CE/CME Amyotrophic Lateral Sclerosis Diagnosis and Appropriate Management

Michele Roth-Kauffman, JD, MPAS, PA-C, Jennifer Niebauer, PA-S About 15 new cases of amyotrophic lateral sclerosis (ALS), a disease of exclusion, are diagnosed each day in the United States. ALS impairs voluntary musculature, both in the extremities and the organs involved in speaking, swallowing, and breathing. Life expectancy averages two to fi ve years after diagnosis. No cure yet exists, with one approved

Credit: Chris HarveyShutterstock. Credit: medication appearing to slow the disease process. The importance Lou Gehrig, whose name is closely linked with amyotrophic lateral sclerosis (ALS), died of the of supportive measures and palliative care to optimize quality of life disease after a stellar baseball career. for patients with ALS is clear.

CE/CME INFORMATION

TARGET AUDIENCE: Th is activity has been designed sician Assistants (AAPA) Category I CME credit by the cure server; 4) complete the 10-question posttest by to meet the educational needs of physician assistants Physician Assistant Review Panel. Approval is valid recording the best answer to each question; and 5) and nurse practitioners in primary care with patients for one year from the issue date of July 2012. Partici- record their response to each of the additional eval- who may be experiencing signs or symptoms of amy- pants may submit the self-assessment at any time uation questions. otrophic lateral sclerosis (ALS). during that period. If you have any questions, e-mail CR.evaluations Th is program was planned in accordance with @qhc.com. Upon successful completion of an on- • Original Release Date: July 2012 AAPA’s CME Standards for Enduring Material Pro- line posttest, with a score of 70% or better, and the • Expiration Date: July 31, 2013 grams and for Commercial Support of Enduring completion of the online activity evaluation form, • Estimated Time to Complete Th is Activity: 1 hour Material Programs. a statement of credit will be made available imme- • Medium: Printed journal and online CE/CME Successful completion of the self-assessment is diately. required to earn Category I CME credit. Successful PROGRAM OVERVIEW: Th e primary objective of completion is defi ned as a cumulative score of at least DISCLOSURE OF UNLABELED USE: Th is educa- this educational initiative is to provide clinicians in 70% correct. tional activity may contain discussion of published primary care with the most up-to-date information and/or investigational uses of agents that are not in- regarding the diagnosis and management of ALS. ACCREDITATION STATEMENT: dicated by the FDA. AAPA, Th e NPA, and Quadrant NURSE PRACTITIONERS HealthCom Inc. do not recommend the use of any EDUCATIONAL OBJECTIVES: After completing this Th is program has been approved by the Nurse Practi- agent outside of the labeled indications. activity, the participant should be better able to: tioner Association New York State (Th e NPA) for 1.0 Th e opinions expressed in this educational • Identify ALS clinically, including the confi rmed contact hour. activity are those of the faculty and do not neces- presence of upper and lower signs sarily represent the views of AAPA, Th e NPA, or and symptoms. DISCLOSURE OF CONFLICTS OF INTEREST Quadrant HealthCom Inc. Please refer to the offi - • Discuss diagnostic procedures that can help ex- Th e faculty reported the following fi nancial relation- cial prescribing information for each product for clude disease processes other than ALS. ships or relationships to products or devices they or discussion of approved indications, contraindica- • Explain pharmacologic options intended to prolong their spouse/life partner have with commercial in- tions, and warnings. life and alleviate the symptoms of ALS. terests related to the content of this CME activity: • Describe the elements of supportive care that can Michele Roth-Kauff man, JD, MPAS, PA-C, and Jenni- DISCLAIMER: Participants have an implied respon- help optimize quality of life for the patient with ALS. fer Niebauer, PA-S, reported no signifi cant fi nancial sibility to use the newly acquired information to en- relationship with any commercial entity related to hance patient outcomes and their own professional FACULTY: Michele Roth-Kauff man, JD, MPAS, PA-C, this activity. development. Th e information presented in this ac- is a Professor and Chair of the Physician Assistant De- tivity is not meant to serve as a guideline for patient partment at Gannon University in Erie, Pennsylva- METHOD OF PARTICIPATION: Th e fee for partici- management. Any procedures, medications, or other nia; Jennifer Niebauer, PA-S, is a PA student in clini- pating and receiving CME credit for this activity is courses of diagnosis or treatment discussed or sug- cal rotations at Gannon University. $10.00. During the period July 2012 through July 31, gested in this activity should not be used by clini- 2013, participants must 1) read the learning objec- cians without evaluation of their patient’s conditions ACCREDITATION STATEMENT: tives and faculty disclosures; 2) study the education- and the possible contraindications or dangers in use, PHYSICIAN ASSISTANTS al activity; 3) go to www.clinicianreviews.com/CE review of any applicable manufacturer’s product in- Th is program has been reviewed and is approved for Courses.aspx, follow links to the posttest for this ac- formation, and comparison with recommendations a maximum of 1.0 hour of American Academy of Phy- tivity, and provide payment information via our se- of other authorities.

