Showing posts with label NMDA. Show all posts
Showing posts with label NMDA. Show all posts

Friday, July 4, 2025

Boquete: Answer to Prayers!



According to old Chinese advice, it is wise never to discuss politics or religion even amongst best friends.  

Religious belief can often blur judgment in the wisest of people.

Forty plus years ago, a patient of mine was unconscious for 23 days and it was mother's belief that it was through prayer that her daughter was saved. I did not argue with her then.

But perhaps God works through his people in his own way. Discoveries in Medicine should therefore enhance our faith rather than the other way round.

It took nearly 30 years for the real answer to her prayers to really emerge.

 ©2012 Am Ang Zhang
I was staying at our resort in Boquete and was having dinner with three friends all of them with medical connections. One was in hospital administration and one a nurse. The husband of the nurse was a pharmacist. Somehow the conversation drifted into medical topics and knowing that I am a Child Psychiatrist the pharmacist started talking about his nephew who was nearly sent to a mental institution as he suffers from catatonia and doctors eventually diagnosed schizophrenia and put him on antipsychotics. Luckily the catatonic symptom probably saved him as some bright young thing just read the book Brain On Fire and gave him the Clock Test. That led to the NMDAR antibody testing that proved positive. He responded well to the treatment regime that has been developed and is off all antipsychotic medication.

My Teratoma patient was lucky as she belong to that group that improved without further treatment once the Teratoma was removed. She eventually had a baby.


The Power of Prayers & Teratoma: Brain & NMDA!


Anti-NMDA Receptor Encephalitis

NEW ORLEANS — A mysterious, difficult-to-diagnose, and potentially deadly disease that was only recently discovered can be controlled most effectively if treatment is started within the first month that symptoms occur, according to a new report by researchers from the Perelman School of Medicine at the University of Pennsylvania. The researchers analyzed 565 cases of this recently discovered paraneoplastic condition, called Anti-NMDA Receptor Encephalitis, and determined that if initial treatments fail, second-line therapy significantly improves outcomes compared with repeating treatments or no additional treatments (76 percent versus 55 percent). The research is being presented at the American Academy of Neurology's 64th Annual Meeting in New Orleans.

565 cases! Not so rare!

The condition occurs most frequently in women (81 percent of cases), and predominately in younger people (36 percent of cases occurring in people under 18 years of age, the average age is 19). Symptoms range from psychiatric symptoms, memory issues, speech disorders, seizures, involuntary movements, to decreased levels of consciousness and breathing. Within the first month, movement disorders were more frequent in children, while memory problems and decreased breathing predominated in adults.

My patient was under 18 and presented with catatonia symptoms. She later lose consciousness and was ventilated.

"Our study establishes the first treatment guidelines for NMDA-receptor encephalitis, based on data from a large group of patients, experience using different types of treatment, and extensive long-term follow-up," said lead author Maarten TitulaerMD, PhD, clinical research fellow in Neuro-oncology and Immunology in the Perelman School of Medicine at the University of Pennsylvania. "In addition, the study provides an important update on the spectrum of symptoms, frequency of tumor association, and the need of prolonged rehabilitation in which multidisciplinary teams including neurologists, pediatricians, psychiatrists, behavioral rehabilitation, and others, should be involved."

The disease was first characterized by Penn's Josep Dalmau, MD, PhD, adjunct professor of Neurology, and David R. Lynch, MD, PhD, associate professor of Neurology and Pediatrics, in Annals of Neurology in 2007. One year later, the same investigators in collaboration with Rita Balice-Gordon, PhD, professor of Neuroscience, characterized the main syndrome and provided preliminary evidence that the antibodies have a pathogenic effect on the NR1 subunit of the NMDA receptor in the Lancet Neurology in December 2008. The disease can be diagnosed using a test developed at the University of Pennsylvania and currently available worldwide. With appropriate treatment, almost 80 percent of patients improve well and, with a recovery process that may take many months and years, can fully recover.

Teratoma: finally!

