Neuro 3…

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Neuro 3

• Meningitis..

Encephalitis
Trigeminal Neuralgia
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Meningitis
Meningeal inflammation ...around brain and
spinal cord
Cause Viral vs Bacterial vs other..
Classic sx HA, NV, neck stiffness, fever
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epidemiology
Viral Meningitis definition
Viral (Aseptic) Meningitis Meningeal
inflammation w/ neg. bacterial cultures w/ No
associated neurologic dysfunction

• WHOinfants lt1yr
• children 5 -10yr
• WHEN
• highest incidence late Spring to Fall
• reflecting peak activity of enteroviral and
  arthropod-borne infections

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VIRAL MENINGITIS PATHOGENESIS
Few viral particles replicate in the nasopharynx
with spread/replication in resp. tract
lymphatics.
Most viral particles bind to specific receptors
on enterocytes traverse the intestinal lining
cells to reach the Peyer's patches in the lamina
propia, where they replicate on mucosal surfaces
of the respiratory GI tract

• --gtprimary viremia (onset of illness) seeding of
  other organs (liver/spleen/heart)
• second viremia (seeding of the CNS during first
  or second viremia)
• s/sx of infx

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Viral meningitis Causes

• MOST COMMON
• Enterovirus (esp.Spring/Fall)
• Coxsackie
• Echovirus
• other non-poliovirus enteroviruses

• OTHER CAUSES
• Mycobacteria
• Fungi
• Spirochetes
• parameningeal infections
• Medications
• (Amox,. Bactrim, NSAIDS, zantac)
• malignancy

?arbovirus

• OTHER VIRUSES
• HSV HIV West Nile virus (WNV)
• varicella-zoster virus (VZV) Mumps
• lymphocytic choriomeningitis virus (LCM)

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Most common cause Enteroviruses

• EV 85 -95 viral meningitis
• Nonpolio-EV serotypes cycle from year to year
• however, certain serotypes have remained
  prevalent.
• Most common 2000-2005 Coxsackieviruses A9,
  B5, and B1
• Echoviruses 6, 9, 13, 18, and 30
• lt3mo usually group B coxsackie viruses and
  parecho viruses
• EV 71, closely related to coxsackie virus A16,
  the viral agent of hand-foot-mouth disease, has
  emerged as a significant cause of aseptic
  meningitis, encephalitis, myelitis.

TRANSMISSION
Humans only known reservoir Transmission
fecal-oral route. (Raredroplet
inhalation) Possible Transplacental -gt
stillbirth, abortion, neonatal infx
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Risk factors for EV
Seasonality In temperate climates most EV
infections outbreak during the warmest months
however, sporadic cases can develop throughout
the year. In US infections more frequent June -
October In tropical and subtropical regions
consistent thru year

• Host factors
• severe nonpolio EV infx if immunodeficient, age
  extremes
• risk of chronic meningoencephalitis if child w/
  deficient humoral immunodeficiency, especially
  X-linked agammaglobulinemia

Incubation period for EV infection is approx. 3-6d
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Other virusesHerpes viruses

• All members of the Herpes viridae family can
  cause aseptic meningitis
• USUALLY HSV
• INFREQUENTLY CMV, VZV, human herpesvirus
  (HHV)-6, and Epstein-Barr virus (EBV)
• Neonatal CNS infxs are the most devastating
• Primary infection is followed by lifelong
  infection, w/ potential for reactivation
• Humans are the only reservoir for transmission
• Infections occur worldwide without seasonal
  prevalence

• ? mechanisms of spread to the brain include
  hematogenous dissemination, direct extension
  nasopharyngeal mucosa, or via neurogenic pathways

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VZV

• Aseptic meningitis is a rare complication of
  chickenpox and herpes zoster
• The syndrome known as zoster sine herpete is
  characterized by
• CSF pleocytosis
• documented CNS infection with VZV by PCR
• absence of typical skin lesions

Decreased incidence since introduction of
varicella vaccine
CMV and EBV
RARELY CAUSE Aseptic Meningitis however, aseptic
meningitis is the most common neurologic
complication seen in patients with primary EBV
infection
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OTHER CAUSES HHV-6 and HHV-7

• HHV-6, (roseola or exanthem subitum)
• common cause of febrile sz meningitis in
  infancy
• HHV-7, (also exanthem subitum)
• causes febrile seizures in infancy
• causes meningitis in children