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myotrophic lateral ercise, nutrition, support groups, ry lateral sclerosis, progressive TABLE 1 sclerosis (ALS) is prob- and counseling, are important muscular atrophy, progressive Pathogenesis of Motor ably best known to the tools to enhance quality of life for , and pseudobulbar majority of the US pop- the patient with ALS.2 palsy.6 Neuron Degeneration A in ALS3,17,18,20,21 ulation as Lou Gehrig’s disease, Primary care providers need Primary lateral sclerosis in- named for the New York Yankee to be aware of ALS, recognize volves Genetic factors 7 who died of ALS after a stellar 17- its symptoms in their patients, (UMN) dysfunction in the limbs. Excitotoxicity year baseball career in the 1920s and manage those aff ected on Progressive muscular atrophy re- Oxidative stress and ’30s. Gradually, the general a case-by-case basis. Because sults from degeneration of the public is gaining familiarity with of the challenges in diagnostic anterior horn cells in the spinal Mitochondrial dysfunction the characteristics of ALS, a dis- evaluation, the rapidly evolving cord and is associated with lower Impaired axonal transport ease with no single identifi able nature of the disease, and the motor neuron (LMN) defi cits in Neurofilament aggregation cause and no known cure. dire prognosis of ALS, any patient the limbs. Protein aggregation About 5,600 people receive a suspected of having ALS should is a Inflammatory dysfunction diagnosis of ALS in the US each be referred immediately to a neu- progressive UMN and LMN dis- year (about 15 per day), making it rologist. Providers need to edu- order of the cranial muscles. Th is Deficits in neurotrophic factors the most common form of motor cate patients and their caregiv- condition may occasionally stay Dysfunction of signaling neuron disease.1 Most patients ers regarding the disease process isolated in the bulbar segment, pathways present with progressive muscle and ensure that patients receive but more commonly, UMN and Sources: Wijesekera and Leigh. Orphanet weakness in an extremity, which appropriate care to meet their LMN signs and symptoms spread J Rare Dis. 20093; Vance et al. Science. 200917; Sreedharan et al. Science. 200818; ultimately leads to respiratory needs and preferences. to involve other segments. Th is is Cheah et al. Curr Med Chem. 201020; failure and death. then referred to as bulbar-onset Paubel et al. Arch Neurol. 2008.21 Generally, patients with ALS ALS DEFINED ALS. Th ere have been no reports have no cognitive disability and ALS is a progressive neurodegen- of specifi c pathology in progres- Accumulating evidence suggests are aware of their physical de- erative disease that aff ects both sive bulbar palsy. that military service and smok- cline. Th ese patients are faced the upper and lower motor neu- Pseudobulbar palsy results ing may also contribute to the with important decisions as their rons. Th e disease is considered from an UMN lesion in the cor- development of ALS.11-15 Children condition worsens: Will they terminal. Although life may be ticobulbar pathway in the pyra- and siblings of ALS patients are at want nutritional support through prolonged by the one currently midal tract. It is characterized by increased risk for ALS, while mili- a gastrostomy? For respiratory available pharmacologic agent, diffi culty chewing and swallow- tary personnel have 1.5 times the assistance, will their preference no treatment option is yet capable ing, and slurred speech (mani- risk.11 be noninvasive ventilation or of stopping or reversing progres- festations that may also represent Investigation of the precise link mechanical ventilation via tra- sion of the disease.3 While ALS the initial presentation of ALS). between military service and ALS cheostomy? was once believed to be a purely Patients with pseudobulbar palsy is ongoing, but factors may in- Not only do ALS patients un- motor disorder, the accompany- may exhibit inappropriate, exces- clude intense exertion, traumatic dergo deterioration of motor ing degeneration of nonmotor sive yawning and emotional out- injuries, viral