Neuropsychology

From Wikipedia, the free encyclopedia

 https://en.wikipedia.org/wiki/Neuropsychology

Neuropsychology is a branch of psychology that is concerned with how the brain and the rest of the nervous system influence a person's cognition and behaviors. More importantly, professionals in this branch of psychology often focus on how injuries or illnesses of the brain affect cognitive functions and behaviors.

It is both an experimental and clinical field of psychology that aims to understand how behavior and cognition are influenced by brain functioning and is concerned with the diagnosis and treatment of behavioral and cognitive effects of neurological disorders. Whereas classical neurology focuses on the pathology of the nervous system and classical psychology is largely divorced from it, neuropsychology seeks to discover how the brain correlates with the mind through the study of neurological patients. It thus shares concepts and concerns with neuropsychiatry and with behavioral neurology in general. The term neuropsychology has been applied to lesion studies in humans and animals. It has also been applied in efforts to record electrical activity from individual cells (or groups of cells) in higher primates (including some studies of human patients).

In practice, neuropsychologists tend to work in research settings (universities, laboratories or research institutions), clinical settings (medical hospitals or rehabilitation settings, often involved in assessing or treating patients with neuropsychological problems), or forensic settings or industry (often as clinical-trial consultants where CNS function is a concern).

History

Neuropsychology is a relatively new discipline within the field of psychology. The first textbook defining the field, Fundamentals of Human Neuropsychology, was initially published by Kolb and Whishaw in 1980. However, the history of its development can be traced back to the Third Dynasty in ancient Egypt, perhaps even earlier. There is much debate as to when societies started considering the functions of different organs. For many centuries, the brain was thought useless and was often discarded during burial processes and autopsies. As the field of medicine developed its understanding of human anatomy and physiology, different theories were developed as to why the body functioned the way it did. Many times, bodily functions were approached from a religious point of view and abnormalities were blamed on bad spirits and the gods. The brain has not always been considered the center of the functioning body. It has taken hundreds of years to develop our understanding of the brain and how it affects our behaviors.

Ancient Egypt

In ancient Egypt, writings on medicine date from the time of the priest Imhotep. They took a more scientific approach to medicine and disease, describing the brain, trauma, abnormalities, and remedies for reference for future physicians. Despite this, Egyptians saw the heart, not the brain, as the seat of the soul.

Aristotle

Senses, perception, memory, dreams, action in Aristotle's biology. Impressions are stored in the seat of perception, linked by his Laws of Association (similarity, contrast, and contiguity).

 

Aristotle reinforced this focus on the heart which originated in Egypt. He believed the heart to be in control of mental processes, and looked on the brain, due to its inert nature, as a mechanism for cooling the heat generated by the heart. He drew his conclusions based on the empirical study of animals. He found that while their brains were cold to the touch and that such contact did not trigger any movements, the heart was warm and active, accelerating and slowing dependent on mood. Such beliefs were upheld by many for years to come, persisting through the Middle Ages and the Renaissance period until they began to falter in the 17th century due to further research. The influence of Aristotle in the development of neuropsychology is evident within language used in modern day, since we "follow our hearts" and "learn by the heart."

Hippocrates

Hippocrates viewed the brain as the seat of the soul. He drew a connection between the brain and behaviors of the body, writing: "The brain exercises the greatest power in the man." Apart from moving the focus from the heart as the "seat of the soul" to the brain, Hippocrates did not go into much detail about its actual functioning. However, by switching the attention of the medical community to the brain, his theory led to more scientific discovery of the organ responsible for our behaviors. For years to come, scientists were inspired to explore the functions of the body and to find concrete explanations for both normal and abnormal behaviors. Scientific discovery led them to believe that there were natural and organically occurring reasons to explain various functions of the body, and it could all be traced back to the brain. Hippocrates introduced the concept of the mind – which was widely seen as a separate function apart from the actual brain organ.

René Descartes

Philosopher René Descartes expanded upon this idea and is most widely known for his work on the mind-body problem. Often Descartes's ideas were looked upon as overly philosophical and lacking in sufficient scientific foundation. Descartes focused much of his anatomical experimentation on the brain, paying special attention to the pineal gland – which he argued was the actual "seat of the soul." Still deeply rooted in a spiritual outlook towards the scientific world, the body was said to be mortal, and the soul immortal. The pineal gland was then thought to be the very place at which the mind would interact with the mortal and machine-like body. At the time, Descartes was convinced the mind had control over the behaviors of the body (controlling the person) – but also that the body could have influence over the mind, which is referred to as dualism. This idea that the mind essentially had control over the body, but the body could resist or even influence other behaviors, was a major turning point in the way many physiologists would look at the brain. The capabilities of the mind were observed to do much more than simply react, but also to be rational and function in organized, thoughtful ways – much more complex than he thought the animal world to be. These ideas, although disregarded by many and cast aside for years led the medical community to expand their own ideas of the brain and begin to understand in new ways just how intricate the workings of the brain really were, and the complete effects it had on daily life, as well as which treatments would be the most beneficial to helping those people living with a dysfunctional mind. The mind-body problem, spurred by René Descartes, continues to this day with many philosophical arguments both for and against his ideas. However controversial they were and remain today, the fresh and well-thought-out perspective Descartes presented has had long-lasting effects on the various disciplines of medicine, psychology and much more, especially in putting an emphasis on separating the mind from the body in order to explain observable behaviors.

Thomas Willis

Thomas Willis

It was in the mid-17th century that another major contributor to the field of neuropsychology emerged. Thomas Willis studied at Oxford University and took a physiological approach to the brain and behavior. It was Willis who coined the words 'hemisphere' and 'lobe' when referring to the brain. He was one of the earliest to use the words 'neurology' and 'psychology'. Rejecting the idea that humans were the only beings capable of rational thought, Willis looked at specialized structures of the brain. He theorized that higher structures accounted for complex functions, whereas lower structures were responsible for functions similar to those seen in other animals, consisting mostly of reactions and automatic responses. He was particularly interested in people who suffered from manic disorders and hysteria. His research constituted some of the first times that psychiatry and neurology came together to study individuals. Through his in-depth study of the brain and behavior, Willis concluded that automated responses such as breathing, heartbeats and other various motor activities were carried out within the lower region of the brain. Although much of his work has been made obsolete, his ideas presented the brain as more complex than previously imagined, and led the way for future pioneers to understand and build upon his theories, especially when it came to looking at disorders and dysfunctions in the brain.

