Consult Dr.Devendra Kumar MD(Homeo)
You can describe your problem in brief here:
Your Name:
Your Email Address:
Subject:
Message:
Image Verification: Please enter the text from the image: [ Refresh Image ] [ What's This? ]

Bipolar Affective Disorder:

Author: Stephen Soreff, MD, President of Education Initiatives, Nottingham, NH; Faculty, Metropolitan College of Boston University, Boston, MA
Coauthor(s): Lynne Alison McInnes, MD, Associate Adjunct Professor of Psychiatry and Genetics and Genomic Sciences, Department of Psychiatry and Human Genetics, Mount Sinai School of Medicine

Introduction
Background
Bipolar disorder, or manic-depressive illness (MDI), is one of the most common, severe, and persistent mental illnesses. Bipolar disorder is characterized by periods of deep, prolonged, and profound depression that alternate with periods of an excessively elevated and/or irritable mood known as mania. The symptoms of mania include a decreased need for sleep, pressured speech, increased libido, reckless behavior without regard for consequences, grandiosity, and severe thought disturbances, which may or may not include psychosis. Between these highs and lows, patients usually experience periods of higher functionality and can lead a productive life. Bipolar disorder is a serious lifelong struggle and challenge.1
Bipolar disorder, or manic-depressive illness, has been recognized since at least the time of Hippocrates, who described such patients as "amic" and "melancholic." In 1899, Emil Kraepelin defined manic-depressive illness and noted that persons with manic-depressive illness lacked deterioration and dementia, which he associated with schizophrenia.

Bipolar disorder constitutes one pole of a spectrum of mood disorders including bipolar I (BPI), bipolar II (BPII), cyclothymia (oscillating high and low moods), and major depression. Bipolar I disorder is also referred to as classic manic-depression, characterized by distinct episodes of major depression contrasting vividly with episodes of mania, which lead to severe impairment of function. In comparison, bipolar II disorder is a milder disorder consisting of depression alternating with periods of hypomania. Hypomania may be thought of as a less severe form of mania that does not include psychotic symptoms or lead to major impairment of social or occupational function.

For related information, see Medscape's Bipolar Disorder Resource Center.


Pathophysiology
The etiology and pathophysiology of bipolar disorder have not been determined, and no objective biological markers correspond definitively with the disease state. However, twin, family, and adoption studies all indicate that bipolar disorder has a genetic component. In fact, first-degree relatives of a person with bipolar disorder are approximately 7 times more likely to develop bipolar disorder than the rest of the population.

Bipolar disorder is a complex genetic disorder however, meaning that it is likely caused by multiple different common disease alleles, each contributing relatively low risk for the disorder on their own. It can be difficult to find such disease genes without very large sample sizes, on the order of thousands of subjects.

Fortunately, four genome-wide association studies of large samples of subjects with bipolar disorder have now been published2,3,4,5 and a collaborative analysis of the latter 3 studies give combined support for two particular genes, ANK3 (ankyrin G) and CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel) in a sample of 4,387 case and 6,209 controls.5 ANK3 is an adaptor protein found at axon initial segments that regulates the assembly of voltage-gated sodium channels and both ANK3 and subunits of the calcium channel are down-regulated in mouse brain in response to lithium, indicating a possible therapeutic mechanism of action of one of the most effective treatments for bipolar disorder.6

The first genome-wide association study of bipolar disorder used a much smaller sample size2 , an initial sample of 461 patients with bipolar disorder from the NIMH consortium and a follow-up sample of 563 patients collected in Germany, however it remains of interest in that the strongest association signals were detected in genes also involved in biochemical pathways regulated by lithium. The strongest hit was at a marker within the first intron of diacylglycerol kinase eta (DGKH) gene. DGKH is a key protein in the lithium-sensitive phosphatidyl inositol pathway.

Three of the other associated genes in this study also interact with the Wnt signaling pathway upstream and downstream of glycogen synthase kinase 3-beta (GSK3β). Lithium-mediated inhibition of GSK3β is thought to result in down-regulation of molecules involved in cell death and upregulation of neuroprotective factors (see below). Additionally, GSK3β is a central regulator of the circadian clock and lithium-mediated modulation of circadian periodicity is thought to be a critical component of its therapeutic effect. In fact, another major coup for bipolar disorder research has been the finding that a dominant-negative mutation in the CLOCK gene normally contributing to circadian periodicity in humans results in manic-like behavior in mice.7
Manic behavior in CLOCK mutant mice includes hyperactivity, decreased sleep, reduced anxiety, and an increased response to cocaine. The latter finding also provides a shared biological basis for the high rate of substance abuse observed in clinical populations of subjects with bipolar disorder. Furthermore, the experimenters were able to abolish the manic behaviors by rescuing expression of normal CLOCK specifically in the ventral tegmental area of the mouse brain. This area is rich in D2 receptors. Joseph Coyle hypothesizes in his commentary in the paper on the same issue that the efficacy of atypical antipsychotics in acute mania might, in part, be achieved by their ability to lower activity in neurons specifically within the ventral tegmental area.

Findings from gene expression studies of postmortem brain tissue from persons with bipolar disorder versus controls have yielded exciting new insights into the pathophysiology of the disorder. In particular, levels of expression of oligodendrocyte-myelin-related genes appear to be decreased in brain tissue from persons with bipolar disorder.8,9,10
Oligodendrocytes produce myelin membranes that wrap around and insulate axons to permit the efficient conduction of nerve impulses in the brain. Therefore, loss of myelin is thought to disrupt communication between neurons, leading to some of the thought disturbances observed in bipolar disorder and related illnesses. Brain imaging studies of persons with bipolar disorder also show abnormal myelination in several brain regions associated with this illness.

Interestingly, gene expression and neuroimaging studies of persons with schizophrenia and major depression also demonstrate similar findings, indicating that mood disorders and schizophrenia, may share some biological underpinnings, possibly related to psychosis. These types of data may also lead to the future revision of psychiatric diagnostic manuals based on a new understanding of the etiology of these disorders.



[#CommonGene]The national institutes of health report on recent genome-wide association studies demonstrated that bipolar disorder and schizophrenia could indeed share common susceptibility genes on chromosome 6. These genes are located in a section of the chromosome containing genes involved in immunity and controlling how and when genes turn on and off. This connection can help explain the link between environmental stress and schizophrenia and possibly bipolar disorder.11

Another approach to delineating the pathophysiology of bipolar disorder involves studying changes in gene expression induced in rodent brains after administration of pharmacologic agents used to treat bipolar disorder. For example, investigators have demonstrated that 2 chemically unrelated drugs (lithium and valproate) used to treat bipolar disorder both up-regulate the expression of the cytoprotective protein Bcl-2 in the frontal cortex and the hippocampus of rat brains. Neuroimaging studies of individuals with bipolar disorder or other mood disorders also suggest evidence of cell loss or atrophy in these same brain regions. Thus, another suggested cause of bipolar disorder is damage to cells in the critical brain circuitry that regulates emotion. According to this hypothesis, mood stabilizers and antidepressants are thought to alter mood by stimulating cell survival pathways and increasing levels of neurotrophic factors to improve cellular resiliency.

For a review of novel drugs and therapeutic targets for severe mood disorders that focus on increasing neuroplasticity and cellular resiliency please see Mathew et al, 2008.12
Post and associates proposed a mechanism involving electrophysiologic kindling and behavioral sensitization processes, a method that also resonates with the previous hypothesis based on neuronal injury. Post asserts that an individual who is susceptible to bipolar disorder experiences an increasing number of minor neurologic insults, perhaps caused by drugs of abuse, excessive glucocorticoid stimulation resulting from acute or chronic stress, or other factors, which eventually result in mania.13 Subsequently, sufficient brain damage might persist such that mania could recur even with no or minor environmental or behavioral stressors. This type of formulation helps explain the effective role of anticonvulsant medications, eg, carbamazepine and valproate, in the prevention of the highs and lows of bipolar disorder. It also supports clinical observations that the more episodes a person experiences, the more he or she will have in the future, underscoring the need for long-term treatment.


Frequency
United States
The lifelong prevalence of bipolar disorder in the United States has been noted to range from 1-1.6%. Studies indicate differences in lifetime prevalence estimates for bipolar I, bipolar II, and subthreshold bipolar disorders: 1.0% for bipolar I disorder, 1.1% for bipolar II disorder, and 2.4-4.7% for subthreshold bipolar disorders.8
International
Lifelong prevalence rate is 0.3-1.5%.

Mortality/Morbidity
Bipolar disorder has significant morbidity and mortality rates. In the United States during the early part of the 1990s, the cost of lost productivity resulting from this bipolar disorder was estimated at approximately $15.5 billion annually. Approximately 25-50% of individuals with bipolar disorder attempt suicide, and 11% actually commit suicide.

Race
No racial predilection exists. However, a point of historical interest is that clinicians often tend to consider populations of African Americans and Hispanics as more likely to be diagnosed with schizophrenia than with affective disorders and bipolar disorder.

Sex
Bipolar I disorder occurs equally in both sexes; however, rapid-cycling bipolar disorder (4 or more episodes a year) is more common in women than in men. Incidence of bipolar II disorder is higher in females than in males.

Age
The age of onset of bipolar disorder varies greatly. The age range for both bipolar I and bipolar II is from childhood to 50 years, with a mean age of approximately 21 years. Most cases commence when individuals are aged 15-19 years. The second most frequent age range of onset is 20-24 years. Some patients diagnosed with recurrent major depression may indeed have bipolar disorder and go on to develop their first manic episode when older than 50 years. They may have a family history of bipolar disorder. However, for most patients, the onset of mania in people older than 50 years should lead to an investigation for medical or neurologic disorders such as cerebrovascular disease.

