• Description: The most common type of headache, often described as a tight band or squeezing pressure around the head.

• Location: Bilateral (affects both sides of the head).

• Triggers: Stress, poor posture, dehydration, lack of sleep, and muscle tension.

• Symptoms:

  • Dull, aching pain across the forehead or around the head

  • Muscle tightness in the neck and shoulders

  • Mild sensitivity to light or sound (but not as severe as migraines)

• Treatment: Over-the-counter pain relievers, stress management, proper hydration, and relaxation techniques.

summary of headaches

• Migraines → Throbbing one-sided headache, often with nausea, photophobia, and phonophobia.

• Cluster Headaches → Severe pain around one eye, occurring in clusters with periods of remission.

• Tension Headaches → Most common; feels like a tight band around the head, usually caused by stress.

A person arrives at the clinic and reports a unilateral headache for 2 days that worsens with movement and light. No trauma has occurred. You suspect:

1. subarachnoid hemorrhage.

2. cerebral tumor.

3. chronic paroxysmal hemicrania.

4. migraine headache.

migrane headache

explanation: Migraine is diagnosed when it is not attributable to any other disorder and when any two of the following features occur: unilateral head pain, pulsating pain, pain worsening with activity, moderate or severe pain intensity; and at least one of the following: nausea or vomiting, or both, or photophobia and phonophobia.

Chronic paroxysmal hemicrania

Chronic Paroxysmal Hemicrania (CPH) is a rare but severe primary headache disorder that falls under trigeminal autonomic cephalalgias (TACs), similar to cluster headaches but with key differences.

Characteristics:

• Unilateral pain (always affects one side of the head).

• Severe, stabbing, or throbbing pain, usually around the eye, temple, or forehead.

• Short-duration attacks (last 2 to 30 minutes per episode).

• Frequent attacks (occurs several times per day, sometimes up to 40 times daily).

• Autonomic symptoms (similar to cluster headaches):

  • Eye redness and tearing (conjunctival injection & lacrimation).

  • Nasal congestion or runny nose (rhinorrhea).

  • Drooping eyelid (ptosis) and pupil constriction (miosis).

Key Differences from Cluster Headaches:

• More frequent but shorter attacks compared to cluster headaches.

• No long remission periods (CPH is chronic and does not have pain-free intervals).

• 100% responsive to indomethacin, an NSAID (this response is diagnostic for CPH).

Treatment:

• Indomethacin (a nonsteroidal anti-inflammatory drug) is the first-line and most effective treatment.

• If indomethacin is not tolerated, alternatives include calcium channel blockers, melatonin, or gabapentin.

Summary:

CPH is a severe, frequent headache disorder with unilateral attacks lasting minutes and occurring multiple times daily. It is distinguished from cluster headaches by its responsiveness to indomethacin and the absence of remission periods.

Infection and Inflammation of the Central Nervous System

• Caused by bacteria, viruses, fungi, parasites, or mycobacteria(produces TB)

• Cardinal signs: fever, head or spine pain, generalized or focal neurologic dysfunction

• Pathophysiology: altered tissue function, inflammatory response, direct invasion of bacteria or neurotoxins

• Types:

➢ Meningitis (bacterial meningitis thats gonna be an infection in the pia matter, arachnoid villi, and subarachnoid space that infection is going to get into the ventricular system and it’ll spread through the CSF)

➢ Abscesses

➢ Encephalitis

➢ NeuroAIDS (HIV infection, in the microglia and can also infect neurons direcrly and astrocytes)

Infections of the CNS can be caused by bacteria, viruses, fungi, parasites, or mycobacteria (such as tuberculosis-causing mycobacteria). These infections trigger an inflammatory response, leading to tissue damage, neurological dysfunction, and systemic symptoms.

Cardinal Signs of CNS Infections:

1. Fever – Due to systemic infection and immune response.

2. Head or Spine Pain – Resulting from inflammation affecting the meninges, brain, or spinal cord.

3. Neurological Dysfunction – Can be generalized (confusion, altered mental status, seizures) or focal (weakness, paralysis, cranial nerve deficits).

Pathophysiology:

• Direct invasion of pathogens or their toxins into the CNS.

• Inflammatory response leads to swelling (edema), increased intracranial pressure, and tissue damage.

• Altered tissue function can result in neurological deficits, seizures, or coma.

Types of CNS Infections:1. Meningitis (Inflammation of the meninges)

• Causes:

  • Bacterial (e.g., Neisseria meningitidis, Streptococcus pneumoniae) → Medical emergency.

  • Viral (e.g., enteroviruses, HSV) → Usually milder.

  • Fungal (Cryptococcus neoformans) → Common in immunocompromised patients. (causes dementia?)

• Symptoms:

  • High fever, stiff neck, severe headache, projectile vomiting

  • Photophobia (light sensitivity).

  • Altered mental status, seizures in severe cases.

• Diagnosis: Lumbar puncture (CSF analysis).

• Treatment:

  • Bacterial: IV antibiotics, corticosteroids.

  • Viral: Supportive care, antivirals (e.g., acyclovir for HSV).

2. Brain Abscess (Localized pus collection in the brain)

• Causes:

  • Bacterial or fungal infection spreading from the sinuses, ears, or bloodstream.

• Symptoms:

  • Headache, fever, neurological deficits (depending on location in brain).

