Alien Limb Phenomenon After Diffuse Corpus Callosum Ischemic Stroke

Abstract

The alien limb is a phenomenon characterized by a cluster of clinical features wherein the limb behaves autonomously and as separated from a person’s identity. We herein report a 36-year-old Indian female with multiple comorbidities who presented with recurrent episodes of limb-shaking transient ischemic attacks for 1 year, followed by left-sided hemiplegia. During recovering, the patient noticed a feeling that as if her left hand did not belong to herself and acted autonomously (alien limb phenomenon) along with visuospatial deficits. Magnetic resonance imaging of the brain revealed ischemic stroke diffusely involving corpus callosum. Magnetic resonance angiography was suggestive of compromised right-sided anterior circulation. This was corroborated by digital subtraction angiography that revealed reduced flow in right internal carotid artery. Diffuse infarction of the corpus callosum requires involvement of both the anterior and the posterior circulation. Due to the lack of clinical features suggestive of chronic internal carotid artery dissection, occlusive atherosclerotic disease of the anterior cerebral circulation associated with possible steal phenomenon from the posterior circulation was the most probable underlying mechanism for the callosal stroke. Steal phenomenon has been proposed as a compensatory mechanism in hemodynamically compromised ischemic parenchyma and it can explain the co-existence of anterior and posterior circulation strokes. This case also highlights how both anterior and posterior types of the alien limb phenomenon can co-exist in a background of vascular insult, resulting from intra-cranial atherosclerotic disease.

Introduction

In 1965, Norman Geschwind ¹ outlined a framework of pure disconnection network, which revolutionized concepts of neurology and paved the way for development of various syndromes in future, based on involvement of the association fibers. One of these disconnection syndromes is the alien limb phenomenon, characterized by a cluster of clinical features wherein the limb behaves autonomously and as separated from a person’s identity. ² Voluntary goal directed activities become impossible to perform, as if the limb had a mind of its own and was “alien” or foreign to one’s self. ² Alien hand syndrome was first described by Kurt in 1908 in a patient with abnormal left hand movement, but the term “alien hand” was coined by Brion and Jedinak in 1972 as “le signe de la main étrangére.” ³ In 1991, Della Sala et al. ⁴ attempted a scientific description for this phenomenon for the first time.

We herein report a unique case of a patient with an alien limb phenomenon (depicting features of both anterior and posterior variants), following a vascular event, with diffuse involvement of the corpus callosum and underlying intra-cranial atherosclerotic disease.

Case Presentation

A 36-year-old Indian female complained for the last 1 year of recurrent episodes of tremulousness of left upper limb lasting for 3–4 min after which she had a feeling of “give away” and need for sitting down for support. She noticed that most of these episodes occurred in upright posture and none were associated with preceding aura, loss of consciousness, abnormal posturing of limbs/trunk/face or sphincter incontinence. She has been diagnosed to have type-2 diabetes mellitus (3 years) and arterial hypertension (1 year), which were inadequately controlled with medications.

Three months prior to admission, she had developed acute onset left-sided hemiplegia. The weakness persisted for 10 days during which she received medications (oral antihypertensive, oral antidiabetic agents, aspirin, and atorvastatin) and physiotherapy. However, she reported persistent dragging of her left lower limb during walking for about 1 month after the event. During recovery, she noticed a feeling that as if her left hand did not belong to her. She reported waking up frightened at night with a feeling that someone was stroking her hair. When she used her right hand to remove the “entity which was stroking her hair,” she realized after seeing that it was her left hand. She also reported that her left hand “did not allow” her right hand occasionally to do activities that she desired to perform. She also described episodes of tonic grasping of objects by her left hand, which she could not release even with conscious efforts, as well as transient episodes where she was not able to reach her destination within her own house; when inquired by her family members, she said she “did not know how to reach there.” On being prompted, however, she could reach her destination. Family members reported that she had also episodes of anger outburst and would laugh and cry sometimes with minimal stimulus and sometimes even without it.

