Transient global amnesia

 

Contributors

Alfredo Ardila MD PhD, author. Dr. Ardila of Florida International University has no relevant financial relationships to disclose.

 

Martin Farlow MD, editor. Dr. Farlow of Indiana University School of Medicine received research grant support from BristolMyersSquibb, Danone, Elan, Eli Lilly, Forest Laboratories, Novartis, OctaPharma, Pfizer, and Sonexa; honorariums from Eisai, Forest Laboratories, Pfizer, and Novartis for speaking engagements; and fees from Accera, Adamas, Adlyfe, AstraZeneca, Astellas, Bayer, BioRx, CoMentis, Cortex Pharmaceuticals, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Medivation, Merck,  Novartis, Noven, OctaPharma, Prana, QR Pharm., Sanofi-Aventis, Schering-Plough, Seven Life Sciences Ltd., and Toyama Pharm for consultancy. His spouse was employed by Eli Lilly.

 

Publication dates

Originally released September 18, 1995; last updated May 25, 2010; expires May 25, 2013

Key points

  • Transient global amnesia is characterized by acute onset of transient global anterograde amnesia that is not associated with any other major neurologic signs or symptoms.

  • Amnesia resolves gradually, usually within about 2 to 12 hours.

  • Recurrence is low, about 2.5% to 5% per year.

  • In a significant percentage of cases, a precipitant factor (physical or psychological) can be identified.

 

Historical note and nomenclature

  Fisher and Adams coined the term "transient global amnesia," but this syndrome was first described in 1956 by Bender as the "syndrome of [an] isolated episode of confusion with amnesia" and by Guyotat and Courjon as "les ictus amnesiques" (Bender 1956; Guyotat and Courjon 1956; Fisher and Adams 1958). The essential features are an episode of acute onset of transient global anterograde amnesia, with a variable degree of impairment of retrograde memory, which is not associated with any other major neurologic signs or symptoms (Bender 1956). Since this syndrome's recognition, controversy has surrounded its pathogenesis, treatment, and prognosis.

Clinical manifestations

  Typically, the onset is abrupt, and anterograde memory is profoundly impaired. Patients are disoriented in time and often in place but never to person. Particulars are forgotten even after repeated practice, resulting in ideational and motor perseveration. Patients recognize their memory deficits and repeatedly ask orienting questions and also, "Why can't I remember?" (Bender 1956). Retrograde memory is variably disturbed, lasting hours to years. Patients often do not recognize acquaintances but can usually recall their own name and recognize close relatives. Immediate memory, as demonstrated by the patient's ability to immediately repeat several digits or words, and procedural memory, as demonstrated by the patient's ability to do complex tasks (eg, driving), are preserved (Evers et al 2002). Patients appear confused, tending to get lost once outside familiar surroundings. Alertness is normal. General knowledge and ability to perform complex tasks, such as arithmetic, reading, writing, or driving a car, are usually unaffected. During the attack, approximately 10% complain of a headache (Hodges and Warlow 1990a; Zorzon et al 1995). Transient oculomotor abnormalities may be present (Yang et al 2009). No other major neurologic symptoms, signs, or overt seizure manifestations are present. Resolution is gradual, with subjective recovery occurring in two thirds of patients within 2 to 12 hours and, in almost all, within 24 hours.

  Detailed neuropsychological testing has been performed during attacks of transient global amnesia. An almost complete loss of short-term memory occurs, and a striking retrograde amnesia for both verbal and nonverbal facts is present, although the extent of the retrograde amnesia is variable, with more distant memories usually being spared. A defect in dating past memories exists. Immediate memory (ie, digit span) is spared. The impairment of anterograde memory is global, affecting verbal and nonverbal memory to a similar degree, and it is not material specific (Kritchevsky et al 1997). Jia and colleagues studied 3 patients with transient global amnesia using the mini-mental state examination (MMSE), revised Wechsler memory scale (WMS-R), and MRI scans. Using (18)F-labeled deoxyglucose as the tracer, patients were given a PET examination at different periods during recovery. No obvious abnormality was found in MMSE and MRI scans in the 3 patients. However, WMS-R examination and cerebral PET imaging displayed cognitive dysfunction of various degrees and low metabolism in local areas related to memory in 2 of 3 patients. It was concluded that in transient global amnesia patients, cognitive function and cerebral metabolic levels are closely correlated with duration of symptoms (Jia et al 2002).

  Personality and complex cognition, such as abstract thinking, problem solving, and language, are preserved. Memory of material required to give meaning and continuity to sensory experience is normal. During recovery, distant memories tend to return before more recent ones (Hodges and Ward 1989). Significant impairments of both anterograde and retrograde episodic memory during the acute phase, with a relative preservation of personal and conceptual semantic knowledge, are generally found. Retrograde amnesia recovers before the anterograde amnesia and anterograde episodic memory recovers gradually (Guillery-Girard et al 2004). Guillery and colleagues report 3 patients who were tested during a transient global amnesia attack, 2 in the early recovery phase and the third during the acute phase, with a semantic priming task involving a restructuring process of conceptual knowledge (Guillery et al 2001). During transient global amnesia, all patients demonstrated priming effects. Results obtained the day after the episode with the same task showed that these effects persisted at least 1 day. The authors concluded that episodic memory does not seem necessary for the acquisition of semantic information.