  • Seizures, increased intracranial pressure if severe.

• Diagnosis: MRI or CT with contrast.

• Treatment: IV antibiotics, drainage if needed.

3. Encephalitis (Inflammation of the brain tissue)

• Causes:

  • Viral infections (e.g., herpes simplex virus, arboviruses from mosquito bites, rabies).

• Symptoms:

  • Fever, headache, altered mental status, personality changes.

  • Seizures, movement disorders, coma in severe cases.

• Diagnosis: MRI, lumbar puncture, PCR for viral detection.

• Treatment:

  • HSV encephalitis: IV acyclovir.

  • Supportive care (fluids, seizure control).

4. NeuroAIDS (Neurological Complications of HIV/AIDS)

• Causes:

  • HIV directly infects the CNS and leads to opportunistic infections (e.g., toxoplasmosis, cryptococcal meningitis).

• Symptoms:

  • Cognitive impairment (HIV-associated neurocognitive disorder - HAND).

  • Weakness, seizures, personality changes.

• Diagnosis: MRI, lumbar puncture, HIV testing.

• Treatment: Antiretroviral therapy (ART), treating opportunistic infections.

Summary:

• Meningitis → Inflammation of the meninges, presents with fever, stiff neck, and headache.

• Brain Abscess → Pus-filled infection in the brain, can cause focal neurological symptoms.

• Encephalitis → Brain inflammation, often viral, leads to confusion, seizures, and coma.

• NeuroAIDS → HIV-related CNS complications, including cognitive decline and infections.

Infection and Inflammation of the Central Nervous System

• Bacterial meningitis

-bacterial meningitis, a serious infection that causes inflammation of the meninges (the protective membranes covering the brain and spinal cord)

-viral meningitis is usually not as severe but you can still hace throbbing headache, mild photophobia, mild neck pain and stiffness, fatigue/malaise, fever (treatment is antiviral drugs or supress the immune system with steroids)

1. Initial Infection:

   • Nasopharyngeal colonization: Bacteria first enter and colonize the upper respiratory tract (nasopharynx).

   • Bacteremia: The bacteria enter the bloodstream, allowing them to spread.

   • Meningeal invasion: The bacteria cross the blood-brain barrier and enter the subarachnoid space, leading to infection of the meninges.

2. Bacterial Multiplication & Immune Response:

   • The bacteria multiply and release endotoxins, which trigger a strong inflammatory response.

   • Leukocyte infiltration: White blood cells enter the CSF to fight the infection, leading to further inflammation.

   • Cytokine release: Inflammatory cytokines (chemical messengers) are released, worsening the immune response.

3. Inflammatory Effects on the Brain:

   • Ventricular and subarachnoid space inflammation causes swelling and increased pressure in the brain.

   • Vasculitis, vasospasm, and thrombosis occur, leading to loss of vascular autoregulation, which impairs blood flow to the brain.

   • Increased permeability of the blood-brain barrier leads to brain edema (swelling).

4. Complications and Brain Damage:

   • Intracranial hypertension: Increased pressure inside the skull.

   • Cerebral ischemia and necrosis: Reduced blood flow leads to tissue death.

   • Neurotoxic environment: Toxins from bacteria and immune response damage brain cells.

   • CSF outflow obstruction & hydrocephalus: Blockage of cerebrospinal fluid circulation causes fluid buildup, increasing pressure in the brain.

   • Brain edema (swelling) worsens neurological dysfunction.

   • Apoptosis (cell death) and brain damage result from prolonged inflammation.

   • Cerebral infarction (stroke): Severe cases can lead to areas of dead brain tissue.

Summary:Bacterial meningitis begins with an infection, spreads to the bloodstream, and invades the meninges. The immune response triggers severe inflammation, leading to swelling, increased pressure, impaired blood flow, and potential brain damage. If untreated, complications such as hydrocephalus, brain edema, stroke, and permanent neurological damage can occur

Infection and Inflammation of the Central Nervous System

• Brain or Spinal Cord Abscess

-bacterial or viral

-area of the brain where you have some issue that is causing activation of the immune system and local inflmmation and that would end up causing a abscess

-abscesses are localized collections of pus(neutrophils cause pus)

-often going to be because of an infection(usually from outside the CNS)

-cut it out or suck it out

The image depicts a gross pathology specimen of the brain, highlighting a brain abscess, which is a localized collection of pus within the brain tissue due to infection. The abscess appears as a well-circumscribed lesion with a central necrotic (yellowish-white) core, surrounded by an area of inflammation and edema.

Key Features of Brain Abscess:

1. Cause:

   • Bacterial, fungal, or parasitic infection leading to pus accumulation in the brain.

   • Common sources include sinus infections, ear infections, endocarditis, or trauma.

   • Streptococcus, Staphylococcus, and anaerobic bacteria are frequent culprits.

2. Pathophysiology:

   • Infection leads to localized inflammation and breakdown of tissue.

   • The immune system walls off the infection, forming a fibrotic capsule around the pus-filled core.

   • Surrounding tissue may show edema (swelling) and gliosis (scarring response of the brain).

3. Clinical Symptoms:

   • Headache

   • Fever

   • Neurologic deficits (weakness, seizures, or altered mental status)

   • Increased intracranial pressure (vomiting, papilledema)

Infection and Inflammation of the Central Nervous System

• Encephalitis

-acute febrile illness?

