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Transient global amnesia: Diagnosis in the emergency department
Transient Global Amnesia: Diagnosis in the Emergency Department JEANNE BASIOR, MD,* STEPHEN VOGEL, MD,t JOSEPH MITTON, MDT
Among neuropsychiatric emergencies, acute change in mental status is one of the most common presentations seen in the emergency department (ED). The abrupt occurrence of a transient amnesia in the absence of associated neurological abnormalities was first noted by Bender,’ and the syndrome of transient global amnesia (TGA) was originally described by Fisher and Adams2 in 1964. Other authors have since contributed further case reports and examined predisposing factors and prognoses. Transient global amnesia is a sudden, temporary amnesia during which personal identity and neurological function remain intact. It ends with complete restoration of memory function except for a permanent amnesia of the period of the attack. Twenty cases were diagnosed in the emergency department of Evanston Hospital, a teaching hospital with 36,000 annual ED visits. This covered a five-year period, and did not include direct hospital admissions that bypassed the ED. A retrospective review was undertaken to evaluate which patient characteristics and diagnostic factors are present when an individual is first seen in the emergency department. The purposes of this review were the following: 1) to document the frequency of occurrence of ED patients with a final diagnosis of TGA; 2) to examine signs, symptoms, physical findings, and laboratory parameters; 3) to increase the ED physician’s suspicion for and ability to detect this form of memory disorder; and 4) to evaluate whether the availability of computerized tomographic (CT) scans has added to our knowledge and understanding of this syndrome.
From the “Section of Emergency Medicine, Department icine, Northwestern University Medical School, Chicago, and the tDivision of Emergency Medicine, Department icine, Evanston Hospital/McGaw Medical Center of western University, Evanston, Illinois. Manuscript received July 22, 1984; revision received 26, 1984; revision accepted December 7, 1984.
of MedIllinois, of MedNorth-
November
Address reprint requests to Dr. Vogel: Division of Emergency Medicine, Evanston Hospital, 2650 Ridge Avenue, Evanston, IL 60201.
Key Words: Amnesia, transient
352
global.
METHODS Case records of patients presenting to the ED with TGA over a five-year period (January 1979 to January 1984), including emergency department and in-patient hospitalization data, were retrospectively examined. Only patients with a final diagnosis of TGA were included; patients with other evidence of neurological dysfunction were excluded, despite the possibility of their having concurrent amnesia. The records were analyzed with respect to the patient history at onset, clinical characteristics and examination, precipitating factors, risk factors, and outcome. Follow-up records were obtained from the individual physicians or consulting neurologists involved.
RESULTS Demographics. Twenty cases of TGA were diagnosed in the emergency department during this fiveyear period. The patients ranged in age from 34 to 81 years, with a mean age of 60 years and a median of 60 years (Table 1). The group included ten males and ten females. The duration of symptoms ranged from 1’12 to 20 hours. Although the longest episode occurred in the oldest patient, no other correlation between age and duration of episode was found. History. The majority of patients were in good health at the time of the attack. Eight patients were using medication. Four were using antihypertensive drugs, one was using nitrates and a beta-blocker, one was using digoxin, one was using a thyroid supplement, and one was using a non-steroidal anti-inflammatory agent (Table 1). In 11 patients, risk factors for cerebrovascular disease. such as hypertension, arrhythmia, a history of cardiac murmur, or cigarette smoking were present, including one patient with peripheral vascular disease who had sustained an acute myocardial infarction two months earlier. Specific exacerbating factors were elicited in several patients, including two patients with post-coital attacks, two with vomiting episodes, and three with preceding or concurrent headache. Three patients reported having had a similar episode ( I. 18. and 24 months earlier). Two patients reported episodes of
BASIOR
TABLE1. Historical
Factors
in 20 Patients
with Transient
ET AL l TRANSIENT
GLOBAL
AMNESIA
Global Amnesia
Duration of Symptoms (hours)
Medications
59lMale
2
-
JO/Male 64lMale
3 2
Age (years)/Sex
Synthroid
GO/Female 59/Male GO/Male 53/Female 72/Female
5 6 12 12 12
lnderal;
64/Male 461Male
12 6
Digoxin
62/Female
6
Tolectin
BE/Female
6
59/Female 46lMale 48lMale 34lMale
12 12 12 1.5
8ltFemale
20
73/Female
4
69IFemale
2
66/Female
12
aldomet -
Enduron
-
Minipress; hygroton Corgard; nitrodur
Hydrochlorothiazide; clonidine; hydralazine
syncope several years previously. Two patients had two to four ounces of alcohol several hours prior to the onset of symptoms. One patient presented in great pain with an acute anterior shoulder dislocation and developed amnesia shortly after receiving 6 mg of morphine in incremental intravenous doses; there was no change with naloxone. Examination. Although symptoms were characteristic, physical findings and laboratory parameters were nonspecific. No significant localizing neurological deficits were present upon examination in the emergency department, except for two patients with decreased left-knee jerk thought to be secondary to lumbar radiculopathy, and one patient with decreased bilateral auditory acuity to air conduction who also had absent knee and ankle jerks and a history of degenerative joint disease (Table 2). Eight patients were hypertensive in the emergency department, and two patients, one of whom was on a diuretic, exhibited
Past Medical
History
Remote head trauma; syncope
