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Motor neuron diseases

Care management in amyotrophic lateral sclerosis

M.-H. Soriani *, C. Desnuelle

Centre de référence maladies neuromusculaire/SLA, university hospital of Nice, CS 51069, 06001 Nice cedex 1, France

info article abstract

Article history: Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal neurodegenerative
Received 30 September 2016 disease characterized by progressive weakness of voluntary muscles of movement as well
Accepted 27 March 2017 as those for swallowing, speech and respiration. In the absence of curative treatment, care
Available online xxx can improve quality of life, prolong survival, and support ALS patients and their families,
and also help them to anticipate and prepare for the end of life. Multidisciplinary mana-
Keywords: gement in tertiary centers is recommended in close collaboration with general practitioners,
Amyotrophic lateral sclerosis home carers and a dedicated health network. Patients’ follow-up deals mainly with motor
ALS management impairment and physical disability, adaptation, nutrition and respiratory function. Invol-
Non-invasive ventilation vement of palliative care as part of the multidisciplinary team management offers patients
Nutrition the possibility of discussing their end of life issues. This review summarizes the different
Palliative care aspects of ALS care, from delivering the diagnosis to the end of life, and the organization of
Ethics its management.
Rehabilitation # 2017 Elsevier Masson SAS. All rights reserved.

classified as familial [5]. To date, the genetic etiology is

1. Introduction
Amyotrophic lateral sclerosis (ALS) is a relentlessly progres-
sive and fatal neurodegenerative disease. With an incidence of
around 2/100,000 person-years, ALS is the most common form
of motor neuron disease and the third most common
neurodegenerative disease [1]. Degeneration of both the lower
(LMNs) and upper motor neurons (UMNs) leads to progressive
weakness of voluntary muscles of movement as well as the
swallowing, speech and respiratory muscles. A variable degree
of spasticity and pseudobulbar affect can be observed too.
Roughly 50% of ALS patients develop mild cognitive and/or
behavioral disorders and 5–15% develop dementia, usually of
the frontotemporal type [2–4]. About 90% of ALS cases are
sporadic of unknown origin, whereas the remaining 10% are
identified in approximately two out of three cases of familial
ALS and in around 10% of sporadic cases [6].
The presentation and progression of the disease as well as
the age of onset vary considerably between individuals. The
rate of disease increases with age to peak in the group aged 65–
75 years. Nevertheless, disease can also arise in young adults
(< 30 years) and in the elderly (> 80 years). Median survival
time is 3–5 years from symptom onset, although 5–10% of
patients may survive for a decade or more [1,7]. These data
emphasize the necessary adaptation of clinical management
according to the patients’ age and course of disease.
The first consensus meeting on ALS management in France
was held in 2005. More recently, French ALS care recommen-
dations were reviewed as part of the French national protocol
for diagnosis and care [8]. At the same time, a European

* Corresponding author.
E-mail address: soriani.mh@chu-nice.fr (M.-H. Soriani).
http://dx.doi.org/10.1016/j.neurol.2017.03.031
0035-3787/# 2017 Elsevier Masson SAS. All rights reserved.

Please cite this article in press as: Soriani M-H, Desnuelle C. Care management in amyotrophic lateral sclerosis. Revue neurologique (2017),
http://dx.doi.org/10.1016/j.neurol.2017.03.031
NEUROL-1780; No. of Pages 12
2 revue neurologique xxx (2017) xxx–xxx
Federation of Neurological Sciences (EFNS) task force on the
management of ALS and the American Academy of Neurology
(AAN) published guidelines for clinical care in ALS [9,10]. In the
absence of curative treatment, the aim of management is to
maximize quality of life (QOL), prolong survival, and support
ALS patients, their families and their caregivers to help them
anticipate and prepare for the end of life.
The present review summarizes the organization of such
management and the different aspects of ALS care, from
delivering the diagnosis to the end of life, and includes
neuroprotective and symptomatic treatments, nutritional and
respiratory management, rehabilitation, psychological and
social management and, finally, palliative and end-of-life care.
2. ALS centers and multidisciplinary
management
Because of (i) the diversity of ALS damage, involving physical
functions, breathing, nutrition, communication, cognition
and emotions, in association with complex needs related to
health and psychosocial aspects, and (ii) the progressive
evolution of the disease with often rapid changes, multidisci-
plinary care (MDC) is recommended at tertiary centers (ALS
centers) [9,11,12].
Patients receiving care at ALS centers have longer survival
than those supported by general neurology clinics [12,13].
Most observational studies have shown that MDC is effective
in several ways including increased use of (i) riluzole, (ii) non-
invasive ventilation (NIV), (iii) adaptive equipment and, in
some studies, increased use of gastrostomy [13]. Although
certain treatments and assistive devices may increase
survival, no study has yet clearly demonstrated their survival
benefits for patients managed at ALS centers. However,
better decision-making in complex situations by experienced
Fig. 1 – The multidisciplinary network of care in
amyotrophic lateral sclerosis (ALS) tertiary care centers.
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practitioners may also contribute to better survival. In
addition to extending survival, studies have demonstrated
improved QOL for patients receiving care at ALS centers
[14,15], with patients at ALS centers having fewer unplanned
admissions for acute events, which contributes to the
increased QOL for patients while decreasing the costs to the
healthcare system, with no negative effects on patient
outcomes [12].
The multidisciplinary ALS team usually includes health-
care practitioners and a social counsellor, and provides
management services for ALS patients (Fig. 1). Tertiary centers
offer appointments covered by a single visit, decreasing
patients’ trips to hospital and, consequently, their tiredness.
Quarterly appointments are usually proposed, with variations
according to disease progression. To facilitate patients’
management, effective communication and good coordina-
tion are essential between the center’s multidisciplinary team,
home practitioners and the palliative care team.
3. Breaking the news
Delivering the ALS diagnosis to patients and their relatives is
challenging for both patients and clinicians. While there is no
standardized procedure, it has been reported that many
factors influence how the announcement of bad news is
experienced [16–18]. Disclosing the diagnosis of ALS requires a
specific environment. The physician should meet with the
patient in a quiet comfortable room, with the presence of
relatives if expected by the patient, as soon as the diagnosis
has been confirmed. To help personalize the announcement,
the physician should take into account the patient’s personal
history, social and environmental context, what the patient
already knows about the disease and what he wants to know.
Such an announcement requires good communication
skills, empathy, honesty, and use of simple and careful words.
Information should include the name of the disease, the
nature of its progression and the wide variability of the
prognosis. Reassurance is important at this time and should
comprise information about neuroprotective treatments and
the research, and assure the patient and family that they will
not be left on their own to face the disease. Time should be
made available for the patient to ask questions. As diagnostic
announcements may lead to psychological trauma, the
intervention of a psychologist is usually proposed.
The patient’s general practitioner should also be promptly
informed by being sent a report specifying the delivered
information.
Finally, to evaluate the patient’s perception and unders-
tanding of the diagnosis, another appointment should be
proposed in the month following the diagnosis. These two-
tiered appointments give the patient the opportunity to
handle the changed perspective of his life [19].
4. Therapeutic management
This is based on the establishment of neuroprotective and
symptomatic treatments.
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4.1. Neuroprotective treatment 4.2. Symptomatic treatments

4.1.1. Riluzole These treatments aim to improve patients’ QOL. Symptoms

Riluzole (50 mg twice daily) is the only drug that has shown
efficacy in slowing the course of the disease, with an increase
in survival of around 3 months [20–22]. Its mechanism of
action, however, is controversial: the neuroprotective effect
could be the result of antiglutamatergic action. It should be
initiated as early as possible after the diagnosis and at a low
dose to minimize its minor adverse effects. Riluzole should be
used with caution in patients with known hepatic dysfunc-
tion. A moderate rise in transaminases and/or g-glutamyl
transferase (GGT) may appear early in treatment, but usually
regresses within the first 3 months. In exceptional cases,
neutropenia has been reported. Consequently, monthly
monitoring of blood counts and liver function is recommen-
ded during the first 3 months, then quarterly for 1 year. In the
absence of data for the long-term effectiveness of the
treatment, it is usually continued throughout the course of
the disease.
4.1.2. Alpha-tocopherol
Alpha-tocopherol (500 mg twice daily) may help to slow
progression in milder ALS states, as assessed by the ALS
Health State Scale, due to its antioxidant properties [23]. The
French National Health Authority (HAS) recommends its use
in combination with riluzole.
are the result of injury to UMNs (spasticity, emotional liability)
and/or LMNs (cramps) or of disability (pain, mood disorders
and sleep disorders). Symptoms should be treated as soon as
they become incapacitating [9]. Table 1 summarizes the main
symptomatic treatments.
4.2.1. Cramps
Cramps are the most frequent cause of pain in the initial and
intermediate stages of disease, especially at night. No
controlled trial has been conducted other than those with
tetrahydrocannabinol, which failed to demonstrate any
efficacy [24]. More recently, a phase-II randomized trial of
mexiletine suggested efficacy for cramps [25], while a small
open-label pilot study with levetiracetam also suggested
efficacy [26].
In clinical practice in France, quinine is the most
commonly used therapy, whereas EFNS guidelines recom-
mend levetiracetam as the first line of treatment. The adverse
effects of quinine are mainly cardiac and dose-dependent. In
association with this pharmacotherapy, physiotherapy and
hydrotherapy may also be helpful.
4.2.2. Spasticity
Spasticity can be a very disabling problem in ALS and often
inhibits normal voluntary activities, thereby affecting QOL.

