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European Journal of Neurology 2005, 12: 921–938 EFNS task force on management of amyotrophic lateral sclerosis: guidelinesfor diagnosing and clinical care of patients and relatives An evid ence-bas ed rev iew w ith good practice points The EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis:P. M. Andersena, G. D. Borasiob, R. Denglerc, O. Hardimand, K. Kollewec, P. N. Leighe,P.-F. Pradatf, V. Silanig and B. TomikhaDepartment of Neurology, Umea˚ University Hospital, Umea˚, Sweden; bInterdisciplinary Center for Palliative Medicine and Department of Neurology, Munich University Hospital, Grosshadern, Munich, Germany; cDepartment of Neurology, Medizinische Hochschule Hannover, Hannover, Germany; dDepartment of Neurology, Beaumont Hospital, Dublin, Ireland; eDepartment of Clinical Neuroscience, King's College London, Institute of Psychiatry, De Crespigny Park, London, UK; fFe´de´ration des Maladies du Syste me Nerveux, Hoˆpital de la Salpeˆtrie re, Paris, France; gDepartment of Neurology and Laboratory of Neuroscience, ÔDino FerrariÕ Center – IRCCS Istituto Auxologico Italiano – University of Milan Medical School, Milan, Italy; and hDepartment of Neurology, Institute of Neurology, Collegium Medicum, Jagiellonian University, Krakow, Poland Despite being one of the most devastating diseases known, there is little evidence for ALS/SLA/MND, break- diagnosing and managing patients with amyotrophic lateral sclerosis (ALS). Although ing the diagnosis, bron- specific therapy is lacking, correct early diagnosis and introduction of symptomatic and chial secretions, diagnosis, specific therapy can have a profound influence on the care and quality of life of the DNA-testing, drooling, patient and may increase survival time. This document addresses the optimal clinical nutrition, palliative care, approach to ALS. The final literature search was performed in the spring of 2005.
symptomatic treatment, Consensus recommendations are given graded according to the EFNS guidance regu- terminal care, ventilation lations. Where there was lack of evidence but consensus was clear we have stated ouropinion as good practice points. People affected with possible ALS should be examined Received 1 August 2005 as soon as possible by an experienced neurologist. Early diagnosis should be pursued and Accepted 3 August 2005 a number of investigations should be performed with high priority. The patient should beinformed of the diagnosis by a consultant with a good knowledge of the patient and thedisease. Following diagnosis, the patient and relatives should receive regular supportfrom a multidisciplinary care team. Medication with riluzole should be initiated as earlyas possible. PEG is associated with improved nutrition and should be inserted early. Theoperation is hazardous in patients with vital capacity <50%. Non-invasive positivepressure ventilation improves survival and quality of life but is underused. Maintainingthe patients ability to communicate is essential. During the entire course of the disease,every effort should be made to maintain patient autonomy. Advance directives forpalliative end of life care are important and should be fully discussed early with thepatient and relatives respecting the patients social and cultural background.
of primarily upper (UMN) and lower (LMN) motor neurons, leading to progressive weakness of bulbar, Amyotrophic lateral sclerosis (ALS, also known as limb, thoracic and abdominal muscles. Other brain functions, including oculomotor and sphincter func- amyotrophique (SLA) is a fatal syndrome character- tions, are relatively spared, although these may be ized by onset of symptoms and signs of degeneration involved in some cases. Cognitive dysfunction is seenin 20–50%, and 3–5% develop dementia that is usu-ally of frontotemporal type (Abrahams et al., 1996).
Correspondence: Peter M. Andersen, MD DMSc, Associate professor Death due to respiratory failure follows on average 2– of Neurology, Department of Neurology, Umea˚ Universityhospital,SE-901 85 Umea˚, Sweden (tel.: +46 (0)90 785 2372; fax: 4 years after onset, but a small group may survive for +46 (0)90 143 107; e-mail: [email protected]).
a decade or more (Forsgren et al., 1983). The meanage of onset is 47–52 years in familial cases (FALS) This is a Continuing Medical Education paper and can be found and 58–63 years in sporadic (SALS) cases (Haverkamp with corresponding questions on the Internet at: http://www.
et al., 1995). The lifetime risk of developing ALS is blackwellpublishing.com/products/journals/ene/mcqs. Certificates forcorrectly answering the questions will be issued by the EFNS.
about 1:1000 [approximately half the risk of getting P. M. Andersen et al.
Figure 1 Schematic illustration of the relationship between ALS and some other motor neuron syndromes and motor neuronopathies. Onthe far left are syndromes affecting lower motor neurons (LMN) and/or the peripheral motor axons, on the right syndromes affecting theupper motor neurons and/or the corticospinal and corticobulbar tractsystems. The approximate clinical spectrum associated withmutations in some genes is shown below the bar. At present, 44 genes have been associated with motor neuron disease or neuronopathy.
CMT, Charcot-Marie-Tooth; HMN, distal hereditary motor neuronopathies; PMA, progressive spinal muscular atrophies; PLS, primarylateral sclerosis syndrome; HSP, hereditary spastic paraplegias.
multiple sclerosis], with male sex, increasing age and hereditary disposition being the main risk factors(Bobowick and Brody, 1973). When diagnosing and Ten central issues in the management of ALS were ad- managing a patient with ALS it is important to dressed by the Task Force. The following is an abbre- recognize that ALS is a heterogeneous syndrome that viated report, the full report with all tables, figures and overlaps with a number of other conditions (Fig. 1; references is available at http://www.efns.org. Supple- Ince et al., 1998; Brugman et al., 2005). This system- mentary material presented on http://www.efns.org only atic review comprises of an objective appraisal of the is listed as tables S1–S7. The guidelines were prepared evidence in regard to the diagnosis and clinical man- following the EFNS criteria (Brainin et al., 2004) and the agement of patients with ALS. The primary aim has level of evidence and grade of recommendation are ex- been to establish evidence-based and patient and carer pressed in accordance with this reference. Where there centered guidelines, with secondary aims of identifying was lack of evidence but consensus was clear we have areas where further research is needed.
stated our opinion as good practice points.
