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Amyotrophic Lateral Sclerosis Rabia Malik, MD1

Andrew Lui, PT, DPT2

Catherine Lomen-Hoerth, MD, PhD1

1 Department of Neurology, UCSF Medical Center, San Francisco,

California 2 Department of Physical Therapy and Rehabilitation Science, UCSF Medical Center, San Francisco, California

Address for correspondence Catherine Lomen-Hoerth, MD, PhD, Department of Neurology, UCSF Medical Center, 505 Parnassus Ave, San Francisco, CA 94143 (e-mail: [email protected]).

Abstract Keywords

► amyotrophic lateral sclerosis ► orthoses ► wheelchair ► exercise ► respiratory ► nutrition ► spasticity

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting 20,000 to 30,000 people in the United States. The mainstay of care of patients affected by this disease is supportive and given the multifaceted nature of their needs is provided most efficiently through multidisciplinary clinics that have shown to prolong survival and improve quality of life. The authors discuss in detail evidence-based management of individuals affected by this condition.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig disease, is a progressive neurodegenerative disorder of the nervous system where survival ranges from a median of 37 to 49 months. The goal of care for these patients is to provide clinical support and meet their rehabilitation needs in an attempt to prolong survival and improve quality of life (QoL). As described by Charcot, the clinical syndrome of motor weakness results from a progressive loss of upper and lower motor neurons. However, there is now abundant evidence to suggest that this disease is not restricted to the pyramidal system, but may affect other parts of the central nervous system (CNS).1 Patients typically present with asymmetric, painless extremity weakness. Less commonly they may have bulbar weakness as their initial symptom with impaired speech or swallowing. Upper motor neuron (UMN) dysfunction may produce spasticity, bradykinesia, pathological hyperreflexia, and Babinski signs. The accompanying lower motor neuron (LMN) signs may include atrophy, fasciculations, cramps, and diminished or absent reflexes. Emotional lability seen in these patients, termed pseudobulbar affect, is also thought to be due to a dysfunction of the corticospinal tracts.2 El Escorial criteria were proposed for diagnosing ALS and require the presence of clinical and electrophysiological evi-

Issue Theme Neurologic Rehabilitation; Guest Editors, Karunesh Ganguly, MD, PhD, and Gary M. Abrams, MD, FAAN

dence of LMN as well as UMN signs in one or more of the four body regions: craniobulbar, cervical, thoracic, and lumbosacral. In 2008, Awaji criteria were proposed and are thought to enable an earlier diagnosis of ALS.3 Early in the disease course, diagnosis may be uncertain and an extensive clinical and diagnostic workup is recommended to exclude ALS mimics because ALS is a diagnosis of exclusion.4 In 1994, antiglutamate agent, riluzole was shown to demonstrate a favorable effect on survival particularly with bulbar-onset ALS and is the only Food and Drug Administration (FDA) approved medication for this disease, slowing the disease process by 10%. However, the mainstay of care is supportive and centered around optimizing health, QoL, and independence of the affected individuals.

Clinical Case EV was a 36-year-old right-handed man when he first presented to the multidisciplinary ALS clinic for an evaluation in 2005. His symptoms started 2 years prior to his presentation; they consisted of muscle cramps and twitching of his arms. A year later, he developed weakness of the left-foot dorsiflexors and noted that his toes would drag on his surfboard. Around the same time, he noted weakness in the pincer grip of his left

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DOI http://dx.doi.org/ 10.1055/s-0034-1396007. ISSN 0271-8235.