infections, and ex- brain regions, such bursts; these manifestations are posure to certain chemicals or PRIMARYPOINT as frontal and tem- referred to as emotional inconti- metals.11 Research suggests the poral cortical neu- nence.8 risk is independent of time peri- Growing evidence suggests that military rons, is considered od, years of service, or branch of service may contribute to development by some to be part EPIDEMIOLOGY service. Geographic location ap- of ALS; possible factors include traumatic of the clinicopatho- In North America, it is estimated pears to be an independent fac- injuries and exposure to chemicals. logic spectrum of that ALS aff ects 1.5 to 2.7 people tor, although there does seem to ALS.4 per 100,000 between ages 20 and be a strong association between function, but many experience Th ere are two forms of ALS: 80; most frequently, the disease deployment during the 1991 Gulf muscle cramping, generalized sporadic and familial. Sporadic presents between ages 55 and 65. War and the risk for ALS.12-14 pain, and depression. Only one ALS is by far the more common, ALS develops infrequently before Recently, smoking has been medication is currently approved accounting for 90% to 95% of age 30.3,9 implicated as a potential risk fac- to treat ALS patients, with the cases. Th e remaining 5% to 10% While no gender diff erence is tor in the disease.3,15 Certain en- benefi t of prolonging life by a few of ALS cases are of the familial apparent in patients with familial vironmental exposures have also months. In addition to symptom form, which can be autosomal- ALS, sporadic ALS predominately been recognized as a possible management, supportive mea- dominant or autosomal-reces- aff ects males more than females risk factor. In Guam, an ALS-like sures, including physical, occu- sive.5 (although the accepted ratio of syndrome has been identifi ed pational, and speech therapy, ex- 1.5:1 appears to be in decline9). among members of the Chamor- The Degenerative After age 65, men and women are ro tribe. Th is syndrome has been Michele Roth-Kauffman is a Profes- Motor Neuron Diseases equally impacted.10 linked to a neurotoxin in the seed sor and Chair of the Physician Assis- Weakness and muscle wasting of the cycad nut, a tropical plant tant Department at Gannon University in Erie, Pennsylvania; there, Jennifer characterize several degenerative RISK FACTORS endemic to the area, which was Niebauer is a PA student in clinical motor neuron diseases. In addi- Established risk factors for ALS used in the 1950s and 1960s in rotations. tion to ALS, these include prima- include age and family history. the human food supply.3,16

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ETIOLOGY FUS, and the DNA-binding pro- mate (which have been detected bination of factors is involved in Familial ALS is a genetically tein TDP-43, have all been iden- in cerebrospinal fl uid and serum the development of sporadic ALS. transmitted degenerative dis- tifi ed in cases of familial ALS.17,18 of patients with ALS), mitochon- ease. Twenty percent of cases Th e exact etiology of sporadic drial dysfunction, free radical PATHOPHYSIOLOGY involve the long arm of chromo- ALS remains unknown, but gene injury, programmed cell death, Th e pathophysiology of ALS in- some 21, which is responsible for mutations have also been impli- neurofi lament defects, viral in- volves degeneration of the UMN coding of superoxide dismutase cated, including the ANG gene21 fections, and autoimmune dys- and LMN , which leads to (SOD1). Mutations in SOD1, an and TDP-43.18 Other theories in- function19,20 (see Table 1,3,17,18,20,21 glial scarring and possible im- RNA-processing protein called clude increased levels of gluta- page 16). It is possible that a com- pairment of the glial cells’ abil-