Smoker; thyroidectomy; syncope Hypertension Peptic ulcerative disease Hypertension; Meniere’s disease Atrial fibrillation Cardiac murmur Hypertension; degenerative joint disease Hypertension; old myocardial infarction? Left mastectomy Remote head trauma Hypertension Acute myocardial infarction; peripheral vascular disease Degenerative joint disease; radiculopathy Hypertension; right mastectomy Degenerative joint disease Hypertension; left bundle branch block
Initiating
Factors
Vomiting Tension
headache -
Headache Vomiting Post-coital intake?) Frontal
(wine
headache
Alcohol intake? Post-coital -
Playing
piano
Shoulder dislocationgiven morphine Headache
mild postural blood pressure changes. There were no fundoscopic findings other than mild hypertensive retinopathy. All patients displayed marked memory deficits and dramatic inability to grasp the facts of their situation in the emergency department, frequently asked repetitive questions, and showed a common deficit in retaining new information for more than a few seconds. Laboratory findings. Abnormalities were noted in two patients with elevated leukocyte counts and normal differentials, in one patient on diuretic therapy with a serum potassium level of 2.7 mEq/l, and in one patient with an anion gap who had vomited prior to presentation (Table 2). No patient had hypoglycemia or evidence of toxic ingestion. Electrocardiograms (ECGs) were normal except for one patient with left bundle branch block and another with a myocardial infarction two months earlier. Computerized tomographic scans with and without 353
AMERICAN
JOURNAL
TABLE2. Clinical
Age (years)/Sex
OF EMERGENCY
and Laboratory
Results
Physical Examination
MEDICINE
n Volume 3, Number 4 l July 1985
in 20 Patients
with Transient
Laboratory
Global Amnesia
CT’
EEGt
Other
Anion gap = 21 Normal
Negative
Negative
-
Negative
-
Orthostatic BP* = 1601108 Normal Left knee hyporeflexia Normal
WBC = 12.4 Normal Normal Normal
Negative Negative Negative Negative
Bitemporal slow waves with hyperventilation Negative Negative Negative Negative
Normal
Negative
Cholesterol = 284 Normal Normal Cardiomegaly; WBC = 13.5
68/Female 59IFemale
BP* = 160/98; orthostatic Normal Normal BP* = 140/100; bilateral knee/ ankle jerks absent Normal BP* = 170/100
Normal Normal
46/Male 48lMale
Normal Normal
34IMale
Decreased right leg pulses
dl/Female
Left knee jerk absent; decreased hearing BP* = 1601100
Normal Potassium = 2.7 mEq/l S/P Myocardial infarction on EKG Normal
59/Male
Normal
50/Male
BPS = 150/100
64lMale GO/Female 59lMale GO/Male 53iFemale 72/Female 64iMale 46iMale 62/Female
73iFemale 69IFemale
66/Female
BP* = 170/90; shoulder dislocation BP+ = 2181132
Recurrent
episode -
Negative
Bitemporal sharp transients Negative
Not done Negative
Negative Not done Not done
-
Negative Negative
Not done Not done
Negative
Negative Negative
Negative
Negative
Negative
Not done
-
Normal
Negative
Not done
Normal
Not done
Not done
Similar episode 24 months earlier -
Normal
Negative
Negative
-
Similar episode 18 months earlier -
Similar episode month earlier
Off medication 3 days
1
for
* Computerized tomography. T Electroencephalogram. $ Blood pressure in mm Hg.
infusion were performed on 18 patients, and the results were interpreted as being within normal limits or as demonstrating diffuse cortical atrophy consistent with age. Electroencephalographic results obtained after resolution of symptoms in 13 patients were normal, except for one patient with sharp transient waves in the bitemporal area and one patient with bitemporal slow waves elicited with hyperventilation. Both patterns have been reported with TGA and are considered to be of no specific diagnostic significance.3,4 In three patients in whom non-invasive carotid evaluations were completed with phonoangiography and oculoplethysmography, results were negative for vascular disease. One patient underwent arteriographic evalu354
ation of the carotid arteries and was found to have 50% left carotid stenosis without ulcerated plaque. Outcome. All patients remain well, without neurological deficits, seizures, or transient ischemic attacks (TIAs) (follow-up 4 to 60 months). One patient has since had a recurrent episode consistent with TGA. In no patients have symptoms of cerebral ischemia occurred. DISCUSSION Transient global amnesia involves an isolated neurological deficit of memory function. The episode resolves spontaneously after several hours. rarely
BASIOR
lasting longer than twenty-four hours.s During the episode, a simultaneous impairment of retrograde and anterograde memory occurs. The retrograde amnesia extends for a variable time, from hours to years, during which a patient may not be aware of recent significant events of his life, such as the birth of, a grandchild or a recent trip. The anterograde amnesia is manifest by the patient’s puzzlement over his situation, with characteristic repetitive questioning regarding his surrounding circumstances. The inability to retain new memory tracings results in a permanent amnesia of the episode. Patients usually become aware of the predicament in which they find themselves. Personal identification remains intact, as well as complex neurological functions such as perception, recognition, and abstraction. Speech, writing, and language functions are unimpaired. Patients are able to perform complex acts, such as driving an automobile or completing their work; there is a report of a patient who was able to perform in an organ recital during an episode of TGA.6 In rare cases, it takes the observations of a spouse or close relative to appreciate the presence of an abnormality. There are two phases to the typical episode of TGA.’ During the first, the patient is unable to encode recent memory for a variable period, associated with a retrograde anmesia of hours to years; distant recall and immediate memory are retained. The second phase occurs over several hours, during which the retrograde amnesia progressively shrinks, with more distant events returning first, along with recovery of recent memory encoding. There is a persistent amnesia for the acute phase. This is a relatively pure disturbance of memory and is considered global in that all sensory modalities of perception are involved, not in the sense that all aspects of memory are affected.’ Memory can be divided into three distinct functions, each evaluable by different tests. “Immediate memory” or recall is the ability to remember a few bits of information over a period of a few seconds without distraction. It can be tested by the digit span, or the repetition of a series of numbers (usually seven) after presentation by an examiner. This function usually remains intact in TGA. “Recent memory” is the ability to learn new material and retain it; this function is thought to result from the transduction of neural impulses into macromolecular engrams.8 Short-term memory is converted into long-term memory by storage of these engrams. It can be tested by the ability to remember the physician’s name, or several unrelated words or objects for periods of a few minutes in the presence of distraction. It is hypothesized that TGA involves a deficit in this function9; there is a consolidation blocklo that causes the anterograde amnesia. Often the patient can remember the physician’s name for no longer than 30 to 60 seconds. “Remote
