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== Natural History, Complications, and Prognosis== | == Natural History, Complications, and Prognosis== | ||
== Diagnosis== | == Diagnosis== | ||
*Many tests have been developed to evaluate apraxia but most are difficult to apply in clinics as they are not rapid tests. Additionally, most of those lack in sensitivity and validity. | |||
**''De Renzi ideomotor apraxia test''for ideomotor apraxia assessment, can be tested in either side brain damage. It is a 24-item scale test.<ref name="De Renzi1980">{{cite journal|last1=De Renzi|first1=Ennio|title=Imitating Gestures|journal=Archives of Neurology|volume=37|issue=1|year=1980|pages=6|issn=0003-9942|doi=10.1001/archneur.1980.00500500036003}}</ref> | |||
**''Test of upper limb apraxia (TULIA)''is a 48 item test, is preferred test as it has a good validity and reliability. It can be used to test- | |||
***non-symbolic (meaningless) | |||
***intransitive (communicative) | |||
***transitive (tool-related) gestures.20 | |||
**''Apraxia Screen of TULIA (AST)'' is a short bedside test with 12 items, with a high sensitivity and specificity. The basis of this test is TULIA test.<ref name="VanbellingenKersten2010">{{cite journal|last1=Vanbellingen|first1=T.|last2=Kersten|first2=B.|last3=Van Hemelrijk|first3=B.|last4=Van de Winckel|first4=A.|last5=Bertschi|first5=M.|last6=Müri|first6=R.|last7=De Weerdt|first7=W.|last8=Bohlhalter|first8=S.|title=Comprehensive assessment of gesture production: a new test of upper limb apraxia (TULIA)|journal=European Journal of Neurology|volume=17|issue=1|year=2010|pages=59–66|issn=13515101|doi=10.1111/j.1468-1331.2009.02741.x}}</ref> | |||
===Diagnostic Study of Choice=== | ===Diagnostic Study of Choice=== | ||
=== History and Symptoms=== | === History and Symptoms=== | ||
| Line 84: | Line 93: | ||
===Other Imaging Findings=== | ===Other Imaging Findings=== | ||
===Other Diagnostic Studies=== | ===Other Diagnostic Studies=== | ||
==Treatment== | ==Treatment== | ||
Revision as of 05:41, 16 July 2020
Template:DiseaseDisorder infobox
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Parul Pahal, M.B.B.S[2] Norina Usman, M.B.B.S[3]
Synonyms and keywords: Dyspraxia
Overview
'Praxis', a Greek work, is the ability to perform the learned movements. It usually comprises of three components, namely, ideation, motor planning, and execution that results in purposeful movements. Apraxia, however, is the inability to perform these skilled and learned movements when there is a breakdown in any component of praxis. This disorder makes it difficult to perform daily tasks and negatively impact the quality of life. Apraxia is a complex neurological disease with cognitive-motor dysfunction. It can occur as a result of brain trauma/disease, and higher motor functional neuronal pathways damage in the setting of preserved comprehension, coordination, elementary sensory and motor systems. The most common types of apraxia are Ideational and Ideomotor.
Historical Perspective
- Steinthal introduced the term 'apraxia' in 1971. However, a German physician, Hugo Lipmann first established the conceptual knowledge and published complete description of apraxia after studying the gestures in a 48-year old stroke patient who had a left hemispheric stroke.[1]
- Lipmann noticed that, despite of resolution of the paresis, the patient was unable to perform tasks such as buttoning the shirt, with no affect on spontaneous movements, and doing simple tasks on command. He observed this phenomenon specifically in patients with left hemispheric lesions. He also concluded that the planning of the motor movements occurs in the motor area of the left side of the brain.Lipmann further proposed that the 'praxis' information flows from the posterior brain areas (parietal and occipital lobes) to the anterior (motor cortex).[1]
- The major subtypes classified by Lipmann were ideational, ideomotor, and limb-kinetic apraxia.[1]
- One of the behavioral neurologist, Norman Geschwind, presented that the superior longitudinal fasciculus involvement disconnects the Wernike's are from the left premotor cortex, leading to 'apraxia'.[2]
Classification
- The most common types of apraxia are-
- Ideational apraxia, like the name depicts, problem in conceptualization of the task. The person may be able to name the objects correctly but fails to coceptualize how that object is used.