TABLE 2 Signs and Symptoms Associated With ALS3,7,23,24 UMN signs UMN symptoms LMN signs LMN symptoms LIMB Stiffness, slowness and W eakness of hand, proximal W eakness and atrophy, arm S lowed rapid incoordination of movement, arm and leg and/or hand, leg and/or foot alternating movements hand/arm, leg/foot Foot drop D ifficulty performing activities Increased Difficulty performing P oor heel- and/or toe- of daily living “Preserved” reflexes activities of daily living walking D ifficulty manipulating small in weak/atrophic Difficulty manipulating small Poor rise from chair objects or writing muscles objects or writing Poor squat Difficulty rising from chair or floor Hoffman’s sign Gait dysfunction, difficulty Gait disorder Difficulty climbing stairs Crossed adduction turning Waddling Foot drop Upgoing toe Poor balance, frequent falls Reduced reflexes Tripping, falling Triple flexion Spontaneous clonus M uscle atrophy and Fasciculations Gait disorder Spontaneous flexor spasms fasciculations Cramps

BULBAR Increased jaw J aw stiffness with difficulty W eak masseters and/or Incomplete eye closure Jaw spasticity opening the mouth pterygoids Difficulty opening and/or F acial diparesis (may S pontaneous clenching or D ifficulty maintaining jaw closing the jaw be asymmetric) biting closure Difficulty chewing I ncreased facial Trismus F acial diparesis (may be Disarticulation of the reflexes Spontaneous jaw clonus asymmetric) temporomandibular joint when Palmomental sign Poor palatal elevation severe P oor palatal elevation Tongue weakness Poor lip closure and seal S low tongue Laryngospasm M uscle atrophy and Dysphagia movement P seudobulbar affect fasciculations Tongue weakness (inappropriate laughing, Pharyngeal muscle weakness crying, and/or yawning) Coughing and choking induced by Sialorrhea (drooling) drinking, eating, or saliva secretion D ifficulty managing (often with thin liquids, followed pharyngeal secretions by solids and thick liquids) Dysarthria Slurred, nasal and/or hoarse speech RESPIRATORY N/A N/A Tachypnea Dyspnea and/or orthopnea Reduced vocal volume Low speech volume Shortened sentences Weak cough Frequent breath pauses Sleep-disordered breathing U se of accessory respiratory F requent nocturnal muscles awakenings with dyspnea Abdominal paradox E xcessive daytime sleepiness and/or fatigue Morning Confusion Hallucinations AXIAL Absent abdominal Stiffness and imbalance Neck extension weakness Head drop reflexes T runcal extension weakness; D ifficulty maintaining erect posture bent spine Increased lumbar lordosis A bdominal protuberance Abdominal protuberance Increased lumbar lordosis Cramps Abbreviations: UMN, upper motor neuron; LMN, . Sources: Wijesekera and Leigh. Orphanet J Rare Dis. 20093; Tartaglia et al. Arch Neurol. 20077; Rowland. Muscle Nerve. 201023; Shoesmith et al. J Neurol Neurosurg Psychiatry. 2007.24

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ity to store excess glutamate.22 bulbar muscles are aff ected, re- time hypersomnolence, morning ALS aff ects the central nervous sulting in dysphagia, dysarthria, , impaired concentra- TABLE 4 system, specifi cally the anterior and dysphasia. Occasionally, tion, irritability, anorexia, mood Differential Diagnosis 3,44 horn cells in the and patients encounter bladder dys- changes, dyspnea, orthopnea, of ALS the cranial nerve nuclei (X, XI, function (urgent micturition), and disturbed sleep; or they may Cerebral lesions XII) of the LMNs, and the corti- sensory symptoms, and cognitive experience type 2 respiratory fail- cospinal tract and corticobulbar symptoms (eg, , parkin- ure.28,29 Skull base lesions pathway of the UMNs. Bulbar sonism).26 Multisystem involve- Patients with axial symptoms O culopharyngeal muscular and limb muscles innervated ment is possible. Ultimately, re- of ALS present with neck weak- dystrophy by LMNs are subject to atrophy, spiratory compromise or other ness and may complain of pos- Primary lateral sclerosis whereas cognition, coordination, pulmonary complications ensue, terior neck pain or strain with a sensation, the oculomotor sys- representing a primary cause of gradually worsening tendency of tem, and sphincters are typically mortality in ALS patients.3,24 the head to tip forward. Th ese pa- H uman T-cell leukemia virus spared.3 In bulbar-onset ALS, patients tients often support the chin with fi rst notice symptoms of dys- one hand. Th ose with axial trun- C ervical spondylotic CLINICAL FEATURES phasia