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Other causes Arboviruses
Highest incidence tropical, developing
regions US most common after EV The incubation
period 1 - 18 days Most important endemic US
arboviruses St. Louis encephalitis virus West
Nile virus Eastern equine encephalitis
virus Western equine encephalitis
virus California encephalitis viruses
Pathogenesis Viruses are inoculated
subcutaneously or intravenously per vecotor
(mosquito) bite Replication in the skin or
muscle -gt primary viremia -gt spreads to to the
reticuloendothelial system or CNS.
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Ask about symptoms
HISTORY..ask about exposure
?rodents (LCM) ?ticks (Lyme)
?mosquitos ?human contacts ?TB ?sexual
activity (HSV-2, HIV, syphilis)

• Nonspecific sx
• Fever HA
• Nausea vomiting Photophobia
• Nuchal rigidity Altered mental status
• (Kernigs/Brudzinskis usu. neg)

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MENINGEAL IRRITATION
Physical Exam.look for
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Signs of meningeal irritation
PE
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PE Examination for nuchal rigidity

• Passive or active neck flexion inability to
  touch the chin to chest
• lateral motion less reliable finding
• Kernig's Brudzinski's signs were originally
  developed and tested in patients with severe,
  late stage meningitis
• Brudzinski's sign spontaneous flexion of the
  hips during attempted passive flexion of the
  neck.
• Kernig's sign inability or reluctance to allow
  full extension of the knee when the hip is flexed
  90º.
• When LP was performed w/ suspected meningitis
• sensitivity extremely low (5 for each sign 30
  for nuchal rigidity)
• specificity 95 for each sign 68 for nuchal
  rigidity.
• Jolt accentuation of headache more sensitive for
  dx meningitis.
• Sensitivity 97 specificity of 60 for dx of
  CSF pleocytosis

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DX CSF
PE.. look for rash

• Diffuse maculopapular exanthem in mildly ill pt
• ?enteroviral infection, primary HIV, or
  syphilis. ?meningococcal infection RMSF
• Parotitis mumps meningitis in unvaccinated pt.
• Severe vesicular, ulcerative genital lesions
  HSV-2
• Oral thrush cervical lymphadenopathy HIV
• Asymmetric flaccid paralysis West Nile Virus

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csf
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TREATMENT if unclear etiology
TREATMENT Suspected viral meningitis 
Usually self-limited (vs bact.meningitis)
Resolves without specific therapy

• Consider empiric therapy x 48hrs if Elderly,
  prior antibiotics,
  immunocompromised
• Otherwise, consider observation
• If suspect HIV check HIV RNA and HIV antibody
• If suspect HSV acyclovir 10 mg/kg IV q8hr

• empiric antibiotics after blood / CSF cultures
• OR observation with repeat LP in 6 - 24 hrs.
• If symptomatically improved and culture negative
  DC antibiotics w/o repeat LP
• If persistent SX w/o clear dx repeat LP

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HOSPITALIZE IF..

• Ill-appearance
• Signs of encephalitis
• altered mental status, behavior, or personality
• motor or sensory deficits
• speech or movement disorders hemiparesis
  flaccid paralysis paresthesias
• seizures
• Need for empiric antimicrobial therapy.
• Need for IV hydration or aggressive pain control.
  
• Immunocompromised host.
• Age younger than one year.

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Bacterial Meningitis purulent meningitis

• Meningitis is an inflammatory disease of the
  lepto-meninges, the tissues surrounding the brain
  and spinal cord, and is defined by an abnormal
  number of WBCs in CSF .

• Meninges
• pia
• arachnoid
• dura maters
• Bacterial meningitis infx of arachnoid mater and
  CSF in both the subarachnoid space and cerebral
  ventricles.

