12.12.07 honeycutt
TRANSCRIPT
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Amyotrophic Lateral Sclerosis
Andrea Honeycutt
AM Report
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ALS: Epidemiology
ALS is the most common form of motorneuron disease.
Sporadic forms (unknown cause) accountfor about 90-95 percent of ALS cases. Familial forms (AD inherited disease)
make up approximately 5-10 percent.
Slight male predominance for sporadicALS.
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ALS: Epidemiology
The incidence of ALS increases with eachdecade, especially after age 40 years.
Peak age of onset is 50-70s.
The only established risk factors for ALS are ageand family history.
Increased risk for developing ALS has beensuggested for laborers engaged in agricultural
work, factory work, heavy manual labor,exposure to welding or soldering, and work inthe plastics industry.
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ALS: Clinical Features
The clinical hallmark of ALS is thecombination of upper motor neuron and
lower motor neuron signs. UMN signs include hyperreflexia,spasticity, extensor plantar response (upgoing toes), and positive jaw jerk.
LMN signs include weakness, muscleatrophy, cramps and fasciculations.
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ALS: Clinical Features
The loss of motor neurons results in the primaryclinical symptoms and signs ALS. These may
produce impairment affecting limb, bulbar, axialand respiratory function.
Differences in site of onset, pattern and speed ofspread, and the degree of upper motor neuron
(UMN) and/or lower motor neuron (LMN)dysfunction produce a disorder that isremarkably variable between individuals.
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ALS: Initial Clinical Features
Asymmetric limb weakness is the most commonpresentation of ALS (80 percent).
Bulbar symptoms, usually manifested asdysarthria or dysphagia, is the next mostcommon presentation (20 percent).
Less common patterns of ALS onset include: respiratory muscle weakness (1 to 3 percent)
generalized weakness in the limbs and bulbar muscles(1 to 9 percent) axial muscle weakness weight loss with muscle atrophy.
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ALS: Clinical Features of LimbWeakness
Upper extremity onset is most oftenheralded by hand weakness but may
begin in the shoulder girdle muscles. Patients with hand weakness may
complain that they drop things and have
difficulty with tasks such as pinching,writing, typing, managing buttons orzippers, and picking up small objects.
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ALS: Clinical Features of LimbWeakness
Patients with shoulder girdle weaknessmay report difficulty using their arms in
activities such as washing, drying, orcombing their hair as well as lifting thingsabove their head.
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ALS: Clinical Features of LimbWeakness
Lower extremity onset of ALS most oftenbegins with foot drop.
Patients with proximal leg weakness oftencomplain of difficulty climbing stairs anddifficulty arising from chairs.
Either proximal or distal leg weakness cancause falls.
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ALS: Clinical Features of BulbarWeakness
Patients with dysarthria complain of slurring ofspeech that is often worse at the end of the day
or with more vigorous use of their voice. Patients with dysphagia initially complain ofdifficulty swallowing thin liquids, and may reportthe need to swallow multiple times in order to
manage a single liquid bolus.
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ALS: Clinical Features of BulbarWeakness
With progression, patients may choke orcough when drinking thin liquids and
eventually develop difficulty managingthicker liquids, their own secretions, andsolids.
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ALS: Clinical Features ofRespiratory Muscle Weakness
Initially complain of fatigue/shortness ofbreath triggered by decreasing levels of
activity or by lying flat. Often develop disturbed nocturnal sleep
with frequent awakenings and excessive
daytime sleepiness.
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ALS: Clinical Features of AxialMuscle Weakness
Patients with axial neck weakness complain ofposterior neck pain or strain with a graduallyworsening tendency for head drop.
Patients with axial truncal weakness complain ofdifficulty maintaining an erect posture whenstanding and of stooping when walking. Some
will support their trunk by placing their hands intheir front pants pockets or on their upperthighs.
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ALS: Other Clinical Features
Frontotemporal executive dysfunction mayprecede or follow the onset of UMN and
LMN dysfunction. Symptoms include changes in personality,
impairment of judgment, and
development of obsessional behaviors.