- Ideomotor apraxia can be seen more frequently in neurodegenerative disorders and stroke patients. In this disorder, there is difficulty or inability to execute familiar or learned movements on command despite of understanding the command and willingness to perform that action. The characteristic of this type of apraxia is the inability to a transitive movement. For example, the person can describe how a tool such as comb is used, but, when asked to use that tool, he is unable to perform the task (i.e. combing the hair) using the comb
- Limb-kinetic apraxia[3][4]
- Certain task-specific apraxia[5]have been identified, and these include-
- Sitting apraxia
- Dressing apraxia
- Eyelid opening apraxia
- Gait apraxia
- Other types of apraxia, include-
- Buccofacial apraxia
- Classic apraxia
- Constructional apraxia
- Ideokinetic apraxia
- Motor apraxia
- Oculomotor apraxia
Pathophysiology
- 'Praxis' comprises three components, which include ideation, motor planning, and execution to carry out the purposeful movement. There are particular regions of the brain that represent specific component functions, and these regions together work as a ‘praxis system’ to process and execute a purposeful movement. Dysfunction in any of these regions, namely, frontal and parietal cortex, basal ganglia, and the white matter which connects theses areas, leads to apraxia.
- The movements which requires tools are transitive movements, and the ones which do not require tools are intransitive. The intransitive movements are gestural which can be meaningful (communicative), or meaningless movements (not representational). In apraxia, transitive movements are affected more frequently as compared to intransitive movements[6][7].
- The observations of the patients in the clinical practice is the basis of most of the knowledge about 'apraxia'. Apraxia has been mostly seen in chronic left hemispheric lesions and Alzheimer's disease[8][9][10][11]. The left hemispheric lesions cause more difficulty to perform transitive movements, as compared to intransitive movements and imitating gestures. Left hemisphere has a major role in 'praxis' and this may be due to specific stored representations in left hemisphere and their retrieval. On the other hand, Alzheimer's patients have preserved transitive movements, but shows deficits in gestures. Therefore, the type of apraxia depends on the type of neurological disease and the area of the brain affected by it.[11][12][13]
- Different brain regions which have role in cognition and movement are involved in complex 'Praxis' movements. The conceptualization of a purposeful task involves prefrontal, left premotor, middle temporal and parietal areas of the brain.[14].
- Neuroimaging studies have been done to investigate praxis correlations, but studies done so far vary widely on focus areas of praxis. One of the study reported left temporal lobe correltion with praxis because of its role in somatic memory retrieval.[15][16][17]. Left premotor cortex, left parietal lobule, and parietal cortex have also been shown to have a role in praxis as they are involved in knowledge of tools and their use, grasping movements, spatiotemporal information integration, respectively.[18][19]. Stronger left lateralization (especially posterior parietal and premotor cortex) for gesture production in praxis has been suggested by neuroimaging studies.[20][21][22]
Causes
Differentiating Apraxia from Other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications, and Prognosis
Diagnosis
- Many tests have been developed to evaluate apraxia but most are difficult to apply in clinics as they are not rapid tests. Additionally, most of those lack in sensitivity and validity.
- De Renzi ideomotor apraxia testfor ideomotor apraxia assessment, can be tested in either side brain damage. It is a 24-item scale test.[23]
- Test of upper limb apraxia (TULIA)is a 48 item test, is preferred test as it has a good validity and reliability. It can be used to test-
- non-symbolic (meaningless)
- intransitive (communicative)
- transitive (tool-related) gestures.20
- Apraxia Screen of TULIA (AST) is a short bedside test with 12 items, with a high sensitivity and specificity. The basis of this test is TULIA test.[24]
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X-ray
Echocardiography and Ultrasound
CT scan
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
- No standardized treatment is available for apraxia. The frequency of limb apraxia in left hemispheric stroke patients is reported to be nearly 51%[25][26]and, hence, the therapeutic efforts are so far mostly concentrated towards stroke patients (left hemispheric stroke patients). Based on the studies, following treatment modalities have been considered so far-
- With treatment, an improvement in praxis and daily living activities is seen in apraxia patients, based on some studies. The communicative gestures training has led to significant improvement of the gestures which were practiced during the training sessions, with some unpracticed gestures also showing some improvement[27]. However, the sustainability of these positive results is not clear. Although rehabilitative training has been reported to benefit, but, for sustained benefit, training alone is not sufficient.
