Transcript Migraine

Neurological System
Symptom Overview
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Headache
Dizziness and vertigo
Confusion
Memory/mental status changes
Paresthesia
Tremors
Common Symptoms
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Headache
Inflammation/Constriction
Dizziness and vertigo
Irritation
Confusion/memory/mental status changes
Executive Function
Paresthesia
Nerve Inhibition
Tremors
Nerve Excitation
Basis of Neurological Problems
• Autoimmune/Degenerative
– Pathologic excitation/inhibition nerve fibers
– Degeneration/Destructions nerve fibers
• Circulatory
– Ischemia/hypoxemia
• Decreased blood flow/decreased oxygen levels
• Genetic
– Mutations causing abnormal biochemistry
• Infection/Trauma
– Abnormal pathology through injury
Degenerative Conditions
• Parkinson’s disease
• Multiple sclerosis
• Brain tumors
Circulatory
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TIA/CVA
Aneursym
AV Malformation
Headaches
– Migraine
– Tension
– Cluster
• Peripheral neuropathy
Infection/Trauma
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Meningitis and encephalitis
Viral meningitis
Seizure disorders/ epilepsy
Bell’s palsy
Trigeminal neuralgia
Nerve Fibers
Pressure/Ischemia = Neuropathy
• Peripheral (extremity)
• Radiculopathy (“root”)
• Myelopathy (muscle/nerve)
• Small myelinated axons are
responsible for light touch, pain
temperature.
• Small unmyelinated axons are also
sensory and subserve pain and
temperature.
• Neuropathies involving these are
called small fiber neuropathies
• Nerves have a limited number of ways to
respond to injury
• Damage can occur at the level of the axon—
this generally results in degeneration of both
the axon and the myelin sheath
• Damage at the motor neuron or dorsal root
ganglion is often incomplete
• Damage at the level of the myelin sheath are
often inflammatory or hereditary—these can
yield a rapid recovery or a progressive
diffuse course of illness
Severed = Paralysis
Results of Neuropathy
• Pain
– Burning
• Parathesia
– Numbness
• Hyperasthesia
– Sensitivity
• Paralysis
– Loss of movement
Various Neuropathy Conditions
• Back pain
– Radiculopathy
– Sciatica
– Myelopathy
• Neuralgia/Parathesia
– Trigeminal
– Palsy (Bell’s, Ulnar)
– Migraine (?)
• Degenerative
– Multiple Sclerosis
– Amyotrophic Lateral Sclerosis
Radiculopathy/Myelopathy
Radiculopathy/Myelopathy
• Burning pain along nerve
• Loss of muscle strength
– Atrophy
– Injury
Trigeminal Neuralgia
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Cranial Nerve V
Tic douloureux
5TH Decade (V!)
