Amyotrophic Lateral Sclerosis¶
VERSION: 1.1 CREATED: January 27, 2026 REVISED: January 30, 2026 STATUS: Draft - Pending Review
DIAGNOSIS: Amyotrophic Lateral Sclerosis (ALS) / Motor Neuron Disease
ICD-10: G12.21 (Amyotrophic lateral sclerosis), G12.20 (Motor neuron disease, unspecified), G12.29 (Other motor neuron disease)
SCOPE: Comprehensive outpatient-focused management of ALS including diagnostic workup, El Escorial/Awaji criteria application, disease-modifying therapy (riluzole, edaravone, AMX0035), symptomatic management (sialorrhea, spasticity, pseudobulbar affect, pain, dyspnea), respiratory monitoring with BiPAP timing, nutritional support with PEG timing, multidisciplinary clinic model, and palliative care integration. Excludes primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), and pediatric motor neuron disease.
CLINICAL SYNONYMS: Lou Gehrig's disease, motor neuron disease (MND), amyotrophic lateral sclerosis, classical ALS, bulbar-onset ALS, limb-onset ALS, motor neurone disease, Charcot disease, anterior horn cell disease, progressive bulbar palsy, upper and lower motor neuron disease, ALS/MND, sporadic ALS, familial ALS, SOD1-ALS, C9orf72-ALS
KEY CLINICAL FEATURES: - Progressive combined upper motor neuron (UMN) AND lower motor neuron (LMN) signs - UMN signs: spasticity, hyperreflexia, Babinski sign, clonus - LMN signs: weakness, atrophy, fasciculations, hyporeflexia - Typically asymmetric onset; spreads contiguously - Bulbar-onset (25%): dysarthria, dysphagia, tongue fasciculations - Limb-onset (75%): focal limb weakness, foot drop, grip weakness - Cognitive impairment in 35-50%; frontotemporal dementia in 10-15% - Preserved: Eye movements, sphincter function (until late)
MEDIAN SURVIVAL: 3-5 years from symptom onset; 2-3 years from diagnosis
EL ESCORIAL DIAGNOSTIC CRITERIA (Revised):
| Category | UMN + LMN Signs Required |
|---|---|
| Clinically Definite ALS | 3 regions (bulbar, cervical, thoracic, lumbosacral) |
| Clinically Probable ALS | 2 regions with UMN rostral to LMN |
| Clinically Probable - Lab Supported | 1 region with EMG evidence in 2 limbs |
| Clinically Possible ALS | 1 region only, or UMN only in 2+ regions |
AWAJI-SHIMA CRITERIA (2008): EMG findings of acute denervation and chronic reinnervation are equivalent to clinical LMN signs. Fasciculation potentials with chronic neurogenic changes support diagnosis.
PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting
MULTIDISCIPLINARY CARE IS ESSENTIAL
ALS patients managed in multidisciplinary clinics have improved survival (7-10 months) and better quality of life. Coordinate neurology, pulmonology, nutrition, PT, OT, speech, respiratory therapy, social work, and palliative care.
═══════════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════════
1. LABORATORY WORKUP¶
1A. Essential/Core Labs¶
| Test | ED | HOSP | OPD | ICU | Rationale | Target Finding |
|---|---|---|---|---|---|---|
| CBC with differential (CPT 85025) | STAT | STAT | ROUTINE | STAT | Baseline; exclude infection | Normal |
| CMP (CPT 80053) | STAT | STAT | ROUTINE | STAT | Baseline; monitor for riluzole hepatotoxicity | Normal; ALT <3x ULN |
| TSH (CPT 84443) | URGENT | ROUTINE | ROUTINE | URGENT | Thyroid disease can mimic weakness | Normal |
| Vitamin B12 (CPT 82607) | URGENT | ROUTINE | ROUTINE | URGENT | B12 deficiency causes myelopathy | >300 pg/mL |
| CPK (CPT 82550) | URGENT | ROUTINE | ROUTINE | URGENT | Often mildly elevated in ALS; rule out myopathy | Mildly elevated OK; <5x ULN |
| ESR (CPT 85652) / CRP (CPT 86140) | URGENT | ROUTINE | ROUTINE | URGENT | Inflammatory markers | Normal or mildly elevated |
| Hemoglobin A1c (CPT 83036) | - | ROUTINE | ROUTINE | - | Diabetic neuropathy in differential | <6.5% |
| Fasting lipid panel (CPT 80061) | - | ROUTINE | ROUTINE | - | Cardiovascular risk assessment | LDL goal per guidelines |
| Serum protein electrophoresis (SPEP) (CPT 86334) | - | ROUTINE | ROUTINE | - | Exclude monoclonal gammopathy | No monoclonal spike |
| Urinalysis (CPT 81003) | STAT | ROUTINE | ROUTINE | STAT | Baseline; UTI assessment | Normal |
1B. Extended Workup (Second-line)¶
| Test | ED | HOSP | OPD | ICU | Rationale | Target Finding |
|---|---|---|---|---|---|---|
| HIV (CPT 87389) | - | ROUTINE | ROUTINE | - | HIV-associated motor neuron disease | Negative |
| Lyme serology (CPT 86618) (endemic areas) | - | ROUTINE | ROUTINE | - | Lyme disease causes neuropathy | Negative |
| Copper (CPT 82525) and ceruloplasmin (CPT 82390) | - | ROUTINE | ROUTINE | - | Wilson disease in younger patients | Normal |
| Parathyroid hormone (PTH) (CPT 83970) | - | ROUTINE | ROUTINE | - | Hyperparathyroidism causes weakness | Normal |
| Anti-GM1 antibodies (CPT 86255) | - | ROUTINE | ROUTINE | - | Multifocal motor neuropathy (treatable mimic) | Negative |