- Noninvasive brain stimulation- This method had been used widely for many neurological disorders, but there is very limited data for its use in cognitive disorders. However, some studies have shown that this technique has been tried for therapeutic and investigational purpose for this complex neurological disorder and may show some positive results. This technique when used with rehabilitative training, may be useful. Through this technique and different stimulation settings, inhibitory or excitatory influences are exerted on cortical excitability or plasticity[28]. The synergistic approach using this technique prior to rehabilitative training, not only increases the efficacy, but it also increases the sustainability of the improvement seen. Some examples of non-invasive brain stimulation techniques which have been used in some neurological conditions with some improvement in the cognitive function components of the disease can be tried-
- Transcranial direct current stimulation (tDCS)[29]-low-level continuous electric current is delivered to influence plasticity and excitabililty of the cortex. In this, anodal tDCS works in excitatory ways, and cathodal tDCS in inhibitory ways.
- single-pulse or rTMS[30]- It can be delivered in either low frequency (0.2–1 Hz) for inhibitory mode, or in high frequency (≥5 Hz) for excitatory mode.
- theta-burst stimulation (TBS)[31]-It is also a magnetic stimulation method like rTMS, but it shows equal efficacy even with shorter stimulation period.
- paired associative stimulation (PAS)[32]- This stimulation technique can be used to tackle physiological mechanisms underlying memory using long-term depression (LTD), and long-term potentiation (LTP)
Medical Therapy
Interventions
Surgery
Primary Prevention
Secondary Prevention
Overview
Apraxia is a neurological disorder characterized by loss of the ability to execute or carry out learned purposeful movements, despite having the desire and the physical ability to perform the movements. It is a disorder of motor planning which may be acquired or developmental, but may not be caused by incoordination, sensory loss, or failure to comprehend simple commands (which can be tested by asking the person tested to recognize the correct movement from a series). The root word of Apraxia is praxis, Greek for an act, work, or deed. It is preceded by a privative a, meaning 'without'.
Types
There are several types of apraxia including:
- ideomotor (inability to carry out a motor command, for example, "act as if you are brushing your teeth" or "salute") - the form most frequently encountered by physicians,
- ideational (inability to create a plan for or idea of a specific movement, for example, "pick up this pen and write down your name"),
- limb-kinetic (inability to make fine, precise movements with a limb),
- verbal (difficulty planning the movements necessary for speech), also known as Apraxia of Speech (see below)
- constructional (inability to draw or construct simple configurations),
- oculomotor (difficulty moving the eye)
Each type may be tested at decreasing levels of complexity; if the person tested fails to execute the commands, you can make the movement yourself and ask that the person mimic it, or you can even give them a real object (like a tooth brush) and ask them to use it.
Apraxia may be accompanied by a language disorder called aphasia.
Apraxia of speech
Developmental Apraxia of Speech (DAS) presents in children who have no evidence of difficulty with strength or range of motion of the articulators, but are unable to execute speech movements because of motor planning and coordination problems. This is not to be confused with phonological impairments in children with normal coordination of the articulators during speech.
Symptoms of Acquired Apraxia of Speech (AOS) and Developmental Apraxia of Speech (DAS) include inconsistent articulatory errors, groping oral movements to locate the correct articulatory position, and increasing errors with increasing word and phrase length. AOS often co-occurs with Oral Apraxia (during both speech and non-speech movements) and Limb Apraxia.
Causes
Ideomotor apraxia is almost always caused by lesions in the language-dominant (usually left) hemisphere of the brain, and as such these patients often have concomitant aphasia, especially of the Broca or conduction type. Left-side ideomotor apraxia may be caused by a lesion of the anterior corpus callosum.
Ideational apraxia is commonly associated with confusion states and dementia.
Treatment
Generally, treatment for individuals with apraxia includes physical therapy, occupational therapy or speech therapy, or Oral Motor Therapy and IVIG. If apraxia is a symptom of another disorder (usually a neurologic disorder), the underlying disorder should be treated.