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Semin Neurol 2014;34:534–541.

hand. By the time he was seen in ALS clinic his weakness had progressed. On his initial exam, his pulmonary function test was normal with a forced vital capacity (FVC) of 5.45 L (91% predicted) and mean inspiratory force (MIF) < -60. He had mild weakness of the tongue and tongue fasciculations, but other cranial nerves were normal. Speech was normal except for occasionally stumbling over “s” words. There was decreased bulk in the muscles of his hands and distal legs. His tone was normal. Strength was severely decreased in the distal left leg and moderately decreased in the distal right leg. The proximal leg muscles were relatively intact with only mild weakness. There was moderate weakness (left more than right) in the distal arms and only mild weakness proximally in the upper extremities. Deep tendon reflexes were absent in the arms and þ3 in the lower extremities with mute plantar responses bilaterally. After a thorough workup to evaluate for alternative causes that was negative, a diagnosis of ALS was made. He was given a prescription for riluzole. The therapist recommended the use of bilateral forearm crutches as he had good proximal strength in his upper extremities. In addition, he was given bilateral wrist splints. The dietician recommended weekly weight checks as well as use of high caloric and protein supplements. Over the next 3 years, his weakness progressed so that he became quadriplegic and went from using a wheeled walker to a power chair. His shortness of breath became so severe that communication became difficult and he adopted the use of an eye-gaze communication system. His respiratory function declined; although there was initial reluctance toward the use of ventilator support, this changed when he experienced an episode of severe laryngospasm. Although ALS had physically devastated EV, he had been successfully using rehabilitation equipment and techniques to live a very full life. His eye-gaze system had given him the ability to not only communicate with his family, but also connect with his friends via social networking and e-mail. He would frequently go out to movies and concerts. He subsequently underwent tracheostomy and began using a ventilator by night. A year later he was using a ventilator 24 hours per day. A percutaneous endoscopic gastrostomy (PEG) tube was placed for progressive dysphagia and enteral feeds were initiated. He developed temporary diabetes that resolved completely with formula change. Over the past several years his symptoms have remained fairly stable. This case demonstrates that ALS may affect individuals as early as the third decade of life and that the rate of progression of the disease is variable. Care of patients requires collaboration of a team of specialists and each stage of the disease necessitates provision of a unique set of rehabilitation techniques and devices, which is most efficiently provided through a multidisciplinary clinic. A vast number of therapeutic options are available that not only prolong life, but also make significant impact on the QoL of patients with ALS.

Current Methods of Care or Management The American Academy of Neurology (AAN) practice parameters for ALS suggest an early referral to multidisciplinary

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clinics to optimize access, and in turn increase utilization of adaptive devices, riluzole, PEG, and noninvasive ventilation (NIV).5 Care in an ALS multidisciplinary clinic has been proven to not only improve QoL, but improve quantity of life. Many ALS centers have satellite clinics that go into the community to provide care for those unable to travel long distances to clinic, such as the patient described in the case above. Given the multifaceted nature of the deficits seen in this disease, patients with ALS may benefit from being cared for by a team of specialist consisting of a neurologist, respiratory therapist, physical therapist, occupational therapist, speech therapist, dietician, and social worker. These clinics ideally are able to coordinate care with local primary care physicians and services in the community. Because ALS is a progressive disease each stage of the disease is associated with its specific rehabilitation needs.

Evidence-Based Compensatory or Restorative Treatments Orthoses Lower Extremity Orthoses Ankle orthotics are recommended when there is weakness of the distal lower extremities. For medial and lateral ankle instability, support with either Velcro or lace-up fasteners may provide proprioceptive input and mechanical support to reduce ankle sprains and falls. Ankle foot orthoses (AFOs) can address foot drop, as well as knee instability during ambulation. The three most common types (►Fig. 1) are 1. Lightweight AFOs, such as carbon fiber models, which limit foot drop and may reduce risk of falls by maximizing foot clearance during the swing phase of gait, but do not address knee instability during the stance phase of gait 2. Rigid AFOs made of inflexible plastic that may be constructed with hinges at the ankle. These limit ankle dorsiflexion and plantarflexion in addition to minimizing knee buckling. Being the heaviest type of AFOs, these may cause fatigue of the lower extremity muscles and increase energy spent when walking. 3. Stirrup-type AFOs that consist of metal supports on each side of the ankle and are built into the shoe. Foot drop is limited through a spring mechanism; these may provide a modest amount of knee stability during the stance phase of gait. Patients are instructed to wear AFOs with shoes with a closed heel for safety. In addition, an orthotist may recommend a progressive wear schedule for maximum comfort and compliance asking patients to wear the ankle brace for one hour the first day and then increasing use by an hour every day. Ankle orthotics may need to be adjusted after initial use if the patient experiences discomfort or if the skin becomes red or irritated periodically. Furthermore, the orthotics may need to be adjusted if the patient’s body weight changes significantly.6 Although evidence showing the efficacy of AFOs is limited, one study showed that patients rated ankle braces highly with respect to utility and satisfaction.7 Seminars in Neurology