1 Diagnosing ALS/MND Two investigators screened potentially relevant citations Diagnosing ALS is usually considered straight forward independently. We searched the Cochrane Central if the patient has been ill for some time and has gener- Register of Controlled Trials (CENTRAL) (The Coch- alized symptoms (Table 1; Li et al., 1986). Diagnosing rane Library to date); MEDLINE-OVID (January 1966 the disease early in the disease when the patient has only to date); MEDLINE-ProQuest; MEDLINE-EIFL; limited focal symptoms from one or two regions (bulbar, EMBASE-OVID (January 1990 to date); Science Cita- upper limb, truncal, lower limb) may be difficult and tion Index (ISI); The National Research Register; Ox- depends on the presence of signs in other affected regions ford Centre for Evidenced-based Medicine; American and a number of investigations (Wilbourn, 1998; Mei- Speech Language Hearing Association (ASHA); the ninger, 1999). The mean time from onset of symptoms to world Federation of Neurology ALS Page of reviews of confirmation of diagnosis of ALS is 13–18 months published research; the Oxford Textbook of Palliative (Chio, 1999). Delays may arise from a complex referral Medicine, and the UK Department of Health National pathway, and early symptoms are often intermittent and non-specific and may be denied or go unrecognized by National/). We also searched national neurological the patient. However, three studies have shown that the databases (e.g. http://www.alsa.org and http://www.
longest delay occurs after the patient actually has seen alsod.org) and personal collections of references and the neurologist (Chio, 1999). There are four cogent reference lists of articles. There were no constraints reasons for making the diagnosis as early as possible: based on language or publication status. Any differences For psychological reasons, as the progressive loss of at any stage of the review were resolved by discussion.
motor symptoms causes anxiety and discomfort,
2005 EFNS European Journal of Neurology 12, 921–938 EFNS guidelines on management of amyotrophic lateral sclerosis Table 1 Diagnostic criteria for ALS clinical trials (Table 3, adapted from Brooks et al.,2000). The criteria are too restrictive for use in routine The diagnosis of ALS requires the presence of: (positive criteria) clinical practice and are not suitable if the objective is to LMN signs (including EMG features in clinically unaffected establish the diagnosis as early as possible (Ross et al., 1998). In practice, we do not recommend that patients Progression of symptoms and signs are told they have Ôdefinite, probable or possibleÕ ALS.
The diagnosis of ALS requires the absence of: (diagnosis by exclusion) The clinician must decide, on the balance of probability, whether or not the patient has ALS, even in the absence Sphincter disturbancesVisual disturbances of unequivocal UMN and LMN signs (Leigh et al., Autonomic features Basalganglia dysfunctionAlzheimer-type dementia Good practice points ALS ÔmimicÕ syndromes (Table S1) 1 The diagnosis should be pursued as early as possible.
The diagnosis of ALS is supported by: Fasciculations in one or more regions Patients with whom ALS is suspected should be Neurogenic changes in EMG referred with high priority to an experienced neuro- Normal motor and sensory nerve conduction Absence of conduction block 2 All suspected new cases should undergo prompt impairing the patient's social and professional life; for (Tables 1 and 2).
ethical reasons, so that the patient can better plan the 3 In some cases, additional investigations may be nee- remaining part of her or his life; for economic reasons, as ded (Table 2).
many patients go on a tour of the health care system 4 Repetition of the investigations may be needed if the undergoing series of (expensive) unnecessary tests; for initial series of tests do not result in a diagnosis.
neurological reasons to be able to initiate neuroprotec- 5 Review of the diagnosis is advisable if there is no tive medication before too many neuronal cells become evidence of progression or if the patient develops dysfunctional and lost. Although no hard evidence exists atypical features (Table 1).
on the kinetics of cell loss in ALS, it is reasonable toassume that the earlier medication is started the greater 2 Breaking the news: communicating the diagnosis the neuroprotective effect will be (Bromberg, 1999).
Studies in experimental animal models and humans with Telling the patient and the family that the diagnosis is SOD1 gene mutations indicate that loss of motor neu- ALS is a daunting task for the physician. If not per- rons is preceded by a period of cellular dysfunction formed appropriately, the effect can be devastating, (Aggarwal and Nicholson, 2002). Both in humans and leaving the patient with a sense of abandonment and animal models the life prolonging effect of riluzole is destroying the patient–physician relationship (Lind greater the earlier medication is initiated. Also, early et al., 1989). Studies of other fatal illnesses (Damian administration of medication can have a profound and Tattersall, 1991; Doyle, 1996; Davies and Hopkins, positive psychological effect on the patient and carers.
1997) clearly demonstrated the advantages of utilizing The objective is to present guidelines for making the specific techniques (Table 4). Surveys in ALS patients correct diagnosis and doing this as early as possible. As and caregivers have demonstrated that the way the no single investigation is specific for the diagnosis, car- diagnosis is communicated is less than satisfactory in rying out the diagnosis should be based on symptoms, a half of the cases (Borasio et al., 1998; McCluskey et al., thorough clinical examination, electrodiagnostic stud- 2004). Better performance on all attributes of effective ies, neuroimaging and laboratory studies (Tables 1 and communication as well as greater time spent discussing 2; Lima et al., 2003). Great care should be taken to rule the diagnosis was correlated with higher patient/care- out diseases that can masquerade as ALS (Table S1; giver satisfaction (McCluskey et al., 2004). A survey in Evangelista et al., 1996; Traynor et al., 2000). In spe- ALS centers has shown that physicians in 44% of center cialist practice, 5–8% of apparent ALS cases have an usually spend 30 min or less discussing the diagnosis alternative diagnosis, which may be treatable in about (Borasio et al., 2001a). Callous delivery of the diagnosis half the cases (Belsh and Schiffman, 1990; Davenport may affect the psychological adjustment to bereavement et al., 1996; Traynor et al., 2000). Evolution of atypical (Ackerman and Oliver, 1997).
symptoms or failure of the patient to show progress arethe most important Ôred flagsÕ suggesting that the diag- Good practice points nosis may be wrong (Traynor et al., 2000). The revised 1 The diagnosis should be communicated by a con- El Escorial criteria are research diagnostic criteria for sultant with a good knowledge of the patient.

2005 EFNS European Journal of Neurology 12, 921–938 P. M. Andersen et al.
Table 2 Diagnosing ALS/MND: recommended investigations Clinical chemistry in selected cases Erythrocyte sedimentation rate C-reactive protein (CRP) Hematological screen TSH, FT4, FT3 hormone assays Vitamins B12 and folate Serum protein electrophoresis Creatine kinase (CK) Angiotensin converting enzyme (ACE) Hexoaminidase A and B assay Ganglioside GM-1 antibodies Anti-Hu, anti-MAG RA, ANA, anti-DNA Anti-AChR, anti-MUSK antibodies Serology (Borrelia, virus including HIV) DNA analysis (for details see Fig. 1) Total protein concentration Protein electrophoresis including IgG index Serology (Borrelia, virus) Ganglioside antibodies Lead (24 h secretion) Nerve conduction velocity MRI/CAT (head/cervical, thoracic, lumbar) 2 The physician should start the consultation by asking 5 The diagnosis should always be given in person and what the patient already knows or suspects.
never by mail or telephone, with enough time available 3 Respect the cultural and social background of the (at least 45–60 min) on the part of the physician.
patient by asking whether the patient wishes to re- 6 Provide printed materials about the disease, about ceive information or prefers that the information be support and advocacy organizations, and about communicated to a family member.
informative websites on the internet. Optionally, a 4 The physician should give the diagnosis to the patient letter or audiotape summarizing what the physician and discuss its implications in a stepwise fashion, has discussed can be very helpful for the patients and checking repeatedly if the patient understands what is said, and reacting appropriately to the verbal and 7 Assure the patient that he or her and their family will non-verbal cues of the patient.
not be on their own (ÔabandonedÕ) but will be
2005 EFNS European Journal of Neurology 12, 921–938 EFNS guidelines on management of amyotrophic lateral sclerosis Table 3 Revised El Escorial research diagnostic criteria for ALS neurologist. Make arrangements for a close follow- up visit before the end of the consultation, ideallywithin 2–4 weeks (or sooner if appropriate).