and dysphagia. Th ey may cal weakness often complain of myelopathy In most patients, ALS symptoms complain of slurred speech, nasal diffi culty maintaining erect pos- Other cervical characterize either limb onset or or low-volume speech, and/or in- ture when standing and of stoop- Foramen magnum lesions bulbar onset (see Table 2,3,7,23,24 hibited tongue mobility. Th e risk ing as they walk. Some patients Intrinsic and extrinsic tumors page 17), with limb onset being for aspiration is increased. Th e support the trunk by placing their the more common (about 75% vs majority of patients with bulbar- hands in their front pants pockets Syringomyelia about 25% of cases, respective- onset ALS experience sialorrhea or on their upper thighs. Th ey Conus lesions 1 ly). Typically, patients with limb- (excessive drooling) because may report some relief when Lumbosacral radiculopathy onset ALS complain of rapidly they have diffi culty swallowing pushing a grocery cart.7,23,24 progressive, asymmetric weak- their saliva. In most patients, Symptoms of ALS can be pres- Inclusion body myositis ness in an extremity, followed by mild UMN-type bilateral facial ent for weeks or months before Myasthenia gravis focal muscle atrophy with cramp- weakness aff ects the lower half of a patient consults with a health C ramp/fasciculation/myokymia ing and fasciculations, and even- the face.3 As is the case with limb- care provider. Th e average time syndromes tually, spasticity. Weakness gen- onset ALS, bulbar-onset ALS pro- span from onset of initial symp- Hereditary spastic paraparesis erally begins in one hand, arm, gresses to respiratory compro- toms to diagnosis of ALS is about foot, or leg. Patients may notice mise.27 one year.1 Due to the unpredict- M ultifocal motor neuropathy with conduction block increased episodes of tripping, In less than 3% of patients with able pattern of progression and clumsiness when they run or ALS, presentation begins with variability of symptoms among K ennedy’s disease walk, a “dropped foot” gait, and/ respiratory weakness and no patients, it is diffi cult to approxi- (spinobulbar muscular or a decline in manual dexterity.25 signifi cant limb or bulbar symp- mate a time frame for symptom atrophy) Th e weakness often develops toms.24,28 Patients with respirato- progression; for some patients, Lead intoxication insidiously; patients may notice ry-onset ALS experience symp- the disease progresses slowly, Lyme disease that symptoms are exacerbated toms associated with nocturnal while others deteriorate rapidly.30 3 A dult-onset Tay-Sachs disease by cold weather. Eventually, the hypoventilation, including day- (patients younger than 40) PHYSICAL EXAMINATION Sources: Wijesekera and Leigh. Orphanet FINDINGS J Rare Dis. 20093; Baek and Desai. Pract TABLE 3 At onset, the typical presentation Neurol. 2007.44 37-39 Complications of ALS of ALS includes muscle weakness Laryngospasm or other laryngeal dysfunction in one limb as well as visible fas- UMN disorder, leading to slow, N utritional deficiency resulting from dysphagia (possibly ciculations. As the disease pro- slurred speech or speech with necessitating gastrostomy tube placement) gresses, focal wasting of muscle a nasal quality. Tongue fascicu- groups occurs in all four extremi- lations will be present, as will R espiratory compromise (with a potential need for mechanical ventilation) ties. Particularly involved are the atrophy and diminished mobil- muscles of the hands, forearms, ity of the tongue.33 Th e gag re- Aspirational pneumonia or shoulders in the upper limbs; fl ex remains intact, even brisk, Pulmonary embolism and of the proximal thigh or dis- but weakness may occur in the D ecubitus ulcers from prolonged bedridden status and tal foot muscles in the lower muscles of the soft palate.3 Facial wheelchair use limbs.31 Deep tendon refl exes are weakness is sometimes seen late Depression symmetrically brisk. Spasticity, in the disease, as evidenced by Anxiety evident in the upper limbs, may diffi culty sealing the lips or puff - present as increased tone.32 ing out the cheeks. Th e jaw jerk Fatigue In patients with bulbar dys- will be brisk, indicating that cra- Increased risk for suicide function, dysarthria may arise nial nerve V is intact.34 Sources: Rabkin et al. . 200537; Vignola et al. Eur J Neurol. 200838; Fang et al. from either LMN pathology or A pseudobulbar aff ect, which Brain. 2008.39 pseudobulbar palsy caused by a is best described as emotional