-viral origin often

-orthropod born viruses(mosquito bites), HSV

The image presents MRI scans of the brain, demonstrating encephalitis, which is an inflammation of the brain parenchyma. Encephalitis is most commonly caused by viral infections (e.g., herpes simplex virus, arboviruses, enteroviruses), though bacterial, autoimmune, and other infectious agents can also contribute.

Key Features of the Image:

1. Hyperintensities in MRI Scans (FLAIR sequences):

   • The bright areas in the MRI images suggest brain inflammation and edema.

   • The temporal lobes (especially in image C) are prominently affected, which is characteristic of Herpes Simplex Virus (HSV) Encephalitis.

2. Affected Brain Regions:

   • Image A & B: Show bilateral signal abnormalities in the cortex, indicating widespread inflammation.

   • Image C: Highlights unilateral temporal lobe involvement, which strongly suggests HSV encephalitis.

   • Image D: Shows brainstem and cerebellar involvement, which can occur in certain viral or autoimmune encephalitis cases.

Clinical Features of Encephalitis:

• Fever

• Altered mental status (confusion, disorientation, personality changes)

• Seizures

• Headache

• Neurologic deficits (speech disturbances, motor weakness)

Viral Infections and NeuroAIDS

-what you see in neuroAIDS is neuro cognitive impairment and behavioral disturbances, plus some motor distrubacxes that have to do with the primary infection by HIV, its going to lead to degenration in the spinal cord and degenration of some of the neurons in the brain

-dementia, increased opportunistic infections, more vulnerable to neoplasms

1. Neurons (Primary signaling cells in the brain)

Viruses affecting neurons:

• Herpes Simplex Virus (HSV-1 & HSV-2): Causes encephalitis and can establish latency in neurons.

• Rabies Virus: Affects neurons, leading to fatal encephalitis with symptoms like aggression and hydrophobia.

• West Nile Virus: Can cause viral encephalitis and neuronal death.

• Nipah Virus: Leads to severe encephalitis with high mortality.

• Equine Encephalitis Viruses (Eastern, Western, Venezuelan): Cause brain inflammation and neuronal damage.

• Mumps Virus: Can invade the central nervous system (CNS) and cause viral meningitis or encephalitis.

• Varicella-Zoster Virus (VZV): Causes shingles and, in some cases, encephalitis or vasculopathy.

• Measles Virus (SSPE - Subacute Sclerosing Panencephalitis): A rare but fatal disease that results from persistent measles virus infection in the brain.

• Cytomegalovirus (CMV): Can cause encephalitis in immunocompromised individuals.

➡ Impact on neurons: These infections lead to direct neuronal death, inflammation, and long-term neurological damage.

2. Oligodendrocytes (Cells that produce myelin for nerve insulation)

Viruses affecting oligodendrocytes:

• JC Virus (JCV): Causes Progressive Multifocal Leukoencephalopathy (PML), a fatal demyelinating disease in immunocompromised patients.

• Cytomegalovirus (CMV): Can cause demyelination and white matter damage in the brain.

➡ Impact on oligodendrocytes: These infections lead to loss of myelin, impairing nerve signal transmission and causing severe neurological dysfunction.

3. Microglia and Perivascular Macrophages (Brain's immune cells)

Viruses affecting microglia and macrophages:

• HIV: Causes HIV-associated neurocognitive disorders (HAND) due to chronic inflammation and immune activation in the brain.

• Cytomegalovirus (CMV): Can also infect microglia, leading to encephalitis in immunocompromised patients.

➡ Impact on microglia: These infections lead to chronic neuroinflammation, neuronal damage, and cognitive decline.

4. Astrocytes (Support and protect neurons)

Viruses affecting astrocytes:

• Equine Encephalitis Viruses: Cause severe brain inflammation.

• HIV: Infects astrocytes indirectly, leading to neurological damage.

• JC Virus (JCV): Can contribute to PML (Progressive Multifocal Leukoencephalopathy).

• Cytomegalovirus (CMV): Can cause astrocyte dysfunction.

• HTLV-1 (Human T-Lymphotropic Virus 1): Associated with tropical spastic paraparesis, affecting motor function.

➡ Impact on astrocytes: Dysfunction in these cells leads to altered neurotransmitter regulation and increased brain inflammation.

5. Endothelial Cells (Blood-Brain Barrier - BBB)

Viruses affecting endothelial cells:

• Nipah Virus: Causes BBB disruption, allowing pathogens to enter the brain, leading to severe encephalitis.

• Cytomegalovirus (CMV): Also damages endothelial cells, increasing the risk of neurological infections.

➡ Impact on the BBB: Infection weakens the brain’s defense, making it more vulnerable to other infections and inflammation.

Demyelinating Disorders

-autoimmune disorders where you’re attacking your own cells in the CNS

-autorreactive T cells and B cells, you’re producing antibodies against your soft proteins and their protein constituents of the myelin itself

• Multiple sclerosis (CNS)

• Guillain-Barré syndrome(PNS)

Demyelinating Disorders – Multiple Sclerosis

-progressive, chronic, inflammatory demyelinating condition caused by your reactive T and B cells against the brain tissue itself and it occurs most frequently in women 

-remyelination, remission then it comes back (clinical presentation symptom), dysfunction of the axon→ slow action potential activation, tretament: vitamin d therapy, stem cell therapy

1. Left Side - Brain Cross-Section (Macroscopic Pathology)

• This is a coronal section of the brain showing pathological changes due to MS.