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Fig. 1 (A) Lightweight carbon fiber ankle foot orthosis. (B) Solid ankle hinged ankle foot orthosis. (C) Stirrup-type ankle foot orthosis.

Upper Extremity Orthoses Splints for the wrist and hand may be prescribed in the context of distal weakness of the upper extremities. Functional wrist splints, such as the wrist cock-up splint, can improve function by supporting the wrist and optimizing mechanics during reaching and grasping tasks. Resting-hand splints can be used to reduce contractures and edema in the context of significant upper extremity spasticity or weakness.8 Shoulder slings can reduce discomfort and protect the glenohumeral joint from progressive subluxation due to rotator cuff muscle weakness. The Giv–Mohr sling is most effective in reducing shoulder subluxation, and can be easier to don, doff, and adjust than other arm slings.9 In addition, the use of lapboards and armrests may reduce discomfort and risk of subluxation.10

fatigue, and balance issues. The equipment should be prescribed based on the nature of the impairments, and assessed for effectiveness and safety by a qualified clinician. It is expected that each patient’s equipment needs will change as the disease progresses. In general, gait devices are selected to maximize energy efficiency. For example, four-wheeled walkers have been shown to reduce energy expenditure compared with nonrolling walkers.12

Wheelchairs Wheelchairs are indicated to address weakness, balance issues, respiratory insufficiency, and fatigue. A lightweight manual wheelchair may be used initially, as they are easily transported and managed by caregivers. However, as weakness, instability, and fatigue progresses, patients will require a power wheelchair. These typically feature fully automatic

Spine Orthoses Cervical collars may be prescribed for neck extensor weakness. Soft collars made out of foam provide minimal support and are thus useful only if there is mild neck weakness. Semirigid collars (such as Philadelphia and Miami-J collar) combine foam and plastic materials and provide additional support, but may be less comfortable making swallowing difficult, and may increase anxiety about breathing.11 Cervical collars with more open designs, such as the Headmaster collar (Symmetric Designs, Ltd, Salt Spring Island, Canada) (►Fig. 2), may provide good support with improved comfort compared with conventional semirigid collars. Thoracolumbar corsets may be prescribed to address truncal weakness. Such an orthotic may reduce anterior and lateral thoracolumbar flexion, providing comfort and theoretically optimizing respiratory capacity. However, corsets may not be comfortable for extended use and may limit ribcage excursion during breathing. Evidence for the efficacy of orthotics is lacking in this population and in general, recommendations are based on expert opinion.

Gait-Assist Devices Walking aids such as canes, walking sticks, crutches, and walkers can be introduced as needed to address weakness, Seminars in Neurology

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Fig. 2 Headmaster semirigid cervical collar (Symmetric Designs, Ltd, Salt Spring Island, Canada).