Clinically definite ALSUMN and LMN signs in three regions 8 Avoid the following: withholding the diagnosis, providing insufficient information, delivering infor- Clinically definite ALS – Laboratory supportedUMN and/or LMN signs in one region and the patient is a carrier of mation callously, or taking away or not providing a pathogenic gene mutation hope. Remember to switch off mobile phones andpagers, and put up ÔDo not disturbÕ signs.
Clinically probable ALSUMN and LMN signs in two regions with some UMN signs rostral 3 Multidisciplinary care in management of ALS Clinically probable ALS – laboratory supportedUMN signs in one or more regions and LMN signs defined by EMG Specialist multidisciplinary (MD) clinics provide sec- in at least two regions ondary or tertiary services to patients with ALS.
Clinically possible ALS These clinics comprise a wide range of health care UMN and LMN signs in one region, or professionals with expertise in ALS. Ideally, such UMN signs in at least two regions, or clinics provide both diagnostic and management ser- UMN and LMN signs in two regions with no UMN signs rostral vices, and facilitate continuity of care by close liaising with the primary care physician and community-based services (Chio et al., 2001; Howard and Orrell, supported by a professional ALS-care team (where 2002; Leigh et al., 2003; Traynor et al., 2003). The available) and with regular follow-up visits to a Table 4 How should a physician tell the patient that they have ALS modified from Miller et al. (1999) Quiet, comfortable, and private In person, face-to-faceConvenient time (at least 45–60 min)Enough time to ensure no rushing or interruptionsMake eye contact and sit close to patient Know the patient before the meeting including family, emotional and social situation, case history, and all relevant test results. Have all the facts at hand Have patient's support network present (relatives). Have a clinical nurse specialist or equivalent present or available Find out what the patient already knows about the conditionAscertain how much the patient wants to know about ALS and tailor your information accordinglyGive a warning comment that bad news is coming. The whole truth may need to come by installmentsUse the correct ALS-term, not Ôwear and tear of the motor nervesÕExplain the anatomy of the disease (make a simple drawing)If the patient indicates that they want to know the course of the disease, be honest about the probable progression and prognosis but give a broad time frame, and recognize the limitations of any predictions There is no cure, symptoms tend to steadily worsen, and prognosis is highly variable.
Some patients survives 5 or 10 or more years Acknowledge and explore patient's reaction and allow for emotional expressionSummarize the discussion verbally, in writing, and/or audiotapeAllow plenty of time for questions Acknowledge that this is devastating news but discuss reasons for hope such as research, drug trials and the variability of the disease Explain that the complications of ALS are treatableReassure that every attempt will be made to maintain the patient's function and that the patient's treatment decisions will be respected Reassure that the patient will continue to be cared for and will not be abandonedInform about patient support groups (offer contact details and leaflets)Inform about neuroprotective treatment (i.e. riluzole) and ongoing researchDiscuss opportunities to participate in research treatment protocols (if available)Acknowledge willingness to get a second opinion if the patient wishes Emotional manner: warmth, caring, empathy, respectBe honest, sympathetic but not sentimentalGive news at person's pace; allow the patient to dictate what he or she is told Simple and careful word choice, yet direct; no euphemisms or medical jargon
2005 EFNS European Journal of Neurology 12, 921–938 P. M. Andersen et al.
emphasis of care should be on patient autonomy and two class I studies (Bensimon et al., 1994; Lacomblez choice. Patients who attend specialist MD clinics tend et al., 1996; Cochrane review by Miller et al., 2002).
to be younger and to have had symptoms for longer Patients with early disease, (i.e. with suspected or poss- than those who do not (Lee et al., 1995; Traynor ible ALS according to the El Escorial Criteria) were not included. Oral administration of 100 mg riluzole daily cohorts and population-based cohorts of patients prolonged survival by about 3 months after 18 months have confirmed a referral bias (Lee et al., 1995; treatment. There was a clear dose effect. In clinical Traynor et al., 2003). However, an independent sur- practice, retrospective phase IV studies from three clin- vival benefit has been identified in two studies, which ical databases indicate that the overall gain in survival is independent of other prognostic factors including (i.e. over the whole extend of the disease experience), may age, disease duration, bulbar onset disease and rate of extend from
6 to 20 months, although these estimates progression (Traynor et al., 2003; Chio et al., 2004a).
are almost certainly subject to various statistical biases Importantly, patients attending a multidisciplinary (Brooks et al., 2001; Turner et al., 2002; Traynor et al., clinic have fewer hospital admissions and shorter 2003b). The drug is safe with few serious side- durations of stay than those who attend general effects. Guidelines for monitoring have been pub- clinics (Chio et al., 2004a). Increased use of non- ¼simple&ss¼ALS). Although patients with progressive earlier referral to palliative referral services prob- spinal muscular atrophy (PMA) or primary lateral ably contribute to the increased survival of those sclerosis (PLS) were not included in the riluzole trials, attending MD clinics (Leigh et al., 2003; Traynor pathological and genetic studies show that some PMA et al., 2003a).
and PLS cases fall within the ALS-syndrome (Fig. 1;Andersen et al., 2003; Brugman et al., 2005). Riluzole Good practice points may have little effect in late stage ALS and it is not clear if 1 Multidisciplinary care should be available for people and when treatment should be terminated. A large affected by ALS as attendance at a MD clinic number of other drugs have been tested in ALS alas with improves care, and may extend survival.
negative results (Table 5).
2 The following specialists should be part of or be readily available to the MD team: a consultant in Good practice points neurology, pulmonologist, gastroenterologist, reha- 1 ALS patients should be offered treatment with bilitation medicine physician, social counselor, occu- riluzole 50 mg twice daily (class IA).
pational therapist, speech therapist, specialized nurse, 2 Patients treated with riluzole should be monitored physical therapist, dietitian, psychologist, dentist.
regularly for safety (class IA).
3 Schedule clinical visits every 2–3 months and more 3 Treatment should be initiated as early as possible frequently if needed. This is particularly often the after the patient has been informed of the diagnosis case in the first half year following diagnosis, and in taking into account expected therapeutic benefits and late stages of the disease. Patients with very slowly potential safety issues (Class IA). Realistic expecta- progressing disease can be seen once or twice a year.
tions for treatment effects and potential side effects 4 It is important that between visits the patient support should be discussed with the patient and caregivers.
team maintain regular contact with the patient and 4 Treatment with riluzole should be considered in relatives (e.g. by phone, letter or email).
