Transient Global Amnesia

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Transient global amnesia was first described by Fisher and Adams in 1964 as a transient event in which there is altered behavior with prominent memory loss. Patients with this condition are typically

Table 60

Diagnostic Criteria for Olfactory Reference Syndrome

A. A preoccupation with imagined body odor (including halitosis) persisting despite reassurance.

B. At some point during the course of the disorder, the person recognizes that the preoccupation (obsession/compulsion) is excessive or unreasonable.

C. The symptoms cause clinically significant distress or impairment in social, occupational, or other areas of functioning.

D. Does not occur solely during the course of another disorder (e.g., body dysmorphic disorder, hypochondriasis, social anxiety disorder, mood disorder, and obsessive-compulsive disorder)

E. The disturbance is not the result of the direct physiological effects of an exogenous substance or medication or a general medical condition (e.g., hyperthyroidism).

Reprinted with permission from Lochner C, Stein DJ. Olfactory reference syndrome: diagnostic criteria and differential diagnosis. Postgrad Med J 2003;49:328-331 and from BMJ Publishing Group.

Table 61

Diagnostic Criteria for Primary Progressive Aphasia

1. Insidious onset and gradual progression of word finding object naming, or word-comprehension impairments as manifested during spontaneous conversation or as assessed, through formal neuropsychological tests of language.

2. All limitation of daily living activities attributable to the language impairment, for at least 2 years after onset.

3. Intact premorbid language function (except for developmental dyslexia).

4. Absence of significant apathy, disinhibition, memory dysfunction for recent events, visuospatial impairment, visual recognition deficits, or sensory-motor dysfunction within the first 2 years of the illness. This criterion can be fulfilled by history, survey of daily living activities, or formal neuropsychological testing.

5. Acalculia and ideomotor apraxia may be present even in the first 2 years. Mild constructional deficits and perseveration (as assessed in the go/no-go task) are also acceptable as long as neither visuospatial deficits nor disinhibition influences daily living activities.

6. Other domains possibly affected after the first 2 years, but language remains the most impaired function throughout the course of the illness and deteriorates faster than other affected domains.

7. Absence of "specific" causes, such as stroke or tumor, as ascertained by neuroimaging.

Adapted with permission from Mesulam MM. Primary progressive aphasia. Ann Neurol 2001;49:425-432, and from John Wiley and Sons.

Table 62

Diagnostic Criteria for Transient Global Amnesia

1. Information should be available about the beginning of the attack from a capable observer.

2. The patient should be examined during the attack to be certain that neurological signs and symptoms do not accompany the amnesia.

3. There should be no accompanying neurological signs.

4. The memory loss should be transient.

Adapted from Caplan LR. Transient global amnesia. In: Vinken PJ, Bruyn GW, Klawans HL, eds. Handbook of Clinical Neurology, vol 1. Amsterdam: Elsevier Science, 1985;205-218.

agitated during the event, often asking repeated questions. The etiology of transient global amnesia is unknown, with theories ranging from cerebrovascular events, migrainous phenomena, and epilepsy being proffered. Recent studies with functional neuroimaging including single-photon emission computed tomography and diffusion-weighted magnetic resonance imaging have shown that regional blood flow and focal brain abnormalities occur during the attack. Many of the described cases in the literature consist of a transient global amnesia syndrome as the presenting feature of another disorder, or that resulted in permanent neurological deficits. A strict categorical definition was proposed by Caplan in 1985 in analysis of a large case series. Four points were central to the diagnosis in the ideal case and are listed in Table 62.


Exclusion Features Common to Each Clinical Syndrome


All features (see Table 55) must be absent. Early severe amnesia, early spatial disorientation, logoclonic speech with loss of train of thought, and myoclonus are features designed to exclude Alzheimer's disease.


All features should be absent (when the relevant information is available). Relative Diagnostic Exclusion Features

These are features (see Table 55) that caution against, but do not firmly exclude, a diagnosis of frontotemporal lobar degeneration (FTLD). A history of alcohol abuse raises the possibility of an alcohol-related basis for a frontal lobe syndrome. However, excessive alcohol intake may also occur in patients with frontotemporal dementia (FTD) as a secondary manifestation of social disinhibition or hyperoral tendencies. The presence of vascular risk factors, such as hypertension, ought to alert investigators to a possible vascular etiology. Nevertheless, such risk factors are common in the general population and may be present coincidentally in some patients with FTLD, particularly in those of more advanced age.

