The Transient Global Amnesia Project has added a new section on its website: www.tgaproject.com titled HEADLINES. Within the Headlines section there are buttons to link readers to up to date TGA news. The following interview by TGA Project founder Richard Holl (USA) was conducted with Dr. Ralph Werner (Germany) utilizing several email conversations to maximize Dr. Werner’s available time for an interview with us.
The Neurological Enigma of Transient Global Amnesia
An Interview with Dr. Ralph Werner by Richard Holl
April 3, 2023
Transient Global Amnesia (TGA) patients and their families have since 1956 faced a neurological enigma with no definitive triggers, an episode duration of up to approximately 24 hours, complete loss of short-term memory processes, and quite often lingering “brain fog” and/or anxiety. To understand this enigma, we must travel back in time to 1956. Morris Bender wrote a paper titled Syndrome of Isolated Episode of Confusion with Amnesia. J Hillside Hospital. 1956; 5: 212–215. https://psycnet.apa.org/record/1958-00708-001 In the American Psychological Association PsycNet link above for Bender’s article is the following abstract:
“12 post-menopausal patients suffering non-recurring episodes of defective memory with subsequent amnesia defy current classification. A transient circulatory disturbance of the brain seems most acceptable, but future biochemical studies may clarify the etiology.” (PsycINFO Database Record (c) 2016 APA, all rights reserved)
67 years later, a TGA patient still has little information to wrap their brain around. So that leads this author to follow-up with well known and respected neurological medical providers to delve into the TGA enigma. The TGA Project website has a research database with currently 1,128 TGA related articles. Our database is categorized from 2023 to 1819. From that database, articles are researched for content and email addresses that provide a potential interview list.
(Photo of Dr. Ralph Werner courtesy of Katholisches Klinikum Koblenz-Montabaur Hospital, Germany)
The first doctor to respond for an interview is Dr. Ralph Werner from Germany. He has three articles listed in our database:
2021: Prevalence of Mimics and Severe Comorbidity in Patients with Clinically Suspected Transient Global Amnesia. Cerebrovasc Dis.2021;50(2):171-177.
https://www.karger.com/Article/Abstract/512602
2020: Increased Incidence of Transient Global Amnesia During the Covid-19 Crisis? Neurological Research and Practice. 2020; 2:26. https://neurolrespract.biomedcentral.com/track/pdf/10.1186/s42466-020-00077-x
2019: Demographic and Hemodynamic Characteristics of a Large Cohort of Patients with Transient Global Amnesia. Neurology. 2019; 92 (15 Supplement).
https://n.neurology.org/content/92/15_Supplement/P3.9-076
Doctor of Medicine Ralph Werner is a German neurologist who works at Katholisches Klinikum Koblenz-Montabaur (academic teaching hospital) as an attending physician. His main interests are stroke and related disorders (like TGA). In 2019, he was awarded the renowned Robert Wartenberg Prize of the German Neurological Society (DGN) for his work on angioedema in acute stroke.
TGA: “Thank you, Dr. Werner for taking the time to answer our questions. The first question was asked to be sure we had all of his TGA articles listed correctly in our website’s research database. Dr. Werner, have we included all of your articles on TGA?”
Dr. Werner: “Yes, the list is complete, besides these articles I had several oral and poster presentations at national and international conferences (European Stroke Conference, Athens 2018; AAN meeting, Philadelphia 2019). Currently I’m working on new articles on hemodynamics and the influence of the socioeconomic status in TGA.”
The TGA Project began in 2017 as a hobby for this author to help with his depression and anxiety that followed his 2013 TGA. His TGA was triggered by sexual intercourse with his wife of 42 years. During his 27 hours of TGA blankness and for an undetermined length of time preceding his TGA, he has no memories. When he was coming out of his TGA, his answers to the neurological test of day, month, year, and president were: “Three I don’t knows and President Nixon. It must be 1974. I’m a Corporal in the USMC.” After further tests he was diagnosed with TGA by exclusion. His family and he were very pleased to learn it wasn’t a stroke, but we had never heard of TGA.
In 2013, the information we found while at the hospital on the subject of TGA was on the Mayo Clinic website: https://www.mayoclinic.org/diseases-conditions/transient-global-amnesia/symptoms-causes/syc-20378531 The Mayo website was informative, but left many unanswered questions. To answer these unanswered questions the TGA Project was founded.
TGA: “What led you to write about the neurological enigma called TGA?”
