7/28/2019 12.12.07 Honeycutt

1/30

7/28/2019 12.12.07 Honeycutt

2/30

Amyotrophic Lateral Sclerosis

Andrea Honeycutt

AM Report

7/28/2019 12.12.07 Honeycutt

3/30

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.

7/28/2019 12.12.07 Honeycutt

4/30

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.

7/28/2019 12.12.07 Honeycutt

5/30

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.

7/28/2019 12.12.07 Honeycutt

6/30

7/28/2019 12.12.07 Honeycutt

7/30

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.

7/28/2019 12.12.07 Honeycutt

8/30

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.

7/28/2019 12.12.07 Honeycutt

9/30

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.

7/28/2019 12.12.07 Honeycutt

10/30

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.

7/28/2019 12.12.07 Honeycutt

11/30

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.

7/28/2019 12.12.07 Honeycutt

12/30

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.

7/28/2019 12.12.07 Honeycutt

13/30

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.

7/28/2019 12.12.07 Honeycutt

14/30

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.

7/28/2019 12.12.07 Honeycutt

15/30

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.

7/28/2019 12.12.07 Honeycutt

16/30

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.

7/28/2019 12.12.07 Honeycutt

17/30

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.

7/28/2019 12.12.07 Honeycutt

18/30

7/28/2019 12.12.07 Honeycutt

19/30

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.

7/28/2019 12.12.07 Honeycutt

20/30

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

7/28/2019 12.12.07 Honeycutt

21/30

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.

7/28/2019 12.12.07 Honeycutt

22/30

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.

7/28/2019 12.12.07 Honeycutt

23/30

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.

7/28/2019 12.12.07 Honeycutt

24/30

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.

7/28/2019 12.12.07 Honeycutt

25/30

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.

7/28/2019 12.12.07 Honeycutt

26/30

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.

7/28/2019 12.12.07 Honeycutt

27/30

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

7/28/2019 12.12.07 Honeycutt

28/30

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

7/28/2019 12.12.07 Honeycutt

29/30

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

7/28/2019 12.12.07 Honeycutt

30/30