Transient global amnesia (TGA) most commonly occurs in the middle-aged or elderly, more frequently in men, and it results in a period of amnesia lasting several hours. It is characterized by repetitive questioning, and there may be some confusion, but patients do not report any loss of personal identity (they know who they are). It is sometimes preceded by headache or nausea, a stressful life event, a medical procedure, or vigorous exercise. Hodges and Ward⁽¹⁾ found that the mean duration of amnesia was 4 h and the maximum was 12 h. In 25 per cent of their sample, there was a past history of migraine, which was considered to have a possible aetiological role. In a further 7 per cent of the sample, the patients subsequently developed unequivocal features of epilepsy (there had been no focal signs or features of epilepsy during the original attack) and the memory loss was therefore attributed, in retrospect, to previously undiagnosed epilepsy. There was no association with either a past history of vascular disease, clinical signs suggestive of vascular pathology, or known risk factors for vascular disease. In particular, there was no association with transient ischaemic attacks. In 60 to 70 per cent of the sample, the underlying aetiology was unclear.

More recently, Quinette et al.⁽²⁾ reviewed the findings in 1353 patients reported in the clinical literature since 1956 and their own data from 142 patients, seen between 1994 and 2004. In general, the findings were consistent across the two sources. There was no sex bias, and the vast majority of attacks occurred between the ages of 50 and 80 (mean = 60.3 ± 9.6). Most patients had a single attack, but the annual rate of recurrence ranged from 2.9 per cent to 26.3 per cent (6.3 per cent in their own study). In the literature, the duration of attacks ranged from 15 min to 24 h and, in their own investigation, the range was 30 min to 16 h (mean = 5.6 h). These authors investigated putative predisposing and precipitating factors in great detail, concluding that TGA may encompass at least three different groups of patients: (i) younger patients with a history of migraine, in whom spreading neurochemical depression may be implicated, (ii) women who have experienced acute emotional or physical stress, and often have a history of anxiety or depression, and (iii) men who, following physical exertion, develop venous congestion in the context of insufficient jugular vein valves and a precipitating Valsalva manoeuvre.

In instances of TGA where neuropsychological tests have been administered to patients during the acute episode of memory loss,^(1,3) the patients show a profound anterograde amnesia, as expected, on tests of both verbal and non-verbal memory. However, performance on tests of retrograde memory is variable. Follow-up studies show either complete or almost complete recovery of memories, several weeks to months after the acute attack. In general, retrograde amnesia recovers before anterograde amnesia; the degree of shrinkage of retrograde amnesia is heterogeneous; and anterograde memory (new learning) recovers gradually.

The general consensus is that the amnesic disorder results from transient dysfunction in limbic-hippocampal circuits, crucial to memory formation. Medial temporal abnormalities have been reported bilaterally in terms of single-photon emission CT (SPECT) measures of perfusion, positron emission tomography (PET) measures of metabolism, diffusion weighted imaging (DWI), and small hippocampal cavities on T2 reversed magnetic resonance imaging (MRI) images.^(4,5) In addition, venous duplex sonography has shown jugular vein valve insufficiency in a proportion of cases.⁽⁵⁾

This term was coined by Kapur,⁽⁶⁾ and it refers to the minority of patients with transient global amnesia in whom epilepsy appears to be the underlying cause of the syndrome.⁽¹⁾ Where epilepsy has not previously been diagnosed, the main predictive factors for an epileptic aetiology are brief episodes of memory loss (an hour or less) with multiple attacks.⁽¹⁾ It is important to note that standard electroencephalography (EEG) and CT findings are often normal. However, an epileptic basis to the disorder may be revealed on sleep EEG recordings.^(1,7)

Patients with transient epileptic amnesia may show residual deficits in between their attacks, associated with their underlying neuropathology. Kopelman et al.⁽⁷⁾ found a moderate degree of residual anterograde memory impairment in their patient, related to subsequent (unpublished) findings of small foci of MRI signal alteration and PET hypometabolism bilaterally in the medial temporal lobes. Several authors have reported patients who describe ‘gaps’ in past personal memories, and Manes et al.⁽⁸⁾ have reported disproportionate inter-ictal retrograde amnesia. The latter group also reported abnormal long-term forgetting of verbal material, but whether these gaps in memory result from faulty encoding (because of subclinical ictal activity), impaired consolidation (giving rise to accelerated forgetting), or deficits in retrieval remains controversial.

