Background:&nbsp;Alien limb phenomenon occurs in 50&ndash;60% of patients with corticobasal syndrome (CBS) and usually presents with an &ldquo;alien hand&rdquo; phenomenon. The &ldquo;alien foot&rdquo; presentation is rarer and may be misdiagnosed, as foot involvement can lead to erroneous localization of the clinical problem to the knee, hip, or back. Subsequently misdiagnoses such as myelopathy, radiculopathy, functional disorder, stiff leg syndrome, neuromyotonia, and painful leg moving toes syndrome may occur.Case report:&nbsp;We describe two patients with alien foot symptoms that resulted in multiple opinions from different specialists, multiple diagnostic and therapeutic procedures, and delayed diagnosis. Eventually a diagnosis of CBS was made in both. Alien foot symptoms may be more common than initially thought and can result in a delayed diagnosis of CBS.Conclusion:&nbsp;The inclusion of this clinical finding in recently proposed diagnostic criteria highlights the need for increased clinical awareness.&nbsp;</p

Allan McCarthy

Brian Magennis

Brian Murray

Diana A. Olszewska

Sean Connolly

Tim Lynch

Tremor and Other Hyperkinetic Movements

Directory of Open Access Journals

A Wolf in Sheep's Clothing: An "Alien Leg" in Corticobasal Syndrome

Background: Alien limb phenomenon occurs in 50–60% of patients with corticobasal syndrome (CBS) and usually presents with an “alien hand” phenomenon. The “alien foot” presentation is rarer and may be misdiagnosed, as foot involvement can lead to erroneous localization of the clinical problem to the knee, hip, or back. Subsequently misdiagnoses such as myelopathy, radiculopathy, functional disorder, stiff leg syndrome, neuromyotonia, and painful leg moving toes syndrome may occur.

Case report: We describe two patients with alien foot symptoms that resulted in multiple opinions from different specialists, multiple diagnostic and therapeutic procedures, and delayed diagnosis. Eventually a diagnosis of CBS was made in both. Alien foot symptoms may be more common than initially thought and can result in a delayed diagnosis of CBS.

Conclusion: The inclusion of this clinical finding in recently proposed diagnostic criteria highlights the need for increased clinical awareness

