Betrayed By My Body: The Science Behind Alien Hand Syndrome
Lucas Angles
Illustrations by: Cherrie Chang
You wake up in the middle of the night to someone’s hand around your throat. You struggle and thrash as hard as you can, but the fingers tighten, and you begin to lose consciousness. You manage to turn on your nearby lamp to get a glimpse of the assailant. When the room illuminates, you open your eyes and see… no one. The space around you is empty, but as you look down, you see the hands that are gripping you so tightly. They are your own.
This nightmarish experience can be common for those with alien hand syndrome (AHS), a disorder that causes a limb to act on its own accord. Those with AHS frequently find their hands performing actions that they would never do, such as hitting or forcefully gripping objects, other people, or even themselves. These complex movements are smooth and purposeful, distinct from spasms and seizures, but occur without the knowledge of the individual. One of the best-known examples of AHS in popular media is the film Dr. Strangelove, where the titular character suffers from a fictionalized variant of AHS. The German scientist is unable to stifle the Nazi salute of his right hand in front of American officials, eventually having to restrain the hand with his other. Although used for the sake of parody here, AHS affects many dealing with, or recovering from, brain damage worldwide.
From Possession to Physiology: The Discovery of Alien Hand Syndrome
The curious phenomenon of involuntary movement has puzzled physicians for over a hundred years. When prominent German neurologist Kurt Goldstein first described such phenomena at the turn of the 20th century, the superstitious belief that seizures were the result of possession still held sway over many. The complex, sometimes harmful, movements associated with AHS were thought to be the work of the devil [1]. Goldstein described a woman recovering from a stroke whose left arm moved with purpose, without her knowledge or control. The hand would stroke her hair or rub her nose as if she were initiating the movements herself. At one point, the hand even attempted to strangle the woman during an examination, only stopping after being restrained by force [2]. It was not until 1972, nearly 70 years after Goldstein’s observations, that physicians coined the term “alien hand.” When shown their afflicted hand, those with the disorder cannot recognize it as their own [3]. In fact, many people with AHS name their aberrant limb, viewing it as a totally separate entity [4].
The field of neuroscience has grown exponentially in the past 50 years. In particular, the advancement of brain-imaging technology has significantly developed our understanding of alien hand syndrome. The invention of magnetic resonance imaging (MRI) allowed for one brain’s overall structure to be referenced and compared to others via images. The visualization of healthy brains prompted the analysis of abnormal brains. People with neurological disorders no longer have to wait until after their deaths to be diagnosed. Using MRI, neurologists can precisely determine the “where,” “when,” “why,” and “how” of diseases like AHS.
Cell Death Brings the Alien Hand to Life
After patients with AHS underwent MRI, physicians were able to identify the primary cause of the disorder: widespread cell death. This destruction is the product of a wide range of diseases and trauma, and can lead to significant impairment in day-to-day cognitive function. Neurologists have tracked similar destructive patterns across those diagnosed with AHS [4].
Strokes are the most common cause of universal cell loss, affecting more than 800,000 people in the US every year [5]. But what are strokes, and how do they happen? Imagine the blood vessels in your brain as a plumbing system. Blood carries oxygen and nutrients to cells and washes waste and carbon dioxide away in order to maintain proper cellular functioning. When a stroke occurs, it either happens in the form of a burst pipe (i.e. a hemorrhage), or a blockage in the plumbing (i.e. ischemia). Oxygenated blood cannot reach a specific brain area, depriving neurons and other brain cells of oxygen and killing these cells if the stroke cannot be reversed in time. Strokes are usually localized to a particular region of the brain; individuals may exhibit slurred speech, paralysis, among other symptoms — usually limited to one side of the body — depending on where the stroke occurs [5]. Some stroke victims may even completely lose their ability to understand language [6]. Strokes can affect any area of the brain with equal likelihood; there is no one region that is always affected, which causes stroke victims to display a wide array of symptoms.
