Amyotrophic Lateral Sclerosis Andrea HoneycuttAM Report

ALS: EpidemiologyALS is the most common form of motor neuron disease.Sporadic forms (unknown cause) account for about 90-95 percent of ALS cases.Familial forms (AD inherited disease) make up approximately 5-10 percent. Slight male predominance for sporadic ALS.

ALS: EpidemiologyThe incidence of ALS increases with each decade, especially after age 40 years.Peak age of onset is 50-70s.The only established risk factors for ALS are age and family history. Increased risk for developing ALS has been suggested for laborers engaged in agricultural work, factory work, heavy manual labor, exposure to welding or soldering, and work in the plastics industry.

ALS: Clinical FeaturesThe clinical hallmark of ALS is the combination of upper motor neuron and lower motor neuron signs. UMN signs include hyperreflexia, spasticity, extensor plantar response (up going toes), and positive jaw jerk.LMN signs include weakness, muscle atrophy, cramps and fasciculations.

ALS: Clinical FeaturesThe loss of motor neurons results in the primary clinical symptoms and signs ALS. These may produce impairment affecting limb, bulbar, axial and respiratory function.Differences in site of onset, pattern and speed of spread, and the degree of upper motor neuron (UMN) and/or lower motor neuron (LMN) dysfunction produce a disorder that is remarkably variable between individuals.

ALS: Initial Clinical FeaturesAsymmetric limb weakness is the most common presentation of ALS (80 percent).Bulbar symptoms, usually manifested as dysarthria or dysphagia, is the next most common 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 weaknessweight loss with muscle atrophy.

ALS: Clinical Features of Limb WeaknessUpper extremity onset is most often heralded 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 or zippers, and picking up small objects.

ALS: Clinical Features of Limb WeaknessPatients with shoulder girdle weakness may report difficulty using their arms in activities such as washing, drying, or combing their hair as well as lifting things above their head.

ALS: Clinical Features of Limb WeaknessLower extremity onset of ALS most often begins with foot drop. Patients with proximal leg weakness often complain of difficulty climbing stairs and difficulty arising from chairs. Either proximal or distal leg weakness can cause falls.

ALS: Clinical Features of Bulbar WeaknessPatients with dysarthria complain of slurring of speech that is often worse at the end of the day or with more vigorous use of their voice. Patients with dysphagia initially complain of difficulty swallowing thin liquids, and may report the need to swallow multiple times in order to manage a single liquid bolus.

ALS: Clinical Features of Bulbar WeaknessWith progression, patients may choke or cough when drinking thin liquids and eventually develop difficulty managing thicker liquids, their own secretions, and solids.

ALS: Clinical Features of Respiratory Muscle WeaknessInitially complain of fatigue/shortness of breath triggered by decreasing levels of activity or by lying flat.Often develop disturbed nocturnal sleep with frequent awakenings and excessive daytime sleepiness.

ALS: Clinical Features of Axial Muscle WeaknessPatients with axial neck weakness complain of posterior neck pain or strain with a gradually worsening tendency for head drop. Patients with axial truncal weakness complain of difficulty maintaining an erect posture when standing and of stooping when walking. Some will support their trunk by placing their hands in their front pants pockets or on their upper thighs.

ALS: Other Clinical FeaturesFrontotemporal executive dysfunction may precede or follow the onset of UMN and LMN dysfunction.Symptoms include changes in personality, impairment of judgment, and development of obsessional behaviors.

ALS: DiagnosisThe clinical standard for diagnosis is the Revised El Escorial World Federation of Neurology criteria 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 and lumbosacral) Absence of electrophysiological, pathological or neuroimaging evidence of other disease processes.

ALS: DiagnosisALS is primarily a clinical diagnosis, sensory and motor nerve conduction studies and electromyography (EMG) are a standard part of the evaluation of motor neuron disease.EMG findings in ALS combine features of acute and chronic denervation.Sensory and motor NCS are most often normal in ALS.

ALS: Differential DiagnosisOther Motor Neuron DiseasesPrimary lateral sclerosis (UMN only)Progressive muscular atrophy (LMN only)Progressive bulbar palsy NeuropathiesGB, CIDPMyopathiesPM, inclusion body myositisNM JunctionMyasthenia gravis

Neurodegenerative DiseasesParkinsons, Progressive Supranuclear Palsy, MSMalignancyPrimary/mets CNSMotor neuron syndromes with MM, Lymphoma, lung, breastToxic ExposureEtOH, heavy metalsEndocrineTSH, adrenal, pituitaryInfectiousHIV, CMV

ALS: Progression and PrognosisALS is a relentlessly progressive disorder with a clinical course that is nearly always linear, with a relatively constant slope. (ie no remissions or exacerbations)Rate of progression varies between individuals.Symptoms initially spread within the segment of onset and then to other regions in a relatively predictable pattern.

ALS: Progression and PrognosisPatients with unilateral limb onset the pattern of spread is to the contralateral limb, then to the ipsilateral U/LE, then to the contralateral remaining U/LE, and then to the bulbar muscles. In patients with bulbar onset the most common pattern of spread is to one arm and then to the contralateral arm.

ALS: Progression and PrognosisThe life-threatening aspects of ALS are neuromuscular 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 or more.

ALS: Supportive TreatmentProgressive neuromuscular respiratory failure is the most common cause of death in ALS. Intiation of noninvasive positive pressure ventilation (in patients with FVC < 50%) can prolong survival up to 20 months.5 to 10 percent of patients choose tracheostomy and permanent ventilation when respiratory compromise becomes severe.

ALS: Supportive TreatmentDysphagia poses a risk for aspiration of food, liquids, or secretions with resultant pneumonia and may also lead to malnutrition and dehydration.Symptoms can be minimized in patients who choose gastrostomy tube insertion with aggressive management of secretions.

ALS: Pharmacologic TreatmentRiluzole (Rilutek) is the only currently available medications for the treatment of ALS.Glutamate Inhibitor although precise mechanism of action in ALS is unclear.Clinical trials have shown prolonged survival of approximately 2-3 months.

ALS: Pharmacologic TreatmentPatients most likely to benefit from treatment include those who have:Definite or probable ALS by El-Escorial criteria in whom other causes of progressive muscle atrophy have been ruled out Symptoms present for less than five years Vital capacity (VC) greater than 60 percent of predicted No tracheostomy

ALS: Board Review QuestionsA 50yoM is evaluated for 4month h/o progressive R foot drop and slurred speech. PE reveals tongue weakness associated with tongue fasciculations, atrophy and +jaw jerk. R leg is atrophic w/faciculations. He has R ankle clonus and extensor plantar response. Sensory exam is normal. Most likely diagnosis is?ALSSpinal Muscle AtrophyMyasthenia GravisCervical spondylosis

ALS: Board Review Questions50yoM h/o ALS is evaluated for 6mo h/o progressive SOB. He has been unable to lie flat to sleep for several months, awakens at night and is extremely fatigued throughout the day. PE reveals diffuse fasciculations and RLE atrophy and weakness. FVC is 20% predicted. Most appropriate therapy?High flow O2RiluzoleBiPAPIVIG