ET AL
W TRANSIENT
GLOBAL
AMNESIA
memory” is the ability to recall or retrieve information learned in the past and can be tested by remembrance of personal information (birth dates or schools) and a recollection of learned material, such as listing presidents or months. A deficit in remote memory also occurs in TGA,‘O and this additional retrieval block accounts for the retrograde amnesia. Memory function is anatomically associated with the core of the limbic system in the temporal lobes, which includes the mamillary bodies (posterior hypothalamus), the hippocampus (medial portion of the temporal lobe), and the fornix. The vascular supply to this area arises from the posterior cerebral artery branches of the vertebrobasilar system. Transient global amnesia most commonly occurs in individuals 50 to 70 years of age, and slight male preponderance is rep0rted.j Patients are in good general and mental health and are usually free of previous neurological signs or symptoms. Mild transient neurological deficits have been noticed to resolve with memory improvement.5 Frequently, there is an association with hypertension,5 and patients may have one or more risk factors for cerebrovascular disease, such as age, sex, history of heart disease, or previous stroke.2-4g” Patients have no impairment of consciousness, and neurological examination results are usually otherwise normal. Seizure activity, prodromes, automatic behaviors, and psychiatric symptoms such as illusions, hallucinations, or delusions, are conspicuously absent. Specific inciting factors have been indicated in previous case reports, and these should be sought in the history.2*3.‘1 Strenuous activity, exposure to cold water, driving, sexual intercourse, or painful stimuli have frequently preceded the onset of an episode of TGA, as seen in several of our patients. These factors all have components of being highly emotional experiences. No specific abnormalities in laboratory results are involved. Other causes of impaired mental status, such as hypoglycemia, intoxication with alcohol or drugs, and central nervous system (CNS) infection, are absent, as was the case in our group. The results of CT scans of the brain are uniformly normal. The patients reported here represent the largest reported group of patients with TGA who underwent diagnostic CT scanning. Electroencephalographic recordings done after symptoms resolve are normal or show nonspecific abnormalities without seizure activity. The differential diagnosis should be directed to ruling out other causes of CNS dysfunction besides toxic encephalopathy or encephalitis. A history of head trauma should be sought from the patient or relatives. Post-anoxic or post-herpetic encephalopathy can usually be ascertained by history. The amnesia of chronic alcohol abuse is not a transient phenomenon. Confusional states or dementia will have additional ev355
AMERICAN
JOURNAL
OF EMERGENCY
MEDICINE
n Volume 3, Number 4 n July 1985
idence of neurological or mental-status abnormalities on examination. Psychogenic amnesia can be differentiated by the patient’s relative lack of concern for his or her situation, as well as the inability to recall personal data such as name or birth place that is associated with this type of amnesia. The absence of an aura or significant automatic behavior, as well as the relatively longer length of amnesia in TGA, differentiates this syndrome from temporal lobe epilepsy, although this distinction can be difficult to make without an EEG made during the episode. There are reports of CNS tumors’3,‘4 in the anatomical locus of memory function, as well as a localized left temporal hemorrhage,15 causing isolated amnestic symptoms. For this reason, all patients with a presumptive diagnosis of TGA should undergo CT scanning both with and without infusion, although this may not be necessary on an emergency basis. Migraine and its variants usually can be excluded by the additional signs and manifestations of headache symptoms or by EEG studies done during the episode. Mere forgetfulness results from difficulty in retrieval of stored information; the patient may be able to remember after cueing or clues. Transient global amnesia is a result of transient hippocampal dysfunction.3 Although the precise pathophysiological basis is unknown, it was generally accepted as being because of transient cerebrovascular insufficiency in the vertebral basilar territory, which supplies the ascending reticular activating system and the para-hippocampal-fornical-mamillary system of the inferomedial temporal lobe.3,4*1* When these patients have had angiographic studies, no convincing correlation with vascular disease has been found. The etiology, then, remains unclear. No EEG evidence of seizure activity has been demonstrated during the acute episode, although Fisher notes that the usually highly emotional factors initiating TGA suggest an electrophysiological disturbance consistent with seizure.12 Amnestic syndromes have also been associated with polycythemia, myxomatous degeneration of the mitral valve, emboli arising during coronary angiography, and mitral-valve prolapse.” There are reports of a permanent amnestic stroke caused by posterior cerebral artery occlusion.4s’6 Some series have reported TIA-like symptoms both of the carotid and vertebral basilar systems in association with TGA.4,5 In addition, TGA has been observed following both therapeutic and toxic doses of clioquinal, an anti-diarrhea1 agent (not available in the U.S.).” Transient global amnesia is a benign condition, is unlikely to recur, and has a generally good prognosis. Although Mathew and Meyer4 concluded that higher recurrence rates of TGA and progressive memory deficits may occur in the elderly or in those with risk factors for cerebrovascular disease, subsequent studies by Nauseida and ShermanI and Shuping et al.,” and a prospective study by Jensen and 01ivarius3 refute this conclusion. It is accepted that the prognosis 356