Table 1 – Main symptomatic treatments for amyotrophic lateral sclerosis (ALS).

Symptoms Treatments Posology Main cautions and adverse events Associated
management
Cramps Quinine benzoate 1–2 pills twice daily Ventricular conduction abnormalities Physiotherapy
80 mg (Okimus1) Severe renal insufficiency Hydrotherapy
Immunoallergic manifestations
Spasticity Baclofen 10 mg Initial dose: 10 mg twice dailya High blood pressure Physiotherapy
(Liorésal1) Dizziness, drowsiness Cryotherapy
Dantrolen 25 mg Initial dose: 25 mg once dailya Hepatotoxicity
(Dantrium1) Control liver functions before starting
treatment, then 1 month after
starting, then every 2 months
Tizanidine 4 mg Initial dose: 2 mg twice dailya Renal insufficiency
(Sirdalud) Hepatic insufficiency
Emotional lability Clomipramine Initial dose: 10–15 mg/daya Glaucoma Psychological intervention
(Anafranil1) Prostatic hypertrophy/urinary
Amitriptyline retention
(Laroxyl1) Cardiac arrhythmia
Fluoxetine 20 mg Begin with half the dosea
(Prozac1)
Paroxetine 20 mg
(Deroxat1)
Sialorrhea Clomipramine Initial dose: 10–15 mg/daya Glaucoma
(aAnafranil1) Prostatic hypertrophy/urinary
Amitriptyline retention
(aLaroxyl1) Cardiac arrhythmia
Scopolamine 1 patch every third day Angle-closure glaucoma
(Scopoderm1 1 mg) Local immunoallergic manifestations
Confusion
Urinary retention
Atropine drops 1% 2–4 drops Angle-closure glaucoma
3 or 4 times a day
a
Increase dosage depending on tolerability and effectiveness.