| Anti-MAG antibodies (CPT 86255) | - | ROUTINE | ROUTINE | - | Demyelinating neuropathy | Negative |
| Lead level (CPT 83655) | - | EXT | EXT | - | Lead neuropathy mimics ALS | <10 mcg/dL |
| Hexosaminidase A (CPT 82762) | - | EXT | EXT | - | Adult Tay-Sachs (rare mimic) | Normal activity |
| Very long chain fatty acids (CPT 82726) | - | EXT | EXT | - | Adrenomyeloneuropathy (X-linked) | Normal |
| Serum immunofixation (CPT 86334) | - | ROUTINE | ROUTINE | - | Paraprotein-associated neuropathy | No monoclonal protein |
1C. Rare/Specialized (Refractory or Atypical)¶
| Test | ED | HOSP | OPD | ICU | Rationale | Target Finding |
|---|---|---|---|---|---|---|
| SOD1 genetic testing (CPT 81405) | - | EXT | EXT | - | Familial ALS (10%); affects prognosis and therapy | Document mutation |
| C9orf72 repeat expansion (CPT 81401) | - | EXT | EXT | - | Most common familial ALS mutation; FTD link | <30 repeats normal |
| ALS gene panel (FUS, TARDBP, etc.) (CPT 81479) | - | EXT | EXT | - | Familial ALS with family history | Document variants |
| Muscle biopsy (CPT 88305) | - | EXT | EXT | - | Only if myopathy suspected | Neurogenic changes |
| CSF analysis (CPT 89051) | - | EXT | EXT | - | Atypical cases; exclude inflammatory | Protein mildly elevated OK |
| Anti-voltage-gated calcium channel Ab (CPT 86255) | - | EXT | EXT | - | Lambert-Eaton syndrome | Negative |
| Anti-acetylcholine receptor Ab (CPT 86235) | - | EXT | EXT | - | Myasthenia gravis | Negative |
2. DIAGNOSTIC IMAGING & STUDIES¶
2A. Essential/First-line¶
| Study | ED | HOSP | OPD | ICU | Timing | Target Finding | Contraindications |
|---|---|---|---|---|---|---|---|
| EMG (CPT 95886) with nerve conduction studies (CPT 95907-95913) | - | URGENT | ROUTINE | URGENT | At diagnosis; within 2 weeks | Widespread denervation (3+ regions), fibrillations, fasciculations, chronic reinnervation; normal sensory studies | Anticoagulation (relative) |
| MRI brain without contrast (CPT 70551) | - | ROUTINE | ROUTINE | ROUTINE | At diagnosis | No mass, stroke, or demyelination | Pacemaker |
| MRI cervical spine without contrast (CPT 72141) | - | ROUTINE | ROUTINE | ROUTINE | At diagnosis | No cord compression; mild spondylosis OK | Pacemaker |
| Chest X-ray (CPT 71046) | STAT | STAT | ROUTINE | STAT | Baseline; aspiration screen | Clear or evidence of aspiration | None |
| Pulmonary function tests (FVC sitting and supine) (CPT 94010) | - | ROUTINE | ROUTINE | - | Baseline respiratory status | FVC >80% predicted | Severe bulbar dysfunction |
2B. Extended¶
| Study | ED | HOSP | OPD | ICU | Timing | Target Finding | Contraindications |
|---|---|---|---|---|---|---|---|
| MRI thoracic/lumbar spine (CPT 72146/72148) | - | ROUTINE | ROUTINE | - | If thoracic/lumbosacral symptoms predominant | Exclude cord compression | Pacemaker |
| Videofluoroscopic swallow study (VFSS) (CPT 74230) | - | URGENT | ROUTINE | - | Bulbar symptoms; dysphagia | Quantify aspiration risk | Severe aspiration (relative) |
| Fiberoptic endoscopic evaluation of swallowing (FEES) (CPT 92612) | - | URGENT | ROUTINE | - | Alternative to VFSS | Laryngeal function, aspiration | Severe nasal obstruction |
| Sleep study (polysomnography) (CPT 95810) | - | ROUTINE | ROUTINE | - | Suspected nocturnal hypoventilation | Assess for REM hypoventilation, AHI | None |
| Sniff nasal inspiratory pressure (SNIP) | - | ROUTINE | ROUTINE | - | More sensitive for bulbar patients | >40 cmH2O normal | Nasal obstruction |
| Arterial blood gas (CPT 82803) | STAT | STAT | EXT | STAT | Acute respiratory failure | pH, pCO2, pO2 | Severe coagulopathy |
2C. Rare/Specialized¶
| Study | ED | HOSP | OPD | ICU | Timing | Target Finding | Contraindications |
|---|---|---|---|---|---|---|---|
| Transcranial magnetic stimulation (TMS) (CPT 95928) | - | EXT | EXT | - | Research; UMN localization | Prolonged central motor conduction time | Seizure history, pacemaker |
| PET-FDG brain (CPT 78816) | - | EXT | EXT | - | Cognitive symptoms, FTD evaluation | Frontotemporal hypometabolism | Unable to cooperate |
| Neuropsychological testing (CPT 96132) | - | ROUTINE | ROUTINE | - | Cognitive concerns; FTD screening | Document cognitive profile | Severe dysarthria (limited) |
| Diaphragm ultrasound (CPT 76604) | - | EXT | ROUTINE | EXT | Assess diaphragm function | Reduced excursion | None |
| Maximum inspiratory/expiratory pressure | - | ROUTINE | ROUTINE | - | Additional respiratory metrics | MIP >60 cmH2O; MEP >40 cmH2O | Poor mouth seal |
3. TREATMENT¶
CRITICAL: ALS is a progressive, incurable disease. Treatment goals are to slow progression, manage symptoms, maintain function, and optimize quality of life. Early palliative care integration is essential.