Young age ? MS
Multiple Cause
Paroxysmal
Unilateral
Trigger
Bell’s Palsy/Nerve Palsy
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Nerve paralysis
Facial Nerve (VII)
Motor not Sensory
Sir Charles Bell
Idiopathic
Altered Taste
Hyper Lacrimation
Nerve Palsies
• Neuropathy
• “Saturday Night
Palsy”
• Nerve pressure
causing paralysis
• Sleeping standing up
• Hours to Months
EPS
Testing Neuropathies
• Electromyography (EMG)
– Needles into the muscle
– Measures muscle action potentials
– A surface EMG (SEMG) is not accurate
• Nerve Conduction Velocity (NCV)
– Usually done at the same time as EMG
• Evoked potential
– Basis for EMG, can be auditory, visual
EMG
Treatment for Neuropathies
• First treat the underlying cause then
symptom management
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TCAs
Muscle relaxants
SSRIs
Antiseizure meds
Vitamin B12
Lidocaine patch
Analgesics
TENS unit, acupuncture, Biofeedback
Headache
Headaches
• Migraines
• Cluster Headaches
– “Cluster cycle”
• Tension Headaches
– “Stress”, muscle
tension, neck pain
Migraines
Migraine Headaches
• Types
– Simple or Classic
– Complex
• Hemiplegic
• Possible Aggravating factors
(“triggers”)
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Stress / Emotion
Glare
Alcohol
Exercise
Stimulants: Excess
Caffeine, cocaine,
amphetamines
– Foods
– Analgesic rebound
– Estrogen
Migraines
• Trigeminal Nerve
Symptoms
• Several Criteria
– Photophobia
– Nausea/Vomiting
– Aura
• Recurrent
MRI of a Migraine
Diagnostic Requirements of
Migraine
• At least two of the following features:
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Unilateral location
Throbbing character
Worsening pain with routine activity
Moderate to severe intensity
• At least one of the following features:
– Nausea and/or vomiting
– Photophobia and phonophobia
International Headache Society Classification of
Headache
Acute Migraine Treatment
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Ergotamine
• Caffeine
– - Unknown
– “Abortive” or “rescue” tx
– Dosage forms – oral, sublingual,
rectal, parenteral
– Increases intestinal
absorption of
ergotamine
• Peripheral vascular disease
– Potentiates
vasoconstriction and
pain relief when
combined with
ergotamine and
analgesics
• Cerebrovascular disease
– Adverse effects
– Contraindications
• Cardiac disease
• Sepsis
• GI disturbances
• Advanced Liver and Kidney disease
• Nausea
• Pregnancy, Breast Feeding
• Vomiting
• Anorexia
Acute Migraine TreatmentTriptans
• Sumatriptan
– Dosage Forms
• Drug Interactions
– Ergot alkaloids
• Subcutaneous injection
– Lithium
• Oral tablet
– Serotonin-specific
reuptake inhibitors
• Nasal Spray
– Adverse effects
• Oral - nausea and vomiting,
malaise, dizziness
• Intranasal – bitter, unpleasant
taste
• Subcutaneous Injection - mild
pain, redness, rebound HA
– Other triptans
– Monoamine Oxidase
Inhibitors - use with
these products may
precipitate serotonin
syndrome
Acute Migraine Treatment
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Second Generation triptans
• Eli-, zolma-, nara-, frova-
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Acute treatment of migraines
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Comparison to sumatriptan
– Similar pharmacologic features
– Improved oral bioavailability
– Able to cross blood brain
barrier
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Possible reasons for treatment
failures
– Medication administration
too late
– Swallowing Sublingual
products
– Vomiting tablet prior to
absorption
– Rebound headache due to
overuse
– Dehydration/
ketosis/acidosis
– Analgesic rebound
– Diagnosis?
Intractable migraines
• Sumatriptan subcutaneous injection
• Parenteral form of ergot derivatives
• IV antiemetic
• Corticosteroid - oral or parenteral
• Hydration!
• Parenteral Narcotic analgesics
Migraine Adjunctive therapy
• Antiemetics
– Systemic relief of nausea and vomiting
– Increased absorption of other
medications, prokinetic
• NSAIDS
– Not approved by FDA for migraine
headache indication
– Selected NSAIDS effective as abortive
therapy
Migraine Prophylactic therapy
• Goals
– Reduces frequency
– Reduces severity
• Criteria
– Headaches that occur twice monthly or more
often
– Disabling headache that occurs less frequently
but are unresponsive to usual abortive therapy
– Abortive agents contraindicated
– Headaches that occur in unpredictable patterns
Migraine Prophylactic
therapy- cont’d.