Definitions of Clinical Features

This information is adapted from Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998;51:1546-1554. It gives operational definitions to the terms used in Lists 1-4.

Frontotemporal Dementia

See Table 52. Core Features

Insidious Onset and Gradual Progression. There should be no evidence of an acute medical or traumatic event precipitating symptoms. Evidence for a gradually progressive course should be based on historic evidence of altered functional capacity (e.g., inability to work) over a period of at least 6 months, and may be supported by a decline in neuropsychological test performance. The degree of anticipated change is not specified, because it is highly variable. In some patients, change is dramatic over a 12-month period, whereas in others it is manifest only over a period of several years. Dramatic social and domestic events leading to perturbations in the patient's behavior must be distinguished from ictal occurrences of a neurological or psychological nature. Only the latter are grounds for exclusion.

Early Decline in Social Interpersonal Conduct. This refers to qualitative breaches of interpersonal etiquette that are incongruent with the patient's premorbid behavior. This includes decline in manners, social graces, and decorum (e.g., disinhibited speech and gestures, and violation of interpersonal space), as well as active antisocial and disinhibited verbal, physical, and sexual behavior (e.g., criminal acts, incontinence, sexual exposure, tactlessness, and offensiveness). "Early" for this and other features implies that the abnormality should be present at initial presentation of the patient.

Early Impaired Regulation of Personal Conduct. This refers to departures from customary behavior of a quantitative type, ranging from passivity, inertia, and inactivity to overactivity, pacing, and wandering; and increased talking, laughing, singing, sexuality, and aggression.

Early Emotional Blunting. This refers to an inappropriate emotional shallowness with unconcern and a loss of emotional warmth, empathy, and sympathy, and an indifference to others.

Early Loss of Insight. This is defined as a lack of awareness of mental symptoms, evidenced by frank denial of symptoms or unconcern about the social, occupational, and financial consequences of mental failure.

Supportive Features: Behavioral Disorder

Decline in Personal Hygiene and Grooming. The caregivers' accounts of failure to wash, bathe, groom, apply makeup, and dress appropriately as before are reinforced by clinical observations of unkemptness, body odor, clothing stains, garish makeup, and inappropriate clothing combinations.

Mental Rigidity and Inflexibility. This refers to egocentricity and loss of mental adaptability, evidenced by reports of any one of the following: the patient has to have his or her own way, is unable to see another person's point of view, adheres to routine, and is unable to adapt to novel circumstances.

Distractibility and Impersistence. These are reflected in failure to complete tasks and inappropriate digressions of attention to nonrelevant stimuli.

Hyperorality and Dietary Changes. This refers to overeating, bingeing, altered food preferences and food fads, excessive consumption of liquids, alcohol, and cigarettes, and the oral exploration of inanimate objects.

Perseverative and Stereotyped Behavior. This encompasses simple repetitive behaviors, such as hand rubbing and clapping, counting aloud, tune humming, giggling, and dancing, as well as complex behavioral routines, such as wandering a fixed route, collecting and hoarding objects, and rituals involving toileting and dressing.

Utilization Behavior. This is stimulus-bound behavior during which patients grasp and repeatedly use objects in their visual field, despite the objects' irrelevance to the task at hand (e.g., patients repeatedly switch lights on and off, open and close doors, or continue eating if unlimited supplies of food are within reach). During clinical interview, they may drink repeatedly from an empty cup or use scissors placed before them.

Speech and Language

Altered Speech Output. There are two types of altered speech output: aspontaneity and economy of utterance, and press of speech. In aspontaneity and economy of utterance, either the patient does not initiate conversation or output is limited to short phrases or stereotyped utterances. Responses to questions involve single-word replies or short, unelaborated phrases, such as "don't know." Encouragement to amplify responses are unsuccessful. In press of speech, the patient speaks interruptedly, monopolizing a conversational interchange.

Stereotypy of Speech. These are single words, phrases, or entire themes that the patient produces repeatedly and habitually either spontaneously or in response to questions, replacing appropriate conversational discourse.

Echolalia. Echolalia refers to a repetition of the utterances of others, either completely or in part, sometimes with change of syntax (e.g., Interviewer: "Did you go out yesterday?" Patient: "Did I go out yesterday") when this is a substitute for, and not a precursor to, an appropriate elaborated response.