Franz Joseph Gall

Neuroanatomist and physiologist Franz Joseph Gall made major progress in understanding the brain. He theorized that personality was directly related to features and structures within the brain. However, Gall's major contribution within the field of neuroscience is his invention of phrenology. This new discipline looked at the brain as an organ of the mind, where the shape of the skull could ultimately determine one's intelligence and personality. This theory was like many circulating at the time, as many scientists were taking into account physical features of the face and body, head size, anatomical structure, and levels of intelligence; only Gall looked primarily at the brain. There was much debate over the validity of Gall's claims however, because he was often found to be wrong in his predictions. He was once sent a cast of René Descartes' skull, and through his method of phrenology claimed the subject must have had a limited capacity for reasoning and higher cognition. As controversial and false as many of Gall's claims were, his contributions to understanding cortical regions of the brain and localized activity continued to advance understanding of the brain, personality, and behavior. His work is considered crucial to having laid a firm foundation in the field of neuropsychology, which would flourish over the next few decades.

Jean-Baptiste Bouillaud

Jean-Baptiste Bouillaud

Towards the late 19th century, the belief that the size of ones skull could determine their level of intelligence was discarded as science and medicine moved forward. A physician by the name of Jean-Baptiste Bouillaud expanded upon the ideas of Gall and took a closer look at the idea of distinct cortical regions of the brain each having their own independent function. Bouillaud was specifically interested in speech and wrote many publications on the anterior region of the brain being responsible for carrying out the act of ones speech, a discovery that had stemmed from the research of Gall. He was also one of the first to use larger samples for research although it took many years for that method to be accepted. By looking at over a hundred different case studies, Bouillaud came to discover that it was through different areas of the brain that speech is completed and understood. By observing people with brain damage, his theory was made more concrete. Bouillaud, along with many other pioneers of the time made great advances within the field of neurology, especially when it came to localization of function. There are many arguable debates as to who deserves the most credit for such discoveries, and often, people remain unmentioned, but Paul Broca is perhaps one of the most famous and well known contributors to neuropsychology – often referred to as "the father" of the discipline.

Paul Broca

Inspired by the advances being made in the area of localized function within the brain, Paul Broca committed much of his study to the phenomena of how speech is understood and produced. Through his study, it was discovered and expanded upon that we articulate via the left hemisphere. Broca's observations and methods are widely considered to be where neuropsychology really takes form as a recognizable and respected discipline. Armed with the understanding that specific, independent areas of the brain are responsible for articulation and understanding of speech, the brains abilities were finally being acknowledged as the complex and highly intricate organ that it is. Broca was essentially the first to fully break away from the ideas of phrenology and delve deeper into a more scientific and psychological view of the brain.

Karl Spencer Lashley

Lashley's works and theories that follow are summarized in his book Brain Mechanisms and Intelligence. Lashley's theory of the Engram was the driving force for much of his research. An engram was believed to be a part of the brain where a specific memory was stored. He continued to use the training/ablation method that Franz had taught him. He would train a rat to learn a maze and then use systematic lesions and removed sections of cortical tissue to see if the rat forgot what it had learned.

Through his research with the rats, he learned that forgetting was dependent on the amount of tissue removed and not where it was removed from. He called this mass action and he believed that it was a general rule that governed how brain tissue would respond, independent of the type of learning. But we know now that mass action was a misinterpretation of his empirical results, because in order to run a maze the rats required multiple cortical areas. Cutting into small individual parts alone will not impair the rats' brains much, but taking large sections removes multiple cortical areas at one time, affecting various functions such as sight, motor coordination and memory, making the animal unable to run a maze properly.

Lashley also proposed that a portion of a functional area could carry out the role of the entire area, even when the rest of the area has been removed. He called this phenomenon equipotentiality. We know now that he was seeing evidence of plasticity in the brain: within certain constraints the brain has the ability for certain areas to take over the functions of other areas if those areas should fail or be removed - although not to the extent initially argued by Lashley.

Approaches

Experimental neuropsychology is an approach that uses methods from experimental psychology to uncover the relationship between the nervous system and cognitive function. The majority of work involves studying healthy humans in a laboratory setting, although a minority of researchers may conduct animal experiments. Human work in this area often takes advantage of specific features of our nervous system (for example that visual information presented to a specific visual field is preferentially processed by the cortical hemisphere on the opposite side) to make links between neuroanatomy and psychological function.

Clinical neuropsychology is the application of neuropsychological knowledge to the assessment (see neuropsychological test and neuropsychological assessment), management, and rehabilitation of people who have suffered illness or injury (particularly to the brain) which has caused neurocognitive problems. In particular they bring a psychological viewpoint to treatment, to understand how such illness and injury may affect and be affected by psychological factors. They also can offer an opinion as to whether a person is demonstrating difficulties due to brain pathology or as a consequence of an emotional or another (potentially) reversible cause or both. For example, a test might show that both patients X and Y are unable to name items that they have been previously exposed to within the past 20 minutes (indicating possible dementia). If patient Y can name some of them with further prompting (e.g. given a categorical clue such as being told that the item they could not name is a fruit), this allows a more specific diagnosis than simply dementia (Y appears to have the vascular type which is due to brain pathology but is usually at least somewhat reversible). Clinical neuropsychologists often work in hospital settings in an interdisciplinary medical team; others work in private practice and may provide expert input into medico-legal proceedings.

Cognitive neuropsychology is a relatively new development and has emerged as a distillation of the complementary approaches of both experimental and clinical neuropsychology. It seeks to understand the mind and brain by studying people who have suffered brain injury or neurological illness. One model of neuropsychological functioning is known as functional localization. This is based on the principle that if a specific cognitive problem can be found after an injury to a specific area of the brain, it is possible that this part of the brain is in some way involved. However, there may be reason to believe that the link between mental functions and neural regions is not so simple. An alternative model of the link between mind and brain, such as parallel processing, may have more explanatory power for the workings and dysfunction of the human brain. Yet another approach investigates how the pattern of errors produced by brain-damaged individuals can constrain our understanding of mental representations and processes without reference to the underlying neural structure. A more recent but related approach is cognitive neuropsychiatry which seeks to understand the normal function of mind and brain by studying psychiatric or mental illness.

Connectionism is the use of artificial neural networks to model specific cognitive processes using what are considered to be simplified but plausible models of how neurons operate. Once trained to perform a specific cognitive task these networks are often damaged or 'lesioned' to simulate brain injury or impairment in an attempt to understand and compare the results to the effects of brain injury in humans.

