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Dementias See Box 16-3 for classification
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Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Dec 25, 2015

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Page 1: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

DementiasSee Box 16-3 for classification

Page 2: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Alzheimer’s Disease

Degenerative, progressive, – #1 cause of dementia (60-80% all cases)– #6 cause of death in US– > 5 million Americans affected

Disruption of neuron communication, metabolism, repair

Page 3: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Average life expectancy 8 years after diagnosis

No specific antemortem test—dx by exclusion early, then post mortem– MRI, CT scans will reveal shrinking of

cortices as disease progresses– EEG traces slow in activity as progresses

50% of population over 85 probably affected– Exercise helps delay onset and progression

Page 4: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Histopathology of Alzheimers

Neurofibrillary tangles of tau protein and collapse of neuron skeleton inside neurons

Senile plaques of beta amyloid in interstitial fluid around neurons– byproduct of normal amyloid precursor

protein (membrane protein)– Believe that plaques cause tau protein to form

Page 5: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Beta amyloid plaques– accumulation disrupts inter-neuronal

communication make neurons more susceptible to ischemia

– inflammation and microglial invasion might complicate matters

Loss of cholinergic neurons Loss of choline acetyl transferase and

somatostatin (50%) Disruption of neuron communication,

metabolism, and repair, leading to cell death

Page 6: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Alzheimer’s Disease

Early onset AD appears before 65 – autosomal dominant trait (3 genes)– 5-10% of all cases

Late onset AD – one copy of apolipoprotein E epsilon 4 in

genome predisposes to late AD– May be better predictor for Caucasian than

Hispanic or African Americans

Page 7: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Stages of AD

I 1-3 years II 2-10 years III 8-12 years

Page 8: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Signs and Symptoms

Initial damage to memory: first hippocampus, then cerebral cortex– Loss of language skill; impaired judgment; personality

changes– Emotional outbursts; wandering (sundowners);

agitation– Progressively more apathetic

Bedridden; incontinent by Stage 3– Rigid, flexed limbs, severe mental deterioration

Page 9: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Diagnostic tests

Diagnose by exclusion or on PM– CBC/CS (include electrolytes), thyroid tests,

Vitamin B 12– Review all medications being taken

CT scans—cortical atrophy, ventricular expansion, no masses (Stage 2 & 3)

MRI, PET scans CSF protein analysis

Page 10: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Potential complicating factors in development of pathology

Inflammation--Use of NSAIDS to decrease incidence of AD

Oxidative stress—free radicals from metabolic reactions damage DNA, cell membranes

Long term damage from subclinical interruptions of blood flow

Mental stagnation---use it or lose it

Page 11: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Other dementias characterized by tangles of amyloid fibrils

– Prion diseases—BSE– Parkinson’s Disease– Huntington’s Disease

Page 12: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Nutritional dementias

B vitamin deficiency (esp B1, B6, B12, niacin, pantothenic acid

Alcoholism– Alcoholics often malnourished, have chronic

illnesses and untreated infections

Page 13: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Central Motor Disorders

Page 14: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Parkinson’s Disease Most common disorder of extrapyramidal

system, 2nd most common CNS problem in US

Most cases are idiopathic, onset usually 60+, no known cure

Characterized by loss of dopamine production and neurons in basal ganglia and substantia nigra

Diagnosed by response to L-dopa

Page 15: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Signs and Symptoms

Rigidity, tremor at rest, loss of postural reflexes, akinesia or bradykinesia– Muscle rigidity may be unilateral or bilateral

“lead pipe rigidity”“cogwheel rigidity”

Increased tonus of both extensors and flexors– Tremor at rest, worse if stressed or tired– Cramped, small handwriting

Page 16: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Shuffling, stumbling gait, stooped forward posture, pill rolling

Loss of facial expression, low & monotonous voice

ANS disruption—sweating, oily skin, drooling, constipation

Decreased ability to swallow

Page 17: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Multiple Sclerosis

One of the most common neurologic diseases in young adults

Affects females 2X as often as males – Autoimmune – Onset 15-60 years, average = 30– Most are < 40 when diagnosed