• The white matter appears damaged, showing multiple sclerosis plaques (areas of demyelination).

• The labeled structures:

  • P (Plaque): Indicates an area of demyelination where myelin has been destroyed.

  • V (Ventricle): Represents the ventricular system, which appears enlarged due to brain atrophy, commonly seen in MS patients.

• The irregular lesions in white matter indicate loss of myelin, which is characteristic of MS.

2. Right Side - Diagram of Neuronal Damage in MS

• Normal Nerve:

  • Shows a neuron with an intact myelin sheath surrounding the axon.

  • Oligodendrocytes (purple cells) are responsible for producing and maintaining myelin in the CNS.

• Damaged Nerve in MS:

  • The myelin sheath is damaged, exposing the axon (yellow structure).

  • Oligodendrocytes are affected, leading to impaired nerve signal transmission.

  • Damage results in slower or disrupted nerve impulses, causing symptoms such as muscle weakness, coordination problems, and sensory disturbances.

• Immune Response Involvement (Magnified Section)

  • Activated T cells and macrophages (microglia) attack myelin, leading to chronic inflammation.

  • These immune cells cause progressive demyelination and axonal damage.

  • This immune-mediated attack is the hallmark of MS, where the body's defense system mistakenly attacks its own nervous tissue.

Key Takeaways from the Image:

• MS is a demyelinating disorder, meaning it destroys the protective myelin sheath, leading to nerve dysfunction.

• The left image shows actual brain pathology, with visible white matter lesions (MS plaques).

• The right image explains the cellular mechanisms, showing how the immune system attacks myelin, leading to nerve signal disruption.

• Oligodendrocytes fail to repair damage, worsening neurological decline.

• Symptoms of MS include vision problems, muscle weakness, fatigue, and coordination issues due to damaged nerve conduction.

Demyelinating Disorders – Guillain-Barré Syndrome

-autoimmune function against schawnn cells in the peripheral nervous system

-does not have a gender prefernce

-occurs in one episdoe, either lives and recovers or dies

-often occurs after a viral infection

-ascending motor paralysis starting from the feet

-treatment: plasmapheresis(It involves separating blood, discarding plasma, and replacing it with a substitute), intravenous immunoglobulins

1. Left Image (Panel A) – Normal Myelinated Nerve Fibers

• This image shows a healthy peripheral nerve cross-section stained to visualize myelin sheaths.

• The dark rings represent intact myelin sheaths around nerve axons, indicating proper nerve function.

• Asterisks (*) likely mark normal axons with well-preserved myelin.

• Key Features:

  • Uniform dark rings indicate intact myelin sheaths.

  • Regular distribution of nerve fibers, showing a normal peripheral nerve.

2. Right Image (Panel B) – Guillain-Barré Syndrome (Demyelination)

• This image shows peripheral nerve damage due to GBS, an autoimmune-mediated demyelinating disorderaffecting the peripheral nervous system (PNS).

• Arrowheads point to nerve fibers with thinner or absent myelin sheaths, indicating demyelination.

• The lighter appearance of some nerve fibers suggests myelin loss, disrupting normal nerve signal conduction.

• Key Features:

  • Irregular myelin sheaths (thinning or absent in some nerves).

  • Inflammatory response likely contributed by autoimmune attack on Schwann cells (which produce myelin in the PNS).

  • Nerve conduction is impaired, leading to symptoms like muscle weakness, tingling, and paralysis.

Key Takeaways from the Image:

• Guillain-Barré Syndrome (GBS) is a demyelinating disorder of the PNS, caused by an immune attack on Schwann cells.

• The left image (A) shows normal peripheral nerve fibers, while the right image (B) highlights demyelinationwith disrupted or lost myelin sheaths.

• Loss of myelin impairs nerve signal transmission, leading to weakness, paralysis, and sensory disturbancesseen in GBS patients.

• Unlike Multiple Sclerosis (MS), which affects the CNS, GBS affects the peripheral nerves.

• GBS is often triggered by infections (e.g., Campylobacter jejuni, viral infections) and can be life-threatening if it affects respiratory muscles

Peripheral Nervous System Disorders

• Neuropathies(dysfunction in peripheral nerves)

➢ Generalized symmetric polyneuropathies (neuropathy in the feet=starts in the legs, ascending of the legs) (diabetic neuropathy: poor circulation, pain, numbeness, foot ulcers)

➢ Generalized neuropathies (affects sensory OR motor)

➢ Focal or multifocal neuropathies (affects sensory AND motor)

-muscle atrophy in those affected muscles because of the decreased activation of the lower motor neurons

Neuropathies refer to disorders affecting the peripheral nervous system (PNS), which consists of all the nerves outside the brain and spinal cord. These disorders can result from various causes, including diabetes, infections, autoimmune diseases, toxins, or genetic conditions. Neuropathies are classified into three main types:

1. Generalized Symmetric Polyneuropathies

• These affect multiple peripheral nerves symmetrically (on both sides of the body).

• Common causes include diabetes (diabetic polyneuropathy), vitamin deficiencies, and toxic exposures.

