EsclerosisLateralAmiotrófica

Klgo.Mg.JorgeMolinaBlameyMagísterdeGestiónenSalud

EspecialistaenKinesiologíaRespiratoria.(Denake)EspecialistaenTerapiaRespiratoria(CLCPTR)

DirectorKinesiologíaClínicaAlemana-UniversidaddelDesarrolloDirectorDiplomadoKinesiterapiaUPCCAS-UDD

DirectorDenakePast-President DivisióndeKinesiologíaSociedadChilenadeMedicinaIntensiva

Corporación ELA Septiembre 2016

Definición

• EnfermedadDegenerativaProgresivadelSistemaNerviosoCentral.

• EscasaPrevalencia.

• EsperanzadeVida:3-5añosdesdequeseDg.

• 10%sobrevivemásaños.

Quées

https://beyondthedish.files.wordpress.com/2015/12/myelin_sheath.jpg

Incidenciayprevalencia

• Incidencia:1–2casosnuevos100.000háb/año

• Prevalencia:4-6casos100.000háb.

Original article

Variation in worldwide incidence ofamyotrophic lateral sclerosis: a meta-analysis

Benoıt Marin,1,2,3,4,5,6 Farid Boumediene,1,2,3 Giancarlo Logroscino,5,6

Philippe Couratier,1,2,7 Marie-Claude Babron,8,9

Anne Louise Leutenegger,8,9 Massimilano Copetti,10

Pierre-Marie Preux1,2,3 and Ettore Beghi4,*

1INSERM, U1094, Tropical Neuroepidemiology, Limoges, France, 2Univ. Limoges, UMR_S 1094, TropicalNeuroepidemiology, Institute of Neuroepidemiology and Tropical Neurology, CNRS FR 3503 GEIST, F-87000 Limoges, France, 3CHU Limoges, Centre d’Epidemiologie de Biostatistique et de Methodologie dela Recherche, Limoges, France, 4Laboratorio di Malattie Neurologiche, IRCCS Istituto di RicercheFarmacologiche Mario Negri, Milano, Italy, 5Department of Basic Medical Sciences, Neuroscienceand Sense Organs, University of Bari ‘Aldo Moro’, Bari, Italy, 6Unit of Neurodegenerative Diseases,University of Bari ‘Aldo Moro’, at ‘Pia Fondazione Cardinale G. Panico’, Lecce, Italy, 7CHU Limoges,Service de Neurologie, Limoges, France, 8INSERM UMR 946, Genetic Variability and Human Diseases,Paris, France, 9University Paris Diderot, UMR 946, Paris, France and 10Unit of Biostatistics, IRCCS‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo, Italy

*Corresponding author. Mario Negri IRCCS Institute for Pharmacological Research, Via La Masa 19, 20156 Milano, Italy.

E-mail: ettore.beghi@marionegri.it

Accepted 4 March 2016

Abstract

Background: To assess the worldwide variation of amyotrophic lateral sclerosis (ALS) in-cidence, we performed a systematic review and meta-analysis of population-based datapublished to date.Methods: We reviewed Medline and Embase up to June 2015 and included all population-based studies of newly diagnosed ALS cases, using multiple sources for case ascertain-ment. ALS crude and standardized incidence (on age and sex using the US 2010 popula-tion) were calculated. Random effect meta-analysis and meta-regression were performedusing the subcontinent as the main study level covariate. Sources of heterogeneity relatedto the characteristics of the study population and the study methodology were investigated.Results: Among 3216 records, 44 studies were selected, covering 45 geographical areasin 11 sub-continents. A total of 13 146 ALS cases and 825 million person-years of follow-up (PYFU) were co-nsidered. The overall pooled worldwide crude ALS incidence was at1.75 (1.55–1.96)/100 000 PYFU; 1.68 (1.50–1.85)/100 000 PYFU after standardization.Heterogeneity was identified in ALS standardized incidence between North Europe [1.89(1.46–2.32)/100 000 PYFU] and East Asia [0.83 (0.42–1.24)/100 000 PYFU, China and JapanP ¼ 0.001] or South Asia [0.73 (0.58–0.89)/100 000/PYFU Iran, P ¼ 0.02]. Conversely,homogeneous rates have been reported in populations from Europe, North America and

VC The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association 1This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-

nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way,

and that the work properly cited. For commercial re-use, please contact journals.permissions@oup.com

International Journal of Epidemiology, 2016, 1–18

doi: 10.1093/ije/dyw061

Original article

Int. J. Epidemiol. Advance Access published July 27, 2016

by guest on September 6, 2016

http://ije.oxfordjournals.org/D

ownloaded from

Distribución heterogéneaenelmundo

Figure 2. Distribution of ALS worldwide: crude incidence and age- and sex-standardized incidence on USA 2010 population.

International Journal of Epidemiology, 2016, Vol. 00, No. 00 7

by guest on September 6, 2016

http://ije.oxfordjournals.org/D

ownloaded from

Review

Assessment of the upper motor neuron in amyotrophic lateral sclerosis

William Huynh a,b,⇑, Neil G. Simon c, Julian Grosskreutz d, Martin R. Turner e, Steve Vucic f,Matthew C. Kiernan a

aBrain and Mind Centre, University of Sydney, NSW, Australiab Prince of Wales Clinical School, University of New South Wales, NSW, AustraliacDepartment of Neurology, St Vincent’s Hospital, Darlinghurst, AustraliadHans-Berger Department of Neurology, University Hospital Jena, Jena, GermanyeNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UKfWestern Clinical School, University of Sydney, Sydney, Australia

a r t i c l e i n f o

Article history:Accepted 27 April 2016Available online 5 May 2016

Keywords:Amyotrophic lateral sclerosisMotor neuron diseaseUpper motor neuronImagingTranscranial magnetic stimulation

h i g h l i g h t s

! Clinical signs of UMN involvement are an important component in diagnosis of ALS.! Novel neuroimaging and electrophysiology may facilitate demonstration of UMN degeneration in ALS.! Improving early ALS diagnosis can facilitate the development of effective therapies.

a b s t r a c t

Clinical signs of upper motor neuron (UMN) involvement are an important component in supporting thediagnosis of amyotrophic lateral sclerosis (ALS), but are often not easily appreciated in a limb that is con-currently affected by muscle wasting and lower motor neuron degeneration, particularly in the earlysymptomatic stages of ALS. Whilst recent criteria have been proposed to facilitate improved detectionof lower motor neuron impairment through electrophysiological features that have improved diagnosticsensitivity, assessment of upper motor neuron involvement remains essentially clinical. As a result, thereis often a significant diagnostic delay that in turn may impact institution of disease-modifying therapyand access to other optimal patient management. Biomarkers of pathological UMN involvement are alsorequired to ensure patients with suspected ALS have timely access to appropriate therapeutic trials. Thepresent review provides an analysis of current and recently developed assessment techniques, includingnovel imaging and electrophysiological approaches used to study corticomotoneuronal pathology in ALS.! 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. This is anopen access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26442. Literature search strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26443. Clinical neurophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2645

3.1. Spinal reflex changes in MND/ALS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26453.1.1. Deep tendon reflexes and the H-reflex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26453.1.2. Plantar reflexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26453.1.3. Other spinal interneuronal networks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2645

3.2. Transcranial magnetic stimulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26453.2.1. Single-pulse TMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26473.2.2. Paired-pulse TMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26473.2.3. Triple stimulation technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2649

http://dx.doi.org/10.1016/j.clinph.2016.04.0251388-2457/! 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

⇑ Corresponding author at: Brain and Mind Centre, University of Sydney, and Institute of Neurological Sciences, Prince of Wales Hospital, NSW, AustraliaE-mail address: w.huynh@neura.edu.au (W. Huynh).

