Download ALTERATIONS IN NEUROLOGIC FUNCTIONING

Dementias
See Box 16-3 for classification
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
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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
Histopathology of Alzheimers
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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
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Beta amyloid plaques
– accumulation disrupts inter-neuronal
communication make neurons more
susceptible to ischemia
– inflammation and microglial invasion might
complicate matters
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Loss of cholinergic neurons
Loss of choline acetyl transferase and
somatostatin (50%)
Disruption of neuron communication,
metabolism, and repair, leading to cell
death
Alzheimer’s Disease
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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
Stages of AD
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I 1-3 years
II 2-10 years
III 8-12 years
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
Diagnostic tests

Diagnose by exclusion or on PM
– CBC/CS (include electrolytes), thyroid tests,
Vitamin B 12
– Review all medications being taken
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CT scans—cortical atrophy, ventricular
expansion, no masses (Stage 2 & 3)
MRI, PET scans
CSF protein analysis
Potential complicating factors in
development of pathology
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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
Other dementias characterized by
tangles of amyloid fibrils
– Prion diseases—BSE
– Parkinson’s Disease
– Huntington’s Disease
Nutritional dementias
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B vitamin deficiency (esp B1, B6, B12,
niacin, pantothenic acid
Alcoholism
– Alcoholics often malnourished, have chronic
illnesses and untreated infections
Central Motor
Disorders
Parkinson’s Disease
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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
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”
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Increased tonus of both extensors and
flexors
– Tremor at rest, worse if stressed or tired
– Cramped, small handwriting
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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
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
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
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
Established Syndromes

Mixed/generalized (50%)
– Visual system attacked
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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
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Amaurotic (5%)
– blindness
Signs and symptoms (any
combination)
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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
MS
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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
Chronic, progressive MS
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Primary progressive--steady, gradual
decline
– Fairly rare
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Secondary progressive--eventually affects
2/3 of pts
– Relapsing/remission form
– Start to experience decline between attacks
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Progressive relapsing--rarest, no remission
– Occasional bouts of increased severity
ALS—Amyotrophic lateral sclerosis
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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)
ALS
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NO sensory loss, no memory loss, patient
remains aware of everything
Fast glycolytic fibers go first, fast oxidative next
– Slow twitch fibers go last
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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
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Usually die 2-6 years after diagnosis, of
respiratory failure
Pathophysiology of ALS
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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
Lower Motor Neuron diseases:
Myasthenia gravis
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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
Generalized autoimmune
myasthenia
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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)
Signs and symptoms
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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
Signs are aggravated by:
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Hormonal imbalance (PG, phases of
menstrual cycle, thyroid)
Concurrent illness or emotional stress
Alcohol, especially Gin &Tonic
Diagnosis
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EMG of muscle in repetitive action
Serum antibodies to ACh receptors (80%
of patients)
Tensilon test—ACh esterase inhibitor
– immediate improvement
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70-80% have abnormal thymus (males)
Increased risk of other AI diseases
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Crisis—unable to swallow, clear
respiratory secretions, or breathe
adequately
– Myasthenic crisis

Usually occurs 3-4 hours post meds
– Cholinergic crisis
Drug OD, occurs within 1 hours of meds
 See other signs of increased smooth muscle
activity
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Death from respiratory arrest in either case
Infections of CNS
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Meningitis
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Encephalitis
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Reye syndrome
Meningitis
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Etiology
– Viral meningitis—usually self limiting
Enteroviruses, Herpes viruses, Myxoviruses
 Also called aseptic meningitis, non-purulent
mengitis, lymphocytic meningitis