In earlier reports, 59 percent of patients had tumors, most commonly ovarian teratoma, but in the latest update, 54 percent of women over 12 years had tumors, and only six percent of girls under 12 years old had ovarian teratomas. In addition, relapses were noted in 13 percent of patients, 78 percent of the relapses occurred in patients without teratomas.
As Anti-NMDA Receptor Encephalitis, the most common and best characterized antibody-mediated encephalitis, becomes better understood, quicker diagnosis and early treatment can improve outcomes for this severe disease.
The study was presented in a plenary session on Wednesday, April 25, 2012 ET at 9:35 AM at the American Academy of Neurology's annual meeting.
[PL01.001] Clinical Features, Treatment, and Outcome of 500 Patients with Anti-NMDA Receptor Encephalitis

Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies

Of 100 patients with anti-NMDA-receptor encephalitis, a disorder that associates with antibodies against the NR1 subunit of the receptor, many were initially seen by psychiatrists or admitted to psychiatric centres but subsequently developed seizures, decline of consciousness, and complex symptoms requiring multidisciplinary care. While poorly responsive or in a catatonic-like state, 93 patients developed hypoventilation, autonomic imbalance, or abnormal movements, all overlapping in 52 patients. 59% of patients had a tumour, most commonly ovarian teratoma. Despite the severity of the disorder, 75 patients recovered and 25 had severe deficits or died.

Who knows, I would not be surprised if Dr. Dalmau is eventually awarded the Nobel.

Related paper:

Anti-NMDA Receptor Encephalitis: Diagnosis, Psychiatric Presentation, and Treatment


Chapter 29  The Power of Prayers

The following is extracted from The Cockroach Catcher: Chapter 29 The Power of Prayers.

According to old Chinese advice, it is wise never to discuss politics or religion even amongst best friends.  

         Religious belief can often blur judgement in the wisest of people. In psychiatry it is sometimes not easy. This is particularly true in cases of florid psychosis, which often presents with symptoms of hallucination, delusion and even vision.

         I remember my early days of psychiatry in a mental hospital in Hong Kong. Yes, it was the days of 2000-bed hospitals. Yes, it was the days of Medical Superintendents who had supreme power and all doctors of whatever rank and experience were Mental Health Officers with special authority to sign papers for compulsory admissions. The forensic unit was contained within the same complex.         Those were the days when we encountered psychosis in the raw so to speak. All the colony’s really mad people were admitted to this one place set in the furthest corner of the colony. In our year seven of us decided without much discussion that we all wanted to go into psychiatry. That was over 10% and all had quite idealistic reasons. It was perhaps a bit of a disappointment to our parents that we did not pursue a more conventional specialty that might provide us with more status and financial reward. Then there was the fear of contamination that somehow one might become mad too. Recent day medical students are said to shy away from psychiatry for these same reasons.         Education seems to have little effect on superstition.
                                     ......................................….read the full Chapter: HERE

Brain on Fire   



Scientific America: https://www.scientificamerican.com/article/brain-on-fire-my-month-of/

Wednesday, August 4, 2021

The Power of Prayers & Teratoma: Brain & NMDA!

As the BBC reported on the work on NMDA, this blog post was from Sep 1, 2013 and it was an answer to my case of Teratoma induced coma/psychosis.

In medicine, truly new discoveries are uncommon and with the emergence of guidelines and protocols it has become even more difficult to make new discoveries. It has taken over 30 years before I could understand what happened to my Teratoma patient. Luckily for her, the treatment she received would have been in line with what we know now of the condition.


Hospital Medicine indeed has its important place and most important of all in the discovery of new conditions and establishing diagnostic and treatment programmes.

It is perhaps timely to remind the next generation of Bright Young Things that become doctors to remember that psychiatric symptoms presented by a patient may indeed be the presentation of a neurological condition.

This is more so for bizarre combinations of psychiatric and other symptoms. It was in the last five years or so that much progress has been made on what is now called Anti-NMDA Receptor Encephalitis.

Who knows, one day medical scientists might be able to decipher the most difficult of psychiatric conditions: Schizophrenia. Bright Young Psychiatrist might have noticed that Clozapine, one of the most effective drugs for schizophrenia has a marked effect on the immune system. 

In the mean time Pennsylvania might have something they could be proud of: the discovery of this new neurological condition.


WoodlochPennsylvania ©2012 Am Ang Zhang

For now, my patient’s parents’ prayer has been answered. 