More common in cooler climates– Rare in tropics

Page 18: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

MS

Idiopathic but probably follows viral illness—worse after gamma interferon– Precipitating factors include PG, infection,

injury, emotional stress– Probably multiple causes– Familial patterns suggests common exposure

or genetic predisposition History of attacks followed by periods of

remission with progressive damage

Page 19: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Underlying pathology

Widespread demyelination in CNS, with hard, yellow plaques in white matter– Pyramidal tracts, dorsal columns most often

affected– Cerebellar peduncles, brainstem, optic nerve

and tract– As myelin degenerates, macrophages enter and

remove debris

Page 20: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Established Syndromes

Mixed/generalized (50%)– Visual system attacked

Spinal (30-40%)– Weakness or numbness in one or more limbs– UMN signs are unilateral, spinal signs are

bilateral, legs more often than arms Cerebellar (5%)

– Symmetrical deficits, nystagmus, ataxia Amaurotic (5%)

– blindness

Page 21: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Signs and symptoms (any combination)

Visual problems most often initial symptoms Sensory disorders—dorsal column problems Spastic weakness of limbs—one or more Nystagmus, uncoordinated movement

– Cerebellar dysfunction Bladder dysfunction—corticospinal tracts Euphoria or dementia —frontal lobes

Page 22: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

MS

No single diagnostic test—MRI might show plaques

CSF—elevated WBC, IgG, and myelin basic protein

Progression is variable—disability in 10-20 years in most cases

Relapsing-remitting form is most common

Page 23: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Chronic, progressive MS Primary progressive--steady, gradual

decline– Fairly rare

Secondary progressive--eventually affects 2/3 of pts– Relapsing/remission form– Start to experience decline between attacks

Progressive relapsing--rarest, no remission– Occasional bouts of increased severity

Page 24: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

ALS—Amyotrophic lateral sclerosis

AKA Lou Gehrig’s Disease Progressive, idiopathic neurologic deterioration of

40-70 year olds– 5-10% have an inherited form

Destruction of upper and lower neurons in motor tracts– Ventral horns of spinal cord, lower brainstem, cerebral

cortex are destroyed– No inflammation

Results in muscular atrophy– Pt presents with hand or leg weakness, incoordination,

or difficulty speaking (stammer, stutter)

Page 25: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

ALS NO sensory loss, no memory loss, patient

remains aware of everything Fast glycolytic fibers go first, fast oxidative next

– Slow twitch fibers go last Cranial often goes before caudal

– Difficulty chewing, swallowing, speaking, breathing– Fatigue in arms or legs, tripping, drop objects– Control of eye and bladder are lost last

Usually die 2-6 years after diagnosis, of respiratory failure

Page 26: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Pathophysiology of ALS Evidence that damage to SOD1 (superoxide

dismutase) gene allows damage to neuron by free radicals

First signs of degeneration begin at distal axon near synapse– accumulation of xs neurofilaments and disruption

of microtubules blocks nutrient transport inside neuron

– Later dysfunction of proteosomes in cell body allow buildup of degenerative products

– Breakdown of surrounding glial cells

Page 27: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Lower Motor Neuron diseases:Myasthenia gravis

Only neuromuscular disease with rapid fatigue and prolonged recovery

Younger patients: Women 3X as likely as men to be affected

Patients > 50 are more often males Usually die from respiratory insufficiency Histology—autoimmune destruction of

ACh receptor at myoneural junction

Page 28: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Generalized autoimmune myasthenia

May have periodic relapses with prolonged remission

May be slowly progressive with no remission

May be rapidly fulminating and fatal Often graded I (ocular disease only)

through IV (crisis)

Page 29: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Signs and symptoms Progressive weakness and fatigability—

eye and face often first– Double vision (diplopia) and drooping

lids (ptosis)– Hanging jaw sign, inability to swallow

Weakness increases with activity, strength improves with rest

Strength improves with ACh esterase inhibitors

Page 30: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Signs are aggravated by:

Hormonal imbalance (PG, phases of menstrual cycle, thyroid)

Concurrent illness or emotional stress Alcohol, especially Gin &Tonic

Page 31: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Diagnosis

EMG of muscle in repetitive action Serum antibodies to ACh receptors (80%

of patients) Tensilon test—ACh esterase inhibitor

– immediate improvement 70-80% have abnormal thymus (males) Increased risk of other AI diseases