Functional neuroimaging uses specific neuroimaging technologies to take readings from the brain, usually when a person is doing a particular task, in an attempt to understand how the activation of particular brain areas is related to the task. In particular, the growth of methodologies to employ cognitive testing within established functional magnetic resonance imaging (fMRI) techniques to study brain-behavior relations is having a notable influence on neuropsychological research.

In practice these approaches are not mutually exclusive and most neuropsychologists select the best approach or approaches for the task to be completed.

Methods and tools

Standardized neuropsychological tests

These tasks have been designed so the performance on the task can be linked to specific neurocognitive processes. These tests are typically standardized, meaning that they have been administered to a specific group (or groups) of individuals before being used in individual clinical cases. The data resulting from standardization are known as normative data. After these data have been collected and analyzed, they are used as the comparative standard against which individual performances can be compared. Examples of neuropsychological tests include: the Wechsler Memory Scale (WMS), the Wechsler Adult Intelligence Scale (WAIS), Boston Naming Test, the Wisconsin Card Sorting Test, the Benton Visual Retention Test, and the Controlled Oral Word Association.

Brain scans

The use of brain scans to investigate the structure or function of the brain is common, either as simply a way of better assessing brain injury with high resolution pictures, or by examining the relative activations of different brain areas. Such technologies may include fMRI (functional magnetic resonance imaging) and positron emission tomography (PET), which yields data related to functioning, as well as MRI (magnetic resonance imaging) and computed axial tomography (CAT or CT), which yields structural data.

Global Brain Project

Brain models based on mouse and monkey have been developed based on theoretical neuroscience involving working memory and attention, while mapping brain activity based on time constants validated by measurements of neuronal activity in various layers of the brain. These methods also map to decision states of behavior in simple tasks that involve binary outcomes.

Electrophysiology

The use of electrophysiological measures designed to measure the activation of the brain by measuring the electrical or magnetic field produced by the nervous system. This may include electroencephalography (EEG) or magneto-encephalography (MEG).

Experimental tasks

The use of designed experimental tasks, often controlled by computer and typically measuring reaction time and accuracy on a particular tasks thought to be related to a specific neurocognitive process. An example of this is the Cambridge Neuropsychological Test Automated Battery (CANTAB) or CNS Vital Signs (CNSVS).

Hemispatial neglect

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Hemispatial_neglect 

 

Hemispatial neglect
Other names	Hemiagnosia, hemineglect, unilateral neglect, spatial neglect, contralateral neglect, unilateral visual inattention, hemi-inattention, neglect syndrome, one-side neglect, or contralateral hemispatialagnosia
Hemispatial neglect is most frequently associated with a lesion of the right parietal lobe (in yellow, at top).
Specialty	Psychiatry, Neurology

Hemispatial neglect is a neuropsychological condition in which, after damage to one hemisphere of the brain is sustained, a deficit in attention to and awareness of one side of the field of vision is observed. It is defined by the inability of a person to process and perceive stimuli on one side of the body or environment, where that inability is not due to a lack of sensation. Hemispatial neglect is very commonly contralateral to the damaged hemisphere, but instances of ipsilesional neglect (on the same side as the lesion) have been reported.

Presentation

Hemispatial neglect results most commonly from strokes and brain unilateral injury to the right cerebral hemisphere, with rates in the critical stage of up to 80% causing visual neglect of the left-hand side of space. Neglect is often produced by massive strokes in the middle cerebral artery region and is variegated, so that most sufferers do not exhibit all of the syndrome's traits. Right-sided spatial neglect is rare because there is redundant processing of the right space by both the left and right cerebral hemispheres, whereas in most left-dominant brains the left space is only processed by the right cerebral hemisphere. Although it most strikingly affects visual perception ('visual neglect'), neglect in other forms of perception can also be found, either alone or in combination with visual neglect.

For example, a stroke affecting the right parietal lobe of the brain can lead to neglect for the left side of the visual field, causing a patient with neglect to behave as if the left side of sensory space is nonexistent (although they can still turn left). In an extreme case, a patient with neglect might fail to eat the food on the left half of their plate, even though they complain of being hungry. If someone with neglect is asked to draw a clock, their drawing might show only the numbers 12 to 6, or all 12 numbers might be on one half of the clock face with the other half distorted or blank. Neglect patients may also ignore the contralesional side of their body; for instance, they might only shave, or apply make-up to, the non-neglected side. These patients may frequently collide with objects or structures such as door frames on the side being neglected.

Neglect may also present as a delusional form, where the patient denies ownership of a limb or an entire side of the body. Since this delusion often occurs alone, without the accompaniment of other delusions, it is often labeled as a monothematic delusion.

Neglect not only affects present sensation but memory and recall perception as well. A patient suffering from neglect may also, when asked to recall a memory of a certain object and then draw said object, draw only half of the object. It is unclear, however, if this is due to a perceptive deficit of the memory (to the patient having lost pieces of spatial information of the memory) or whether the information within the memory is whole and intact but simply being ignored, the same way portions of a physical object in the patient's presence would be ignored.

Some forms of neglect may also be very mild—for example, in a condition called extinction where competition from the ipsilesional stimulus impedes perception of the contralesional stimulus. These patients, when asked to fixate on the examiner's nose, can detect fingers being wiggled on the affected side. If the examiner were to wiggle his or her fingers on both the affected and unaffected sides of the patient, the patient will report seeing movement only on the ipsilesional side.

Sequelae

Though frequently underappreciated, unilateral neglect can have dramatic consequences. It has more negative effect on functional ability, as measured by the Barthel ADL index, than age, sex, power, side of stroke, balance, proprioception, cognition, or premorbid ADL status. Its presence within the first 10 days of a stroke is a stronger predictor of poor functional recovery after one year than several other variables, including hemiparesis, hemianopsia, age, visual memory, verbal memory, or visuoconstructional ability. Neglect is likely among the reasons that patients with right hemisphere damage are twice as likely to fall as those with left brain damage. Patients with neglect rehabilitate longer and make less daily progress than other patients with similar functional status. And patients with neglect are less likely to live independently than even patients who have both severe aphasia and right hemiparesis.

Causes

Brain areas in the parietal and frontal lobes are associated with the deployment of attention (internally, or through eye movements, head turns or limb reaches) into contralateral space. Neglect is most closely related to damage to the temporo-parietal junction and posterior parietal cortex. The lack of attention to the left side of space can manifest in the visual, auditory, proprioceptive, and olfactory domains. Although hemispatial neglect often manifests as a sensory deficit (and is frequently co-morbid with sensory deficit), it is essentially a failure to pay sufficient attention to sensory input.