Epilepsy may, of course, give rise to automatisms or post-ictal confusional states. Where there is an automatism in such circumstances, there is always bilateral involvement of the limbic structures involved in memory formation, including the hippocampal and parahippocampal structures bilaterally as well as the mesial diencephalon. Consequently, amnesia for the period of automatic behaviour is always present and is usually complete.

In head injury, it is important to distinguish between a brief period of retrograde amnesia, which may last only a few seconds or minutes but can be weeks or months, a longer period of post-traumatic amnesia, and islands of preserved memory within the amnesic gap.⁽⁹⁾ Occasionally post-traumatic amnesia may exist without any retrograde amnesia, although this is more common in cases of penetrating lesions. Sometimes there is a particularly vivid memory for images or sounds occurring immediately before the injury, on regaining consciousness, or during a lucid interval between the injury and the onset of post-traumatic amnesia. These vivid °memories may become the intrusive flashbacks of a post-traumatic stress disorder (PTSD) syndrome.

Post-traumatic amnesia (PTA) is generally assumed to reflect the degree of underlying diffuse brain pathology, in particular rotational forces giving rise to axonal tearing and generalized cognitive impairment. The length of PTA is predictive of eventual cognitive outcome, psychiatric outcome, and social outcome.⁽¹⁰⁾ However, the duration of PTA is often not well documented in medical records, and these relationships are often weaker than is generally assumed. In addition, contusion to the frontal and anterior temporal lobes is a common consequence of head injury. The clinical features and underlying pathophysiology of head injury have recently been well described elsewhere.⁽¹¹⁾

Post-traumatic amnesia needs to be distinguished from the persisting anterograde memory impairment, which may be detected on clinical assessment or cognitive testing long after the period of PTA has ended. Moreover, forgetfulness is a common complaint within the context of a post-traumatic syndrome, which may include anxiety, irritability, poor concentration, and various somatic complaints. Commonly, these complaints persist long after the settlement of any compensation issues.⁽¹¹⁾

Alcoholic blackouts are discrete episodes of memory loss for significant events, which should not be confused with withdrawal seizures or other ictal phenomena. Alcoholic blackouts are associated with severe intoxication, usually in the context of a history of prolonged alcohol abuse. Goodwin et al.⁽¹²⁾ described two types of blackout—the fragmentary and the en bloc. However, alcohol-induced state-dependent experiences can be viewed as related phenomena, and it has been suggested that the three represent gradations of alcohol-induced memory impairment. In state-dependent effects, subjects when sober cannot remember events or facts from an episode of intoxication, which they recall easily when they again become intoxicated. In fragmentary blackouts, the subjects are aware of their memory loss on being told later of an event; there are islands of preserved memory; and the amnesia tends to recover partially through time by shrinkage of the amnesic gap. In en bloc blackouts there is an abrupt beginning and end to the period of memory loss, and the lost memories are very seldom recovered. Blackouts may be more common in binge drinkers, because they are related to a high blood alcohol level. Hypoglycaemia may also be a contributory factor, and blackouts are more common where there is a history of previous head injuries.

This is an iatrogenic form of transient amnesia. Benzodiazepines and anticholinergic agents can also give rise to transient memory loss in more moderate form.⁽¹³⁾

Subjects tested within a few hours of electroconvulsive therapy (ECT) show a retrograde impairment for information from the preceding 1 to 3 years, a pronounced anterograde memory impairment on both recall and recognition memory tasks, and an accelerated rate of forgetting.⁽¹⁴⁾ When retested approximately 6 to 9 months after completion of a course of ECT, memory generally returns to normal on objective tests. However, complaints of memory impairment can persist, and they may be evident three or more years after a course of ECT has been completed.⁽¹⁵⁾ It seems that patients with persistent complaints of memory loss tend to be those who have recovered least well from their depression,^(14,15) although their complaints tend to focus upon the period for which there was an initial retrograde and anterograde amnesia. A recent American study suggested that sine wave stimulation induces cognitive slowing in terms of reaction time, and that multiple bilateral ECT administrations can produce impairments in autobiographical memory retrieval 6 months following treatment.⁽¹⁶⁾

Verbal memory appears to be particularly sensitive to disruption. Unilateral electroconvulsive therapy to the non-dominant hemisphere produces considerably less memory impairment than bilateral ECT, although it is important to identify the non-dominant hemisphere by a valid procedure. Attempts to minimize memory disruption by either making changes in premedication or the concomitant administration of other substances—such as glycopyrrolate, physostigmine, thyroxine, dexamethasone, or acetylcholine—have produced limited or no benefit.