On examination, the patient was conscious with periods of emotionally inappropriate responses. She had no complaints of dysphagia or choking spells; jaw jerk was absent and no signs of upper motor neuron-type bulbar dysfunction were noted. Hence, pseudobulbar affect seemed to be a distant consideration. General survey failed to reveal any significant abnormality. Fundoscopy revealed microaneurysms. On detailed cognitive examination, the major domains tested were normal. Praxis (tangible and intangible) for her right upper limb was unimpaired, whereas testing praxis for her left upper limb revealed features of complete non-purposeful movements on intended action. Tests for hemineglect and homonymous hemianopia were non-contributory. Cranial nerve examination revealed features suggestive of upper motor neuron-type paralysis of left-sided facial nerve. Motor system examination revealed residual left-sided spastic hemiparesis (mMRC grade 4+/5) with extensor left plantar response. Sensory system examination was normal except impaired cortical sensations over her left hand. Cerebellar examination was normal. No levitation could be demonstrated for her left hand. Tonic grasping of her left upper limb was demonstrated; however, any other signs pertaining to frontal release phenomenon could not be elicited.

Magnetic resonance imaging of the brain, which was obtained during the acute stroke, showed hyperintense lesions on T2-weighted imaging and T2-fluid attenuated inversion recovery sequences involving entire corpus callosum (rostrum, body, genu, and splenium) with restricted diffusion (Figures 1 and 2), which clinched the diagnosis of ischemic stroke. Computed tomography angiography (Figure 3) and magnetic resonance angiography (MRA) with gadolinium of the brain revealed post-clinoid narrowing of the terminal part of right internal carotid artery (ICA) and non-visualization of the post ophthalmic segment of both right ICA and right middle cerebral artery. MRA of the extra-cranial vessels of neck and arch of aorta did not show any significant abnormality. Cerebral digital subtraction angiography (DSA) revealed a “rat-tail tapering” of right ICA, 2–3 cm distal to the bifurcation of common carotid artery, with dye holding at the carotid bulb and reduced intra-cranial flow, and no distal flow into right anterior and middle cerebral arteries, as well as significant cortico-cortical collaterals from right posterior circulation and the left anterior circulation (see Supplementary Video). Left anterior circulation revealed narrowing of A1 segment of anterior cerebral artery and no significant flow from anterior communicating or posterior communicating arteries. Intra-cranial and extra-cranial vasculitides were also considered, but no such evidence was found, such as beading of intra-cranial vessels on DSA or presence of multiple small vessel ischemic changes on brain imaging. DSA of the vessels of the neck arising from aortic arch divulged no evidence of extra-cranial disease in other vessels, except the narrowing of the right ICA as detailed above; evaluation of renal arteries failed to reveal any features suggestive of underlying pathology. To exclude other diagnoses and establish the etiology of ischemic stroke, a complete workup was performed.

Figure 1.

Axial diffusion weighted imaging (DWI) sequences showing restrictions over genu, rostrum and splenium of corpus callosum.

Figure 2.

Axial T2-fluid attenuated inversion recovery image showing hyperintense corpus callosal lesions.

Figure 3.

Computed tomography angiography of the brain showing post-clinoid narrowing of the terminal part of right internal carotid artery (ICA) and non-visualization of the post ophthalmic segment of both right ICA and right middle cerebral artery. Right A1 segment of anterior cerebral artery is non-visualised and A2 segment of right anterior cerebral artery is receiving supply via anterior communicating artery.