Although hemispatial neglect has been identified following left hemisphere damage (resulting in the neglect of the right side of space), it is most common after damage to the right hemisphere. This disparity is thought to reflect the fact that the right hemisphere of the brain is specialized for spatial perception and memory, whereas the left hemisphere is specialized for language - there is redundant processing of the right visual fields by both hemispheres. Hence the right hemisphere is able to compensate for the loss of left hemisphere function, but not vice versa. Neglect is not to be confused with hemianopsia. Hemianopsia arises from damage to the primary visual pathways cutting off the input to the cerebral hemispheres from the retinas. Neglect is damage to the processing areas. The cerebral hemispheres receive the input, but there is an error in the processing that is not well understood.

Theories of mechanism

Researchers have argued whether neglect is a disorder of spatial attention or spatial representation.

Spatial attention

Spatial attention is the process where objects in one location are chosen for processing over objects in another location. This would imply that neglect is more intentional. The patient has an affinity to direct attention to the unaffected side. Neglect is caused by a decrease in stimuli in the contralesional side because of a lack of ipsilesional stimulation of the visual cortex and an increased inhibition of the contralesional side. In this theory neglect is seen as disorder of attention and orientation caused by disruption of the visual cortex. Patients with this disorder will direct attention and movements to the ipsilesional side and neglect stimuli in the contralesional side despite having preserved visual fields. The result of all of this is an increased sensitivity of visual performance in the unaffected side. The patient shows an affinity to the ipsilesional side being unable to disengage attention from that side.

Spatial representation

Spatial representation is the way space is represented in the brain. In this theory it is believed that the underlying cause of neglect is the inability to form contralateral representations of space. In this theory neglect patients demonstrate a failure to describe the contralesional side of a familiar scene, from a given point, from memory. 

To support this theory, evidence from Bisiach and Luzzatti's study of Piazza del Duomo can be considered. For the study, patients with hemispatial neglect, that were also familiar with the layout of the Piazza del Duomo square, were observed. The patients were asked to imagine themselves at various vantage points in the square, without physically being in the square. They were then asked to describe different landmarks around the square, such as stores. At each separate vantage point, patients consistently only described landmarks on the right side, ignoring the left side of the representation. However, the results of their multiple descriptions at the different vantage points showed that they knew information around the entire square, but could only identify the right side of the represented field at any given vantage point.When asked to switch vantage points so that the scene that was on the contralesional side is now on the ipsilesional side the patient was able to describe with details the scene they had earlier neglected.

The same patterns can be found with comparing actual visual stimuli to imaging in the brain (Rossetti et al., 2010). A neglect patient who was very familiar with the map of France was asked to name French towns on a map of the country, both by a mental image of the map and by a physical image of the map. The image was then rotated 180 degrees, both mentally and physically. With the mental image, the neglect stayed consistent with the image; that is, when the map was in its original orientation, the patient named towns mostly on the East side of France, and when they mentally rotated the map they named towns mostly on the West side of France because the West coast was now on the right side of the represented field. However, with the physical copy of the map, the patient's focus was on the East side of France with either orientation. This leads researchers to believe that neglect for images in memory may be disassociated from the neglect of stimuli in extrapersonal space. In this case patients have no loss of memory making their neglect a disorder of spatial representation which is the ability to reconstruct spatial frames in which the spatial relationship of objects, that may be perceived, imagined or remembered, with respect to the subject and each other are organized to be correctly acted on.

This theory can also be supported by neglect in dreams (Figliozzi et al., 2007). The study was run on a neglect patient by tracking his eye movements while he slept, during the REM cycle. Results showed that the majority of the eye movements were aimed to his right side, indicating that the images represented in his dreams were also affected by hemispatial neglect.

Another example would be a left neglect patient failing to describe left turns while describing a familiar route. This shows that the failure to describe things in the contralesional side can also affect verbal items. These findings show that space representation is more topological than symbolic. Patients show a contralesional loss of space representation with a deviation of spatial reference to the ipsilesional side. In these cases we see a left-right dissimilarity of representation rather than a decline of representational competence.

Diagnosis

In order to assess not only the type but also the severity of neglect, doctors employ a variety of tests, most of which are carried out at the patient's bedside. Perhaps one of the most-used and quickest is the line bisection. In this test, a line a few inches long is drawn on a piece of paper and the patient is then asked to dissect the line at the midpoint. Patients exhibiting, for example, left-sided neglect will exhibit a rightward deviation of the line's true midpoint. Another widely used test is the line cancellation test. Here a patient is presented with a piece of paper that has various lines scattered across it and is asked to mark each of the lines. Patients who exhibit left-sided neglect will completely ignore all lines on the left side of the paper. Visual neglect can also be assessed by having the patient draw a copy of a picture with which they are presented. If the patient is asked to draw a complex picture they may neglect the entire contralesional side of the picture. If asked to draw an individual object, the patient will not draw the contralesional side of that object. A patient may also be asked to read a page out of a book. The patient will be unable to orient their eyes to the left margin and will begin reading the page from the center. Presenting a single word to a patient will result in the patient either reading only the ipsilesional part of the word or replacing the part they cannot see with a logical substitute. For example, if they are presented with the word "peanut", they may read "nut" or say "walnut".

Varieties

Neglect is a heterogenous disorder that manifests itself radically differently in different patients. No single mechanism can account for these different manifestations. A vast array of impaired mechanisms are found in neglect. These mechanisms alone would not cause neglect. The complexity of attention alone—just one of several mechanisms that may interact—has generated multiple competing hypothetical explanations of neglect. So it is not surprising that it has proven difficult to assign particular presentations of neglect to specific neuroanatomical loci. Despite such limitations, we may loosely describe unilateral neglect with four overlapping variables: type, range, axis, and orientation.

Type

Types of hemispatial neglect are broadly divided into disorders of input and disorders of output. The neglect of input, or "inattention", includes ignoring contralesional sights, sounds, smells, or tactile stimuli. Surprisingly, this inattention can even apply to imagined stimuli. In what's termed "representational neglect", patients may ignore the left side of memories, dreams, and hallucinations.

Output neglect includes motor and pre-motor deficits. A patient with motor neglect does not use a contralesional limb despite the neuromuscular ability to do so. One with pre-motor neglect, or directional hypokinesia, can move unaffected limbs ably in ipsilateral space but have difficulty directing them into contralesional space. Thus a patient with pre-motor neglect may struggle to grasp an object on the left side even when using the unaffected right arm.