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ALS: Diagnosis
The clinical standard for diagnosis is the RevisedEl Escorial World Federation of Neurologycriteria which requires:
Evidence of LMN degeneration by clinical,electrophysiological, or neuropathological examination Evidence of UMN degeneration by clinical examination Progressive spread of symptoms or signs within a
region or to other regions (The body is divided into
four regions: cranial, cervical, thoracic andlumbosacral)Absence of electrophysiological, pathological or
neuroimaging evidence of other disease processes.
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ALS: Diagnosis
ALS is primarily a clinical diagnosis, sensory andmotor nerve conduction studies andelectromyography (EMG) are a standard part ofthe evaluation of motor neuron disease.
EMG findings in ALS combine features of acuteand chronic denervation.
Sensory and motor NCS are most often normalin ALS.
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ALS: Differential Diagnosis
Other Motor Neuron Diseases Primary lateral sclerosis (UMN
only) Progressive muscular atrophy
(LMN only)
Progressive bulbar palsy
Neuropathies GB, CIDP
Myopathies PM, inclusion body myositis
NM Junction Myasthenia gravis
Neurodegenerative Diseases Parkinsons, Progressive
Supranuclear Palsy, MS
Malignancy Primary/mets CNS Motor neuron syndromes with
MM, Lymphoma, lung, breast
Toxic Exposure EtOH, heavy metals
Endocrine TSH, adrenal, pituitary Infectious
HIV, CMV
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ALS: Progression and Prognosis
ALS is a relentlessly progressive disorder with aclinical course that is nearly always linear, with arelatively constant slope. (ie no remissions orexacerbations)
Rate of progression varies between individuals. Symptoms initially spread within the segment of
onset and then to other regions in a relativelypredictable pattern.
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ALS: Progression and Prognosis
Patients with unilateral limb onset thepattern of spread is to the contralateral
limb, then to the ipsilateral U/LE, then tothe contralateral remaining U/LE, and thento the bulbar muscles.
In patients with bulbar onset the mostcommon pattern of spread is to one armand then to the contralateral arm.
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ALS: Progression and Prognosis
The life-threatening aspects of ALS areneuromuscular respiratory failure and
dysphagia. The median survival from the time of
diagnosis is three to five years.
10% of ALS patients can live 10 years ormore.
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ALS: Supportive Treatment
Progressive neuromuscular respiratory failure isthe most common cause of death in ALS.
Intiation of noninvasive positive pressureventilation (in patients with FVC < 50%) canprolong survival up to 20 months.
5 to 10 percent of patients choose tracheostomy
and permanent ventilation when respiratorycompromise becomes severe.
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ALS: Supportive Treatment
Dysphagia poses a risk for aspiration offood, liquids, or secretions with resultant
pneumonia and may also lead tomalnutrition and dehydration.
Symptoms can be minimized in patients
who choose gastrostomy tube insertionwith aggressive management ofsecretions.
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ALS: Pharmacologic Treatment
Riluzole (Rilutek) is the only currentlyavailable medications for the treatment of
ALS. Glutamate Inhibitor although precise
mechanism of action in ALS is unclear.
Clinical trials have shown prolongedsurvival of approximately 2-3 months.
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ALS: Pharmacologic Treatment
Patients most likely to benefit fromtreatment include those who have:
Definite or probable ALS by El-Escorial criteriain whom other causes of progressive muscleatrophy have been ruled out
Symptoms present for less than five years
Vital capacity (VC) greater than 60 percent ofpredicted
No tracheostomy
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ALS: Board Review Questions
A 50yoM is evaluated for 4month h/oprogressive R foot drop and slurred speech. PEreveals tongue weakness associated with tongue
fasciculations, atrophy and +jaw jerk. R leg isatrophic w/faciculations. He has R ankle clonusand extensor plantar response. Sensory exam isnormal. Most likely diagnosis is?ALS
Spinal Muscle Atrophy Myasthenia Gravis Cervical spondylosis
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ALS: Board Review Questions
50yoM h/o ALS is evaluated for 6mo h/oprogressive SOB. He has been unable to lie flatto sleep for several months, awakens at night
and is extremely fatigued throughout the day.PE reveals diffuse fasciculations and RLE atrophyand weakness. FVC is 20% predicted. Mostappropriate therapy? High flow O2
Riluzole BiPAP IVIG
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