Clinical
History
The diagnosis of bipolar I disorder requires the presence of a manic episode of at least 1 week's duration that leads to hospitalization or other significant impairment in occupational or social functioning. The episode of mania cannot be caused by another medical illness or by substance abuse. These criteria are based on the specifications of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR).9



•Manic episodes are characterized by the following symptoms:
◦At least 1 week of profound mood disturbance is present, characterized by elation, irritability, or expansiveness.
◦Three or more of the following symptoms are present:
■Grandiosity
■Diminished need for sleep
■Excessive talking or pressured speech
■Racing thoughts or flight of ideas
■Clear evidence of distractibility
■Increased level of goal-focused activity at home, at work, or sexually
■Excessive pleasurable activities, often with painful consequences
◦The mood disturbance is sufficient to cause impairment at work or danger to the patient or others.
◦The mood is not the result of substance abuse or a medical condition.
•Hypomanic episodes are characterized by the following:
◦The patient has an elevated, expansive, or irritable mood of at least 4 days' duration.
◦Three or more of the following symptoms are present:
■Grandiosity or inflated self-esteem
■Diminished need for sleep
■Pressured speech
■Racing thoughts or flight of ideas
■Clear evidence of distractibility
■Psychomotor agitation at home, at work, or sexually
■Engaging in activities with a high potential for painful consequences
◦The mood disturbance is observable to others.
◦The mood is not the result of substance abuse or a medical condition.
•Major depressive episodes are characterized by the following:
◦For the same 2 weeks, the person experiences 5 or more of the following symptoms, with at least 1 of them being either a depressed mood or characterized by a loss of pleasure or interest:
■Depressed mood
■Markedly diminished pleasure or interest in nearly all activities
■Significant weight loss or gain or significant loss or increase in appetite
■Hypersomnia or insomnia
■Psychomotor retardation or agitation
■Loss of energy or fatigue
■Decreased concentration ability or marked indecisiveness
■Preoccupation with death or suicide; patient has a plan or has attempted suicide
◦The symptoms cause significant impairment and distress.
◦The mood is not the result of substance abuse or a medical condition.
•Mixed episodes are characterized by the following:
◦Persons must meet both the criteria for mania and major depression; the depressive event is required to be present for 1 week only.
◦The mood disturbance results in marked disruption in social or vocation function.
◦The mood is not the result of substance abuse or a medical condition.
◦The mixed symptomology is quite common in patients presenting with bipolar symptomology. This often causes a diagnostic dilemma.10
Physical
Use the Mental Status Examination (MSE) to diagnose bipolar disorder. This section highlights the major findings for a person with bipolar disorder. Because the patient's mental status depends on whether he or she is depressed, hypomanic, manic, or mixed, the various areas of the MSE are labeled according to the particular phase of the patient.



•Appearance
◦Depressed episode: Persons experiencing a depressed episode may demonstrate poor to no eye contact. Their clothes may be unkempt, unclean, holed, unironed, and ill-fitting. If the person has lost significant weight, the garments may fit loosely. The personal hygiene of individuals experiencing a depressed episode reflects their low mood, as evidenced by poor grooming, lack of shaving, and lack of washing. In women, fingernails may show different layers of polish or one layer partially removed. They may not have paid attention to their hair. Men may exhibit dirty fingernails and hands.When these individuals move, their depressed affect is demonstrated. They move slowly and very little. They show psychomotor retardation. They may talk in low tones or in a depressed or monotone voice.
◦Hypomanic episode: These patients are busy, active, and involved. They have energy and are always on the go. They are always planning and doing things. Others notice their energy levels and mood changes.
◦Manic episode: In many ways, the behavior of a patient in the manic phase reflects behavior opposite of a person in the depressed phase. Patients experiencing the manic phase are hyperactive and might be hypervigilant. They are restless, energized, and active. They talk and act fast. Their attire reflects the mania. Their clothes might have been put on in haste and are disorganized. Alternately, their garments are often too bright, colorful, or garish. They stand out in a crowd because their dress frequently attracts attention.
•Affect/mood
◦Depressed episode: Sadness dominates the affect of individuals experiencing a depressed episode. They feel sad, depressed, lost, vacant, and isolated. The "2 Hs" often accompany their mood, hopeless and helpless. When in the presence of such patients, one comes away feeling sad and down.
◦Hypomanic episode: Their mood is up, expansive, and often irritable.
◦Manic episode: The mood is inappropriately joyous, elated, and jubilant. They are euphoric. They also may demonstrate annoyance and irritability, especially if the mania has been present for a significant length of time.
◦Mixed episode: The patient exhibits both depression and mania within a brief period (1 wk or less).
•Thought content
◦Depressed episode: Patients experiencing a depression have thoughts that reflect their sadness. They are preoccupied with negative ideas and nihilistic concerns, and they metaphorically see "the glass as half empty." They are likely to focus on death and morbid persons. Many think about suicide.
◦Hypomanic episode: Patients in this state are optimistic, forward thinking, and have a positive attitude.
◦Manic episode: During the manic phase, patients have very expansive and optimistic thinking. They may be excessively self-confident and/or grandiose. They often have a very rapid production of ideas and thoughts. They perceive their minds as being very active and see themselves as being highly engaging and creative. They are highly distractible and quickly shift from one person to another.
◦Mixed episode: Patients in this state can oscillate dramatically between depression and euphoria, and they often demonstrate marked irritability.
•Perceptions
◦Depression episode: Two forms of a major depression are described. One has psychotic features and the other does not. With psychosis, the patient experiences delusions and hallucinations that are either consistent or inconsistent with the mood. In the former, the patient's delusions of having sinned are accompanied by guilt and remorse or the patient feels he or she is utterly worthless and should live in total deprivation and degradation. Hence, the delusional content remains consistent with the depressed mood. In contrast, some patients experience delusions that are inconsistent with the depression, such as paranoia or persecutory delusions.
◦Hypomanic episode: Patients in this state do not experience perceptual disturbances.
◦Manic episode: Approximately three fourths of patients in the manic phase have delusions. As in major depression, the delusional content is either consistent or inconsistent with the mania. Manic delusions reflect perceptions of power, prestige, position, self-worth, and glory.
◦Mixed episode: Patients might exhibit delusions and hallucinations consistent with either depression or mania or congruent to both.
•Suicide/self-destruction
◦Depressed episode: Depressed patients have a very high rate of suicide. They are the individuals who attempt and succeed at killing themselves. Query patients to determine if they have any thoughts of hurting themselves (suicidal ideation) and any plans to do so. The more specific the plan, the higher the danger. As patients emerge from a period of depression, their suicide risk may increase. This may be because, as the illness remits, executive functions are improved such that the person is again capable of making and carrying out a plan while the subjective feeling of depression and accompanying suicidal thoughts may persist.
◦Hypomanic episode: Incidence of suicide is low.
◦Manic episode: Incidence of suicide is low.
◦Mixed episode: The depressed phases put the patient at risk for suicide.
•Homicide/violence/aggression
◦Depressed episode: Generally, suicide remains the paramount issue. However, certain persons in the depths of a depression not only see the world as hopeless and helpless for themselves but also for others. Frequently, that perspective can create and lead to a homicide followed by a suicide. One example of this occurred when a 42-year-old mother of 2 was experiencing a significant depression as part of her bipolar disorder. She believed the earth was doomed and was a terrible place to dwell. Furthermore, she thought that if she died, her children would be left in a wretched place. Because of this view, she planned to kill her 2 children and then herself. Fortunately, her family recognized the state of affairs, which led to an emergency intervention and her hospitalization.
◦Hypomanic episode: Patients who are hypomanic frequently show evidence of irritability and aggressiveness. They can be pushy and impatient with others.
◦Manic episode: Persons in mania can be openly combative and aggressive. They have no patience or tolerance for others. They can be highly demanding, violently assertive, and highly irritable. The homicidal element particularly emerges if these individuals have a delusional content to their mania. They are acting out of the grandiose belief that others must obey their commands, wishes, and directives. If their delusions become persecutory in nature, they may defend themselves against others in a homicidal fashion.
◦Mixed episode: Persons in a mixed episode may exhibit aggression, especially in the manic phases.
•Judgment/insight
◦Depressed episode: Depression clouds and dims these individuals' judgment and colors their insights. They fail to make important actions because they are so down and preoccupied with their own plight. They see no tomorrow; therefore, planning for it is difficult. Frequently, persons in the middle of a depression have done things such as forgetting to pay their income taxes. At that time, they have little insight into their behavior. Often, others have to persuade them to seek therapy because of their lack of insight.
◦Hypomanic episode: Generally, these people have good but expansive judgment. They may take on too many tasks or become over-involved. Often, their distractibility impairs their judgment, and they have little insight into their driven qualities. They see themselves as productive and conscientious, not as hypomanic.
◦Manic episode: The hallmark of this phase is seriously impaired judgment. They make terrible decisions in their work and family. They may invest the family fortune in very questionable programs. They may become professionally over-involved in work activities or with coworkers. They start a series of dramatic very unsound fiscal or professional ventures. They do not listen to any feedback, suggestions, or advice from friends, family, or colleagues. They have no insight into the extreme nature of their demands, plans, and behavior. Often, commitment proves the only way to contain them.
◦Mixed episode: Major shifts in affect during short lengths of time severely impair their judgment and interfere with their insight.
◦Cognition: Impairments in orientation and memory are seldom observed in patients with bipolar disorder unless they are very psychotic. They know the time and their location, and they recognize people. They can remember immediate, recent, and distant events. In some cases of hypomanic and even manic episodes, their ability to recall information can be extremely vivid and expanded. In extremes of depression and mania, they may experience difficulty in concentrating and focusing.
Although the Mental Status has been used here to highlight key aspects of the examination, the clinician must pay particular attention to the patient's physical health. As Fagiolini points out, patients with bipolar disorder have a high incidence of endocrine disorders, cardiovascular disorders, and obesity. These factors must be considerations when prescribing any medications.13,14

Causes
Bipolar disorder has a number of contributing factors, including genetic, biochemical, psychodynamic, and environmental elements.