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Acute worsening of spasticity should prompt clinicians to look
for a trigger, such as infection, pain or constipation, and to
treat it. Non-pharmacological and pharmacological treat-
ments are commonly combined to manage spasticity. Passive
stretching and postural exercises represent the most frequent
non-pharmacological measures. Cryotherapy may be propo-
sed in association with these measures.
Oral medications comprise central-acting agents, such as
baclofen, benzodiazepines and tizanidine, and the peripheral-
acting dantrolene. Baclofen and dantrolene are the most
commonly prescribed drugs. Considering their respiratory
depressant effects, benzodiazepines are a second-line drug. In
France, tizanidine is only available with temporary authoriza-
tion from the National agency for the safety of medicines and
health products. For very spastic forms refractory to medical
management, intrathecal baclofen pump placement can be
considered, but only a few cases have been reported so far
[27,28]. Botulinum toxin A (BTXA) has recently shown good
efficacy in a few patients and suggests that BTXA should be
considered as part of spasticity therapy in ALS [29].
4.2.3. Nociceptive pain
Nociceptive pain is common due to the loss of joint mobility or
secondary to pressure because of prolonged immobility. While
pain frequency increases at later stages of disease, this
symptom may be present at an early stage too. In any case,
this symptom impacts QOL [30–32]. Physiotherapy and
adaptive equipment are important for alleviating pain, but
pharmacological treatment may be necessary and should be
prescribed following analgesic treatment guidelines [33].
4.2.4. Neuropathic pain
Neuropathic pain is rare. Specific treatments such as
imipramine, amitriptyline and pregabalin may be proposed
[32]. Small-fiber neuropathy has recently been reported in ALS,
but this pathology seems to be rarely associated with
neuropathic pain [25,34].
4.2.5. Sialorrhea
Sialorrhea (excessive oral secretions, or drooling) is common
and can be socially disabling. It may be treated initially with
anticholinergic medications, such as tricyclic antidepressants,
scopolamine transdermal patches or sublingual atropine
drops (off-label), either used alone or in combination. In cases
of refractory sialorrhea, BTXA and BTXB injections into the
salivary glands may be proposed [35,36]. However, as the toxin
can spread to locoregional muscles and worsen dysphagia, it
should therefore be reserved only for patients with a
gastrostomy. Radiotherapy of salivary glands as per specific
protocols represents another option with fewer side-effects,
but does not last as long as BTX [36].
4.2.6. Pseudobulbar emotional liability
Pseudobulbar emotional liability is characterized by patholo-
gical laughing and crying, and affects up to half of all ALS
patients [37]. The impact on social situations and QOL is
evident. Until recently, pharmacological treatment of this
‘‘pseudobulbar affect’’ (PBA) consisted of off-label use of
antidepressants. Indeed, while randomized clinical trials are
available for stroke and multiple sclerosis, only a few small
Please cite this article in press as: Soriani M-H, Desnuelle C. Care management in amyotrophic lateral sclerosis. Revue neurologique (2017),
http://dx.doi.org/10.1016/j.neurol.2017.03.031
placebo-controlled studies or case reports involve ALS [38,39].
The most commonly used agents are tricyclic antidepressants
(amitriptyline) and selective serotonin reuptake inhibitors
(SSRIs; such as citalopram) [40]. More recently, two randomi-
zed controlled trials using a fixed-dose combination of
dextromethorphan (20 mg)/quinidine (10 mg) have shown
efficacy for PBA [41,42]. However, this treatment has not been
approved in France and is not available so far.
4.2.7. Mood disorders
Anxiety is common at the diagnostic stage [43]. Depression
negatively affects patients’ QOL [44] and higher depressive
scores are associated with greater progression of disease
[45,46]. Mood disorders may require psychotropic treatments.
However, benzodiazepines must be used with caution because
of their respiratory depressant effects. Psychological inter-
ventions may help to reduce anxiety and depression in these
patients.
4.2.8. Insomnia and fatigue
Sleep disorders and asthenia may be symptoms of respiratory
insufficiency and should be investigated. On the other hand,
insomnia may be secondary to anxiety, depressive syndrome
or pain, which then requires specific treatment of the cause.
Fatigue is a disabling symptom and may be experienced as
whole-body tiredness or weakness [47]. Only one small study
using modafinil revealed a significant reduction of fatigue [48].
This result now needs to be confirmed in a larger study.
4.2.9. Venous thromboembolism
Depending on the degree of impaired respiratory function and
immobility, ALS patients may be at increased risk of deep
venous thrombosis. According to a recent study, venous
thromboembolism may be underestimated because of the
prevalence of leg swelling and pain in ALS patients. Respira-
tory muscle weakness and shortness of breath may also mask
symptoms of pulmonary embolism [49]. Management of risk
factors using stockings, limb elevation and physiotherapy is
recommended. The potential benefit of long-term prophylac-
tic anticoagulation has not been demonstrated so far.
5. Rehabilitation: adaptive and assistive
equipment
Rehabilitation is defined as the process of helping people to
achieve their fullest potential despite their disability. Regular
assessment (every 3–6 months) of functional impairment is
needed to propose adaptive and assistive equipment accord-
ing to the ALS patient’s changing needs. Such management
requires advice from an ALS-experienced rehabilitation
practitioner with good knowledge of assistive technology.
As some patients may consider adaptive devices a sign of
resignation, the rehabilitation team should focus on the
functional-expanding aspect of these assist devices. Moreo-
ver, when proposing adapted equipment, certain factors
should be taken into account: realistic evaluation of expecta-
tions; comfort value; and possible reimbursement for expen-
sive assist devices [50].
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5.1. Lower-body weakness
This leads to less-efficient and more energy-consuming gait
patterns [51]. Braces (ankle–foot orthosis), crutches or walkers
can be used when weakness is mild. Manual and transport
wheelchairs can be useful in the early stages, as they offer
greater safety and conserve energy when traveling long
distances. Power wheelchairs may be proposed to preserve
independence for indoor activities and outdoor travel for
highly disabled patients.
5.2. Upper-body weakness
Adaptive tools are also available for this situation [52]. Simple
devices allow the patient to get dressed, wash and eat
independently, read and write, and use computers. Environ-
mental control devices enable patients with significant
disability to independently access equipment in their own
environments.
5.3. Dropped-head syndrome
This is characterized by a severe kyphotic deformity of the
cervical spine due to neck extensor weakness. It is the first
symptom observed in 2% of patients with ALS, but may
present at a later stage of disease [53]. Cervical orthosis may be
proposed to prevent pain or compensate for the head-
dropping, and include soft and hard collars.
5.4. Communication
Dysarthria is frequent in ALS, affecting up to 70% of
patients with limb onset at a later stage, while 25–30% of
ALS patients have dysarthria as the first or predominant
sign in early-stage disease. Augmentative and alternative
communication systems increase patients’ QOL and can
also reduce their carers’ burden [54]. Low-tech systems,
such as writing boards, pointing boards with figures or
words and text-to-speech applications, are easily accessible.
Eye-pointing, eye-gaze or head-tracking augmentative high-
tech devices may be useful. More recently, brain–computer
interfaces (BCI) have been developed. The principle of BCI is
to interpret the brain’s electrical signals and translate them
into commands. The P300-Speller, a paradigm for BCI
communication, has already been tested in small groups
of ALS patients, with encouraging positive results in terms
of usability.
5.5. Physical exercises
In healthy people, physical exercise provides a wide range of
benefits for health and well-being, notably an increase in
muscle strength and possibly a neuroprotective effect. In ALS,
whether physical activity promotes or prevents progression of
motor neuron degeneration is still debated. A recent Cochrane
analysis concluded that the results of two previously reported
studies are inconclusive as to whether muscle-strengthening
exercises are beneficial for ALS patients [55]. While a more
recent study reported that closely monitored exercise should
reduce motor deterioration [56], this result was from a small
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5
sample of ALS patients and needs to be confirmed in a larger
population.
6. Nutrition and deglutition
It has been clearly demonstrated that loss of weight is an
independent poor prognostic factor in ALS patients [57–59].
Mildly obese ALS patients experienced slower declines on the
revised ALS functional rating scale (ALSFRS-R), and longer
survival times than underweight patients [60]. These results
underline the major place of nutritional issues in ALS and,
therefore, the importance of nutritional assessment and
management at early stages of disease. Three main reasons
can explain the risk of weight loss: muscle wasting; increasing
resting energy expenditures; and poor food intakes. The latter
may be due to dysphagia, anxiety, mood disorders or severe
upper-limb disability. Muscle wasting due to motor neuron
degeneration cannot be dealt by specific treatment, but other
parameters can be managed.
6.1. Dysphagia
A swallowing impairment is reported by 85% of ALS patients at
some point of the disease process [61]. Because of weakness
and/or rigidity of the swallowing muscles, the oropharyngeal
stage of swallowing may be impaired. Dysphagia increases
eating duration and decreases eating desire, and also
generates a burden and, thus, has a negative impact on QOL
[62,63]. Moreover, dysphagia may be the major cause of
malnutrition leading to weight loss [64]. Respiratory compli-
cations can arise due to choking and pulmonary aspiration.
Consequently, regular swallowing assessment is proposed to
identify a swallowing impairment early.
Dysphagia management includes: (1) adapting food and
fluid consistency, and adjusting posture to improve degluti-
tion and avoid penetration and aspiration; (2) high-calorie,
high-protein feeding and the use of oral nutritional sup-
plements to avoid loss of weight secondary to decreased
intakes; (3) percutaneous endoscopic gastrostomy (PEG) tube
placement to circumvent an oral feeding deficit (Table 2)
[65,66].
6.2. Energy expenditure
Energy homeostasis is the result of a balance between energy
intakes and energy expenditures. If a reduced food intake is
contributing to energy imbalance, then other factors should be
considered. First, an increase in resting energy expenditure
(hypermetabolism) due to unknown causes is observed in
> 50% of ALS patients. Increased physical activity is another
potential contributor to energy imbalance [67–69]. As for
energy expenditures related to respiratory changes and the
impact of mechanical ventilation, data are scarce. Altogether,
estimation of total energy expenditures and, as a corollary,
energy needs requires taking into account patients’ increasing
basal metabolism, respiratory status and physical activity.
Supplementing with a high-calorie diet might prevent weight
loss in these ALS patients [70].
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Table 2 – Dysphagia and nutritional management of amyotrophic lateral sclerosis (ALS).
Recommendations
Food and fluid adaptation
Postural adjustment
High-calorie, high-protein feeding
Consider gastrostomy after taking into account
Dysphagia
Weight loss > 10%
Worsening of respiratory function
Home parenteral nutrition
6.3. Nutritional assessment
This is recommended at diagnosis and at each quarterly
multidisciplinary evaluation, and involves weight measurement
and assessment of body mass index (BMI = weight in kg/height in
m), nutritional and fluid intakes, swallowing evaluation (by a
speech therapist as well, if necessary), motor skill of the upper
limbs for eating and drinking, duration of mealtimes and causes
of reduced food intakes (such as posture, mood disorders,
gastrointestinal symptoms, fear of choking in social situations).
6.4. Enteral nutrition
Enteral nutrition aims to sustain nutritional intakes and
alleviate the difficulties caused by advanced dysphagia. In
some cases, brachial diplegia with total dependence during
eating may lead to enteral nutrition too.
Gastrostomy feeding should be considered in first inten-
tion. Two main methods currently used for ALS patients are
percutaneous endoscopic gastrostomy (PEG) and percuta-
neous radiological gastrostomy (PRG). According to the
literature, there is little evidence available regarding the
choice of method and timing of tube placement. However,
according to an expert task force on ALS management, PEG is
considered the standard procedure, but should be performed
before vital capacity falls to < 50% of predicted value [9,71,72].
Otherwise, non-invasive ventilation should be initiated prior
to gastrostomy insertion [73]. PRG has the advantage of not
requiring patient sedation for insertion and seems to be safer
in ALS cases with moderate-to-severe respiratory impairment
[74]. While the impact of gastrostomy on QOL and survival has
not been clearly demonstrated, many studies have suggested
that gastrostomy could be beneficial for survival, QOL and
nutritional outcomes [75–77].
Nasogastric tube insertion can be performed in all patients.
However, because of drawbacks such as nasopharyngeal
discomfort, an increase in oropharyngeal secretions and even
esophageal ulceration, it represents only a temporary alter-
native to gastrostomy.
Home parenteral nutrition has recently been proposed as
an alternative to enteral feeding for patients with advanced
ALS and poor respiratory function [78,79].
7. Respiratory management
Weakness of the respiratory muscles affects most ALS
patients as the disease progresses. It affects both inspiratory
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Main goals
Improve deglutition
Avoid aspiration
Avoid weight loss
Avoid aspiration
Circumvent oral feeding deficit
May be used when gastrostomy is not suitable (patients with advanced
ALS)
(primarily the diaphragm) and expiratory muscles, resulting in
reduced pulmonary volumes, ineffective cough and secretion
retention. Respiratory failure, the main cause of death in ALS,
is the consequence of both severe diaphragmatic weakness
and ineffective cough. Detecting respiratory dysfunction early
in the disease is important for preventing complications such
as pulmonary infection and secretion retention.
7.1. Respiratory assessment
Respiratory assessment is based first on the evaluation of
symptoms suggestive of respiratory insufficiency (Table 3).
However, as clinical symptoms usually arise late in the
disease, functional respiratory tests should be performed at
diagnosis and then every 3–6 months.
Spirometry provides data on volume and flow that are
useful in clinical practice to make the diagnosis. Slow (SVC)
and forced vital capacity (FVC) measurements are widely used
parameters, but are not sensitive for early detection of
respiratory failure [80]. However, repeated measurements of
SVC and FVC are an efficient way to detect loss of lung
function. Moreover, when upright and supine SVC measure-
ments are compared, an SVC decrease of > 30% in supine
position may be a useful sign for detecting diaphragmatic
weakness.
Maximal inspiratory pressure (MIP) and sniff nasal ins-
piratory pressure (SNIP) are the most widely used tests to
specifically assess inspiratory muscle strength. MIP is an early
indicator of respiratory muscle weakness, but may be difficult
in practice because of lip leakage in bulbar patients [81]. SNIP is
quick and easy to do, is not affected by bulbar muscle
weakness, is strongly correlated with invasively measured
transdiaphragmatic muscle strength and reproducible in
advanced stages of disease [82], making SNIP a good
prognostic tool. Indeed, a SNIP of < 40 cmH2O correlates with
nocturnal hypoxemia [83] and, even in early-stage disease,
assessment of SNIP may help to identify patients with high
risk of death [84].
Maximal expiratory pressure (MEP) is a marker of expira-
tory function and reflects the ability to cough. Peak cough flow
(PCF) is a simple and generally accepted means of assessment.
For all these assessments, it should be borne in mind that
voluntary effort is dependent on corticobulbar and corticos-
pinal pathways, which are frequently affected in pseudo-
bulbar patients. Thus, the ability to carry out forced exercise
may be reduced and respiratory function underestimated.
Measurement of gas exchange represents a complementary
way to assess ventilation.
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Table 3 – Symptoms and signs of respiratory insuffi-