Perseveration. "Perseveration" is defined as a repetition of a patient's own responses. It is a word or phrase that, once uttered, intrudes into the patient's subsequent utterances. It differs from a stereotypy in that the repeated word or phrase is not habitual. Perseverations may occur spontaneously in conversation or are elicited in naming tasks (e.g., the patient names scissors as "scissors" and later names a clock as "scissors"). Perseveration includes palilalia, in which there is immediate repetition of a word, phrase, or sentence (e.g., "I went down town, down town, down town").

Mutism. This is an absence of speech or speech sounds. Patients may pass through a transitional phase of "virtual mutism," during which they generate no propositional speech, yet echolalic responses and some automatic speech (e.g., "three" when prompted with "one, two") may still be present.

Physical Signs

Primitive Reflexes. At least one of the following is present: grasp, snout, sucking reflexes.

Incontinence. This refers to voiding of urine or feces without concern.


Significant Impairment on Frontal Lobe Tests in the Absence of Severe Amnesia, Aphasia, or Perceptuospatial Disorder. Impairment on frontal lobe tests is defined operationally as failures (scores lower than the fifth percentile) on conventional tests of frontal lobe function (e.g., Wisconsin/Nelson card sort, Stroop, Trail Making) in which a qualitative pattern of performance typically associated with frontal lobe dysfunction is demonstrated: concreteness, poor set shifting, perseveration, failure to use information from one trial to guide subsequent responses, inability to inhibit overlearned responses, and poor organization and temporal sequencing. Abnormal scores that arise secondary to memory, language, or perceptuospatial disorder (such as forgetting instructions or the inability to recognize or locate test stimuli) would not be accepted as evidence of impairment on frontal lobe tests as operationally defined.

Patients with FTD may perform inefficiently on formal memory, language, perceptual, and spatial tests as a secondary consequence of deficits associated with frontal lobe dysfunction, such as inattention, poor self-monitoring and checking, and a lack of concern for accuracy. Poor test scores per se would not therefore exclude a diagnosis of FTD. An absence of severe amnesia, aphasia, or perceptuospatial disorder would be demonstrated by patchiness or inconsistency in performance (e.g., failure on easy items and pass on more difficult items) or demonstration that correct responses can be elicited by cuing or by directing the patient's attention to test stimuli.


Normal Despite Clinically Evident Dementia. Conventional electroencephalogram reveals frequencies within the normal range for the patient's age (minimal 0 would be considered within normal limits). There are no features of focal epileptiform activity.

Brain Imaging (Structural or Functional)

Predominant Frontal or Anterior Temporal Abnormality. Atrophy, in the case of structural imaging (computed tomography or magnetic resonance imaging), and tracer uptake abnormality, in the case of functional brain imaging (positron-emission tomography or single-photon emission computed tomography), is more marked in the frontal or anterior temporal lobes. Anterior hemisphere abnormalities may be bilaterally symmetric or asymmetric, affecting the left or right hemisphere disproportionately.

Progressive Nonfluent Aphasia

Definitions are for features (see Table 53) that differ from or are in addition to those of FTD.

Core Features

Nonfluent Spontaneous Speech With at Least One of the Following: Agrammatism, Phonemic Paraphasias, Anomia. Nonfluent speech is defined as hesitant, effortful production, with reduced rate of output. Agrammatism refers to the omission or incorrect use of grammatical terms, including articles, prepositions, auxiliary verbs, inflexions, and derivations (e.g., "man went town;" "he comed yesterday").

"Phonemic paraphasias" are sound-based errors that include incorrect phoneme use (e.g., "gat" for "cat") and phoneme transposition (e.g., "aminal" for "animal"). The frequency of such errors should exceed that reasonably attributed to normal slips of the tongue.

"Anomia" is defined as a difficulty in naming manifest by an inability to find the correct word, by prolonged word retrieval latencies relative to the norm, or by incorrect word production. The availability of partial knowledge of a word, such as the initial letter, would be consistent with anomia, as would several attempts to produce a word, each yielding a close approximation (e.g., "scinners... sivvers... scivvers. . . scissors").

Supportive Diagnostic Features: Speech and Language

Stuttering or Oral Apraxia. Articulation is effortful, and repetition of parts of a word, particularly the first consonant, occurs in the patient's effort to produce a complete utterance. (Developmental stuttering is excluded.)

Impaired Repetition. The patient has a reduced repetition span (less than five digits forward; less than four monosyllabic words) or makes phonemic paraphasias when attempting to repeat polysyllabic words, word sequences, or short phrases.

Alexia and Agraphia. Reading is nonfluent and effortful. Sound-based errors are produced (phonemic paralexias). Writing is effortful, contains spelling errors, and may show features of agrammatism.