•Genetics
◦Bipolar disorder, especially bipolar I, has a major genetic component. The evidence indicating a genetic role in bipolar disorder takes several forms.
◦First-degree relatives of people with BPI are approximately 7 times more likely to develop BPI than the general population. Remarkably, offspring of a parent with bipolar disorder have a 50% chance of having another major psychiatric disorder.
◦Twin studies demonstrate a concordance of 33-90% for BPI in identical twins.
◦Adoption studies prove that a common environment is not the only factor that makes bipolar disorder occur in families. Children whose biologic parents have either bipolar I or a major depressive disorder remain at increased risk of developing an affective disorder, even if they are reared in a home with adopted parents who are not affected. For more information on bipolar disorder in children, see Medscape's CME Activity New Findings in Childhood Bipolar Disorder.
◦Numerous genetic studies of BPI suggest that multiple different genetic loci, each of small effect, contribute to the affected phenotype. Four genome-wide association studies of bipolar disorder have now been published and a collaborative analysis of the 3 largest studies implicate 2 genes coding for proteins that either regulate or are subunits of ion channels ANK3 and CACNA1C.2,3,4,5 These findings suggest that bipolar disorder might be, in part, an ion channelopathy, similar to epilepsy. Another interesting candidate gene for mania is the CLOCK gene involved in circadian periodicity.7 A mouse CLOCK mutant was recently shown to exhibit features of mania.
◦An interesting finding in psychiatric genetics heralds the future revision of DSM-IV-TR according to an etiological rather than descriptive basis. Using probands from the Maudsley Twin Register in London, Cardno and colleagues showed that schizophrenic, schizoaffective, and manic syndromes share genetic risk factors and that the genetic liability for schizoaffective disorder was the same as the other 2 syndromes.15 This finding suggests an independent genetic liability for psychosis shared by both mood and schizophrenia spectrum disorders as Berrettini16 previously speculated.
◦A study by Tsuang et al further indicates the genetic contribution to manic-depressive illness with psychotic features. Their findings show the link between schizophrenia and bipolar disorder.17 ◦As discussed above, gene expression studies also demonstrate that persons with bipolar disorder, major depression, and schizophrenia share similar decreases in the expression of oligodendrocyte-myelin-related genes and abnormalities of white matter in various brain regions.
•Biochemical causes
◦Multiple biochemical pathways likely contribute to bipolar disorder, which is why detecting one particular abnormality is difficult.
◦A number of neurotransmitters have been linked to this disorder, largely based on patients' responses to psychoactive agents.
◦Evidence is mounting of the contribution of glutamate to both bipolar and major depressions. A postmortem study of the frontal lobes with both these disorders revealed that the glutamate levels were increased.18 ◦The blood pressure drug reserpine, which depletes catecholamines from nerve terminals, was noted incidentally to cause depression. This led to the catecholamine hypothesis, which holds that an increase in epinephrine and norepinephrine causes mania and a decrease in epinephrine and norepinephrine causes depression.
◦Drugs like cocaine, which also act on this neurotransmitter system, exacerbate mania.
◦Other agents that exacerbate mania include L-dopa, which implicates dopamine and serotonin-reuptake inhibitors, which, in turn, implicate serotonin.
◦Calcium channel blockers have been used to treat mania, which also may result from a disruption of calcium regulation in neurons. The proposed disruption of calcium regulation may be caused by various neurologic insults such as excessive glutaminergic transmission or ischemia. Interestingly, valproate specifically up-regulates expression of a calcium chaperone protein, GRP 78, which may be one of its chief mechanisms of cellular protection.
◦Hormonal imbalances and disruptions of the hypothalamic-pituitary-adrenal axis involved in homeostasis and the stress response may also contribute to the clinical picture of bipolar disorder.
◦Tricyclic antidepressants can trigger mania.19 •Psychodynamic
◦Many practitioners see the dynamics of manic-depressive illness as being linked through one common pathway.
◦They see the depression as the manifestation of the losses, ie, the loss of self-esteem and the sense of worthlessness. Therefore, that mania serves as a defense against the feelings of depression. (Melanie Klein was one of the major proponents of this formulation.)
•Environmental
◦In some instances, the cycle may be directly linked to external stresses or the external pressures may serve to exacerbate some underlying genetic or biochemical predisposition.
◦Pregnancy is a particular stress for women with a manic-depressive illness history and increases the possibility of postpartum psychosis.20 ◦Because of the nature of their work, certain individuals have periods of high demands followed by periods of few requirements. For example, one person was a landscaper and gardener. In the spring, summer, and fall, he was busy. During the winter, he was relatively inactive except for plowing snow. Thus, he appeared manic for a good part of the year, and then he would crash and hibernate for the cold months.

Apraxia and Related Syndromes:

Author: Jasvinder Chawla, MBBS, MD, MBA, Associate Professor of Neurology, Director of Neurology Residency Training Program, Director of Clinical Neurophysiology Laboratory, Assistant Director of Neurology Clerkship Program, Department of Neurology, Loyola University Medical Center
Coauthor(s): Daniel H Jacobs, MD, Associate Professor of Neurology, University of Central Florida College of Medicine

Introduction
Background
Apraxia is one of the most important and least understood major behavioral neurology syndromes. It is one of the best localizing signs of the mental status examination and also predicts disability in patients with stroke or dementia (unlike aphasia). Patients with apraxia cannot use tools; therefore, they are unlikely to perform activities of daily living well. Patients with aphasia, without coexisting apraxia, can live independently, take the bus or subway, and lead a relatively normal life; a patient with significant limb apraxia is likely to remain dependent.

Heilman defined apraxia in negative terms, "Apraxia is defined as a disorder of skilled movement not caused by weakness, akinesia, deafferentation, abnormal tone or posture, movement disorders such as tremors or chorea, intellectual deterioration, poor comprehension, or uncooperativeness."1 To simplify matters, apraxia can be considered a form of a motor agnosia. Patients are not paretic but have lost information about how to perform skilled movements.



There is no consensus on how to divide and organize the many different syndromes known as apraxias. Authors have divided apraxias based on the following:

•Body part affected (eg, limb apraxia or buccofacial apraxia)
•Dysfunctional sensory area (left inferior parietal) or motor areas (left premotor and left supplementary motor)
•If use of tools is affected (transitive vs intransitive)
•If knowledge about the use of tools is preserved (conceptual)
•Deficits in pantomiming tool use and gesture (ideomotor)
The term apraxia is used to describe a variety of syndromes, including the following, which are not considered true apraxias by some.

•Dressing apraxia - Usually associated with right parietal lesions and part of a neglect syndrome
•Constructional apraxia - Inability to copy 2-dimensional drawings or 3-dimensional assemblies (may be associated with right or left parietal and left frontal among other brain regions)
•Gait apraxia - Part of the triad of symptoms of normal pressure hydrocephalus
•Gaze apraxia - Part of Balint syndrome
•Apraxia of eyelid opening
•Magnetic apraxia

Pathophysiology
Apraxia is a syndrome reflecting motor system dysfunction at the cortical level, exclusive of primary motor cortex. In planning movements, previously learned, stored complex representations of skilled movements are used. These 3-dimensional, supramodal codes, also called representations or movement formulae, are stored in the inferior parietal lobule of the left hemisphere. Diseases that involve this part of the brain, including strokes, dementias, and tumors, can cause loss of knowledge about how to perform skilled movements.

Apraxia can occur with lesions in other locations as well. Information contained in praxis representations is transcoded into innervatory patterns by the premotor cortices, including the supplementary motor area (SMA) and possibly the convexity of the premotor cortex; the information is then transmitted to the primary motor cortex and a movement is performed. Lesions of the SMA or other premotor cortices also can cause apraxia; in this case, knowledge about movement is still present, but the ability to perform movement is absent.

Apraxia also occurs with lesions of the corpus callosum, such as tumors or anterior cerebral artery strokes. Although the corpus callosum is not known to be involved directly in the performance of skilled movements, it contains crossing fibers from the right hemisphere to the premotor cortex. This type of apraxia represents a classic disconnection syndrome; patients with callosal apraxia typically are apractic only with the left hand.

Frequency
United States
Few data are available regarding the frequency of apraxia; however, it commonly occurs after stroke and in dementia—2 of the most frequent neurological illnesses.

International
Few data are available regarding the frequency of apraxia.

Mortality/Morbidity
Apraxia is not a disease but a syndrome; consequently, it has no attributable morbidity or mortality.

Race
No data are available.

Sex
No good data are available.

Age
No good data exist concerning the occurrence of apraxia in different age groups. However, it is more common in older age groups, as they typically have higher frequencies of stroke and dementia.

Clinical
History
Frequently, patients with apraxia are unaware of their deficits. Accordingly, history of a patient's ability to perform skilled movements should be obtained from both the patient and caregivers. Caregivers should be asked about the ability of patients to perform activities of daily living, especially those that involve household tools (eg, using a knife, fork, and toothbrush correctly; using kitchen utensils safely and correctly to prepare a meal; using tools such as a hammer or scissors correctly). Caregivers should also be queried about the overall activity level of the patient and whether reductions in their total activities have occurred. The patient may simply sit on the couch and watch television, uninterested in previously important activities. This apathy can be associated with many different kinds of brain dysfunction, but occasionally occurs because the patient is not able to perform his or her usual activities.