ciency and nocturnal hypoxemia.
Symptoms of Dyspnea on effort or speech
respiratory Shortness of breath
insufficiency Cognitive impairment (memory,
concentration)
Clinical signs of Tachypnea
respiratory Orthopnea
insufficiency Use of accessory respiratory muscles
Thoracoabdominal asynchrony
Sweating
Weight loss
Symptoms of Frequent nocturnal awakenings
nocturnal Excessive daytime sleepiness
hypoxemia Nocturnal polyuria
Morning headache
Vivid or bad dreams

7.2. Nocturnal gas exchange

Hypoventilation due to respiratory muscle weakness leads to

a decrease in gas exchanges and, consequently, to hypoxemia
and hypercapnia. Nocturnal hypoventilation may precede
respiratory symptoms and may be an indicator of when to
start non-invasive ventilation.
The most appropriate strategy to identify sleep hypoventi-
lation is yet to be clearly defined. In clinical practice,
hypoventilation is assessed by nocturnal pulse oximetry
(NPO) and morning arterial blood gas (ABG) values. Recently,
many studies have suggested that continuous transcutaneous
carbon-dioxide partial pressure (TcPCO2) monitoring throu-
ghout the night may be useful for detecting nocturnal
hypercapnia [85], while respiratory polygraphy represents
an alternative to NPO, providing detailed information of
nightly respiration and peripheral blood oxygenation. Poly-
somnography offers an interesting analysis of sleep architec-
ture, but is more time-consuming and costly, which is why it is
proposed only for complex cases.
7.3. Non-invasive ventilation (NIV)
Non-invasive ventilation (NIV) is an established effective
long-term treatment for ALS patients. It uses a face or nasal
mask, with a volume-cycled or bilevel pressure-limited
ventilator that provides intermittent positive pressure to
support ventilation. Continuous positive ventilation is not
recommended for ALS patients because, with constant
pressure during both inspiration and expiration, the work of
breathing is increased [86]. Many studies have demonstrated
that NIV may be associated with improved sleep-related
symptoms and QOL [87]. In addition, early NIV treatment may
offer survival benefits, particularly in the subgroup of patients
with normal or moderately impaired bulbar function, without
increasing the burden for carers [88–91].
An FVC < 50% plus symptoms and clinical signs of
respiratory failure have been widely applied as the threshold
for initiating NIV. Decreased inspiratory muscle strength
(SNIP < 40 cmH2O), hypoxia on nocturnal oximetry and
hypercapnia on morning ABG are also strong evidence for
starting NIV.
However, the presence of bulbar symptoms with increased
oropharyngeal secretions, the inability to manually adjust the
Fig. 2 – Algorithm of respiratory insufficiency management
for amyotrophic lateral sclerosis (ALS). FVC: Forced vital
capacity; NIV: Non-invasive ventilation; MIP: Maximal
inspiratory pressure; MIV: Mechanical invasive
ventilation; SNIP: Sniff nasal inspiratory pressure.
mask due to upper-limb deficit and the presence of cognitive
disorders represent the main factors that adversely affect the
tolerability of NIV [92]. Difficulty acclimatizing to the mask
because of the inspiratory air pressure and a sense of
claustrophobia may represent further factors of NIV intole-
rability. In such cases, low-dose anxiolytic treatment may help
with relaxation. Fig. 2 summarizes the management of
respiratory insufficiency.
7.4. Invasive mechanical ventilation (IMV)
This bypasses the upper airways through the use of a
tracheostomy or endotracheal tube. It prevents aspiration
and provides more effective ventilator pressures and better
gas exchange, which is why IMV theoretically increases
survival time from months to years, despite the progression
of ALS disease. However, IMV presents some risks and
drawbacks, such as increased bronchial secretions and
infections, and tracheoesophageal fistula and tracheal steno-
sis [93]. However, the most important point about tracheos-
tomy in ALS is the possible discrepancy between patients’ and
caregivers’ attitudes. While most patients receiving tracheos-
tomy ventilation at home report satisfactory QOL, the heavy
burden on caregivers is frequently reported [94,95]. This is why
attitudes about ventilation options need to be periodically
explored with both patients and their caregivers throughout
the course of disease, and why healthcare professionals