Chapter 29  The Power of Prayers


Anti-NMDA Receptor Encephalitis

NEW ORLEANS — A mysterious, difficult-to-diagnose, and potentially deadly disease that was only recently discovered can be controlled most effectively if treatment is started within the first month that symptoms occur, according to a new report by researchers from the Perelman School of Medicine at the University of Pennsylvania. The researchers analyzed 565 cases of this recently discovered paraneoplastic condition, called Anti-NMDA Receptor Encephalitis, and determined that if initial treatments fail, second-line therapy significantly improves outcomes compared with repeating treatments or no additional treatments (76 percent versus 55 percent). The research is being presented at the American Academy of Neurology's 64th Annual Meeting in New Orleans.

565 cases! Not so rare!

The condition occurs most frequently in women (81 percent of cases), and predominately in younger people (36 percent of cases occurring in people under 18 years of age, the average age is 19). Symptoms range from psychiatric symptoms, memory issues, speech disorders, seizures, involuntary movements, to decreased levels of consciousness and breathing. Within the first month, movement disorders were more frequent in children, while memory problems and decreased breathing predominated in adults.

My patient was under 18 and presented with catatonia symptoms. She later lose consciousness and was ventilated.

"Our study establishes the first treatment guidelines for NMDA-receptor encephalitis, based on data from a large group of patients, experience using different types of treatment, and extensive long-term follow-up," said lead author Maarten TitulaerMD, PhD, clinical research fellow in Neuro-oncology and Immunology in the Perelman School of Medicine at the University of Pennsylvania. "In addition, the study provides an important update on the spectrum of symptoms, frequency of tumor association, and the need of prolonged rehabilitation in which multidisciplinary teams including neurologists, pediatricians, psychiatrists, behavioral rehabilitation, and others, should be involved."

The disease was first characterized by Penn's Josep Dalmau, MD, PhD, adjunct professor of Neurology, and David R. Lynch, MD, PhD, associate professor of Neurology and Pediatrics, in Annals of Neurology in 2007. One year later, the same investigators in collaboration with Rita Balice-Gordon, PhD, professor of Neuroscience, characterized the main syndrome and provided preliminary evidence that the antibodies have a pathogenic effect on the NR1 subunit of the NMDA receptor in the Lancet Neurology in December 2008. The disease can be diagnosed using a test developed at the University of Pennsylvania and currently available worldwide. With appropriate treatment, almost 80 percent of patients improve well and, with a recovery process that may take many months and years, can fully recover.

Teratoma: finally!

In earlier reports, 59 percent of patients had tumors, most commonly ovarian teratoma, but in the latest update, 54 percent of women over 12 years had tumors, and only six percent of girls under 12 years old had ovarian teratomas. In addition, relapses were noted in 13 percent of patients, 78 percent of the relapses occurred in patients without teratomas.
As Anti-NMDA Receptor Encephalitis, the most common and best characterized antibody-mediated encephalitis, becomes better understood, quicker diagnosis and early treatment can improve outcomes for this severe disease.
The study was presented in a plenary session on Wednesday, April 25, 2012 ET at 9:35 AM at the American Academy of Neurology's annual meeting.
[PL01.001] Clinical Features, Treatment, and Outcome of 500 Patients with Anti-NMDA Receptor Encephalitis

Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies

Of 100 patients with anti-NMDA-receptor encephalitis, a disorder that associates with antibodies against the NR1 subunit of the receptor, many were initially seen by psychiatrists or admitted to psychiatric centres but subsequently developed seizures, decline of consciousness, and complex symptoms requiring multidisciplinary care. While poorly responsive or in a catatonic-like state, 93 patients developed hypoventilation, autonomic imbalance, or abnormal movements, all overlapping in 52 patients. 59% of patients had a tumour, most commonly ovarian teratoma. Despite the severity of the disorder, 75 patients recovered and 25 had severe deficits or died.

Related paper:




NHS 1978: Hope, Faith & Supermarket


Cahalan's new memoir is called 

Brain on Fire 

-My Month of Madness.                                


Brain on Fire   


Chapter 29  The Power of Prayers                                       


        

Friday, February 12, 2021

Bright Young Doctors & Rainbow: NMDA & Autoimmune Encephalitis

In Medicine, it is amazing what the Bright Young Doctors can offer. In my day and now!