PMA and PLS patients who have a first degree 5 Ideally, from the outset the patient should be fol- relative with ALS.
lowed by a single named neurologist working in close 5 Patients with sporadic PMA, sporadic PLS or liason with the patients primary care physician HSP should as a rule not be treated with riluzole.
(family general practitioner).
6 Irrespectively of familial disposition, all patients with 6 Effective channels of communication and co-ordina- a symptomatic motor neuron disease and carrying a tion are essential between the hospital based SOD1 gene mutation should be offered treatment MD-team, the primary care team, the palliative care with riluzole.
team and community services.
7 Currently, there is insufficient evidence to recommend treatment with vitamins, testosterone, anti-oxidantslike co-enzyme Q-10 and gingko biloba, intravenous 4 Neuroprotective treatment immunoglobuline therapy, cyclosporin, interferones, At present, only riluzole, a presumed glutamate-release copaxone, ceftriaxone, minocycline, VEGF, stem antagonist, has been shown to slow the course of ALS in
2005 EFNS European Journal of Neurology 12, 921–938 EFNS guidelines on management of amyotrophic lateral sclerosis Table 5 Summary of the most important controlled therapeutic of saliva rather than from overproduction. Sialorrhea is treatable. Most evidence, however, comes fromstudies in other conditions. Amitriptyline is commonly used with reasonable efficacy at low cost (Forshew Brain-derived neurotrophic factor (BDNF)* and Bromberg, 2003). Oral doses of not more than Branched-chain amino acids* 25–50 mg twice to three times a day are usually Ciliary neurotrophic factor (CNTF)* (two trials) Atropine drops can be administered sublingually. A Creatine* (three trials)Cyclosporine* class IV study in seven patients with Parkinson's disease demonstrated statistically significant decline in saliva production (Hyson et al., 2002). For ALS patients Glial-derived neurotrophic factor (GDNF)* 0.25–0.75 mg three times a day is recommended empi- rically (Leigh et al., 2003). Glycopyrrolate (in nebulized Interferon beta-1a*Insulin-like growth factor (IGF-1)* or iv form) has been shown to be effective in patients Lamotrigine* (two trials) with cerebral palsy or developmental disabilities in a Lymphoid irradiation* class I study (Mier et al., 2000), but no studies in ALS are known. Hyoscine (scopolamine) can be given orally or applied as a dermal patch. Two class IV studies (Talmi et al., 1989, 1990) showed a reduction of saliv- ary flow with transdermal scopolamine (1.5 mg every 3 day). Patients with severe drooling may need two Benztropine demonstrated in a class I study in Vitamin E* (two trials)Xaliproden* Ongoing phase II/III trials (summer of 2005) drooling up to 70% (Camp-Bruno et al., 1989). An alternative to anticholinergic drugs is botulinum toxin: In a class IV study in ALS-patients, Giess IGF-1 polypeptide et al., 2000 showed a reduction of sialorrhea by Phase III trials being planned or considered injections of botulinum toxin type A into the salivary glands. The effect faded in several months, and repeated injections were necessary. Studies with sim- ilar results have been carried out in patients with other neurological disorders (Porta et al., 2001; Dogu IGF-1 – viral deliveryMemantine et al., 2004). However, serious side-effects have been NAALADase inhibitors reported (Tan et al., 2001; Winterholler et al., 2001).
There are no studies using botulinum toxin type B.
Sodium phenylbutyrate Three class IV studies in ALS-patients showed satis- factory results in the treatment of drooling with external radiation of the parotid and submandibular glands (Andersen et al., 2001; Harriman et al., 2001;Stalpers and Moser, 2002). Low dosage palliative *No therapeutic benefit was observed.
radiation in a single fraction of 7–8 Gy to the parotidglands is a simple, fast, safe and inexpensive proce-dure to reduce drooling in ALS patients.
5 Symptomatic treatment Surgical interventions, such as transtympanic neur- Symptomatic treatment aims to improve the quality of ectomy, parotid duct ligation and relocation and life of patients and care givers. Symptoms should be submandibular gland excision, showed effective long- treated as they become prominent and incapacitating in term results in children with drooling (Burton, 1991; Hockstein et al., 2004). Case reports suggests lessefficacy in ALS patients with reports of increased secretions of thick mucus production and side-effects Sialorrhea (drooling or excessive salivation) is a socially like recurrent jaw dislocation and inflammation (Janzen disabling symptom. It results from impaired handling et al., 1988; Winterholler et al., 2001).

2005 EFNS European Journal of Neurology 12, 921–938 P. M. Andersen et al.
Good practice points 6 Cricopharyngeal myotomy may be helpful in the rare 1 Treat sialorrhea in ALS with oral or transdermal cases with frequent episodes with cricopharyngeal hyoscine, atropine drops, glycopyrrolate or ami- spasm and severe bronchial secretions.
Pseudobulbar emotional lability Pseudobulbar signs such as pathological weeping, 3 Botulinum toxin injections into the parotid glands laughing or yawning can be socially disabling. Emo- can be tried but insufficient data are available yet to tional lability occurs in at least 50% of ALS patients appraise safety and long-term efficacy, and this and can be seen in patients without bulbar motor signs intervention is judged as still experimental.
(Gallagher, 1989). Occasionally, the emotional out- 4 Irradiation of the salivary glands may be tried when bursts are more troubling for the relatives and nursing pharmacological treatment fails.
staff than the patient, and treatment may not be 5 Surgical interventions are not recommended.
necessary. A randomized controlled trial of a combi-nation of dextrometorphan and quinidine showed this Bronchial secretions to be effective in improving emotional lability and Clearing tenacious secretions can be difficult for the quality of life (Brooks et al., 2004). Side-effects were patient with respiratory insufficiency causing much experienced by 89% of patients and 24% discontinued distress to the patient. The mucosa of the nasal treatment during the trial's 4-week duration. Fluvox- cavity, larynx, trachea, bronchial airways and lungs amine (Iannaccone and Ferini-Strambi, 1996), ami- contribute a constant flow of serous and particularly triptyline, citalopram and even dopamine and lithium mucoid fluids. Stimulation of cholinergic receptors have been tested with good effect in other neurological produces thin serous secretions whereas stimulation of diseases (Schiffer et al., 1985; Andersen et al., 1993).
b-adrenergic receptors produces thick protein- and There appears to be no advantage for a particular mucus-rich secretions. A portable home suction de- medication so the emphasis should be on tolerability, vice is useful for clearing the upper airways (and safety and cost.
excess saliva in the mouth). However, secretions inthe lower airways can be difficult to reach. Medica- Good practice points tion with mucolytics like guaifenesin or N-acetylcy- steine, a b-receptor antagonist (such as metoprolol or emotional lability is not a sign of a mood disorder propranolol) and/or an anticholinergic bronchodilator but is due to an organic lesion in the brain (Poeck, like ipratropium and/or theophylline or even furo- semide can be of value, but no controlled studies in 2 Only troublesome emotional lability should be trea- ALS exist (Newall et al., 1996). Mechanical cough ted. If treatment is deemed necessary, an antide- assisting devices (insufflator-exsufflator) via a face mask was very effective in ALS patients in uncon- citalopram is usually sufficient.
trolled trials (Hanayama et al., 1997; Sancho et al., 3 A combination of dextrometorphan and quinidine has been shown to be effective in a class IA study butfurther experience on the long-term side-effects and Good practice points tolerability are needed.