• Topomax
Use in low dose of 25 to 50 mg
at hs to prevent migrane
• Valproic Acid
– 1000mg po q HS prophylaxis
Cluster Headaches
• Gender - males>females
• Onset - second and fourth decade of
life
• Intensity of Headache Pain
• Same side of head, tearing, flush
• Severe throbbing/stabbing
• Not preceded by aura
• Last 45-60 minutes
Cluster Headache Abortive
Therapy
• Oxygen inhalation
• Ergotamine
Tension Type Headaches
• Gender - women 88%, males 69%
• Intensity of headache pain
• No aura
• No nausea, vomiting
• No photophobia
Tension Headache Therapy
• Abortive– NSAID’s
• Non-drug
techniques
– Muscle relaxants
– Massage
– Anxiolytics
– Hot bath
– Analgesics
– Acupuncture
• Prophylactic
– Antidepressants
– Biofeedback
Seizures
• VFib of the brain
• Various Reasons
– Electrical
– Ischemic
– Chemical
Seizure DisordersPharmacologic Treatment
• Optimization of drug therapy
• Choice of appropriate AED
• Individualization of dosing
• Compliance
Therapeutic endpoints: Patient
response
• Seizure frequency and severity
• Presence and severity of symptoms of
dose related toxicity
Serum drug concentrations
• Indications for use
– Uncontrolled seizures
despite greater than
average doses
– Seizure recurrence in a
previously controlled
patient
– Documentation of
intoxication
– Assessment of compliance
• When dosage changes are
made
– Interpretation of serum
concentrations
– Laboratory variability
– Interindividual variability
– Active metabolites of
AED’s may not be measured
– Binding of serum proteins
• Therapeutic blood levels
useful for:
– Dose change
– Phenytoin
– Assessment of therapy in
patients with infrequent
seizures
– Valproate
– Carbamazepine
– Phenobarbital
Idiopathic Grand Mal Epilepsy
• Drugs
– Phenytoin (hydantoins) (Dilantin)
– Valproic Acid=Depakote
– Carbamazepine (Tegretol)
– Phenobarbital (barbiturates)
– Topiramate (Topomax)
• Duration of therapy
– Seizure free for 2-5 years or may be lifetime
• Withdrawal of AED’s
– Two to three months withdrawal schedule
– Multiple therapy - each drug tapered separately
Complex Partial Seizures with
secondary generalization
• Carbamazepine (Tegretol)
• Lamotrigine (Lamictal)
• Gabapentin (Neurontin)
• Tiagabine=Gabitril
• Levatiracetam=Keppra
• Oxcarbazepine=Trileptal
• Pregabalin=Lyrica
Absence Seizures
• Valproate when secondary tonic/clonic
also
• Clonazepam
Febrile Seizures
• Fever control
• Anticipatory management in the
future
Testing Seizures
• EEG
EEG
Circulation Problems
Think Vascular
CVA/TIA
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Vascular insult
Dyslipidemia
Clotting/emboli
Risk Factors
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Age
Family history
Smoking
Dyslipidemia
Diabetes
Two kinds of CVA
Hemorrhagic
Embolic
Hemorrhage
Embolic
• Multiple causes
– Fat
– Air
– Blood
• ‘Brain attack’
• Destroys nerves
• ‘Cuts the wires’
Testing for Vascular Problems
• MRA
• Angiography
• Ultrasound
Consequences of wrong test
Medications for embolic CVA
• IV tissue plasminogen activator tPA
0.9mg/kg in highly selected cases
within 3 hours of ischemic stroke
• ECASA
• Dipyridamole-aspirin (Aggrenox)
extended release, 200mg/25mg
capsule PO BID
• Clopidogrel (Plavix) 75mg/day
• Warfarin INR adjusted dose
Surgical Measures
• Carotid endartectomy (CEA) is indicated
for stenosis of 70-99%
• CEA is of modest benefit for carotid
stenosis of 50-69% and depends on risk
factors
• No benefit <50%
Risk Factor Management
• Blood Pressure
– 130/80
– JNC 7
– Starting antihypertensive drug therapy
after TIA/Stroke
– ACE Inhibitors
Risk Factor Management
• SMOKING
“the risk of stroke in persons of either sex
and all ages was 50 percent higher in
smokers than in nonsmokers”
– Smoking cessation
Risk Factor Management
• Blood lipid levels
– Statin
• Diabetes mellitus
– Increases the overall risk by 25 to 50%
• Antiplatelet therapy
– clopidogrel (Plavix), ticlopidine (Ticlid),
and aspirin-dipyridamole (Aggrenox)
• Aspirin
• 50-325mg/day
Degenerative Disease
Think progressive
Parkinsons
• Reduction of
Dopamine
production
• Causes resting
tremors
Dopamine/Acetylcholine
Testing for Parkinson’s
Parkinson’s Symptoms
• Symptom spectrum
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Bradykinesia/ akinesia
Rest tremor
Mask facies
Progressive dementia
Depression (functional?)