Please cite this article in press as: Soriani M-H, Desnuelle C. Care management in amyotrophic lateral sclerosis. Revue neurologique (2017),
http://dx.doi.org/10.1016/j.neurol.2017.03.031
NEUROL-1780; No. of Pages 12
8 revue neurologique xxx (2017) xxx–xxx
should provide opportunities for discussion focused on
various issues [96]. Ideally, unplanned IMV should be avoided,
with the patient’s advance directives established before
respiratory complications arise [97]. Taking into account the
recent changes in the French legislative framework, the
patient should be informed of the ethical issues regarding
IMV discontinuation (the Claeys–Leonetti law). Indeed, while
both euthanasia and assisted suicide remain illegal, ‘‘deep and
continuous sedation until death’’ is allowed, albeit only under
certain circumstances.
7.5. Diaphragmatic pacing (DP)
Diaphragmatic pacing (DP) is a surgical procedure developed to
restore permanent efficient breathing in patients with high-
level spinal cord injuries and central hypoventilation syn-
drome. In 2015, a multicenter, open-label, randomized control-
led trial showed that the addition of DP to standard care during
NIV was associated with reduced survival [98]. At the same
time, a French multicenter, double-blind, randomized control-
led trial was prematurely terminated because of a statistically
significant excess mortality rate in patients receiving active
stimulation (article accepted for publication). Given these
results and the present state of knowledge, DP should not be
a routine treatment for respiratory failure for ALS patients.
7.6. Airway clearance
Impaired cough efficacy predisposes ALS patients to accu-
mulate bronchial secretions, whereas improving secretion
clearance is important for promoting QOL, improving NIV
tolerability and decreasing the risk of infection. An effective
cough requires the inspiratory muscles to generate deep
inspiration of around 2–4 L, followed by closure of the glottis,
and a PCF of 360–1000 L/min in adults, depending on age, body
size and gender. This is the level of expiratory flow after glottal
opening required to shear away secretions and debris from the
airways, then lift them up into the upper airways and mouth.
When PCF is < 270 L/min, teaching patients and caregivers
how to perform a manually assisted cough is the simplest and
most effective step. Air stacking, using a lung volume
recruitment bag with a one-way valve (‘‘Ambu’’ bag), can
work, but demands good glottal control. When PCF is < 160 L/
min, mechanical insufflation–exsufflation (MI–E) is increasin-
gly recommended. Despite the lack of large randomized trials,
there is cumulative evidence that MI–E increases PCF and, in
combination with NIV, may prolong survival. High-frequency
oscillation combined with MI–E has been developed and may
help to clear away airway secretions [99].
Mucosal clearing may justify the addition of pharmacolo-
gical treatment. Beta-receptor antagonists (propranolol, meto-
prolol) or a nebulizer with saline and/or an anticholinergic
bronchodilator may be useful, although there are no control-
led trials in ALS. Mucolytics (N-acetylcysteine) should only be
used when sufficient cough flow is present.
7.7. Vaccination
The AAN recommends that ALS patients be vaccinated for
both pneumococcal disease (Pneumovax) and influenza [73].
Please cite this article in press as: Soriani M-H, Desnuelle C. Care management in amyotrophic lateral sclerosis. Revue neurologique (2017),
http://dx.doi.org/10.1016/j.neurol.2017.03.031
Beware: given their effect as a respiratory depressant,
benzodiazepines should be used with caution in patients with
incipient respiratory failure. Moreover, patients with early
evidence of respiratory failure should not be treated with
oxygen without other forms of ventilatory support, as oxygen
therapy in respiratory failure suppresses the hypoxic drive
and increases the risk of hypercapnia [86].
8. Cognitive impairment
ALS is associated with mild cognitive or behavioral impair-
ment in 50% of patients [2,100]. Executive dysfunction is
characterized by deficits in attention, cognitive flexibility and
word generation, with relative preservation of visuospatial
capacity. Mild memory decline may also be observed due to an
encoding deficit. ALS behavioral impairment refers to changes
in social interactions unrelated to a psychiatric condition.
Apathy is more commonly reported than disinhibition
[47,101]. Deficits in emotional processing and social cognition
have also been described, but the extent to which these
changes are related to executive dysfunction remains unclear
[102,103]. ALS with dementia that meets the Neary criteria for
frontotemporal dementia (FTD) has an insidious onset and a
gradual progression, and is characterized by emotional
blunting, altered social conduct and loss of insight [104].
Cognitive involvement is more frequent among patients with
bulbar onset, and has been associated with shorter survival
[105].
8.1. Assessment of cognitive impairment
Verbal fluency (1-min letter fluency) deficits are a quick and
sensitive measure of cognitive impairment. To evaluate
executive function, the applicability of cognitive screening
tests is rather limited in ALS patients due to their physical
disability. For this reason, the Edinburgh Cognitive and
Behavioural ALS Screen (ECAS) was developed as a quick
and easy cognitive screening tool specifically designed for ALS
patients [106]. The ECAS has been validated in English, and its
high sensitivity and specificity in characterizing ALS impair-
ment have been demonstrated [107]. Validation of its
effectiveness in the French language is currently ongoing.
8.2. Care of patients with cognitive and behavioral
impairment
The association between ALS and cognitive impairment
creates a challenge for caregivers, who need to be aware that
executive dysfunction can manifest as difficulty in managing
affairs/finances, planning for the future, making decisions and
learning new tasks. In such patients, non-compliance with
symptomatic treatment (gastrostomy and NIV) is high and
survival is low [108]. Adaptation and the use of assist devices
may be more difficult too. Irritability is a very common
symptom of behavioral impairment, and can manifest as
mood swings and bursts of anger, often over trivia. Self-
centeredness and a lack of empathy may also be observed.
Cognitive and/or behavioral impairment is commonly asso-
ciated with high levels of stress and burden in caregivers [109].
NEUROL-1780; No. of Pages 12
revue neurologique xxx (2017) xxx–xxx
In the absence of evaluated pharmacological treatments for
such impairment in ALS, recommendations as for FTD may be
applied [110].
9. Palliative and end-of-life care
Involvement in palliative care (PC) by the multidisciplinary
team helps to improve QOL, symptom control and caregiver
burden [111,112]. Although the EFNS task force recommends
the PC approach from diagnosis onwards, the timing of
specialist PC intervention varies widely in different countries.
Early referral to palliative services allows the patient sufficient
time to establish a relationship with the PC staff and to
address end-of-life issues. The optimal PC approach relies on
three important ethical principles: autonomy, dignity and
QOL.
In France, the new law recently developed by two members
of the French parliament (A. Claeys and J. Leonetti) and passed
on 2 February 2016 extends patients’ rights at the end of life.
First, the law encourages all individuals to set out advance
directives that healthcare providers are now required by law to
follow and, second, the law strengthens the position of PC by
promoting the integration of PC throughout supportive care.
These new legislative inputs reinforce the notion of comple-
mentarity among healthcare teams. It is also important to
note that effective communication between the multidisci-
plinary ALS team, the primary-care physician and the PC team
is essential for appropriate management.
In addition, the new law clearly specifies that hydration
and artificial nutrition are now classified as treatment rather
than supportive care, and can therefore be withdrawn when
the decision to limit treatment is made. Moreover, ‘‘deep and