Range

Hemispatial neglect can have a wide range in terms of what the patient neglects. The first range of neglect, commonly referred to as "egocentric" neglect, is found in patients who neglect their own body or personal space. These patients tend to neglect the opposite side of their lesion, based on the midline of the body, head, or retina. For example, in a gap detection test, subjects with egocentric hemispatial neglect on the right side often make errors on the far right side of the page, as they are neglecting the space in their right visual field.

The next range of neglect is "allocentric" neglect, where individuals neglect either their peri-personal or extrapersonal space. Peri-personal space refers to the space within the patient's normal reach, whereas extrapersonal space refers to the objects/environment beyond the body's current contact or reaching ability. Patients with allocentric neglect tend to neglect the contralesional side of individual items, regardless of where they appear with respect to the viewer. For example, In the same gap detection test mentioned above, subjects with allocentric hemispatial neglect on the right side will make errors on all areas of the page, specifically neglecting the right side of each individual item.

This differentiation is significant because the majority of assessment measures test only for neglect within the reaching, or peri-personal, range. But a patient who passes a standard paper-and-pencil test of neglect may nonetheless ignore a left arm or not notice distant objects on the left side of the room.

In cases of somatoparaphrenia, which may be caused by personal neglect, patients deny ownership of contralesional limbs. Sacks (1985) described a patient who fell out of bed after pushing out what he perceived to be the severed leg of a cadaver that the staff had hidden under his blanket. Patients may say things like, "I don't know whose hand that is, but they'd better get my ring off!" or, "This is a fake arm someone put on me. I sent my daughter to find my real one."

Axis

Most tests for neglect look for rightward or leftward errors. But patients may also neglect stimuli on one side of a horizontal or radial axis. For example, when asked to circle all the stars on a printed page, they may locate targets on both the left and right sides of the page while ignoring those across the top or bottom.

In a recent study, researchers asked patients with left neglect to project their midline with a neon bulb and found that they tended to point it straight ahead but position it rightward of their true midline. This shift may account for the success of therapeutic prism glasses, which shift left visual space toward the right. By shifting visual input, they seem to correct the mind's sense of midline. The result is not only the amelioration of visual neglect, but also of tactile, motor, and even representational neglect.

Orientation

An important question in studies of neglect has been: "left of what?" That is to say, what frame of reference does a subject adopt when neglecting the left half of his or her visual, auditory, or tactile field? The answer has proven complex. It turns out that subjects may neglect objects to the left of their own midline (egocentric neglect) or may instead see all the objects in a room but neglect the left half of each individual object (allocentric neglect).

These two broad categories may be further subdivided. Patients with egocentric neglect may ignore the stimuli leftward of their trunks, their heads, or their retinae. Those with allocentric neglect may neglect the true left of a presented object, or may first correct in their mind's eye a slanted or inverted object and then neglect the side then interpreted as being on the left. So, for example, if patients are presented with an upside-down photograph of a face, they may mentally flip the object right side up and then neglect the left side of the adjusted image. In another example, if patients are presented with a barbell, patients will more significantly neglect the left side of the barbell, as expected with right temporal lobe lesion. If the barbell is rotated such that the left side is now on the right side, patients will more significantly neglect the left side of the object, even though it is now on the right side of space. This also occurs with slanted or mirror-image presentations. A patient looking at a mirror image of a map of the World may neglect to see the Western Hemisphere despite their inverted placement onto the right side of the map.

Various neuropsychological research studies have considered the role of frame of reference in hemispatial neglect, offering new evidence to support both allocentric and egocentric neglect. To begin, one study conducted by Dongyun Li, Hans-Otto Karnath, and Christopher Rorden examined whether allocentric neglect varies with egocentric position. This experimental design consisted of testing eleven right hemispheric stroke patients. Five of these patients showed spatial neglect on their contralesional side, while the remaining six patients showed no spatial neglect. During the study, the patients were presented with two arrays of seven triangles. The first array ran from southwest to northeast (SW-NE) and the second array ran from southeast to northwest (SE-NW). In a portion of the experimental trials, the middle triangle in the array contained a gap along one side. Participants were tested on their ability to perceive the presence of this gap, and were instructed to press one response button if the gap was present and a second response button if the gap was absent.

To test the neglect frame of reference, the two different arrays were carefully situated so that gap in the triangle fell on opposite sides of the allocentric field. In the SW-NE array, the gap in the triangle fell on the allocentric right of the object-centered axis along which the triangle pointed. In the SE-NW configuration, the gap in the triangle fell on the allocentric left of the object-centered axis. Furthermore, varying the position of the arrays with respect to the participant's trunk midline was used to test egocentric neglect. The arrays were therefore presented at 0° (i.e. in line with the participant's trunk midline), at −40° left, and at +40° right. Ultimately, varying the position of the array within the testing visual field allowed for the simultaneous measurement of egocentric neglect and allocentric neglect. The results of this experimental design showed that the spatial neglect patients performed more poorly for the allocentric left side of the triangle, as well as for objects presented on the egocentric left side of the body. Furthermore, the poor accuracy for detecting features of the object on the left side of the object's axis was more severe when the objects were presented on the contralesional side of the body. Thus, these findings illustrate that both allocentric and egocentric biases are present simultaneously, and that egocentric information can influence the severity of allocentric neglect.

A second study, conducted by Moscovitch and Behrmann, investigated the reference frame of neglect with respect to the somatosensory system. Eleven patients with parietal lobe lesions and subsequent hemispatial neglect were analyzed during this experiment. A double simultaneous stimulation procedure was utilized, during which the patients were touched lightly and simultaneously on the left and right side of the wrist of one hand. The patients were tested both with their palms facing down and with their palms facing up. This experimental condition allowed the scientists to determine whether neglect in the somatosensory system occurs with respect to the sensory receptor surface (egocentric) or with respect to a higher-order spatial frame of reference (allocentric). The results of this experiment showed the hemispatial neglect patients neglected somatosensory stimuli on the contralesional side of space, regardless of hand orientation. These findings suggest that, within the somatosensory system, stimuli are neglected with respect to the allocentric, spatial frame of reference, in addition to an egocentric, sensory frame of reference. Ultimately, the discoveries made by these experiments indicate that hemispatial neglect occurs with respect to multiple, simultaneously derived frames of reference, which dictate the nature and extent of neglect within the visual, auditory, and tactile fields.

Treatment

Treatment consists of finding ways to bring the patient's attention toward the left, usually done incrementally, by going just a few degrees past midline, and progressing from there. Rehabilitation of neglect is often carried out by neuropsychologists, occupational therapist, speech-language pathologists, neurologic music therapists, physical therapists, optometrists, and orthoptists.