Other significant contributors to AHS cases include neurodegenerative disorders like Alzheimer's Disease (AD) and Corticobasal Degeneration (CBD) [4]. Physicians characterize these conditions by the continuous death of neurons. These cells are attacked and destroyed as a byproduct of an exaggerated immune response. Patients with AD may lose 15% of their brain volume in a year due to cell death [7]. A critical component of the degeneration observed in AD and CBD is the misfolding of specific proteins. If cells are the building blocks of life, proteins are the cellular "workers" that make that life possible. With a vast array of functions, from the formation of skeletal structure to the creation of DNA to even making other proteins, the different shapes of these molecules determine their function in our bodies. A long thin protein may end up in a person's hair, while a protein that the body can stretch may work well in an athlete's muscles. However, in AD and CBD, proteins cannot perform their designated functions. Much like a crumpled ball of paper compared to a carefully folded paper airplane, improperly folded proteins are essentially useless and can be toxic to the body. In both CBD and AD, a protein called tau misfolds and accumulates within the cell [8]. Tau makes up much of the scaffolding that holds each cell together. When it misfolds, tau can no longer keep the neuron's structure and the cell collapses.
While extremely rare, most cases of the neurodegenerative prion disorder Creutzfeldt-Jakob Disease (CJD) result in AHS. Prions are similar to misfolded proteins that are "zombified." Upon contact, a prion refolds proteins of the same type into the diseased state. These newly infected proteins then spread the disease throughout the entire body exponentially [9]. The immune system identifies clumps of prions as a foreign body and targets that area of the brain, killing all the normal surrounding cells in the process. In the 1980s and 90s, panic swept the United Kingdom after 177 people died from consuming beef tainted with "mad cow disease," a bovine variant of CJD. Because prions can jump from one animal to another if they are sufficiently related, concern for public safety forced the U.K. to slaughter 4 million cattle [10].
The degeneration that contributes to AHS primarily affects the brain's white matter rather than grey matter [4]. When looking at the brain, the two types of tissue are very apparent. White matter gets its name from the color of the enormous number of axons that comprise it. Axons are the parts of the neuron that carry signals and are the primary way the brain communicates with itself. Think of white matter regions as the telephone lines of the brain. As they collect and transmit information, the entire system coordinates thought and action [11]. Grey matter, on the other hand, is primarily found on the outside surface of the brain and is composed of neuronal cell bodies. This is where the nucleus and most other structures within the cell are located, and is the site of signal reception [11]. In cases of AHS, destruction of the brain's white matter irreparably shuts down the communication system between brain regions. As a result, many areas are completely cut off from others and therefore cannot coordinate activities with each other [4]. On a cellular level, each end of the brain is the equivalent of thousands of miles apart! Without the axonal information highways that connect these regions, they are working in the dark.
A Breakdown in Communication
It is tempting to place very distinct purposes and functions on each region, or lobe, of the brain. These concrete separations make it easier for physicians to simplify understanding of cognition. There is a lobe for vision, a lobe for hearing, a lobe for touch, and so on. However, in reality, the brain is inextricably interconnected. You would never be able to recognize a chair as a chair, have emotional responses to different smells, or unlock certain memories from the foods you eat without the communication of any given region with another. The prefrontal cortex (PFC), which encompasses the front half of your brain, is considered the “mission control” of the brain. Frequently, different lobes communicate with the PFC, where “decision making” occurs. The PFC makes choices, is responsible for much of our knowledge, and represents the largest contributor to each of our individual differences [12]. When you move, such as when you contract the muscles in your fingers to turn a page, your PFC has already decided to do so long before. The PFC then sends these signals straight behind it to the motor cortex. There, neurons pass through the basal ganglia, the site of movement regulation, and span the brain and down the spinal cord, eventually branching off and attaching to muscle tissue [13]. When these neurons pass down a signal sent from the brain, their corresponding muscles contract. Because information flows from the PFC in the front of the brain to the motor cortex behind it, researchers have termed this process “front-to-back movement” [14].
In the neurodegeneration characteristic of AHS, front-to-back movement is disrupted. The reduction of white matter prevents the PFC from communicating with the brain region that coordinates movement, aptly named the motor cortex. This lack of coordination causes the motor cortex to activate on its own and creates movement in the absence of any conscious choice by the PFC. Functional magnetic resonance imaging (fMRI) has revealed the distinct lack of interaction between the motor cortex, the PFC, and the basal ganglia. Unlike MRI, which can only show the general structure of a subject’s brain, fMRI allows us to clearly observe areas of neural activity in real-time [15]. What usually is a synchronized orchestra of various brain regions in normal brain functioning devolves into many different instruments playing out of tune in the AHS brain. This absence of coordination and inhibition leads to the unconscious movement characteristic of AHS.