continuous sedation until death’’ is allowed when patients
consider that treatment represents aggressive therapy.
Patients receiving mechanical ventilation now also have the
right to discontinue their respiratory support, and the
withdrawal of mechanical ventilation must be practised in a
manner that causes minimal discomfort to the patient. In a
recent review of how life support is withdrawn, the Canadian
authors found significant variations in actual practice [113].
However, preparations to withdraw life-sustaining therapy,
including information to the family, organizing the care team
and adapting the care environment, appeared to be consen-
sual. In addition, all of the studies recommended the use of
pharmaceutical agents to help alleviate distressing symp-
toms. In particular, the authors suggested opioids for pain and
dyspnea, and benzodiazepine for anxiety or agitation. Never-
theless, there were significant differences among physicians
as to how and when life-sustaining therapy should be
withdrawn, especially in cases of mechanical ventilation.
10. Conclusion
The development of specialized multidisciplinary ALS centers
and life-support assistive devices improves QOL and increases
survival in ALS patients. Partnering with patients to help them
choose the appropriate assist devices and to set down their
advance directives ensures that their autonomy will be
Please cite this article in press as: Soriani M-H, Desnuelle C. Care management in amyotrophic lateral sclerosis. Revue neurologique (2017),
http://dx.doi.org/10.1016/j.neurol.2017.03.031
9
respected. This requires good listening skills, weighted
communication and ethical considerations on the part of
caregivers. These skills are all essential for accompanying the
patient with sensitivity up to the final stage of the disease.
Disclosure of interest
The authors declare that they have no competing interest.
references
[1] Soriani MH, Desnuelle C. [Epidemiology of amyotrophic
lateral sclerosis]. Rev Neurol 2009;165(8–9):627–40.
[2] Ringholz GM, Appel SH, Bradshaw M, Cooke NA, Mosnik
DM, Schulz PE. Prevalence and patterns of cognitive
impairment in sporadic ALS. Neurology 2005;65(4):586–90.
[3] Strong MJ, Grace GM, Freedman M, Lomen-Hoerth C,
Woolley S, Goldstein LH, et al. Consensus criteria for the
diagnosis of frontotemporal cognitive and behavioural
syndromes in amyotrophic lateral sclerosis. Amyotroph
Lateral Scler 2009;10(3):131–46.
[4] Gordon PH, Delgadillo D, Piquard A, Bruneteau G, Pradat
PF, Salachas F, et al. The range and clinical impact of
cognitive impairment in French patients with ALS: a cross-
sectional study of neuropsychological test performance.
Amyotroph Lateral Scler 2011;12(5):372–8.
[5] Marangi G, Traynor BJ. Genetic causes of amyotrophic
lateral sclerosis: new genetic analysis methodologies
entailing new opportunities and challenges. Brain Res
2015;1607:75–93.
[6] Renton AE, Chio A, Traynor BJ. State of play in
amyotrophic lateral sclerosis genetics. Nat Neurosci
2014;17(1):17–23.
[7] Logroscino G, Traynor BJ, Hardiman O, Chio A, Couratier P,
Mitchell JD, et al. Descriptive epidemiology of amyotrophic
lateral sclerosis: new evidence and unsolved issues. J
Neurol Neurosurg Psychiatry 2008;79(1):6–11.
[8] PNDS-Sclérose latérale amyotrophique. http://www.has-
sante.fr/portail/upload/docs/application/pdf/2015-11/
pnds-sclerose_laterale_amyotrophique_sla.pdf. Accessed:
Nov 18 2015.
[9] Andersen PM, Abrahams S, Borasio GD, de Carvalho M,
Chio A, Van Damme P, et al. EFNS guidelines on the
clinical management of amyotrophic lateral sclerosis
(MALS) – revised report of an EFNS task force. Eur J Neurol
2012;19(3):360–75.
[10] Miller RG, Jackson CE, Kasarskis EJ, England JD, Forshew D,
Johnston W, et al. Practice parameter update: the care of
the patient with amyotrophic lateral sclerosis:
multidisciplinary care, symptom management, and
cognitive/behavioral impairment (an evidence-based
review): report of the Quality standards subcommittee of
the American academy of neurology. Neurology
2009;73(15):1227–33.
[11] Leigh PN, Abrahams S, Al-Chalabi A, Ampong MA,
Goldstein LH, Johnson J, et al. The management of motor
neurone disease. J Neurol Neurosurg Psychiatry
2003;74(Suppl. 4):iv32–47.
[12] Chio A, Bottacchi E, Buffa C, Mutani R, Mora G. Positive
effects of tertiary centres for amyotrophic lateral sclerosis
on outcome and use of hospital facilities. J Neurol
Neurosurg Psychiatry 2006;77(8):948–50.
[13] Traynor BJ, Alexander M, Corr B, Frost E, Hardiman O.
Effect of a multidisciplinary amyotrophic lateral sclerosis
NEUROL-1780; No. of Pages 12
10 revue neurologique xxx (2017) xxx–xxx
(ALS) clinic on ALS survival: a population based
study, 1996–2000. J Neurol Neurosurg Psychiatry
2003;74(9):1258–61.
[14] Rooney J, Byrne S, Heverin M, Tobin K, Dick A, Donaghy C,
et al. A multidisciplinary clinic approach improves
survival in ALS: a comparative study of ALS in Ireland and
Northern Ireland. J Neurol Neurosurg Psychiatry
2015;86(5):496–501.
[15] Van den Berg JP, Kalmijn S, Lindeman E, Veldink JH, de
Visser M, Van der Graaff MM, et al. Multidisciplinary ALS
care improves quality of life in patients with ALS.
Neurology 2005;65(8):1264–7.
[16] Delevallez F, Lienard A, Gibon AS, Razavi D. [Breaking bad
news in oncology: the Belgian experience]. Rev Mal Respir
2014;31(8):721–8.
[17] Silani V, Borasio GD. Honesty and hope: announcement of
diagnosis in ALS. Neurology 1999;53(8 Suppl. 5):S37–9
[discussion S40–2].
[18] Borasio GD, Sloan R, Pongratz DE. Breaking the news in
amyotrophic lateral sclerosis. J Neurol Sci 1998;160(Suppl.
1):S127–33.
[19] Seeber AA, Pols AJ, Hijdra A, Grupstra HF, Willems DL, de
Visser M. Experiences and reflections of patients with
motor neuron disease on breaking the news in a two-
tiered appointment: a qualitative study. BMJ Support
Palliat Care 2016.
[20] Bensimon G, Lacomblez L, Meininger V, ALS/Riluzole
study group. A controlled trial of riluzole in amyotrophic
lateral sclerosis. N Engl J Med 1994;330(9):585–91.
[21] Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meininger V,
Amyotrophic lateral sclerosis/Riluzole study group II.
Dose-ranging study of riluzole in amyotrophic lateral
sclerosis. Lancet 1996;347(9013):1425–31.
[22] Miller RG, Mitchell JD, Lyon M, Moore DH. Riluzole for
amyotrophic lateral sclerosis (ALS)/motor neuron disease
(MND). Cochrane Database Syst Rev 2007;1:CD001447.
[23] Desnuelle C, Dib M, Garrel C, Favier A, ALS riluzole-
tocopherol study group. A double-blind, placebo-
controlled randomized clinical trial of alpha-tocopherol
(vitamin E) in the treatment of amyotrophic lateral
sclerosis. Amyotroph Lateral Scler Motor Neuron Disord
2001;2(1):9–18.
[24] Weber M, Goldman B, Truniger S. Tetrahydrocannabinol
(THC) for cramps in amyotrophic lateral sclerosis: a
randomised, double-blind crossover trial. J Neurol
Neurosurg Psychiatry 2010;81(10):1135–40.
[25] Weiss MD, Macklin EA, Simmons Z, Knox AS, Greenblatt
DJ, Atassi N, et al. A randomized trial of mexiletine in ALS:
safety and effects on muscle cramps and progression.
Neurology 2016;86(16):1474–81.
[26] Bedlack RS, Pastula DM, Hawes J, Heydt D. Open-label pilot
trial of levetiracetam for cramps and spasticity in patients
with motor neuron disease. Amyotroph Lateral Scler
2009;10(4):210–5.
[27] McClelland 3rd S, Bethoux FA, Boulis NM, Sutliff MH,
Stough DK, Schwetz KM, et al. Intrathecal baclofen for
spasticity-related pain in amyotrophic lateral sclerosis:
efficacy and factors associated with pain relief. Muscle
Nerve 2008;37(3):396–8.
[28] Marquardt G, Seifert V. Use of intrathecal baclofen for
treatment of spasticity in amyotrophic lateral sclerosis. J
Neurol Neurosurg Psychiatry 2002;72(2):275–6.
[29] Vazquez-Costa JF, Manez I, Alabajos A, Guevara Salazar M,
Roda C, Sevilla T. Safety and efficacy of botulinum toxin A
for the treatment of spasticity in amyotrophic lateral
sclerosis: results of a pilot study. J Neurol 2016.
[30] Wallace VC, Ellis CM, Burman R, Knights C, Shaw CE, Al-
Chalabi A. The evaluation of pain in amyotrophic lateral
sclerosis: a case controlled observational study.
Please cite this article in press as: Soriani M-H, Desnuelle C. Care management in amyotrophic lateral sclerosis. Revue neurologique (2017),