Clinical Neurophysiology 127 (2016) 2643–2660

Contents lists available at ScienceDirect

Clinical Neurophysiology

journal homepage: www.elsevier .com/locate /c l inph

corticomotoneuronal involvement as well as PMA being part of theMND/ALS clinical spectrum. In addition, patients with MND/ALSalso showed clusters of relative hypermetabolism within the cere-bellum, occipital cortex, upper brain stem, and medial temporalcortex (Van Laere et al., 2014). Patients with PLS demonstrated amore widespread abnormality with symmetrically reducedmetabolism bilaterally in the prefrontal cortex, anterior cingulate,pericentral cortex, and thalamus (Van Laere et al., 2014). One studyproposed that the most discriminating regions (between pheno-types of MND: ALS, PMA and PLS) were the prefrontal cortex,thalamus, posterior cingulate, and anterior cingulate (Van Laereet al., 2014). Reductions in metabolism in frontal lobe regions wereprominent in MND/ALS patients with cognitive impairment espe-cially those with executive dysfunction such as verbal fluency(Abrahams et al., 1996; Cistaro et al., 2012), and extensive fron-totemporal hypometabolism was predictive for a lower survival(Burrell et al., 2016; Van Weehaeghe et al., 2016). Further studieshowever are needed to compare patients with MND to patientswith mimic disorders to better define the sensitivity and specificityof 18FDG-PET in the diagnosis of MND. Longitudinal studies are alsorequired to investigate both the neuroradiological course of thedisease using 18FDG-PET but its change in relation to potentiallydisease-modifying agents.

15O2 and H215O were originally used to study regional cerebralblood flow (rCBF), permitting the introduction of activation studies(Kew et al., 1993). Attention shifted to the utilisation of tracerligands such as 18F-6-fluorodopa and 11C-Flumazenil to identifychanges in specific neurochemical and cellular systems in MND/ALS (Turner and Leigh, 2000). Studies using Flumazenil as aGABA-A receptor ligand demonstrated similar regions of decreasedtracer uptake in the motor and extramotor regions of the brain(Cistaro et al., 2014), and profound serotonergic receptor bindingreductions were observed in frontotemporal regions of non-depressed, non-demented MND/ALS patients (Turner et al., 2005b).

5. Combining multiple electrophysiological and imagingmodalities

As the abovementioned novel electrophysiological and imagingbecome more readily accessible in clinical practice, it seems likelythat combining structural and functional diagnostic biomarkers

more likely increases the likelihood of objectively demonstratingUMN dysfunction in MND thereby facilitating earlier diagnosisand institution of potentially disease-modifying agents (Pohlet al., 2001b; Kaufmann et al., 2004; Turner et al., 2005a; Furtulaet al., 2013; Grieve et al., 2015; Bae et al., 2016). In a study thatcombined structural imaging and electrophysiological approachesrevealed that the presence of precentral gyrus cortical thinningor paired-pulse TMS abnormalities was evident in 88% of MNDpatients, while temporal region cortical thinning or TMS abnormal-ities were evident in 96% (Grieve et al., 2015). Further, TMS abnor-malities did not correlate with cortical thinning, suggesting thatfunctional and structural cortical abnormalities may act as comple-mentary diagnostic biomarkers of UMN dysfunction in MND/ALS(Grieve et al., 2015). Prior to this study, another group of investiga-tors also combined the use of MRS with single-pulsed TMS tech-niques to examine the presence of UMN abnormalities inpatients with MND/ALS (Pohl et al., 2001b). The authors found thatabnormal MRS findings were present in 53% whilst abnormal TMSin 63%. Abnormalities in either study was demonstrated in 78%whilst abnormalities in both in 39%, again suggesting that theuse of a combined imaging and electrophysiological approachmay complement each other and increase the yield of detectingUMN abnormalities. Of particular relevance, the combinedapproach detected UMN abnormalities in 60% of those MNDpatients without clinical UMN signs (that included patients inthe suspected and possible EEC categories). Furthermore, morethan 60% of these patients upon follow-up later developed clinicalUMN signs (Pohl et al., 2001b).

6. Conclusions and future directions

There remains considerable challenges in the development of adiagnostic tool that fulfils all of the requirements necessary to con-stitute a biomarker of UMN dysfunction in MND/ALS patients(Table 1). It requires replicable data in a large number of patientswith different clinical phenotypes and at various stages of the dis-ease. Currently, neurophysiological and neuroimaging techniquesutilised in the assessment of UMN function are either not readilyaccessible outside a research setting or exhibit poor sensitivity orspecificity in early stage of the disease process. For this reason, for-mulating a diagnostic algorithm based on the use of these novel

Fig. 11. 18F-fluorodeoxyglucose PET analysis in ALS patients demonstrating hypometabolism. The images show three-dimensional rendering of the brain cortical surface ofthe clusters of voxels in which patients with ALS show hypometabolism compared with healthy controls. Uptake is substantially impaired mainly in the frontal and anteriorcingulate cortex. Reproduced with permission (Chio et al., 2014).

W. Huynh et al. / Clinical Neurophysiology 127 (2016) 2643–2660 2655

Biomarcadores,técnicas dedifusión, tomografía,espectroscopía

n e u r o l a r g . 2 0 1 4;6(2):91–95

Neurología Argentina

www.elsev ier .es /neuro larg

Revisión

Esclerosis lateral amiotrófica (ELA): seguimientoy tratamiento

Cecilia Quarracinoa,∗, Raúl Carlos Reyb y Gabriel Eduardo Rodríguezc

a Residente de Neurología, División Neurología, Hospital Ramos Mejía, Centro Universitario de Neurología José María Ramos Mejía,

Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentinab Jefe de División de Neurología, Hospital Ramos Mejía, Centro Universitario de Neurología José María Ramos Mejía,

Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentinac Sector Enfermedades de motoneurona, División de Neurología, Hospital Ramos Mejía, Centro Universitario de Neurología

José María Ramos Mejía, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

información del artículo

Historia del artículo:

Recibido el 1 de noviembre de 2013

Aceptado el 19 de febrero de 2014

On-line el 26 de abril de 2014

Palabras clave:

Esclerosis lateral amiotrófica

Seguimiento

Tratamiento de sostén

r e s u m e n

La esclerosis lateral amiotrófica es una enfermedad neurológica degenerativa que afecta a

la vía piramidal a lo largo de su primera y segunda neuronas motoras. La supervivencia al

diagnóstico ronda el 20% a los 3-5 anos.