Prognosis
The prognosis for individuals with apraxia varies. With therapy, some patients improve significantly, while others may show very little improvement. Some individuals with apraxia may benefit from the use of a communication aid.
Related Chapters
References
- Epstein, O. (2003). Clinical Examination. London: Mosby. p. 294. ISBN 0-7234-3229-5. Unknown parameter
|coauthors=ignored (help) - Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL. Harrison's Principles of Internal Medicine. New York: McGraw-Hill, 2005. ISBN 0-07-139140-1.
Template:Skin and subcutaneous tissue symptoms and signs Template:Nervous and musculoskeletal system symptoms and signs Template:Urinary system symptoms and signs Template:Cognition, perception, emotional state and behaviour symptoms and signs Template:Speech and voice symptoms and signs Template:General symptoms and signs
- ↑ 1.0 1.1 1.2 Park, Jung E (2017). "Apraxia: Review and Update". Journal of Clinical Neurology. 13 (4): 317. doi:10.3988/jcn.2017.13.4.317. ISSN 1738-6586.
- ↑ Geschwind, Norman (1965). "DISCONNEXION SYNDROMES IN ANIMALS AND MAN". Brain. 88 (3): 585–585. doi:10.1093/brain/88.3.585. ISSN 0006-8950.
- ↑ Foki, T.; Vanbellingen, T.; Lungu, C.; Pirker, W.; Bohlhalter, S.; Nyffeler, T.; Kraemmer, J.; Haubenberger, D.; Fischmeister, F. Ph. S.; Auff, E.; Hallett, M.; Beisteiner, R. (2016). "Limb-kinetic apraxia affects activities of daily living in Parkinson's disease: a multi-center study". European Journal of Neurology. 23 (8): 1301–1307. doi:10.1111/ene.13021. ISSN 1351-5101.
- ↑ Mendoza, J. E.; Apostolos, G. T.; Humphreys, J. D.; Hanna-Pladdy, B.; O'Bryant, S. E. (2009). "Coin Rotation Task (CRT): A New Test of Motor Dexterity". Archives of Clinical Neuropsychology. 24 (3): 287–292. doi:10.1093/arclin/acp030. ISSN 0887-6177.
- ↑ . PMID 8071915. Missing or empty
|title=(help) - ↑ Roy, Eric A.; Square-storer, Paula; Hogg, Sharon; Adams, Scott (2009). "Analysis of task demands in Apraxia". International Journal of Neuroscience. 56 (1–4): 177–186. doi:10.3109/00207459108985414. ISSN 0020-7454.
- ↑ . PMID 10456799. Missing or empty
|title=(help) - ↑ Buxbaum, Laurel J.; Johnson-Frey, Scott H.; Bartlett-Williams, Megan (2005). "Deficient internal models for planning hand–object interactions in apraxia". Neuropsychologia. 43 (6): 917–929. doi:10.1016/j.neuropsychologia.2004.09.006. ISSN 0028-3932.
- ↑ Buxbaum, Laurel J.; Shapiro, Allison D.; Coslett, H. Branch (2014). "Critical brain regions for tool-related and imitative actions: a componential analysis". Brain. 137 (7): 1971–1985. doi:10.1093/brain/awu111. ISSN 1460-2156.
- ↑ Baumard, Josselin; Lesourd, Mathieu; Jarry, Christophe; Merck, Catherine; Etcharry-Bouyx, Frédérique; Chauviré, Valérie; Belliard, Serge; Moreaud, Olivier; Croisile, Bernard; Osiurak, François; Le Gall, Didier (2016). "Tool use disorders in neurodegenerative diseases: Roles of semantic memory and technical reasoning". Cortex. 82: 119–132. doi:10.1016/j.cortex.2016.06.007. ISSN 0010-9452.
- ↑ 11.0 11.1 Jarry, Christophe; Osiurak, François; Besnard, Jérémy; Baumard, Josselin; Lesourd, Mathieu; Croisile, Bernard; Etcharry-Bouyx, Frédérique; Chauviré, Valérie; Le Gall, Didier (2016). "Tool use in left brain damage and Alzheimer's disease: What about function and manipulation knowledge?". Journal of Neuropsychology. 10 (1): 154–159. doi:10.1111/jnp.12097. ISSN 1748-6645.