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lability, may be present. Th e pa- tient may have a history of exag- FIGURE gerated expression of emotion, such as uncontrollable crying, T2-weighted MRI images showing white matter edema (left) and peduncular edema (right), laughing, or both.35 Cognition, both characteristic findings in the patient with ALS. coordination, sensation, the ocu- lomotor system, and sphincters are generally spared. However, cases of frontotemporal demen- tias coexisting with ALS have been reported; aff ected patients exhibit cognitive impairment, compulsive behaviors, and per- sonality changes, and they may experience shorter survival.4,24,36 Evidence of known complica- tions of ALS may also be noted during the physical examination; see Table 337-39 (page 18).

DIAGNOSIS OF ALS In current research, use of struc- tural MRI, magnetic resonance spectroscopy, and diff usion ten- sor imaging is being examined to detect thinning in the primary Courtesy of Keith Hentel, MD, Chief, Emergency/Musculoskeletal Imaging, Department of Radiology, NewYork–Presbyterian Hospital; and Associate motor cortex, fractional anisot- Professor of Clinical Radiology, Weill Cornell Medical College, New York. ropy in the corpus callosum, patterns of gray and white mat- multifocal motor neuropathy, dures that are useful in excluding among ALS patients and may be ter atrophy, and other proposed lead intoxication, and Lyme dis- other disease processes include hastened with advancing age, fe- diagnostic markers for ALS.40-43 ease.45 blood and cerebrospinal fl uid male gender, presence of bulbar However, no single specifi c di- Imaging studies are not re- (CSF) samples,3,44 four-limb elec- features, and absence of a signifi - agnostic test has yet been proven quired in ALS cases that have tromyography (EMG),44 nerve cant other.37,53,54 to identify ALS; rather, it remains clinically defi nite disease with conduction studies, motor unit Th e average life span for a a disease of exclusion (see Table bulbar or pseudobulbar onset.47 number estimations, and muscle patient with limb-onset ALS is 4,3,44 page 18). For a confi rmed Otherwise, the essential role of biopsies.47 two to fi ve years from diagnosis, diagnosis of ALS to be made, the neuroimaging is to exclude a Autopsy results of patients whereas patients aff ected by the patient must display: treatable structural lesion that with ALS demonstrate: bulbar form usually succumb • Evidence of LMN degenera- may mimic ALS by producing • Neuron loss, especially in within six to 18 months.30,53 In tion as found through clini- UMN and LMN signs in varying lumbar and cervical enlarge- patients who present with respi- cal, neuropathologic, or elec- degrees.48 ments ratory symptoms, Shoesmith et trophysiological examination Typically, MRI of the head and • Nonexistent or atrophic neu- al24 have reported a mean time • UMN degeneration detected spine is ordered in patients with rons in the motor nuclei of of 14.9 months from initial symp- suspected ALS (see the pons and medulla, and in toms to need for full-time venti- PRIMARYPOINT fi gure, above); MRI the anterior horn cells of the lation, and of 27.0 months from can reveal lesions spinal cord symptom onset to death. Advance directives, end-of-life care, and in the corticospinal • Degeneration of the lateral Advance directives, end-of-life respiratory and nutritional management tracts that occur columns of the spinal cord, care, and respiratory and nutri- should be discussed at the time of in ALS. Th e most and tional management become es- diagnosis or shortly thereafter. characteristic fi nd- • Atrophy of the ventral sential issues during late stages ing on T2-weighted roots.31,51 of ALS; thus, they should be dis- by clinical examination, and MRI is