Page 32: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Crisis—unable to swallow, clear respiratory secretions, or breathe adequately – Myasthenic crisis

Usually occurs 3-4 hours post meds

– Cholinergic crisisDrug OD, occurs within 1 hours of medsSee other signs of increased smooth muscle

activity

Death from respiratory arrest in either case

Page 33: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Infections of CNS

Meningitis

Encephalitis

Reye syndrome

Page 34: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Meningitis Etiology

– Viral meningitis—usually self limitingEnteroviruses, Herpes viruses, MyxovirusesAlso called aseptic meningitis, non-purulent

mengitis, lymphocytic meningitis– Bacterial meningitis

Meningococcus and PneumococcusUsually begins in another part of the bodyMay spread to ventricles and CSF

Page 35: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Pathophysiology Bacteria enter bloodstream, break through

choroid plexus into subarachnoid space– Inflammatory reaction in meningeal vessels– Purulent exudate may obstruct villi and produce

interstitial edema

Abrupt onset of severe, throbbing headache, fever, stiff neck– Photophobia, decreased LOC if spread to brain– May/may not have nausea, vomiting, abdominal pain,

malaise

Page 36: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Encephalitis Acute, febrile, usually viral origin Signs of meningitis plus decreased level of

consciousness – Delirium, confusion, seizures– Increased ICP– Herpes associated with hallucinations, abnormal

behavior Much poorer prognosis than meningitis Differentiate from brain abscesses, tumors,

parasites– Brain abscess may follow any case of encephalitis

Page 37: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Reye syndrome

Associated with giving aspirin to children with influenza or other viral infections– 2 phase illness--viral infection then Reyes

Syndrome Appear to recover from viral illness, then

vomiting, convulsions, delirium– Acute, rare, multi-organ (liver and brain

typically) in apparently healthy child– NO FEVER at this time

Page 38: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Dysfunction of hepatic mitochondria underlies pathology

Fatty infiltration of liver, heart and kidneys but no inflammation or necrosis– Profound hypoglycemia, hyperammonemia– Increase in short chain FA in serum

Electrolyte disturbances (decreased Na and K, high ammonia)– Cerebral edema, increased ICP, swelling of

mitochondria in neurons Mortality 25-50%, survivors may have

permanent CNS damage--retardation, seizures, paralysis

Page 39: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Spinal Cord Trauma

Most often in young, single males Etiology—car accidents, falls, sports

injuries– hyperextension, hyperflexion, vertical

compression, rotational forces Quadriplegia—injuries to cervical spine Paraplegia—injuries to thoracic, lumbar,

and sacral spine

Page 40: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Mechanism of Injury

Most damage occurs at time of initial injury

Area above damage usually survives– 2º damage from continued movement, rubbing

on damaged vertebrae– ischemia after trauma major damage

(methylprednisolone) XS glutamate damages surviving cells

Page 41: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Common complications

Chronic pain and muscle spasms Bed sores from constant pressure Deep vein thrombosis from inactivity CHF, pulmonary edema from compromised

circulation Pneumonia from accumulation of mucous in

upper respiratory tract

Page 42: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Life expectancy has improved

Infection is #1 cause of death– Quadriplegics usually die within 5 years

Renal failure #2 cause of death

Page 43: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Quality of life depends on level of damage to cord

C1 rare but usually fatal C2- 4 life threatening—phrenic nerve C5 retain head, neck, shoulder,

respiratory control C6 retain control through wrist C7 retain some finger control C7-T-1 retain hand control

Page 44: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Paraplegia

T2-12 retain upper body and some trunk control

L1-5 usually retain full trunk control and some leg control

S1-5 some bowel and bladder dysfunction

Page 45: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Spinal shock--SNS is in T-L spine

temporary loss of cord function initial loss of reflex activity below level of

injury—flaccid paralysis loss of T control, loss of vasomotor tone,

atonic bowel and bladder recovery in hours to weeks (30 days) must maintain BP and urine flow with

fluids; keep bowel emptied

Page 46: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Autonomic dysreflexia (hyperreflexia)

Occurs after recovery from spinal shock– The higher the cord lesion, the more likely this

will develop Loss of higher level control on SNS

outflow– In effect, an Upper Motor Neuron syndrome

Page 47: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Irritation stimulates massive SNS activity—arterial spasm, increased BP