Taking Control of the Alien Hand: Therapeutic Options and Future Directions
Today, there is no definitive cure for AHS. Nonetheless, treatments exist that mitigate symptoms for those with the condition so that they can recover a sense of autonomy. Treatments mainly consist of cognitive-behavioral therapy (CBT) in conjunction with medication or rehabilitation exercises [4]. CBT, a mainstay in the treatment of major depressive disorder and bipolar disorder, seeks to correct harmful behavior by creating new ways of approaching issues and problem-solving to manage stress [16]. For AHS patients who are terrified that their own body is working against them, CBT serves to stave off the anxiety associated with the disorder, allowing patients to better utilize the affected hand [4]. The more calm and focused individuals with AHS are, the more receptive they are to treatment [4].
Medicinal drugs are now the fastest growing field in the treatment of AHS. Medication treatments for AHS primarily focus on reducing movement in general, in an effort to halt non-voluntary motion. Clonazepam, an anti-seizure medication, is frequently used to treat constant repetitive movement called dystonia. Clonazepam is a benzodiazepine, or a “benzo,” meaning it operates by decreasing overall neural activity, especially within the motor cortex. Benzos like clonazepam are believed to quell self-activation of the cortex, stopping AHS-characteristic movements altogether [17]. Botulinum toxin A, or “botox,” is frequently employed to paralyze muscles for cosmetic purposes. In the case of AHS, small doses of botox can retain voluntary movement while blocking any abnormal activity, like how a strainer lets liquids through while keeping out solids [17].
Rehabilitative exercises are currently the most effective treatment for AHS, and are widely preferred to medication. These tasks serve to distract or restrain the limb, and are used to manage a variety of motor and sensory disorders. One of the simplest forms of treatment involves “distracting” the freely moving limb with a task to complete, such as gripping or carrying an object. This diversion occupies the problematic limb with a job, substituting any destructive movements with constructive behavior [18]. In other cases, restricting the limb either with a free hand or inhibitive casting — like those used by patients who have broken their arms — reduces the frequency of destructive incidents [4]. A cast restricts the limb, and “muffles'' any sort of involuntary movement. In fact, this same strategy is used in patients with cerebral palsy to overcome the seizing of specific body parts [19]. Diverting and restricting movement are the most productive forms of recovery from AHS, preventing potentially harmful side-effects that may result from the improper use of medication.
Despite being categorized more than a century ago, alien hand syndrome continues to puzzle physicians and neurologists alike. Advancements in imaging technology have allowed us to gain insight into the seemingly counterintuitive way neural destruction can lead to the production of coordinated movement. However, the neural correlates of the condition are nebulous. How is activity in the motor cortex generated, if not from coordination with the PFC? Why are these movements so complex instead of seizure-like spasms? How can an individual move voluntarily at one point and lose control the next? With the constant creation of novel, efficient techniques to peer inside the brains of those with AHS, scientists may soon answer these questions. With each new finding, AHS offers advanced knowledge into how and why the body “chooses” to move. Through the analysis and treatment of such rare diseases, we can better appreciate the underlying mechanisms behind our everyday actions.
