Stress can cause amnesia

Time out for memory

The preparations for the celebration of her husband's 75th birthday had kept Hanna Walter very busy over the past few days and weeks. In the end, however, she was no longer sure that she would be able to cope with the event. One day before the birthday celebrations, Herbert Walter met his wife in the laundry room: "How do I get here?" She kept asking. "And who turned on the washing machine?" Herbert Walter tried to calm his wife down, but she kept repeating the same questions: "What is this about? What am I doing here?"

At the hospital, the doctors ordered a computed tomography of the brain. The examination showed no abnormalities. Over the next few hours, the gaps in Hanna Walter's memory gradually closed again, only the memory for a period of around three hours did not return completely. Neurologists call what Hanna Walter has suffered a "transient global amnesia" (TGA for short) or an "amnesiac episode" - a clinical picture that deeply impresses not only those affected, but also relatives and doctors.

The main symptom of the amnestic episode is a sudden disturbance of the short-term memory. It is typical that during the episode the patient is no longer able to assess the time and situation, the orientation towards the person - "Who am I?", "What is my name?" - but is also retained, as is the ability to perform complex courses of action. Patients often stand out because they keep asking the same questions but cannot remember the answers. Long-term memory can also be affected by the disorder, in particular events from the recent past are forgotten. The disorder usually regresses, but for exactly the period in which the symptoms were fully pronounced, sometimes for a short period before, a permanent memory gap remains. For example, an affected person can safely steer his car through traffic and park it, but then no longer knows where he left the car. Other neurological deficits, such as paralysis or speech disorders, do not occur in transient global amnesia.

The phenomenon has been known to science since the 1950s. In 1956, the American neurologist M. Bender described a "syndrome of isolated episode of confusion with amnesia", a syndrome that is associated with temporary confusion and amnesia. In the same year the French neurologists J. Guyotat and J. Courjon published a clinical picture under the name "l’ictus amnesique", amnestic seizure. The term "transient global amnesia" was introduced in 1964 by C. Miller Fisher and Raymond Adams of Massachusetts General Hospital. The two renowned neurologists recorded 18 abrupt, typical amnesias in detail. Since then, neurologists have been investigating the clinical picture - but until recently without much further knowledge.

It is generally known from memory that it is not located in a single place or precisely defined regions in the brain, but is a service that is performed jointly by many different areas of the brain. Nevertheless, the scientists were able to identify various anatomical structures, the interaction of which is essential for memory. With certain restrictions, these brain regions can be assigned to different forms of memory: Depending on how long information is stored, a distinction is made between short-term or working memory and long-term memory.

The hippocampus, a brain structure that is located in the inner and anterior portions of the temporal lobe, plays a decisive role in the storage of information. Connections to the hippocampus lead from all brain regions; numerous connections lead away from it and pull into different areas of the cerebral cortex. In addition, the hippocampus is linked to the "limbic system", a region of the brain that is important for emotions and learning. The connections that the hippocampus forms with other brain regions can now be made visible with special magnetic resonance tomographic processes, so-called fiber tracking techniques.

 
The magnetic resonance imaging (left) shows the right hippocampus of a healthy person. The paired hippocampus is located in the temporal lobe. Its shape is similar to a seahorse (Latin hippocampus), hence the name.
Fiber tracking techniques are a further development of what is known as diffusion tensor imaging. It allows the mobility of water molecules (= diffusion) in the brain tissue to be characterized in all three spatial directions. The movement of the water molecules is - depending on the tissue - differently pronounced: the diffusion is faster along the nerve fiber bundles than perpendicular to the fiber course because the sheaths of the nerve fiber bundles hinder the diffusion.

These specifications can be used to calculate how fiber strands run in the brain. Color coding, for example, is used for graphical representation. In this way, large fiber systems in the brain become visible in color. Together with colleagues from the Institute for "Functional Magnetic Resonance Imaging of the Brain" at Oxford University, we have succeeded in using this technique to depict the complex connections between the hippocampus and other regions of the human brain. The results are summarized in the illustration on page 19.