3A. Disease-Modifying Therapy¶
| Treatment | Route | Indication | Dosing | Pre-Treatment Requirements | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|---|
| Riluzole (Rilutek) | PO | Slows disease progression; extends survival 2-3 months | 50 mg :: PO :: BID :: 50 mg PO BID; take 1 hour before or 2 hours after meals for best absorption | Baseline LFTs | ALT >5x ULN; hepatic impairment | LFTs monthly x 3 months, then q3 months; CBC if neutropenia suspected | - | ROUTINE | ROUTINE | - |
| Edaravone (Radicava) - IV formulation | IV | Antioxidant; slows functional decline in selected patients | 60 mg :: IV :: daily (cycle) :: Initial cycle: 60 mg IV daily x 14 days, then 14 days off; subsequent cycles: 60 mg IV daily x 10 of 14 days, then 14 days off | Baseline renal function, IV access established | Hypersensitivity to edaravone or sodium bisulfite | Infusion reactions; renal function; gait (sulfite sensitivity) | - | ROUTINE | ROUTINE | - |
| Edaravone oral suspension (Radicava ORS) | PO | Oral alternative to IV edaravone | 105 mg :: PO :: daily (cycle) :: Initial cycle: 105 mg PO daily x 14 days, then 14 days off; subsequent cycles: 105 mg PO daily x 10 of 14 days, then 14 days off | Baseline renal function | Hypersensitivity to edaravone or sodium bisulfite | Infusion reactions; renal function; gait (sulfite sensitivity) | - | ROUTINE | ROUTINE | - |
| ~~AMX0035 / Relyvrio (sodium phenylbutyrate-taurursodiol)~~ | PO | WITHDRAWN — Voluntarily removed from US market April 2024 after PHOENIX trial failed to confirm benefit | N/A | N/A | N/A | N/A | - | - | - | - |
| Tofersen (Qalsody) - for SOD1 mutations | IT | SOD1-ALS only; reduces SOD1 protein | 100 mg :: IT :: monthly :: Loading: 100 mg IT on Days 1, 15, 29; Maintenance: 100 mg IT q28 days | SOD1 gene mutation confirmed; lumbar access | No SOD1 mutation; contraindication to IT injection | Neurofilament levels; CSF analysis; myelopathy monitoring | - | ROUTINE | ROUTINE | - |
3B. Symptomatic Treatments¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Glycopyrrolate | PO | Sialorrhea (excess saliva) | 1 mg :: PO :: TID :: Start 1 mg PO TID; may increase to 2 mg TID; max 8 mg/day | Narrow-angle glaucoma; urinary retention; GI obstruction | Dry mouth (paradoxical thick secretions), constipation, urinary retention | - | ROUTINE | ROUTINE | - |
| Atropine 1% ophthalmic drops (sublingual) | SL | Sialorrhea (rescue) | 1-2 drops :: SL :: q4-6h PRN :: 1-2 drops sublingual q4-6h as needed; max 4 doses/day | Narrow-angle glaucoma; cardiac arrhythmia | HR, dry mouth, urinary retention | - | ROUTINE | ROUTINE | - |
| Scopolamine transdermal patch | TOP | Sialorrhea (continuous) | 1.5 mg :: TOP :: q72h :: Apply 1.5 mg patch behind ear; replace every 72 hours | Narrow-angle glaucoma; urinary retention; GI obstruction | Confusion (especially elderly), dry mouth, constipation | - | ROUTINE | ROUTINE | - |
| Botulinum toxin A (salivary gland injection) | IM | Refractory sialorrhea | 30-50 units per parotid :: IM :: q3 months :: 30-50 units per parotid gland + 10-20 units per submandibular gland (total 80-140 units); effects last 3-4 months | Hypersensitivity; neuromuscular disease (use cautiously) | Dysphagia worsening (rare); dry mouth | - | - | ROUTINE | - |
| Dextromethorphan-quinidine (Nuedexta) | PO | Pseudobulbar affect (PBA) | 20/10 mg :: PO :: daily :: Start 20/10 mg (DM/Q) daily x 7 days, then increase to 20/10 mg BID | QT prolongation; concurrent quinidine or CYP2D6 substrates; hepatic impairment | Baseline ECG; QTc monitoring; avoid with other QT-prolonging drugs | - | ROUTINE | ROUTINE | - |
| Baclofen | PO | Spasticity | 5 mg :: PO :: TID :: Start 5 mg PO TID; increase by 5 mg/dose q3 days; max 80 mg/day in divided doses | Abrupt withdrawal (risk of seizures, hallucinations) | Sedation, weakness (may unmask underlying weakness); taper to discontinue | STAT | ROUTINE | ROUTINE | STAT |
| Tizanidine | PO | Spasticity (alternative to baclofen) | 2 mg :: PO :: qHS :: Start 2 mg qHS; may increase by 2-4 mg q6-8h; max 36 mg/day | Concurrent CYP1A2 inhibitors (ciprofloxacin, fluvoxamine); hepatic impairment | LFTs at baseline, 1 month, 3 months; sedation, hypotension, dry mouth | - | ROUTINE | ROUTINE | - |
| Gabapentin | PO | Muscle cramps; neuropathic pain | 300 mg :: PO :: qHS :: Start 300 mg qHS; titrate by 300 mg/day q1-3 days; max 3600 mg/day divided TID | Severe renal impairment (adjust dose) | Sedation, dizziness; reduce dose if CrCl <60 | - | ROUTINE | ROUTINE | - |
| Mexiletine | PO | Muscle cramps (refractory) | 150 mg :: PO :: BID :: Start 150 mg PO BID; may increase to 300 mg BID; max 1200 mg/day | Cardiogenic shock; 2nd/3rd degree AV block without pacemaker | Baseline ECG; monitor for arrhythmia; GI upset | - | ROUTINE | ROUTINE | - |