hyperintensity of the cor- cussed with patients and their • Progressive spread of signs or ticospinal tracts, which is visual- PROGNOSIS relatives at the time of diagnosis symptoms within a region or ized best in the brain and brain- Th e overall fi ve-year survival rate or shortly thereafter. to other regions.3,45-47 stem, and to a lesser extent in the for patients with ALS has been re- Other disease processes that spinal cord.49 Decreased signal ported between 7% and 14%,52,53 TREATMENT might explain the signs of UMN intensity in the motor cortex has and the mortality rate rises in pa- Pharmacologic Options and/or LMN degeneration must been reported on MRI in cases of tients older than 75 and in those Th ere are currently no treatments be excluded, such as cervical spi- ALS.50 with bulbar signs.30 Th e rate of to halt the progression of ALS or nal disease, myasthenia gravis, Additional diagnostic proce- disease progression varies greatly to reverse the disease process.

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Riluzole, currently the only FDA- identifi ed accurately, using ap- tarily, is reduced.60 As breathing means may be needed. Loss of approved drug for treatment of propriate clinical tools, before becomes increasingly diffi cult, physical strength and mobil- ALS, has been shown to slow the SSRIs (eg, citalopram) or other patients may require respiratory ity and diffi culties with speech, loss of muscle strength and to medications (eg, amitriptyline) support. Noninvasive ventilation, swallowing, and breathing can prolong life by an average of two are prescribed3; these agents using either continuous or bilevel challenge even the strongest pa- to three months.55 Riluzole targets should not be used presumptive- positive airway pressure, may be tient’s coping skills; even more and blocks glutamate transport- ly,37 as estimates of prevalence of implemented early in patients diffi cult can be the increased ers on the presynaptic neuron, depression among ALS patients with respiratory-onset ALS, and dependence on caregivers, the decreasing glutamate release and range from 2% to 75%.2,37,38,54 Es- later in the disease process for loss of income, and the fi nan- reducing excitotoxicity20 (ie, over- timates of anxiety prevalence in other patients, to prevent apnea cial burdens incurred in health stimulation of the postsynaptic these patients range from 0% to and hypoventilation.28,62 Mechan- care– related expenses. In some receptors). Th ese eff ects support 30%, refl ecting the importance ical ventilation via tracheostomy patients, the severity of disease, the theory that ALS may result of accurate diagnosis before lo- is the most invasive method to the lack of eff ective treatments, from excess glutamate and help razepam or other agents are pre- address respiratory dysfunction and the loss of independence to explain the increased levels scribed.3,38 in patients with ALS; however, may trigger thoughts of suicide of glutamate found in the serum Promising results have been like noninvasive ventilation, noc- or the wish to “hasten death.”37,39 and CSF of ALS patients.19 reported in the use of modafi nil turnal mechanical ventilation has Th e importance of counseling, Riluzole is typically dosed at to manage fatigue in patients with been shown to extend survival in support groups, spirituality or 50 mg by mouth twice a day, al- ALS.59 For patients with pseudo- these patients.28,63,64 religion, and palliative care, from though 200-mg/d doses have bulbar aff ect, Diaphragm pacing stimula- early in the disease process, can- also been examined in clinical 20 mg/ sulfate 10 mg is tion (DPS) has emerged as a not be overstated.3,37 trials.20,55 Generally, the drug is an FDA-approved treatment.35 possible alternative to mechani- Some of these considerations well tolerated, with common ad- Vitamins and other supple- cal ventilation for ALS patients. may also be of benefi t to spouses verse eff ects including asthenia, ments, including creatine, vita- Th e pacing system consists of a and other nonpaid caregivers of nausea, gastrointestinal upset, min E, coenzyme Q10, and ace- battery-operated