Abstract
Alien hand syndrome (AHS) is a rare disorder of involuntary limb movement together with a sense of loss of limb ownership. It most commonly affects the hand, but can occur in the leg. The anterior (frontal, callosal) and posterior variants are recognized, with distinguishing clinical features and anatomical lesions. Initial descriptions were attributed to stroke and neurosurgical operations, but neurodegenerative causes are now recognized as most common. Structural and functional imaging and clinical studies have implicated the supplementary motor area, pre-supplementary motor area, and their network connections in the frontal variant of AHS, and the inferior parietal lobule and connections in the posterior variant. Several theories are proposed to explain the pathophysiology. Herein, we review the literature to update advances in the understanding of the classification, pathophysiology, etiology, and treatment of AHS.
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Goldstein K. Zur Lehre von der motorischen Apraxie. J Psychol Neurol. 1908;11:169–87.
Akelaitis AJ. Studies on the corpus callosum IV. Diagonistic dyspraxia in epileptics following partial and complete section of the corpus callosum. Am J Psychiatr. 1945;101:494–9.
Denny-Brown D. The nature of apraxia. J Nerv Ment Dis. 1958;126(1):9–32.
Brion S, Jedynak CP. [Disorders of interhemispheric transfer (callosal disonnection). 3 cases of tumor of the corpus callosum. The strange hand sign]. Troubles du transfert interhemispherique (callosal disconnection). A propos de trois observations de tumeurs du corps calleux. Le signe de la main etrangere. Rev Neurol. 1972;126(4):257–66.
Bogen JE. The callosal syndrome. In: Valenstein H, editor. Clinical neuropsychology. New York: Oxford University Press; 1993. p. 337–407.
Goldberg G, Bloom KK. The alien hand sign. Localization, lateralization and recovery. Am J Phys Med Rehabil. 1990;69(5):228–38.
Della Sala S, Marchetti C, Spinnler H. The anarchic hand: a fronto-mesial sign. In: Boller JGF, editor. Handbook of neuropsychology. Amsterdam: Elsevier; 1994.
Feinberg TE et al. Two alien hand syndromes. Neurology. 1992;42(1):19–24.
Levine DN, Rinn WE. Opticosensory ataxia and alien hand syndrome after posterior cerebral artery territory infarction. Neurology. 1986;36(8):1094–7.
Ay H et al. Sensory alien hand syndrome: case report and review of the literature. J Neurol Neurosurg Psychiatry. 1998;65(3):366–9.
Bundick Jr T, Spinella M. Subjective experience, involuntary movement, and posterior alien hand syndrome. J Neurol Neurosurg Psychiatry. 2000;68(1):83–5.
Doody RS, Jankovic J. The alien hand and related signs. J Neurol Neurosurg Psychiatry. 1992;55(9):806–10.
Aboitiz F et al. The alien hand syndrome: classification of forms reported and discussion of a new condition. Neurol Sci. 2003;24(4):252–7.
Brainin M, Seiser A, Matz K. The mirror world of motor inhibition: the alien hand syndrome in chronic stroke. J Neurol Neurosurg Psychiatry. 2008;79(3):246–52.
Nowak DA et al. Recovery and outcome of frontal alien hand syndrome after anterior cerebral artery stroke. J Neurol Sci. 2014;338(1–2):203–6.
Watson RT, Heilman KM. Callosal apraxia. Brain. 1983;106(Pt 2):391–403.
Giroud M, Dumas R. Clinical and topographical range of callosal infarction: a clinical and radiological correlation study. J Neurol Neurosurg Psychiatry. 1995;59(3):238–42.
Chan JL, Liu AB. Anatomical correlates of alien hand syndromes. Neuropsychiatry Neuropsychol Behav Neurol. 1999;12(3):149–55.
Geschwind DH et al. Alien hand syndrome: interhemispheric motor disconnection due to a lesion in the midbody of the corpus callosum. Neurology. 1995;45(4):802–8.