1 Teach the patient and carers the technique of assisting expiratory movements using a manual assisted cough (can also be performed by a physical therapist).
Cramps may be an early and troublesome symptom in 2 Provide a portable home suction device and a room ALS, in particular before falling asleep. Class I studies in patients with non-ALS leg cramps with quinine sulfate 3 Consider using a mucolytic like N-acetylcysteine, and vitamin E (Connolly et al., 1992; Diener et al., 2002) 200–400 mg three times daily.
showed a positive effect only for quinine. Empirically, 4 If these measures are insufficient, try a nebulizer with massage, physical exercise (in the evening), hydro- saline and a b-receptor antagonist and/or an anti- therapy, Mg2+, carbamazepine, diazepam, phenytoin, cholinergic bronchodilator and/or a mucolytic and/ verapamil, gabapentin can alleviate muscle cramps.
or furosemide in combination.
5 The use of a mechanical insufflator-exsufflator may Good practice points be helpful, particularly in the setting of an acute 1 Treat cramps in ALS with physiotherapy, physical exercise and/or hydrotherapy.

2005 EFNS European Journal of Neurology 12, 921–938 EFNS guidelines on management of amyotrophic lateral sclerosis 2 If necessary, treat cramps in ALS with quinine sul- Good practice points 1 Treat depression in ALS with an appropriate anti- 3 Mg2+, carbamazepine, phenytoin, verapamil, gab- depressant, e.g. amitriptyline or an SSRI.
apentin are alternatives.
2 Treat insomnia with amitriptyline or appropriate hypnotics (e.g. zolpidem, diphenhydramine).
3 Treat anxiety with bupropion or benzodiazepines Spasticity can be a troublesome symptom in patients with such as diazepam tablets or suppositories, temesta ALS. Physical therapy is vital and helped reducing tablets 0.5 mg two to three times daily, or lorazepam spasticity in a class IIB study (Drory et al., 2001).
Modalities such as hydrotherapy, heat, cold, ultrasound,electrical stimulation, and in rare cases surgery can be used, although no controlled studies in ALS exist. In a Pain occurs frequently in ALS. Some familial ALS class III study of 20 patients with spinal cord injury, the syndromes include pain of neuralgic type. Treatment is use of hydrotherapy in heated pools three times per week unspecific and should follow accepted principles. Opi- produced a significant decrease in spasm severity and oids can be used, following the 1990-WHO analgesic reduction of oral baclofen medication (Kesiktas et al., ladder guidelines, when non-narcotics fail (Miller, 2004). Cryotherapy of the facial muscles reduced spas- 2001): Begin with simple analgesics such as paracet- ticity to facilitate dental care in 24 patients with cerebral amol, followed by weak opioids such as tramadol, fol- palsy (dos Santos and de Oliveira, 2004). Oral baclofen lowed by strong opioids such as morphine or (up to 80 mg daily) revealed no significant effect in ketobemidon. Liberal use of opioids may be appropri- spasticity in ALS in one small study (Norris et al., 1979).
ate when non-narcotics fail and have the secondary Intrathecal baclofen in two ALS-patients with intract- advantages of alleviating dyspnea and anxiety. How- able spasticity was more effective than oral medication ever, constipation may become a problem.
and greatly improved the patient's quality of life (Mar-quardt and Seifert, 2002). Other drugs have not been Good practice point tested formally in ALS, but in clinical practice gabap- Treat pain in ALS following accepted guidelines.
entin (900–2400 mg daily), tizanidine (6–24 mg daily),memantine (10–60 mg daily), dantrolene (25–100 mg Venous thrombosis daily) and diazepam (10–30 mg daily) have been used Patients with leg paralysis have an increased risk of with effect. Botulinum toxin A has successfully been used venous thrombosis.
to treat trismus and stridor in case reports (Winterholleret al., 2002).
Good practice pointsPhysiotherapy, limb elevation, compression stockings Good practice points can be used. Prophylactic treatment with anti-coagu- 1 Physical therapy should be available regularly when lants is not recommended.
there is significant spasticity.
2 Hydrotherapy with exercises in heated pools with 32– 6 Genetic testing and counseling 34C warm water, and cryotherapy should be con-sidered.
In different populations, the frequency of FALS is 3 Antispastic drugs such as baclofen and tizanidine reportedly 5–10% of all ALS cases (Table 6) but may may be tried.
be underestimated for a number of reasons (Table S2).
Presently four genes have been found to cause ALS Depression, anxiety and insomnia (Figs 1 and 2), SOD1, VAPB, SETX and ALSIN. At Depression occurs frequently at all stages of ALS as present mutations in the latter three genes appears to be well as insomnia (Dengler, 1999). Anxiety can become very rare and analysis is only performed in a scientific marked when respiratory insufficiency occurs. The four mostly used antidepressants in ALS are amitriptyline, Since 1993 some 119 mutations have been found in sertraline, fluoxetine and paroxetine. Amitriptyline has the SOD1 gene with five different modes of inherit- the best therapeutic effect and the lowest costs. For ance (Fig. 2; http://www.ALSOD.org; Andersen et al., insomnia in ALS, amitriptyline and zolpidem are the 2003). The most frequent mutation is the D90A, most commonly used medications (Forshew and which in most European countries is inherited as a Bromberg, 2003). There are no systematic studies on recessive trait with a characteristic slowly progressing anxiolytics in ALS, but oral diazepam or sub-lingual phenotype (Andersen et al., 1996). Twelve to 23% of lorazepam are useful.
diagnosed FALS and 2–7% of apparently SALS
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P. M. Andersen et al.
Table 6 Frequency of FALS in some epidemiological studies Haberlandt (1959) Murros and Fogelholm (1983).
Haverkamp et al. (1995) Thijs et al. (2000) Nova Scotia, Canada Murray et al. (1974) Wa¨rmland, Sweden Gunnarsson and Palm (1984) Forsgren et al. (1983) Giagheddu et al. (1983) Højer-Pedersen et al. (1989) Fong et al. (1996) Jokelainen (1977) patients carry a SOD1 mutation (Table 7). It must be as providing some prognostic information (Tables S5 emphasized that diminished disease penetrance is not and S6; Andersen et al., 1996). Pre-symptomatic infrequent and that SOD1 mutations can be found in (predictive) genetic testing should only be performed cases of apparently SALS (Tables S3 and S4; Jones in first degree adult blood-relatives of patients with et al., 1995). A DNA-SOD1 diagnostic test speeds up a known SOD1 gene mutation. Testing should the diagnostic process and can be of help in patients only be performed on a strictly volunteer basis as with atypical features (Andersen et al., 2003) as well Figure 2 The different patterns of inheritance and genetic loci found in ALS. It is important to remember that reduced disease penetrance hasbeen recognized in many families with ALS. Some cases diagnosed as SALS are in fact FALS with very low disease penetrance, recessiveinheritance or oligogenic inheritance in a complicated pattern not always understood. CuZn–SOD, SOD1, copper-zinc superoxide dismutase.