Forty years ago, a patient of mine was unconscious for 23 days and it was mother's belief that it was through prayer that her daughter was saved. I did not know anything about NMDA or Autoimmune Encephalitis then nor did Queen Square.

The Bright Young Doctor in my days:

" A good doctor is one who is not afraid to ask for help but he must also know where to ask.
         “Get me Great Ormond Street.”
         “I already did.”
         She is going to be a good doctor.
         “Well, the Regional unit said that they had no beds so I thought I should ring up my classmate at GOS and she talked to her SR who said “send her in”.”
         Who needs consultants when juniors have that kind of network?  This girl will do well.
         “Everything has been set up. The ambulance will be here in about half an hour and if it is all right I would like to go with her.”
         “Yes, you do and thanks a lot.”   ............."                     full ChapterHERE


But perhaps God works through his people in his own way. Discoveries in Medicine should therefore enhance our faith rather than the other way round.

It took nearly 40 years for the real answer to her prayers to really emerge.

 ©2012 Am Ang Zhang


The Bright Young Doctor now:

I was staying at our resort in Boquete and was having dinner with three friends all of them with medical connections. One was in hospital administration and one a nurse. The husband of the nurse was a pharmacist. Somehow the conversation drifted into medical topics and knowing that I am a Child Psychiatrist the pharmacist started talking about his nephew who was nearly sent to a mental institution as he suffers from catatonia and doctors eventually diagnosed schizophrenia and put him on antipsychotics. Luckily the catatonic symptom probably saved him as some bright young thing just read the book Brain On Fire and gave him the Clock Test. That led to the NMDAR antibody testing that proved positive. He responded well to the treatment regime that has been developed and is off all antipsychotic medication.

My Teratoma patient was lucky as she belong to that group that improved without further treatment once the Teratoma was removed. She eventually had a baby.


The Power of Prayers & Teratoma: Brain & NMDA!


Anti-NMDA Receptor Encephalitis

NEW ORLEANS — A mysterious, difficult-to-diagnose, and potentially deadly disease that was only recently discovered can be controlled most effectively if treatment is started within the first month that symptoms occur, according to a new report by researchers from the Perelman School of Medicine at the University of Pennsylvania. The researchers analyzed 565 cases of this recently discovered paraneoplastic condition, called Anti-NMDA Receptor Encephalitis, and determined that if initial treatments fail, second-line therapy significantly improves outcomes compared with repeating treatments or no additional treatments (76 percent versus 55 percent). The research is being presented at the American Academy of Neurology's 64th Annual Meeting in New Orleans.

565 cases! Not so rare!

The condition occurs most frequently in women (81 percent of cases), and predominately in younger people (36 percent of cases occurring in people under 18 years of age, the average age is 19). Symptoms range from psychiatric symptoms, memory issues, speech disorders, seizures, involuntary movements, to decreased levels of consciousness and breathing. Within the first month, movement disorders were more frequent in children, while memory problems and decreased breathing predominated in adults.

My patient was under 18 and presented with catatonia symptoms. She later lose consciousness and was ventilated.

"Our study establishes the first treatment guidelines for NMDA-receptor encephalitis, based on data from a large group of patients, experience using different types of treatment, and extensive long-term follow-up," said lead author Maarten TitulaerMD, PhD, clinical research fellow in Neuro-oncology and Immunology in the Perelman School of Medicine at the University of Pennsylvania. "In addition, the study provides an important update on the spectrum of symptoms, frequency of tumor association, and the need of prolonged rehabilitation in which multidisciplinary teams including neurologists, pediatricians, psychiatrists, behavioral rehabilitation, and others, should be involved."

The disease was first characterized by Penn's Josep Dalmau, MD, PhD, adjunct professor of Neurology, and David R. Lynch, MD, PhD, associate professor of Neurology and Pediatrics, in Annals of Neurology in 2007. One year later, the same investigators in collaboration with Rita Balice-Gordon, PhD, professor of Neuroscience, characterized the main syndrome and provided preliminary evidence that the antibodies have a pathogenic effect on the NR1 subunit of the NMDA receptor in the Lancet Neurology in December 2008. The disease can be diagnosed using a test developed at the University of Pennsylvania and currently available worldwide. With appropriate treatment, almost 80 percent of patients improve well and, with a recovery process that may take many months and years, can fully recover.