Physical
•Testing for ideomotor apraxia can be performed at the bedside with simple tests for the ability to use tools. The examiner asks patients to perform 3 pantomimes of activities. The author of this article asks patients to pantomime hammering a nail into the (imaginary) wall in front of them, screwing a screw into the wall, and using a pair of scissors to cut a piece of paper. Nevertheless, many other pantomimes could be performed, including brushing teeth, cutting with a saw, whipping eggs with an eggbeater, or peeling a potato.
◦A healthy response to any of these commands is to perform a crisp, well-planned movement. Patients should perform the movement with the hand oriented correctly to hold an imaginary tool, with the tool held at the correct orientation and distance from the target (wall, screw, paper, respectively), and with the motion performed in such a way that the action gets performed. In other words, the author would like to see an action that would successfully cut a piece of paper, as if scissors and paper were really there.
◦Any type of error in performing the above activities (in the absence of aphasia or lack of comprehension of the command or lack of motor deficit) implies a loss of knowledge about the movement to be performed. If the hand is not oriented to hold the tool correctly, if the action is performed in the wrong plane, if the target (eg, wall) is not located correctly, or if movement is performed incorrectly, the response is scored as an error.
•Buccofacial apraxia implies a completely different process and lesion; it is tested separately. Unlike limb apraxia, in which a patient cannot perform skilled movements with the limbs, in buccofacial apraxia (also called oral apraxia), patients cannot perform skilled actions involving the lips, mouth, and tongue in the absence of paresis. Localization too is unique.
◦In buccofacial apraxia, the lesion is usually in or near area 44 (ie, the Broca area). To test for buccofacial apraxia, the patient should be asked to perform tasks with his mouth, like blow out a match, kiss, or brush his teeth.
◦Neighborhood signs also should be checked. Buccofacial apraxia usually occurs with Broca aphasia, whereas limb apraxia due to a parietal lesion may co-occur with Wernicke aphasia if the temporal lobe also is involved, or conduction aphasia or features of Gerstmann syndrome (ie, acalculia, right-left confusion, alexia with agraphia) if the angular gyrus also is involved.
•The nature of the response is also important. Additional tests of apraxia might include the ability to imitate commands (in aphasic patients), ability to select by choice correct and incorrect movements, or the ability to perform commands with each hand. Patients may be asked to actually use a tool or to perform an act when viewing a tool.
•Conceptual apraxia is defined as the loss of knowledge about tools and movements associated with their use. Patients with parietal lesions may have conceptual apraxia. These patients may be contrasted with patients with SMA lesions or other lesions of the premotor cortex. The latter type of patient would have normal knowledge about how to move, yet be unable to perform the movement correctly because of faulty transcoding of the "innervatory patterns" in the motor cortex.
•In a report published in 2008, Goldenberg hypothesized that “imitation of meaningless gestures and use of tool and objects depend on left parietal lobe integrity because of their demands on categorical apprehension of spatial relationships between multiple objects or between multiple parts of objects.”18 •Sometimes, testing the patient in a more practical setting may be necessary. For example, a patient may perform well by imitating movements, without the use of tools. However, if a dinner tray with a fork, a pencil, and a toothbrush are presented, selection of the wrong tool may be more obvious and evident.
•Magnetic apraxia is a type of forced grasp response, which often may be associated with frontal lesions and a degenerative disease known as corticobasal degeneration with neuronal achromasia (Rebeiz syndrome) or related conditions such as Alzheimer disease and progressive supranuclear palsy. This apraxia may be unilateral (affecting either side) and may resemble utilization behaviors or the alien hand syndrome. Patients may be unable to disengage from objects in front of them.
•Unilateral apraxia may be the presenting sign of corticobasal degeneration; memory is typically unaffected early. (Rarely, Alzheimer disease, progressive supranuclear palsy, Pick disease, and nonspecific degenerative dementia can present with that phenotype.) In addition to apraxia, patients may develop a truly useless limb and bizarre behaviors with the limb, including magnetic responses, forced grasping, and levitation of the limb. These clinical features are common but not absolutely necessary for the diagnosis. The pathology described in this condition, balloon cells with neuronal achromasia, is unique.
•Rothi has described a number of apraxia error types. These include errors of orientation of the hand around the object, errors of external spatial orientation, and movement errors. Other error types include perseverative errors (ie, repeating a previously made movement), body part as tool errors (ie, using the hand as the hammer rather than holding a hammer), and body part as object errors (ie, hand as the object of the action). While these errors can confirm that apraxia is present, no correlation can be made between lesion site and error type.
•Other (non)apraxia types
◦Dressing apraxia refers to inattention to the left side when dressing; it signifies a feature of the neglect syndrome rather than the loss of the ability to use tools. Typically, a right hemisphere lesion is implicated. It has no relationship with ideomotor apraxia.
◦Limb-kinetic apraxia (as distinct from limb apraxia) means a clumsy hand. Typically, it refers to the inability to make precise movements with the limb, especially the fingers contralateral to a brain injury. For example, patients may not be able to make rapid finger movements, to grasp objects in a pincer fashion, or to perform tapping movements.
◦Constructional apraxia refers to the inability to draw or copy quality pictures such as interlocking pentagons or complex figures such as the Rey-Osterreith figure. Constructional apraxia can localize damage to several brain areas, including frontal or left or right parietal. Patients with frontal damage tend to perseverate on or repeat elements of the figure, or to transform elements into familiar elements, such as transforming the circle with 3 dots into a face. Patients with right hemisphere damage (especially parietal) on the whole do worse than patients with left hemisphere damage at integrating the basic elements of the diagram, although left hemisphere-damaged patients also made many errors. Error types were described by Lezak.2 •Gait apraxia (also called Bruns ataxia) is observed in patients with normal pressure hydrocephalus. It has no relationship to ideomotor apraxia.
•Gaze apraxia, seen in Balint syndrome, has no relationship to ideomotor apraxia. Apraxia of eyelid opening has no relationship to ideomotor apraxia.
Causes
As discussed in the introduction, apraxia has a neurological cause that localizes fairly well to the left inferior parietal lobule, frontal lobes (especially the premotor cortex, supplementary motor area, and convexity), or corpus callosum. Any disease of these areas can cause apraxia, although stroke and dementia are the most common causes. Interestingly, callosal apraxia is rare after callosotomy and is much more common with anterior cerebral artery strokes or tumors.

Aphasia:

Author: Howard S Kirshner, MD, Professor of Neurology, Psychiatry and Hearing and Speech Sciences, Vice Chairman, Department of Neurology, Vanderbilt University School of Medicine; Director, Vanderbilt Stroke Center; Program Director, Stroke Service, Vanderbilt Stallworth Rehabilitation Hospital; Consulting Staff, Department of Neurology, Nashville Veterans Affairs Medical Center
Coauthor(s): Daniel H Jacobs, MD, Associate Professor of Neurology, University of Central Florida College of Medicine

Introduction
Background
Aphasia is an acquired disorder of language due to brain damage. Aphasia does not include (1) developmental disorders of language, often called dysphasia in the United States; (2) purely motor speech disorders, limited to articulation of speech via the oral-motor apparatus, referred to as stuttering, dysarthria, and apraxia of speech; or (3) disorders of language that are secondary to primary thought disorders, such as schizophrenia.

Encompassed under the term aphasia are selective, acquired disorders of reading (alexia) or writing (agraphia). Closely related to aphasia are the family of disorders called apraxias (disorders of learned or skilled movements), agnosias (disorders of recognition), acalculias (disorders of calculation ability), and more global neurobehavioral deficits such as dementia and delirium. Such related syndromes may coexist with aphasia or exist independently.



Pathophysiology
Aphasia may occur secondary to brain injury or degeneration and involves the left cerebral hemisphere to a greater extent than the right. Language function lateralizes to the left hemisphere in 96-99% of right-handed people and 60% of left-handed people. Of the remaining left-handed people, about one half have mixed hemisphere language dominance, and about one half have right hemisphere dominance. Left-handed individuals may develop aphasia after a lesion of either hemisphere, but the syndromes from left hemisphere injury may be milder or more selective than those seen in right-handed people.

Most aphasias and related disorders are due to stroke, head injury, cerebral tumors, or degenerative diseases. The neuroanatomic substrate of language comprehension and production is complex, including auditory input and language decoding in the superior temporal lobe, analysis in the parietal lobe, and expression in the frontal lobe, descending via the corticobulbar tracts to the internal capsule and brainstem, with modulatory effects of the basal ganglia and the cerebellum.

Aphasia syndromes have been described based on patterns of abnormal language expression, repetition, and comprehension. These classical syndromes have been roughly correlated with specific left hemisphere locations, though clear overlaps and individual differences make the aphasia syndromes limited in specificity. Patients may lose the ability to produce speech, to comprehend speech, to repeat, and to hear and read words in many nuanced ways. Classical aphasia syndromes (see Aphasia syndromes in History) include global, Broca, Wernicke, and conduction aphasia, as well as transcortical motor, transcortical sensory, and transcortical mixed aphasia. Pure alexia and optic aphasia are often discussed with the classical aphasias.

