Download Neuromuscular Junction & Infectious Disorders

NEUROMUSCULAR
JUNCTION AND
INFECTIOUS DISORDERS
Dayna Ryan, PT, DPT
Winter 2012
NEUROMUSCULAR
JUNCTION DISEASES
Botulism
• Myasthenia Gravis
• Lambert-Eaton Syndrome
•
BOTULISM
Latin: “botulus,” meaning sausage
• Etiology
- Neurotoxin produced by Clostridium Botulinum
- Anaerobic, Gram-positive rods
- Found in improperly preserved or canned foods
& contaminated wounds
• Classification (mode of acquisition)
- Food-borne (ingested)
- Wound
- Unclassified
• Lesion
- Pre-synatic terminals
• Mechanism
1. Botulinum toxin enters presynaptic terminals
2. Blocks the fusion of ACh vesicles with
presynaptic membrane
3. Inhibit ACh release into neuromuscular junction
4. Nerve impulse fails to transmit across the
neuromuscular junction
5. Muscle paralysis
• Progression
- Typically get full recovery in both adult & infant
MECHANISM OF ACTION OF BOTULINUM TOXIN
INCIDENCE
10 adult & 100 infant cases in US each year
Infant botulism
Age 3 wk - 9 month
Signs and symptoms
Develop within 12-36 hours following ingestion of contaminated food
Mortality rate from 1990 – 1996 in US
Type A (6.7%), type E (6.5%), type B (0%)
Gradual recovery over weeks - 12 months
SIGNS & SYMPTOMS
 Develops
within 12-36 hours following
ingestion of contaminated food
 Flaccid symmetrical paralysis
 Blurred & double vision, photophobia
 Dry mouth, nausea, & vomiting
 Difficulty in swallowing & speech
 Respiratory failure can occur in 6-8 hours
TREATMENT




ABE serum antitoxin (antibodies of type A,
B, E toxin)
Debridement & antibiotics for wound
Removal of toxin from GI (gastric lavage)
Supportive measures, e.g. IV, mechanical
vent
MYASTHENIA GRAVIS
•
•
Fluctuating weakness &
fatigability
Autoimmune disorder
–
•
Abnormal Thymus function in 75% of cases
Classifications of MG
–
–
–
Ocular myasthenia (~10-15%)
Generalized weakness (~85%)
Myasthenic crisis: respiratory failure
MECHANISM OF MG
Antibodies
block & damage ACh receptors
 ACh
receptors # reduced; Decreased efficiency
of neuromuscular transmission
 Nerve impulse fails to pass across the
neuromuscular junction to cause muscle
contraction
MYASTHENIA GRAVIS
 Prevalence:
14/100,000
 Ratio of women-to-men= 3:2
 Factors
that exacerbate MG: hyper- or
hypothyroidism, menstrual cycle
 Disease


Progression:
Slowly, progressive weakness (maximal
weakness occurs in first year in 2/3 of all
cases)
After 15-20 years, weakness becomes fixed
 Remissions
occur in about 25% of cases
SIGNS & SYMPTOMS
Generalized weakness:
proximal muscles more
affected
 Fatigability of skeletal
muscles
progressive muscular
weakness on exertion,
followed by recovery of
strength after rest
 Respiratory
impairments

SIGNS & SYMPTOMS



Muscle weakness varies day to
day and over long periods of time
Cranial muscles are the first
to show weakness
Patients compensate for weak
muscles (e.g. use of thumb to
close jaw)
Eyelids fatigue with
sustained upward gaze
DIAGNOSIS

Test anti-Ach receptor antibodies


if +, then MG
Tensilon test
Repetitive movements or holding a position
 Compare performance following giving Tensilon
(anticholinesterase) vs. Placebo (saline)
 If strength/endurance is improved, then MG