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Bacterial Meningitis - Causes
There are at least 50 causative bacteria

• Community Acquired
• Streptococcus pneumo (pneumococcus)
• Neisseria meningitidis (meningococcus)
• Listeria monocytogenes (50-60ys, immunideficient)
• Haemophilus influenzae type b (Hib)

• Healthcare-associated
• (after neurosurgery, ventricular drains, w/trauma
  )
• usually staphylococci
• aerobic gram-negative bacilli

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Symptoms

• Quite ill
• Rapid onset
• Classic Triad
• Fever (gt38) (95x 4d)
• Mental status changes (78)
• Nuchal rigidity (88 x7d)
• Also
• Severe, generalized headache
• Photophobia
• Nausea/vomiting
• Rash 11-26 N. meningitidis, petechiae and
  palpable purpura
• Arthritis 7 N. meningitidis,

PHOTO
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Additional Symptoms

• Decreased consciousness
• Rapid breathing
• Agitation
• Opisthotonos
• Bulging fontanelles
• Poor feeding
• Irritability
• NEWBORN FUO

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Possible Complications

• Hearing loss
• Brain damage
• Loss of vision
• Hydrocephalus
• Waterhouse-Friderichsen syndrome (WFS) or
  hemorrhagic adrenalitis (Neisseria meningitidis )

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Differentials

• Viral meningitis
• Encephalitis
• Febrile viral syndromes
• Drug induced meningitis

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BACT. MENINGITIS DX Tests
CSF glucose -lt40 mg/dL or lt1/2 serum CSF
CELL count - WBCs gt1000/microL with a
predominance of neutrophils PROTEIN elevated
gt0.4g/dl POSITIVE gram stain/culture

• LP
• Blood cx positive
• Other labCBC, chem
• Chest x-ray
• (r/o other sites of infx)
• Head CT scan (?ICP )
• (r/o hydrocephalus, abscess or deep swelling)

H. Influenzae b Gram Stain
REFER!
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LABORATORY FEATURES
FYI
Routine blood work is often unrevealing. WBC
usually elevated, with left shift Leukopenia
possible w/ severe infection Platelet count may
be reduced. Leukopenia and thrombocytopenia
poor outcome Coagulation studies may have
DIC. Serum chemistry may have metabolic acidosis
or hyponatremia Blood cultures often positive
(50- 90) Obtain Two sets of blood cultures prior
to the initiation of antimicrobial therapy
Cultures obtained after antimicrobial therapy
are much less likely to be positive, esp.
meningococcus Tests of urine, mucosal surfaces
for bacterial antigens are not generally helpful
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LUMBAR PUNCTURE
FYI

• Every patient w/suspected meningitis should have
  CSF obtained unless LP contraindicated.
• PROs of CT then LP
• exclude a mass lesion or increased ICP, which
  rarely leads to cerebral herniation during LP
• However, a screening CT scan is not usually
  necessary
• Study CT24had abnl finding, but only 5 had
  mass effect.
• Abnl CT scan predicted by a suspicious hx/Exam
• -immunosuppression
• -previous CNS disease
• seizure within the previous week
• reduced LOC
• motor or cranial abnormalities, papilledema
• CONS of CT then LP2hr delay in dx, 1hr delay in
  rx.

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If LP is delayed
fyi
Obtain blood cultures Start antibiotics
empirically before the imaging study Also give
dexamethasone (0.15mg/kg IV q6hr) shortly before
or at the same time as the antibiotics (? rate
of hearing loss other neuro complications,
mortality) (Adjunctive dexamethasone should not
be given after antimicrobial therapy b/c unlikely
to improve pt outcome) Prior administration of
antimicrobials tends to have minimal effects on
the chemistry and cytology findings, but can
reduce the yield of Gram stain and culture
. However, a pathogen can still be cultured from
the CSF in most patients up to several hours
after the administration of antibiotics
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TREATMENT
FYI

• TRUE medical emergency
• requires immediate admission

• Antibiotics - depending on organism
• Extremes of age (lt3m or gt60 yrs)
• cover for listeria with ampicillin.
• Empiric therapy rocephin (2grams Q12h) plus
  vancomycin
• Treatment of secondary symptoms including
  cerebral edema, shock, sz

Any form of bacterial meningitis that is
untreated or treated very late in its course is
almost uniformly fatal.
Sequelae
In-hospital mortality 27 Neurologic deficit at
discharge 9 independent predictors of adverse
outcome hypotension altered mental
status seizures
ADVERSE OUTCOME no RF 9 1 RF 33 2-3
RF 56
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Antibiotics
FYI
B/C uncertain effect of dexamethasone on the CSF
penetration of vancomycin Begin with
vancomycin plus either ceftriaxone or
cefotaxime. If susceptibility studies show
intermediate susceptibility (MIC 2 mcg/mL) to
ceftriaxone and cefotaxime, add rifampin B/C
vancomycin penetration into the CSF starts at a
high level in the presence of bacterial
meningitis.. impairment in penetration to a level
that will reduce efficacy is not likely in the
first few days before susceptibility studies are
available.
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Patient Education

• Seek immediate medical attention if a child has
  any of the symptoms
• Early treatment is key to good outcome.
• Prevention of hflu HiB vaccine
• Prevention of pneumococcal Prevnar
• Prevention, high school students Menactra
• Prophylaxis of household
• contacts w/ preventative antibiotics
• highly recommended.