| Quinine sulfate | PO | Muscle cramps (limited use) | 200-300 mg :: PO :: qHS :: 200-300 mg PO at bedtime; FDA warns against off-label use for cramps | Thrombocytopenia; G6PD deficiency; prolonged QT; myasthenia | CBC, cardiac rhythm; FDA black box warning for thrombocytopenia | - | - | EXT | - |
| Lorazepam | PO/SL | Anxiety; dyspnea (end of life) | 0.5 mg :: PO/SL :: q8h PRN :: 0.5-1 mg PO/SL q8h PRN for anxiety or dyspnea; use low doses due to respiratory depression risk | Severe respiratory insufficiency (relative); acute narrow-angle glaucoma | Respiratory status, sedation; paradoxical agitation | - | ROUTINE | ROUTINE | ROUTINE |
| Morphine | PO/SL | Dyspnea (palliative) | 2.5 mg :: PO/SL :: q4h PRN :: Start 2.5-5 mg PO/SL q4h PRN for dyspnea; titrate to comfort; may reduce respiratory distress without significantly worsening ventilation | Active respiratory failure without comfort focus | Respiratory rate, comfort, sedation | - | ROUTINE | ROUTINE | ROUTINE |
| Modafinil | PO | Fatigue | 100 mg :: PO :: qAM :: Start 100 mg PO every morning; may increase to 200 mg; avoid afternoon dosing | Hypersensitivity; cardiac arrhythmia | Headache, insomnia, cardiac monitoring if history | - | - | ROUTINE | - |
| Amitriptyline | PO | Sialorrhea; insomnia; depression | 10 mg :: PO :: qHS :: Start 10 mg PO qHS; increase by 10 mg weekly; max 75-100 mg qHS | Cardiac conduction abnormality; recent MI; urinary retention | ECG if dose >50 mg; anticholinergic effects; sedation | - | ROUTINE | ROUTINE | - |
| Sertraline | PO | Depression; anxiety | 25 mg :: PO :: daily :: Start 25 mg PO daily; increase by 25-50 mg q1-2 weeks; max 200 mg/day | Concurrent MAOIs; caution with QT-prolonging drugs | Suicidality (first weeks), GI upset, sexual dysfunction | - | ROUTINE | ROUTINE | - |
3C. Respiratory Support¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| BiPAP (noninvasive ventilation) | INH | FVC <50% predicted OR symptoms of nocturnal hypoventilation | IPAP 8-12 cmH2O; EPAP 4-6 cmH2O :: INH :: nightly/continuous :: Start with nocturnal use; IPAP 8-12, EPAP 4-6; titrate for comfort; increase time as tolerated; extend to daytime as needed | Severe bulbar dysfunction with aspiration (relative); inability to clear secretions | Comfort, adherence, transcutaneous CO2 or ABG, mask fit | - | URGENT | ROUTINE | STAT |
| Mechanical insufflation-exsufflation (Cough Assist) | - | Weak cough; peak cough flow <270 L/min | +40/-40 cmH2O :: — :: 2-4 cycles, 2-4 times daily :: Set insufflation +40 cmH2O, exsufflation -40 cmH2O; 2-4 cycles per session; 2-4 sessions daily; use before meals and PRN | Bullous emphysema; pneumothorax | Secretion clearance, respiratory status | - | URGENT | ROUTINE | STAT |
| Portable suction | - | Secretion management | N/A :: — :: PRN :: Oral or pharyngeal suction PRN for secretion management | None | Secretion burden, mucosal trauma | STAT | STAT | ROUTINE | STAT |
| Oxygen supplementation | INH | Hypoxemia | 1-4 L/min NC PRN :: INH :: PRN :: Use cautiously; O2 may suppress respiratory drive; BiPAP preferred; use only for hypoxemia with BiPAP | May suppress respiratory drive in hypercapnic patients | SpO2, pCO2, respiratory rate | STAT | STAT | ROUTINE | STAT |
| Diaphragm pacing (NeuRx) | - | Diaphragm weakness | Surgical implantation :: — :: :: Laparoscopic implantation of intramuscular diaphragm electrodes; controversial efficacy; FDA approved but limited evidence | Severe diaphragm atrophy; unable to tolerate surgery | Diaphragm function, surgical complications | - | - | EXT | - |
3D. Nutritional Support¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Oral nutritional supplements | PO | Weight loss; inadequate oral intake | 1-3 supplements daily :: PO :: daily :: High-calorie, high-protein supplements (e.g., Ensure Plus, Boost Plus) 1-3 daily between meals | Aspiration risk | Weight, caloric intake, albumin | - | ROUTINE | ROUTINE | - |
| Thickened liquids | PO | Dysphagia with thin liquid aspiration | Nectar to honey thick consistency :: PO :: with all liquids :: Thicken all thin liquids per SLP recommendation; nectar, honey, or pudding thick consistency | None | Hydration status, swallow function | - | ROUTINE | ROUTINE | - |
| Percutaneous endoscopic gastrostomy (PEG) | - | Dysphagia with weight loss >10% or FVC declining toward 50% | N/A :: — :: — :: Place electively when FVC >50% predicted; allows continued oral intake for pleasure; start tube feeds gradually | FVC <50% (higher risk; consider RIG or PIG); severe coagulopathy | Weight, tube site, aspiration | - | URGENT | ROUTINE | - |
| Radiologically-inserted gastrostomy (RIG) | - | PEG contraindicated; FVC <50% | N/A :: — :: — :: Alternative to PEG when FVC <50% or unable to tolerate endoscopy; fluoroscopic placement | Severe ascites; peritoneal adhesions | Weight, tube site | - | URGENT | ROUTINE | - |
| Per-oral image-guided gastrostomy (PIG) | - | Alternative to PEG/RIG | N/A :: — :: — :: Transoral placement under endoscopic and radiologic guidance; may tolerate lower FVC | Same as RIG | Weight, tube site | - | URGENT | ROUTINE | - |