Language function can be parsed in several important ways other than assignment to the classical aphasia syndromes. A variety of types of evidence have noted that certain specific language functions (such as naming pictures) activate widespread neural networks involving many parts of both hemispheres of the brain. Producing, receiving, and interpreting speech requires specific and distinct cognitive processes such as phonologic decoding and encoding, orthographic decoding and encoding (for reading), lexical access, lexical-semantic representations of words, and semantic interpretation of language. Differentiation of these processes involves testing patients with different aphasia types and attempting to find double dissociations among groups of patients to determine the neurologic basis of specific cognitive processes.

The lesion method, the principal source of information about aphasia from autopsy studies in the 19th and early to mid 20th centuries and from brain imaging modalities since the 1970s, remains a useful source of information. However, it has been abetted by cortical stimulation studies, mainly in patients with epilepsy, and functional neuroimaging, such as fMRI and PET scanning often carried out during language testing in healthy individuals, to determine the language function of specific areas of the brain.


Frequency
United States
Data on incidence of aphasia in the United States are limited. Aphasia occurs in a variety of cerebrovascular, traumatic, and degenerative conditions. Stroke is likely the most common cause of aphasia, and it has been estimated that about 20% of stroke patients develop aphasia. More than 700,000 strokes occur in the United States each year, and approximately 170,000 new cases of aphasia every year are related to stroke. The number of patients with language disorders secondary to traumatic brain injury, brain tumors, and other brain lesions such as arteriovenous malformations is not precisely known. Patients with neurodegenerative disorders such as Alzheimer disease and frontotemporal dementia frequently manifest language deficits. The prevalence of Alzheimer disease in the United States is approximately 5 million cases.



Mortality/Morbidity
Aphasia is a condition, not a disease; therefore, it has no attributable mortality rate.

Race
No reliable data exist on the incidence of aphasia in different racial groups. Within disease entities, however, such differences are well known. In stroke, for example, African Americans have almost a 2-fold higher incidence as compared with whites. In addition, specific types of stroke, such as cerebral hemorrhage, lacunar infarctions, and intracranial artery stenoses, are known to be more common in African Americans than Caucasians. One might therefore surmise that poststroke aphasias would be more common in African Americans.



Sex
Not enough data are available to evaluate differences in the incidence and clinical features of aphasia in men and women. Some studies suggest a lower incidence of aphasia in women because they may have more bilaterality of language function. Differences may also exist in aphasia type, with more women than men developing Wernicke aphasia.



Age
Age may be an important factor in recovery. Some studies suggest that recovery from aphasia due to a stroke is less favorable in patients older than age 70 than in younger patients. However, at any age, recovery of various degrees can occur, even at times remote from the brain injury.

Clinical
History
Because patients with aphasia sometimes cannot provide a complete history, the clinical information obtained about the cause may depend on the acumen of those around the patient and the history provided by family members. Medical personnel without neurologic training may misdiagnose aphasia as confusion.

Aphasia develops abruptly in patients with a stroke or head injury. Patients with neurodegenerative diseases or mass lesions may develop aphasia insidiously, over weeks, months, or even years. "Neighborhood signs" suggestive of deficits of adjacent cortical areas, or of fiber tracts running near language areas, should be elicited. These signs include difficulties with vision, especially hemianopia; deficits of motor or sensory function; or related neurobehavioral deficits such as alexia, agraphia, acalculia, or apraxia. Patients should be asked about any indications of subtle seizures, such as staring spells or automatisms, or previous aphasic episodes. Rarely, aphasia is caused by herpes simplex encephalitis, a treatable condition but one that offers only a short window for diagnosis. Clues to the diagnosis include a history of fever, seizures, headache, and behavior changes.

A history of headache, acute or chronic, may also be important to the diagnosis of underlying conditions such as brain tumors or arteriovenous malformations. The patient should be asked about any history of memory impairment or of difficulty performing activities of daily living at home, because language dysfunction may be part of a more generalized neurodegenerative condition such as dementia (especially Alzheimer disease or frontotemporal dementia). The patient's handedness should be recorded, as should a history of hypertension, previous brain hemorrhage, cardiac disease, carotid or intracranial vascular disease, or amyloid angiopathy (a cause of lobar intracerebral hemorrhage in older patients).

•Anatomic considerations: Although all of the syndromes described later in this section have clinical and historical validity, they also have numerous limitations.
◦One-to-one mapping of lesions to deficits is often difficult. Many parts of both hemispheres contribute to the production and comprehension of speech. Individual differences also confuse the correlation of structure with function.
◦Patients who have had a stroke may evolve from one type of aphasia to another as they recover. The time of evaluation of the patient is therefore important in the syndrome diagnosis.
◦Patients with slowly growing tumors may have mild disease because the lesions grow slowly, allowing adjacent tissues to compensate for functional deficits.
◦In patients with severe congenital abnormalities, symptoms may develop in an anomalous fashion, and they have mild or no aphasia. Factors affecting the severity of findings include handedness, initial severity of the illness, time since onset, etiology, nature of the underlying vascular lesion (if any), and patient's age. Patients with severe, left hemisphere injury at a young age may have no residual language deficits.
◦Status of the contralateral hemisphere is also important for diagnosis and for estimating prognosis for recovery.
•Aphasia syndromes
◦Many specific aphasic syndromes have been reported. Classic nosology of the perisylvian aphasias includes Broca, Wernicke, conduction, and global aphasias. The nonperisylvian aphasias include anomic, transcortical motor, transcortical sensory, and mixed transcortical, sometimes called the isolation of the speech area syndrome. Other more specific language syndromes include aphemia, alexia with and without agraphia, and pure word deafness. Subcortical aphasia syndromes are defined more by the anatomy of the lesion than by the language characteristics.
◦The syndromes are broad phenotypes that may accompany different types of brain dysfunction, but they are useful because they provide a terminology to permit clinicians to communicate with one another regarding the patient. The presentations of the types of aphasia vary and overlap considerably, but recent studies of both stroke patients and of normal subjects undergoing functional brain imaging have supported the general classification of aphasia syndromes and the localizations of specific language functions.
◦Of the aphasia types mentioned, the most common and most widely appreciated are the cortical aphasias, including Broca, Wernicke, conduction, and global aphasias.
◦Specific information should be obtained, including the patient's reading and writing ability, the time frame of symptom onset, any word-finding difficulty, and underlying problems (eg, previous stroke, chronic difficulty with memory).

Physical
Bedside evaluation of language

Careful assessment of language function with an evaluation of neighborhood signs is important in the diagnosis of the localization and cause of aphasia. Neighborhood signs are often, but not invariably, seen; they are specific to the individual aphasic syndromes and are a great help in localization.

Although bedside examination can usually reveal the type of aphasia, formal cognitive testing by a neuropsychologist or speech/language therapist may be important to determine fine levels of dysfunction, to plan therapy, and to assess the patient's potential for recovery. Neuropsychologists and speech/language therapists commonly administer language testing batteries, including the Boston Diagnostic Aphasia Examination, the Western Aphasia Battery, the Boston Naming Test, the Token Test, and the Action Naming Test.

This assessment must be broad enough to detect subtle disorders of language in patients in whom aphasia is suspected. Each component of language should be tested individually and thoroughly. Components of bedside language examination include assessments of spontaneous speech, naming, repetition, comprehension, reading, and writing.

•Spontaneous speech should be assessed for fluency (ease and rapidity of producing words), amount of speech (number of words produced), initiation of speech, the presence of spontaneous paraphasic errors (semantic or phonemic), word-finding pauses, hesitations or circumlocutions, and prosody. Semantic or verbal paraphasias are substitutions of incorrect words (eg, "fork" for "spoon"), whereas phonemic or literal paraphasias are substitution of incorrect sounds or phonemes (eg, "poon" for "spoon"). These aspects of expressive language are helpful in the diagnosis of aphasia. Dysarthria (consistent mispronunciation of phonemes), apraxia of speech (inconsistent phoneme errors, often at the beginning of a word), and abnormalities of prosody (the emotional intonation of speech, often abnormal with right hemisphere disorders) should also be noted.
•Some patients initially perform well during the beginning of an examination, and a deficit becomes apparent only with prolonged testing. Hence, a cursory examination, as in a surgeon's progress note, may be inadequate to detect aphasia.
•Confrontation naming is tested with several items involving objects (ring, pen, watch, glasses, paper clip), object parts (watchband, winding stem, crystal), body parts (thumb, palm of the hand, wrist, elbow), and colors. Some naming disorders are particular to the class of items. For example, patients with Broca aphasia and frontal lobe lesions often have more problems with verb naming, and those with temporal lobe lesions and Wernicke or anomic aphasia have more difficulty with noun naming.
•The letter-fluency task requires the patient to generate words beginning with particular letters—as many as possible in 1 minute. Often the letters F, A, or S are used because good normal values for these letters are available. A similar test is the animal naming test of the Boston Diagnostic Aphasia Examination, in which the patient is asked to produce as many animal names as possible in 1 minute. The result of such tests may be considered a measure of frontal lobe function but not language function; however, the outcome may provide a rough measure of the number of words spoken spontaneously.