Parkinson’s Disease
Non-pharmacologic Interventions
• Exercise
• Physical activity
• Nutrition
• Psychologic support
Parkinson’s Pharmacologic
Interventions: Dopamine Agonists
• Amantadine
– Mechanism of action
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– ↑ dopamine release
from presynaptic
nerve terminals
• Initiation of
therapy
– Twice daily, Morning
and lunch
• Adverse effects
– Anticholinergic
• Gastrointestinal
• Cardiovascular
• CNS
– Mild elevations of BUN
and alkaline phosphatase
• Monitoring Parameters
– GI and CNS complaints
– BUN, Cr every 3 months
Parkinson’s- cont’d.
• Dopamine agonists- besides
amantidine
– Pramipexole (Mirapex)
– Bromocriptine (Parlodel)
– Pergolide (Permax)
– Ropinirole (Requip)
• Monoamine Oxidase-B Inhibitors:
Selegiline (Eldepryl))
• Antioxidant Therapy- questionable
efficacy
Serotonin Syndrome
Symptoms Associated with Serotonin Syndrome
Mental status changes
Confusion (51%)
Agitation (34%)
Hypomania (21%)
Anxiety (15%)
Coma (29%)
Cardiovascular
Sinus tachycardia (36%)
Hypertension (35%)
Hypotension (15%)
Gastrointestinal
Nausea (23%)
Diarrhea (8%)
Abdominal pain (4%)
Salivation (2%)
References 2, 4
Motor Abnormalities
Myoclonus (58%)
Hyperreflexia (52%)
Muscle rigidity (51%)
Restlessness (48%)
Tremor (43%)
Ataxia/incoordination (40%)
Shivering (26%)
Nystagmus (15%)
Seizures (12%)
Other
Diaphoresis (45%)
Unreactive pupils (20%)
Tachypnea (26%)
Hyperpyrexia (45%)
(Nolan, 2005)
Anticholinergics
• Mechanism of action
– Blocks excitatory
neurotransmitter Ach in
substantia nigra
• Aids treatment of
tremor
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less effective than
levodopa/carbidopa or
dopamine agonists
• Drugs
– trihexyphenidyl (Artane)
– benztropine (Cogentin)
• Adverse effects
– Increased intraocular
pressure
– Confusion
– Impairment of recent
memory
– Hallucinations
– Delusions
– Dry mouth
– Blurred vision
– Constipation
– Urinary retention
Parkinson’s Tremor
• Symptoms may be
• Levodopa Drug interactions
controllable with Benadryl
– Neuroleptic drugs –
(Phenothiazine,
• Dopamine Precursors
Prochlorperazine,
(Levodopa - Sinemet –
Fluphenazine,
Stalevo)
Chlorpromazine)
– Initiation of therapy
– Butyrophenones: Haloperidol
• E.g. sinemet 10/100
t.i.d., increase q 2-3
days as tol
– Antihypertensives –
(Reserpine and Methyldopa)
– Adverse effects
– MAOi’s- serotonin syndrome
• Dyskinesias
– Other: Metoclopramide,
Pyridoxine, Ferrous sulfate,
Phenytoin, Benzodiazepines
• Mental changes
Adjunctive Treatment of
Parkinsonian Tremor
• B-adrenergic blockers
• Clozapine
• Surgery
• Deep brain stimulation
• Potential dietary/nutritional
interactions
– Tryptophan, tyramine, melatonin
Multiple Sclerosis
• Demyelination
– Energy Diffusion
– Reduced conduction
– Nerve degeneration
Types of MS
• Relapsing-remitting (80%)
– Periods of relapse, when symptoms flare up
– Periods of remission, when symptoms improve
• Secondary progressive
– Develops from Relapsing/Remitting
– shorter periods of remission and worse symptoms during
relapses.