• Symptoms: Numbness, tingling, burning pain, and weakness, usually starting in the feet and progressing upward (a "stocking-glove" distribution).

Generalized Neuropathies

• Affect a specific type of nerve function (e.g., sensory, motor, or autonomic nerves).

• Examples:

  • Sensory neuropathies – cause loss of sensation and pain (e.g., in small fiber neuropathy).

  • Motor neuropathies – lead to muscle weakness and atrophy (e.g., in Guillain-Barré syndrome).

  • Autonomic neuropathies – affect involuntary body functions like heart rate, digestion, and blood pressure (e.g., diabetic autonomic neuropathy).

Focal or Multifocal Neuropathies

• Affect one (focal) or multiple (multifocal) specific nerves rather than widespread nerve damage.

• Focal neuropathies involve a single nerve, often due to compression, injury, or inflammation (e.g., carpal tunnel syndrome affecting the median nerve in the wrist).

• Multifocal neuropathies affect several nerves in different areas, but not symmetrically (e.g., multifocal motor neuropathy, which leads to asymmetric muscle weakness).

Radiculopathies

-inflammation of the spinal nerve roots

-disorders of the spinal nerve root, often going to be caused by compression on the spinal nerves although it can be caused by things like infection, inflammation, ischemia, or trauma

-one case where youll see radiculpathies are with avulsion injuries (tearing type injuries where you’re pulling out the root of that spinal nerve

-clinical implications: if this is the cervical vertebrae you will see paralysis or loss of sensory function in the shoulders and arms, if its a lumbar vertebrae you’re going to see the same types of symptoms in the legs

-surgery, antiimmalfatory therapies: antibodies or steroids

The image provides an overview of radiculopathies, which are conditions caused by compression or irritation of spinal nerve roots.

Left Side (Cervical Spine Anatomy)

• The image depicts the cervical spine, highlighting:

  • Vertebrae – The bony structures that protect the spinal cord.

  • Intervertebral Discs – Cushion-like structures between vertebrae that provide flexibility and shock absorption.

  • Nerve Roots – Yellow structures that branch out from the spinal cord and extend through openings in the vertebrae to supply different parts of the body.

Right Side (Healthy vs. Damaged Vertebra)

• Healthy Vertebra (Top Image):

  • Shows a normal spinal cord and nerve roots without compression.

  • The intervertebral disc is intact and maintains spacing between vertebrae.

• Damaged Vertebra (Bottom Image):

  • Displays pathological changes leading to radiculopathy, including:

    • Bone spurs (osteophytes) forming on the vertebrae, which can impinge on nerves.

    • Thickening of the ligamentum flavum, which reduces space for nerve roots.

    • Disc degeneration or herniation, leading to pressure on nerve roots.

Implications of Radiculopathies

• Nerve compression in the cervical spine can cause symptoms such as:

  • Neck pain.

  • Radiating pain, numbness, or weakness in the arms and hands.

  • Loss of reflexes and coordination.

Plexus Injuries

-Clinical manifestations: present with motor weakness, muscle atrophy and sensory loss

-treatment is to remove the cause of that particular dysfunction, amino acids to the site can help

Right Side: Brachial Plexus Anatomy

• The diagram outlines the structure of the brachial plexus, showing its components from nerves to branches:

  • Nerves (Roots): C5, C6, C7, C8, and T1.

  • Trunks: Upper, Middle, and Lower.

  • Divisions: Each trunk divides into an anterior and posterior division.

  • Cords: Lateral, Posterior, and Medial cords are formed based on the divisions.

  • Branches: Major peripheral nerves include:

    • Musculocutaneous nerve (innervates biceps and forearm flexors)

    • Axillary nerve (deltoid and teres minor)

    • Radial nerve (triceps, wrist extensors)

    • Median nerve (flexor muscles of forearm, thumb)

    • Ulnar nerve (intrinsic hand muscles)

Left Side: Affected Regions in Plexus Injuries

• The color-coded dermatomal map highlights the areas affected by brachial plexus injuries:

  • C5 (Shoulder - Purple): Injury may cause weakness in the deltoid and biceps.

  • C6 (Elbow - Red): Loss of wrist extension and weakness in the biceps.

  • C7 (Wrist - Green): Issues with wrist flexion and finger extension.

  • C8 & T1 (Hand - Blue): Loss of fine motor control and intrinsic hand muscle weakness.

Clinical Relevance

• Brachial plexus injuries occur due to trauma, childbirth complications, or nerve compression.

• Common conditions include:

  • Erb's Palsy (C5-C6 injury) – Weakness in shoulder abduction and elbow flexion.

  • Klumpke's Palsy (C8-T1 injury) – Paralysis affecting hand muscles, leading to a "claw hand" deformity.

  • Radial nerve injury – Leads to wrist drop due to extensor muscle weakness.