The production of fewer than 8 words beginning with the letter F in 1 minute, excluding proper names and their derivatives, is abnormal in adult native English speakers. Abnormality signifies frontal dysfunction, and aphasia may or may not be present. This test result is often abnormal in dementing illnesses or among patients with frontal dysfunction of any etiology. Category fluency such as animal or fruit naming in one minute also has well-established normal values and is less precisely a measure of frontal lobe function than is letter fluency.
•For some rare syndromes, patients should be tested with objects presented both in the visual and tactile modalities. In a condition called optic aphasia (originally described by Freud), patients cannot name objects presented visually, especially on cards, but their performance improves when the items are presented as real objects that may be palpated, or if the definition of the object is given.
•Complete assessment of language production should include oral and written modalities. A patient who can point to the object (a real object or a picture of it from among choices) or who can write the name of the object if he or she cannot say it might be said to have an inability to access the lexical form (ie, a retrieval deficit) but not a complete loss of semantic information about the object.
•Assessment should indicate repetition testing. Abnormal repetition is the hallmark of the perisylvian aphasias, the classic aphasias associated with lesions near the Sylvian fissure. Perisylvian aphasias include Broca, Wernicke, conduction, and global aphasias. Preservation of repetition is a major distinguishing feature in nonperisylvian aphasias, including anomic aphasia, the transcortical aphasias, and some subcortical or thalamic aphasias.
•Comprehension should be assessed in the oral and written modalities, with both simple and grammatically complex items and with sentences containing at least 2 clauses. Asking patients to perform 1- and 2-part commands is an adequate means to assess comprehension.
•Reading should always be assessed as part of language examination. Patients with alexia with agraphia and alexia without agraphia have different anatomic lesions, the former associated with left parietal lesions, the latter with left occipital lesions, usually a stroke in the left posterior cerebral artery territory. Spelling aloud, writing, and spelling words aloud to the patient are all preserved in patients with alexia without agraphia, but not in alexia with agraphia.
•Assessing a patient with phonologically regular but complex words (eg, "furniture") and irregular words (eg, "yacht") can be useful to determine if a preexisting dyslexia is present, and, occasionally, whether or not an unusual aphasia syndrome (deep vs surface alexia) is present.
•Writing should be assessed for quality, spelling, grammar, and quantity, as well as for the accuracy of the productions. In addition, patients should be tested for apraxia. Apraxia refers to the inability to understand or use tools (such as a pencil or pen) correctly in the absence of a primary motor deficit, and can occur in patients with or without aphasia. Thus, apractic agraphia should be differentiated from aphasic agraphia.
•The patient's performance should be interpreted in light of the entire mental status examination. The types of errors, such as omission of functor words (eg, a, the) and telegraphic writing or speech (see Broca aphasia below) should be noted. Patients may be unable to read because of nonlinguistic cognitive dysfunction. For example, in neglect dyslexia, which is usually due to a right hemispheric lesion, patients may fail to attend to and read or write the left side of a word or sentence.
•Silent reading may be more effective than oral reading and can be deduced by means of comprehension tests. This condition is common in patients with conduction aphasia and occasionally occurs in patients with Wernicke aphasia.
•Physical findings of aphasias
•Broca aphasia
◦This aphasia syndrome contains a number of distinct components that occur in various combinations. In the complete syndrome, patients present with a nonfluent aphasia. They speak haltingly, without intonation, and have difficulty producing spontaneous speech, naming, and repeating. They may initially be mute, and their articulation may be impaired. Patients are often hypophonic. Comprehension is relatively spared, though it is not normal. Phrases are short and may be telegraphic or agrammatic, including major nouns and verbs but no functor words (articles, adjectives, adverbs, or conjunctions). Patients have telegraphic speech, also called agrammatism. Naming of actions is typically worse than naming of objects.
◦A writing deficit usually parallels the phonologic deficit.
◦Repetition is abnormal and often consists of omission of functor words. Patients almost always have syntactic and comprehension deficits. Comprehension of passive constructions and of complex syntactic constructions, such as dependent clauses, may be abnormal. Neighborhood signs include buccofacial or limb apraxia and right hemiparesis, often involving the face and arm more than the leg.
◦Buccofacial apraxia can be tested by asking the patient to pantomime blowing a kiss or blowing out a match. Speech therapists may observe oral apraxia and difficulty swallowing. Limb apraxia may also accompany Broca aphasia, but it is most commonly caused by a large lesion including additional areas in the parietal or frontal lobes. Depression is extremely frequent because patients are typically aware of their deficits; in extreme form, this is associated with a complete withdrawal, termed by Kurt Goldstein the catastrophic reaction.
◦Reading is often more affected than auditory comprehension. Patients may make semantic errors (eg, reading "symphony" when the word is "concert"), one of the components of deep dyslexia. Patients may lose the ability to sound out words (they can no longer map graphemes to phonemes) but may be able to read frequent, previously learned, highly imageable words by recognition (they could read "tree" but not "proscription").
◦Typically, the lesions in Broca aphasia are localized to the dorsolateral frontal cortex (the posterior two thirds of the inferior frontal gyrus operculum), though some cases have associated lesions in the anterior parietal cortex and lateral striate and periventricular white matter. Frontal subcortical connections, such as the subcallosal fasciculus, are important for speech initiation and may disrupt thalamofrontocortical connections. Alexander et al argued that the full syndrome would not occur without involvement of the underlying white matter tracts.1 ◦Kreisler et al have attempted to relate specific components of the common aphasia syndromes with neurologic localization. The authors investigated 107 patients with a standard aphasia battery and looked at 69 predetermined areas of interest. They found an analysis to identify 67-94% of patients. They found the following:2 ■Nonfluent aphasias depended on frontal or putamenal lesions (mutism, low fluency).
■Repetition depended on insula-external capsule lesions and posterior internal capsule rather than the classically described arcuate fasciculus.
■Comprehension depended on posterior lesions of the temporal gyri or inferior frontal gyrus.
■Phonemic paraphasias depend on external capsule lesions extending to the posterior temporal lobe or internal capsule.
■Verbal paraphasias depended upon temporal or caudate lesions.
■Perseveration depended upon caudate lesions.
◦Note that these localizations largely confirm teachings about aphasia that have been in circulation since the writings of Broca and Wernicke, and others, in the 19th century.
◦Studies involving functional imaging, including positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) suggest that separate modules within the left inferior frontal gyrus subserve different aspects of speech, including semantic, syntactic, and phonologic functions. Complete Broca aphasia syndrome occurs with a large lesion destructive of the whole area, whereas partial syndromes occur with smaller lesions. In fact, patients with large left perisylvian lesions often have global aphasia in the early days and weeks after their strokes, and they slowly evolve into Broca aphasia. Patients with isolated Broca area lesions may have Broca aphasia on the first day of their stroke. On the receptive side, comprehension of complex sentences with embedded clauses requires activation of the left frontal cortex of the Broca area, and this task is usually deficient in patients with Broca aphasia.
◦Recovery from Broca aphasia may occur over months and sometimes years. Patients may progress in the nosology of Broca aphasia and may develop anomic aphasia or become normal over time.
◦Broca area aphasia, also called a baby-Broca lesion, occurs with a lesion limited to area 44 (the frontal operculum). This aphasia includes what has been called aphemia, cortical dumbness, anarthria, and subcortical motor aphasia. The condition is also closely tied to what speech/language pathologists call apraxia of speech. This condition affects production of phonemes, especially multiconsonant words, and may not represent a true language disorder or aphasia. Aphemia often improves rapidly. A similar syndrome can occur with a lesion limited to the lower prerolandic fissure. Patients may be mute, or they may express themselves in slow, effortful productions, with normal or nearly normal language and syntax. Foreign-accent syndrome is a variant of aphemia, involving damage to the motor speech outflow mechanism. Foreign accent syndrome is more of a cortical dysarthria, akin to acquired stuttering, than a true aphasia.
•Wernicke aphasia
◦Patients with Wernicke aphasia have fluent language expression, but their speech sounds empty and does not convey meaning. There may be fluent phrases without nouns and verbs, containing nonexistent word forms (neologisms). The patient's speech and writing may include paraphasic errors with sound substitutions (phonemic paraphasias), word substitutions (semantic paraphasias), hesitations, pauses, and circumlocutions. Grammar is better preserved than it is in Broca aphasia. This abnormal speech output is called paragrammatic, as compared to the agrammatic output of Broca aphasia.
◦Naming and repetition are typically impaired, but the most significant problem is the abnormal language comprehension. Although reading impairment often parallels the auditory comprehension deficit, patients occasionally have preserved oral reading or even reading comprehension. This is important in establishing communication with the patient. Written expression is abnormal; unlike patients with Broca aphasia, these patients can write fluently, but their word choice and spelling are usually very abnormal. In mild Wernicke aphasia, abnormal spelling in written productions may be a clue to the deficit. In acute stroke with Wernicke aphasia, patients may seem confused in addition to their language deficits, and they may even appear psychotic.
◦Patients with Wernicke aphasia are not always aware of their deficits, and over time they may become frustrated that others do not understand them. Some patients become overtly paranoid about their failure to communicate. Patients with Wernicke aphasia may recognize their errors if the mistakes are presented to them offline (eg, on an audio tape).
◦The lesion is variable but usually involves the posterior one-third of the superior temporal gyrus. Involvement of deep temporal white matter, the middle or inferior temporal gyri, or the inferior parietal lobule may predict a lesser degree of recovery. Wernicke aphasia is most typically associated with embolic strokes affecting the inferior division of the middle cerebral artery, supplying the temporal cortex and sparing the frontal, motor cortex.