is not likely to involve the high risk of subsequent neurological impairment seen with TIAs, unless other risk factors for cerebrovascular disease are present. Emergency department evaluation includes a complete history with particular attention to temporal development , progression of memory impairment, and the basic state of health. Specifics should include any cardiovascular risk factors, previous neurological impairment, possible head trauma, drug ingestion, toxic exposure, or anoxia. Immediate inciting events surrounding the occurrence of amnesia should be detailed. Physical examination should include a thorough neurological and mental status check. Laboratory analysis is directed toward toxic, metabolic, and infectious causes of confusion and requires complete determinations of leukocyte count, hemoglobin, hematocrit, glucose level, serum electrolytes, blood urea nitrogen, creatinine, calcium levels, blood-alcohol levels, and serum and urine toxicity. Electrocardiograms are routine. Coagulation profiles will indicate any hemorrhagic diathesis. Ideally, an electroencephalogram with nasopharyngeal leads should be conducted on an emergency basis during the acute episode, as EEGs obtained after resolution of symptoms are of questionable value. Studies of brain-wave patterns during these attacks may help unravel the possible etiology behind TGA. Neurological consultation may be helpful, but is not required emergently if other causes of amnesia can be ruled out. The neurologist should be offered the opportunity, however, to see the patient while still symptomatic. Computerized axial tomography of the head with and without dye infusion should be performed emergently if there is an unreliable or unobtainable history. To secure the diagnosis, it is necessary to rule out other causes of amnesia and observe complete recovery of baseline mental status. After emergency department evaluation, patients with a presumptive diagnosis of TGA should be admitted for a brief period of observation to assure resolution of amnesia. Some sources recommend a trial of short-term antiplatelet therapy,- 3,4 although there is no documentation that this treatment is beneficial as a prophylaxis. There is no role for systemic anticoagulation. If symptoms have not fully cleared within 24 hours of onset, a further neurological workup should be initiated, including lumbar puncture and EEG. Therapy should be aimed at recognition and treatment of any underlying disease or risk factors. Routine follow-up by the internist or family physician, with attention to the development of new signs or symptoms of new neurological dysfunction or recurrence of episodes of amnesia, is recommended. SUMMARY Transient global amnesia is a not uncommon presentation of acutely altered neuropsychiatric status. It
BASIOR
is, however, a clinical diagnosis that requires a careful history with attention to inciting events, risk factors for cerebrovascular disease, the absence of other abnormalities on neurological examination, and normal results of laboratory studies. Knowledge of the generally benign course of TGA can facilitate the care and psychological support of these patients and their families.
The authors thank Dr. Shirley J. Forbes of the Division rology and Ms. Barbara Williams for their assistance.
of Neu-
REFERENCES 1. Bender MB. Syndrome of isolated episode of confusion with amnesia. J Hillside Hosp 1956;5:212-215. 2. Fisher C, Adams RD. Transient global amnesia. Acta Neural Stand 1964;40 (suppl 19):1-63. 3. Jensen TS, Olivarius BDF. Transient global amnesia-Its clinical and pathophysiological basis and prognosis. Acta Neurol Stand 1981;63:220-230. 4. Mathew NT, Meyer JS. Pathogenesis and natural history of transient global amnesia. Stroke 1974;5:303-311. 5. Whitty CWM. Transient global amnesia. In Whitty CWM, Zangwill OL (eds). Amnesia. New York: Appleton-CenturyCrofts, 1966:93-103. 6. Byer JA, Crowley WJ Jr. Musical performance during transient global amnesia. Neurology 1980;30:80-82.
ET AL n TRANSIENT
GLOBAL
AMNESIA
7. Patten BM. Transient global amnesia syndrome. JAMA 1971;217:690-691. 8. Hechter 0, Halkerstan I. On the nature of macromolecular coding in neuronal memory. Perspect Biol Med 1964;7:183-198. 9. Shuttleworth EC, Morris CE. The transient global amnesia syndrome. Arch Neural 1966;15:515-520. 10. Gordon B, Marin OSM. Transient global amnesia: An extensive case report. J Neural Neurosurg Psychiatry 1979;42:572-575. 11. Shuping JR, Rollinson RD, Toole JF. Transient global amnesia. Ann Neural 1979;7:281-284. 12. Fisher CM. Transient global amnesia-Precipitating activities and other observations. Arch Neural 1982;39:605608. 13. Shuping JR, Toole JF, Alexander E Jr. Transient global amnesia due to glioma in the dominant hemisphere. Neurology 1980;30:88-90. 14. Findler G, Feinsod M, Lijovetzky G, et al. Transient global amnesia associated with a single metastasis in the nondominant hemisphere. J Neurosurg 1983;58:303-305. 15. Landi G, Giusti MC, Guidotti M. Transient global amnesia due to left temporal hemorrhage. J Neural Neurosurg Psychiatry 1982;00:1062-1063. 16. Benson DF, Marsden CD, Meadows JC. The amnesiac syndrome of posterior cerebral artery occlusion. Acta Neural Stand 1974;50:133-145. 17. Mumenthaler M, Kaeser HE, Meyer A, et al. Transient global amnesia after clioquinal. J Neural Neurosurg Psychiatry 1979;42:1084-1090. 18. Nausieda PA, Sherman IC. Long-term prognosis in transient global amnesia. JAMA 1979;241:392-393.