Neuromuscular Junction Disorders

• Disorders associated with autoantibodies

         1. Myasthenia gravis (autoimmune chronic, the antibodies are directed against the acetylcholine receptors themselves, immunoglobulin specifically IgG),

         2. Lambert-Eaton myasthenic syndrome (prevent neurotransmitter release from those lower motor neurons, so the neurotransmitter cant be released because you cant mobilize the vesicles that contain the neurotransmitter, you dont get activation at the neuromuscular junction because you cant release the acetylcholine) (autoantibodies are directed against calcium channels on the pre somatic nerve terminals)

              • Autoantibodies to calcium channels on presynaptic nerve terminals

• Some disorders are mutations in different key proteins

         ➢ Inherited (congenital) myasthenic syndromes

The neuromuscular junction (NMJ) is the site where motor neurons communicate with muscle fibers to initiate movement. Disorders of the NMJ can lead to muscle weakness and fatigue due to impaired signal transmission. These disorders can be categorized based on their underlying cause, such as autoantibodies or genetic mutations.

1. Autoantibody-Associated Neuromuscular Junction Disorders

These are autoimmune diseases in which the body's immune system mistakenly attacks key proteins involved in neurotransmission at the NMJ.

A. Myasthenia Gravis (MG)

• Cause: Autoantibodies (mainly IgG) target acetylcholine receptors (AChRs) at the postsynaptic membrane.

• Effect:

  • Reduced number of functional AChRs.

  • Impaired muscle activation.

  • Progressive muscle weakness and fatigue, especially with repeated use.

• Symptoms:

  • Ptosis (drooping eyelids).

  • Diplopia (double vision).

  • Weakness in limbs and respiratory muscles.

• Treatment:

  • Acetylcholinesterase inhibitors (e.g., pyridostigmine) to increase acetylcholine levels.

  • Immunosuppressants (e.g., corticosteroids).

  • Plasmapheresis or IVIG for severe cases.

B. Lambert-Eaton Myasthenic Syndrome (LEMS)

• Cause: Autoantibodies target presynaptic voltage-gated calcium channels (VGCCs).

• Effect:

  • Disruption in calcium entry into the presynaptic neuron.

  • Failure to mobilize acetylcholine-containing vesicles.

  • Decreased acetylcholine release, leading to muscle weakness.

• Symptoms:

  • Weakness that improves with repeated activity (opposite of MG).

  • Commonly associated with small cell lung cancer (paraneoplastic syndrome).

• Treatment:

  • 3,4-Diaminopyridine (3,4-DAP) to enhance neurotransmitter release.

  • Cancer treatment (if associated with malignancy).

  • Immunosuppression.

2. Genetic Neuromuscular Junction Disorders

Some NMJ disorders arise due to genetic mutations affecting key proteins involved in neurotransmission.

Congenital Myasthenic Syndromes (CMS)

• Cause: Mutations in genes responsible for NMJ function (e.g., AChR subunits, presynaptic vesicle proteins, or synaptic enzymes).

• Effect:

  • Defective acetylcholine release, receptor function, or synaptic maintenance.

  • Muscle weakness present from birth or early childhood.

• Symptoms:

  • Generalized muscle weakness.

  • Respiratory issues in severe cases.

• Treatment:

  • Depends on the specific mutation (some benefit from acetylcholinesterase inhibitors, while others worsen with these drugs).

Neuromuscular Junction Disorders – Myasthenia Gravis

• Autoimmune disease against AChR

-decreased ability to contract muscles

-can occur in kids and newborns, happens in the eyes(first manifest symptom=ocular myasthenia, weakness and fatigue in the eyes, double vision) then it moves onto the face and the body

-nicotinic acetylcholine recpetor

-muscle weakening that then leads to respiratory distress

-treatment: anticholinesterase drugs

A. Normal Neuromuscular Junction (Left Side)

• The presynaptic terminal releases acetylcholine (ACh) into the synaptic cleft when an action potential arrives.

• Acetylcholine binds to acetylcholine receptors (AChRs) on the postsynaptic membrane of the muscle fiber.

• This binding triggers sodium (Na⁺) influx, leading to muscle contraction.

• Acetylcholinesterase (AChE) breaks down acetylcholine to terminate the signal.

• MuSK (Muscle-Specific Kinase) plays a role in maintaining AChR function.

B. Myasthenia Gravis (Right Side)

• Autoantibodies attack key neuromuscular junction components, disrupting normal signaling.

• Types of antibodies involved:

  • AChR antibodies block or destroy acetylcholine receptors, preventing muscle activation.

  • MuSK antibodies interfere with receptor clustering, further weakening the signal.

  • Presynaptic calcium channel antibodies (less common) can reduce ACh release.

• Effects:

  • Decreased receptor availability leads to reduced muscle activation.

  • Muscle weakness and fatigue, worsening with repeated activity.

  • Incomplete neuromuscular transmission, making it difficult to sustain contraction.

Key Takeaways

• Normal NMJ: Efficient ACh signaling → muscle contraction.

• MG NMJ: Autoantibodies disrupt ACh binding → impaired muscle activation → weakness.

• Treatment Strategies:

  • Acetylcholinesterase inhibitors (e.g., pyridostigmine) to increase ACh availability.

  • Immunosuppressants to reduce antibody production.

Plasmapheresis or IVIG in severe cases to remove autoantibodies.

Brain Tumors

-primary tumors: tumors that are going to arise from the cells that are inherent in the CNS

-secondary tumors: basically metastases and so they travel to the brain tissue from a site that outside of the CNS, much more common than primary brain tumors

-brain is a major site for metastases

-often tumors are going to presnet with visual disturbances, loss of equilibrium in carnival nerve dysfunction(headache), seizures

-treatment: radio theraphies

Tumors of the Central Nervous System

• Meningiomas: Parasagittal meningioma and Sphenoidal ridge meningioma—tumors that arise from the meninges (protective layers of the brain).