No existe en la actualidad tratamiento curativo para ella, si bien se encuentran en investi-

gación y desarrollo nuevas opciones terapéuticas. Como contrapartida, han sido muchos los

fármacos investigados y muchas veces puestos en práctica que no han demostrado eficacia

terapéutica.

Esto determina que el diagnóstico de la enfermedad implique un abordaje multidiscipli-

nario que apunta principalmente a proporcionar un bienestar adecuado a cada una de las

complicaciones de su evolución.

En este trabajo describimos la sintomatología más frecuentemente desarrollada por el

paciente y sus opciones de tratamiento, considerando la bibliografía nacional e internacional

así como la experiencia de nuestro servicio.

Nos abocamos a: debilidad muscular, sialorrea, secreciones bronquiales, afección seudo-

bulbar, calambres, espasticidad, insuficiencia respiratoria, edema de miembros inferiores,

depresión y disfagia.

Nos interesa resaltar que contra la creencia generalizada de «no hay nada más que hacer»,

se resumen algunas, y solo algunas, de las herramientas que es necesario conocer y utilizar

en tiempo y forma, para el adecuado tratamiento de esta patología.

© 2013 Sociedad Neurológica Argentina. Publicado por Elsevier España, S.L. Todos los

derechos reservados.

∗ Autor para correspondencia.Correo electrónico: cecquarr@hotmail.com (C. Quarracino).

1853-0028/$ – see front matter © 2013 Sociedad Neurológica Argentina. Publicado por Elsevier España, S.L. Todos los derechos reservados.http://dx.doi.org/10.1016/j.neuarg.2014.02.004

Documento descargado de http://www.elsevier.es el 06/09/2016. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato.

National Clinical Guideline Centre

.

Motor neurone disease Motor neurone disease: assessment and management

NICE guideline NG42 Methods, evidence and recommendations

February 2016

.

Commissioned by the National Institute for Health and Care Excellence

48 | JANUARY 2012 | VOLUME 8 www.nature.com/nrneurol

Rudolf Magnus Institute of Neuroscience, Department of Neurology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands (L. Vlam, W.-L. van der Pol, E. A. Cats, D. C. Straver, S. Piepers, H. Franssen, L. H. van den Berg).

Correspondence to: L. H. van den Berg l.h.vandenberg@umcutrecht.nl

Multifocal motor neuropathy: diagnosis, pathogenesis and treatment strategiesLotte Vlam, W.-Ludo van der Pol, Elisabeth A. Cats, Dirk C. Straver, Sanneke Piepers, Hessel Franssen and Leonard H. van den Berg

Abstract | Multifocal motor neuropathy (MMN) is a rare inflammatory neuropathy characterized by slowly progressive, asymmetric distal limb weakness without sensory loss. The clinical presentation of MMN may mimic amyotrophic lateral sclerosis, other variants of motor neuron disease, or chronic inflammatory demyelinating polyneuropathy with asymmetric onset. Differentiation is important, as these diseases differ in prognosis and treatment. The electrophysiological finding of conduction block in the absence of abnormalities in sensory nerves is the hallmark of MMN, but can be difficult to detect. Intravenous immunoglobulin is efficacious in most patients, but long-term maintenance therapy does not prevent slowly progressive axonal degeneration. Moreover, cyclophosphamide, although effective, has substantial adverse effects, and the efficacy of other immunosuppressive drugs, including rituximab, is not established. The underlying pathological mechanisms of MMN are unclear, but IgM autoantibodies against the ganglioside GM1 may cause changes in nodal and perinodal structures that compromise nerve conduction. Further elucidation of the disease mechanisms may ultimately lead to improved treatment strategies. In this Review, we discuss the diagnostic criteria for MMN, and provide an update on the current understanding of MMN pathogenesis. We also describe available treatments and promising new therapeutic strategies.

Vlam, L. et al. Nat. Rev. Neurol. 8, 48–58 (2012); published online 22 November 2011; doi:10.1038/nrneurol.2011.175

IntroductionMultifocal motor neuropathy (MMN), which was first described in 1985, is a rare disorder, with a prevalence of around 0.6 per 100,000 individuals.1 It is a purely motor neuropathy with slowly progressive, asymmetric, predomi-nantly distal weakness of limbs. Conduction block was identified as the electrophysiological characteristic that dis-tinguished MMN from motor neuron disease (MND).2–4 In 1988, the association of MMN with high serum levels of IgM antibodies against the ganglioside GM1 were reported, together with the positive effects of treatment with the immunosuppressive agent cyclophosphamide.5 These groundbreaking reports were followed by larger case series that described the clinical and electrophysiological characteristics of patients with MMN in more detail.6–12

High-dose intravenous immunoglobulin (IVIg) remains the treatment of choice, following clinical trials that showed this approach to be efficacious and safe.13–16 Moreover, early intervention with IVIg may prevent axonal damage.17 As such, MMN is regarded as a treatable disorder with a rela-tively favorable prognosis compared with its most impor-tant mimic, amyotrophic lateral sclerosis (ALS). However, the effect of IVIg on MMN may decline after several years, and many patients experience progression of neurological

deficits despite increasing IVIg doses.17,18 Alternative treat-ment strategies that prevent perma nent weakness are, therefore, needed. Although clinical, immunological and electrophysiological studies have improved our under-standing of MMN, the under lying pathogenic mechanisms need further dissection.

In this Review, we discuss the clinical characteristics, differential diagnosis, and diagnostic criteria for MMN. We summarize what is known about the pathophysiology of MMN, the evidence supporting the validity of estab-lished treatment strategies, and the treatment options in refractory cases. Finally, we highlight potential novel therapeutic strategies.

Clinical featuresDemographicsMales are more commonly affected by MMN than are females, with an approximate male:female ratio of 2.7:1.1 In almost 80% of patients, the first symptoms appear before the age of 50 years. The mean age at onset is 40 years (range 20–70 years).1,19,20 Onset is generally at an earlier age in men (38 years) than in women (45 years).1 In contrast to chronic inflammatory demyelinating polyneuropathy (CIDP), onset of MMN has not been reported in patients over 70 years of age.