357
Among neuropsychiatric emergencies, acute change in mental status is one of the most common presentations seen in the emergency department (ED). The abrupt occurrence of a transient amnesia in the absence of associated neurological abnormalities was first noted by Bender,’ and the syndrome of transient global amnesia (TGA) was originally described by Fisher and Adams2 in 1964. Other authors have since contributed further case reports and examined predisposing factors and prognoses. Transient global amnesia is a sudden, temporary amnesia during which personal identity and neurological function remain intact. It ends with complete restoration of memory function except for a permanent amnesia of the period of the attack. Twenty cases were diagnosed in the emergency department of Evanston Hospital, a teaching hospital with 36,000 annual ED visits. This covered a five-year period, and did not include direct hospital admissions that bypassed the ED. A retrospective review was undertaken to evaluate which patient characteristics and diagnostic factors are present when an individual is first seen in the emergency department. The purposes of this review were the following: 1) to document the frequency of occurrence of ED patients with a final diagnosis of TGA; 2) to examine signs, symptoms, physical findings, and laboratory parameters; 3) to increase the ED physician’s suspicion for and ability to detect this form of memory disorder; and 4) to evaluate whether the availability of computerized tomographic (CT) scans has added to our knowledge and understanding of this syndrome.
From the “Section of Emergency Medicine, Department icine, Northwestern University Medical School, Chicago, and the tDivision of Emergency Medicine, Department icine, Evanston Hospital/McGaw Medical Center of western University, Evanston, Illinois. Manuscript received July 22, 1984; revision received 26, 1984; revision accepted December 7, 1984.
of MedIllinois, of MedNorth-
November
Address reprint requests to Dr. Vogel: Division of Emergency Medicine, Evanston Hospital, 2650 Ridge Avenue, Evanston, IL 60201.
Key Words: Amnesia, transient
352
global.
METHODS Case records of patients presenting to the ED with TGA over a five-year period (January 1979 to January 1984), including emergency department and in-patient hospitalization data, were retrospectively examined. Only patients with a final diagnosis of TGA were included; patients with other evidence of neurological dysfunction were excluded, despite the possibility of their having concurrent amnesia. The records were analyzed with respect to the patient history at onset, clinical characteristics and examination, precipitating factors, risk factors, and outcome. Follow-up records were obtained from the individual physicians or consulting neurologists involved.
RESULTS Demographics. Twenty cases of TGA were diagnosed in the emergency department during this fiveyear period. The patients ranged in age from 34 to 81 years, with a mean age of 60 years and a median of 60 years (Table 1). The group included ten males and ten females. The duration of symptoms ranged from 1’12 to 20 hours. Although the longest episode occurred in the oldest patient, no other correlation between age and duration of episode was found. History. The majority of patients were in good health at the time of the attack. Eight patients were using medication. Four were using antihypertensive drugs, one was using nitrates and a beta-blocker, one was using digoxin, one was using a thyroid supplement, and one was using a non-steroidal anti-inflammatory agent (Table 1). In 11 patients, risk factors for cerebrovascular disease. such as hypertension, arrhythmia, a history of cardiac murmur, or cigarette smoking were present, including one patient with peripheral vascular disease who had sustained an acute myocardial infarction two months earlier. Specific exacerbating factors were elicited in several patients, including two patients with post-coital attacks, two with vomiting episodes, and three with preceding or concurrent headache. Three patients reported having had a similar episode ( I. 18. and 24 months earlier). Two patients reported episodes of
BASIOR
TABLE1. Historical
Factors
in 20 Patients
with Transient
ET AL l TRANSIENT
GLOBAL
AMNESIA
Global Amnesia
Duration of Symptoms (hours)
Medications
59lMale
2
-
JO/Male 64lMale
3 2
Age (years)/Sex
Synthroid
GO/Female 59/Male GO/Male 53/Female 72/Female
5 6 12 12 12
lnderal;
64/Male 461Male
12 6
Digoxin
62/Female
6
Tolectin
BE/Female
6
59/Female 46lMale 48lMale 34lMale
12 12 12 1.5
8ltFemale
20
73/Female
4
69IFemale
2
66/Female
12
aldomet -
Enduron
-
Minipress; hygroton Corgard; nitrodur
Hydrochlorothiazide; clonidine; hydralazine
syncope several years previously. Two patients had two to four ounces of alcohol several hours prior to the onset of symptoms. One patient presented in great pain with an acute anterior shoulder dislocation and developed amnesia shortly after receiving 6 mg of morphine in incremental intravenous doses; there was no change with naloxone. Examination. Although symptoms were characteristic, physical findings and laboratory parameters were nonspecific. No significant localizing neurological deficits were present upon examination in the emergency department, except for two patients with decreased left-knee jerk thought to be secondary to lumbar radiculopathy, and one patient with decreased bilateral auditory acuity to air conduction who also had absent knee and ankle jerks and a history of degenerative joint disease (Table 2). Eight patients were hypertensive in the emergency department, and two patients, one of whom was on a diuretic, exhibited
Past Medical
History
Remote head trauma; syncope
Smoker; thyroidectomy; syncope Hypertension Peptic ulcerative disease Hypertension; Meniere’s disease Atrial fibrillation Cardiac murmur Hypertension; degenerative joint disease Hypertension; old myocardial infarction? Left mastectomy Remote head trauma Hypertension Acute myocardial infarction; peripheral vascular disease Degenerative joint disease; radiculopathy Hypertension; right mastectomy Degenerative joint disease Hypertension; left bundle branch block