3E. Acute/Emergent Care¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Noninvasive ventilation (acute) | INH | Acute respiratory failure | IPAP 12-20; EPAP 5-8 :: INH :: continuous :: IPAP 12-20 cmH2O, EPAP 5-8 cmH2O; FiO2 to maintain SpO2 >92%; close monitoring for escalation | Inability to protect airway; hemodynamic instability | ABG, respiratory rate, work of breathing | STAT | STAT | - | STAT |
| Intubation and mechanical ventilation | - | Respiratory failure not responding to NIV | N/A :: — :: — :: Discuss advance directives; many ALS patients decline invasive ventilation; if desired, standard intubation and ventilation | Patient declines; DNI documented | Ventilator parameters, sedation | STAT | - | - | STAT |
| IV fluids | IV | Dehydration | 1000-2000 mL NS or LR daily :: IV :: daily :: 1-2 L IV daily; adjust for cardiac status | Fluid overload | I/O, electrolytes, edema | STAT | STAT | - | STAT |
| Empiric antibiotics (aspiration pneumonia) | IV | Suspected aspiration pneumonia | Ampicillin-sulbactam 3g IV q6h :: IV :: q6h :: 3g IV q6h; alternative: piperacillin-tazobactam 4.5g q6h; cover oral flora and anaerobes | Allergies | WBC, fever curve, respiratory status | STAT | STAT | - | STAT |
4. OTHER RECOMMENDATIONS¶
4A. Referrals & Consults¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Neurology (ALS specialist/multidisciplinary clinic) for diagnosis confirmation, disease-modifying therapy, and comprehensive management coordination | URGENT | STAT | ROUTINE | STAT |
| Pulmonology for respiratory function monitoring, BiPAP initiation, and ventilator management decisions | URGENT | URGENT | ROUTINE | STAT |
| Physical therapy for mobility assessment, strengthening (submaximal), range of motion, and assistive device prescription | - | STAT | ROUTINE | STAT |
| Occupational therapy for ADL assessment, adaptive equipment, energy conservation, and home modification | - | STAT | ROUTINE | URGENT |
| Speech-language pathology for swallow evaluation, communication strategies, and AAC device assessment | - | URGENT | ROUTINE | URGENT |
| Respiratory therapy for BiPAP setup and titration, cough assist training, and secretion management | - | STAT | ROUTINE | STAT |
| Nutrition/dietitian for caloric needs assessment, weight optimization, and tube feeding management | - | URGENT | ROUTINE | URGENT |
| Palliative care for symptom management, goals of care discussions, and quality of life optimization | - | URGENT | ROUTINE | URGENT |
| Social work for financial resources (SSDI, Medicaid), caregiver support, and ALS Association resources | - | ROUTINE | ROUTINE | ROUTINE |
| Psychiatry/psychology for depression, anxiety, and adjustment disorder common in ALS | - | ROUTINE | ROUTINE | ROUTINE |
| Gastroenterology for PEG placement when FVC declining toward 50% or significant dysphagia | - | URGENT | ROUTINE | - |
| Hospice care for end-of-life care when prognosis <6 months and/or patient declines aggressive interventions | - | ROUTINE | ROUTINE | ROUTINE |
| Genetic counseling for familial ALS, gene testing interpretation, and family planning implications | - | ROUTINE | ROUTINE | - |
4B. Patient Instructions¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| Return immediately for increased shortness of breath, choking episodes, or inability to clear secretions (may indicate respiratory failure requiring urgent intervention) | STAT | - | STAT |
| Return for fever, worsening cough, or change in sputum color (may indicate aspiration pneumonia) | STAT | - | STAT |
| Do not drive if experiencing significant weakness or fatigue that could impair vehicle control | URGENT | - | ROUTINE |
| Continue eating foods that are safe to swallow; use thickened liquids if recommended by speech therapy | - | ROUTINE | ROUTINE |
| Use BiPAP as prescribed, even if initially uncomfortable; adherence improves symptoms and survival | - | ROUTINE | ROUTINE |
| Perform prescribed exercises but avoid exhaustion; rest before becoming overly fatigued | - | ROUTINE | ROUTINE |
| Complete advance directives including healthcare proxy, living will, and decisions about mechanical ventilation and feeding tubes | URGENT | URGENT | ROUTINE |
| Contact ALS Association (www.als.org) for educational resources, support groups, and equipment loan programs | - | ROUTINE | ROUTINE |
| Attend multidisciplinary ALS clinic visits every 2-3 months for comprehensive care coordination | - | - | ROUTINE |
| Consider joining ALS research registries and clinical trials (www.clinicaltrials.gov) | - | - | ROUTINE |
4C. Lifestyle & Prevention¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| Aspiration precautions including upright positioning during meals, small bites, and chin-tuck swallowing technique | STAT | STAT | ROUTINE |