external pulse the patient with ALS, at least half and abnormal liver test results. tylcysteine, have not been shown generator with electrodes placed of whom report feeling physical- Liver function should be moni- to improve survival in this patient after laparoscopic mapping on ly or psychologically unwell.37,68 tored regularly during riluzole population.3 the diaphragm.65 Natural respira- Even when professional nursing therapy, with elevations in serum tion is mimicked as stimulation services or hospice support are alanine transferase of particular Nonpharmacologic from the external pulse generator available, caregivers often de- concern.55 Interventions prompts the diaphragm to con- vote 12 hours or more per day to Additional agents have been Supportive measures for ALS in- tract. Researchers have shown nonprofessional patient care.69 used to reduce muscle spastic- clude physical and occupational that the minimally invasive sur- Strategies that support the care- therapy. In speech gery (including use of general giver can reduce the patient’s PRIMARYPOINT and language anesthesia) required to install perception of burden in that indi- therapy, breathing the DPS system can be safely per- vidual.37 Use of diaphragm pacing stimulation, and relaxation pat- formed on patients with ALS, and which mimics natural respiration, may terns can be used its use can delay the need for a CONCLUSION delay the need for mechanical to correct ineff ec- ventilator by 24 months.65,66 Use Th e exact cause or causes of ALS ventilation by as much as 24 months. tive compensa- of the DPS device was granted remain unknown, making it dif- tory behaviors and FDA approval in 2011, under the fi cult to predict who will present ity, muscle cramping and fas- help patients “economize” their Humanitarian Device Exemption with a disease that appears im- ciculations, and the associated speaking eff orts.60 program.67 possible to prevent. Health care pain some patients experience, Nutritional support is also im- providers in any practice should attributable in part to lack of ac- portant in patients who have dif- Addressing Quality of Life be aware of the signs of ALS and tivity and/or infl ammation.56 For fi culty swallowing, although this For the patient with ALS, quality familiar with its symptoms in or- spasticity, tizanidine or baclofen can be alleviated somewhat by of life is an important consider- der to provide optimal manage- (orally, a maximum of 20 mg in changes in posture (eg, lower- ation throughout disease man- ment for potentially aff ected pa- divided doses; or lower doses ad- ing the chin before attempting to agement. According to numerous tients. ministered intrathecally, for pa- swallow) and by use of thickened research teams, quality of life for Any cause for suspicion of ALS tients who experience sedation fl uids; those with immobility of these patients depends less on (ie, recent-onset limb weakness and fatigue with high oral dos- the tongue may fi nd swallowing physical function and strength or atrophy; diffi culty swallowing es56,57) are often used. Carbam- easier with the head tilted back.60 and more on social relationships, or speaking) warrants immedi- azepine and phenytoin are most Once oral alimentation is no lon- existential issues, and spiritual- ate patient referral to a neurolo- commonly used to relieve mus- ger possible, enteral tube feed- ity.2,37,54 A high level of quality of gist. Evaluation should include a cle cramps.56 For some patients, ing is an option that may prolong life can be sustained in patients comprehensive history and phys- NSAIDs may be adequate to con- survival.60,61 with ALS, despite the decline they ical examination, with emphasis trol moderate to severe pain, but As ALS progresses, dysphagia experience in physical function. on the musculoskeletal and neu- others may require opioids.2,56,58 may be aggravated as the abil- Addressing depression and rologic exams; MRI of the spine Depressive disorders must be ity to cough, refl exively or volun- anxiety by nonpharmacologic and head, analysis of blood and

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