Dr. Werner: “After having seen a lot of patients in the emergency department (and each patient’s TGA experience was fascinating and unique) I started to build a monocentric TGA registry in order to find new aspects concerning the etiology of TGA (that has not been elucidated yet).”
TGA: “Other than one of your articles, can you refer our readers to a few of your favorite TGA articles as must reads?”
Dr. Werner: “The brand-new review article of Allan Ropper’s (Ropper AH. Transient Global Amnesia. N Engl J Med. 2023 Feb 16;388(7):635-640) provides an excellent overview of the current knowledge of TGA (and it is understandable for non-specialists). The group from Lausanne/Switzerland also recently published two interesting papers (Piffer et al. Transient global amnesia with unexpected clinical and radiological findings: A case series and systematic review. J Neurol Sci. 2022 Oct 15;441:120349. doi: 10.1016/j.jns.2022.120349; Piffer S et al. Acute neurological disease as a trigger or co-occurrence of transient global amnesia: a case series and systematic review. Neurol Sci. 2022 Oct;43(10):5959-5967. doi: 10.1007/s10072-022-06259-6).”
The TGA Project is pleased to say that Allan Ropper’s February 2023 article is our Featured Article for March 2023 and is listed in our database. The two articles by Silvio Piffer are in our database too. Here are the links for those 3 articles:
Ropper: https://www.nejm.org/doi/full/10.1056/NEJMra2213867
Piffer: https://pubmed.ncbi.nlm.nih.gov/35944401/
Piffer: https://pubmed.ncbi.nlm.nih.gov/35838848/
During a TGA episode, all of TGA patients inquire repeatedly the same 4 or 5 questions every three to five minutes no matter what the language. Yet the time span of these TGAs varies between a few hours and to around 24 hours.
TGA: “What is the speculation for this spread of hours and then just as quickly we return to ourselves?”
Dr. Werner: “This is one of the open questions concerning the pathophysiology of TGA …”
(Readers: Please note the 3 dots at the end of Dr. Werner’s answer. It seems the enigma continues in 2023…)
This author’s spouse tells the following story of his “brain fog” during his one and only TGA episode in 2013. When the general neurological brief survey was given to him:
1. “What day of the week is it?”
2. “What is today’s date?”
3. “Who is the leader of our country?”
His answers to those questions came from back in 1974. He gave the standard military safety net answer of:
1. “Don’t know.”
2. “Don’t know.”
3. “Name, rank, and serial number, Sir” and added “President Nixon of course!”
TGA: My answer above seems to vary quite a lot from the information the TGA Project has gathered from its current level of 839 TGA patients world-wide. Most just recall just “snapping out of the fog.” What returns to normal have you noticed?
Dr. Werner: “I did not notice a spectacular “awakening” in most of the patients, and the patients also did not seem to experience something special at the moment when their short-term memory started to work properly again.”
Regarding TGA triggers, there seems to be several that are possible based on witness answers to an Emergency Dept doctor’s questions. However; the topic of etiology is still a matter of debate.
TGA: “What are your current thoughts on the etiology of a TGA?”
Dr. Werner: “In my opinion, TGA has a multi-factorial etiology, potentially comprising temporarily increased metabolic demand in the hippocampus (resulting from physical and/or psychological stress) that cannot be fulfilled due regional perfusion restrictions that might result either from reduced arterial inflow or restricted venous outflow.”
Looking at our TGA website Census Page, there are only 2 TGA patients who have joined the TGA Project’s free census from Germany. The TGA census only collects: first name, email address, and either US state or an international country. USA leads with 418, followed by UK with 70, Australia with 42, Canada with 35. Many other countries are represented, but their numbers are much lower.
TGA: “What insights might you have to the lack of German TGA patients in our Census?”
Dr. Werner: “ One reason might be the fact that German TGA patients with (in our cohort) an average of 65 years (with men slightly younger than women) prefer websites in German language (although yours provides a translation) or from Germany.”
In the many conversations this author has had with TGA patients and their families, I haven’t heard one complaint about the medical providers and their following Stroke Protocol. The consistent remarks the TGA patients hear are:
“Be happy it wasn’t a stroke”
“Take a couple days of rest and you should be back to normal”
“Follow up with your primary medical provider”
and the Emergency Doctor saying “They’ve never had a TGA patient here before.”
We have a saying in the TGA world:
“TGA isn’t life threatening, but life changing!”