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recline, tilt in space, seat elevator, and elevating leg rests allowing for trunk and neck support. Although modern designs allow these fully adjustable power wheelchairs to fit through standard doorways, these wheelchairs require some modifications to the passenger vehicle or a special van to be transported. Though the cost of these fully adjustable power wheelchairs is high, patients who use power wheelchairs interact more with their community and are more satisfied with their level of activity than patients who use manual wheelchairs.13 In addition, 88% of patients who obtained fully adjustable power wheelchairs reported that they would get the same type of wheelchair again, and 81% reported that the wheelchair was a good value for the cost.14 Scooters are not recommended for patients with ALS as they are not adaptable for progressive disability.

Transfer Equipment Transfer equipment lessens the amount of work required for transfers and in turn reduces fatigue, risk of injury, and falls for the patient and their caregivers. Transfer slings or belt go around the waist, hips, or thighs and may reduce injury to the patient that may occur by pulling on a weak shoulder or arm. These devices may also reduce injury to the caregiver by providing a secure hold for improved body mechanics. Pivot disks are rotating disks that may be used for patients who are able to bear weight on their lower extremities, but have difficulty with moving their feet to turn. Caregivers may use transfer boards to aid in sliding patients from one seat to the other with less risk of injury and falls. One level III study found that patients rated sliding boards highly for usefulness and satisfaction.7 Mechanical lifts include ceiling track lifts and Hoyer-type lifts. Both systems use a sling that fully support the patient and allow transfers with less biomechanical and psychological stress for caregivers.15 Although both types of lifts are safe, ceiling track lifts are more space efficient, although assembly is more costly requiring home modifications. Hoyertype lifts, on the other hand, take up more space, but are freestanding and are less costly. Other adaptive equipment can facilitate safe and efficient mobility. For instance, bed rails are used when patients have good arm strength, but have difficulty getting in and out of bed. Hospital beds that allow height adjustment and elevation of the head and foot of the bed may increase independence and may also address orthopnea. Air mattresses providing alternating pressure are used when there is difficulty with frequent turning to prevent pressure ulcers. Safety bars, elevated toilet seats or commodes, shower seat, sliding tub transfer benches, and rolling shower chairs may maximize safety and energy conservation for patients with significant weakness. A self-reported satisfaction survey showed that patients rated elevated toilet seats, safety bars, and shower seats high for utility and satisfaction.7

Assistive Devices for Activities of Daily Living Assistive devices have been shown to minimize energy expenditure and increase independence with self-care and activities of daily living (ADLs) for patients with neuromus-

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cular diseases.16–19 These devices include, but are not limited to reachers, dressing sticks, long-handled sponges, shoe horns, button hooks, zipper hooks, and sock aids. Clothing adaptation for easy dressing and undressing includes the use of Velcro fasteners, elastic waistbands, elastic shoelaces, and slip-on shoes.20 Equipment to assist patients with self-feeding, including universal cuffs, plate guards, nose cups, rocker knives, angled spoons and forks, and long straws may also reduce energy costs and increase independence in patients with ALS.11 Use of cylindrical tubing on writing instruments, utensils, and personal care items, can maximize independence for patients with reduced grip strength and dexterity.21 Although there is limited evidence for the efficacy of assistive devices, a level III study demonstrated that patients reported higher usefulness and satisfaction with slip-on shoes than with button hooks, dressing sticks, and longhandled reaching tools.7

Home Modifications Therapists make home visits to assess and recommend modifications unique to the patient’s needs and living conditions. Wheelchair users may need the installation of ramps, lifts, or elevators to negotiate stairs, as well as wider doorways and a roll-in shower for optimum accessibility. Home modifications should follow regulations noted in the Americans with Disabilities Act. In some cases, these modifications may not be feasible, and patients may need to move to a more accessible residence.6

Patient and Caregiver Education Educating patients and caregivers on compensatory strategies for daily activities is paramount for gait, transfers, dressing, feeding, and toileting in an attempt to improve safety, conserve energy, save time, and decrease frustration and psychological stress.6