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Meningitis (bacterial vs viral) vs Encephalitis

• Bacterial Meningitis
• Very serious
• Meningeal irritation
• CSF Gram stain positive
• CSF WBC gt1000/microL (neuts)
• CSF glucose lt40 mg/dL

Nl brain function

• Viral Meningitis
• less severe
• meningeal irritation
• fever, HA, NV
• seizures
• hemiparesis
• flaccid paralysis
• paresthesias
• resolves w/o specific Rx
• CSF WBClt500/ microL
• CSF protein lt80 100mg/dL
• CSF glucose normal
• Gram stain negative

Abnl brain function
Encephalitis Viral, invades brain tissue altered
mental status (confused.. obtunded) motor or
sensory deficits (paresis, ? DTRs) altered
behavior personality speech or movement d/o No
meningeal irritation
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Encephalitis

• Viral Inflammation of the brain
• Rare disease
• (0.5 per 100,000)
• Most common in
• children
• elderly
• Immuno-compromised

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Encephalitis PATHOGENESIS

• Two viral mechanisms
• 1.directly invade brain tissue (acute viral
  encephalitis)
• virus cultured from the brain
• viremia from viral meningitis
• spread from peripheral nerves (rabies, HSV)
• 2.Post-infectious encephalitis (autoimmune
  response)
• No virus detected
• hx of illness or vaccination 2-4wk prior to S/S
• Need neuroimaging to differentiate.

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EncephalitisS/S

• subtle to profound
• Altered mental status confused, agitated,
  obtunded
• Behavior
• Personality
• Speech
• movement.. Motor or sensory deficits
  hemiparesis, cranial nerve palsies, exaggerated
  DTRs
• Seizures are common

NO S/S of meningeal irritation photophobia,
nuchal rigidity VS aseptic meningitis
nonspecific, fever, headache, nausea, vomiting,
photophobia, nuchal rigidity nl cerebral function
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Neonates and young infants

•  As with other infections in neonates (0-28d) and
  young infants, the presentation can be
  nonspecific.
• Fever (variable )
• seizure
• poor feeding
• Irritability
• Lethargy

• In a series of 63 neonates with HSV1 CNS dz
• 49 lethargy
• 57 seizure
• 63 skin vesicles
• 44 fever

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Children and adolescents 
SS at admission prospective series of 50
children (6wks-18yrs) 100Encephalopathy 80
Fever 78 Seizure 56 Other Focal
neuro signs 47 ? LOC
Complications  status epilepticus cerebral
edema inappropriate ADH cardiorespiratory
failure DIC
defined as depressed or altered LOC (lethargy,
extreme irritability, significant change in
personality or behavior) x 24hr
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Encephalitis - Causes
measles
Many different viruses Most cause meningitis or
encephalitis
Postinfectious encephalitis MMR, VZV, influenza
Sporadic encephalitisHSV1
Geographic location (eg, St. Louis encephalitis
in North America, Japanese encephalitis in Asia)
rmsf
lyme

• Tick Exposure
• Colorado tick fever (w. US) or
• non-viral, ie Lyme dz or RMSF

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Encephalitis-Causes
Mosquito exposure

• Arboviruses (east.equine, west. equine, St. Louis
  (NA, Midwest/So.US)

• Venezuelan equine encephalitis

2009

• WNV (multiple continents including Asia, Africa,
  Europe, NA)
• weakness, rash
• rare lt 1999,now most commonly CNS arboviral infx