  Quinette and colleagues analyzed working memory and executive functions during transient global amnesia episodes. They showed that subcomponents of working memory, such as the phonological loop and visuospatial sketch pad, were spared in transient global amnesia patients (Quinette et al 2003). Specific executive functions that entailed inhibitory control, dual task performance, updating, and shifting mechanisms were also found to be normal. However, the researchers found that transient global amnesia patients were significantly impaired in the recollection of their episodic memories. They also made reduced numbers of “remember” compared with “know” judgments in the episodic memory test several days after transient global amnesia. They supposed that the selective deficit in recollective episodic memories observed in transient global amnesia may be principally related to medial temporal lobe abnormalities that have been reported in this syndrome.

  A meta-analysis on 152 effect sizes (effect size –d- provides information about how much change is evident across all studies and for subsets of studies) from 25 studies showed that transient global amnesia is characterized by a significant reduction of anterograde (d = 1.89) and a milder reduction of retrograde (d = 1.28) episodic long-term memory. Furthermore, it was found that not only memory is affected, but also executive functions are diminished (d=0.79), although in a lesser degree (Jager et al 2009). Episodic long-term memory and executive function slowly recover.

  Until recently, it was believed that the memory impairment associated with transient global amnesia resolved completely within 24 hours; although it was recognized that memory did not recover for the period during the attack and for a period of 30 minutes to 2 hours just before the onset of the attack (Hodges and Ward 1989). Based on comparisons of patients who have had transient global amnesia with age- and IQ-matched control subjects, neuropsychological evidence shows a mild persistent impairment of both anterograde and retrograde memory after an attack (probably due to the attack itself) although a preexistent deficit cannot be excluded (Hodges and Oxbury 1990; Stillhard et al 1990). These deficits in antegrade and retrograde memory improve slowly, sometimes over a period of several months, usually to within the normal range (Hodges and Oxbury 1990). Kessler and colleagues analyzed 14 patients with transient global amnesia and observed impairments in both verbal and nonverbal long-term memory and verbal fluency 3 to 4 days after the end of their transient global amnesia (Kessler et al 2001). Caffarra and colleagues have also noted that even at 6 months, verbal memory may still be significantly impaired after an attack of transient global amnesia (Caffarra et al 1981). Long-term difficulties in memory retrieval of both recent semantic and episodic information has been reported (Guillery-Girard 2006). Reduction of categorical learning, attention, and qualitative alterations of spatial strategies suggestive of a planning defect has also been suggested after the clinical recovery (Le Pira et al 2005).

  Recognized precipitating events include strenuous exercise, intense emotion, sexual intercourse (Bucuk et al 2004), pain, temperature extremes (eg, those produced by swimming in cold water or taking a hot bath), cervical manipulation, coughing spells, and medical procedures (eg, cerebral and cardiac angiography) (Hodges and Warlow 1990a; Minuk et al 1990; Zorzon et al 1995; Benke et al 2005). Such precipitants are present in 33% to 84% of attacks (Frederiks 1993; Zorzon et al 1995). Using a logistic regression analysis, Agosti and colleagues observed that an increased number of trigger events was associated with a higher probability of recurrence of transient global amnesia (Agosti et al 2006). Savitz and Caplan reported a case of transient global amnesia after sildenafil (Viagra) use (Savitz and Caplan 2002). About 50% of the patients report Valsalva-like activities preceding transient global amnesia (Sander et al 2000). Transient global amnesia has also been reported to be associated with bilateral vertebral artery dissection (Michel et al 2004) and aortic dissection (Mondon et al 2007) and has been reported following the use of ergotamine and dihydroergotamine to treat migraine (Gil-Martinez and Galiano 2004). Hippocampal resection for therapeutic purposes in some epileptic patients is another factor suggested as a precipitant for transient global amnesia (Dupont et al 2008). Noteworthy, the onset of transient global amnesia has also been significantly associated with lower daily, monthly, and seasonal temperature. Using a series of 223 patients, Akkawi and colleagues found that most cases were observed when the temperature was less than 6.9 degrees C, whereas the frequency of transient global amnesia was minimal when it was more than 24 degrees C (Akkawi et al 2006).

  Quinette and colleagues analyzed 1,353 cases reported in the literature between June 1990 and May 2005 and 142 of their own cases collected at the Caen University Hospital (France) (Quinette et al 2006). In their own cases, 106 EEGs were conducted during or after the episode. Eighty-five (80%) were unremarkable. The remaining 26 revealed minor abnormalities but with no epileptic features. One hundred and two brain CT scans were obtained. Eight (7.8%) revealed minor abnormalities. Forty out of 41 Doppler scans of the supra-aortic vessels were normal. Taking together their own cases with those reported in the literature, the authors present the following general conclusions: (1) differences in the gender ratio are observed when comparing different reports; risk factors may be different in men and women; (2) the vast majority of attacks occur between the ages of 50 and 80; (3) although recurrences have been reported, in most patients, transient global amnesia occurs only once; (4) the only factor significantly associated with an increased risk of transient global amnesia –particularly in younger patients, is migraine; (5) psychological and emotional instability history is frequently found in transient global amnesia patients; these patients may be particularly sensitive to psychological stress; (6) precipitating events (observed in more than 50% of the cases) include emotional stress, physical effort, water contact (temperature change), and sexual intercourse; (7) associated symptoms (more than 70% of the cases) include headache, nausea, and dizziness; (8) more frequently (more than 50% of the cases) the episode begins in the morning; duration is usually 1 to 9 hours; (9) a hierarchical cluster analysis revealed different subgroups of patients; in women, episodes are mainly associated with an emotional precipitating event and certain personality traits, whereas in men, they are usually more frequently associated with physical precipitating events. In younger patients, a history of migraine represents an important risk factor. The authors suggest that transient global amnesia may represent a single manifestation of several physiopathological phenomena.

 

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