Exercise There is some dispute regarding the effect of exercise on muscles already weakened by motor neuron disease. A study performed with a transgenic mouse model with mutated copper/zinc superoxide dismutase indicated that highintensity endurance exercise did not delay onset of clinical symptoms and led to a more rapid decline in motor performance and death in male mice.22 In contrast, another study using the same mouse model showed that vigorous activity did not hasten the progression of motor neuron degeneration23 and other studies using moderate intensity exercise have shown a neuroprotective effect.24–27 In addition, motor neuron protection and maintenance of the motor neuronsurrounding environment using a moderate intensity swimming protocol have been demonstrated.28 Two systematic reviews have examined the effects of exercise on patients with ALS. An earlier review including four studies found small to moderate degree of benefit of moderate exercise with no adverse effect on disease progression.29 On the other hand, a more recent study found only two randomized trials that met inclusion criteria, which the Seminars in Neurology

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authors concluded were too small to determine benefits and risks of strengthening exercise for this population.30 Three types of exercise training are relevant to patients with ALS: (1) Flexibility or stretching exercise, (2) aerobic exercise, and (3) strength exercise. Stretching exercises can minimize contractures and spasticity in patients with neuromuscular disease and therefore may reduce the risk of pain and disability from musculoskeletal dysfunction, including the risk of falls. As such, stretching exercise is recommended at each stage of the disease.31 Patients with weakness of the shoulder girdle should be cautioned against the risk of subluxation of the shoulder joint and should be coached by a therapist on how to perform shoulder stretches safely. As weakness progresses caregivers may be trained to carry these out for the patient. Patients with ALS may engage in aerobic exercise, such as swimming, walking, and bike riding. Aerobic exercise prescription will depend on the cardiopulmonary status of the patient, as well as safety considerations, such as impaired balance. Studies have shown that patients with ALS show a similar training response to cardiovascular exercise as healthy controls, and that functional and respiratory decline may be slowed by aerobic activities.32 Although three studies have described the benefits of strength training programs for patients with ALS, optimal exercise protocols for this population have not been established.33–35 Because the goals of training for these patients is to maintain muscle strength and endurance without undue risk of overuse weakness, most investigators have utilized moderate load and moderate intensity exercise based on tolerance. For muscle groups that are too weak to lift a body part against gravity (Medical Research Council [MRC] Scale grade < 3), resistance exercise is generally avoided.35 The intensity of the exercise should be adjusted to prevent fatigue. Pain, fasciculations, or muscle cramping may indicate overuse; 30 to 45 minutes of exercise in two or three sessions may be considered up to 4 to 5 days per week.36

Respiratory Management Clinical features of early respiratory failure may include dyspnea on exertion, orthopnea, insomnia, and weak cough with increased difficulty clearing secretions. In supine position, the diaphragm acts as the key muscle for inspiration so early diaphragmatic weakness is typically noted in this position. Frequent awakenings at night and daytime somnolence may be associated with nocturnal hypoxemia while early morning headaches may signify hypercarbia.37 Respiratory symptoms in ALS are thought to be secondary to diaphragmatic and respiratory muscle weakness. However, there is evidence to suggest that central dysfunction of the mechanism of breathing may be an additional factor.38,39 Forced vital capacity and MIF are commonly performed and are predictors of survival in ALS patients. However, FVC is an insensitive marker and may not fall until there is considerable respiratory muscle weakness. In addition, both FVC and MIF may be difficult to obtain in patients who cannot form a tight seal around a mouthpiece as a result of their bulbar weakness. Supine FVC may be better than erect FVC. Sniff nasal inspiraSeminars in Neurology

