Management

Neuroprotection

At present there is only one agent that has been demonstrated to slow progression of ALS. Riluzole delays time to death or tracheostomy (surgical insertion of a tube into the airway below the larynx (voice box) to achieve access to the respiratory tract) by an average of 3-4 months. The drug is typically used for variants of ALS since they are considered to be within the spectrum of ALS.

Routine Follow-Up

Since ALS is progressive, frequent follow-up visits are essential to keep pace with changing symptoms. Time between visits should be based upon speed of progression and presence of life threatening issues of dysphagia and or respiratory muscle weakness. Follow-up every 2-4 months is most common.

At a minimum, each visit should include: weight, review of present symptoms, physical examination, and measurement of forced vital capacity (FVC) (Performed using a device called a spirometer. The patient is instructed to take a really deep breath and then blow out all of the air into the spirometer. The spirometer measures the volume of air that the patient expels and compares it to the predicted volume [percent predicted FVC] based upon patient height, weight, gender, and smoking history. Normal volume is 80 to 120% of predicted.).

 

Management of Symptoms (palliation)

Drooling (sialorrhea) or salivary production may be reduced by using:
A.    Oral anticholinergic medications
1.    Glycopyrolate (Robinul)
2.    Hyocyamine (Levsin)
3.    Atropine (Saltropine)
B.    Transcutaneous (through the skin) medication (Transderm-scopolamine)
C.    Botulinum toxin injection into salivary glands (parotid or submandibular)
D.    Radiation therapy (to parotid or submandibular glands).

Salivary production may be managed using absorptive pads and tissues or a portable suction. Excessive posterior pharyngeal and upper airway secretions may be managed by:
A.    Reducing and managing salivary production (as above)
B.    Thinning mucus (mucolytics)
1.    Oral guaifenesin (Mucinex, Robitussin)
2.    Nebulized N-acetylcysteine (Mucomyst)
C.    Reducing mucus production
1.    Oral anticholinergic medications (listed previously)
2.    Nebulized anticholinergic (ipratropium bromide)
3.    Nebulized albuterol

Consider tracheostomy if the patient has recurrent aspiration pneumonias or severe pharyngeal and tracheal secretion issues and failure of other treatments.

Involuntary jaw clenching may be treated with clonazepam (Klonopin) or injection of Botulinum toxin into the masseter muscle. A bite guard or dental bumper may also be used if biting of the cheek or lip is a problem. 
A weak cough may be addressed using a cough assist (insufflator-exsufflator) which may be coupled with secretion management described previously. 

Dysphagia (swallowing difficulty) may be treated using compensatory strategies as recommended by a speech therapist. These strategies include chin tuck, multiple swallows, and following swallow with a liquid. Fluid may be thickened while solids may be pureed. For those with severe dysphagia or a weight loss of more than 10% of body weight, gastrostomy tube insertion may be considered.

Dysarthria (slurred speech) or anarthria (inability to speak) may be addressed with compensatory strategies. A palatal lift may be done to relieve the nasal quality of speech. Augmentative and alternative communication (AAC) may be used. These range from low tech solutions such as writing or the use of a letterboard to high tech solutions such as voice synthesizing computers and brain computer interfaces. 

Pseudobulbar affect (inappropriate emotional expression disorder) may be treated with antidepressants such as:
A.    Selective Serotonin Re-Uptake Inhibitors (SSRI)
1.    Fluoxetine (Prozac)
2.    Sertraline (Zoloft)
3.    Citalopram (Celexa, Lexapro)
4.    Venlafaxine (Effexor)
B.    Tricyclic Antidepressants
1.    Amitriptyline (Elavil)
2.    Nortriptyline (Pamelor)

       
Neck extension weakness is treated with the use of positioning, collar brace, and wheelchair adaptations. Arm and hand weakness is managed with the use of ADL aids and bracing such as a wrist brace. Leg weakness is addressed using bracing such as an ankle-foot-orthosis (AFO). Canes, walkers, wheelchairs, and transfer aids may also be used. The use of a walker may help those with trunk weakness.