Tanaka Y et al. Diagonistic dyspraxia. Clinical characteristics, responsible lesion and possible underlying mechanism. Brain J Neurol. 1996;119(Pt 3):859–73.
Chan JL, Ross ED. Alien hand syndrome: influence of neglect on the clinical presentation of frontal and callosal variants. Cortex. 1997;33(2):287–99.
Chan JL, Chen RS, Ng KK. Leg manifestation in alien hand syndrome. J Formos Med Assoc. 1996;95(4):342–6.
Assal F, Schwartz S, Vuilleumier P. Moving with or without will: functional neural correlates of alien hand syndrome. Ann Neurol. 2007;62(3):301–6.
Lewis TM, McClain M, Pittinger A. Alien hand syndrome & sensory ataxia: a case study of a unique presentation of the disorder. Arch Clin Neuropsychol. 1997;12(4):357–8.
Marey-Lopez J et al. Posterior alien hand syndrome after a right thalamic infarct. J Neurol Neurosurg Psychiatry. 2002;73(4):447–9.
Ventura MG, Goldman S, Hildebrand J. Alien hand syndrome without a corpus callosum lesion. J Neurol Neurosurg Psychiatry. 1995;58(6):735–7.
Graff-Radford J et al. The alien limb phenomenon. J Neurol. 2013;260(7):1880–8. Largest case series of alien hand syndrome, detailing clinical and imaging features.
Bartolo M et al. Alien hand syndrome in left posterior stroke. Neurol Sci. 2011;32(3):483–6.
Kessler J, Hathout G. Dominant posterior-variant alien hand syndrome after acute left parietal infarction. Clin Neurol Neurosurg. 2009;111(7):633–5.
Pappalardo A et al. Posterior alien hand syndrome: case report and rehabilitative treatment. Neurorehabil Neural Repair. 2004;18(3):176–81.
Rohde S et al. Posterior alien hand syndrome: case report. Neuroradiology. 2002;44(11):921–3.
Rubin M et al. The alien limb phenomenon and Creutzfeldt-Jakob disease. Parkinsonism Relat Disord. 2012;18(7):842–6. Largest case series of alien limb due to CJD.
Hu WT et al. MRI correlates of alien leg-like phenomenon in corticobasal degeneration. Mov Disord. 2005;20(7):870–3.
Serrano-Vicente J et al. Bilateral alien hand syndrome in cerebrovascular disease: CT, MR, CT angiography, and 99mTc-HMPAO-SPECT findings. Clin Nucl Med. 2015;40(3):e211–4.
Panikkath R et al. The alien hand syndrome. Proc (Baylor Univ Med Cent). 2014;27(3):219–20.
Spector AR, Freeman WD, Cheshire WP. The stroke that struck back: an unusual alien hand presentation. J Stroke Cerebrovasc Dis Off J Nat Stroke Assoc. 2009;18(1):72–3.
Yuan JL et al. Acute infarct of the corpus callosum presenting as alien hand syndrome: evidence of diffusion weighted imaging and magnetic resonance angiography. BMC Neurol. 2011;11:142.
Lunardelli A et al. Intermittent alien hand syndrome and callosal apraxia in multiple sclerosis: implications for interhemispheric communication. Behav Neurol. 2014;2014:873541.
Kloesel B et al. Sequelae of a left-sided parietal stroke: posterior alien hand syndrome. Neurocase. 2010;16(6):488–93.
Takenouchi T, Solomon GE. Alien hand syndrome in parry-Romberg syndrome. Pediatr Neurol. 2010;42(4):280–2.
Huang Y, Jia J. Corpus callosum hematoma secondary to cerebral venous malformation presenting as alien hand syndrome. Neurocase. 2013;19(4):377–81.
Kang SY, Kim JS. Anterior cerebral artery infarction: stroke mechanism and clinical-imaging study in 100 patients. Neurology. 2008;70(24 Pt 2):2386–93.