Teratoma: finally!

In earlier reports, 59 percent of patients had tumors, most commonly ovarian teratoma, but in the latest update, 54 percent of women over 12 years had tumors, and only six percent of girls under 12 years old had ovarian teratomas. In addition, relapses were noted in 13 percent of patients, 78 percent of the relapses occurred in patients without teratomas.
As Anti-NMDA Receptor Encephalitis, the most common and best characterized antibody-mediated encephalitis, becomes better understood, quicker diagnosis and early treatment can improve outcomes for this severe disease.
The study was presented in a plenary session on Wednesday, April 25, 2012 ET at 9:35 AM at the American Academy of Neurology's annual meeting.
[PL01.001] Clinical Features, Treatment, and Outcome of 500 Patients with Anti-NMDA Receptor Encephalitis

Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies

Of 100 patients with anti-NMDA-receptor encephalitis, a disorder that associates with antibodies against the NR1 subunit of the receptor, many were initially seen by psychiatrists or admitted to psychiatric centres but subsequently developed seizures, decline of consciousness, and complex symptoms requiring multidisciplinary care. While poorly responsive or in a catatonic-like state, 93 patients developed hypoventilation, autonomic imbalance, or abnormal movements, all overlapping in 52 patients. 59% of patients had a tumour, most commonly ovarian teratoma. Despite the severity of the disorder, 75 patients recovered and 25 had severe deficits or died.

Related paper:

Anti-NMDA Receptor Encephalitis: Diagnosis, Psychiatric Presentation, and Treatment


Chapter 29  The Power of Prayers

The following is extracted from The Cockroach Catcher: Chapter 29 The Power of Prayers.
According to old Chinese advice, it is wise never to discuss politics or religion even amongst best friends.           Religious belief can often blur judgement in the wisest of people. In psychiatry it is sometimes not easy. This is particularly true in cases of florid psychosis, which often presents with symptoms of hallucination, delusion and even vision.         I remember my early days of psychiatry in a mental hospital in Hong Kong. Yes, it was the days of 2000-bed hospitals. Yes, it was the days of Medical Superintendents who had supreme power and all doctors of whatever rank and experience were Mental Health Officers with special authority to sign papers for compulsory admissions. The forensic unit was contained within the same complex.         Those were the days when we encountered psychosis in the raw so to speak. All the colony’s really mad people were admitted to this one place set in the furthest corner of the colony. In our year seven of us decided without much discussion that we all wanted to go into psychiatry. That was over 10% and all had quite idealistic reasons. It was perhaps a bit of a disappointment to our parents that we did not pursue a more conventional specialty that might provide us with more status and financial reward. Then there was the fear of contamination that somehow one might become mad too. Recent day medical students are said to shy away from psychiatry for these same reasons.         Education seems to have little effect on superstition.                                     ......................................….read the full ChapterHERE



Cahalan's new memoir is called Brain On Fire-My Month of Madness.      

Brain on Fire      

                     

Sunday, April 14, 2019

Norway and The Answer to Prayer: Teratoma.


We provided World Class Medicine without trying. A quote from a fellow blogger, Dr. No.


Dr No said...
Excellent post - and yes, that is exactly how it used to be. World class medicine without even trying - we just did it, because that is what we did, just as the dolphin swims, and the eagle soars. A key, even vital feature was that the doctors looking after their patients did not need to worry about money or managers. They just got on with it. There was no market to get in the way of truly integrated care. Some may point out that 13 year olds with teratomas are rare, and that is true, but what this case shows us, precisely because of its complexity, is just how capable the system was. And most of the time (of course not always), it dealt just as capably with more routine cases. "How is (sic) the new Consortia going to work out the funding and how are the three Foundation Trust Hospitals going to work out the costs." Exactly. And then: who is going to pay for the staff and their time to work out out all those costs and conduct the transactions?
What many politicians may not know is that pride in what we do is often more important than money or anything else. Our pride is one sure way to ensure quality of practice.

Do we really want to take that away now? Years of heartless re-organisation has left many of us dedicated doctors disillusioned. Many young ones have left. Poorly trained doctors that have no right to be practising medicine now even have jobs in some of these well known hospitals. 