REFERENCES
Gross, R. A. (1992). A brief history of epilepsy and its therapy in the western hemisphere. Epilepsy Research, 12(2), 65–74. doi:10.1016/0920-1211(92)90028-R
Brainin, M., Seiser, A., & Matz, K. (2007). The mirror world of motor inhibition: The alien hand syndrome in chronic stroke. Journal of Neurology, Neurosurgery & Psychiatry. doi:10.1136/jnnp.2007.116046
Brion, S., & Jedynak, C. P. (1972). [Disorders of interhemispheric transfer (callosal disconnection). 3 cases of tumor of the corpus callosum. The strange hand sign]. Revue Neurologique, 126(4), 257–266. PMID: 4350533
Sarva, H., Deik, A., & Severt, W. L. (2014). Pathophysiology and treatment of alien hand syndrome. Tremor and Other Hyperkinetic Movements (New York, N.Y.), 4, 241. doi:10.7916/D8VX0F48
Ovbiagele, B., Nguyen-Huynh, M.N. Stroke epidemiology: Advancing our understanding of disease mechanism and therapy. Neurotherapeutics 8, 319 (2011). doi:10.1007/s13311-011-0053-1
Musuka, T. D., Wilton, S. B., Traboulsi, M., & Hill, M. D. (2015). Diagnosis and management of acute ischemic stroke: Speed is critical. Canadian Medical Association Journal, 187(12), 887. doi:10.1503/cmaj.140355
Traini, E., Carotenuto, A., Fasanaro, A. M., & Amenta, F. (2020). Volume analysis of brain cognitive areas in Alzheimer’s Disease: Interim 3-year results from the ASCOMALVA trial. Journal of Alzheimer’s Disease, 76(1), 317–329. doi:10.3233/JAD-190623
Chahine, L. M., Rebeiz, T., Rebeiz, J. J., Grossman, M., & Gross, R. G. (2014). Corticobasal syndrome. Neurology: Clinical Practice, 4(4), 304. doi:10.1212/CPJ.0000000000000026
Geschwind, M. D. (2015). Prion diseases. CONTINUUM: Lifelong Learning in Neurology, 21(6), 1612. doi:10.1212/CON.0000000000000251
Manix, M., Kalakoti, P., Henry, M., Thakur, J., Menger, R., Guthikonda, B., & Nanda, A. (2015). Creutzfeldt-Jakob disease: Updated diagnostic criteria, treatment algorithm, and the utility of brain biopsy. Neurosurgical Focus FOC, 39(5), E2. doi:10.3171/2015.8.FOCUS15328
Wen, Q., & Chklovskii, D. B. (2005). Segregation of the brain into gray and white matter: A design minimizing conduction delays. PLOS Computational Biology, 1(7), e78. doi:10.1371/journal.pcbi.0010078
Siddiqui, S. V., Chatterjee, U., Kumar, D., Siddiqui, A., & Goyal, N. (2008). Neuropsychology of prefrontal cortex. Indian Journal of Psychiatry, 50(3), 202. doi:10.4103/0019-5545.43634
Ebbesen, C. L., & Brecht, M. (2017). Motor cortex—To act or not to act? Nature Reviews Neuroscience, 18(11), 694–705. doi:10.1038/nrn.2017.119
Kayser, A. S., Sun, F. T., & D’Esposito, M. (2009). A comparison of Granger causality and coherency in fMRI-based analysis of the motor system. Human Brain Mapping, 30(11), 3475–3494. doi:10.1002/hbm.20771
Assal, F., Schwartz, S., & Vuilleumier, P. (2007). Moving with or without will: Functional neural correlates of alien hand syndrome. Annals of Neurology, 62(3), 301–306. doi:10.1002/ana.21173
Hofmann, S. G., Asnaani, A., Vonk, I. J. J., Sawyer, A. T., & Fang, A. (2012). The efficacy of cognitive behavioral therapy: A review of meta-analyses. Cognitive Therapy and Research, 36(5), 427–440. doi:10.1007/s10608-012-9476-1
Haq, I. U., Malaty, I. A., Okun, M. S., Jacobson, C. E., Fernandez, H. H., & Rodriguez, R. R. (2010). Clonazepam and botulinum toxin for the treatment of alien limb phenomenon. The Neurologist, 16(2), 106–108. doi:10.1097/NRL.0b013e3181a0d670
Kikkert, M. A., Ribbers, G. M., & Koudstaal, P. J. (2006). Alien hand syndrome in stroke: A report of 2 cases and review of the literature. Archives of Physical Medicine and Rehabilitation, 87(5), 728–732. doi:10.1016/j.apmr.2006.02.002
Blackmore, A. M., Boettcher-Hunt, E., Jordan, M., & Chan, M. D. Y. (2007). A systematic review of the effects of casting on equinus in children with cerebral palsy: An evidence report of the AACPDM. Developmental Medicine & Child Neurology, 49(10), 781–790. doi:10.1111/j.1469-8749.2007.00781.x