This clinically important syndrome is described in Chapter 4.6.2. Post-traumatic stress disorder (PTSD) is characterized by vivid, intrusive thoughts and memories (‘flashbacks’), avoidance and anxiety phenomena, and hyper-arousal and hyper-vigilance symptoms. However, there may be instances of brief memory loss, distortions, or even frank confabulations. For example, a victim of the Herald of Free Enterprise disaster at Zeebruge described trying to rescue a close friend still on board the ship, when other witnesses reported that the close friend had, in fact, not been seen by the victim from the moment the ship turned over. Cases of PTSD may, of course, be confounded by other factors, such as head injury. Nevertheless, it is of interest that PTSD symptoms can occur even when a subject is completely amnesic for an episode.⁽¹⁷⁾ PTSD victims can show deficits in anterograde memory on formal tasks many years after the original trauma, and there is also evidence that they may show loss of hippocampal volume on magnetic resonance imaging (MRI) brain scan, which has been attributed by some to a surge in glucocorticoid secretion. Brewin⁽¹⁸⁾ has recently reviewed four controversies in autobiographical memory for trauma. He found that qualitative and quantitative differences do exist between trauma and non-trauma memories in PTSD victims, and that memories for trauma can be either better or worse than non-trauma memories. In other words, some incidents may be recalled particularly vividly, and others may be forgotten.

A fugue state is a syndrome consisting of a sudden loss of all autobiographical memories and knowledge of personal identity, usually associated with a period of wandering, for which there is a subsequent amnesic gap on recovery. Characteristically, fugue states last a few hours or days, up to about 3 weeks. There are also
descriptions in the literature of persisting autobiographical memory loss, in which personal identity has been ‘re-learned’, and these are better known as ‘psychogenic focal retrograde amnesia’.⁽¹⁹⁾ However, whenever such complaints persist, the suspicion of simulation must arise. Fugue states differ from transient global amnesia or transient epileptic amnesia in that the subject does not know who he or she is, and repetitive questioning is not a characteristic feature in fugues.

As discussed elsewhere,⁽²⁰⁾ fugue states are always preceded by a severe precipitating stress. Second, depressed mood is also an extremely common antecedent for a psychogenic fugue state, and may be associated with manifest suicidal ideas just before or following recovery from the fugue. Third, various authors have noted that there is often a past history of a previous transient neurological amnesia, such as epilepsy or head injury. In brief, it appears that patients who have experienced a previous transient organic amnesia, and who become depressed and/or suicidal, are particularly likely to go into a fugue in the face of a severe, precipitating stress. That stress may consist of marital or emotional discord, bereavement, financial problems, a criminal charge, or stress during wartime. Fugues have been described as a ‘flight from suicide’. Recent neuro-imaging investigations have examined people purportedly in a fugue state with very inconsistent results, probably because the delay until imaging, the imaging techniques employed, and the clinical situations themselves have varied considerably across studies.

This is a phenomenon commonly brought to the attention of psychiatrists, particularly forensic psychiatrists, although the empirical literature on this disorder is scanty. Amnesia is claimed by 25 to 45 per cent of offenders in cases of homicide, approximately 8 per cent of perpetrators of other violent crimes, and a small percentage of non-violent offenders.⁽²¹⁾ It is necessary to exclude underlying neurological or endocrine factors such as an epileptic automatism, post-ictal confusional state, head injury, sleepwalking, or hypoglycaemia. Underlying medical disorder can be grounds for a so-called ‘insane’ automatism in English law (if the result of an internal brain disease) or a ‘sane’ automatism (if the consequence of an external agent), but otherwise amnesia per se does not constitute grounds for alleviation of responsibility for an offence.

Amnesia for an offence is most commonly associated with the following:

Pyszora et al.⁽²²⁾ examined the psychiatric reports of all offenders given a life sentence in England and Wales in 1994, 29 per cent of whom claimed amnesia. Detailed, follow-up reports at 3 years were also examined, and these suggested that approximately one-third of those who had claimed amnesia at trial reported complete recovery, one-third showed partial recovery, and one-third reported no change in their amnesias. Only about 2 per cent were thought to have been malingering.

As mentioned, this is the result of nutritional depletion, namely a thiamine deficiency. Korsakoff⁽²⁴⁾ described this condition as resulting from alcohol abuse or from a number of other causes, but by far the most common nowadays is alcohol abuse.