Initiating
Factors
Vomiting Tension
headache -
Headache Vomiting Post-coital intake?) Frontal
(wine
headache
Alcohol intake? Post-coital -
Playing
piano
Shoulder dislocationgiven morphine Headache
mild postural blood pressure changes. There were no fundoscopic findings other than mild hypertensive retinopathy. All patients displayed marked memory deficits and dramatic inability to grasp the facts of their situation in the emergency department, frequently asked repetitive questions, and showed a common deficit in retaining new information for more than a few seconds. Laboratory findings. Abnormalities were noted in two patients with elevated leukocyte counts and normal differentials, in one patient on diuretic therapy with a serum potassium level of 2.7 mEq/l, and in one patient with an anion gap who had vomited prior to presentation (Table 2). No patient had hypoglycemia or evidence of toxic ingestion. Electrocardiograms (ECGs) were normal except for one patient with left bundle branch block and another with a myocardial infarction two months earlier. Computerized tomographic scans with and without 353
AMERICAN
JOURNAL
TABLE2. Clinical
Age (years)/Sex
OF EMERGENCY
and Laboratory
Results
Physical Examination
MEDICINE
n Volume 3, Number 4 l July 1985
in 20 Patients
with Transient
Laboratory
Global Amnesia
CT’
EEGt
Other
Anion gap = 21 Normal
Negative
Negative
-
Negative
-
Orthostatic BP* = 1601108 Normal Left knee hyporeflexia Normal
WBC = 12.4 Normal Normal Normal
Negative Negative Negative Negative
Bitemporal slow waves with hyperventilation Negative Negative Negative Negative
Normal
Negative
Cholesterol = 284 Normal Normal Cardiomegaly; WBC = 13.5
68/Female 59IFemale
BP* = 160/98; orthostatic Normal Normal BP* = 140/100; bilateral knee/ ankle jerks absent Normal BP* = 170/100
Normal Normal
46/Male 48lMale
Normal Normal
34IMale
Decreased right leg pulses
dl/Female
Left knee jerk absent; decreased hearing BP* = 1601100
Normal Potassium = 2.7 mEq/l S/P Myocardial infarction on EKG Normal
59/Male
Normal
50/Male
BPS = 150/100
64lMale GO/Female 59lMale GO/Male 53iFemale 72/Female 64iMale 46iMale 62/Female
73iFemale 69IFemale
66/Female
BP* = 170/90; shoulder dislocation BP+ = 2181132
Recurrent
episode -
Negative
Bitemporal sharp transients Negative
Not done Negative
Negative Not done Not done
-
Negative Negative
Not done Not done
Negative
Negative Negative
Negative
Negative
Negative
Not done
-
Normal
Negative
Not done
Normal
Not done
Not done
Similar episode 24 months earlier -
Normal
Negative
Negative
-
Similar episode 18 months earlier -
Similar episode month earlier
Off medication 3 days
1
for
* Computerized tomography. T Electroencephalogram. $ Blood pressure in mm Hg.
infusion were performed on 18 patients, and the results were interpreted as being within normal limits or as demonstrating diffuse cortical atrophy consistent with age. Electroencephalographic results obtained after resolution of symptoms in 13 patients were normal, except for one patient with sharp transient waves in the bitemporal area and one patient with bitemporal slow waves elicited with hyperventilation. Both patterns have been reported with TGA and are considered to be of no specific diagnostic significance.3,4 In three patients in whom non-invasive carotid evaluations were completed with phonoangiography and oculoplethysmography, results were negative for vascular disease. One patient underwent arteriographic evalu354
ation of the carotid arteries and was found to have 50% left carotid stenosis without ulcerated plaque. Outcome. All patients remain well, without neurological deficits, seizures, or transient ischemic attacks (TIAs) (follow-up 4 to 60 months). One patient has since had a recurrent episode consistent with TGA. In no patients have symptoms of cerebral ischemia occurred. DISCUSSION Transient global amnesia involves an isolated neurological deficit of memory function. The episode resolves spontaneously after several hours. rarely
BASIOR
lasting longer than twenty-four hours.s During the episode, a simultaneous impairment of retrograde and anterograde memory occurs. The retrograde amnesia extends for a variable time, from hours to years, during which a patient may not be aware of recent significant events of his life, such as the birth of, a grandchild or a recent trip. The anterograde amnesia is manifest by the patient’s puzzlement over his situation, with characteristic repetitive questioning regarding his surrounding circumstances. The inability to retain new memory tracings results in a permanent amnesia of the episode. Patients usually become aware of the predicament in which they find themselves. Personal identification remains intact, as well as complex neurological functions such as perception, recognition, and abstraction. Speech, writing, and language functions are unimpaired. Patients are able to perform complex acts, such as driving an automobile or completing their work; there is a report of a patient who was able to perform in an organ recital during an episode of TGA.6 In rare cases, it takes the observations of a spouse or close relative to appreciate the presence of an abnormality. There are two phases to the typical episode of TGA.’ During the first, the patient is unable to encode recent memory for a variable period, associated with a retrograde anmesia of hours to years; distant recall and immediate memory are retained. The second phase occurs over several hours, during which the retrograde amnesia progressively shrinks, with more distant events returning first, along with recovery of recent memory encoding. There is a persistent amnesia for the acute phase. This is a relatively pure disturbance of memory and is considered global in that all sensory modalities of perception are involved, not in the sense that all aspects of memory are affected.’ Memory can be divided into three distinct functions, each evaluable by different tests. “Immediate memory” or recall is the ability to remember a few bits of information over a period of a few seconds without distraction. It can be tested by the digit span, or the repetition of a series of numbers (usually seven) after presentation by an examiner. This function usually remains intact in TGA. “Recent memory” is the ability to learn new material and retain it; this function is thought to result from the transduction of neural impulses into macromolecular engrams.8 Short-term memory is converted into long-term memory by storage of these engrams. It can be tested by the ability to remember the physician’s name, or several unrelated words or objects for periods of a few minutes in the presence of distraction. It is hypothesized that TGA involves a deficit in this function9; there is a consolidation blocklo that causes the anterograde amnesia. Often the patient can remember the physician’s name for no longer than 30 to 60 seconds. “Remote