SymptomsMMN is characterized by asymmetric, predominantly distal limb weakness that follows the distribution of

Competing interestsW.-L. van der Pol, E. A. Cats, H. Franssen and L. H. van den Berg declare associations with the following company: Baxter International. See the article online for full details of the relationships. The other authors declare no competing interests.

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50 | JANUARY 2012 | VOLUME 8 www.nature.com/nrneurol

compatible with LSS than with MMN are a relapsing–remitting disease course, progression of symptoms in a matter of weeks, and clear clinical sensory deficits that are confirmed by decreased sensory nerve action potential amplitudes. Other ancillary investigations are less helpful in differentiating between the two diseases. Cerebrospinal fluid (CSF) protein levels in most cases of MMN and LSS are normal or slightly increased (<1 g/l), unlike in CIDP. The presence of a high GM1-specific antibody titer could suggest MMN, but marginally increased titers have low sensitivity and do not exclude LSS or lower motor neuron disease.45,48,49,51,52 Whether LSS represents a nosologically distinct entity or a focal variant of CIDP, or is more closely related to MMN, continues to be debated.44–46,48,50,52,53

Finally, entrapment neuropathy and hereditary neuro-pathy with liability to pressure palsies are other mimics of MMN, but can be relatively easily distinguished by nerve conduction abnormalities at sites of compression.55

Diagnostic criteriaSeveral groups and consortia have proposed sets of diagnostic criteria for MMN, which show considerable overlap.28,41,56–58 The diagnosis of MMN is based on clini-cal and electrophysiological characteristics, and may be supported by results from ancillary investigations—that is, normal or slightly increased CSF protein (<1 g/l), the presence of GM1-specific IgM antibodies, and abnormal MRI signals in the brachial plexus. The diagnostic criteria are summarized in Box 1 and presented in more detail in Supplementary Box 1 online.

Electrophysiological findingsMotor conduction block—the inability of motor axons to propagate action potentials—outside common sites of entrapment is the electrophysiological hallmark of MMN. In an affected nerve segment, conduction block in numer-ous axons may result in a reduction of the compound

muscle action potential (CMAP) following proximal versus distal stimulation of the muscle—a phenomenon known as decrement. Decrement can also occur owing to increased temporal dispersion, which results from an increase in the difference in conduction velocities of various axons in a nerve. This causes desynchronized arrival of action potentials at the motor end plate and, sub sequently, increased cancellation of the positive and nega tive phases of the motor unit action potentials that con stitute the CMAP. Phase cancellation is suggested to be more prominent when the motor unit action poten-tials contributing to the CMAP are polyphasic owing to collateral reinnervation following partial denervation.59 Criteria for conduction block should, therefore, exclude decrement caused by temporal dispersion or increased phase cancellation.

We define definite conduction block as a greater than 50% reduction of the CMAP area over a long nerve seg-ment (between Erb’s point and the axilla, upper arm, fore arm or lower leg) or a CMAP amplitude reduction of at least 30% over a short distance (2.5 cm), detected by inching. We define probable conduction block as a reduction in CMAP amplitude of at least 30% over a long segment of an arm nerve. Both definitions require the CMAP amplitude on stimulation of the distal segment to be at least 1 mV.41

Whether conduction block is always part of MMN is an important issue and depends on the criteria used to define this feature and the number of nerves investi-gated.60 Extensive nerve conduction studies are essential for finding proximal conduction blocks. As patients with MMN with and without conduction block have similar clinical features and respond equally well to IVIg infu-sions,1,61 a diagnosis of possible MMN in the absence of conduction block was included in consensus cri-teria.28,41 Features of demyelination other than conduc-tion block, lack of denervation in the paraspinal muscles,

Table 1 | Differential diagnosis of multifocal motor neuropathy

Feature Multifocal motor neuropathy

Amyotrophic lateral sclerosis

Lower motor neuron disease

Chronic inflammatory demyelinating polyneuropathy

Lewis–Sumner syndrome

Distribution of weakness Asymmetric Asymmetric Asymmetric Symmetric Asymmetric

Prominent sensory symptoms No No No Yes Yes

Tendon reflexes Normal or decreased in weakened muscles*

Increased in weakened muscles

Decreased in weakened muscles

General hyporeflexia or areflexia

Decreased in weakened muscles

Disease course Slowly progressive Rapidly progressive

Slowly or rapidly progressive

Progressive or relapsing Progressive or relapsing

Cerebrospinal fluid protein >1 g/l

No No No Yes Rare

Increased titers of GM1-specific IgM antibodies

Common Rare Rare Rare Rare

Abnormal MRI signal in the brachial plexus

Asymmetric No No Symmetric Asymmetric

Response to intravenous immunoglobulin

Yes No No Yes Yes

Response to corticosteroids No‡ No No Yes Yes

*In some patients, reflexes are brisk. ‡May aggravate symptoms.

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NATURE REVIEWS | NEUROLOGY VOLUME 8 | JANUARY 2012 | 55

Although the long-term effects of immunoglobulin maintenance treatment have been confirmed in several studies,17,18,20,91,126 IVIg treatment does not prevent a mild gradual decline in muscle strength—probably due to ongoing axonal degeneration—over time.17,18,59

Other therapiesImmunomodulatory therapies other than IVIg have been investigated in open-label trials and in one placebo-controlled trial. Prednisolone and plasmapher-esis are ineffective in most patients with MMN and may even exacerbate symptoms.20,127–129 Cyclophosphamide was the first drug used to treat patients with MMN, and has been reported to be effective in several case series. In a recent review of these studies,130 28 patients (68%) reported some or significant improvement, but the sub-stantial adverse effects of cyclophosphamide restrict its long-term use.60

Uncontrolled studies28,130–132 have suggested benefi-cial effects of treatment with interferon-β, cyclosporine, metho trexate, azathioprine and mycophenolate mofetil in some patients with MMN. However, a randomized placebo-controlled trial showed that adjunctive treat-ment with mycophenolate mofetil did not alter the dis-ease course of patients with MMN, and did not allow signi ficant reduction of IVIg doses.133 Treatment with eculi zumab, a monoclonal antibody directed against

complement factor C5, did not allow dose reduction of IVIg in most patients, although some improvements in objective motor performance measures and conduction block were observed after treatment in an open-label study of 13 patients.134 Several case reports and small uncon-trolled studies have described treatment experiences with ritixumab, a monoclonal antibody directed against the B-cell-specific antigen CD20.135–140 The results from these studies are inconsistent (Table 2). A randomized controlled trial is, therefore, needed to further establish the safety and efficacy of ri tuximab treatment in patients with MMN.

ConclusionsMMN is a treatable disorder and should, as such, be differen tiated from MND. Conduction block is the electro physiological hallmark of MMN but may be dif-ficult to identify. Nerve conduction studies should, there-fore, be as extensive as required—including proximal nerve segments—in patients with asymmetric, progres-sive limb weakness without evident sensory disturbance or upper motor neuron signs. Although treatment with IVIg is efficacious in most patients with MMN, a slowly progressive decline in muscle strength during long-term IVIg treatment usually occurs. Determinants of perma-nent weakness are the number of years without IVIg treatment and the amount of axon loss. Future treatment strategies should aim to prevent axon loss.