| Energy conservation with scheduled rest periods and prioritization of activities to reduce fatigue | - | ROUTINE | ROUTINE |
| Home safety evaluation to remove fall hazards, install grab bars, and ensure wheelchair accessibility | - | ROUTINE | ROUTINE |
| Maintain optimal nutrition with high-calorie, high-protein diet; weight loss accelerates decline | - | ROUTINE | ROUTINE |
| Sleep with head of bed elevated 30 degrees if using BiPAP or experiencing orthopnea | - | ROUTINE | ROUTINE |
| Smoking cessation is essential to optimize respiratory function and reduce aspiration risk | - | ROUTINE | ROUTINE |
| Limit alcohol as it may worsen weakness, sedation, and respiratory depression | - | - | ROUTINE |
| Frequent repositioning if immobile to prevent pressure ulcers | - | STAT | ROUTINE |
| Emotional and spiritual support for patient and caregivers; caregiver burnout is common | - | ROUTINE | ROUTINE |
| Consider assistive technology early (voice banking, eye-tracking devices) before speech becomes unintelligible | - | - | ROUTINE |
═══════════════════════════════════════════════════════════════ SECTION B: REFERENCE (Expand as Needed) ═══════════════════════════════════════════════════════════════
5. DIFFERENTIAL DIAGNOSIS¶
| Alternative Diagnosis | Key Distinguishing Features | Tests to Differentiate |
|---|---|---|
| Cervical spondylotic myelopathy | Sensory level, bladder dysfunction, neck pain; UMN signs only | MRI cervical spine shows cord compression |
| Multifocal motor neuropathy (MMN) | Pure LMN; treatable with IVIg; no UMN signs; asymmetric | Anti-GM1 antibodies; NCS shows conduction block |
| Kennedy disease (SBMA) | X-linked; gynecomastia; sensory involvement; slower progression | Androgen receptor gene CAG repeat expansion |
| Primary lateral sclerosis (PLS) | Pure UMN for >4 years; no LMN signs; slower progression | EMG normal; clinical course |
| Progressive muscular atrophy (PMA) | Pure LMN; no UMN signs; may evolve to ALS | EMG; clinical follow-up |
| Myasthenia gravis | Fatigable weakness; ptosis, diplopia; reflexes preserved | AChR antibodies; RNS decrement; edrophonium test |
| Lambert-Eaton myasthenic syndrome | Proximal weakness; autonomic symptoms; improves with exercise | Anti-VGCC antibodies; RNS increment |
| Inclusion body myositis (IBM) | Finger flexor and quadriceps weakness; older males; inflammatory | Muscle biopsy; CPK mildly elevated |
| Post-polio syndrome | History of polio; new weakness in previously affected limbs | Clinical history; EMG |
| Hirayama disease | Young males; asymmetric hand weakness; self-limited | Cervical MRI in flexion shows posterior dural detachment |
| Monomelic amyotrophy | Unilateral limb LMN findings; non-progressive after years | EMG limited to one limb; clinical course |
| Hereditary spastic paraplegia | Pure UMN; family history; sensory neuropathy in some types | Genetic testing |
| Adrenomyeloneuropathy | X-linked; adrenal insufficiency; sensory neuropathy | Very long chain fatty acids elevated |
| Hexosaminidase A deficiency | Early onset; may have psychiatric symptoms; Jewish ancestry | Hexosaminidase A enzyme level |
| Copper deficiency myelopathy | Sensory ataxia; prior gastric surgery; anemia | Serum copper and ceruloplasmin low |
6. MONITORING PARAMETERS¶
| Parameter | Frequency | Target/Threshold | Action if Abnormal | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Forced vital capacity (FVC) sitting and supine | Every clinic visit (q2-3 months); more often if declining | >50% predicted | Initiate BiPAP when <50% or symptoms; discuss PEG when declining toward 50% | STAT | STAT | ROUTINE | STAT |
| ALSFRS-R score | Every clinic visit | Document decline rate | Adjust care intensity; prognostic indicator | - | ROUTINE | ROUTINE | - |
| Weight | Every clinic visit | Stable; <5% loss/3 months | Nutrition consult; consider PEG if >10% loss | STAT | ROUTINE | ROUTINE | STAT |
| LFTs (ALT/AST) | Monthly x 3 months on riluzole, then q3 months | ALT <3x ULN | Hold riluzole if ALT >5x ULN; reduce dose if 3-5x ULN | - | ROUTINE | ROUTINE | - |
| Respiratory symptoms (orthopnea, morning headache, daytime somnolence) | Every visit | None | Initiate or titrate BiPAP | STAT | ROUTINE | ROUTINE | STAT |
| SpO2 and EtCO2 (if on BiPAP) | Each visit | SpO2 >92%; pCO2 <45 | Adjust BiPAP settings | STAT | STAT | ROUTINE | STAT |
| Swallowing function | Every visit | Safe swallow | SLP evaluation; diet modification; consider PEG | - | URGENT | ROUTINE | - |
| Peak cough flow | Every visit | >270 L/min | Initiate cough assist if <270 L/min | - | ROUTINE | ROUTINE | - |
| Mood screening (PHQ-9) | Every visit | PHQ-9 <5 | Antidepressant; psychology referral | - | ROUTINE | ROUTINE | - |
| Caregiver stress | Every visit | Manageable | Social work; respite care; support groups | - | ROUTINE | ROUTINE | - |