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Peds..causes
Enteroviruses major cause. clear seasonality
(78 June - October)
HSV 1/11..5 all age groups but 75 neonatal
infection
Epstein-Barr virus 10
Arbovirus La Crosse encephalitis most common
arbovirus in children Seasonal (July -
September)??usu 5-9yr\o
Arbovirus West Nile virus .. rare
Influenza virus 5 usuallylt 5yo
Other viruses MMR rare b/c vaccinations
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physical examination
IF Parotitis/mental status changesMumps
encephalitis

• IF Flaccid paralysis WNV infection
• Misdiagnosed as Guillain-Barre syn.
• Maculopapular rash 50
• IF Tremors of eyelids, tongue, lips, extremities
  
• St. Louis encephalitis or WN encephalitis
• IF Hydrophobia, aerophobia, pharyngeal spasms,
  hyperactivity encephalitic rabies.
• Atypical seizures, cranial nerve palsies,
  myoclonus
• IF Grouped vesicles in a dermatomal pattern
  varicella-zoster virus

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Encephalitis - Differentials
fyi
noninfectious etiologies intracranial
tumors collagen vascular disorders vasculitis neop
lastic diseases adverse effects of medications
Other non-viral infectious etiologies Brain
abscess Syphilis tuberculous meningitis fungal
meningitis (eg, coccidioides
REFER!!
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Encephalitis - Diagnostics

• Lumbar puncture
• Serology test to detect the presence of
  antibodies
• EEG
• Brain imaging

• Color Clear
• high pressure
• WBC, usually lt 250/mm3.
• predominance of lymphocytes
• early infection -gt Ý neuts
• repeat _at_ 8 hr shift to lymphs
• protein lt 150 mg/dL.
• glucose nl (gt50 of blood)
• red cells 0
• (presence suggests HSV-1 )

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DIAGNOSIS
FYI
Etiology in most cases remains undefined CSF
VS bacterial meningitis higher WBC
(gt2000/mm3) w/ neuts predominantly higher
protein concentration (gt200 mg/dL) usually
hypoglycorrhachia Culture Viral culture of CSF
routinely ordered but viruses recovered
6 polymerase chain reaction (PCR) tests for
viruses PCR testing has replaced viral culture of
CSF For HSV-1, HSV-2, and enteroviruses
Most important viral etiology to r/o is
HSV usually fatal if untreated
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Imaging
fyi
CT/MRI may or may be abnormal CT r/o
space-occupying lesions or brain abscess.
MRIdetects demyelination
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EMPIRIC THERAPY
no specific therapies for most CNS viral
infections. EXCEPT HSV-1 / VZV Acyclovir (10
mg/kg IV Q8h) initiated as soon as possible
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Prognosis
IF diffuse cerebral edema or intractable
seizures poor neurologic recovery and increased
risk of mortality IF self-limited seizure
activity rapid recovery IF HSV encephalitis
Even with prompt initiation of acyclovir,
significant morbidity and mortality. one-year
mortality14 epilepsy 24 neuropsychiatric
sequelae 22
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Encephalitis Pt Education

• Mosquito avoidance!
• Avoid being outside at dawn and dusk (when
  mosquitoes are most active)
• Wear protective clothing
• Use insect repellent
• Drain standing water (breeding grounds for
  mosquitoes)
• Vaccinate Animal against rabies
• Acute phase lasts up to one week
• Full recovery can take several wks - months

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Trigeminal Neuralgia

• An extremely painful
• inflammation of the
• largest nerve in the
• skull Trigeminal Nerve

SX Sudden, severe spasms usually
unilateral Brief 1-3 sec stabbing or
lancinating recurrent episodes Facial muscle
spasms continuous dull pain b/t no nite awakening
pain in the distribution of one or more
branches of the fifth cranial (trigeminal) nerve
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Distribution of Pain

• Distribution of pain usually V2 and/or V3
  subdivisions of the trigeminal nerve (5CN)
• V1 subdivision is involved in lt5 of pt
• (V1 common in postherpetic neuralgia)
• Trigger zones in the distribution of the affected
  nerve may be present and are often located near
  the midline.
• Lightly touching these zones often triggers an
  attack,
• Pain is triggered by touch or sounds
• Pain during chewing, eating, drinking, shaving,
  or brushing teeth

Distribution of pain
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ANATOMY
FYI detail
The trigeminal nerve (5th NN) is the sensory
supply to the face the sensory motor supply
to muscles of mastication.
It has three major divisions Ophthalmic
(V1) Maxillary (V2) Mandibular (V3)
The nerve starts at the midlateral surface of the
pons, and its sensory ganglion (gasserian
ganglion) resides in Meckel's cave in the floor
of the middle cranial fossa.
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triggers of paroxysms
Triggers chewing talking brushing teeth cold
air smiling grimacing dental procedures
Course variable Duration wks - months,
followed by pain-free intervals. Recurrence
common, some have continuous pain.
Severityvaries
"pretrigeminal neuralgia" dull, continuous,
aching pain in the jaw evolving eventually into
TN.
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EPIDEMIOLOGY
One of the most frequently seen neuralgias in the
elderly.