– 50% to the secondary progressive stage in first 10 years
• Primary progressive (3 in 20)
– no periods of remission
– This causes increasing disability, and can reduce life
expectancy
MS Testing
• MRI Brain and spinal cord
– Remember MS is CNS
– White matter “Demyelination”
• Lumbar Puncture
– WBCs, Antibodies
• EMG Studies
MS Treatment Options General Considerations
• Exercise
• Appropriate exercise program is beneficial
• Simple exercises such as normal walking,
swimming, using exercise bike
• strongly advise against overheating (saunas,
hot tubs, sunbathing, etc.) to prevent
declines in neurologic function. Exercising in
a cool, well aerated environment is strongly
encouraged.
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MS Treatment Cont.
• Physical Therapy
• PT/OT including ankle braces and
devices that provide assistance with
walking, personalized exercise program
and counseling on work and daily
activities.
• Nutrition
• MS Society recommends low fat, low
cholesterol diet
• Obese patients appear to lose any reserve
muscle strength they may have left because
of their weight.
• Some patients with medullary lesions and
difficulty swallowing may require feeding
tubes to prevent aspiration and resulting
pneumonia.
• Treatment of Infections and Elevated Body
Temperatures
• Increased body temperature may lead to
transient increase in neurologic symptoms
or even precipitate exacerbation.
• If a fever is due to an infection, infection
needs to be identified and treated, and
antipyretics need to be administered.
• UTI’s are common
Treatment of Relapses
• Solu-Medrol (Methylprednisone) is
often used for treatment of severe
exacerbations.
• Typical doses range from 500 to 1000
mg/day for 3 to 5 days
Prevention of Relapses
• recombinant interferon-ß's
– Betaseron
– Avonex
• Copaxone
• Rebif
Treatment Options Symptomatic Therapy
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Fatigue
Vertigo
Spasticity and Muscle Spasms
Psychological Problems
Urinary Dysfunction
Sexual Problems
Tremor and Incoordination
Pain
Cognitive Dysfunction
Huntington’s Disease
• Degenerative Disease of the Brain
– Tremors
– Progressive dementia
• Genetic Inheritance
• 5 in 100,000 cases
• Diagnosed at symptom onset
– Usually after 30
– Usually after children are born
Compare…
Testing Huntington’s Disease
• CT/MRI (Specific finding)
– loss of a normally convex bulge of the
caudate nucleus into the lateral ventricles
– Enlarged lateral ventricles
• Labs
– Genetic testing
Dementia
Think Multi-causal
degeneration
DR SEUSS ON AGING
I cannot see
I cannot pee
I cannot chew
I cannot screw
Oh, my God, what can I do?
My memory shrinks
My hearing stinks
No sense of smell
I look like hell
My mood is bad -- can you tell?