Spasticity is treated with positioning, stretching, or anti-spasticity agents such as baclofen, tizanidine (Zanaflex), clonazepam (Klonopin), and gabapentin (Neurontin).

Depression is treated with psychotherapy and anti-depressants.

 

Pain which may be related to immobility secondary to weakness may be treated with range of motion exercises, stretching, massage, and injections (shoulders, hip). Pain medications may also be used. Some examples include acetaminophen (Tylenol), non-steroidal anti-inflammatory drugs (NSAIDS) (ibuprofen and naproxen), anti-seizure medications (gabapentin [Neurontin], lamotrigine [Lamictal], pregabalin [Lyrica]), and antidepressants (duloxetine [Cymbalta]).

 

Management of Life-Threatening Aspects of ALS    
Advance decision making is important. Expressing a choice before a serious medical condition occurs is ideal. Remember you can change your mind as long as you are alert, awake, and maintain the capacity to make medical decisions.

A person has capacity for medical decision making if he has the ability to understand the medical condition and options for treatment, make a choice, understand the consequences (risks, benefits) of that choice and explain how the decision makes sense within the context of their values and beliefs, and communicate their decision. Questions that need to be addressed include: Have all barriers (sedating medications, language barrier, time, privacy) to communication been removed? Is the decision reasonably stable over time? Are there social issues that may be unduly influencing the decision (e.g. threats, financial pressure)?

Frontotemporal dementia may limit capacity for decision making which may progressively decline over time. Try to discuss advance decision making before development of dysphagia and respiratory muscle weakness. Encourage the appointment of a surrogate decision maker or a durable medical power of attorney.

Once respiratory muscle weakness begins, it will progress and will ultimately lead to death from respiratory failure. Advance directive discussion should be triggered when respiratory muscle weakness is first detected (FVC below 80% predicted), significant respiratory muscle weakness is first detected (the FVC reaches 50% predicted or below) with or without respiratory symptoms, cognitive dysfunction starts to become evident, or whenever the patient wants to discuss it.

Initial management may include non-invasive ventilation. Non-invasive ositive pressure ventilation (NIPPV) is more common than non-invasive volume ventilation (NIVV). Both may utilize full or nasal mask or nasal interface. Initiate either when FVC < 50% predicted. It is best to initiate non-invasive ventilation during nighttime sleep for at least 4 hours per day. Pressure support can be adjusted upwards as respiratory muscle weakness and symptoms increase. Usage time can also be increased. These strategies will eventually fail in the face of very severe respiratory muscle weakness.

With end-stage management, the patient may elect for tracheostomy for long term mechanical ventilation (LTMV). This is best if performed as a scheduled procedure in a hospital rather than rely upon emergency services following respiratory duress or even cessation of respiration. NIPPV can be a bridge to LTMV.

Considerations include where the patient will be cared for, cost, communication needs (Tracheostomy placed below the larynx or voice box may make communication by speech impossible. Speech may be possible if the cuff is deflated, a fenestrated tube is used, or a Passy-Muir valve is used.), and swallowing since having a tracheostomy may make eating safely impossible requiring the placement of a gastrostomy tube.

ALS will continue to progress despite LTMV and may culminate in the locked-in state when all voluntary movement including eye movements and blinking cease, making communication impossible.

Patients with decision-making capacity may elect to discontinue LTMV at any time. Patients without capacity for decision-making may have their designated surrogates elect for them to discontinue LTMV. Medications are used to prevent any suffering.

If a patient elects to forego or avoid tracheostomy for LTMV, palliative care usually through hospice should be initiated. Respiratory symptoms are managed by using NIPPV or morphine for dyspnea not managed adequately by NIPPV. At all times, try to minimize or eliminate suffering and maintain quality of life.

With severe dysphagia with severe (>10%) weight loss, patients may elect for gastrostomy tube placement which virtually eliminates life threatening malnutrition and or dehydration. If the patient elects to forego or avoid gastrostomy tube insertion institute hospice care and manipulate consistency of liquids and solids.