Table 2 | Studies of rituximab treatment in MMN

Study feature Pestronk et al. (2003)135

Rojas-García et al. (2003)136

Ruegg et al.(2004)137

Gorson et al.(2007)138

Stieglbauer et al. (2009)139

Chaudhry & Cornblath(2010)140

Study design Prospective, open-label, controlled study

Case series Case report Prospective, open-label, uncontrolled study

Case series Prospective, open-label, uncontrolled study

Participants 21 patients with IgM-associated polyneuropathies with insufficient effect of IVIg

Two patients with chronic motor neuropathy and declining response to IVIg

One patient with MMN and declining response to IVIg

Six patients with IVIg-dependent, relapsing immune polyneuropathy

Three patients with MMN and declining response to IVIg

Six patients with MMN receiving periodic IVIg infusions

Number of patients with MMN

14 1 1 2 3 6

Mean disease duration (years)

Not mentioned 5 12 Not mentioned 7 18

IgM anti-ganglioside antibodies

Yes Yes No No No No

Follow-up 2 years 12 weeks 5 years 1 year 27–39 months 1 year

Rituximab regimen Monotherapy Monotherapy Add-on therapy Add-on therapy Monotherapy Add-on therapy

Clinical outcome Mean increase in strength of 22%, versus 0% in control group

Clinical deterioration after 2 months

IVIg dosing interval increased from 7 days to 12 days,and subjective clinical improvement

IVIg dose reduction of 43% and increase in strength in one patient, but IVIg dose increased by 24% in other patient

Sustained clinical improvement in all patients

No significant improvement in group mean scores;subjective and objective improvements in strength and disability in individual patients; IVIg dosing interval increased from 4 weeks to 5 weeks in one patient

Number of patients experiencing improvement

At least 11* 0 1 1 3 4

*Not mentioned solely for MMN patients (improvement of strength in 18 of 21 patients). Abbreviations: IVIg, intravenous immunoglobulin; MMN, multifocal motor neuropathy.

REVIEWS

© 2011 Macmillan Publishers Limited. All rights reservedNATURE REVIEWS | NEUROLOGY VOLUME 8 | JANUARY 2012 | 55

Although the long-term effects of immunoglobulin maintenance treatment have been confirmed in several studies,17,18,20,91,126 IVIg treatment does not prevent a mild gradual decline in muscle strength—probably due to ongoing axonal degeneration—over time.17,18,59

Other therapiesImmunomodulatory therapies other than IVIg have been investigated in open-label trials and in one placebo-controlled trial. Prednisolone and plasmapher-esis are ineffective in most patients with MMN and may even exacerbate symptoms.20,127–129 Cyclophosphamide was the first drug used to treat patients with MMN, and has been reported to be effective in several case series. In a recent review of these studies,130 28 patients (68%) reported some or significant improvement, but the sub-stantial adverse effects of cyclophosphamide restrict its long-term use.60

Uncontrolled studies28,130–132 have suggested benefi-cial effects of treatment with interferon-β, cyclosporine, metho trexate, azathioprine and mycophenolate mofetil in some patients with MMN. However, a randomized placebo-controlled trial showed that adjunctive treat-ment with mycophenolate mofetil did not alter the dis-ease course of patients with MMN, and did not allow signi ficant reduction of IVIg doses.133 Treatment with eculi zumab, a monoclonal antibody directed against

complement factor C5, did not allow dose reduction of IVIg in most patients, although some improvements in objective motor performance measures and conduction block were observed after treatment in an open-label study of 13 patients.134 Several case reports and small uncon-trolled studies have described treatment experiences with ritixumab, a monoclonal antibody directed against the B-cell-specific antigen CD20.135–140 The results from these studies are inconsistent (Table 2). A randomized controlled trial is, therefore, needed to further establish the safety and efficacy of ri tuximab treatment in patients with MMN.

ConclusionsMMN is a treatable disorder and should, as such, be differen tiated from MND. Conduction block is the electro physiological hallmark of MMN but may be dif-ficult to identify. Nerve conduction studies should, there-fore, be as extensive as required—including proximal nerve segments—in patients with asymmetric, progres-sive limb weakness without evident sensory disturbance or upper motor neuron signs. Although treatment with IVIg is efficacious in most patients with MMN, a slowly progressive decline in muscle strength during long-term IVIg treatment usually occurs. Determinants of perma-nent weakness are the number of years without IVIg treatment and the amount of axon loss. Future treatment strategies should aim to prevent axon loss.

Table 2 | Studies of rituximab treatment in MMN

Study feature Pestronk et al. (2003)135

Rojas-García et al. (2003)136

Ruegg et al.(2004)137

Gorson et al.(2007)138

Stieglbauer et al. (2009)139

Chaudhry & Cornblath(2010)140

Study design Prospective, open-label, controlled study

Case series Case report Prospective, open-label, uncontrolled study

Case series Prospective, open-label, uncontrolled study

Participants 21 patients with IgM-associated polyneuropathies with insufficient effect of IVIg

Two patients with chronic motor neuropathy and declining response to IVIg

One patient with MMN and declining response to IVIg

Six patients with IVIg-dependent, relapsing immune polyneuropathy

Three patients with MMN and declining response to IVIg

Six patients with MMN receiving periodic IVIg infusions

Number of patients with MMN

14 1 1 2 3 6

Mean disease duration (years)

Not mentioned 5 12 Not mentioned 7 18

IgM anti-ganglioside antibodies

Yes Yes No No No No

Follow-up 2 years 12 weeks 5 years 1 year 27–39 months 1 year

Rituximab regimen Monotherapy Monotherapy Add-on therapy Add-on therapy Monotherapy Add-on therapy

Clinical outcome Mean increase in strength of 22%, versus 0% in control group

Clinical deterioration after 2 months

IVIg dosing interval increased from 7 days to 12 days,and subjective clinical improvement

IVIg dose reduction of 43% and increase in strength in one patient, but IVIg dose increased by 24% in other patient

Sustained clinical improvement in all patients

No significant improvement in group mean scores;subjective and objective improvements in strength and disability in individual patients; IVIg dosing interval increased from 4 weeks to 5 weeks in one patient

Number of patients experiencing improvement

At least 11* 0 1 1 3 4

*Not mentioned solely for MMN patients (improvement of strength in 18 of 21 patients). Abbreviations: IVIg, intravenous immunoglobulin; MMN, multifocal motor neuropathy.