• Annual incidence 4 - 13 per 100,000
• Approximately 15,000 new cases in US/yr

• Increases gradually with age
• Most idiopathic cases gt50yr
• May occur 20s, 30s, rarely children

• M F ratio 11.5

So.. suspect TN if F gt50yo w/ sudden,
lancinating, spasmodic facial pain
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ETIOLOGY
Usually caused by compression of the trigeminal
nerve root, usually w/i a few mm of entry into
pons 80-90Compression by an aberrant loop of
an artery or vein
Corrupt Slide!

• OTHERS
• acoustic neuroma
• Meningioma
• epidermoid or other cyst
• rarely a saccular aneurysm or AVM

vascular compression classic TN structural
lesions secondary TN Mechanism nerve
compression -gt demyelination in a circumscribed
area around the compression -gt sx
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DIAGNOSIS per IHS
FYI
Based on Sx paroxysms of pain in trigeminal
nerve pathway
The International Headache Society (IHS) dx
criteria Paroxysmal attacks of pain lasting
from a fraction of a second to 2, affecting one
or more divisions of the trigeminal nerve Pain
has at least one of the following
characteristics Intense, sharp, superficial, or
stabbing Precipitated from trigger areas or by
trigger factors Attacks are stereotyped in the
individual patient There is no clinically evident
neurologic deficit Not attributed to another
disorder
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Trigeminal Neuralgia - Differentials

• Dental pain
• Sinusitis
• Parotitis
• Temporal arteritis
• HSV type I
• Cluster or migraine headaches
• Posterior fossa tumors
• TMJ pain

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Neuroimaging
REFER!!
head CT or MRIr/o structural lesion (tumor,
demyelinating lesions -MS) high resolution
MRI/MRA identify vascular compression Consider
MRI if Patients with trigeminal sensory
loss Patients with bilateral symptoms Young
patients (under the age of 40) Routine brain
imaging identified a only 2 cause of TN in 15
Insufficient evidence to support or refute the
utility of MRI to identify neurovascular
compression in classic TN.
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Electrophysiologic tests
FYI

• Trigeminal reflex testing probably useful for
  distinguishing classic TN from secondary TN
• trigeminal evoked potentials not useful for
  making this distinction
• Trigeminal reflex tests includes
• the blink reflex (obtained by recording from the
  orbicularis oculi muscles after electrical
  stimulation of the supraorbital nerve V1)
• the masseter inhibitory reflex (obtained after
  electrical stimulation of the infraorbital V2
  and mental V3 nerves).
• Responses are recorded by surface electrodes
  using standard electromyography equipment.
• Normal in patients with classic TN.

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TN Treatment
FYI
INITIAL
REFRACTORY..

• Anticonvulsants -
• Most common
• 1carbamazepine (Tegretol)
• 2 oxcarbazepine (Trileptal)
• 4phenytoin (Dilantin)
• Other anticonvulsants
• 3 lamotrigine (Lamictal)
• 4 gabapentin (Neurontin)
• Antispasticity Agents -
• 3 baclofen
• Tricyclic Antidepressants -
• Amitriptiline (Elavil)

• Alcohol injection - temporary pain relief by
  numbing the affected areas of face
• Surgery - goal
• either to stop the blood vessel from compressing
  the trigeminal nerve,
• or to damage the trigeminal nerve to keep it from
  malfunctioning.

1 EFFECTIVE, 2 PROBABLY EFFECTIVE, 3 POSSIBLY
EFFECTIVE 4 UNCERTAIN EFFECTIVENESS
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Patient Education

• Avoidance of triggers
• Coping with pain
• Medication side effects
• Lab monitoring re blood dyscrasias

The end