• Gliomas: 

-Glioblastoma multiforme: WORST PROGNOSIS A highly aggressive tumor affecting the cerebral hemispheres 

-Oligodendroglioma: Arises from oligodendrocytes, cells that support nerve function

-Astrocytomas(most common type of tumor in the CNS): Includes Frontal astrocytoma and Cystic astrocytoma of the cerebellum. Symptoms: Headaches, behavioral changes, seizures

• Medulloblastoma: Found in the cerebellum, common in children, primitive cells

• Ependymoma: Found in the fourth ventricle, originating from ependymal cells.

• Metastatic Tumors: Can originate from cancers elsewhere (e.g., lung cancer).

• Craniopharyngioma: A tumor near the pituitary gland.

Pituitary Adenoma

A noncancerous tumor in the pituitary gland.

Tumors of the Central Nervous System (Cont.)

Neoplasm (Tumor) Initiation

• The tumor (neoplasm) can cause problems through invasion and compression.

Effects of Invasion and Compression

• Invasion leads to focal deficits depending on the tumor's location in the brain.

• Compression results in cerebral edema (swelling of the brain), which contributes to increased intracranial pressure.

Increased Intracranial Pressure (ICP)

• A direct result of tumor growth, edema, and compression.

• Causes several neurological symptoms.

Symptoms and Effects of ICP:

• Diminished cognitive functioning, which can lead to behavioral alterations.

• Headache

• Vomiting

• Seizures

• Papilledema (swelling of the optic disc, often linked to increased brain pressure).

• Unsteady gait (difficulty walking due to brain dysfunction).

• Loss of sphincter control (issues with bladder and bowel control).

Primary Brain Tumors

• Primary intracranial

➢ Gliomas

-Astrocytomas (most common) (treatment: surgery for grade 1 and 2)

-Oligodendrogliomas (tumors of oligodendrocytes) (usually benign) (surgery is the stadard course of treatment)

-Edendymomas (arise from the ependymal cells)(rare in the CNS)(surgical resection is effective)(slow growing)

• Primary extracranial

➢ Meningiomas (tumors of the meninges)(slow growing)(seizures)

Primary brain tumors originate within the brain or its surrounding structures, unlike metastatic tumors, which spread from cancers in other parts of the body. These are classified as intracranial (inside the brain) and extracranial (outside the brain but still affecting the CNS).

Primary Intracranial Tumors (Inside the Brain)

1. Gliomas (arise from glial cells, which support neurons)

   • Astrocytomas

     • Most common type of glioma.

     • Arise from astrocytes, star-shaped glial cells that support brain function.

     • Treatment:

       • Low-grade (Grade 1 & 2): Surgery is the primary treatment.

       • High-grade (Grade 3 & 4, including glioblastoma): Often require chemotherapy and radiation. VERY POOR PROGNOSIS(3-4 Months)

   • Oligodendrogliomas

     • Develop from oligodendrocytes, which produce myelin (the protective sheath around nerve fibers).

     • Usually benign (slow-growing and less aggressive than other gliomas).

     • Treatment: Surgery is the standard approach.

   • Ependymomas

     • Arise from ependymal cells, which line the ventricles and spinal canal, producing cerebrospinal fluid (CSF).

     • Rare in the CNS but can occur in children and young adults.

     • Slow-growing, making surgical removal effective.

     • Treatment: Surgical resection is usually effective.

Primary Extracranial Tumors (Outside the Brain but Affecting the CNS)

• Meningiomas

  • Develop from the meninges, the protective membranes covering the brain and spinal cord.

  • Typically slow-growing and benign, but their location can cause neurological issues.

  • Symptoms: Can cause seizures due to brain irritation.

  • Treatment: Surgery is often the preferred approach if the tumor causes significant symptoms.

Primary Brain Tumors – Astrocytomas

-most common in the CNS

-nicely encapsulated(that is why surgery is good)

-not a very aggressive

-can become a glioblastoma which is a very aggressive tumor with bad prognosis

Brain Metastases

-most common type of brain tumor, multiple locations around the brain

Traumatic brain injury (TBI) is an alteration in brain function or other evidence of brain pathology caused by an external force.

Primary brain injury is caused by an impact and can be focal or diffuse with open- or closed-head injury.

Severity of TBI is graded using the Glasgow Coma Score.

Focal brain injury includes coup and contrecoup, contusion (bruising of the brain), laceration (tearing of brain tissue), extradural hematoma (accumulation of blood above the dura mater), subdural hematoma (blood between the dura mater and arachnoid membrane), intracerebral hematoma (bleeding into the brain), and open-head trauma.

Open-head injury involves a skull fracture with exposure of the cranial vault to the environment. The types of skull fracture include compound fracture or perforated fracture and linear, comminuted, and basilar skull fracture.

Closed-head injuries occur in a precise location, and most are mild. More severe damage includes contusions and epidural, subdural, subarachnoid, and intracerebral hemorrhage.

Diffuse axonal injury (DAI) results from mechanical forces of acceleration, deceleration, and rotation that cause stretching and shearing of axons and can only be seen microscopically. The injury can be mild, moderate, or severe.