Forms of treatment that have been tested with variable reports of success include prismatic adaptation, where a prism lens is worn to pull the vision of the patient towards the left, constrained movement therapy where the "good" limb is constrained in a sling to encourage use of the contralesional limb. Eye-patching has similarly been used, placing a patch over the "good" eye. Pharmaceutical treatments have mostly focused on dopaminergic therapies such as bromocriptine, levodopa, and amphetamines, though these tests have had mixed results, helping in some cases and accentuating hemispatial neglect in others. Caloric vestibular stimulation (CVS) has been shown to bring about a brief remission in some cases. however this technique has been known to elicit unpleasant side-effects such as nystagmus, vertigo and vomiting. A study done by Schindler and colleagues examined the use of neck muscle vibration on the contralesional posterior neck muscles to induce diversion of gaze from the subjective straight ahead. Subjects received 15 consecutive treatment sessions and were evaluated on different aspects of the neglect disorder including perception of midline, and scanning deficits. The study found that there is evidence that neck muscle stimulation may work, especially if combined with visual scanning techniques. The improvement was evident 2 months after the completion of treatment.

Other areas of emerging treatment options include the use of prisms, visual scanning training, mental imagery training, video feedback training, trunk rotation, galvanic vestibular stimulation (GVS), transcranial magnetic stimulation (TMS) and transcranial direct-current stimulation (tDCS). Of these emerging treatment options, the most studied intervention is prism adaptation and there is evidence of relatively long-term functional gains from comparatively short-term usage. However, all of these treatment interventions (particularly the stimulation techniques) are relatively new and randomised, controlled trial evidence is still limited. Further research is mandatory in this field of research in order to provide more support in evidence-based practice.

In a review article by Pierce & Buxbaum (2002), they concluded that the evidence for Hemispheric Activation Approaches, which focuses on moving the limb on the side of the neglect, has conflicting evidence in the literature. The authors note that a possible limitation in this approach is the requirement for the patients to actively move the neglected limb, which may not be possible for many patients. Constraint-Induced Therapy (CIT), appears to be an effective, long-term treatment for improving neglect in various studies. However, the use of CIT is limited to patients who have active control of wrist and hand extension. Prism Glasses, Hemispatial Glasses, and Eye-Patching have all appear to be effective in improving performance on neglect tests. Caloric Stimulation treatment appears to be effective in improving neglect; however, the effects are generally short-term. The review also suggests that Optokinetic Stimulation is effective in improving position sense, motor skills, body orientation, and perceptual neglect on a short-term basis. As with Caloric Stimulation treatment, long-term studies will be necessary to show its effectiveness. A few Trunk Rotation Therapy studies suggest its effectiveness in improving performance on neglect tests as well as the Functional Independence Measure (FIM). Some less studied treatment possibilities include treatments that target Dorsal Stream of visual processing, Mental Imagery Training, and Neck Vibration Therapy. Trunk rotation therapies aimed at improving postural disorders and balance deficits in patients with unilateral neglect, have demonstrated optimistic results in regaining voluntary trunk control when using specific postural rehabilitative devices. One such device is the Bon Saint Côme apparatus, which uses spatial exploratory tasks in combination with auditory and visual feedback mechanisms to develop trunk control. The Bon Saint Côme device has been shown to be effective with hemiplegic subjects due to the combination of trunk stability exercises, along with the cognitive requirements needed to perform the postural tasks.

Anosognosia

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Anosognosia 

 

Anosognosia
Pronunciation	/æˌnɒsɒɡˈnoʊziə/, /æˌnɒsɒɡˈnoʊʒə/
Specialty	Psychiatry, Neurology

Anosognosia is a deficit of self-awareness, a condition in which a person with a disability is unaware of having it. It was first named by the neurologist Joseph Babinski in 1914. Anosognosia results from physiological damage to brain structures, typically to the parietal lobe or a diffuse lesion on the fronto-temporal-parietal area in the right hemisphere, and is thus a neuropsychiatric disorder. Phenomenologically, anosognosia has similarities to denial, which is a psychological defense mechanism; attempts have been made at a unified explanation. Anosognosia is sometimes accompanied by asomatognosia, a form of neglect in which patients deny ownership of body parts such as their limbs. The term is from Ancient Greek ἀ- a-, "without", νόσος nosos, "disease" and γνῶσις gnōsis, "knowledge".

Causes

Relatively little has been discovered about the cause of the condition since its initial identification. Recent studies from the empirical data are prone to consider anosognosia a multi-componential syndrome or multi-faceted phenomenon. That is it can be manifested by failure to be aware of a number of specific deficits, including motor (hemiplegia), sensory (hemianaesthesia, hemianopia), spatial (unilateral neglect), memory (dementia), and language (receptive aphasia) due to impairment of anatomo-functionally discrete monitoring systems.

Anosognosia is relatively common following different causes of brain injury, such as stroke and traumatic brain injury; for example, anosognosia for hemiparesis (weakness of one side of the body) with onset of acute stroke is estimated at between 10% and 18%. However, it can appear to occur in conjunction with virtually any neurological impairment. It is more frequent in the acute than in the chronic phase and more prominent for assessment in the cases with right hemispheric lesions than with the left. Anosognosia is not related to global mental confusion, cognitive flexibility, other major intellectual disturbances, or mere sensory/perceptual deficits. 

The condition does not seem to be directly related to sensory loss but is thought to be caused by damage to higher level neurocognitive processes that are involved in integrating sensory information with processes that support spatial or bodily representations (including the somatosensory system). Anosognosia is thought to be related to unilateral neglect, a condition often found after damage to the non-dominant (usually the right) hemisphere of the cerebral cortex in which people seem unable to attend to, or sometimes comprehend, anything on a certain side of their body (usually the left). 

Anosognosia can be selective in that an affected person with multiple impairments may seem unaware of only one handicap, while appearing to be fully aware of any others. This is consistent with the idea that the source of the problem relates to spatial representation of the body. For example, anosognosia for hemiplegia may occur with or without intact awareness of visuo-spatial unilateral neglect. This phenomenon of double dissociation can be an indicator of domain-specific disorders of awareness modules, meaning that in anosognosia, brain damage can selectively impact the self-monitoring process of one specific physical or cognitive function rather than a spatial location of the body.

There are also studies showing that the maneuver of vestibular stimulation could temporarily improve both the syndrome of spatial unilateral neglect and of anosognosia for left hemiplegia. Combining the findings of hemispheric asymmetry to the right, association with spatial unilateral neglect, and the temporal improvement on both syndromes, it is suggested there can be a spatial component underlying the mechanism of anosognosia for motor weakness and that neural processes could be modulated similarly. There were some cases of anosognosia for right hemiplegia after left hemisphere damage, but the frequency of this type of anosognosia has not been estimated.