http://dx.doi.org/10.1016/j.neurol.2017.03.031
Amyotroph Lateral Scler Frontotemp Degen 2014;15(7–
8):520–7.
[31] Hanisch F, Skudlarek A, Berndt J, Kornhuber ME.
Characteristics of pain in amyotrophic lateral sclerosis.
Brain Behav 2015;5(3):e00296.
[32] Moisset X, Cornut-Chauvinc C, Clavelou P, Pereira B, Dallel
R, Guy N. Is there pain with neuropathic characteristics in
patients with amyotrophic lateral sclerosis?. A cross-
sectional study. Palliat Med 2016;30(5):486–94.
[33] Lanteri-Minet M. [Treatment of nociceptive pain in
primary care setting]. Rev Prat 2013;63(6):788–94.
[34] Dalla Bella E, Lombardi R, Porretta-Serapiglia C, Ciano C,
Gellera C, Pensato V, et al. Amyotrophic lateral
sclerosis causes small fiber pathology. Eur J Neurol
2016;23(2):416–20.
[35] Petracca M, Guidubaldi A, Ricciardi L, Ialongo T, Del
Grande A, Mulas D, et al. Botulinum toxin A and B in
sialorrhea: long-term data and literature overview.
Toxicon 2015;107(Pt A):129–40.
[36] Banfi P, Ticozzi N, Lax A, Guidugli GA, Nicolini A, Silani V.
A review of options for treating sialorrhea in amyotrophic
lateral sclerosis. Respir Care 2015;60(3):446–54.
[37] Miller A, Pratt H, Schiffer RB. Pseudobulbar affect: the
spectrum of clinical presentations, etiologies and
treatments. Expert Rev Neurother 2011;11(7):1077–88.
[38] Szczudlik A, Slowik A, Tomik B. [The effect of
amitriptyline on the pathological crying and
other pseudobulbar signs]. Neurol Neurochir Pol
1995;29(5):663–74.
[39] Iannaccone S, Ferini-Strambi L. Pharmacologic
treatment of emotional lability. Clin Neuropharmacol
1996;19(6):532–5.
[40] King RR, Reiss JP. Treatment of pseudobulbar affect
with citalopram in a patient with progressive
multifocal leukoencephalopthy. J Clin Neurosci
2012;19(1):185–6.
[41] Brooks BR, Thisted RA, Appel SH, Bradley WG, Olney RK,
Berg JE, et al. Treatment of pseudobulbar affect in ALS
with dextromethorphan/quinidine: a randomized trial.
Neurology 2004;63(8):1364–70.
[42] Pioro EP, Brooks BR, Cummings J, Schiffer R, Thisted RA,
Wynn D, et al. Dextromethorphan plus ultra low-dose
quinidine reduces pseudobulbar affect. Ann Neurol
2010;68(5):693–702.
[43] Vignola A, Guzzo A, Calvo A, Moglia C, Pessia A, Cavallo E,
et al. Anxiety undermines quality of life in ALS patients
and caregivers. Eur J Neurol 2008;15(11):1231–6.
[44] Tramonti F, Bongioanni P, Di Bernardo C, Davitti S, Rossi B.
Quality of life of patients with amyotrophic lateral
sclerosis. Psychol Health Med 2012;17(5):621–8.
[45] Cui F, Zhu W, Zhou Z, Ren Y, Li Y, Li M, et al. Frequency
and risk factor analysis of cognitive and anxiety-
depressive disorders in patients with amyotrophic lateral
sclerosis/motor neuron disease. Neuropsychiatr Dis
Treatment 2015;11:2847–54.
[46] Jelsone-Swain L, Persad C, Votruba KL, Weisenbach SL,
Johnson T, Gruis KL, et al. The relationship between
depressive symptoms, disease state, and cognition in
amyotrophic lateral sclerosis. Frontiers Psychol
2012;3:542.
[47] Gibbons ZC, Richardson A, Neary D, Snowden JS.
Behaviour in amyotrophic lateral sclerosis. Amyotroph
Lateral Scler 2008;9(2):67–74.
[48] Rabkin JG, Gordon PH, McElhiney M, Rabkin R, Chew S,
Mitsumoto H. Modafinil treatment of fatigue in patients
with ALS: a placebo-controlled study. Muscle & nerve
2009;39(3):297–303.
[49] Gladman M, Dehaan M, Pinto H, Geerts W, Zinman L.
Venous thromboembolism in amyotrophic
NEUROL-1780; No. of Pages 12
revue neurologique xxx (2017) xxx–xxx
lateral sclerosis: a prospective study. Neurology
2014;82(19):1674–7.
[50] Majmudar S, Wu J, Paganoni S. Rehabilitation in
amyotrophic lateral sclerosis: why it matters. Muscle
Nerve 2014;50(1):4–13.
[51] Menotti F, Felici F, Damiani A, Mangiola F, Vannicelli R,
Macaluso A. Charcot-Marie-Tooth 1A patients with low
level of impairment have a higher energy cost of walking
than healthy individuals. Neuromuscul Disord
2011;21(1):52–7.
[52] Dal Bello-Haas V, Kloos AD, Mitsumoto H. Physical
therapy for a patient through six stages of amyotrophic
lateral sclerosis. Phys Ther 1998;78(12):1312–24.
[53] Gourie-Devi M, Nalini A, Sandhya S. Early or late
appearance of ‘‘dropped head syndrome’’ in amyotrophic
lateral sclerosis. J Neurol Neurosurg Psychiatry
2003;74(5):683–6.
[54] Londral A, Pinto A, Pinto S, Azevedo L, De Carvalho M.
Quality of life in amyotrophic lateral sclerosis patients and
caregivers: impact of assistive communication from early
stages. Muscle Nerve 2015;52(6):933–41.
[55] Dal Bello-Haas V, Florence JM. Therapeutic exercise for
people with amyotrophic lateral sclerosis or motor neuron
disease. Cochrane Database Syst Rev 2013;5:CD005229.
[56] Lunetta C, Lizio A, Sansone VA, Cellotto NM, Maestri E,
Bettinelli M, et al. Strictly monitored exercise programs
reduce motor deterioration in ALS: preliminary results of a
randomized controlled trial. J Neurol 2016;263(1):52–60.
[57] Marin B, Desport JC, Kajeu P, Jesus P, Nicolaud B, Nicol M,
et al. Alteration of nutritional status at diagnosis is a
prognostic factor for survival of amyotrophic lateral
sclerosis patients. J Neurol Neurosurg Psychiatry
2011;82(6):628–34.
[58] Desport JC, Preux PM, Truong TC, Vallat JM, Sautereau D,
Couratier P. Nutritional status is a prognostic factor for
survival in ALS patients. Neurology 1999;53(5):1059–63.
[59] O’Reilly EJ, Wang H, Weisskopf MG, Fitzgerald KC, Falcone
G, McCullough ML, et al. Premorbid body mass index and
risk of amyotrophic lateral sclerosis. Amyotroph Lateral
Scler Frontotemp Degen 2013;14(3):205–11.
[60] Reich-Slotky R, Andrews J, Cheng B, Buchsbaum R, Levy D,
Kaufmann P, et al. Body mass index (BMI) as predictor of
ALSFRS-R score decline in ALS patients. Amyotroph
Lateral Scler Frontotemp Degen 2013;14(3):212–6.
[61] Carpenter 3rd RJ, McDonald TJ, Howard Jr FM. The
otolaryngologic presentation of amyotrophic lateral
sclerosis. Otolaryngology 1978;86(3 Pt 1). ORL479-84.
[62] Paris G, Martinaud O, Petit A, Cuvelier A, Hannequin D,
Roppeneck P, et al. Oropharyngeal dysphagia in
amyotrophic lateral sclerosis alters quality of life. J Oral
Rehabil 2013;40(3):199–204.
[63] Tabor L, Gaziano J, Watts S, Robison R, Plowman EK.
Defining swallowing-related quality of life profiles in
individuals with amyotrophic lateral sclerosis. Dysphagia
2016;31(3):376–82.
[64] Kawai S, Tsukuda M, Mochimatsu I, Enomoto H, Kagesato
Y, Hirose H, et al. A study of the early stage of dysphagia in
amyotrophic lateral sclerosis. Dysphagia 2003;18(1):1–8.
[65] Greenwood DI. Nutrition management of amyotrophic
lateral sclerosis. Nutr Clin Pract 2013;28(3):392–9.
[66] Braun MM, Osecheck M, Joyce NC. Nutrition assessment
and management in amyotrophic lateral sclerosis. Phys
Med Rehabil Clin N Am 2012;23(4):751–71.
[67] Vaisman N, Lusaus M, Nefussy B, Niv E, Comaneshter D,
Hallack R, et al. Do patients with amyotrophic lateral
sclerosis (ALS) have increased energy needs? J Neurol Sci
2009;279(1–2):26–9.
[68] Bouteloup C, Desport JC, Clavelou P, Guy N, Derumeaux-
Burel H, Ferrier A, et al. Hypermetabolism in ALS patients:
Please cite this article in press as: Soriani M-H, Desnuelle C. Care management in amyotrophic lateral sclerosis. Revue neurologique (2017),
http://dx.doi.org/10.1016/j.neurol.2017.03.031
11
an early and persistent phenomenon. J Neurol
2009;256(8):1236–42.
[69] Dupuis L, Pradat PF, Ludolph AC, Loeffler JP. Energy
metabolism in amyotrophic lateral sclerosis. Lancet
Neurol 2011;10(1):75–82.
[70] Lee J, Baek H, Kim SH, Park Y. Association between
estimated total daily energy expenditure and stage of
amyotrophic lateral sclerosis. Nutrition 2016.
[71] Heffernan C, Jenkinson C, Holmes T, Feder G, Kupfer R,
Leigh PN, et al. Nutritional management in MND/ALS
patients: an evidence based review. Amyotroph Later Scler
Motor Neuron Disord 2004;5(2):72–83.
[72] Shaw AS, Ampong MA, Rio A, Al-Chalabi A, Sellars ME,
Ellis C, et al. Survival of patients with ALS following
institution of enteral feeding is related to pre-procedure
oximetry: a retrospective review of 98 patients in a single
centre. Amyotroph Lateral Scler 2006;7(1):16–21.
[73] Miller RG, Jackson CE, Kasarskis EJ, England JD, Forshew D,
Johnston W, et al. Practice parameter update: the care of