- ↑ Lesourd, Mathieu; Le Gall, Didier; Baumard, Josselin; Croisile, Bernard; Jarry, Christophe; Osiurak, François (2013). "Apraxia and Alzheimer's Disease: Review and Perspectives". Neuropsychology Review. 23 (3): 234–256. doi:10.1007/s11065-013-9235-4. ISSN 1040-7308.
- ↑ Ochipa, Cynthia; Rothi, Leslie J. Gonzalez; Heilman, Kenneth M. (1992). "CONCEPTUAL APRAXIA IN ALZHEIMER'S DISEASE". Brain. 115 (4): 1061–1071. doi:10.1093/brain/115.4.1061. ISSN 0006-8950.
- ↑ Tranel, Daniel; Kemmerer, David; Adolphs, Ralph; Damasio, Hanna; Damasio, Antonio R. (2010). "NEURAL CORRELATES OF CONCEPTUAL KNOWLEDGE FOR ACTIONS". Cognitive Neuropsychology. 20 (3–6): 409–432. doi:10.1080/02643290244000248. ISSN 0264-3294.
- ↑ Choi, Seong; Na, Duk; Kang, Eunjoo; Lee, Kyung; Lee, Soo; Na, Dong (2001). "Functional magnetic resonance imaging during pantomiming tool-use gestures". Experimental Brain Research. 139 (3): 311–317. doi:10.1007/s002210100777. ISSN 0014-4819.
- ↑ Beauchamp, Michael S.; Lee, Kathryn E.; Haxby, James V.; Martin, Alex (2002). "Parallel Visual Motion Processing Streams for Manipulable Objects and Human Movements". Neuron. 34 (1): 149–159. doi:10.1016/S0896-6273(02)00642-6. ISSN 0896-6273.
- ↑ Chao, Linda L.; Haxby, James V.; Martin, Alex (1999). "Attribute-based neural substrates in temporal cortex for perceiving and knowing about objects". Nature Neuroscience. 2 (10): 913–919. doi:10.1038/13217. ISSN 1097-6256.
- ↑ Watson, Christine E.; Buxbaum, Laurel J. (2015). "A distributed network critical for selecting among tool-directed actions". Cortex. 65: 65–82. doi:10.1016/j.cortex.2015.01.007. ISSN 0010-9452.
- ↑ Assmus, Ann; Marshall, John C; Ritzl, Afra; Noth, Johannes; Zilles, Karl; Fink, Gereon R (2003). "Left inferior parietal cortex integrates time and space during collision judgments". NeuroImage. 20: S82–S88. doi:10.1016/j.neuroimage.2003.09.025. ISSN 1053-8119.
- ↑ Frey, Scott H. (2007). "What Puts the How in Where? Tool Use and the Divided Visual Streams Hypothesis". Cortex. 43 (3): 368–375. doi:10.1016/S0010-9452(08)70462-3. ISSN 0010-9452.
- ↑ Bohlhalter, S.; Hattori, N.; Wheaton, L.; Fridman, E.; Shamim, E. A.; Garraux, G.; Hallett, M. (2008). "Gesture Subtype-Dependent Left Lateralization of Praxis Planning: An Event-Related fMRI Study". Cerebral Cortex. 19 (6): 1256–1262. doi:10.1093/cercor/bhn168. ISSN 1047-3211.
- ↑ Fridman, Esteban A.; Immisch, Ilka; Hanakawa, Takashi; Bohlhalter, Stephan; Waldvogel, Daniel; Kansaku, Kenji; Wheaton, Lewis; Wu, Tao; Hallett, Mark (2006). "The role of the dorsal stream for gesture production". NeuroImage. 29 (2): 417–428. doi:10.1016/j.neuroimage.2005.07.026. ISSN 1053-8119.
- ↑ De Renzi, Ennio (1980). "Imitating Gestures". Archives of Neurology. 37 (1): 6. doi:10.1001/archneur.1980.00500500036003. ISSN 0003-9942.