In studies by Naeser and colleagues3 , destruction of Wernicke area predicted lasting loss of comprehension, and recent, acute studies by Hillis and colleagues4 have found single word comprehension deficits to correlate with hypoperfusion of Wernicke area. Recovery also depends on the size of the lesion, the amount of the traditional Wernicke area that is destroyed, the age of the patient, and the status of the contralateral hemisphere. Recovery can be complete or the aphasia can progress to conduction or anomic aphasia.
◦Similar or identical lesions can produce different syndromes of aphasia at different points in the disease process. Neighborhood signs should be sought to help in localization. In Wernicke aphasia, neighborhood signs include a superior quadrantanopsia due to involvement of optic radiations, limb apraxia due to involvement of the inferior parietal lobule or its connections to the premotor cortices, finger agnosia, acalculia, or agraphia (components of the Gerstmann syndrome) due to involvement of the angular gyrus. The key neighborhood sign is a negative one; patients with Wernicke aphasia usually have no hemiparesis.
◦Research has debated the category specificity of semantic, naming, and language deficits.5 For example, lesions of the fusiform or occipital gyrus may be more likely to cause an inability to name living things or highly imageable words, perhaps due to the proximity to the visual areas. Lesions of the temporal lobes are more likely to affect the naming of tools or inanimate objects, whereas frontal lesions may specifically impair verb naming.
•Conduction aphasia
◦This classical aphasia type is less common than Broca, Wernicke, or global aphasia. Language output is fluent, though some patients make phonemic errors in speech and pause to correct them, giving the speech a somewhat halting quality. This attempt to correct errors is called conduit d'approche. Naming may or may not be impaired. Repetition impairment is the hallmark of conduction aphasia. Careful studies have shown the ability of patients with aphasia to correct their tape-recorded speech, suggesting an offline ability to monitor output in some cases. Auditory comprehension is typically normal in conduction aphasia. Oral reading and writing abilities are variable. Patients with conduction aphasia may have normal comprehension of written language; cases of patients with conduction aphasia who are able to read novels have been reported.
◦The classic disconnection hypothesis, originally formulated by Wernicke and more recently adopted by Geschwind,6 highlights the importance of the arcuate fasciculus connecting the temporal and frontal language cortices, thereby connecting comprehension with speech-output centers. By this theory, a disconnection between these centers results in the inability to repeat, in the setting of intact comprehension and verbal fluency. Other theories of conduction aphasia include a deficit of auditory-verbal short-term (immediate) memory or “inner speech.”
◦The supramarginal gyrus is often affected in conduction aphasia, though disruption of the subcortical connections in the arcuate fasciculus may also be important. Research has implicated the supramarginal gyrus in the decoding of phonemes in receptive language and presumably their translation into oral expression. Recovery is usually good, but residual semantic and phonologic difficulties may remain. Kreisler et al, in the work cited, could not confirm the roles of the arcuate fasciculus or supramarginal gyrus as classically described.2 ◦Neighborhood signs in conduction aphasia include superior quadrantanopsia, if the lesion undercuts the parietal lobe, and limb apraxia, which is typically more disabling and less often diagnosed than the aphasia itself. Temporal lobe lesions that do not totally damage the Wernicke area may result in conduction aphasia, and such cases do not have associated apraxia, whereas patients with left parietal lesions often have associated limb apraxia.
•Global aphasia
◦In this type of aphasia, the patient has deficits in all aspects of language: spontaneous speech, naming, repetition, auditory comprehension, reading, and writing. The deficits need not be total. Global aphasia may result from strokes, tumors, dementia, or other causes.
◦Global aphasia is commonly seen in patients with large infarctions of the left cerebral hemisphere, typically involving the occlusion of the internal carotid or middle cerebral artery and resulting in a large, wedge-shaped infarction of the frontal, temporal, parietal, and deep portions of the middle cerebral artery territory. Right hemiplegia (face and arm worse than the leg) is the rule, as is right homonymous hemianopsia. Limb apraxia is common. Some patients have a catastrophic reaction, described by Kurt Goldstein as an emotional meltdown when the patient is asked to perform language tasks; this phenomenon is likely related to depression.
◦Global aphasia rarely occurs with right hemispheric lesions (also called crossed aphasia). About one fifth of left-handed people and 1% of right-handed people have global aphasia after mirror-image lesions of the homologous cortex of the right hemisphere; in this case, left homonymous hemianopsia and left hemiplegia are expected.
◦Global aphasia rarely occurs without hemiparesis. In such cases, dual lesions in the left cerebral hemisphere are expected; these spare the motor areas but affect both anterior and posterior perisylvian language areas. Although multiple strokes could produce such a clinical picture, in practice, the possibility of tumors should be considered with such multiple lesions. In cases of aphasia without hemiparesis, a thalamic lesion should also be considered in the differential diagnosis.
◦Although global aphasia is often considered a devastating injury, gradations of global aphasia exist. Many patients with poststroke global aphasia evolve toward Broca aphasia, or mixed nonfluent aphasia, with improvement in language comprehension over time. Many patients with global aphasia are proficient at making their needs understood without spoken or written speech. Prosody, inflection, pointing, and expressions of approval or disapproval are some of the ways in which patients with global aphasia may communicate successfully.
◦Patients with large, left hemisphere lesions and global aphasia are vastly different from patients with large, right hemispheric lesions whose language may appear normal but the nonlinguistic aspect of language expression is lost, including the prosody or emotional aspect of language expression and the ability to understand humor or sarcasm in the speech of others. Patients with such right-hemisphere syndromes are less aware of their deficits than patients with aphasia and may be less responsive to rehabilitation.
◦Factors affecting the prognosis may include the nature of the underlying injury (eg, dementia, tumor, stroke), the age of the patient, area of infarction (if present), the health of the remaining brain, and the availability of rehabilitation services.
◦Recovery in the first 6 months generally outpaces later recovery; however, some patients can recover function years after the initial injury. In one study of patients with global aphasia, more improvement occurred during the second 6 months after the injury than during the first 6 months.
•Pure word deafness
◦Patients with pure word deafness cannot comprehend spoken language, but they are not deaf. Their verbal output and reading comprehension are said to be intact, but most published cases have shown some degree of fluent, paraphasic speech.
◦The condition can occur because of damage to the superior temporal (Heschl) gyrus bilaterally, but cases have been described with unilateral, left temporal lesions. Disconnection theory proposes that inputs from both Heschl gyri are cut off from input into the left hemisphere Wernicke area where sounds are decoded into language.
◦Pure word deafness should be differentiated from cortical deafness, in which both language and nonlinguistic sounds are affected, and also from auditory nonverbal agnosia. Patients with cortical deafness may appear deaf, but they often have some sparing of pure-tone hearing, especially as recovery occurs. Auditory nonverbal agnosia involves failure of recognition of familiar sounds, such as the moo of a cow or the ringing of a bell. A related disorder is phonagnosia, in which familiar voices are not recognized. All of these cortical auditory deficits (pure word deafness, cortical deafness, auditory nonverbal agnosia, and phonagnosia) usually reflect bilateral temporal lobe lesions.
•Transcortical aphasias
◦The term transcortical aphasia was originally chosen by Lichtheim to indicate aphasias related to primary lesions not involving the language cortex but rather connected areas of the association cortex, which he called the "area of concepts." By definition, patients with transcortical aphasia can repeat, but they have difficulty naming or producing spontaneous speech or understanding spoken speech. Patients with transcortical motor aphasia can comprehend speech but have diminished speech output and an inability to name items. Sometimes they speak only in single words, after a delay, or in a soft voice.

Transcortical motor aphasia involves a deficit in the initiation of speech, reduced phrase length, and abnormal grammar. Mutism may be present initially. Repetition may be relatively unimpaired, distinguishing these patients from those with Broca aphasia who cannot repeat fluently. In some patients, a stroke in the anterior cerebral artery territory is the cause; leg greater than arm weakness, shoulder greater than hand weakness, and often an involuntary grasp response are associated findings.
◦In transcortical sensory aphasia, patients can produce fluent speech, but it is often empty and paraphasic. Patients also have a severe deficit in comprehension of speech. Their naming is often abnormal, and they lose semantic associations of speech. In general, they act much like patients with Wernicke aphasia, except they can repeat. This type of aphasia is typically seen in advancing Alzheimer disease and other progressive dementias, but it is also seen occasionally in patients with stroke, typically those with bilateral lesions in the parieto-occipital cortex or a lesion in the left temporo-occipital cortex.
◦Mixed transcortical aphasia, also called the syndrome of isolation of the speech area, involves ability to repeat but not to produce spontaneous speech or comprehend language. Patients may repeat in an echolalic fashion, and they may complete common phrases begun by the examiner. This syndrome resembles global aphasia, except for the preserved repetition.
•Anomic aphasia
◦Patients with anomic aphasia present with fluent speech, intact or mostly intact repetition, intact auditory comprehension, reading, and writing, but an inability to name objects and body parts. Anomic aphasia may follow recovery from another type of aphasia. Anomic aphasia can be an initial presentation of an aphasia syndrome, and it warrants its own aphasia syndrome.
◦Anomic aphasia is less specific in lesion localization than the other syndromes mentioned previously. Anomia may occur with lesions in the dorsolateral frontal cortex, temporal or temporo-occipital cortex, or thalamus. Tumors of the left temporal lobe may present with anomic aphasia. This aphasia type is also the typical language deficit in patients with early Alzheimer disease.
•Subcortical aphasias
◦Broca reported lesions of the deep basal ganglia with cortical lesions in his original autopsy report of his famous patient, Tan-tan. More controversial than that association is whether a basal ganglia lesion by itself can cause aphasia.
◦A series of reports in the early 1980s, which used computed tomography (CT) as the primary neuroimaging modality, associated lesions of the head of the caudate nucleus, anterior putamen, and anterior limb of the internal capsule with a nonfluent aphasia syndrome, often with dysarthria and with better repetition and comprehension than typically seen with Broca aphasia.7,8,9,10 This syndrome has been called the anterior subcortical aphasia syndrome. When the lesion extends into the temporal isthmus area, subcortical versions of Wernicke and even global aphasia can occur. The diagnosis of subcortical aphasia is based more on the imaging of a subcortical lesion than on the specific language characteristics of the aphasia syndrome.
◦In some cases, MRIs have revealed cortical lesions in patients with aphasia whose CT scans demonstrated only subcortical lesions. Blood-flow imaging has shown flow abnormalities in the cortex of patients whose MRIs depicted only lesions in the basal ganglia. Such diminished flow may partly reflect cortical ischemia and partly reflect a reduced perfusion of functionally connected areas called diaschisis.
◦Weiller et al examined patients with striatocapsular lesions, some with aphasia or neglect, and some without. On MRI, lesions in both groups were similar. However, patients with aphasia and neglect had low blood flow in the cortex, suggesting that cortical ischemia may also be important in some subcortical aphasias. Weiller also found that among patients with identical vascular syndromes, those who had strokes due to atrial fibrillation typically had aphasia and neglect, whereas those who had strokes due to large vessel stenosis did not. They attributed the finding to the ability of patients with chronic low flow due to large vessel stenosis to develop collaterals, whereas those with a sudden occlusion due to an embolus could not do so.11 •Thalamic aphasias
◦Thalamic aphasia, like the subcortical aphasia syndromes, is defined by the anatomic documentation of a lesion in the thalamus rather than by the specific language characteristics of the aphasia syndrome. Patients with thalamic aphasia usually present with fluent language disorders, often without hemiparesis. Associated findings include anomia, jargon speech, semantic paraphasic errors, intact repetition, and relatively preserved comprehension. Such patients may also manifest an acute affective syndrome with abulia or severe depression.
◦Thalamic aphasia was initially described in patients with left thalamic hemorrhage. The first author reported a left-handed patient with a right thalamic hemorrhage, indicating that language dominance extends down to thalamic level. In hemorrhage, of course, the language disorder possibly results from mass effect or pressure on adjacent structures rather than on the specific focus of the hemorrhage. More recent cases of thalamic aphasia secondary to ischemic stroke have solidified the evidence that the thalamus is important to language function.