Early Preservation of Word Meaning (Understanding Preserved at Single-Word Level). Patients should show an understanding of the nominal terms employed during a routine clinical examination. There should be a demonstrable discrepancy between word comprehension and naming: Patients should show understanding of words that they have difficulty retrieving.


Early Preservation of Social Skills. The language disorder should be the presenting symptom. At the time of onset of language disorder, patients should demonstrate preserved interpersonal and personal conduct.

Late Behavioral Changes in FTD. The changes outlined for FTD in conduct, if they occur, should not be presenting symptoms. There should be a clear, documented period of circumscribed language disorder before their development.


Nonfluent Aphasia in the Absence of Severe Amnesia or Perceptuospatial Disorder. There is difficulty in verbal expression. The language impairment may compromise performance on verbal memory tasks, so that poor scores on memory tests per se would not exclude a diagnosis of progressive aphasia. The presence of normal scores on one or more tests of visual memory, or a demonstration of normal rates of forgetting (i.e., no abnormal loss of information from immediate to delayed recall/recognition), would provide evidence for an absence of severe amnesia. An absence of a severe perceptual disorder would be demonstrated by accurate recognition of the line drawings employed during routine naming tasks, as determined by the patient's ability to produce a correct name, an approximation to the name, a functional description of the object's use, or a pertinent gesture or action pantomime. An absence of severe spatial disorder is demonstrated by normal performance on two or more spatial tasks, such as dot counting, line orientation, and drawing/copying.

Semantic Aphasia and Associative Agnosia Core Features

Fluent, Empty, Spontaneous Speech. Speech production is effortless, without hesitancies, and the patient does not search for words. However, little information is conveyed, reflecting reduced use of precise nominal terms, and increased use of broad generic terms such as "thing." In the early stages of the disorder, the "empty" nature of the speech output may become apparent only on successive interviews, which reveal a limited and repetitive conversational repertoire.

Loss of Word Meaning. There must be evidence of a disorder both of single-word comprehension and naming. A semantic deficit may be alerted by patients' remarks of the type, "What's a_? I

don't know what that is." However, impairment may not be immediately apparent in conversation because the patient's effortless speech gives an impression of facility with language. Word comprehension impairment needs to be established by word definition and object-pointing tasks. A range of stimuli needs to be tested, both animate and inanimate, because meaning may be differentially affected for different material types.

Semantic Paraphasias. Semantically related words replace correct nominal terms. Although these may include superordinate category substitutions (e.g., "animal" for camel), coordinate category errors (e.g., "dog" for elephant; "sock" for glove) must be present to meet operational criteria.

Prosopagnosia. This is impaired recognition of familiar face identity, not attributable to anomia. It is demonstrated by the patient's inability to provide defining or contextual information about faces of acquaintances or well-known celebrities.

Associative Agnosia. This is an impairment of object identity present both on visual and tactile presentation that cannot be explained in terms of nominal difficulties. It is indicated historically by reports of misuse of objects or loss of knowledge of their function. It is demonstrated clinically by patients' reports of lack of recognition and by their inability to convey the use of an object either verbally or by action pantomime.

Preserved Perceptual Matching and Drawing Reproduction. There should be some demonstration that the patient's inability to recognize faces or objects does not arise at the level of elementary visual processing. Demonstration of an ability to match for identity (to identify identical object pairs, shapes, or letters) or to reproduce simple line drawings (e.g., of a clock face, a flower, or a simple abstract design) would provide the minimum requirement to fulfill criteria for diagnosis.

Preserved Single-Word Repetition. The relative preservation of repetition skills is a central feature of the disorder. This typically includes the ability to repeat short phrases and sequences of words, although for such complex material, errors may emerge ultimately in advanced disease in the context of severe semantic loss. Demonstration of accurate repetition at least at the level of a single polysyllabic word is required to fulfill criteria for diagnosis.

Preserved Ability to Read Aloud and to Write to Dictation Orthographically Regular Words. The ability to read without comprehension is central to the disorder. However, reading performance is not entirely error free. Orthographically irregular words commonly elicit "surface dyslexic"-type errors (e.g., "pint" read to rhyme with "mint;" "glove" to rhyme with "rove" and "strove"). Patients should demonstrate the ability to read aloud accurately at least one-syllable words with regular spelling-to-sound correspondence. Writing of orthographically irregular words also typically reveals regulariza-tion errors (e.g., "caught" written as "cort"). Patients should demonstrate accurate writing to dictation at least of one-syllable orthographically regular words.