Can we continue to practise World Class Medicine even if we wanted to?

According to old Chinese advice, it is wise never to discuss politics or religion even amongst best friends.  

Religious belief can often blur judgment in the wisest of people.

Thirty years ago, a patient of mine was unconscious for 23 days and it was mother's belief that it was through prayer that her daughter was saved. I did not argue with her then.

But perhaps God works through his people in his own way. Discoveries in Medicine should therefore enhance our faith rather than the other way round.

It took nearly 30 years for the real answer to her prayers to really emerge.

My recent visit to this beautiful church in Norway reminded me of my patient. and i cannot believe that it took another 30 years for the true answer to arrive. 


Beautiful Church in Tromso, Norway.


© 2019 Am Ang Zhang

The following is extracted from The Cockroach Catcher: Chapter 29 The Power of Prayers.

  Some time in early February of 1978 I was called to do a Home Visit on a thirteen year old girl by Dr Pinkerton, a paediatric consultant. Dr Pinkerton had been the local Paed for years and was generally well regarded. She had, in my short time as consultant, referred a couple of cases, most notably that of a Tourette syndrome and a boy with non-stoppable hiccups. Both cases put me in her A-list and I gathered that not many were on that list. Needless to say I realised too that her cases were never straightforward or simple.  Those she would have dealt with herself. The girl had upper arm stiffness on the left side and Dr Pinkerton could not find much else wrong with her, and so it crossed her mind that perhaps there was something psychiatrically wrong.  The girl was also carrying out some strange rituals around the house and Dr Pinkerton did wonder about psychosis or even catatonia.
...............


 The x-ray came back. The tell tale tooth was there and yes – a Teratoma[5], the distinctive type of tumour that can include teeth, hair, sometimes, even a jaw and tongue.  I guessed just a split second before the results came back. How annoying.
         Working diagnosis: Teratoma with possible toxic psychosis.
         Emergency operation was arranged. Yes, she would be fine a little while after the operation, I reassured the parents.
         The paediatric junior arrived and took some history and did a quick physical before she was prepared for the theatre. This petite doctor with a very babyish face told me that on her first day in her last job she had to do an emergency tracheotomy. This time she had been on call for the last three nights and the battery in her old Mini could not cope with the heavy frost so she had to wait for AA before coming. She was most apologetic for not having got in earlier.
         She asked if I had seen many toxic psychosis cases and I asked if she had come across any in her psychiatric placement. As with all good psychiatrists answering a question with another is in our blood and here it worked well.
         Neither of us knew what was to hit us next.
         At 2 A.M. I had a call from her.
         “Your patient – I mean our patient could not be aroused after the operation. Yes they removed the teratoma, complete and intact. It is bigger than any specimen I have seen but she could not be aroused.  Any ideas?”
         “Call the paediatrician on call in the regional paediatric unit and I will be in.”
         What happened?  I asked myself as I drove to the hospital.
         What had we done? This was fast becoming a nightmare situation.
         What was I going to say to the parents?

         Something else was going on here, and I was not happy because I did not know what it was. I was supposed to know and I generally did. After all I was the consultant now.........


Read the whole chapter: Chapter 29  The Power of Prayers


In medicine, truly new discoveries are uncommon and with the emergence of guidelines and protocols it has become even more difficult to make new discoveries. It has taken over 30 years before I could understand what happened to my Teratoma patient. Luckily for her, the treatment she received would have been in line with what we know now of the condition.

Hospital Medicine indeed has its important place and most important of all in the discovery of new conditions and establishing diagnostic and treatment programmes.

It is perhaps timely to remind the next generation of Bright Young Things that become doctors to remember that psychiatric symptoms presented by a patient may indeed be the presentation of a neurological condition.

This is more so for bizarre combinations of psychiatric and other symptoms. It was in the last five years or so that much progress has been made on what is now called Anti-NMDA Receptor Encephalitis.

Who knows, one day medical scientists might be able to decipher the most difficult of psychiatric conditions: Schizophrenia. Bright Young Psychiatrist might have noticed that Clozapine, one of the most effective drugs for schizophrenia has a marked effect on the immune system.

In the mean time Pennsylvania might have something they could be proud of: the discovery of this new neurological condition.



For now, my patient’s parents’ prayer has been answered. 