TGA: “What suggestions do you have besides spending money to get our diagnosis by exclusion and TGA Project website into the hands of cardio- and neuro-medical providers?”
Dr. Werner: “I think that a thorough diagnostic approach is very important. Because in up to 10% of suspected TGA cases you will either find a different diagnosis (TGA mimics) or a serious medical condition that might be related to or even have provoked TGA.”
This author’s communications with the TGA Project patients relates the after effects of TGA similar to a Bell Curve.
“A few reports of no after effects.”
“A large middle of the curve with a foggy brain.”
“A few like (this author) who now have Mild Cognitive Impairment and very short-term memory of names, general time, and verbal directions.”
TGA: “How can there be such a disparity?”
Dr. Werner: “Bell curves are a quite frequent finding in clinical cohorts (Gaussian function). But the prevalence of sequelae of TGA is still a matter of debate.”
(Readers: Gaussian functions are widely used in statistics to describe the normal distributions. The graph of a Gaussian is a characteristic symmetric "bell curve" shape.) https://en.wikipedia.org/wiki/Gaussian_function
(Readers: A typical sequela is a chronic complication of an acute condition—in other words, a long-term effect of a temporary disease or injury—which follows immediately from the condition. Sequelae differ from late effects, which can appear long after—even several decades after—the original condition has resolved. In general, non-medical usage, the terms sequela and sequelae mean consequence and consequences.)
The possibility that sexual intercourse and/or orgasm as a TGA trigger is repeatedly mentioned in many research articles. As most TGA patients are in their late 50’s to mid 60’s, it sometimes seems giving up sex would “cure” the TGA condition. The other thought is some TGA patients are having a middle life crisis and are involved in extra marital relationships which would lead to them not wanting to go to an ED and have to answer questions.
TGA: “Some of our TGA community patients have been told that one or two little white spots showed up in their MRI. How could the possible triggers to a TGA (orgasm, migraines, cold water immersion, or extreme stress) be related to those white spots?
Dr. Werner: “The answer to your question is quite complicated. Up to date, we don't know what the little white spot in the hippocampus exactly means. All the triggers you mentioned have in common that they evoke a kind of stress to the brain (positive or negative), sometimes resulting in TGA. But although the exact patho-physiological cascade is still unknown, the little white spot (professional term: area of restricted diffusion or DWI lesion) might be very helpful for making the diagnosis of TGA.”
The mimic factor of a TGA (to the following: stroke, Transient Epileptic Amnesia (TEA), drug use, head injury, and brain surgery) seems from this author’s conversations with TGA witnesses to be the largest factor in “scaring” the family during the testing phase. We understand protocol and reasons for testing. Yet the tests that are ordered and waited for cause further anxiety in the family due to those tests being connected to life threatening conditions. When the TGA patient becomes normal again, the Emergency Doctor releases the TGA patient as a confused individual that remembers nothing compared to their “scared” family members with the following unanswered questions of:
“What was that?”
“Will it happen again?”
“How can the family answer the TGA patient’s questions?”
And the numerous other things families and patients think about days later.
TGA: “What do you think are the missing components of diagnosis and follow up care?” Occasionally an emergency department evaluation for a patient exhibiting TGA symptoms had a serious different diagnosis (most often stroke). Even the few repeat TGA patients should always be admitted for observation and stroke protocol implemented ASAP until a stroke is ruled out.
Dr. Werner: “Fortunately, in most of the cases you can make the diagnosis of TGA based on a comprehensive clinical neurological examination and a third-party medical history (if you know the syndrome). Therefore, we need more neurological expertise in emergency departments.”
Some TGA patients joke that they were abducted by “aliens” instead of talking about “mind-blowing sex”. We seem to face giggles when we mention either one. We can’t seem to get past the humor. Yet we live daily for the rest of our lives knowing we could lose our memory at most anytime. We are told its okay to drive, to watch our grandchildren, to work in a licensed profession, to have sex again, and other normal routines.
TGA: “The human brain ranks at the top of the complexity scale. What options can you offer from what questions we’ve posed and from what you have seen in your years of experience?”
Dr. Werner: “To tell you the truth, after 25 years of working with neurological patients I’m still impressed by the complexity of the human brain (perhaps, today even more than in my beginnings as a resident), and I gain experience with every new patient.”
TGA: “As we conclude this interview, we thank you for taking time from your busy medical practice to be a part of this interview. We look forward to future conversations with you and to future reading of new research by you.”