Those diagnosed with Alzheimer's disease often display this lack of awareness and insist that nothing is wrong with them.

Anosognosia may occur as part of receptive aphasia, a language disorder that causes poor comprehension of speech and the production of fluent but incomprehensible sentences. A patient with receptive aphasia cannot correct his own phonetics errors and shows "anger and disappointment with the person with whom s/he is speaking because that person fails to understand her/him". This may be a result of brain damage to the posterior portion of the superior temporal gyrus, believed to contain representations of word sounds. With those representations significantly distorted, patients with receptive aphasia are unable to monitor their mistakes. Other patients with receptive aphasia are fully aware of their condition and speech inhibitions, but cannot monitor their condition, which is not the same as anosognosia and therefore cannot explain the occurrence of neologistic jargon.

Psychiatry

Although largely used to describe unawareness of impairment after brain injury or stroke, the term 'anosognosia' is occasionally used to describe the lack of insight shown by some people with anorexia nervosa. They do not seem to recognize that they have a mental illness. There is evidence that 'anosognosia' related to schizophrenia may be the result of frontal lobe damage. E. Fuller Torrey, a psychiatrist and schizophrenia researcher, has stated that among those with schizophrenia and bipolar disorder, anosognosia is the most prevalent reason for not taking medications.

Diagnosis

Clinically, anosognosia is often assessed by giving patients an anosognosia questionnaire in order to assess their metacognitive knowledge of deficits. However, neither of the existing questionnaires applied in the clinics are designed thoroughly for evaluating the multidimensional nature of this clinical phenomenon; nor are the responses obtained via offline questionnaire capable of revealing the discrepancy of awareness observed from their online task performance. The discrepancy is noticed when patients showed no awareness of their deficits from the offline responses to the questionnaire but demonstrated reluctance or verbal circumlocution when asked to perform an online task. For example, patients with anosognosia for hemiplegia may find excuses not to perform a bimanual task even though they do not admit it is because of their paralyzed arms.

A similar situation can happen on patients with anosognosia for cognitive deficits after traumatic brain injury when monitoring their errors during the tasks regarding their memory and attention (online emergent awareness) and when predicting their performance right before the same tasks (online anticipatory awareness). It can also occur among patients with dementia and anosognosia for memory deficit when prompted with dementia-related words, showing possible pre-attentive processing and implicit knowledge of their memory problems. Patients with anosognosia may also overestimate their performance when asked in first-person formed questions but not from a third-person perspective when the questions referring to others.

When assessing the causes of anosognosia within stroke patients, CT scans have been used to assess where the greatest amount of damage is found within the various areas of the brain. Stroke patients with mild and severe levels of anosognosia (determined by response to an anosognosia questionnaire) have been linked to lesions within the temporoparietal and thalamic regions, when compared to those who experience moderate anosognosia, or none at all. In contrast, after a stroke, people with moderate anosognosia have a higher frequency of lesions involving the basal ganglia, compared to those with mild or severe anosognosia.

Treatment

In regard to anosognosia for neurological patients, no long-term treatments exist. As with unilateral neglect, caloric reflex testing (squirting ice cold water into the left ear) is known to temporarily ameliorate unawareness of impairment. It is not entirely clear how this works, although it is thought that the unconscious shift of attention or focus caused by the intense stimulation of the vestibular system temporarily influences awareness. Most cases of anosognosia appear to simply disappear over time, while other cases can last indefinitely. Normally, long-term cases are treated with cognitive therapy to train patients to adjust for their inoperable limbs (though it is believed that these patients still are not "aware" of their disability). Another commonly used method is the use of feedback – comparing clients' self-predicted performance with their actual performance on a task in an attempt to improve insight.

Neurorehabilitation is difficult because, as anosognosia impairs the patient's desire to seek medical aid, it may also impair their ability to seek rehabilitation. A lack of awareness of the deficit makes cooperative, mindful work with a therapist difficult. In the acute phase, very little can be done to improve their awareness, but during this time, it is important for the therapist to build a therapeutic alliance with patients by entering their phenomenological field and reducing their frustration and confusion. Since severity changes over time, no single method of treatment or rehabilitation has emerged or will likely emerge.

In regard to psychiatric patients, empirical studies verify that, for individuals with severe mental illnesses, lack of awareness of illness is significantly associated with both medication non-compliance and re-hospitalization. Fifteen percent of individuals with severe mental illnesses who refuse to take medication voluntarily under any circumstances may require some form of coercion to remain compliant because of anosognosia. Coercive psychiatric treatment is a delicate and complex legal and ethical issue. 

One study of voluntary and involuntary inpatients confirmed that committed patients require coercive treatment because they fail to recognize their need for care. The patients committed to the hospital had significantly lower measures of insight than the voluntary patients.

Anosognosia is also closely related to other cognitive dysfunctions that may impair the capacity of an individual to continuously participate in treatment. Other research has suggested that attitudes toward treatment can improve after involuntary treatment and that previously committed patients tend later to seek voluntary treatment.

Cotard delusion

From Wikipedia, the free encyclopedia

 https://en.wikipedia.org/wiki/Cotard_delusion

 

Cotard's delusion
Other names	Cotard's syndrome, Walking Corpse Syndrome
The neurologist Jules Cotard (1840–89) described "The Delirium of Negation" as a mental illness of varied severity.
Specialty	Psychiatry

Cotard's delusion, also known as walking corpse syndrome or Cotard's syndrome, is a rare mental disorder in which the affected person holds the delusional belief that they are dead, do not exist, are putrefying, or have lost their blood or internal organs. Statistical analysis of a hundred-patient cohort indicated that denial of self-existence is present in 45% of the cases of Cotard's syndrome; the other 55% of the patients presented with delusions of immortality.

In 1880, the neurologist Jules Cotard described the condition as Le délire des négations ("The Delirium of Negation"), a psychiatric syndrome of varied severity. A mild case is characterized by despair and self-loathing, while a severe case is characterized by intense delusions of negation and chronic psychiatric depression.

The case of Mademoiselle X describes a woman who denied the existence of parts of her body and of her need to eat. She said that she was condemned to eternal damnation and therefore could not die a natural death. In the course of suffering "The Delirium of Negation", Mademoiselle X died of starvation.

Cotard's delusion is not mentioned in either the Diagnostic and Statistical Manual of Mental Disorders (DSM) or the tenth edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) of the World Health Organization.