The vascular lesion that affects the anterior thalamus is a small-vessel disease affecting the polar or tuberothalamic artery of the thalamus. The lesion is easily seen on CT scans or MRIs. Lesions in the anterior thalamus also affect memory. Crosson et al argued persuasively for the importance of pulvinar and other posterior structures in language, but their data were based on stimulation rather than lesion ablation.12

Pulvinar strokes causing aphasia are exceedingly rare because of the vascular anatomy of the thalamus. Lesions of the paramedian thalamus (thalamoperforating artery), especially if bilateral (some patients have a single artery, sometimes called the artery of Percheron, supplying both sides), cause deficits in memory and language. In his book , Crosson discusses the possible role of the ventral lateral nucleus in atypical aphasias, but usually this vascular territory (inferolateral arteries) involves a pure sensory stroke, while the posterior choroidal artery territory mainly involves the lateral geniculate body, causing an isolated hemianopia.
◦Lesions of the white matter between the thalamus and the temporal lobe, the temporal isthmus, or temporal stalk may produce aphasia due to deafferentation of the overlying temporal lobe. These aphasias closely resemble Wernicke aphasia. As mentioned above, however, the cases reported have not entirely excluded cortical involvement or hypometabolism as a cause of the syndrome.
•Pure alexia without agraphia
◦Pure alexia is known by a variety of names, including alexia without agraphia, posterior alexia, and literal or letter-by-letter alexia. Patients with pure alexia have normal expressive speech, normal naming (except in some cases for color anomia or inability to name colors), normal repetition, normal auditory comprehension, and even normal ability to write. Their alexia is a relatively pure deficit. Patients may be able to write a sentence, then be unable to read it. They have no difficulty spelling aloud and no difficulty in recognizing words spelled to them aloud or spelled in tactile fashion on the palm of the hand. Patients may be able to read individual letters, then laboriously piece them together and say the words (letter-by-letter alexia).
◦Neighborhood signs useful in the diagnosis of pure alexia include a contralateral (right) superior quadrantanopsia or hemianopia and color anomia. The syndrome is almost always associated with a stroke in the territory of the left posterior cerebral artery. The lesion may also involve the splenium of the corpus callosum and the medial temporal lobe.
◦Dejerine first described this syndrome in 1892, postulating a disconnection between the right occipital cortex (and intact left visual field) and the left hemisphere language area, such that visual information cannot be decoded into language in the left hemisphere.13 Later contributors recognized that the posterior left hemisphere has a word-form recognition area that, if damaged, prevents patients from reading words at a glance, as normal readers do. Nearly a century later, Geschwind6 and then Damasio7 refined the disconnection hypothesis of pure alexia. Cognitive neuropsychologists and behavioral neurologists have recognized the concept of damage to the orthographic recognition areas in the left occipital lobe.
•Alexia with agraphia
◦Alexia with agraphia is also known as the angular gyrus syndrome and central alexia. It is, in effect, an acquired illiteracy; patients lose their previously acquired reading and writing skills. Most lose spelling and the ability to understand words spelled to them. Many patients have fluent, paraphasic speech, unlike the preserved speech of pure alexia without agraphia, but auditory comprehension is much superior to reading comprehension. The lesion usually involves the angular gyrus area in the left inferior parietal lobule. This syndrome was also described by Dejerine.
◦Closely related to the pure alexia with agraphia syndrome is the Gerstmann syndrome. Gerstmann brought together the 4 deficits of agraphia, acalculia, right-left confusion, and finger agnosia and associated them with lesions of the dominant parietal lobe. Alexia, though not originally a cardinal feature of the Gerstmann syndrome, is often associated.
◦Modern authors such as Benton have questioned the validity of the Gerstmann syndrome.14,15 Some patients may have one or more of the deficits without the others. Stimulation studies in epileptic patients, however, have reproduced combinations of these deficits with stimulation in the angular gyrus area, confirming the association of the key elements of the Gerstmann syndrome.
•Right hemisphere language disorders
◦Right hemisphere contributions to language are numerous, and recent research has led to a better understanding of right hemisphere functions related to communication. The right hemisphere can maintain an extensive vocabulary and read at the word and phrase level. Higher functions of right hemisphere speech, subserved in part by right frontal and temporal lobes, include the comprehension of metaphor, sarcasm, and humor, as well as the emotional prosody of speech, ie, the extralinguistic aspects of human communication.
◦Patients with right hemisphere lesions may understand words but fail to understand the emotional context of a conversation or the facial expressions and tones of voice that convey meaning in normal communication. In addition, they may fail to observe normal turn-taking and other pragmatic aspects of a conversation. In patients with normal speech and language comprehension, these deficits can be disabling in a social context. Patients with right hemisphere lesions may have a problem with discourse and have difficulty stringing together several sentences into a spoken paragraph with a beginning, middle, and end, as a storyteller or lecturer would do.

Causes
Aphasia is a symptom and not a disease; it can occur in a variety of types of brain injury and pathology.



•In stroke, the deficit is usually sudden and obvious.
•In substantial head trauma, the deficits may be unrecognized. Exceptions involve hemorrhages or traumatic contusions directly disrupting the left hemisphere language cortex, which may then resemble stroke syndromes.
•Language disorders in dementia take a variety of forms. In dementia, the language problem may be insidious and may require elicitation with the assistance of an experienced physician, speech/language pathologist, or neuropsychologist. Some dementias, such as frontotemporal dementia, primary progressive aphasia, or Pick disease, have aphasic syndromes that closely resemble the aphasic stroke syndromes described above, except that they begin gradually and progressively worsen. If aphasia is the sole deficit over a 2-year period, the term primary progressive aphasia can be used, though many of these patients develop other cognitive deficits over time.

Both nonfluent, Broca-like syndromes and fluent, Wernicke-like or anomic syndromes have been described. The nonfluent syndromes more commonly represent non-Alzheimer dementias (frontotemporal dementia, primary progressive nonfluent aphasia), whereas fluent aphasias often develop in the course of Alzheimer disease. A variant is semantic dementia, in which the patient not only cannot name items, but the very meaning of words is lost. These patients cannot define common words. Most fluent cases of primary progressive aphasia begin with an anomic pattern, then progress to Wernicke or transcortical aphasia syndromes. In most cases, the associated memory deficits, as well as right hemisphere disorders and frontal dysexecutive syndromes make clear the more widespread nature of the dementing illness.
•In multiple sclerosis and Parkinson disease, no language abnormality is usually present, though patients with Parkinson disease can develop language deficits along with dementia. The disease corticobasal degeneration often involves a nonfluent aphasia, sometimes meeting criteria for primary progressive aphasia before the motor deficits of limb apraxia and Parkinsonism begin. Dysarthric speech patterns are common in both multiple sclerosis and Parkinson disease.
•A rare cause of aphasia in children is the Landau-Kleffner syndrome, a syndrome of acquired epileptic aphasia.
◦Symptoms begin in childhood and progress; electroencephalographic (EEG) findings confirm the diagnosis.
◦The syndrome is treatable; however, in some patients, the seizures are controlled more than the aphasia is.
•A rare but important condition not to overlook is herpes simplex encephalitis. The aphasia in herpes simplex encephalitis may mimic Wernicke aphasia mimicking a stroke deficit, but often with associated confusion. The disease usually resents with confusion, fever, headache, and seizures. Over time, the MRI usually shows a classic insula-sparing lesion, involving one or both temporal lobes. Early treatment with antiviral agents is crucial to prevent further injury until the diagnosis can be confirmed, usually by PCR testing of spinal fluid.
•Aphasia is diagnosed based on language examination and the localization of a lesion in the left hemisphere. Careful mental status and language examination is always important to diagnosis