Heart slows because of PNS response to increased BP

Severe pounding headache, flushed /pale skin, goose bumps

Must lower BP or potential stroke

Page 48: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Pain

Assessment is always subjective—no test to measure or confirm

If the patient says she hurts, she hurts

Often accompanied by increased SNS activity and stress response

Page 49: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Classification

Underlying cause– Nocioceptive– Neuropathic (non-nocioceptive)

Duration– Acute – Chronic

Etiology Regional

Page 50: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Physiologic events in nocioceptive (acute) pain

Transduction—noxious stimuli activate nocioceptors– Histamine, bradykinin, TNF and other

inflammatory chemicals Nocioceptors release Substance

Pvasodilation, edema, more bradykinin and histamine– Small myelinated (A-delta—fast) and non-

myelinated (C-slow) fibers transmit AP’s

Page 51: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Transmission along A-delta and C fibers

Synapse with second order neurons, cross spinal cord and rise in anterolateral spinothalamic tract– A-delta fibers are direct with no side

branches—sharp, localized pain– C fibers send information to reticular

formation—burning, aching, diffuseMay be most important tract in chronic pain

Page 52: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Perception Hypothalamus and limbic system modulate

perception Endogenous opioid peptides and receptors

throughout sensory system Pain threshold: point at which stimulus is

perceived as painfulLittle variation between individuals

Pain tolerance: length of time pain is endured without complaint

Page 53: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Pain tolerance

Influenced by: personality, culture, past experiences, mental/emotional state– Decreased by repeated exposures,

fatigue, anxiety, sleep deprivation, fear– Increased by distraction, cold, warmth,

alcohol, hypnosis, cultureFrontal cortex determines response

Page 54: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Acute pain Table 15-2

Sudden onset, specific cause, lasts < 6 months

Resolves after healing or successful drug therapy

See increased SNS response and stress reaction

Page 55: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Visceral acute pain Viscera respond to stretch, ischemia, and

inflammation Visceral pain often stimulates the autonomic

nervous system and induces changes in blood pressure, sweating, vomiting/diarrhea

May see contraction of local muscles– Surgical abdomen, guarding

Typically projects to superficial areas along same dermatome--referred pain– Gall bladder to area between scapulae– Myocardial ischemia to left arm and jaw

Page 56: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Chronic pain Table 15-2 Continuous or intermittent, lasts longer than 6

months– Low back pain is #1 example

Cause often unknown, or not responsive to analgesics

May come on suddenly or over a period of years– May afflict as much as 25% of population– Little or no SNS stimulation at this point– Severe emotional distress, depression, insomnia– Become hypersensitive to any touch—allodynia

Page 57: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Neuropathic pain

Trauma to or disease of nerves– Burning/tingling, shooting, stabbing, gnawing– Not responsive to NSAIDS or analgesics– Intensifies with physical/emotional stress– May be result of CNS or PNS damage

Neurons in dorsal root ganglia become more active with repetitive stimuli– May be result of loss of central inhibition

Page 58: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Peripheral hypersensitivity

Nocioceptors on C fiber neurons are sensitized or directly stimulated by inflammatory mediators– Decreased threshold for excitation– Activation of normally silent receptors

Response is longer and more intense Allodynia: perceive low intensity stimuli as

painful Secondary hyperalgesia of surrounding

tissues may develop

Page 59: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Central Sensitization

Repetitive and high frequency stimulation of C fibers

Release of glutamate and Substance P– Activation of AMPA and NMDA receptors

in CNS May also lose loss of pain inhibition by

GABA or other neurotransmitters

Page 60: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Wind up pain

Chronic NMDA receptor activation causes changes in protein synthesis, density of receptors, and enhanced glutamate release– May develop long term changes in sp9inal

cord (central sensitization) Increased frequency of firing of

neurons Allodynia develops

Page 61: Dementias See Box 16-3 for classification. Alzheimer’s Disease Degenerative, progressive, –#1 cause of dementia (60-80% all cases) –#6 cause of death.

Phantom limb pain

Chronic pain, tingling, burning, itching affecting 50-85% of amputees– More common if limb was painful before

amputation– Most cases decrease significantly over 6 months

May also occur in spinal trauma patients

Not well understood, but probably involves peripheral and central activation