Complete blood cell count, serum electrolytes, lipid profile, plasma glucose profile, renal, liver and thyroid function tests, autoimmune and paraneoplastic antibodies, relevant microbial serologies, vasculitis, prothrombotic profile, high performance liquid chromatography for hemoglobinopathies, and connective tissue diseases panel including serum angiotensin converting enzyme levels, were negative except fasting plasma glucose (226 mg/dl) and elevated hemoglobin-A1c level (11.7%). Cerebrospinal fluid (CSF) analysis revealed pleocytosis with 60 cells (90% mononuclear), slightly depressed glucose levels of 111 mg/dl (corresponding blood glucose 386 mg/dl) and elevated protein of 110 mg/dl. Since CSF showed pleocytosis, possibility of infective vasculopathy was considered. However, polymerase chain reaction and nucleic acid amplification tests for relevant neuro-viruses, bacteria, mycobacteria, protozoa, and fungi were negative. CSF oligoclonal bands were not found and IgG index was normal. Non-infective causes of vasculopathy with CSF pleocytosis (especially, neuro-sarcoidosis, neuro-Bechet’s disease, and central nervous system angiitis) were also considered. But lack of recurrent neurological deficits, headache, and negative inflammatory markers, along with lack of angiographic evidence of central nervous system vasculitis, failed to provide adequate evidences for those.

Electrocardiography and two-dimensional echocardiography with color doppler were normal. Though focal seizure was also considered a possibility for the persistent episodes of left upper limb shakiness, semiology, negative electroencephalography recordings, and absence of epileptogenic lesions on neuroimaging made this possibility unlikely.

Occlusive atherosclerotic disease of the anterior cerebral circulation associated with possible steal phenomenon from the posterior circulation was the most probable underlying mechanism for the callosal stroke. She was managed symptomatically with dual antiplatelet (aspirin 75 mg/day and clopidogrel 75 mg/day), atorvastatin (40 mg/day), clonazepam (1 mg/day), telmisartan (40 mg/day), amlodipine (5 mg/day), and basal-bolus regimen of insulin. On follow-up visit after 3 months, the patient showed improvement in her motor power with persistence of her complaint of alien limb, but had a modified Rankin score of 2. A new MRA showed no abnormality of the extra-cranial arteries.

Discussion

Recurrent attacks of abnormal shaking movements with “give way” sensation involving the left half of body every single time, that occurred mostly while in upright posture, with quick spontaneous recovery, are indicative of limb-shaking transient ischemic attacks (suggestive of a large vessel occlusive disease) in a background of multiple vascular risk factors. Differential diagnoses (focal motor onset seizures, demyelinating, and neurodegenerative disorders, as well as prion diseases) were excluded due to lack of supportive clinical and radiological evidences, further course of disease progression and normal electrophysiological studies.

Episode of acute onset non-crossed left-sided dense hemiparesis was suggestive of lesion involving the right middle cerebral artery territory. This was followed by development of features suggestive of alien limb phenomenon. There are 3 types of alien hand syndromes: frontal and callosal types (these 2 are anterior variants), and posterior variant (Table 1).^5,6

Table 1.

Types of Alien Hand Syndrome.

Variant	Cardinal Features	Methods to Illustrate It
Anterior variant	- Presence of frontal lobe reflexes
Frontal	- Tonic grasping, utilization behavior
Callosal	- Dyspraxia: Ideomotor, diagnostic	- Examining for praxis with pantomiming or with tools
	- Somesthetic transfer and cross-replication of hand posture	- Without visual input, patient is asked to identify similar finger of other hand, which is touched by the examiner
	- Mirror movements	- Movement by non-diseased hand is mirrored
Posterior variant	- Hemianesthesia
	- Homonymous hemianopia
	- Hemianopia-neglect
	- Moderate-severe ataxia
	- Visuospatial deficits
	- Hemiasomatognosia (body schema disturbances) ipsilateral to the alien hand