Supportive Diagnostic Features: Speech and Language

Press of Speech. The patient speaks without interruption. This occurs in many, but not all, patients.

Idiosyncratic Word Usage. Vocabulary is used consistently but idiosyncratically. For example, the word "container" applied to small objects regardless of their facility to contain, and "on the side" applied to spatial locations, both near (e.g., on the table) and distant (e.g., in Australia). The semantic link between the adopted word or phrase and its referent may be tenuous or absent.

Absence of Phonemic Paraphasias in Spontaneous Speech. Sound-based errors are absent in conversational speech. The feature, although characteristic, is not included as a core feature because occasional phonemic errors may emerge in advanced disease in the context of a profound disorder of meaning.

Surface Dyslexia/Dysgraphia. The presence of surface dyslexic errors (described earlier) in reading and writing is a strong supportive feature.

Preserved Calculation. The preserved ability of patients to calculate (to carry out accurately two-digit written addition and subtraction) is characteristic. It is not included as a core feature because calculation skills may break down in advanced disease as a consequence of failure to recognize the identity of Arabic numerals.


Loss of Sympathy and Empathy. Patients are regarded by relatives as self-centered, lacking in emotional warmth, and lacking awareness of the needs of others.

Narrowed Preoccupations. Patients are reported to have a narrowed range of interests that they pursue at the expense of routine daily activities (e.g., doing jigsaw puzzles all day and neglecting the housework).

Parsimony. Patients show an abnormal preoccupation with money or financial economy. This may be demonstrated by hoarding or constant counting of money, by patients' avoidance of spending their own money, by their purchase of the cheapest items regardless of quality, or by their attempts to restrain usage by other family members of household utilities (e.g., electricity and water).


Profound Semantic Loss, Manifest in Failure of Word Comprehension and Naming or Face and Object Recognition; Preserved Phonology and Syntax, and Elementary Perceptual Processing, Spatial Skills, and Day-to-Day Memorizing. Significant impairment should be demonstrated on word comprehension and naming or famous face identification or object recognition tasks. It should be shown that poor scores arise at a semantic level and not at a more elementary level of verbal or visual processing by demonstrating that the patient can repeat words that are not understood, can match for identity, and can copy drawings of objects. Patients should demonstrate normal performance on two or more spatial tasks, such as dot counting and line orientation. Performance on formal memory tests (e.g., involving remembering words or faces) is compromised by patients' semantic disorder. Nevertheless, patients retain the ability to remember autobiographically relevant day-to-day events (e.g., that a grandchild visits on Saturdays). Such preservation is striking clinically but may be difficult to capture on formal tests, which by definition are divorced from daily life.

Features Common to Each Clinical Syndrome Diagnostic Exclusion Features

Early Severe Amnesia. Symptoms of poor memory may be present and inefficient performance demonstrated on memory tests; these may occur secondary to executive or language impairments. However, memory failures are patchy and inconsistent, and patients do not present a picture of classic amnesia. Demonstration that a patient is disoriented in both time and place and shows a consistent, pervasive amnesia for salient contemporary autobiographical events would be incompatible with the clinical syndromes of FTLD.

Spatial Disorientation. Patients with FTD who wander from a familiar environment may become lost because of failure of self-regulation of behavior (i.e., for reasons that are not primarily spatial). They do not exhibit spatial disorientation in familiar surroundings such as their own home. They negotiate their surroundings with ease, and localize objects in the environment with accurate reaching actions. Preservation of primary spatial skills is demonstrable even in patients with advanced disease by their capacity, for example, to align objects and to fold paper accurately. Evidence of poor spatial localization and disorientation in highly familiar surroundings would exclude clinical diagnoses of FTD, progressive nonfluent aphasia, or semantic aphasia and associative agnosia.

Logoclonic, Festinant Speech With Rapid Loss of Train of Thought. Logoclonia is defined as the effortless repetition of the final syllable of a word (e.g., Washington ton ton ton). Festinant speech refers to a rapid, effortless reiteration of individual phonemes. Logoclonic and festinant speech need to be distinguished from stuttering, which has an effortful quality and usually involves repetition of the first consonant or syllable. They need to be distinguished from palilalia, during which there is repetition of complete words and phrases. Loss of train of thought is a common feature of Alzheimer's disease: patients begin sentences that they fail to complete, not only because of word-finding difficulty but also because of rapid forgetting of the intended proposition. A demonstration in conversation that patients are rapidly losing track would be contrary to a diagnosis of FTLD.

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