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tory pressure (SNIP), which involves a sharp inspiratory maneuver, may be easier to obtain and correlates well with diaphragmatic strength. A SNIP value of < 40 cm H2O is associated with nocturnal hypoxia and increased mortality.40 Nocturnal oximetry may be considered to detect nocturnal hypoventilation. Patients with symptoms of respiratory insufficiency, FVC < 50% and SNIP of < 40 cm H2O, nocturnal oxygen desaturation of 90% for at least 1 minute and hypercarbia should be offered NIV.37 According to the practice parameter update put forth by the AAN in 2009, NIV is effective in prolonging survival and slowing the rate of FVC decline.41 Bilevel positive pressure (BiPAP) ventilators applying a smaller expiratory pressure than inspiratory pressure are used rather than continuous positive ventilation (CPAP). The latter provides a constant inspiratory and expiratory pressure and leads to an increase work of breathing. Initial setting for BiPAP is usually at 12 cm H2O for inspiration and 8 cm H2O for expiration. Earlier in the disease course, ventilatory assistance may be needed only at night, but eventually these may be required during the day as well. Positive pressure ventilation may delay the need for tracheostomy and invasive mechanical ventilation by several months.42 The FDA approved diaphragmatic pacing in September 2011. Electrodes are placed laparoscopically into the diaphragm. Stimulating electrode wires are brought out through the epigastric port where a reference electrode is inserted. These are then tunneled subcutaneously to the subclavicular fossa where they are plugged into an external stimulator. These appear to be safe in patients with ALS, but long-term benefit of this intervention with progressive LMN degeneration affecting the phrenic nerve and diaphragm is unclear.43,44 Invasive mechanical ventilation such as a tracheostomy or an endotracheal tube may be considered for patients who feel QoL is still good and who have the resources and social support to fund the high cost of care. As the disease progresses, the patients and their families should consider establishing advanced directives to avoid initiating mechanical ventilation in an emergency situation.

Secretions Excessive salivation or sialorrhea becomes a problem with facial, palatal, and neck weakness and may be embarrassing for the patient. In addition, it may predispose to aspiration pneumonia. Glycopyrrolate at 1 to 2 mg or 1 to 2 drops of 1% atropine solution placed sublingually may be used every 4 hours as needed. Scopolamine patches can be considered. For thickened secretions, hydration and use of mucolytic agents such as liquid Robitussin and Mucinex may be used. Intraparotid or submandibular glands injections with botulinum toxin type B are effective and safe.

Communication Devices Dysarthria affects up to 80% of patients with ALS and significantly reduces QoL leading to social isolation. A mixed spastic and flaccid pattern is seen where there is impaired articulation, slow speech and hypernasality.45 In addition,

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respiratory muscle weakness leads to hypophonia. Communication strategies may include nonverbal gestures such as pointing, facial expressions, and eye contact. Augmentative and alternative communication (AAC) devices that may be used include alphabet boards, picture charts, call bells, etc. Voice amplifiers, recorders that play back previous recorded phrases, and speech synthesis software may be used with desktops and laptops. Voice banking, where the patient records their voice potentially for future use may be considered. This may be recorded as whole words or phrases or a synthesized voice can be created based on the patient’s voice. Computer tablets and phones can now be equipped with communication apps. Updated information about these and other devices can be obtained at the ALS Association website (www.alsa.org/als-care/augmentative-communication/). As the patient becomes anarthric and quadriplegic, devices to translate eye movements into effective communication such as the eye-tracking computer system (ETCS) may be used (►Fig. 3). It allows for communication with caregivers as these are equipped with voice synthesizers and convert text to speech. In addition, it provides access to the Internet so that individuals may surf the web, receive and send electronic mail, and be part of social networks.46

Nutrition A higher body mass index prior to developing ALS and maintenance of good nutritional state is associated with better outcome.47 Patients with ALS are at a high risk of malnutrition from several causes. Bulbar weakness leading to dysphagia may occur at any stage of the disease and may lead to inadequate oral intake as well as increase the risk of aspiration. Other causes of malnutrition include muscle atrophy, hypophagia, and hypermetabolism.48 The AAN recommends monitoring weight and performing a dysphagia assessment every 3 months with referral to a nutritionist or speech therapist when early signs of dysphagia are de-