My body's drooping
Have trouble pooping
The Golden Years have come at last
The Golden Years can kiss my ass
Overview of Dementia
• Population is aging
• Dementia increases with age
• Amnesia
– Isolated memory loss
– may be the first sign of dementia
• Delirium is a deficit of attention
Diagnostic Criteria for
Dementia
• Impaired social or occupational
function
• Impaired memory + 1 or more changes
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Abstract/problem solving
Judgment
Language
Personality
Depression vs. Dementia
• Depression
– Fast onset
– Depressed before
demented
– Patient complains
more than family
• Dementia
– very slow onset
– Demented then
depressed
– Patient denies
Depression vs. Dementia
• Depression
– Appears depressed
– Response of "I don't
know"
– Inconsistent
Cognitive impairment
– antidepressant
works
• Dementia
– May not appear
depressed
– Tries to answer
– Consistent Cognitive
impairment
– Antidepressant may
not work
Causes of Dementia
• Alzheimer's disease
– Most common cause in the elderly
– Incidence:
• 123.3 new cases/100,000 population/ year
– Prevalence:
• 10% over age 65, 47% over age 84
“Probable” Alzheimer's Dementia
• Abnormal clinical exam
• Abnormal Mini Mental status Exam
• Deficits in 2 or more areas of
cognition
• Progressive decline
• No disturbance of consciousness
• Absence of other cause
PET Scan
NORMAL
ALZHEIMERS DISEASE
MMSE - The Clock (1:45)
Risk Factors for Alzheimer's
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Family History of Alzheimer's disease
APO Genotype
Aging and estrogen deficiency
Head injury
Low education
Brain Iron Distribution
Dementia
Normal
Psychotic & Affective
disturbance
• Delusions: (false beliefs)
– 30-70% of patients (Usually simple delusions
• Hallucinations
– Not common. If present usually visual.
• Depression
– very common, difficult to diagnose.
– Suicide is rare.
– Severe depression more in vascular dementia.
Behavior problems
• Personality change:
– apathetic or more impulsive
• Anxiety:
– apprehension over upcoming events
• Aggression:
– physical or verbal
• Wandering
• Screaming
• Sleep disruption & “Sundowning”: very
common
Multi-infarct Dementia
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Abrupt onset with stepwise deterioration
Fluctuating course: improvement between strokes
Relative preservation of personality
Nocturnal confusion
Depression and Somatic complaints
Emotional incontinence
Cardiovascular Hx/Signs
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History of hypertension
Evidence of atherosclerosis (PVD, MI)
Focal Neurological symptoms (TIA)
Focal neurological sign
Normal Pressure Hydrocephalus
• 3 main symptoms:
– Dementia, Gait Apraxia, Incontinence
• Language functions preserved
• Most common cause of gait abnormality plus
Dementia is multiinfarct dementia
• Progressive (months-years) with plateau
• MRI shows large ventricles
• LP may result in temporary improvement
• Treatment is VP or LP shunt
HIV dementia
• Younger patient
• Memory loss
• Frontal lobe dysfunction, personality
change, social withdraw
• Progresses over months
• Sometimes initial symptoms of AIDS
• May have other brain infection/tumor
Other causes of Dementia
• Toxic/Metabolic/Nutritional:
– Alcohol or drugs
– Vitamin deficiencies
– Hormonal disturbances
• Primary progressive Aphasia:
– progressive aphasia without true dementia
• Jacob Creutzfeld Disease:
– progressive dementia with seizures, myoclonus,
ataxia, visual disturbance, motor neuron
dysfunction
Other Dementias
• Chronic infections, vasculitis:
– Cryptococcal, fungal.
• Progressive multifocal leukoencephalopathy
• Bilateral Subdural hematoma
• Brain tumor:
– especially frontal glioma
• Neurodegenerative Disorders
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Parkinson's disease
Lewy body dementia
Progressive supranuclear palsy
Frontotemporal dementias
• (e.g., Pick's disease, primary progressive aphasias)
– Cortical-basal degeneration Hippocampal sclerosis
Infections
Think bug!
Meningitis/Encephalitis
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Inflammatory process
Driven by foreign invaders (usually)
Fungal, Bacterial, Viral, or Parasitic
Symptoms
– Caused by increased pressure/edema
– Pressure on nerve fibers
– Temperature changes
Strep Pneumo Meningitis
Testing for Meningitis
• Lumbar Puncture
• Clinical Exam
• Labs/Blood cultures