- ↑ Vanbellingen, T.; Kersten, B.; Van Hemelrijk, B.; Van de Winckel, A.; Bertschi, M.; Müri, R.; De Weerdt, W.; Bohlhalter, S. (2010). "Comprehensive assessment of gesture production: a new test of upper limb apraxia (TULIA)". European Journal of Neurology. 17 (1): 59–66. doi:10.1111/j.1468-1331.2009.02741.x. ISSN 1351-5101.
- ↑ 25.0 25.1 Smania, N.; Aglioti, S. M.; Girardi, F.; Tinazzi, M.; Fiaschi, A.; Cosentino, A.; Corato, E. (2006). "Rehabilitation of limb apraxia improves daily life activities in patients with stroke". Neurology. 67 (11): 2050–2052. doi:10.1212/01.wnl.0000247279.63483.1f. ISSN 0028-3878.
- ↑ 26.0 26.1 Smania, Nicola; Girardi, Flavia; Domenicali, Chiara; Lora, Elisa; Aglioti, Salvatore (2000). "The rehabilitation of limb apraxia: A study in left-brain–damaged patients". Archives of Physical Medicine and Rehabilitation. 81 (4): 379–388. doi:10.1053/mr.2000.6921. ISSN 0003-9993.
- ↑ Daumüller, Maike; Goldenberg, Georg (2009). "Therapy to improve gestural expression in aphasia: a controlled clinical trial". Clinical Rehabilitation. 24 (1): 55–65. doi:10.1177/0269215509343327. ISSN 0269-2155.
- ↑ Hallett, Mark (2007). "Transcranial Magnetic Stimulation: A Primer". Neuron. 55 (2): 187–199. doi:10.1016/j.neuron.2007.06.026. ISSN 0896-6273.
- ↑ Lefaucheur, Jean-Pascal; Antal, Andrea; Ayache, Samar S.; Benninger, David H.; Brunelin, Jérôme; Cogiamanian, Filippo; Cotelli, Maria; De Ridder, Dirk; Ferrucci, Roberta; Langguth, Berthold; Marangolo, Paola; Mylius, Veit; Nitsche, Michael A.; Padberg, Frank; Palm, Ulrich; Poulet, Emmanuel; Priori, Alberto; Rossi, Simone; Schecklmann, Martin; Vanneste, Sven; Ziemann, Ulf; Garcia-Larrea, Luis; Paulus, Walter (2017). "Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS)". Clinical Neurophysiology. 128 (1): 56–92. doi:10.1016/j.clinph.2016.10.087. ISSN 1388-2457.
- ↑ Lefaucheur, Jean-Pascal; André-Obadia, Nathalie; Antal, Andrea; Ayache, Samar S.; Baeken, Chris; Benninger, David H.; Cantello, Roberto M.; Cincotta, Massimo; de Carvalho, Mamede; De Ridder, Dirk; Devanne, Hervé; Di Lazzaro, Vincenzo; Filipović, Saša R.; Hummel, Friedhelm C.; Jääskeläinen, Satu K.; Kimiskidis, Vasilios K.; Koch, Giacomo; Langguth, Berthold; Nyffeler, Thomas; Oliviero, Antonio; Padberg, Frank; Poulet, Emmanuel; Rossi, Simone; Rossini, Paolo Maria; Rothwell, John C.; Schönfeldt-Lecuona, Carlos; Siebner, Hartwig R.; Slotema, Christina W.; Stagg, Charlotte J.; Valls-Sole, Josep; Ziemann, Ulf; Paulus, Walter; Garcia-Larrea, Luis (2014). "Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS)". Clinical Neurophysiology. 125 (11): 2150–2206. doi:10.1016/j.clinph.2014.05.021. ISSN 1388-2457.
- ↑ Wischnewski, Miles; Schutter, Dennis J.L.G. (2015). "Efficacy and Time Course of Theta Burst Stimulation in Healthy Humans". Brain Stimulation. 8 (4): 685–692. doi:10.1016/j.brs.2015.03.004. ISSN 1935-861X.
- ↑ Wischnewski, Miles; Schutter, Dennis J.L.G. (2016). "Efficacy and time course of paired associative stimulation in cortical plasticity: Implications for neuropsychiatry". Clinical Neurophysiology. 127 (1): 732–739. doi:10.1016/j.clinph.2015.04.072. ISSN 1388-2457.