In our patient, alien hand phenomenon was elicited by 3 characteristics. First, intermanual conflict, in which antagonistic actions between upper limbs were noted. Second, diagnostic dyspraxia, that is, movements that were in opposition or irrelevant to the action planned leading to frustration of the patient. Finally, tonic grasping, that is, difficulty in releasing grip over objects. All of them were suggestive of an anterior type alien limb phenomenon, pertaining to lesions of the anterior to mid callosum or mesial frontal cortex. ⁷ However, intermanual conflict and diagnostic dyspraxia have overlapping domains. Indeed, actions are always opposite (antagonistic) of what normal limb does in intermanual conflict and actions can be aimless or irrelevant (not necessarily being antagonistic) to willed action, in diagnostic dyspraxia. Patients with callosal type alien hand syndrome can also exhibit autocriticism (frustration caused by intermanual conflict). ⁸

On the other hand, visuospatial deficits elicited in history and the impaired cortical sensations over her left hand on examination were suggestive of a posterior alien limb phenomenon, pertaining to lesions of contralateral occipito-parietal cortex, splenium of corpus callosum, or thalamus. ⁷ Distress arises from the perception of onlookers, features of which were elicited in our patient. ⁸

Hence, our patient had features of both anterior and posterior types of alien limb syndrome, which could be explained by diffuse involvement of the corpus callosum in the inciting event. ⁹ The corpus callosum is the major commissural pathway connecting the cerebral hemispheres and it receives its blood supply from the pericallosal artery (branch of anterior cerebral artery) and posterior pericallosal artery (branch of the posterior cerebral artery). ¹⁰ Diffuse infarction of the corpus callosum requires involvement of both the anterior and the posterior circulation. Alternatively, it would indicate the presence and involvement of a median callosal artery as the main blood supply of the corpus callosum. ¹⁰ However, median callosal artery could not be demonstrated on DSA. Specifically, DSA study revealed a compromised anterior circulation with evidence of dilatation at right carotid bulb with reduced flow in right ICA, no flow in right anterior and middle cerebral arteries, and with cortico-cortical collaterals from the external carotid artery. Posterior circulation was normal. Due to the lack of clinical features suggestive of chronic ICA dissection, and that, MRA showed no abnormality of the extra-cranial arteries during the stroke and 3 months following the episode, occlusive atherosclerotic disease of the anterior cerebral circulation associated with possible steal phenomenon from the posterior circulation was the most probable underlying mechanism for the callosal stroke. Steal phenomenon has been proposed as a compensatory mechanism in hemodynamically compromised ischemic parenchyma,^11,12 and could explain the co-existence of anterior and posterior circulation strokes. Vascular steal phenomenon occurs in brain areas with increased proximal resistance like an arterial stenosis. ¹³ When it occurs, the arterioles show a lowered perfusion pressure and respond over time by a chronic compensatory vasodilation. ¹³ This is effective in maintaining resting blood flow until maximal vasodilation is reached. ¹³ However, if a vasodilator stimulus affects the brain, the compromised tissue cannot reduce its resistance, and blood flow is redirected to surrounding healthy tissues with preserved vasodilatory capacity. ¹³ Since we had the opportunity to examine the patient 3 months after her inciting event, transcranial doppler for demonstration of steal phenomenon was not considered.

Management of alien limb phenomenon includes various therapy directed at improving the patient’s daily activities. No specific therapy has been defined. Medications, which have been used, include clonazepam and botulinum toxin.^2,7,8 Behavioral therapy, for example, distracting the hand with some object while the normal hand is free to perform activities, retraining the person to recognize shapes, objects, directions, and applying learned skills to daily life later, have shown some effect.^2,7,8

Conclusion

Our case highlights how both the anterior and posterior types of the alien limb phenomenon can co-exist in a background of vascular insult, resulting from intra-cranial atherosclerotic disease. To the best of our knowledge, this is the first reported case of presence of both anterior and posterior variants of alien limb phenomenon in 1 patient following an acute vascular event.

ORCID iDs

Ritwik Ghosh, MD https://orcid.org/0000-0002-8192-0807

Julian Benito-León, MD, PhD https://orcid.org/0000-0002-1769-4809

Souvik Dubey, MD, DM https://orcid.org/0000-0003-1733-3429