Cohen OS et al. Unusual presentations in patients with E200K familial Creutzfeldt-Jakob disease. Eur J Neurol. 2016;23(5):871–7.
Jurgens U. The efferent and afferent connections of the supplementary motor area. Brain Res. 1984;300(1):63–81.
Denny-Brown D. Positive and negative aspects of cerebral cortical functions. N C Med J. 1956;17(7):295–303.
Wilson, W., 1914
Lhermitte F. ‘Utilization behaviour’ and its relation to lesions of the frontal lobes. Brain. 1983;106(Pt 2):237–55.
Gibson JJ. The ecological approach to visual perception. Boston: Houghton Mifflin; 1979.
McBride J. Exaggerated object affordance and absent automatic inhibition in alien hand syndrome. Cortex. 2013;49(8):2040–54. Description of object affordance theory and studies performed to date.
McBride J et al. Automatic motor activation in the executive control of action. Front Hum Neurosci. 2012;6:82.
Eimer M, Schlaghecken F. Response facilitation and inhibition in subliminal priming. Biol Psychol. 2003;64(1–2):7–26.
Sumner P, Husain M. At the edge of consciousness: automatic motor activation and voluntary control. Neuroscientist. 2008;14(5):474–86.
Riddoch MJ et al. Visual affordances direct action: neuropsychological evidence from manual interference. Cogn Neuropsychol. 1998;15(6–8):645–83.
Grezes J, Decety J. Does visual perception of object afford action? Evidence from a neuroimaging study. Neuropsychologia. 2002;40(2):212–22.
Boy F et al. Supplementary motor area activations in unconscious inhibition of voluntary action. Exp Brain Res. 2010;206(4):441–8.
Cunnington R et al. The preparation and execution of self-initiated and externally-triggered movement: a study of event-related fMRI. Neuro Image. 2002;15(2):373–85.
Fried I et al. Functional organization of human supplementary motor cortex studied by electrical stimulation. J Neurosci. 1991;11(11):3656–66.
Fried I, Mukamel R, Kreiman G. Internally generated preactivation of single neurons in human medial frontal cortex predicts volition. Neuron. 2011;69(3):548–62.
Lau HC et al. Attention to intention. Science. 2004;303(5661):1208–10.
Farrer C, Frith CD. Experiencing oneself vs another person as being the cause of an action: the neural correlates of the experience of agency. Neuro Image. 2002;15(3):596–603.
Wolpe N et al. The medial frontal-prefrontal network for altered awareness and control of action in corticobasal syndrome. Brain. 2014;137(Pt 1):208–20.
Haggard P. Human volition: towards a neuroscience of will. Nat Rev Neurosci. 2008;9(12):934–46.
Frith CD, Blakemore SJ, Wolpert DM. Abnormalities in the awareness and control of action. Philos Trans R Soc Lond B Biol Sci. 2000;355(1404):1771–88.
Blakemore SJ, Wolpert DM, Frith CD. Abnormalities in the awareness of action. Trends Cogn Sci. 2002;6(6):237–42.
Eagleman DM. Neuroscience. The where and when of intention. Science. 2004;303(5661):1144–6.
Berlucchi G. Frontal callosal disconnection syndromes. Cortex. 2012;48(1):36–45.
Hillbom M et al. Diagnosis and management of marchiafava-bignami disease: a review of CT/MRI confirmed cases. J Neurol Neurosurg Psychiatry. 2014;85(2):168–73.
Marti-Fabregas J et al. Alien hand sign after a right parietal infarction. Cerebrovasc Dis. 2000;10(1):70–2.
Pack BC et al. Posterior-variant alien hand syndrome: clinical features and response to rehabilitation. Disabil Rehabil. 2002;24(15):817–8.
Schaefer M, Heinze HJ, Galazky I. Alien hand syndrome: neural correlates of movements without conscious will. PLoS One. 2010;5(12), e15010.
Onofrj M et al. Cortical activation during levitation and tentacular movements of corticobasal syndrome. Medicine (Baltimore). 2015;94(45), e1977.