REVIEWS

© 2011 Macmillan Publishers Limited. All rights reserved

Practice Parameter update: The care of the patient withamyotrophic lateral sclerosis: Drug, nutritional, andrespiratory therapies (an evidence-based review)Report of the Quality Standards Subcommittee of the American Academy of Neurology

R.G. Miller, MD, FAANC.E. Jackson, MD, FAANE.J. Kasarskis, MD,

PhD, FAANJ.D. England, MD,

FAAND. Forshew, RNW. Johnston, MDS. Kalra, MDJ.S. Katz, MDH. Mitsumoto,

MD, FAANJ. Rosenfeld, MD, PhD,

FAANC. Shoesmith, MD, BScM.J. Strong, MDS.C. Woolley, PhD

ABSTRACT

Objective: To systematically review evidence bearing on the management of patients with amyo-trophic lateral sclerosis (ALS).

Methods: The authors analyzed studies from 1998 to 2007 to update the 1999 practice param-eter. Topics covered in this section include slowing disease progression, nutrition, and respiratorymanagement for patients with ALS.

Results: The authors identified 8 Class I studies, 5 Class II studies, and 43 Class III studies in ALS.Important treatments are available for patients with ALS that are underutilized. Noninvasive ven-tilation (NIV), percutaneous endoscopic gastrostomy (PEG), and riluzole are particularly importantand have the best evidence. More studies are needed to examine the best tests of respiratoryfunction in ALS, as well as the optimal time for starting PEG, the impact of PEG on quality of lifeand survival, and the effect of vitamins and supplements on ALS.

Recommendations: Riluzole should be offered to slow disease progression (Level A). PEG shouldbe considered to stabilize weight and to prolong survival in patients with ALS (Level B). NIV shouldbe considered to treat respiratory insufficiency in order to lengthen survival (Level B), and may beconsidered to slow the decline of forced vital capacity (Level C) and improve quality of life (LevelC). Early initiation of NIV may increase compliance (Level C), and insufflation/exsufflation may beconsidered to help clear secretions (Level C). Neurology® 2009;73:1218 –1226

GLOSSARYAAN ! American Academy of Neurology; ALS ! amyotrophic lateral sclerosis; FVC ! forced vital capacity; HFCWO ! highfrequency chest wall oscillation; MIE ! mechanical insufflation/exsufflation; MIP ! maximal inspiratory pressure; NIV !noninvasive ventilation; PCEF ! peak cough expiratory flow; Pdi ! transdiaphragmatic pressure; PEG ! percutaneous endo-scopic gastrostomy; QOL ! quality of life; RIG ! radiologically inserted device; SNP ! sniff nasal pressure; TIV ! tracheos-tomy invasive ventilation.

Amyotrophic lateral sclerosis (ALS) is a neurodegenera-tive disease characterized by loss of motor neurons inthe spinal cord, brainstem, and motor cortex. The causeof the disease is still not known. ALS is not curable, buta number of important therapies are available. In 1999,the American Academy of Neurology (AAN) publishedan evidence-based practice parameter for managing pa-tients with ALS.1 Since that publication, there havebeen some important new studies, including a random-ized controlled trial of noninvasive ventilation in ALS.2

Although only 1 drug, riluzole, has shown modest ben-

efit and received US Food and Drug Administrationapproval (see below), there have been advances in symp-tomatic treatment for patients with this disease. In thisrevision, we update the riluzole practice advisoryand address other management issues for care ofpatients with ALS. This article addresses riluzole,lithium, nutrition, and respiratory care, while acompanion article addresses breaking the news,symptom management, palliative care, cognitiveand behavioral impairment, multidisciplinaryclinics, and communication.

See also page 1227

Supplemental data atwww.neurology.org

Address correspondence andreprint requests to the AmericanAcademy of Neurology, 1080Montreal Avenue, St. Paul, MN55116guidelines@aan.com

From the Department of Neurology (R.G.M., D.F., J.S.K., S.C.W.), California Pacific Medical Center, San Francisco; University of Texas HealthScience Center of San Antonio (C.E.J.); University of Kentucky (E.J.K.), Lexington; Louisiana State University Health Sciences Center (J.D.E.), NewOrleans; Department of Neurology (W.J., S.K.), University of Alberta, Canada; Neurological Institute (NI-9) (H.M.), New York, NY; Division ofNeurology (J.R.), UCSF, Fresno, CA; and London Health Sciences Center (C.S., M.J.S.), London, Canada.

Appendices e-1–e-4, tables e-1 and e-2, and references e1– e26 are available on the Neurology® Web site at www.neurology.org.

Approved by the Quality Standards Subcommittee on November 5, 2008; by the Practice Committee on February 19, 2009; and by the AAN Boardof Directors on July 30, 2009.

Disclosure: Author disclosures are provided at the end of the article.

SPECIAL ARTICLE

1218 Copyright © 2009 by AAN Enterprises, Inc.

Neurology 73,Octuber132009

Recommendation. In patients with ALS with im-paired oral food intake, enteral nutrition via PEGshould be considered to stabilize body weight (Level B).

When is PEG indicated in ALS? We found nostudies that provide ALS-specific indications forPEG. The risk of PEG placement increased whenthe FVC declined below 50% of predicted (ClassIII).14 Risks of PEG placement include laryngealspasm, localized infection, gastric hemorrhage,failure to place PEG due to technical difficulties,and death due to respiratory arrest.20,23

Conclusions. There are no studies of ALS-specificindications for the timing of PEG insertion, al-though patients with dysphagia will possibly beexposed to less risk if PEG is placed when FVC isabove 50% of predicted (1 Class III study).14

Recommendation. There are insufficient data tosupport or refute specific timing of PEG insertion inpatients with ALS (Level U).14

What is the efficacy of nutritional support via PEG in

prolonging survival? Two Class II and 7 Class III studiescompared survival in patients receiving PEG (n ! 585)vs those without PEG (n ! 1619). One Class III studydemonstrated a survival advantage vs control with mul-tivariate analysis (p ! 0.02) but not with univariateanalysis (p ! 0.09).16 A Class III population-basedstudy from Italy found improved survival with PEGcompared to patients with oral intake, also based on amultivariate analysis (3.89-fold; p ! 0.0004).24 TwoClass II studies demonstrated prolonged survival in thePEG group vs PEG refusers.17,20 Shaw et al.25 foundsimilar results when patients with PEG were compared

Figure 1 Nutrition management algorithm

*e.g., Bulbar questions in the Amyotrophic Lateral Sclerosis Functional Rating Scale, or other instrument. †Prolonged mealtime; ending meal prematurely because of fatigue; accelerated weight loss due to poor caloric intake; family concern aboutfeeding difficulties. ‡Percutaneous endoscopic gastrostomy: rule out contraindications.

1220 Neurology 73 October 13, 2009

predictive of death within 5 months in 8/10 pa-tients (Class III).e3 Bach et al. (Class III)e4 showedthat tracheostomy or death was highly likelywithin 2 months of a decrease in daytime SpO2

!95% that could not be corrected by noninvasiveventilation (NIV).