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memory” is the ability to recall or retrieve information learned in the past and can be tested by remembrance of personal information (birth dates or schools) and a recollection of learned material, such as listing presidents or months. A deficit in remote memory also occurs in TGA,‘O and this additional retrieval block accounts for the retrograde amnesia. Memory function is anatomically associated with the core of the limbic system in the temporal lobes, which includes the mamillary bodies (posterior hypothalamus), the hippocampus (medial portion of the temporal lobe), and the fornix. The vascular supply to this area arises from the posterior cerebral artery branches of the vertebrobasilar system. Transient global amnesia most commonly occurs in individuals 50 to 70 years of age, and slight male preponderance is rep0rted.j Patients are in good general and mental health and are usually free of previous neurological signs or symptoms. Mild transient neurological deficits have been noticed to resolve with memory improvement.5 Frequently, there is an association with hypertension,5 and patients may have one or more risk factors for cerebrovascular disease, such as age, sex, history of heart disease, or previous stroke.2-4g” Patients have no impairment of consciousness, and neurological examination results are usually otherwise normal. Seizure activity, prodromes, automatic behaviors, and psychiatric symptoms such as illusions, hallucinations, or delusions, are conspicuously absent. Specific inciting factors have been indicated in previous case reports, and these should be sought in the history.2*3.‘1 Strenuous activity, exposure to cold water, driving, sexual intercourse, or painful stimuli have frequently preceded the onset of an episode of TGA, as seen in several of our patients. These factors all have components of being highly emotional experiences. No specific abnormalities in laboratory results are involved. Other causes of impaired mental status, such as hypoglycemia, intoxication with alcohol or drugs, and central nervous system (CNS) infection, are absent, as was the case in our group. The results of CT scans of the brain are uniformly normal. The patients reported here represent the largest reported group of patients with TGA who underwent diagnostic CT scanning. Electroencephalographic recordings done after symptoms resolve are normal or show nonspecific abnormalities without seizure activity. The differential diagnosis should be directed to ruling out other causes of CNS dysfunction besides toxic encephalopathy or encephalitis. A history of head trauma should be sought from the patient or relatives. Post-anoxic or post-herpetic encephalopathy can usually be ascertained by history. The amnesia of chronic alcohol abuse is not a transient phenomenon. Confusional states or dementia will have additional ev355
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idence of neurological or mental-status abnormalities on examination. Psychogenic amnesia can be differentiated by the patient’s relative lack of concern for his or her situation, as well as the inability to recall personal data such as name or birth place that is associated with this type of amnesia. The absence of an aura or significant automatic behavior, as well as the relatively longer length of amnesia in TGA, differentiates this syndrome from temporal lobe epilepsy, although this distinction can be difficult to make without an EEG made during the episode. There are reports of CNS tumors’3,‘4 in the anatomical locus of memory function, as well as a localized left temporal hemorrhage,15 causing isolated amnestic symptoms. For this reason, all patients with a presumptive diagnosis of TGA should undergo CT scanning both with and without infusion, although this may not be necessary on an emergency basis. Migraine and its variants usually can be excluded by the additional signs and manifestations of headache symptoms or by EEG studies done during the episode. Mere forgetfulness results from difficulty in retrieval of stored information; the patient may be able to remember after cueing or clues. Transient global amnesia is a result of transient hippocampal dysfunction.3 Although the precise pathophysiological basis is unknown, it was generally accepted as being because of transient cerebrovascular insufficiency in the vertebral basilar territory, which supplies the ascending reticular activating system and the para-hippocampal-fornical-mamillary system of the inferomedial temporal lobe.3,4*1* When these patients have had angiographic studies, no convincing correlation with vascular disease has been found. The etiology, then, remains unclear. No EEG evidence of seizure activity has been demonstrated during the acute episode, although Fisher notes that the usually highly emotional factors initiating TGA suggest an electrophysiological disturbance consistent with seizure.12 Amnestic syndromes have also been associated with polycythemia, myxomatous degeneration of the mitral valve, emboli arising during coronary angiography, and mitral-valve prolapse.” There are reports of a permanent amnestic stroke caused by posterior cerebral artery occlusion.4s’6 Some series have reported TIA-like symptoms both of the carotid and vertebral basilar systems in association with TGA.4,5 In addition, TGA has been observed following both therapeutic and toxic doses of clioquinal, an anti-diarrhea1 agent (not available in the U.S.).” Transient global amnesia is a benign condition, is unlikely to recur, and has a generally good prognosis. Although Mathew and Meyer4 concluded that higher recurrence rates of TGA and progressive memory deficits may occur in the elderly or in those with risk factors for cerebrovascular disease, subsequent studies by Nauseida and ShermanI and Shuping et al.,” and a prospective study by Jensen and 01ivarius3 refute this conclusion. It is accepted that the prognosis 356