2005 EFNS European Journal of Neurology 12, 921–938 EFNS guidelines on management of amyotrophic lateral sclerosis Table 7 Frequency of CuZn-SOD (SOD1) mutations in ALS can be aggravated by aspiration and bronchopneumo-nia (Howard and Orrell, 2002). Some patients present with thoracic paresis and respiratory insufficiency 7.3% (3/41) in Italy (Corrado L. et al., personal communication (Table 8). Vital capacity (VC) is the most widely 7% (4/56) in Scotland (Jones et al., 1995) available test of respiratory muscle function and should 6% (3/48) in Italy (Gellera, 2001) be measured regularly in parallel with assessments of 4% (14/355) in Scandinavia (Andersen et al., 1997) symptoms suggestive of respiratory insufficiency (Leigh 3% (5/175) in the UK (Shaw et al., 1998) et al., 2003). Sniff nasal pressure (SNP) may be a more 3% (5/155) in England (Jackson et al., 1997)1.2% (1/87) in Spain (Garcia-Redondo et al., 2002) accurate predictor of respiratory failure than VC, but 0% (0/225) in Italy (Battistini et al., 2005) neither VC nor SNP are sensitive predictors of respir- atory failure in patients with severe bulbar involvement 23.5% (12/51) in Scandinavia (Andersen et al., 1997) (Lyall et al., 2001). Nocturnal oximetry can detect 23.5% (68/290) in the USA (Cudkowicz et al., 1997) nocturnal hypoventilation and can be done at home.
21% (8/38) in the UK (Shaw et al., 1998)19.7% (14/71) in the UK (Orrell et al., 1997) Blood exchange abnormalities (› PCO2) are generally a 18% (2/11) in Spain (Garcia-Redondo et al., 2002) late finding. Non-invasive positive-pressure ventilation 18% (7/39) in Italy (Battistini et al., 2005) (NIV) and invasive mechanical ventilation via trache- 14.3% (10/70) in France (Boukaftane et al., 1998) ostomy (TV) are used to alleviate respiratory symp- 12% (9/75) in Germany (Niemann et al., 2004) toms, improve quality of life and prolong survival.
Without classification to hereditary disposition: 7.2% (148/2045) in There is no clear evidence regarding timing and criteria North America (Andersen et al., 2003).
of use of NIV and TV in ALS patients (Table 9). Theuse of mechanical ventilation varies between countries consideration should be taken before pre-symptomatic with cross-cultural and ethical differences (Miller et al., testing is performed in FALS families where the 1999; Bourke and Gibson, 2004). The patient's advance mutation is associated with reduced disease pene- directives and a clear plan for management of respir- atory failure should be established before respiratory failure occurs (Miller et al., 1999; Leigh et al., 2003;Bourke and Gibson, 2004). The choice of ventilation Good practice points will depend on hypoventilation symptoms and upper 1 Clinical DNA analysis for SOD1 gene mutation airway obstruction symptoms, bronchial secretions and should only be performed in cases with a known factors such as availability, cost, patient preference and familial history of ALS or in SALS cases with the characteristic phenotype of the D90A mutation.
NIV has become the preferred initial therapy to 2 Clinical DNA analysis for SOD1 gene mutations alleviate respiratory symptoms in ALS patients and should not be performed in cases with SALS with a should be considered before TV (Miller et al., 1999; typical classical ALS-phenotype.
Annane et al., 2000; Leigh et al., 2003; Bourke and 3 Before blood is drawn for DNA analysis, the patient should receive genetic counseling. Give the patienttime for consideration. DNA analysis should not be Table 8 Symptoms and signs of respiratory insufficiency in ALS performed without the patients consent.
[modified from Leigh et al. (2003)] 4 Pre-symptomatic genetic testing should only be per- formed in first degree adult blood-relatives ofpatients with a known SOD1 gene mutation. Testing Dyspnoea on exertion or talking should only be performed on a strictly volunteer basis Use of auxillary respiratory as outlined (Table S7).
Frequent nocturnal awakenings Paradoxical movement of 5 Results of DNA analysis performed on patients and their relatives as part of a research project should not Excessive daytime sleepiness Decreased chest movement be used in clinical practice or disclosed to the unaf- fected relative. Also, the results should be kept in a Difficulty clearing secretions separate file, not in the patient's medical chart.
7 Non-invasive and invasive ventilation in ALS patients Papilloedema (rare) Respiratory insufficiency in ALS patients is caused Poor concentration and/or memory SyncopeMouth dryness mainly by respiratory muscle or bulbar weakness and
2005 EFNS European Journal of Neurology 12, 921–938 P. M. Andersen et al.
Table 9 Proposed criteria for NIV [modified from Leigh et al. (2003)] givers and in these cases can improve patientsÕ qualityof life, although some patients become unable to com- 1 Symptoms related to respiratory muscle weakness. At least one of municate in a state of locked-in (Leigh et al., 2003).
However, home TV is costly and has a significant emotional and social impact on patients and caregivers (c) Disturbed sleep not because of pain (Cazzolli and Oppenheimer, 1996; Miller et al., 1999).
(d) Morning headache The advantages and drawbacks of TV are summarized (e) Poor concentration in Table 10. A difficult issue is when to terminate (f) Loss of appetite(g) Excessive daytime sleepiness (ESS > 9) ventilatory support. Parenteral diamorphine, a benzo- 2 Signs of respiratory muscle weakness (FVC < 80% or diazepine and an antiemetic are used when the patient SNP < 40 cm H2O) decides that ventilatory support should be withdrawn 3 Evidence of either: (Miller et al., 1999). For symptomatic treatment of (a) Significant nocturnal desaturation on overnight oximetry, or dyspnea with opioids and/or oxygen, the class of evi- (b) Morning blood-gas pCO2 >6.5 Kpa.
dence is IA in cancer and chronic obstructive pulmon- ESS, Epworth Sleepiness Score.
ary disease (Jennings et al., 2002; Bruera et al., 2003),but no controlled studies in ALS exist.