The peak cough expiratory flow (PCEF) remainsthe most widely used measure of cough effectiveness.Patients with a mean PCEF above 337 L/min had a

significantly greater chance of being alive at 18months (Class III).e5

Conclusions

1. Nocturnal oximetry and MIP are possibly more ef-fective in detecting early respiratory insufficiencythan erect FVC (2 Class III studies).

2. Supine FVC is possibly more effective than erectFVC in detecting diaphragm weakness and corre-

Figure 2 Respiratory management algorithm

PFT " pulmonary function tests; PCEF " peak cough expiratory flow; NIV " noninvasive ventilation; SNP " sniff nasal pressure;MIP " maximal inspiratory pressure; FVC " forced vital capacity (supine or erect); Abnl.nocturnal oximetry " pO2 !4% frombaseline. *Symptoms suggestive of nocturnal hypoventilation: frequent arousals, morning headaches, excessive daytime sleep-iness, vivid dreams. †If NIV is not tolerated or accepted in the setting of advancing respiratory compromise, consider invasiveventilation or referral to hospice.

1222 Neurology 73 October 13, 2009

Historia

• EstudiosdeCharcot.(1865)

• Análisis clínicosdelospacientesysuevoluciónencadapaciente.

• Hallazgosanatómicosenautopsia.

Historia

• EstudiosdeCharcot.(1865)

• “Informedeunamujerjovenconunadebilidadprogresivayqueparalelamentedesarrollaaumentodeltonomuscularconcontracturas,conintelectopreservadoaligualqueelesfínterurinario”

• Locorrelacionaenautopsiaconlesióndegenerativaencordónlateraldelamédulaespinal.

Historia

• EstudiosdeCharcot.(1865)

• Describeposteriormenteladebilidadgloso-faríngea relacionadaalaatrofiadelosnúcleosmotoresdelapartebajadeltroncocerebral.

• Estoseconocecomolaparálisisbulbarprogresiva.

ELA:Características

• Microscopio:• Pérdida deneuronasenelastaanteriormedularyenlosnúcleosmotoresdeltroncoencéfalo,respetandolosresponsablesdelosmovimientosoculares.

ELA:Características

• Dañoenneuronasmotoras:

– Adelgazamientoderaíces anterioresmedulares.– Pérdidademielinaennerviosmotores.– Atrofiamuscularpordenervación.

Epidemiología

• 5-10%deloscasossonfamiliares.(autosómicadominanteorecesiva).

• Masde100mutacionesengencausantepuedenestarpresentes.

Signosysíntomas• Afección delsistemamotorquedirige,regulaymantienelamusculaturaesqueléticaresponsabledelmovimientoydelarelaciónconelentorno.

• Noseafectan:• Neuronasmotorasocularesyesfinterianas.• Sensibilidadsuperficialniprofunda.• Funcióndelamusculaturalisa.• Conciencia.• Funciónsexual.

Signosysíntomas

• Inicioeslocalizadoenalgunaextremidad.• Parálisis totalentre2-4años.

• Insuficienciarespiratoriaesprogresiva.• Principalcausademorbimortalidad.

Signosysíntomas (neuronamotorainferior)

• A.Debilidadmuscular.• Dinamómetro.

pags 29-38 27/8/56 09:05 Página 30

1. Síntomas y signos de neurona motora inferior A.- Debilidad muscular: Es el síntoma más relevante de la ELA y se debe a la muerte progresiva de neuronas motoras. Se manifiesta cuando se ha per-dido el 50% de la población de neuronas motoras. Inicialmente afecta a un grupo de músculos y se va difundiendo hacia otros a medida que avanza la enfermedad.

La debilidad muscular (paresia) se valora mediante el Test Muscular Manual (TMM) que la gradúa de 0 a 5 (Tabla 3). El explorador ejerce fuer-za contra resistencia a la contracción voluntaria de un determinado múscu-lo o grupo muscular.

Tabla 3. Escala de valoración del Test Muscular Manual (TMM).

5: Fuerza muscular normal.

4: Disminución de la fuerza contra resistencia.

3: Imposibilidad de realizar fuerza contra resistencia, pero se mantiene el movimiento completo contra gravedad.

2: Movimiento incompleto contra gravedad.

1: Contracción muscular sin movimiento.

0: Ausencia completa de contracción muscular.

Normalmente es suficiente valorar los siguientes grupos musculares:

• En la región cervical: Flexores y extensores del cuello. • En extremidades superiores:

– Elevación del brazo (deltoides). – Flexión del codo (bíceps). – Extensión del codo (tríceps). – Flexores de la muñeca. – Extensores de la muñeca.

• En extremidades inferiores: – Flexión de la cadera (psoas). – Flexión de la rodilla (músculos isquiotibiales). – Extensión de la rodilla (cuádriceps). – Extensión del tobillo (tibial anterior). – Flexión del tobillo (gemelos).

Para valorar la fuerza de prensión de las manos puede utilizarse un dinamó-metro manual. Otra técnica, que requiere instrumental adecuado, consiste en determinar la fuerza desarrollada por la contracción muscular isométri-

30 SANIDAD

Signosysíntomas

• B.AtrofiaMuscular.– Porladebilidadmuscular.

– Inspección demanos.

– Segeneraliza.

Signosysíntomas

• C.Fasciculaciones.

• D.Calambresmusculares.

• Hipotonía yarreflexia.

Signosysíntomas (neuronamotorasuperior)

• A.Debilidadmuscular.– Torpezaypérdida dedestreza.

– Pérdidadelcontrolinhibitorioqueejercelavíacorticoespinal sobreneuronasmotorasinferioresqueinervanlosmúsculosantagonistas.

Signosysíntomas

• B.Espasticidad.• C.Hiperreflexia.• D.Reflejospatológicos.• E.Labilidademocional.

• Reflejospatológicosenlosmúsculosdelavíaaérea.

FormasdeInicio

• ELAClásica.• Esclerosislateralprimaria.• Amiotrofiaespinalprogresiva.• Parálisisbulbarprogresiva.

Complicacionesbulbares

• Disfagia.

• Disartria.

• Alteracionesdelatos.

• Anartria (sinvoz)

Diagnóstico

• Clínico.

• Electrofisiológico.

• Neuroradiológico.

• Genético.

Tratamiento

• Farmacológico:– FDA.– Riluzol.6mesesa1año.– Menosde5añosdeevolución.– SinTQT.

Tratamiento

• Disfagia:reducción líquidos• Usodesondagástrica.