Olszewska, Diana Angelika

McCarthy, Allan

Murray, Brian

Magennis, Brian

Connolly, Sean

Lynch, Tim

Columbia University Academic Commons

Case ReportsA Wolf in Sheep’s Clothing: An ‘‘Alien Leg’’ in Corticobasal SyndromeDiana Angelika Olszewska1*, Allan McCarthy1, Brian Murray1, Brian Magennis1, Sean Connolly2& Tim Lynch11 Department of Neurology, Dublin Neurological Institute, Mater Misericordiae University Hospital, Dublin, Ireland, 2 Department of Clinical Neurophysiology,St Vincent’s University Hospital, Dublin, IrelandAbstractBackground: Alien limb phenomenon occurs in 50–60% of patients with corticobasal syndrome (CBS) and usually presents with an ‘‘alien hand’’ phenomenon.The ‘‘alien foot’’ presentation is rarer and may be misdiagnosed, as foot involvement can lead to erroneous localization of the clinical problem to the knee, hip, orback. Subsequently misdiagnoses such as myelopathy, radiculopathy, functional disorder, stiff leg syndrome, neuromyotonia, and painful leg moving toes syndromemay occur.Case report: We describe two patients with alien foot symptoms that resulted in multiple opinions from different specialists, multiple diagnostic and therapeuticprocedures, and delayed diagnosis. Eventually a diagnosis of CBS was made in both. Alien foot symptoms may be more common than initially thought and canresult in a delayed diagnosis of CBS.Conclusion: The inclusion of this clinical finding in recently proposed diagnostic criteria highlights the need for increased clinical awareness.Keywords: Alien limb, alien leg, corticobasal syndromeCitation: Olszewska DA, McCarthy A, Murray B, et al. A wolf in sheep’s clothing: an ‘‘alien leg’’ in corticobasal syndrome. Tremor Other Hyperkinet Mov.2017; 7. doi: 10.7916/D86D5ZT8* To whom correspondence should be addressed. E-mail: Diana.angelika.olszewska@gmail.comEditor: Elan D. Louis, Yale University, USAReceived: February 17, 2017 Accepted: March 31, 2017 Published: April 26, 2017Copyright: ’ 2017 Olszewska et al. This is an open-access article distributed under the terms of the Creative Commons Attribution–Noncommercial–No Derivatives License, whichpermits the user to copy, distribute, and transmit the work provided that the original authors and source are credited; that no commercial use is made of the work; and that the work is notaltered or transformed.Funding: None.Financial Disclosures: None.Conflict of Interest: The authors report no conflict of interest.Ethics Statement: All patients that appear on video have provided written informed consent; authorization for the videotaping and for publication of the videotape was provided.Introduction‘‘Alien hand’’ syndrome has been reported in up to 60% of patientswith corticobasal syndrome (CBS).1 The hand moves on its own andfrequently does not obey the patient’s commands. Current criteriafor the probable diagnosis of CBS include an asymmetric presentationand two of the following: limb rigidity/akinesia, limb dystonia, limbmyoclonus plus two of either orobuccal/limb apraxia or corticalsensory deficit or alien limb phenomenon. ‘‘Possible CBS’’ may bediagnosed if there is one of limb rigidity, limb dystonia or limbmyoclonus (may be symmetric) and one of orobuccal/limb apraxia,cortical sensory deficit or alien limb phenomenon. An alien hand iscommonly recognized as part of CBS, but clinicians may not considerthe possibility of an ‘‘alien foot’’ leading to delayed diagnosis andinappropriate investigations and treatment. We present two patientswho presented with alien foot symptoms that led to a delayed diagnosisof CBS.Case reportsCase 1An 80-year-old male complained of right foot pain and a ‘‘tingling’’sensation that spread to the right knee. He was referred to anorthopedic surgeon because of lumbosacral spine disease and L4/L5decompression was performed. However, the symptoms progressed.He developed an involuntary slow abduction/adduction of his toes onthe right side. Magnetic resonance imaging (MRI) of the brain showedsmall vessel ischemic disease (Figure 1A); MRI of the cervical andthoracic spine was normal and the lumbar sacral spine showedpostoperative changes. The abnormal movements spread to the anklewith involuntary dorsiflexion and plantar flexion. He stopped driving.Further MRI of the lumbar spine imaging showed a tight right L4nerve root in the lateral recess. He received nerve root injections and afoot splint for a ‘‘foot drop.’’ Nine months later, at the age of 81 years,he had a right L5 decompression by a different orthopedic surgeonFreely available onlineTremor and Other Hyperkinetic Movementshttp://www.tremorjournal.orgThe Center for Digital Research and ScholarshipColumbia University Libraries/Information Services1with no improvement. At this point neurological opinion was sought.Neurological examination at age 81 showed repetitive movements ofhis right foot, and flexion extension of the toes. The diagnoses con-sidered included an unusual organic disorder such as gait apraxia,‘‘conversion disorder,’’ or ‘‘consciously derived’’ disorder. A secondopinion was sought from a movement disorder specialist. Initially hewas unable to walk during that assessment but after an hour he wasable to run, and a diagnosis of a functional disorder was made. At age82 he was seen by a third neurologist and a diagnosis of ‘‘painful legmoving toes’’ was made because of the slow adduction–abduction toemovements, but a diagnosis of atypical stiff leg syndrome was also con-sidered. Anti-glutamic acid decarboxylase antibodies were negative.Conduction studies of the right peroneal and tibial motor nerveswere normal. Needle electromyography (EMG) found no evidence ofmotor axonal loss in the right-sided L4, L5 or S1 myotomes but briefruns of normal motor unit activity were recorded in tibialis anterior,peroneus longus, extensor hallucis longus and medial gastrocnemiusmuscles, synchronous with visible involuntary movements in the rightlower limb. Motor unit activity was absent at rest and did not occursynchronously in antagonist muscles, making stiff limb syndromeunlikely. A later video shows some jerky foot movements consistentwith myoclonus and undefined toe movements (Video 1). The remain-ing neurological examination was normal, including cognition clonazepam(1 mg morning, 0.5 mg afternoon, 0.5 mg evening) and amitriptyline(25 mg morning, 50 mg evening) did not help.Owing to ongoing pain in his right leg, he was started on a fentanyltransdermal patch 12 mg/hour by a pain specialist.At age 82 he was referred to another specialty movement disorderclinic. By this stage, the patient described the right leg as ‘‘having itsown mind.’’ There were now some involuntary movements in his rightFigure 1. Brain imaging of patient 1. (A) Magnetic resonance imaging brain scan: small vessel ischemic disease. (B) Fludeoxyglucose positron emissiontomography and computed tomography: diffuse moderate left basal ganglia hypometabolism, moderate regional left posterior parietal hypometabolism andmild-moderate left frontal hypo metabolism.Olszewska DA, McCarthy A, Murray B, et al. Alien Leg in Corticobasal SyndromeTremor and Other Hyperkinetic Movementshttp://www.tremorjournal.orgThe Center for Digital Research and ScholarshipColumbia University Libraries/Information Services2hand and left leg. When standing, the doctor had to stand on his rightfoot to hold it in place (Video 2). By the age of 83, right-sidedbradykinesia, stooped posture, and shuffling gait had developed.Frontal release signs (grasp and palmomental reflexes) developed. Hedeveloped right-hand stimulus-sensitive myoclonus, astereognosia,ideomotor apraxia, rigidity, and ‘‘magnetism’’ (the patient’s handfollows the examiner’s hand as if attracted to it like a magnet) (Video 3).Reflexes were brisk (Medical Research Council scale grade 3) withspastic catch at the knees but flexor plantar responses. Pinprick sensationwas decreased up to the right ankle. Proprioception and vibration weregrossly impaired up to the knee on the right side and mildly impairedon the left. Pregabalin 25 mg twice a day and levodopa/carbidopa(Levodopa 100 mg/carbidopa 25 mg (up to three times daily)) wereintroduced. Fludeoxyglucose (18F) positron emission tomography andcomputed tomography PET/CT showed diffuse moderate left basalganglia hypometabolism, moderate regional left posterior parietal hypo-metabolism, and mild–moderate left frontal hypometabolism (Figure 1B).He was diagnosed with CBS. A year later, the patient’s cognition dete-riorated further (Montreal Cognitive Assessment Test score 20/30).The patient is currently bed-bound in a residential care facility.Case 2A 72-year-old female presented with a 2-year history of falls andinability to stop when rushing the net while playing tennis. She wasseen at three different hospitals and by multiple specialists (old agemedicine, orthopedic surgeon, neurologist) but no definite diagnosiswas made. She had a family history of parkinsonism (grandmother andtwo first cousins).She stated: ‘‘when I was climbing a step, suddenly I found myselfsitting down’’ or ‘‘I had to crawl back to bed as I felt that my legs couldnot bear the weight underneath me.’’ She had difficulty putting her leftfoot into her shoe as the foot was moving involuntarily and ‘‘had amind of its own’’ (Video 4). She felt unsteady and was concerned thatthe left leg ‘‘will let her down.’’ She stopped playing tennis as she notedthat her left leg did not obey her when moving side to side on thecourt.At 72 years there was no eye movement abnormality, no agraphe-sthesia, and no astereognosis. She was unsteady on tandem gait andfailed a pull test. She had a stimulus-subtle sensitive myoclonus in bothhands (worse on the right). There was mild rigidity with decreasedcoordination of the left leg and irregular ‘‘wiggling movements’’ werenoted in the tibialis anterior. There was no increased sweating orcramping to suggest neuromyotonia. Power was normal and reflexeswere brisk throughout. Sensation was normal.Investigations for falls were normal, including a 24-hour bloodpressure monitor, Holter monitor, tilt test, and routine blood tests.Lumbar puncture showed a slightly increased protein level at 76 mg/dL (normal, ,45 mg/dL). MRI of the brain was normal and MRI ofthe lumbar spine showed modest spondylosis at L1/2, L2/3 and L5/S1 without nerve root impingement.A nuclear magnetic dopaminergic brain scan (DAT scan) showedsubtle decreased uptake of tracer in the left posterior putamen (Figure 2A).18F PET/CT showed reduced metabolic activity in the bilateral insula,perisylvian regions, and midline pre-frontal cortex (Figure 2B). Therewas additional right parietal and basal ganglia hypometabolism sug-gestive of the diagnosis of CBS. EMG/NCS showed no evidence ofmyotonia or myokymia. She was diagnosed with CBS.Video 3. Patient 1: Right alien leg, magnetism, grasp and stimulussensitive myoclonus in both hands.Video 2. Patient 1: Involuntary movements of the right leg ‘‘alienleg’’. In order for the patient to stand up the doctor had to stand on his rightfoot to hold it in place.Video 1. Patient 1: Abduction and adduction of the toes on the rightside, involuntary dorsiflexion and flexion of the right ankle andmyoclonus.Alien Leg in Corticobasal Syndrome Olszewska DA, McCarthy A, Murray B, et al.Tremor and Other Hyperkinetic Movementshttp://www.tremorjournal.orgThe Center for Digital Research and ScholarshipColumbia University Libraries/Information Services3The patient required a walking aid by the age of 73 years, a rollatorby 74, and wheelchair by 76. At 78 years she was anarthric. Thepatient also developed bilateral hand myoclonus, masked facies, andrigidity in all limbs.She lives in a residential care setting requiring assistance for all heractivities of daily living.DiscussionAlien limb phenomenon is rare at presentation of CBS, but maydevelop in 50–60% of patients.1 While the alien limb phenomenon isgenerally understood as an involuntary movement of a limb, anaccepted definition remains unclear and there is significant variation inthe description of this sign.Figure 2. (A) Patient 2 nuclear magnetic dopaminergic brain scan: subtle left tracer uptake reduction in the putamen. (B) Patient 2 fludeoxyglucosepositron emission tomography and computed tomography: reduced metabolic activity in the bilateral insula, perisylvian regions and midline pre-frontalcortex.Video 4. Patient 1: Left alien leg, difficulty putting a shoe on.Olszewska DA, McCarthy A, Murray B, et al. Alien Leg in Corticobasal SyndromeTremor and Other Hyperkinetic Movementshttp://www.tremorjournal.orgThe Center for Digital Research and ScholarshipColumbia University Libraries/Information Services4Thus the diagnosis is challenging.Alien limb usually presents with an alien hand phenomenon.It rarely presents as an alien foot. Hu et al.2 reported a 58-year-oldfemale with paresthesia and involuntary toe wiggling/complex multi-directional movements of the leg and foot for 2 years before a diagnosisof CBS. MRI of the brain sometimes shows focal atrophy contralateralto the alien limb.In our first patient MRI showed only microvascular changes andwas entirely normal in the second.A review of 108 cases of pathologically confirmed corticobasaldegeneration from the Mayo clinic showed that the alien limbphenomenon is more common (65%) with the left-sided CBS (right-sided hemisphere involvement).3 It is