Chapter 29  The Power of Prayers


Anti-NMDA Receptor Encephalitis


NEW ORLEANS — A mysterious, difficult-to-diagnose, and potentially deadly disease that was only recently discovered can be controlled most effectively if treatment is started within the first month that symptoms occur, according to a new report by researchers from the Perelman School of Medicine at the University of Pennsylvania. The researchers analyzed 565 cases of this recently discovered paraneoplastic condition, called Anti-NMDA Receptor Encephalitis, and determined that if initial treatments fail, second-line therapy significantly improves outcomes compared with repeating treatments or no additional treatments (76 percent versus 55 percent). The research is being presented at the American Academy of Neurology's 64th Annual Meeting in New Orleans.

565 cases! Not so rare!

The condition occurs most frequently in women (81 percent of cases), and predominately in younger people (36 percent of cases occurring in people under 18 years of age, the average age is 19). Symptoms range from psychiatric symptoms, memory issues, speech disorders, seizures, involuntary movements, to decreased levels of consciousness and breathing. Within the first month, movement disorders were more frequent in children, while memory problems and decreased breathing predominated in adults.

My patient was under 18 and presented with catatonia symptoms. She later lose consciousness and was ventilated.

"Our study establishes the first treatment guidelines for NMDA-receptor encephalitis, based on data from a large group of patients, experience using different types of treatment, and extensive long-term follow-up," said lead author Maarten TitulaerMD, PhD, clinical research fellow in Neuro-oncology and Immunology in the Perelman School of Medicine at the University of Pennsylvania. "In addition, the study provides an important update on the spectrum of symptoms, frequency of tumor association, and the need of prolonged rehabilitation in which multidisciplinary teams including neurologists, pediatricians, psychiatrists, behavioral rehabilitation, and others, should be involved."

The disease was first characterized by Penn's Josep Dalmau, MD, PhD, adjunct professor of Neurology, and David R. Lynch, MD, PhD, associate professor of Neurology and Pediatrics, in Annals of Neurology in 2007. One year later, the same investigators in collaboration with Rita Balice-Gordon, PhD, professor of Neuroscience, characterized the main syndrome and provided preliminary evidence that the antibodies have a pathogenic effect on the NR1 subunit of the NMDA receptor in the Lancet Neurology in December 2008. The disease can be diagnosed using a test developed at the University of Pennsylvania and currently available worldwide. With appropriate treatment, almost 80 percent of patients improve well and, with a recovery process that may take many months and years, can fully recover.

Teratoma: finally!

In earlier reports, 59 percent of patients had tumors, most commonly ovarian teratoma, but in the latest update, 54 percent of women over 12 years had tumors, and only six percent of girls under 12 years old had ovarian teratomas. In addition, relapses were noted in 13 percent of patients, 78 percent of the relapses occurred in patients without teratomas.
As Anti-NMDA Receptor Encephalitis, the most common and best characterized antibody-mediated encephalitis, becomes better understood, quicker diagnosis and early treatment can improve outcomes for this severe disease.
The study was presented in a plenary session on Wednesday, April 25, 2012 ET at 9:35 AM at the American Academy of Neurology's annual meeting.
[PL01.001] Clinical Features, Treatment, and Outcome of 500 Patients with Anti-NMDA Receptor Encephalitis

Of 100 patients with anti-NMDA-receptor encephalitis, a disorder that associates with antibodies against the NR1 subunit of the receptor, many were initially seen by psychiatrists or admitted to psychiatric centres but subsequently developed seizures, decline of consciousness, and complex symptoms requiring multidisciplinary care. While poorly responsive or in a catatonic-like state, 93 patients developed hypoventilation, autonomic imbalance, or abnormal movements, all overlapping in 52 patients. 59% of patients had a tumour, most commonly ovarian teratoma. Despite the severity of the disorder, 75 patients recovered and 25 had severe deficits or died.

Related paper:



Post Script:
“Ten years later mother came to see my secretary and left a photo. It was a photo of her daughter and her new baby. She had been working at the local bank since she left school, met a very nice man and now she had a baby. Mother thought I might remember them and perhaps I would be pleased with the outcome.

I was very pleased for them too but I would hate for anyone to put faith or god to such a test too often.”