| Advance directive status | At diagnosis and annually | Documented | Complete/update advance directives | URGENT | URGENT | ROUTINE | URGENT |
| BiPAP adherence | Every visit | >4 hours/night | Education; mask refitting; troubleshoot | - | ROUTINE | ROUTINE | - |
7. DISPOSITION CRITERIA¶
| Disposition | Criteria |
|---|---|
| ICU admission | Acute respiratory failure (FVC <15 mL/kg, pCO2 >50, SpO2 <88% on supplemental O2); aspiration pneumonia with respiratory distress; need for invasive ventilation (if patient desires) |
| Step-down/telemetry | Respiratory compromise improving on BiPAP; autonomic instability; aspiration pneumonia responding to treatment |
| General floor admission | Aspiration pneumonia without respiratory distress; severe dehydration or malnutrition; new bulbar symptoms requiring evaluation; falls with injury |
| Discharge home | Stable respiratory status; adequate nutrition (oral or PEG); caregiver support in place; equipment needs met; follow-up arranged |
| Discharge to skilled nursing facility | Requires 24-hour care that cannot be provided at home; feeding tube with complex care needs; no available caregivers |
| Discharge to hospice | Prognosis <6 months; patient declines aggressive interventions; focus on comfort care; FVC <30% or continuous BiPAP dependence |
| Multidisciplinary ALS clinic follow-up | Every 2-3 months; sooner if rapid decline; coordinate all subspecialty care |
8. EVIDENCE & REFERENCES¶
| Recommendation | Evidence Level | Source |
|---|---|---|
| Riluzole extends survival by 2-3 months | Class I, Level A | Bensimon et al. NEJM 1994; Miller et al. Cochrane 2012 |
| El Escorial diagnostic criteria | Consensus, Level U | Brooks et al. ALS Other Motor Neuron Disord 2000 |
| Awaji-shima criteria enhance diagnostic sensitivity | Class III, Level C | de Carvalho et al. Clin Neurophysiol 2008 |
| BiPAP improves survival and quality of life | Class I, Level A | Bourke et al. Lancet Neurol 2006 |
| Early PEG placement (FVC >50%) safer than late | Class II, Level B | ProGas Study Group. Lancet Neurol 2015 |
| Multidisciplinary clinics improve survival 7-10 months | Class II, Level B | Van den Berg et al. Lancet Neurol 2005 |
| Dextromethorphan-quinidine for pseudobulbar affect | Class I, Level A | Brooks et al. Neurology 2004 |
| Edaravone slows functional decline in selected patients | Class I, Level B | Writing Group. Lancet Neurol 2017 |
| AMX0035 (Relyvrio) slowed ALSFRS-R decline in phase 2; PHOENIX trial negative; withdrawn April 2024 | Class II, Level B (superseded) | Paganoni et al. NEJM 2020 |
| Tofersen reduces SOD1 in SOD1-ALS | Class I, Level B | Miller et al. NEJM 2022 |
| Glycopyrrolate effective for sialorrhea | Class II, Level B | Arbouw et al. J Neurol 2010 |
| Botulinum toxin for refractory sialorrhea | Class II, Level B | Jackson et al. ALS FTD 2009 |
| C9orf72 most common genetic cause | Class II, Level B | DeJesus-Hernandez et al. Neuron 2011 |
| ALSFRS-R validated outcome measure | Class II, Level B | Cedarbaum et al. J Neurol Sci 1999 |
| Early palliative care improves quality of life | Class I, Level A | Temel et al. NEJM 2010 (oncology; extrapolated) |
| FVC and NIF for respiratory monitoring | Class II, Level B | Lechtzin et al. ALS Other Motor Neuron Disord 2002 |
| Cough assist improves secretion clearance | Class III, Level C | Sancho et al. ALS Other Motor Neuron Disord 2004 |
| AAN Practice Parameters for ALS | Guideline | Miller et al. Neurology 2009 |
CHANGE LOG¶
v1.1 (January 30, 2026) - Reformatted lab tables (1A/1B/1C) to match approved plan column order (venues after test name) - Reformatted imaging tables (2A/2B/2C) to match approved plan column order - Annotated AMX0035/Relyvrio as withdrawn from US market (April 2024, PHOENIX trial negative) - Updated Evidence section to reflect Relyvrio withdrawal - Cleaned structured dosing format: starting dose only in first field across all treatment rows - Fixed Edaravone ORS monitoring to be self-contained (removed "Same as IV formulation" cross-reference) - Added ICD-10 codes: G12.20 (motor neuron disease, unspecified), G12.29 (other motor neuron disease) - Standardized em-dash (—) to hyphen (-) for venue "not applicable" markers
v1.0 (January 27, 2026) - Initial template creation - Comprehensive outpatient-focused ALS management - Includes El Escorial and Awaji diagnostic criteria - Disease-modifying therapies: riluzole, edaravone, AMX0035, tofersen - Symptomatic management for sialorrhea, spasticity, PBA, pain, dyspnea - Respiratory monitoring with BiPAP and cough assist protocols - Nutritional support with PEG timing guidance - Multidisciplinary clinic model emphasized - Palliative care integration throughout - PubMed-verified citations in Section 8
APPENDIX A: ALSFRS-R (ALS Functional Rating Scale - Revised)¶
The ALSFRS-R is a 12-item questionnaire assessing function. Each item scored 0-4 (4 = normal). Maximum score = 48.