Gibson, 2004). It is usually initially used for intermit-tent nocturnal support to alleviate symptoms of noc- Good practice points turnal hypoventilation (Table 8). Observational studies 1 Symptoms or signs of respiratory insufficiency suggest that NIV improves survival and quality of life (including symptoms of nocturnal hypoventilation) (Bourke et al., 2003). Secretion management is a major should be checked at each visit.
factor in the success of NIV (Leigh et al., 2003), (see 2 VC is the most available and practical test for the section Bronchial secretions). As respiratory muscle monitoring of respiratory function on a regular basis.
strength declines, daytime NIV usually becomes neces- If possible, VC should be measured both standing/ sary and patients may become dependent on non-stop sitting and lying.
ventilation. Patients who cannot use NIV should be 3 SNP may be used for monitoring of inspiratory informed about the terminal phase, TV, hospice referral muscle strength, particularly in some bulbar patients and palliative care. Patients with flaccid paresis of the who cannot perform VC accurately.
facial muscles may have difficulty using NIV, but the 4 Nocturnal oximetry, available at home, is recom- method should be offered to patients with predomin- mended in patients with symptoms of nocturnal ating UMN bulbar paresis and little atrophy.
TV may be proposed when NIV treatment is not 5 Symptoms or signs of respiratory insufficiency effective because of progression of the disease or when should initiate discussions with the patient and the the patient cannot cooperate with NIV because of loss caregivers about all treatment options such as NIV, of bulbar tone and difficulty clearing secretions (Fig. 3; TV and the terminal phase. Early discussions are Miller et al., 1999). TV can prolong survival for many needed to allow advance planning and directives.
years, can be acceptable for some patients and care- Figure 3 Flowchart for the managementof respiratory dysfunction in ALS.

2005 EFNS European Journal of Neurology 12, 921–938 EFNS guidelines on management of amyotrophic lateral sclerosis Table 10 The advantages and drawbacks of invasive ventilation tuck maneuverÕ) may be helpful. Some patients having difficulty swallowing tap water can drink carbonatedfluids or ice-cold fluids. Empirically, this is particular the (a) preventing aspiration case for patients with predominantly spastic dysphagia.
(b) more secure ventilator – patients interface Sufficient oral fluid intake is important also to improve (c) ability to provide higher ventilator pressures articulation, to maintain good oral hygiene and reduce the risk of constipation. As dysphagia progresses, these (a) more secretions generating measures become insufficient and tube feeding is needed.
(b) impairing swallowing risk(c) increasing aspiration Three procedures obviate the need for major surgery and (d) increasing risk of infections general anesthesia: percutaneous endoscopic gastrosto- (e) tracheoesophageal fistula my (PEG), percutaneous radiologic gastrostomy (PRG (f) tracheal stenosis or tracheomalacia or RIG, radiologically inserted gastrostomy) and naso- gastric tube (NGT) feeding.
(h) 24 h nursing care The PEG is the standard procedure for enteral nutrition in ALS and is wildly available (Desport et al.,2000; Heffernan et al., 2004). PEG improves nutrition, temporary nature of NIV [which is primarily but there is no convincing evidence that PEG prevents directed towards improving quality of life rather aspiration or improves quality of life or survival (Miller than prolonging it (as opposed to TV)]. Care et al., 1999; Heffernan et al., 2004). The procedure re- should adapt to the changing needs of patients and quires mild sedation and is therefore more hazardous in carers over the course of the disease.
patients with respiratory impairment and/or at an ad- 6 NIV should be considered before TV in patients with vanced stage of the disease (Miller et al., 1999; Desport symptoms of respiratory insufficiency.
et al., 2000; Heffernan et al., 2004). Non-invasive ven- 7 TV can prolong survival for many months and can tilation during the PEG procedure may be feasible in improve patient's quality of life, but it has major ALS patients with respiratory impairment (Heffernan impact upon carers, and be undertaken only after full et al., 2004). The timing of PEG is mainly based on discussion of the pro's and con's with the patient and symptoms, nutritional status and respiratory function (Miller et al., 1999; Heffernan et al., 2004). To minim- 8 Unplanned (emergency) TV should be avoided at all ize risks, evidence suggests that PEG should be per- costs through early discussion of end of life issues, formed before VC falls below 50% of predicted palliative care, and advance directives.
(Mathus-Vliegen et al., 1994).
9 Oxygen therapy alone should be avoided as it may PRG is a new alternative to PEG in ALS patients exacerbate CO2 retention and mouth dryness.
(Chio et al., 2004b; Heffernan et al., 2004; Shaw et al., 10 Medical treatment of intermittent dyspnea: 2004). A major advantage of PRG is that it does not • short dyspneic bouts: relieve anxiety and give require sedation and therefore is suitable in patients lorazepam 0.5-2.5 mg sublingually with respiratory impairment or in poor general condi- • longer phases of dyspnea (>30 min): give mor- tion. The success rate of PRG procedure has also been shown to be higher than PEG (Thornton et al., 2002; 11 Medical treatment of chronic dyspnea: start with Chio et al., 2004b). However, this procedure is not yet morphine 2.5 mg orally four to six times daily. For widely available and is less well documented than PEG.
severe dyspnea give morphine sc or iv infusion. Start The NGT is a minor and non-invasive procedure that with 0.5 mg/h and titrate.
can be given to all patients but presents numerousdisadvantages that limit its use (Scott and Austin, 1994;Heffernan et al., 2004). NGT increases oropharyngeal 8 Enteral nutrition in ALS patients secretions and is associated with nasopharyngeal dis- Initial management of dysphagia in patients with ALS is comfort, pain or even ulceration.
based on dietary counseling, modification of food andfluid consistency (blending food, adding thickeners to Good practice points liquids), prescription of high protein and caloric sup- 1 Bulbar dysfunction and nutritional status, including plements and education of the patient and carers in at least weight, should be checked at each visit.
feeding and swallowing techniques such as supraglottic 2 The patient and spouse should be referred to a swallowing and postural changes (Miller et al., 1999; dietician as soon as dysphagia appears. A speech and Desport et al., 2000; Heffernan et al., 2004). Flexing the language therapist (SLT) can give valuable advice on neck forward on swallowing to protect the airway (Ôchin
2005 EFNS European Journal of Neurology 12, 921–938 P. M. Andersen et al.
3 The timing of PEG/PRG is based on an individual thought translation devices can be used as the new approach taking into account bulbar symptoms, malnutrition (weight loss >10%), respiratory func-tion and the patient's general condition. Thus, early Good practice points operation is highly recommended.
1 Regular assessment (i.e. every 3–6 months) of com- 4 When PEG is indicated, patient and carers should be munication by a trained speech therapist is recom- informed: (i) of the benefits and risks of the procedure; (ii) that it is possible to continue to take food orally as 2 The use of appropriate communication support sys- long as it is possible; (iii) that deferring PEG to a late tems (ranging from pointing boards with figures or disease stage may increase the risk of the procedure.
words, to computerized speech synthesizers) should 5 Percutaneous radiologic gastrostomy (PRG; RIG) is be provided as required.
a suitable alternative to PEG. This procedure can beused as the procedure of choice or when PEG is 10 Palliative and end-of-life care deemed hazardous.