EMG

Reduced amplitudes over repetitive stimulation
 Treatment




Anticholinesterase drugs
Thymectomy
Immunosuppressants
Plasmaphoresis
Blood is routed to a machine that
separates the plasma & cells
 Plasma, which contains antibodies,
dissolved proteins, glucose, clotting
factors, etc., is discarded while cells
are returned to the body
 Temporarily (4-6 weeks) reducing
anti-ACh receptors antibodies
 Used to get a patient more stable for
surgery or to get them out of crisis


Intravenous immunoglobulin
(IVIG)
LAMBERT-EATON SYNDROME

Rare but still the most frequent presynaptic
neuromuscular transmission disorders in adults
 Etiology
~50% of cases associated with cancer, especially
small cell carcinoma of the lung
 Others primarily from autoimmune disorders


e.g. RA, thyroid disease, MS
Mechanism
1. Antibodies destroy
voltage-gated Ca++
channel
2. Block of Ca++ into
presynaptic terminal
3. Reduced release of
presynaptic ACh
vesicles
4. Reduced probability
of reaching
depolarization
threshold of a muscle
fiber
SIGNS & SYMPTOMS
Muscle weakness and fatigue
• At proximal limbs & torso (LE > UE)
• Difficulties climbing stairs, lifting
objects
– Early symptoms: aching of thighs
and difficulty walking
– Decreased or absent DTRs
– Cranial nerves usually spared
–
Lambert-Eaton Syndrome
DIAGNOSIS
–
–
–
EMG
• Will see a low
amplitude
response to a
single stimulation
Voltage-gated
calcium channel
antibody
• If +, then LEMS
MRI or CT scan for
lung cancer
INFECTIOUS DISORDERS
OF THE NS
Meningitis
• Encephalitis
• Lyme Disease
• West Nile Virus
•
MENINGITIS
= meninges of the brain and SC become
inflamed


All 3 layers can be involved, but usually pia and
arachnoid
Etiology: bacterial or viral infection
Viral (Aseptic) – most common
 Tuberculous – enter by inhalation
 Bacterial – EMERGENCY!!


Incidence: 2-6/1,000,000 adults
MENINGITIS
• SIGNS & SYMPTOMS







Fever & chills
Severe headache
Stiff & painful neck!
(cardinal sign)
Mental status changes
Sensitivity to light
(photophobia)
Confusion
Vomiting

Pain in lumbar area and
posterior thigh

Positive Kernig sign
SIGNS & SYMPTOMS PROGRESSION

Positive Brudzinski sign
as it progresses

when neck is flexed,
patient flexes leg to
decreased stretch on
meninges
Seizures or coma if
untreated
 Focal neurologic signs,
e.g. CN palsies or
deafness
 Edema, which causes
increased ICP and can
lead to lethargy and
confusion

BACTERIAL MENINGITIS IN A BABY
Fever
 Poor feeding
 Vomiting
 Bulging Fontanels


Soft spots
Seizures
 High-pitched cry

• DIAGNOSIS
Lumbar puncture: CSF analysis & culture
 Blood culture
 CT, MRI: brain abscess or infarction

• Treatment

Bacterial type
Isolation for 3 days
 Bed rest
 Antibiotics ASAP
 Meds for seizure
 Corticosteroids for cerebral
edema or vasculitis


Viral type

Meds to control headache and nausea
ENCEPHALITIS
Lesion Site: gray matter of the CNS
 Etiology: viral or bacterial infection


Most often from viral infection

In US, Herpes simplex encephalitis most common;
1/250,000 – 1/500,000
ENCEPHALITIS

Most cases: only mild symptoms or asymptomatic

Serious cases cause:









Fever & chills
Headache
Nausea & vomiting
Mental status changes; irritability
Lethargy, fatigue
Seizures
Stiff neck (if meninges are involved)
Bulging fontanels (soft spot in skull) in infants
Focal neurological signs, e.g. ataxia, hemiparesis,
aphasia
ENCEPHALITIS

Prognosis depends on type
Mortality rate varies from <1% to 50-70%
 Permanent neural damage is more likely in infants