Speech - 4: Normal speech - 3: Detectable speech disturbance - 2: Intelligible with repeating - 1: Combined with non-vocal communication - 0: Loss of useful speech
Salivation - 4: Normal - 3: Slight excess, may have nighttime drooling - 2: Moderately excessive; may have minimal drooling - 1: Marked excess with some drooling - 0: Marked drooling; requires tissue or handkerchief
Swallowing - 4: Normal eating habits - 3: Early eating problems; occasional choking - 2: Dietary consistency changes - 1: Needs supplemental tube feeding - 0: NPO (exclusively tube fed)
Handwriting - 4: Normal - 3: Slow or sloppy; all words legible - 2: Not all words legible - 1: Able to grip pen but unable to write - 0: Unable to grip pen
Cutting Food/Handling Utensils - 4: Normal - 3: Somewhat slow and clumsy but no help needed - 2: Can cut most foods but slow; some help needed - 1: Food must be cut by someone else - 0: Needs to be fed
Dressing and Hygiene - 4: Normal function - 3: Independent but with reduced efficiency - 2: Intermittent assistance or substitute methods - 1: Needs attendant for self-care - 0: Total dependence
Turning in Bed - 4: Normal - 3: Somewhat slow and clumsy but no help needed - 2: Can turn alone with difficulty - 1: Can initiate but not complete turn - 0: Helpless
Walking - 4: Normal - 3: Early ambulation difficulties - 2: Walks with assistance - 1: Non-ambulatory functional movement - 0: No purposeful leg movement
Climbing Stairs - 4: Normal - 3: Slow - 2: Mild unsteadiness or fatigue - 1: Needs assistance - 0: Cannot do
Dyspnea - 4: None - 3: Occurs when walking - 2: Occurs with one or more ADLs - 1: Occurs at rest, difficulty breathing when sitting or lying - 0: Significant difficulty; considering mechanical support
Orthopnea - 4: None - 3: Some difficulty; does not routinely use >2 pillows - 2: Needs extra pillows (>2) - 1: Can only sleep sitting up - 0: Unable to sleep
Respiratory Insufficiency - 4: None - 3: Intermittent use of BiPAP - 2: Continuous use of BiPAP at night - 1: Continuous use of BiPAP day and night - 0: Invasive ventilation by intubation or tracheostomy
Interpretation: - Rate of decline is prognostic; typical decline is 1-2 points/month - Score <20 associated with significantly reduced survival
APPENDIX B: Respiratory Monitoring Protocol¶
When to Initiate BiPAP (any ONE of): - FVC <50% predicted - Supine FVC drop >20% from sitting - MIP <-60 cmH2O - SNIP <40 cmH2O - Nocturnal SpO2 <88% for >5 min - pCO2 >45 mmHg - Symptoms: orthopnea, morning headaches, daytime somnolence, frequent awakenings
BiPAP Settings: - Start: IPAP 8-10 cmH2O, EPAP 4 cmH2O - Titrate: Increase IPAP by 2 cmH2O as tolerated for comfort - Target: IPAP 12-20 cmH2O, EPAP 4-8 cmH2O - Back-up rate: 12-16/min for safety
When to Initiate Cough Assist (any ONE of): - Peak cough flow <270 L/min - FVC <50% predicted - Frequent respiratory infections - Difficulty clearing secretions
Cough Assist Settings: - Insufflation: +30 to +40 cmH2O - Exsufflation: -30 to -40 cmH2O - Cycle: 2-4 breaths per cycle, 4-6 cycles per session - Frequency: 2-4 times daily; more frequently during respiratory infections
APPENDIX C: Timing of Interventions¶
| Intervention | When to Discuss | When to Implement |
|---|---|---|
| Advance directives | At diagnosis | Before cognitive impairment or crisis |
| BiPAP | When FVC <80% | When FVC <50% OR symptoms OR supine drop >20% |
| PEG tube | When FVC <80% and stable | When dysphagia + weight loss >10% OR FVC approaching 50% |
| Cough assist | When FVC <80% | When PCF <270 L/min OR frequent infections |
| Voice banking | At diagnosis | Before significant dysarthria |
| AAC device | When speech affected | When speech unintelligible >50% of time |
| Wheelchair | When falls occurring | When ambulation unsafe or exhausting |
| Hospital bed | When mobility declining | When transfers difficult or orthopnea present |
| Hospice | When prognosis <12 months | When prognosis <6 months or patient preference |
APPENDIX D: Resources for Patients and Families¶
ALS Association - Website: www.als.org - Helpline: 1-800-782-4747 - Equipment loan programs, support groups, research updates
Muscular Dystrophy Association (MDA) - Website: www.mda.org - Comprehensive ALS clinic network
I AM ALS - Website: www.iamals.org - Patient advocacy and community resources
Clinical Trials - ClinicalTrials.gov (search "amyotrophic lateral sclerosis") - ALS Research Forum: www.alsresearchforum.org
Caregiver Support - Family Caregiver Alliance: www.caregiver.org - Local respite care programs