6 Tubes with relatively large diameter (e.g. 18–22 A palliative care approach should be incorporated into Charriere) is recommended for both PEG and PRG the care plan for patients and carers from the time of in order to prevent tube obstruction.
diagnosis (Borasio et al., 2001b, class III recommenda- 7 Prophylactic medication with antibiotics on the day tion). Early referral to a specialist palliative care team is of the operation may reduce the risk of infections.
often appropriate. Palliative care based in the commu- 8 NGT may be used for short-term feeding and when nity or through hospice contacts (e.g. home care teams) PEG or PRG is not suitable.
can proceed in partnership with clinic-based neuro-logical multidisciplinary care. The aim of palliativecare is to maximize quality of life of patients and families 9 Communication in ALS patients by relieving symptoms, providing emotional, psycholo- Most commonly communication difficulties in ALS gical and spiritual support as needed, removing obsta- result from progressive dysarthria, with language cles to a peaceful death, and supporting the family functions remaining largely intact. However, changes of in bereavement (Oliver et al., 2000). Various other language function may occur, especially in patients with aspects of terminal care have been covered in sections cognitive impairment of frontal type. This is shown by 5, 7, 8 and 9.
reduced verbal output (in rare cases leading to mutism),reduced spelling ability, word finding difficulty and Good practice points auditory comprehension of more complex input (Bak 1 Whenever possible, offer input from a palliative care and Hodges, 2004). In others, the deficits are subtle and team early in the course of the disease.
only exposed on formal testing (Cobble, 1998). Lan- 2 Initiate discussions on end-of-life decisions whenever guage impairment can have a deleterious effect on the the patient asks – or Ôopens the doorÕ – for end-of-life quality of life of the patients and carers, and can make information and/or interventions.
the clinical management of the patient difficult (Cobble, 3 Discuss the options for respiratory support and end- 1998; Murphy, 2004).
of-life issues if the patient has dyspnea, other symp- Communication should be routinely assessed by a toms of hypoventilation (Table 8), or a forced VC speech therapist. The goal of management of commu- nication difficulties in ALS patients is to optimize the 4 Inform the patient of the legal situation regarding effectiveness of communication for as long as possible advance directives and naming of a health care proxy.
and to concentrate not only on the disabled person, but Offer assistance in formulating an advance directive.
on personal partner-to-partner communication as well.
5 Re-discuss the patient's preferences for life-sustaining When dysarthria progresses the use of an augmentive treatments every 6 months.
and alternative communication (AAC) system is nee- 6 Initiate early referral to hospice or home care teams ded. An ACC system substantially improves the quality well in advance of the terminal phase of ALS to of life. Prosthetic treatments (palatal lift and/or palatal facilitate the work of the hospice team.
augmentation prosthesis) can be useful in reduction of 7 Be aware of the importance of spiritual issues for hypernasality and improvement of articulation. For the quality of life and treatment choices. Establish ventilated patients eye-pointing or eye-gaze augmentive a liaison with local pastoral care workers in order high-tech communication devices are useful. Brain- to be able to address the needs of the patient and computer-interfaces, EEG & EP (SCP) methods,
2005 EFNS European Journal of Neurology 12, 921–938 EFNS guidelines on management of amyotrophic lateral sclerosis 8 For symptomatic treatment of dyspnea and/or pain of Supplementary Material intractable cause use opioids alone or in combinationwith benzodiazepines if anxiety is present. Titrating The following material is available online at http:// the dosages against the clinical symptoms will almost never result in a life-threatening respiratory depression Table S1 Diseases that can masquerade as ALS/MND (Sykes and Thorns, 2003, class IA recommendation).
Table S2 Factors that may lead to underrepresenta- 9 For treating terminal restlessness and confusion be- tion of FALS cases cause of hypercapnia neuroleptics may be used, (e.g.
Table S3 Disease penetrance in ALS associated with chlorpromazine 12.5 mg every 4–12 h po, iv or pr).
a SOD1 gene mutation 10 Use oxygen only if symptomatic hypoxia is present.
Table S4 SOD1 gene mutations reported in patients with apparently sporadic ALS (SALS) Table S5 Disease survival time in ALS associated Future developments with SOD1 gene mutations (without artificial ventila- Being a syndrome with low incidence and short survi- tion; Het, heterozygous; hom, homozygous) val, most recommendations are good practice points Table S6 SOD1 gene mutations associated with based on consensus of experts in the ALS field. More atypical features of ALS (like neuralgic pain syndrome, preferably randomized and double-blinded clinical tri- heat sensations, bladder disturbance) als are urgently needed to improve the management of Table S7 Guidelines for pre-symptomatic genetic Research recommendations 1 Further studies of more specific diagnostic tools are needed, in particular in relation to cervical spondyl- Previous guidelines or recommendations are indicated otic myelopathy, inclusion body myositis and motor Abrahams S, Goldstein LH, Kew JJ et al. (1996). Frontal lobe dysfunction in amyotrophic lateral sclerosis. A PET study.
2 There is no data on the effects of MD clinics on quality of life or care burden – the generation of such Ackerman GM, Oliver D (1997). Psychosocial support in an data would be beneficial.
outpatient clinic. Palliat Med 11:167–168.
3 Further studies are required to confirm the benefits of Aggarwal A, Nicholson G (2002). Detection of preclinical MD clinics, and to identify the factors that affect motor neurone loss in SOD1 mutation carriers using motor unit number estimation. J Neurol Neurosurg Psychiatry73:199–201.
4 Further studies are required to optimize the symp- Andersen G, Vestergaard K, Riis JO (1993). Citalopram for tomatic treatment of ALS patients, in particular post-stroke pathological crying. Lancet 342:837–839.
therapies for treating muscle cramps, drooling and Andersen PM, Forsgren L, Binzer M et al. (1996). Auto- somal recessive adult-onset ALS associated with homo-zygosity 5 Better criteria for defining the use of PEG and PRG, mutation. A clinical and genealogical study of 36 patients.
and NIV and TV are urgently needed.
6 Further studies to evaluate the effects of PEG/PRG, Andersen PM, Nilsson P, Kera¨nen M-L et al. (1997). Phen- cough-assisting devices and ventilation support on otypic heterogeneity in MND-patients with CuZn-superox- quality of life and survival are advocated.
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External radiation of the parotid glands significantly 8 Studies of the medico-economical impact of more reduces drooling in patients with motor neurone disease expensive procedures (NIV, TV, cough-assisting with bulbar paresis. J Neurol Sci 191:111–114.
devices, advanced communication equipment) are Andersen PM, Sims KB, Xin WW et al. (2003). Sixteen novel mutations in the gene encoding CuZn-superoxide dismutasein ALS. Amyotrop Lateral Scler Other Motor Neuron Disord These guidelines will be updated when necessary and in any case in not more than 3 years.
Annane D, Chevrolet JC, Chevret S, Raphael JC (2000).
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Bak TH, Hodges JR (2004). The effects of motor neurone The present guidelines were prepared without external disease on language: further evidence. Brain Lang 89:354– financial support. None of the authors report conflict- ing interests.

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Source: http://www.neuromuskularni-sekce.cz/res/file/archiv/Guidelines-ALS-management-EFNS.pdf