– Bacterial meningitis
Meningococcus and Pneumococcus
 Usually begins in another part of the body
 May spread to ventricles and CSF
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Pathophysiology
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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
Encephalitis
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Acute, febrile, usually viral origin
Signs of meningitis plus decreased level of
consciousness
– Delirium, confusion, seizures
– Increased ICP
– Herpes associated with hallucinations, abnormal
behavior
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Much poorer prognosis than meningitis
Differentiate from brain abscesses, tumors,
parasites
– Brain abscess may follow any case of encephalitis
Reye syndrome
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Associated with giving aspirin to children
with influenza or other viral infections
– 2 phase illness--viral infection then Reyes
Syndrome
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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
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
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Electrolyte disturbances (decreased Na and K,
high ammonia)
– Cerebral edema, increased ICP, swelling of
mitochondria in neurons
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Mortality 25-50%, survivors may have
permanent CNS damage--retardation, seizures,
paralysis
Spinal Cord Trauma
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Most often in young, single males
Etiology—car accidents, falls, sports
injuries
– hyperextension, hyperflexion, vertical
compression, rotational forces
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Quadriplegia—injuries to cervical spine
Paraplegia—injuries to thoracic, lumbar,
and sacral spine
Mechanism of Injury
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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)
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XS glutamate damages surviving cells
Common complications
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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
Life expectancy has improved
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Infection is #1 cause of death
– Quadriplegics usually die within 5 years
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Renal failure #2 cause of death
Quality of life depends on level of
damage to cord
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C1
C2- 4
C5
rare but usually fatal
life threatening—phrenic nerve
retain head, neck, shoulder,
respiratory control
C6
retain control through wrist
C7
retain some finger control
C7-T-1 retain hand control
Paraplegia
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T2-12
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L1-5
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S1-5
retain upper body and some trunk
control
usually retain full trunk control
and some leg control
some bowel and bladder
dysfunction
Spinal shock--SNS is in T-L spine
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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
Autonomic dysreflexia (hyperreflexia)
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Occurs after recovery from spinal shock
– The higher the cord lesion, the more likely this
will develop
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Loss of higher level control on SNS
outflow
– In effect, an Upper Motor Neuron syndrome
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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
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Must lower BP or potential stroke
Pain
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Assessment is always subjective—no test
to measure or confirm
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If the patient says she hurts, she hurts
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Often accompanied by increased SNS
activity and stress response
Classification
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Underlying cause
– Nocioceptive
– Neuropathic (non-nocioceptive)
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Duration
– Acute
– Chronic
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Etiology
Regional
Physiologic events in nocioceptive
(acute) pain
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Transduction—noxious stimuli activate
nocioceptors
– Histamine, bradykinin, TNF and other
inflammatory chemicals

Nocioceptors release Substance
Pvasodilation, edema, more bradykinin
and histamine
– Small myelinated (A-delta—fast) and nonmyelinated (C-slow) fibers transmit AP’s
Transmission along A-delta and C
fibers
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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, diffuse
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May be most important tract in chronic pain
Perception
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Hypothalamus and limbic system modulate
perception
Endogenous opioid peptides and receptors
throughout sensory system
Pain threshold: point at which stimulus is
perceived as painful
 Little variation between individuals
Pain tolerance: length of time pain is endured
without complaint
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, culture
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Frontal cortex determines response
Acute pain Table 15-2
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Sudden onset, specific cause, lasts < 6
months
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Resolves after healing or successful drug
therapy
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See increased SNS response and stress
reaction
Visceral acute pain
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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
Chronic pain Table 15-2
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Continuous or intermittent, lasts longer than 6
months
– Low back pain is #1 example
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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
Neuropathic pain
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Trauma to or disease of nerves
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–
–
–
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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
Peripheral hypersensitivity
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Nocioceptors on C fiber neurons are
sensitized or directly stimulated by
inflammatory mediators
– Decreased threshold for excitation
– Activation of normally silent receptors
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Response is longer and more intense
Allodynia: perceive low intensity stimuli as
painful
Secondary hyperalgesia of surrounding
tissues may develop
Central Sensitization
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Repetitive and high frequency
stimulation of C fibers
Release of glutamate and Substance P
– Activation of AMPA and NMDA receptors
in CNS
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May also lose loss of pain inhibition by
GABA or other neurotransmitters
Wind up pain
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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)
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Increased frequency of firing of
neurons
Allodynia develops
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
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Not well understood, but probably involves
peripheral and central activation