Diagnose with spinal tap, EEG, CT scan, or MRI
LYME DISEASE
Lyme disease was first reported in the US in
the town of Old Lyme, Connecticut, in 1975.
Most cases (90%) in mid-Atlantic, northeast,
& north central regions.
•
Lesion Sites:
–
•
CNS and PNS
Incidence on the rise
–
23,763 cases in 2002
 Etiology

Bitten by an infected
tick carrying the
bacterium Borrelia
burgdorferi
 Risk
Factors
 Having a pet
 Outdoor activities
 Walking in high
grasses
Signs




& Symptoms – Early Stage
The initial sign is rash
 Bull's-eye appearances (i.e. erythema migrans)
at the site of tick bite
 Present in ~80% of patients
 Gradually expands to ~ 12” across
Flu-like symptoms: chills, fever, headache,
lethargy, muscle pain
Chronic RA is the most commonly recognized
symptom
Some neurologic and psychiatric symptoms
LYME DISEASE
PROGRESSION OF LYME DISEASE
 Stage

1
Flu-like symptoms and rash (7-14 days after
tick bite)
 Stage
2
Generalized fatigue, loss of appetite, vomiting
 Neurologic or cardiac abnormalities develop
weeks to months later

 Stage

3 (weeks to year later)
RA develops in >50% of people who did not
receive earlier treatment
Affects knees mostly
 Often unilateral presentation of joint involved

SIGNS & SYMPTOMS – LATER STAGES
Swollen knee from
chronic rheumatoid
arthritis is most
commonly recognized
symptom
TREATMENT OF LYME DISEASE
Oral antibiotics
 Removal of tick
 Joint surgeries

**15% of those who received early treatments still
get complications involving heart, joints, and
nervous system
MOST people have complete recovery within weeks
or months of antibiotic treatment
PREVENTION IS KEY
Wear long pants
 Walk on cleared paths
 Wear high socks and appropriate shoes
 Wear light-colored clothing to make ticks easier
to see

WEST NILE VIRUS
It was first discovered in the United States in the
summer of 1999 in New York. Since then, the virus has
spread throughout the United States
•
Lesion: CNS, PNS, Multi-systems
(depends on where bitten)
WEST NILE VIRUS
2009 West Nile Virus Activity in US
(Reported to CDC as of December 2009)
WEST NILE VIRUS

Etiology:
Single-stranded RNA virus from mosquitos primarily
 Flavivirus

No treatment available – only supportive care
 Risk factors: age, hypertension, diabetes, CAD,
immunosuppression

SIGNS & SYMPTOMS
 ~80%
of individuals are asymptomatic
 ~20%
of individuals affected by the virus develop
systemic symptoms

< 1% develop neurological manifestations
 Those
that do develop nervous system involvement
usually evolve a severe illness

Mortality rates 12%-14%
PRESENTING SIGNS AND
SYMPTOMS
 Fever
 Headache
 Muscle
Ache
 Joint Pain
 Fatigue
 Rash (with swollen
lymph nodes)
 Nausea/vomiting
 Periocular pain
 Muscle
weakness
 Altered mental
status
 Backache
 Photophobia
 GI/Respiratory
Symptoms
NEUROLOGIC SIGNS & SYMPTOMS
Encephalitis
 Meningitis
 Meningoencephalitis
 Anterior myelitis


Acute flaccid paralysis
Proximal muscles
affected more than
distal
 From damage to
anterior horn cells
 Painless, asymmetric
weakness
 No sensory
abnormalities

SERIOUS SIGNS & SYMPTOMS
High fever
 Severe headache
 Stiff neck
 Disorientation
 Coma
 Tremors
 Convulsions
 Muscle weakness
 Ataxia and
extrapyramidal signs

CN abnormalities
 Optic neuritis/vision
loss
 Polyradiculitis
 Seizures
 Myelitis
 Photophobia
 Numbness
 Paralysis
