3. Pathology of the Central and Peripheral Nervous Systems

5 Degenerative and demyelinating CNS diseases

– Alzheimer disease
– Parkinson disease and Parkinsonism
– Huntington disease (chorea)
– Amyotrophic lateral sclerosis (ALS)
– Multiple sclerosis

alzheimer disease

Progressive neurodegenerative disease

#1 cause of dementia (> 60%)

Described by Alois Alzheimer in 1906

Alzheimer Disease Causes

Not completely understood

Most cases are sporadic (<2% inherited)

Alzheimer Disease risk factors

mutation of genes:

Epsilon 4 mutation of apolipoprotein E gene (APOE) in 40% to 80% of patients

Other genes also involved

what age group is most likely to develop alzheimer’s

Most patients over 65

Early-onset: From 30s to 50s (10% of cases)

what group is least likely to develop alzheimer’s

Higher education - protective effect

Cognitive reserve to compensate for damage

Alzheimer Disease stages

signs + symptoms classified by stage of the disease:
• Early-stage (mild)
• Middle-stage (moderate)
• Late-stage (severe)

Become progressively worse

Early-stage (mild):

Short-term memory loss

Difficulty with:

• finding correct words and names

• performing familiar and common tasks

• planning and organizing

Middle-stage (moderate):

Increasing impairment of learning and memory

More prominent defects in perception (agnosia) and movement (apraxia)

Loss of vocabulary and fluency of language

Long-term memories start to fade

“Sundowning”

Experience delusions

Tendency to wander and become lost

“Sundowning”

restlessness, confusion, and agitation worsen at dusk

Late-stage (severe):

Memory and cognitive skills worsen

Loss of control of bladder and bowels + muscle mass

Difficulty swallowing

Loss of awareness of surroundings + ability to communicate

Totally dependent on caregivers

Susceptible to infections (pneumonia)

Alzheimer Disease Pathology

Cerebral cortex atrophied, especially hippocampus

difficulty in learning new things or forming new memories

Enlargement of ventricles

neurofibrillary tangles

senile plaques

chronic inflammation

Alzheimer Disease Pathology: Neurofibrillary tangles

collections of tau protein block synaptic communication of neurons

Alzheimer Disease Pathology: Senile plaques

Extracellular amyloid

deposits between neurons that hinder communication

Genes encoding amyloid precursor protein, presenilin 1 and 2 often mutated

Alzheimer Disease Pathology: Chronic inflammation

Caused by neurofibrillary tangles and senile plaques

Damages the neurons

Parkinson Disease

Long-term neurodegenerative disease mostly affecting motor function

Described by James Parkinson in 1817

Parkinson Disease Causes:

Not completely understood

probably a combination of genetic and environmental factors

• Head trauma

• Exposure to pesticides

Parkinson Disease Age:

Most patients are over 60

Early-onset PD: occurs before 50

More common in males

Parkinson Disease Motor signs and symptoms: TRAPs

Tremor at rest

Rigidity

Akinesia/ Bradykinesia

Postural instability 

Parkinson Disease Motor signs and symptoms: Tremor at rest

Usually starts in one hand or leg

Can affect jaws and tongue

Parkinson Disease Motor signs and symptoms: Rigidity

muscle stiffness and limited movement

Parkinson Disease Motor signs and symptoms: Bradykinesia or akinesia 

Bradykinesia (slow movement)

akinesia (no movement), with shuffling gait

Parkinson Disease Motor signs and symptoms: Postural instability 

falls and bone fractures common

Parkinson Disease Non-motor signs and symptoms:

Cognitive deficits (thinking, judgement, planning)

Eye and vision problems: slow or infrequent blinking (“serpentine stare”)

Hallucinations and psychosis (paranoia)

Depression and anxiety

Altered sense of smell (early symptom)

Parkinson Disease Pathology:

Depletion of neurons in substantia nigra in the basal

disrupts production of dopamine

Reduced dopamine

increased # of lewy bodies

results in accumulation of atypical proteins

Parkinson Disease Pathology: basal ganglia

Depletion of neurons in substantia nigra in the basal ganglia

Parkinson Disease Pathology: Reduced dopamine

Less control of movement

Inhibits direct neural pathway, stimulates indirect neural pathway

‘Highway blocked, must use surface roads’

Hypokinetic basal ganglia disease

Parkinson Disease Pathology: Increased number of Lewy bodies

Abnormal proteins in neurons

Damage and kill these cells

Parkinson Disease Pathology: Disrupts production of dopamine

Adversely affects mental capacities and behavior

Parkinson Disease Management:

Levodopa (L-dopa) has been used to replace missing dopamine

this inhibits production of dopamine

Other dopamine agonists are somewhat effective

Parkinsonism

Group of neurological problems that have the features of PD:

Tremor, rigidity, bradykinesia, postural instability

Unlike PD, not caused by degeneration of nerve cells

Parkinsonism Causes 

Brain disease

Secondary effects of medications (e.g., antidepressants)

Toxins including paraquat (herbicide)

Infections including HIV

Chronic traumatic encephalopathy

Parkinsonism: Dementia with Lewy bodies

2nd most common dementia (after Alzheimer disease)

Blocks dopamine production

Parkinsonism: Drug-induced parkinsonism

secondary to drug therapy for some psychoses to block dopamine

chorea

uncontrolled movement

Huntington Disease (Chorea)

Neurodegenerative disease of the basal ganglia

most commonly causing uncontrolled movement (chorea)

Huntington Disease cause

Hereditary

Autosomal dominant

Mutation in huntingtin gene

Production of huntingtin protein damages brain

Huntington Disease (Chorea) Age:

Begins in middle age

Huntington Disease (Chorea) Signs and symptoms: Motor

Jerky, uncontrolled movements (chorea), difficulty chewing and swallowing

Huntington Disease (Chorea) Signs and symptoms: Cognitive

Difficulty in planning, abstract thinking; eventually memory loss and dementia

Huntington Disease (Chorea) Signs and symptoms: Psychiatric

Anxiety, depression, obsessive-compulsive behavior

Huntington Disease (Chorea) Pathology:

Atrophy of caudate nucleus in the basal ganglia, loss of neurons

Reduced secretion of neurotransmitter gamma-aminobutyric acid (GABA)

Hyperkinetic basal ganglia disease, with loss of coordination in movements

Compare with Parkinson disease, which is a hypokinetic basal ganglia disease

Huntington Disease (Chorea) Management:

No cure

Medications can help reduce chorea

Amyotrophic Lateral Sclerosis

Degeneration of corticospinal tracts, anterior horn cells, and/or
bulbar motor nuclei

Lack of nerve stimulation leads to small, weak muscles (amyotrophic)

Degeneration followed by scarring (sclerosis) in nerves

Amyotrophic Lateral Sclerosis Cause

unknown

Hereditary and environmental factors

Amyotrophic Lateral Sclerosis Age

Mostly 40s to 60s, mostly males

Amyotrophic Lateral Sclerosis Signs and symptoms:

Muscle weakness in arms and legs

Weakness in muscles of mastication and speech

Difficulty in swallowing

Cognitive and behavioral problems in 30 – 50%

Death usually in 2-6 years

Multiple Sclerosis

Destruction of myelin sheaths in CNS

Replaced by numerous glial plaques or scars (sclerotic tissue)

Axons can no longer communicate because of failure to conduct nerve impulses

Leads to cognitive, sensory, and motor deficits

Pattern may be sporadic, but ultimately permanent

Multiple Sclerosis Cause

Not fully understood, but immune-mediated

T-cells attack myelin → Demyelinated plaques

“MS attacks Myelin Sheaths”

Multiple Sclerosis Age:

Young adults, more common in females

Multiple Sclerosis Signs and symptoms

May cause difficulty speaking (dysarthria) and swallowing (dysphagia)

May cause facial pain

Difficulty walking and balance (ataxia)

Nystagmus of eye is fairly common

Sensation of pins and needles

Cognitive defects and mood instability

Nystagmus

rapid involuntary movements of the eyes

Multiple Sclerosis Age: Management

No effective treatment

Congenital malformations and perinatal brain injury

Hydrocephalus

Neural tube defects (spina bifida)

Cerebral palsy

Epilepsy

Hydrocephalus

Increase in cerebrospinal fluid (CSF) within brain ventricles

Most common cause of brain surgery in children

Hydrocephalus Causes:

Birth defect

Brain tumor

Meningitis

Subarachnoid hemorrhage

Hydrocephalus Signs and symptoms:

Mostly related to increased intracranial pressure:
• Headaches, nausea, vomiting

Hydrocephalus Pathology:

Arachnoid villi can’t absorb CSF

therefore, CSF can’t be removed in circulatory system

Continuous production of CSF causes head to enlarge

Hydrocephalus Management:

Shunt drains fluid into peritoneum

Neural Tube Defects

Congenital defects in closure of neural tube

Neural tube forms the early brain and spinal cord

Defect occurs in the first month of pregnancy

open NTD

Brain/spinal cord exposed at birth

Most common form of CNS malformation

Neural tube defects

Neural Tube Defects Cause + risk factors 

Unknown

Risk factors include maternal obesity, low folic acid, and diabetes mellitus

Neural Tube Defects Prevention:

Sufficient folic acid during pregnancy

Spina bifida

most important NTD

Spinal cord fails to close

At least some paralysis of legs

Meningocele

meninges protrude (herniate) through opening

Myelomeningocele

both meninges and spinal cord herniate

Spina bifida occulta

Defect in vertebra formation

NO herniation of meninges or spinal cord

Spina bifida Treatment:

Surgery within 2 days of birth

Cerebral Palsy

Heterogenous disease group affecting movement and posture

Non-progressive: does NOT get worse with age

Results in motor neuron dysfunction (reflexes,coordination)

Cerebral Palsy Cause

Injury to the brain, usually affecting white matter
• During pregnancy (75%)
• During birth (5%)
• After birth (20%)

Spastic Cerebral Palsy

most common type (80%)

Nonprogressive motor function impairment

Spastic Cerebral Palsy signs + symptoms

Increased tone; muscles are stiff, movement awkward

Cognitive defects, seizures may occur

Slow, slurred speech

Small bones, including maxillae and mandible

Increased risk for dental caries and periodontitis due to poor manual dexterity as well as drooling and swallowing difficulties

Epilepsy

Group of brain disorders that cause seizures (massive neuronal discharge)

Epilepsy Causes:

May be due to scarring or other causes of brain damage including:
– Head trauma
– Infections (encephalitis or meningitis)
– Tumors
– Arteriosclerosis or ischemia

Epilepsy Generalized seizures:

Massive bursts of electrical energy sweep through the whole brain at once, causing:

• Convulsions (tonic-clonic or grand mal seizures)

• Loss of consciousness

• Falls

• Massive muscle spasms

Epilepsy Partial seizures:

Electrical disturbance occurs in just one part of the brain, affecting whatever physical or mental activity that area controls

More common than generalized seizures

May be absent (petit mal) seizures: staring into space

May warn of bigger seizure to come (aura)

Epilepsy Treatment:

Anticonvulsant medication

Phenytoin (Dilantin) most common

Epilepsy Dental care:

During a seizure, gently position the patient in supine position near the floor

If not in the chair, position the patient on the floor in supine position

infections of the CNS

Meningitis

Poliomyelitis

Meningitis

Inflammation of the meninges around the brain or spinal cord

Meningitis Causes

Infective organisms

Acute Meningitis

CSF Purulent: usually bacteria
CSF Lymphocytic: usually viral

Chronic Meningitis

Usually slow-growing organisms: TB, fungi, some bacteria

Meningitis Signs and symptoms:

Headache, fever, stiff neck

Altered mental function

Photophobia, phonophobia in some cases

severe meningitis symptoms 

In severe cases, edematous brain can enlarge and herniate through the meninges:
– Loss of consciousness
– Affect the trigeminal nerve

Meningitis Patholog

Purulent exudate

Neutrophils and pus in meninges

Poliomyelitis

Infection with poliovirus, an enterovirus

Fecal-oral transmission

Severe forms affect CNS

Occurs naturally only in humans

“Polio” = 

“myelon”=

“itis” =

“Polio” = gray

“myelon” = marrow

“itis” = inflammation

Poliomyelitis Signs and symptoms:

Asymptomatic (70%)

Abortive polio (25%):

Non-paralytic polio (4%)

Paralytic (1% of all infections)

Abortive polio

Flu-like symptoms: myalgia, headache, fever

(25%)

Non-paralytic polio

Flu-like symptoms

Also stiffness, weakness in muscles

(4%)

Paralytic

1% of all infections):

Begins like non-paralytic polio

Tingling sensation

Muscle spasms and pain

Paralysis: most commonly in one leg

Marked atrophy of muscles

Severe cases: difficulty breathing (iron lung) or swallowing

Poliomyelitis Pathology:

Destroys motor neurons in anterior horn cells of the spinal cord

Atrophy of muscles, leading to paralysis

Poliomyelitis Vaccines 

Salk in 1955, Sabin in 1957 are very effective

Post-polio syndrome:

Occurs decades after recovery from polio

Pain, weakness, and atrophy of muscles that may or may not have been involved originally

Pathology of the PNS

Neurofibroma and neurofibromatosis

Schwannoma

Neuroma

Neurofibroma is a _______ tumor of ___________

Benign tumor of neurons, fibroblasts, Schwann cells, and mucin

charcteristics 

Common on skin, rare inside CNS

Single nodule or multinodular (plexiform)

Usually painless, slowly growing, flaccid or rubbery

Plexiform can be painful and become malignant

Most are solitary

Oral Neurofibroma

Usually solitary, occasionally plexiform

Most common on tongue, palate, and buccal mucosa

Soft, non-painful enlargement

Occasionally central in mandible