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tected.41 In addition, early discussion with the patient and caregivers regarding the use of a PEG tube is suggested, emphasizing that this does not eliminate oral feeding, but provides supplemental nutrition as well as means of administering medications and fluids to avoid dehydration. Strategies to maintain oral nutrition include consuming small frequent meals; proper head and neck positioning, which usually involves having the patient sit upright, chintuck position; use of straws; and diet modification, such as solids with semisoft consistency and thickened liquids to avoid aspiration. Nutritional supplements may be recommended to boost caloric intake. Weight loss of 5% to 10% or more denotes risk of malnutrition and is a good indicator that the use of PEG tube should be considered. There are data to suggest that the use of PEG may prolong survival in ALS and help in stabilizing body weight, but there is insufficient data to indicate a specific time of PEG insertion.41 However, gastrostomy should be performed with caution in patients with vital capacity of < 50%.

Muscle Spasticity and Cramps Pain is common in ALS and is secondary to muscle cramps and spasticity. Quinine sulfate may be helpful in reducing muscle cramps while muscle relaxants such as baclofen, tizanidine, and benzodiazepines may be used for spasticity. However, a systemic review of 20 studies could not identify a favorable effect of any of the pharmacologic agents on cramps in motor neuron disease.49 Intrathecal baclofen pump is effective and safe in patients with ALS and is considered for those who are either refractory to treatment or may have dose-limiting side effects.50 In our institution, a test dose of up to 50 µg bolus of intrathecal baclofen is given in an outpatient setting. If no response is seen a second test dose of 75 to 100 µg is given. If the patient responds favorably to this test dose and there is reduced spasticity on exam, they are referred to neurosurgery for an ITB pump implantation. The Medtronic Synchromed II programmable pump is inserted into the lower abdominal subcutaneous or subfascial pocket under general anesthesia. The catheter is placed in the lumbar subarachnoid space under fluoroscopic guidance and threaded up to the thoracic spinal level. Patients are discharged to an inpatient rehabilitation center where over the course of 3 to 5 days they are tapered off their oral baclofen while their intrathecal dose is titrated up. These patients are subsequently followed in clinic for dose adjustments and pump refills.

Interesting Developments in the Therapeutic Pipeline

Fig. 3 Ventilator-dependent patient with advanced amyotrophic lateral sclerosis demonstrating the use of an eye-gaze communication system.

A pilot study by Sanjak et al showed that a regimen of supported treadmill ambulation training was well tolerated and safe for ambulatory patients with ALS. Specifically, patients who completed the study showed a measureable training response in the form of improved gait distance, speed, and step and stride length. In addition, there is an improved work capacity. The authors proposed two mechanisms by which these robust training effects may have Seminars in Neurology

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occurred: (1) protection from overuse weakness and facilitation of gait pattern and stepping practice, and (2) provision of sensory input to activate spinal mediated circuitry for ambulation. The investigators pointed to the need for larger randomized controlled trials to determine the stability of this training effect in relation to the progressive nature of ALS.51 A clinical trial comparing resistance, endurance, and range of motion exercises to assess tolerability and safety in ALS patients is currently on going. Some of the secondary outcome measures include effect on vital capacity, ALS Functional Rating Scale (FRS), and the Quality of Life Scale.52 A multicentered randomized control study is currently underway to assess whether diaphragm pacing in ALS is associated with improved survival and QoL.53 As mentioned above, data with regards to long-term effects of this intervention is lacking thus far. Brain–computer interface or brain–machine interface technology involves the use of cortical signals, recorded via an electroencephalogram or invasive microelectrodes, which are decoded to control an external device such as a cursor on a computer screen or a robotic limb.54 A study conducted in 25 patients with ALS demonstrated that this mode of communication may be of use in individuals severely affected by the disease.55

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Amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting 20,000 to 30,000 people in the United States. The mainstay o...
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