is not likely to involve the high risk of subsequent neurological impairment seen with TIAs, unless other risk factors for cerebrovascular disease are present. Emergency department evaluation includes a complete history with particular attention to temporal development , progression of memory impairment, and the basic state of health. Specifics should include any cardiovascular risk factors, previous neurological impairment, possible head trauma, drug ingestion, toxic exposure, or anoxia. Immediate inciting events surrounding the occurrence of amnesia should be detailed. Physical examination should include a thorough neurological and mental status check. Laboratory analysis is directed toward toxic, metabolic, and infectious causes of confusion and requires complete determinations of leukocyte count, hemoglobin, hematocrit, glucose level, serum electrolytes, blood urea nitrogen, creatinine, calcium levels, blood-alcohol levels, and serum and urine toxicity. Electrocardiograms are routine. Coagulation profiles will indicate any hemorrhagic diathesis. Ideally, an electroencephalogram with nasopharyngeal leads should be conducted on an emergency basis during the acute episode, as EEGs obtained after resolution of symptoms are of questionable value. Studies of brain-wave patterns during these attacks may help unravel the possible etiology behind TGA. Neurological consultation may be helpful, but is not required emergently if other causes of amnesia can be ruled out. The neurologist should be offered the opportunity, however, to see the patient while still symptomatic. Computerized axial tomography of the head with and without dye infusion should be performed emergently if there is an unreliable or unobtainable history. To secure the diagnosis, it is necessary to rule out other causes of amnesia and observe complete recovery of baseline mental status. After emergency department evaluation, patients with a presumptive diagnosis of TGA should be admitted for a brief period of observation to assure resolution of amnesia. Some sources recommend a trial of short-term antiplatelet therapy,- 3,4 although there is no documentation that this treatment is beneficial as a prophylaxis. There is no role for systemic anticoagulation. If symptoms have not fully cleared within 24 hours of onset, a further neurological workup should be initiated, including lumbar puncture and EEG. Therapy should be aimed at recognition and treatment of any underlying disease or risk factors. Routine follow-up by the internist or family physician, with attention to the development of new signs or symptoms of new neurological dysfunction or recurrence of episodes of amnesia, is recommended. SUMMARY Transient global amnesia is a not uncommon presentation of acutely altered neuropsychiatric status. It
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is, however, a clinical diagnosis that requires a careful history with attention to inciting events, risk factors for cerebrovascular disease, the absence of other abnormalities on neurological examination, and normal results of laboratory studies. Knowledge of the generally benign course of TGA can facilitate the care and psychological support of these patients and their families.
The authors thank Dr. Shirley J. Forbes of the Division rology and Ms. Barbara Williams for their assistance.
of Neu-
REFERENCES 1. Bender MB. Syndrome of isolated episode of confusion with amnesia. J Hillside Hosp 1956;5:212-215. 2. Fisher C, Adams RD. Transient global amnesia. Acta Neural Stand 1964;40 (suppl 19):1-63. 3. Jensen TS, Olivarius BDF. Transient global amnesia-Its clinical and pathophysiological basis and prognosis. Acta Neurol Stand 1981;63:220-230. 4. Mathew NT, Meyer JS. Pathogenesis and natural history of transient global amnesia. Stroke 1974;5:303-311. 5. Whitty CWM. Transient global amnesia. In Whitty CWM, Zangwill OL (eds). Amnesia. New York: Appleton-CenturyCrofts, 1966:93-103. 6. Byer JA, Crowley WJ Jr. Musical performance during transient global amnesia. Neurology 1980;30:80-82.
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7. Patten BM. Transient global amnesia syndrome. JAMA 1971;217:690-691. 8. Hechter 0, Halkerstan I. On the nature of macromolecular coding in neuronal memory. Perspect Biol Med 1964;7:183-198. 9. Shuttleworth EC, Morris CE. The transient global amnesia syndrome. Arch Neural 1966;15:515-520. 10. Gordon B, Marin OSM. Transient global amnesia: An extensive case report. J Neural Neurosurg Psychiatry 1979;42:572-575. 11. Shuping JR, Rollinson RD, Toole JF. Transient global amnesia. Ann Neural 1979;7:281-284. 12. Fisher CM. Transient global amnesia-Precipitating activities and other observations. Arch Neural 1982;39:605608. 13. Shuping JR, Toole JF, Alexander E Jr. Transient global amnesia due to glioma in the dominant hemisphere. Neurology 1980;30:88-90. 14. Findler G, Feinsod M, Lijovetzky G, et al. Transient global amnesia associated with a single metastasis in the nondominant hemisphere. J Neurosurg 1983;58:303-305. 15. Landi G, Giusti MC, Guidotti M. Transient global amnesia due to left temporal hemorrhage. J Neural Neurosurg Psychiatry 1982;00:1062-1063. 16. Benson DF, Marsden CD, Meadows JC. The amnesiac syndrome of posterior cerebral artery occlusion. Acta Neural Stand 1974;50:133-145. 17. Mumenthaler M, Kaeser HE, Meyer A, et al. Transient global amnesia after clioquinal. J Neural Neurosurg Psychiatry 1979;42:1084-1090. 18. Nausieda PA, Sherman IC. Long-term prognosis in transient global amnesia. JAMA 1979;241:392-393.
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