 
Diffusion tensor imaging: The left picture shows the direction-dependent color representation of the fiber strands in the brain of a test person (pulling from the left to the right hemisphere in red; from top to bottom in blue; from front to back in green). Right picture: for the enlarged section, the main vector direction of each image unit was superimposed on a black and white representation.
Despite enormous technical advances in the imaging of the living brain over the past decade, no abnormalities were found in the brains of patients who had suffered an amnestic episode, not even in the hippocampus. According to everything that memory research has learned about the function of this structure, it is precisely this brain region that should be affected at least temporarily.

Diffusion imaging was initially disappointing in TGA patients: In 1999, our working group published a first study that found no abnormalities in water diffusion in the brains of patients in the acute stage of transient global anemia. In contrast to stroke patients, where the procedure is used to visualize strokes at an early stage, no signal change was found in TGA patients within the first 24 hours - but at a later point in time. In a subsequent study with 31 TGA patients, we discovered punctiform signal whitening in the hippocampus in 26 patients, which became visible 24 to 48 hours after the onset of the first symptoms. The illustration on page 19 shows an example. Other working groups have since confirmed this result. The significance of these "traces" in the hippocampus of TGA patients has not yet been clarified. The conspicuous bright points are possibly the expression of a delayed onset of cellular damage, which arises as a cause or as a consequence of the transient global amnesia. In any case, they are proof that the hippocampus is involved in the development of this disease.

 
With the help of diffusion tensor imaging, the scientists at the Neurological University Clinic in Mannheim have succeeded in depicting connections between the hippocampus (top left, yellow in the section) and other areas of the brain. The different levels of brightness of the areas marked in blue indicate how likely the fiber connection to the hippocampus is (the lighter, the greater the likelihood of a connection). These results are consistent with animal studies which found connections between the hippocampus and the frontal lobe, the temporal lobe and the posterior parts of the brain.
Despite this topographically reliable assignment, the disease mechanism of transient global amnesia remains unclear. However, the accompanying circumstances of the syndrome point to its development: TGA predominantly affects people between the ages of 50 and 70. The age peak is in the sixth decade, only a few cases occur before the age of 40. For most patients, TGA remains a one-off event. Early anecdotal reports describing situations that typically precede a TGA are particularly revealing. These are usually psychological and / or physical stressors. The neurologists Miller Fisher and Raymond Adams, for example, described swimming in cold water as a triggering factor ("amnesia by the seaside"). Further triggers can be anger, joy, sadness or physical exertion. A current study, in which 98 TGA patients from our clinic took part, determined a psychological trigger factor (e.g. death of a relative) in 40 patients, great physical exertion (e.g. chopping wood) in 24 patients, and psychological and physical trigger factors occurred together in four patients . In 68 of the 98 patients, we were able to show signal abnormalities in the hippocampus using diffusion-weighted magnetic resonance imaging. Remarkably, psychological triggering factors and bilateral signal changes occurred more than randomly together. One possible explanation for these findings is that mental and physical stress sets in motion a cascade which, by releasing messenger substances, leads to an inhibition of the energy supply to the hippocampus, which is particularly sensitive to it. The undersupply also affects other brain regions connected to the hippocampus. This could explain the clinical picture of transient global amnesia.
 
Diffusion-weighted image of a patient with "transient global amnesia": 24 hours after the onset of symptoms, a bright, punctiform change appears in the hippocampus.
The example of transient global amnesia shows that the new imaging processes provide a wide range of information, not only about the structure of the brain, but also about its physiological and pathological function. It is to be expected that with functional magnetic resonance technology, an imaging process that can display activated structures of the brain with high spatial resolution, we will learn even more about the impaired brain performance in transient global amnesia in the coming years. This will be helpful for the interpretation of the results obtained so far. The example of the temporary memory impairment also shows how acute stress can cause illness.

 
Priv.-Doz. Dr. Hansjörg Bäzner is the senior physician at the Neurological University Clinic in Mannheim. His research deals with dementia as well as the diagnosis and treatment of movement disorders and neuromuscular diseases.
Contact: [email protected]
Phone: 0621/3 83 39 5

 
Priv.-Doz. Dr. Kristina Szabo is a senior physician at the Neurological University Clinic in Mannheim. In addition to her clinical work, she works scientifically in the field of cerebral magnetic resonance imaging.
Contact: [email protected]
Phone: 0621/3 83 32 02