Boesebeck F, Ebner A. Paroxysmal alien limb phenomena due to epileptic seizures and electrical cortical stimulation. Neurology. 2004;63(9):1725–7.
Kim IH et al. Intracranial hemorrhage in the corpus callosum presenting as callosal disconnection syndrome: FDG-PET and tractography: a case report. Ann Rehabil Med. 2014;38(6):871–5.
Jang SH, Yeo SS, Chang MC. Unusual compensatory neural connections following disruption of corpus callosum fibers in a patient with corpus callosum hemorrhage. Int J Neurosci. 2013;123(12):892–5.
Sarva H, Deik A, Severt WL. Pathophysiology and treatment of alien hand syndrome. Tremor Other Hyperkinet Mov (N Y). 2014;4:241. Comprehensive review of the history of alien limb, pathophysiology and treatment options.
Gondim Fde A et al. Alien limb syndrome responsive to amantadine in a patient with corticobasal syndrome. Tremor Other Hyperkinet Mov (N Y). 2015;5:309.
Romano D et al. Controlling the alien hand through the mirror box. A single case study of alien hand syndrome. Neurocase. 2014;20(3):307–16.
Nojima I et al. Mirror visual feedback can induce motor learning in patients with callosal disconnection. Exp Brain Res. 2013;227(1):79–83.
Ling H et al. Characteristics of progressive supranuclear palsy presenting with corticobasal syndrome: a cortical variant. Neuropathol Appl Neurobiol. 2014;40(2):149–63.
Goldberg G, Mayer NH, Toglia JU. Medial frontal cortex infarction and the alien hand sign. Arch Neurol. 1981;38(11):683–6.
Starkstein SE, Berthier ML, Leiguarda R. Disconnection syndrome in a right-handed patient with right hemispheric speech dominance. Eur Neurol. 1988;28(4):187–90.
Leiguarda R, Starkstein S, Berthier M. Anterior callosal haemorrhage. A partial interhemispheric disconnection syndrome. Brain. 1989;112(Pt 4):1019–37.
Kikkert MA, Ribbers GM, Koudstaal PJ. Alien hand syndrome in stroke: a report of 2 cases and review of the literature. Arch Phys Med Rehabil. 2006;87(5):728–32.
Rosa A et al. Marchiafava-Bignami disease, syndrome of interhemispheric disconnection, and right-handed agraphia in a left-hander. Arch Neurol. 1991;48(9):986–8.
Gallant RE et al. Alien limb syndrome secondary to multimodal treatment of recurrent oligodendroglioma. J Clin Neurosci. 2015;22(10):1684–5.
Bakheit AM et al. Anarchic hand syndrome following resection of a frontal lobe tumor. Neurocase. 2013;19(1):36–40.
Feinberg TE, Roane DM, Cohen J. Partial status epilepticus associated with asomatognosia and alien hand-like behaviors [corrected]. Arch Neurol. 1998;55(12):1574–6.
Chokar G et al. A case of parry-Romberg syndrome and alien hand. J Neurol Sci. 2014;341(1–2):153–7.
Vincent MB, Hadjikhani N. Migraine aura and related phenomena: beyond scotomata and scintillations. Cephalalgia. 2007;27(12):1368–77.
Nash R et al. Spontaneous pneumocephalus presenting with alien limb phenomena. J Laryngol Otol. 2012;126(7):733–6.
Reyes, A.J., K. Ramcharan, and R. Ramtahal, Novel transient alien limb phenomenon heralding a diabetic hyperosmolar non-ketotic state with leukoaraiosis: a video presentation. BMJ Case Rep, 2015. 2015
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Hassan, A., Josephs, K.A. Alien Hand Syndrome. Curr Neurol Neurosci Rep 16, 73 (2016). https://doi.org/10.1007/s11910-016-0676-z
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DOI: https://doi.org/10.1007/s11910-016-0676-z