the patient with amyotrophic lateral sclerosis: drug,
nutritional, and respiratory therapies (an evidence-based
review): report of the Quality Standards subcommittee of
the American academy of neurology. Neurology
2009;73(15):1218–26.
[74] Chio A, Galletti R, Finocchiaro C, Righi D, Ruffino MA,
Calvo A, et al. Percutaneous radiological gastrostomy: a
safe and effective method of nutritional tube placement in
advanced ALS. J Neurol Neurosurg Psychiatry
2004;75(4):645–7.
[75] Katzberg HD, Benatar M. Enteral tube feeding for
amyotrophic lateral sclerosis/motor neuron disease.
Cochrane Database Syst Rev 2011;1:CD004030.
[76] Mitsumoto H, Davidson M, Moore D, Gad N, Brandis M,
Ringel S, et al. Percutaneous endoscopic gastrostomy
(PEG) in patients with ALS and bulbar dysfunction.
Amyotroph Lateral Scler Motor Neuron Disord
2003;4(3):177–85.
[77] Gastrostomy in patients with amyotrophic lateral
sclerosis (ProGas): a prospective cohort study. Lancet
Neurol 2015;14(7):702–9.
[78] Verschueren A, Monnier A, Attarian S, Lardillier D, Pouget
J. Enteral and parenteral nutrition in the later stages of
ALS: an observational study. Amyotroph Lateral Scler
2009;10(1):42–6.
[79] Abdelnour-Mallet M, Verschueren A, Guy N, Soriani MH,
Chalbi M, Gordon P, et al. Safety of home parenteral
nutrition in patients with amyotrophic lateral sclerosis: a
French national survey. Amyotroph Lateral Scler
2011;12(3):178–84.
[80] Gelinas DF. Pulmonary function screening. Semin Neurol
2003;23(1):89–96.
[81] Evans JA, Whitelaw WA. The assessment of maximal
respiratory mouth pressures in adults. Respir Care
2009;54(10):1348–59.
[82] Gregory SA. Evaluation and management of respiratory
muscle dysfunction in ALS. Neurorehabilitation
2007;22(6):435–43.
[83] Morgan RK, McNally S, Alexander M, Conroy R, Hardiman
O, Costello RW. Use of Sniff nasal-inspiratory force to
predict survival in amyotrophic lateral sclerosis. Am J
Respir Crit Care Med 2005;171(3):269–74.
[84] Capozzo R, Quaranta VN, Pellegrini F, Fontana A, Copetti
M, Carratu P, et al. Sniff nasal inspiratory pressure as a
prognostic factor of tracheostomy or death in
amyotrophic lateral sclerosis. J Neurol 2015;262(3):593–603.
[85] Georges M, Nguyen-Baranoff D, Griffon L, Foignot C,
Bonniaud P, Camus P, et al. Usefulness of transcutaneous
PCO2 to assess nocturnal hypoventilation in restrictive
lung disorders. Respirology 2016;21(7):1300–6.
NEUROL-1780; No. of Pages 12
12 revue neurologique xxx (2017) xxx–xxx
[86] Hardiman O. Management of respiratory symptoms in
ALS. J Neurol 2011;258(3):359–65.
[87] Hazenberg A, Kerstjens HA, Prins SC, Vermeulen KM,
Wijkstra PJ. Is chronic ventilatory support really effective
in patients with amyotrophic lateral sclerosis? J Neurol
2016.
[88] Gonzalez-Bermejo J, Morelot-Panzini C, Arnol N,
Meininger V, Kraoua S, Salachas F, et al. Prognostic value
of efficiently correcting nocturnal desaturations after
1 month of non-invasive ventilation in amyotrophic
lateral sclerosis: a retrospective monocentre observational
cohort study. Amyotroph Lateral Scler Frontotemporal
Degen 2013;14(5–6):373–9.
[89] Pinto S, Carvalho M. Breathing new life into treatment
advances for respiratory failure in amyotrophic
lateral sclerosis patients. Neurodegen Dis Manage
2014;4(1):83–102.
[90] Bourke SC, Tomlinson M, Williams TL, Bullock RE, Shaw
PJ, Gibson GJ. Effects of non-invasive ventilation on
survival and quality of life in patients with amyotrophic
lateral sclerosis: a randomised controlled trial. Lancet
Neurol 2006;5(2):140–7.
[91] Radunovic A, Annane D, Rafiq MK, Mustfa N. Mechanical
ventilation for amyotrophic lateral sclerosis/motor neuron
disease. Cochrane Database Syst Rev 2013;3:CD004427.
[92] Gruis KL, Brown DL, Schoennemann A, Zebarah VA,
Feldman EL. Predictors of noninvasive ventilation
tolerance in patients with amyotrophic lateral sclerosis.
Muscle Nerve 2005;32(6):808–11.
[93] Gonzalez-Bermejo J. Soins palliatifs dans l’insuffisance
respiratoire de la sclérose latérale amyotrophique. Enjeux
éthiques en réanimation. Paris: Springer; 2010: 409–16.
[94] Marchese S, Lo Coco D, Lo Coco A. Outcome and
attitudes toward home tracheostomy ventilation of
consecutive patients: a 10-year experience. Respir Med
2008;102(3):430–6.
[95] Kaub-Wittemer D, Steinbuchel N, Wasner M, Laier-
Groeneveld G, Borasio GD. Quality of life and psychosocial
issues in ventilated patients with amyotrophic lateral
sclerosis and their caregivers. J Pain Symptom Manage
2003;26(4):890–6.
[96] Trail M, Nelson ND, Van JN, Appel SH, Lai EC. A study
comparing patients with amyotrophic lateral sclerosis and
their caregivers on measures of quality of life, depression,
and their attitudes toward treatment options. J Neurol Sci
2003;209(1–2):79–85.
[97] Radunovic A, Mitsumoto H, Leigh PN. Clinical care of
patients with amyotrophic lateral sclerosis. Lancet Neurol
2007;6(10):913–25.
[98] McDermott CJ, Bradburn MJ, Maguire C, Cooper CL, Baird
WO, Baxter SK, et al. Safety and efficacy of diaphragm
pacing in patients with respiratory insufficiency due to
amyotrophic lateral sclerosis (DiPALS): a multicentre,
open-label, randomised controlled trial. Lancet Neurol
2015;14(9):883–92.
[99] Sancho J, Bures E, de La Asuncion S, Servera E. Effect of
high-frequency oscillations on cough peak flows
Please cite this article in press as: Soriani M-H, Desnuelle C. Care management in amyotrophic lateral sclerosis. Revue neurologique (2017),
http://dx.doi.org/10.1016/j.neurol.2017.03.031
generated by mechanical in-exsufflation in medically
stable subjects with amyotrophic lateral sclerosis. Respir
Care 2016;61(8):1051–8.
[100] Lomen-Hoerth C, Murphy J, Langmore S, Kramer JH, Olney
RK, Miller B. Are amyotrophic lateral sclerosis patients
cognitively normal? Neurology 2003;60(7):1094–7.
[101] Witgert M, Salamone AR, Strutt AM, Jawaid A, Massman
PJ, Bradshaw M, et al. Frontal-lobe mediated behavioral
dysfunction in amyotrophic lateral sclerosis. Eur J Neurol
2010;17(1):103–10.
[102] Girardi A, Macpherson SE, Abrahams S. Deficits in
emotional and social cognition in amyotrophic lateral
sclerosis. Neuropsychology 2011;25(1):53–65.
[103] Meier SL, Charleston AJ, Tippett LJ. Cognitive and
behavioural deficits associated with the orbitomedial
prefrontal cortex in amyotrophic lateral sclerosis. Brain J
Neurol 2010;133(11):3444–57.
[104] Neary D, Snowden JS, Gustafson L, Passant U, Stuss D,
Black S, et al. Frontotemporal lobar degeneration: a
consensus on clinical diagnostic criteria. Neurology
1998;51(6):1546–54.
[105] Elamin M, Phukan J, Bede P, Jordan N, Byrne S, Pender N,
et al. Executive dysfunction is a negative prognostic
indicator in patients with ALS without dementia.
Neurology 2011;76(14):1263–9.
[106] Abrahams S, Newton J, Niven E, Foley J, Bak TH.
Screening for cognition and behaviour changes in ALS.
Amyotroph Lateral Scler Frontotemporal Degen
2014;15(1–2):9–14.
[107] Niven E, Newton J, Foley J, Colville S, Swingler R, Chandran
S, et al. Validation of the Edinburgh cognitive and
behavioural amyotrophic lateral sclerosis screen (ECAS): a
cognitive tool for motor disorders. Amyotroph Lateral
Scler Frontotemporal Degen 2015;16(3–4):172–9.
[108] Sorenson EJ, Mandrekar J, Crum B, Stevens JC. Effect of
referral bias on assessing survival in ALS. Neurology
2007;68(8):600–2.
[109] Merrilees J, Klapper J, Murphy J, Lomen-Hoerth C, Miller
BL. Cognitive and behavioral challenges in caring for
patients with frontotemporal dementia and
amyotrophic lateral sclerosis. Amyotroph Lateral Scler
2010;11(3):298–302.
[110] Rabinovici GD, Miller BL. Frontotemporal lobar
degeneration: epidemiology, pathophysiology, diagnosis
and management. CNS Drugs 2010;24(5):375–98.
[111] Karam CY, Paganoni S, Joyce N, Carter GT, Bedlack R.
Palliative care issues in amyotrophic lateral sclerosis: an
evidenced-based review. Am J Hosp Palliat Care
2016;33(1):84–92.
[112] Bede P, Oliver D, Stodart J, van den Berg L, Simmons Z, D
OB, et al. Palliative care in amyotrophic lateral sclerosis: a
review of current international guidelines and initiatives. J
Neurol Neurosurg Psychiatry 2011;82(4):413–8.
[113] Delaney JW, Downar J. How is life support withdrawn in
intensive care units: a narrative review. J Crit Care
2016;35:12–8.