• Disartria:Fonoaudiología.• Sistemasdecomunicación.• “Tobii”

Sistemasdecomunicación• Algunasdelasherramientasquepermitenrealizarseguimientode

ojos,son:• iMotions1 : plataformabiométricaque

ofrece software y hardware (gafasymonitoresdeseguimientodeojos,entreotros)pararealizarelseguimientodeojosyanálisisdelaexpresiónfacial.iMotions secaracterizaporinferirlaimplicaciónemocionalconlaqueseestáobservandomediantedatosrelativosalparpadeo,dilatacióndelapupilaovelocidaddemovimiento2 .

• SMIRedn Professional3 : esunconjuntodesoftwareyherramientasdehardwarequepermitenhacerseguimientodeojosMejoralaarquitecturadelainformaciónyeldiseñodeinterfacesensitioswebestáticosydinámicos,softwareyvideojuegos.Proporcionainformesderendimientodecomportamientoydatos biométricos,analizandolasaccionesdelosusuariosdeformanointrusiva.

• Algunasdelasherramientasquepermitenrealizarseguimientodeojos,son:

• EyeWorks4 : esunaempresaqueofreceserviciosdehardware(cámaras,monitores,sensores,yotrastecnologías)ysoftwaredeseguimientodeojosquesepuedeaplicaradistintosaspectos.

• PyGaze:5 esunpaquetede softwarelibre deseguimientoocularqueenglobavariasaplicacionesyqueestádestinadoapersonasconpocasnocionesdeprogramación.ElcódigosepuedecompartirconcualquiertipodeordenadoryescompatibleconWindows,LinuxyMacOSX.

• Algunasdelasherramientasquepermiten realizarseguimiento deojos,son:• OptiKey6 :esunsoftwaredeseguimientodeojosde códigoabierto ygratuitopara

Windows,cuyafunciónesservirdetecladodeayudavirtualyllevarelcontroldeltecladoyelratónparapersonasconlimitacionesmotorasydelhablaquesufrenenfermedadescomoel ELA (EsclerosisLateralAmiotrófica).Sielusuarionodisponededispositivodeseguimientoocular,OptiKey sepuedeutilizarconunratóno cámaraweb.Tambiénesposibleconvertirenvozaquellosquehemosescritoconeltecladovirtual.

• Tobii EyeX7 :softwarequepermite"tocardondesemire",paraunainteracciónconelordenadorportátilmuchomásintuitivaynatural,mejorando laexperienciadelusuario,ysinlanecesidaddeusarelratóno paneltáctil paradarclicenalgúnpuntodelapantalla.Sutecnologíaavanzadaescapazdeatenuarelbrillodelapantallasielusuarionoestámirándolaparaahorrarasíenergíaydarprivacidad.Igualmente,elordenadorpermaneceráactivocuandoelusuario seencuentreenfrentedelapantalladelordenador hastaqueéstesealejedelamisma.

• Gazepoint8 :empresadedicadaalseguimientodeojosparainvestigadores,personascondiscapacidad,diseñadoresweb,empresasdemarketing,entreotros.Susoftware,Analysis UXEdition,permiterealizartests deusabilidad,visualizacionesdemapasdecalor, secuenciasdeclics,etc.

Musculoesquelético

• Tratamientocompletodetodaslasarticulacionesytejidosblandos.

• IncluirATM(separadoresbucales).

• Usodeayudastécnicas.• Sistemasantiescaras.• Transporte.

Sialorrea• Usodeamitriptilina.• 25-50mg/día.• Atropina0.4mgcada4o6hrs.

• Glicopirrolato 2-8mg/día.(anticolinérgico)

• Antihistamínicos.• Toxinabotulínica.

• Radioterapialocalocirugía.

Estreñimiento

• Dietaricaenfibra.

• Líquido.

• Estimulantesdelperistaltismo.

Prevención TVP

• Usosistemasmecánicos.

• Anticoagulación.

• Filtroenvenacava.

Insuficienciarespiratoria

• VMNI.• Traqueostomía (tipo)• VMI.• Eleccióndelosequipos.

• Respaldo,baterías,grupoelectrógeno.• Sistemasdesucción.• “ambú”.

n 1980:Sullivan,aplicaCPAPenpacientesconApneaObstructivadelSueño

n 1990.UsomasivodelaVentilaciónconDosNivelesdePresiónPositiva:BiPAP®deRespironics

VMNI

VENTILADORES

1970s 1980s 1990s 2000

IMV PSV PCV Closed Loop

OpenLoop

Input(parametros)

RESPIRADOR PacientePresión

VolumenFlujo

Operador

H.Abona

ClosedLoop

Input(parametros)

RESPIRADOR(Controlador / Efector) Paciente

Alteraciones

Feedback

+-E

PresiónFlujo oVolumen

Operador

H.Abona

ObjetivosFisiológicos

• Manejoapoyodelintercambiogaseosopulmonar.

• VentilaciónAlveolar.• Oxigenaciónarterial.

• Aumentarelvolumenpulmonar.• MejoríadelaCRF.

• Disminucióndeltrabajorespiratorio.

Int care med 1994;20:64-79

ObjetivosClínicos

• Revertirlahipoxemia.• Revertiracidosis.• Manejodeldistress.• Preveniryrevertiratelectasias.• Revertirlafatigamuscular.

Int care med 1994;20:64-79

PROGRAMACIÓNDELAVM

• Modalidaddeventilación• Frecuenciarespiratoria• Volumencorriente• Fraccióninspiradadeoxígeno• PEEP• RelaciónI:E• Patróndeflujo

CRITERIOSCONEXIÓNVENTILACIÓNMECÁNICA

• Patologíaconpulmónnormal:– DepresióndelSNC– Enf.Neuromusculares– Traumacraneano– Cirugíacardíaca– Fracturascostalesmúltiples– Sepsis– Tétanos– Cirugia

• Patologíaobstructivacrónica:– Asmarefractaria– EPOCagudizada

• Patologíarestrictiva:– SDRA– Edemaagudodelpulmón

MONITOREODELPACIENTEVENTILADO

• Oximetríadepulso• Gasometríaarterial• RayosXdeTórax• Glicemiayelectrolitos• Cultivodesecrecionesseriados• MonitoreodeV,P,fr,FiO2

• Controldecapnografía• Monitoreodesedación

Desdeelpuntodelocompetentequedebemosser?

Competencia: definiciones

• Pero…eneltrabajo.

• Iniciativas.• Tomardecisiones.• Enfrentareventosaleatorios..

• “usosondaNº12oNº14?

Competencia: definiciones

• LeBoterf.• Actuarconcompetencia:• “Seleccionar,combinar,movilizarrecursos”• Recursospropiosydelentorno.• “Pertinente”(adecuadayoportuna)

• Logrodelresultadoaconseguir.

Competencia: definiciones• Existencompetenciascolectivas.• Diversidaddeámbitosoáreas(clínicos,docentes,investigación,gestión).

• Comunicación.• Aprendendesuhistoria.• Reflexivos.

• Estogeneramísticaeidentidad.

GRACIAS