possible that complex corticalphenomena such as an alien limb are under diagnosed in right-sidedCBS (left-hemisphere involvement) similar to the right-sided neglectassociated with left parietal lobe damage. Three alien limb variantsare recognized: two anterior (including frontal and callosal) and aposterior.The frontal variant is due to lesions of the cingulate cortex,dominant medial prefrontal cortex, supplementary motor area, or thecorpus callosum. The callosal variant results from callosal injury. Theposterior variant may be due to thalamic, parietal, or occipital lobeinjury. A distinct pathological location has not been definitely asso-ciated with the alien limb phenomenon as exceptions and overlap arefrequent.3,4Foot and leg involvement can lead to erroneous localization of theproblem to knee, hip, or back. As a result misdiagnoses may be seensuch as myelopathy, radiculopathy, amyotrophic lateral sclerosis,neuromyotonia, stiff leg syndrome, functional movement disorder, orpainful leg moving toes syndrome.5,6 Similarly erroneous diagnoses ofcervical radiculopathy, cervical myelopathy, neuropathy, and painfularm-moving fingers syndrome may occur with the alien arm pheno-menon; however, an alien hand/arm is usually diagnosed quicker thanan alien foot/leg. When CBS presents with complex cortical pheno-mena such as an alien limb, paresthesia, apraxia, or primary progres-sive aphasia without parkinsonism the diagnosis may be delayed ormissed.Why is the alien hand phenomenon more common than the alienfoot? Perhaps because the hand has a much bigger cortical repre-sentation; hence, the neuropathology is more likely to affect the area.Or perhaps an alien foot/leg is more frequently thought to be back,hip, or knee problems, leading to referral to the wrong specialty.Inappropriate investigations, procedures and operations can oftenresult. It is important to acknowledge that the abduction–adductiontoe movements in our first patient are regarded as specific for painfulleg–moving toes syndrome and their presence outside this syndrome isunusual.CBS is usually a sporadic disease; however, our second patient had afamily history of parkinsonism. Intriguingly, the original description ofCorticobasal Ganglionic Degeneration by Reibez et al.7 included anIrish patient with a strong family history of parkinsonism.Both cases highlight the difficult diagnostic path when a patientis seen by multiple specialists (family physician, old age medicine,orthopedic surgeon, neurologists), resulting in unnecessary proceduresand operations.Eventually a diagnosis of CBS was made in both.It is important that clinicians are aware of the ‘‘alien leg’’ pheno-menon given that this is now included in the diagnostic criteria forCBS.8References1. Lang A, Boeve B, Bergeron C. Corticobasal syndrome. In: Jankovic J,Tolosa E, editors. Parkinson’s disease and movement disorders, fifth edition.2007. Lippincott Williams and Wilkins, a Wolters Kluwer business, Philadelphia,USA. p 186–203.2. Hu WT, Josephs KA, Ahiskog E et al. MRI correlates of alien leg-likephenomenon in corticobasal degeneration. Mov Dis J 2005;20:870–873. doi:10.1002/mds.204513. Graff-Radford, Rubin MN, Jones DT et al. The alien limb phenomenon.J Neurol 2013:1880–1888. doi: 10.1007/s00415-013-6898-y4. Sarva H, Deil A, Severt WL. Pathophysiology and treatment of alien handsyndrome. Tremor Other Hyperkinet Mov 2014;4. doi: 10.7916/D8VX0F485. Gozubatik-Celik G, Gunduz A, Oguz S, Kiziltan G, Ertan S. An unusualcase of corticobasal syndrome. Arch Neuropsychiatry 2014;51:410–411. doi: 10.5152/npa.2014.76636. Schneider JA, Watts RL, Gearing M, Brewer RP, Mirra SS. Corticobasaldegeneration: neuropathologic and clinical heterogeneity. Neurology 1997;48:959–69. doi: 10.1212/WNL.48.4.9597. Rebeiz JJ, Kolodny EH, Richardson EP. Corticodentatonigral degenera-tion with neuronal achromasia: a progressive disorder of late adult life. Trans AmNeurol Assoc 1967;92:23–26.8. Armstrong MJ, Litvan I, Lang AE et al. Criteria for the diagnosis ofcorticobasal degeneration. Neurology 2013;80:496–503. doi: 10.1212/WNL.0b013e31827f0fd1Alien Leg in Corticobasal Syndrome Olszewska DA, McCarthy A, Murray B, et al.Tremor and Other Hyperkinetic Movementshttp://www.tremorjournal.orgThe Center for Digital Research and ScholarshipColumbia University Libraries/Information Services5

A Wolf in Sheep's Clothing: An "Alien Leg" in Corticobasal Syndrome

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