Signs and symptoms

Delusions of negation are the central symptom in Cotard's syndrome. The patient usually denies their own existence, the existence of a certain body part, or the existence of a portion of their body. Cotard's syndrome exists in three stages: (i) Germination stage: symptoms of psychotic depression and of hypochondria appear; (ii) Blooming stage: full development of the syndrome and delusions of negation; and (iii) Chronic stage: continued severe delusions along with chronic psychiatric depression.

Cotard's syndrome withdraws the afflicted person from other people due to neglect of their personal hygiene and physical health. Delusions of negation of self prevent the patient from making sense of external reality, which then produces a distorted view of the external world. Such delusions of negation are usually found in schizophrenia. Although a diagnosis of Cotard's syndrome does not require the patient's having had hallucinations, the strong delusions of negation are comparable to those found in schizophrenic patients.

Distorted reality

The article Betwixt Life and Death: Case Studies of the Cotard Delusion (1996) describes a contemporary case of Cotard's delusion which occurred in a Scotsman whose brain was damaged in a motorcycle accident:

[The patient's] symptoms occurred in the context of more general feelings of unreality and [of] being dead. In January 1990, after his discharge from hospital in Edinburgh, his mother took him to South Africa. He was convinced that he had been taken to Hell (which was confirmed by the heat) and that he had died of sepsis (which had been a risk early in his recovery), or perhaps from AIDS (he had read a story in The Scotsman about someone with AIDS who died from sepsis), or from an overdose of a yellow fever injection. He thought he had "borrowed [his] mother's spirit to show [him] around Hell" and that she was asleep in Scotland.

The article Recurrent Postictal Depression with Cotard Delusion (2005) describes the case of a fourteen-year-old epileptic boy who experienced Cotard syndrome after seizures. His mental health history was of a boy expressing themes of death, chronic sadness, decreased physical activity in playtime, social withdrawal, and disturbed biological functions.

About twice a year, the boy suffered episodes that lasted between three weeks and three months. In the course of each episode, he said that everyone and everything was dead (including trees), described himself as a dead body, and warned that the world would be destroyed within hours. Throughout the episode the boy showed no response to pleasurable stimuli and had no interest in social activities.

Pathophysiology

Neural misfiring in the fusiform face area, in the fusiform gyrus (orange), might be a cause of the Cotard delusion.

 

In the cerebrum, organic lesions in the parietal lobe might cause the Cotard delusion.

The underlying neurophysiology and psychopathology of Cotard syndrome might be related to problems of delusional misidentification. Neurologically, Cotard's delusion (negation of the Self) is thought to be related to Capgras delusion (people replaced by impostors); each type of delusion is thought to result from neural misfiring in the fusiform face area of the brain, which recognizes faces, and in the amygdalae, which associate emotions to a recognized face.

The neural disconnection creates in the patient a sense that the face they are observing is not the face of the person to whom it belongs; therefore, that face lacks the familiarity (recognition) normally associated with it. This results in derealization or a disconnection from the environment. If the observed face is that of a person known to the patient, they experience that face as the face of an impostor (Capgras delusion). If the patient sees their own face, they might perceive no association between the face and their own sense of self—which results in the patient believing that they do not exist (Cotard delusion).

Cotard's syndrome is usually encountered in people afflicted with psychosis, as in schizophrenia. It is also found in clinical depression, derealization, brain tumor, and migraine headaches. The medical literature indicate that the occurrence of Cotard's delusion is associated with lesions in the parietal lobe. As such, the Cotard's delusion patient presents a greater incidence of brain atrophy—especially of the median frontal lobe—than do people in control groups.

Cotard's delusion also has resulted from a patient's adverse physiological response to a drug (e.g., acyclovir) and to its prodrug precursor (e.g., valaciclovir). The occurrence of Cotard's delusion symptoms was associated with a high serum-concentration of 9-carboxymethoxymethylguanine (CMMG), the principal metabolite of acyclovir.

As such, the patient with weak kidneys (impaired renal function) continued risking the occurrence of delusional symptoms despite the reduction of the dose of acyclovir. Hemodialysis resolved the patient's delusions (of negating the self) within hours of treatment, which suggests that the occurrence of Cotard's delusion symptoms might not always be cause for psychiatric hospitalization of the patient.

Diagnosis

According to the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition), Cotard's delusion falls under the category of somatic delusions, those that involve bodily functions or sensations.

There are no further diagnostic criteria for Cotard's syndrome within the DSM-5, and identification of the syndrome relies heavily on clinical interpretation.

Cotard's delusion should not be confused with delusional disorders as defined by the DSM-5, which involve a different spectrum of symptoms that are less severe and have lesser detrimental effect on functioning.

Treatment

Pharmacological treatments, both mono-therapeutic and multi-therapeutic, using antidepressants, antipsychotics, and mood stabilizers have been successful. Likewise, with the depressed patient, electroconvulsive therapy (ECT) is more effective than pharmacotherapy.

Cotard's syndrome resulting from an adverse drug reaction to valacyclovir is attributed to elevated serum concentration of one of valacyclovir's metabolites, 9-carboxymethoxymethylguanine (CMMG). Successful treatment warrants cessation of valacyclovir. Hemodialysis was associated with timely clearance of CMMG and resolution of symptoms.

Case studies

• One patient, called WI for privacy reasons, was diagnosed with Cotard's delusion after experiencing significant traumatic brain damage. Damage to the cerebral hemisphere, frontal lobe, and the ventricular system was apparent to WI's doctors after examining magnetic resonance imaging (MRI) and computed tomography (CT) scans. In January 1990, WI was discharged to outpatient care.

Although his family had made arrangements for him to travel abroad, he continued to experience significant persistent visual difficulties, which provoked a referral for ophthalmological assessment. Formal visual testing then led to the discovery of further damage. For several months after the initial trauma, WI continued to experience difficulty recognizing familiar faces, places, and objects. He was also convinced that he was dead and experienced feelings of derealization.

 

Later in 1990, after being discharged from the hospital, WI was convinced that he had gone to Hell after dying of either AIDS or sepsis. When WI finally sought out neurological testing in May 1990, he was no longer fully convinced that he was dead, although he still suspected it. Further testing revealed that WI was able to distinguish between dead and alive individuals with the exception of himself. When WI was treated for depression, his delusions of his own death diminished in a month.

• In November 2016, the Daily Mirror newspaper carried a report of Warren McKinlay of Braintree in Essex, who developed Cotard's delusion following a serious motorbike accident.