Secondary neuronal injury occurs as an indirect result of primary brain injury. Systemic processes include hypotension, hypoxia, anemia, hypoglycemia, hyperglycemia, and hypercapnia or hypocapnia. Cerebral contributions include inflammation, oxidative stress, alterations in the blood-brain barrier, excitotoxicity, cerebral edema, increased intracranial pressure (IICP), decreased cerebral perfusion pressure, cerebral ischemia, and brain herniation.

Complications of TBI include postconcussion syndrome, posttraumatic seizures, and chronic and traumatic encephalopathy

Spinal cord and vertebral injuries occur most often in young men who sustain various kinds of injuries (recreational or travel-related) and older adults because of preexisting degenerative vertebral disorders. Vertebral injuries include fractures, dislocations, compressions, and penetrating bone fragments from shearing and compression force. Fractures can be simple, compressed, or comminuted.

Primary spinal cord injury involves damage to vertebral or neural tissues from shearing, compression, or traction forces.

Secondary spinal cord injury is related to edema, ischemia, excitotoxicity, inflammation, oxidative damage, and activation of necrotic and apoptotic cell death and begins within minutes after injury and continues for weeks

Spinal cord injury often causes spinal shock with cessation of all motor, sensory, reflex, and autonomic functions below any transected area. Loss of motor and sensory function depends on the level of injury.

Neurogenic shock (vasogenic shock) occurs with cervical or upper thoracic cord injury above T5 and may be seen in addition to spinal shock. There is loss of sympathetic activity and unopposed vagal parasympathetic activity with symptoms of hypotension, bradycardia, and hypothermia.

Paralysis of the lower half of the body with both legs involved is called paraplegia. Paralysis involving all four extremities is called quadriplegia.

Return of spinal neuron excitability occurs slowly. Reflex activity can return in 1 to 2 weeks in most people with acute spinal cord injury. A pattern of flexion reflexes emerges, involving first the toes and then the feet and legs. Eventually reflex voiding and bowel elimination appear, and mass reflex (flexor spasms accompanied by profuse sweating, piloerection, and automatic bladder emptying) may develop.

Autonomic hyperreflexia (dysreflexia) is a syndrome of sudden massive reflex sympathetic discharge associated with spinal cord injury at level T5-T6 or above and can cause life- threatening hypertension.

The pathologic findings in degenerative disk disease (DDD) include disk protrusion, spondylosis and/or subluxation, degeneration of the vertebrae (spondylolisthesis), and spinal stenosis.

Low back pain is pain between the lower rib cage and gluteal muscles and often radiates into the thigh.

Most causes of low back pain are unknown; however, some secondary causes are disk prolapse, tumor, bursitis, synovitis, degenerative disk disease, osteoporosis, hyperparathyroidism, fracture, inflammation, and sprain.

Degenerative disk disease is part of normal aging as a response to continuous vertical compression of the spine, usually in the lumbar region. Both genetic and environmental factors contribute to loss of disk connective tissue.

Disks can tear and herniate, pinching nerves and straining the spine. In addition there may be changes in the vertebral body with spondylolysis or spondylolisthesis, or both, degeneration of vertebrae, and spinal stenosis.

Spondylolysis is a structural defect in the pars interarticularis of the vertebral arch with anterior displacement (sliding) of the deficient vertebra (spondylolisthesis) and is a cause of low back pain.

Cervical spondylolysis is facet hypertrophy and disk degeneration with narrowing in the cervical spine predominantly at C5-C6 and C6-C7 and can cause radiculopathy and myelopathy with numbness and tingling in the arms, occipital headache, difficulty walking, altered sensation in the feet, and sphincter disturbances.

Spinal stenosis is narrowing of the spinal canal that causes pressure on the spinal cord and is associated with trauma or arthritis. Symptoms include pain, numbness, and weakness in the areas of affected spinal nerves.

Herniation of an intervertebral disk is a protrusion of part of the nucleus pulposus, most commonly at L5-S1 and L4-L5. The extruded pulposus compresses the nerve root, causing pain that radiates along the sciatic nerve.

Cerebrovascular disease is the most frequently occurring neurologic disorder. Any abnormality of the blood vessels of the brain is referred to as cerebrovascular disease and includes vessel wall abnormalities and vascular malformations, thrombotic or embolic occlusion, and increased blood viscosity or clotting.

 Cerebrovascular disease causes (a) ischemia with or without infarction and (b) hemorrhage. The common clinical manifestation is a cerebrovascular accident (CVA) or stroke syndrome. Hypertension is the greatest risk factor followed by other preventable risks.

CVAs are classified according to pathophysiology and include ischemic (thrombotic, embolic, and hypoperfusion), lacunar (small vessel disease), and hemorrhagic strokes

A transient ischemic attack is a transient episode of neurologic dysfunction resulting from focal cerebral ischemia with risk for progressing to stroke.

Ischemic strokes result from interruption in brain blood flow with a core of irreversible ischemia and necrosis or infarction that appears pale (white infarct).

The zone around the infarction has reversible ischemia, is called the ischemic penumbra, and can regain neurologic function, particularly with thrombolytic treatment. Leaking blood vessels can develop in the infarcted area, resulting in a hemorrhagic transformation (a red infarct) that can be exacerbated by thrombolytic therapy.