Association of Streptococcal Throat Infection With Mental Disorders: Testing Key Aspects of the PANDAS Hypothesis in a Nationwide Study

Sonja Orlovska ¹, Claus Høstrup Vestergaard ², Bodil Hammer Bech ³, Merete Nordentoft ¹, Mogens Vestergaard ², Michael Eriksen Benros ¹

Streptococcal infection has been associated with the development of obsessive-compulsive disorder (OCD) and tic disorders, a concept referred to as pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). This hypothesis is supported by findings of autoantibodies targeting the basal ganglia in the serum of children with PANDAS compared to controls. However, previous studies have been limited in size, and their results have been conflicting, with some not supporting the PANDAS hypothesis. Therefore, the purpose of this study was to investigate the risk of mental disorders following strep throat infection using the largest population-based cohort study to date, utilizing data from nationwide Danish registers that included more than 1 million children.

The population comprised individuals born between 1996 and 2013, who were followed for up to 17 years. During the study period, 40,435 children received a diagnosis of a mental disorder, with 38.1% of them having a previous positive streptococcal test result. Of the 1,078 individuals diagnosed with OCD, 51.6% had a previous positive streptococcal test, while 2,177 individuals were diagnosed with a tic disorder, with 45.6% having a previous positive strep test result.

Those with a positive strep test result had an 18% higher risk of any mental disorder, a 51% higher risk of OCD, and a 35% higher risk of tic disorder compared to individuals who did not undergo a strep test. Interestingly, individuals with a negative streptococcal test result, likely indicating a non-streptococcal throat infection, also showed an increased risk of mental disorders. The study revealed that those with streptococcal throat infections had the highest risk of all mental disorders, particularly OCD, compared to those with non-streptococcal infections. Although an association was found, the absolute risk of OCD and tic disorders following streptococcal throat infection remains small.

Reference:

Orlovska, S., Vestergaard, C. H., Bech, B. H., Nordentoft, M., Vestergaard, M., & Benros, M. E. (2017). Association of Streptococcal Throat Infection With Mental Disorders: Testing Key Aspects of the PANDAS Hypothesis in a Nationwide Study. JAMA psychiatry, 74(7), 740–746. https://doi.org/10.1001/jamapsychiatry.2017.0995

Association-of-Streptococcal-Throat-Infection-With-Mental-Disorders

For the first evaluation, my group had the privilege of having Dr. Manuel Saint Martin for an in-person evaluation. I presented a case of classic obsessive-compulsive disorder. As I was writing up this case, I had to do some research to understand the differential diagnosis and to develop a treatment plan. To enhance my understanding of this topic, I watched Osmosis videos, watched YouTube videos, and read about it on UpToDate. I thought my write-up for this patient was thorough and comprehensive. However, upon presenting it to Dr. Martin, the first thing he asked was if I knew whether the patient had a history of streptococcal throat infection. I told him that I did not ask that, and that’s when Dr. Martin explained how cases of untreated strep throat can be linked to a concept called PANDAS, which stands for “pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections.” This condition links strep infections to psychiatric disorders, particularly OCD and tic disorders. He advised me to do some more reading on this topic and choose an article to present related to it.

For the second evaluation, I picked a Spanish-speaking patient who arrived at the psychiatric emergency room after her son called the NYPD, saying his mother mentioned she would jump in front of a train. The patient denied this, but she was still brought in for a psychiatric evaluation. The patient was newly arrived from South America, so Dr. Martin agreed with my diagnosis of an adjustment disorder with depressed mood due to the stressors she was dealing with. However, Dr. Martin did not agree with my plan. I recommended medication, but an adjustment disorder doesn’t require medication unless a depressive disorder is suspected. I also suggested overnight observation since the patient had alleged suicidal ideation. However, Dr. Martin mentioned that if the patient denies suicidal intention and can be observed at home by family, there is no need to keep the patient overnight.

I also presented my article on PANDAS during my second evaluation, which was the largest cohort study done to date. The article had an interesting conclusion, stating that those with strep throat infection had the highest risk for OCD and tic disorders, but those without bacterial infections also had a higher risk for the same disorders. These evaluations were a great learning experience, and Dr. Martin was very educational. These evaluations were my favorite so far in the clinical year, most likely because I found myself enjoying psychiatry very much.

My rotation experience in Internal Medicine was indeed interesting. It served as a wake-up call, highlighting areas where I still need to learn and improve. One notable aspect of this rotation was observing firsthand the significant presence of physician assistants at NYPQ, many of whom operate with a high level of autonomy. It was inspiring to work alongside so many PAs and witness an environment greatly influenced by their contributions.

One of the highlights of this rotation for me was my time spent in the emergency room. I learned the importance of patient follow-up to track their progress, and I was impressed by how effectively the hospital’s EMR system captured this information. Additionally, I thoroughly enjoyed my experiences in the stroke unit, particularly when I had the opportunity to assist during stroke codes. I gained valuable insight into performing the NIH stroke scale and received excellent instruction from the PA and attending physicians who were part of the stroke team.

In the emergency room, I had the chance to practice various clinical skills, such as arterial blood gas sampling, IV placement, and venipuncture. I even had the privilege of assisting in a lumbar puncture. The nurses were incredibly helpful and took the time to teach me their techniques for drawing blood via IV, which is much gentler on the patient. I’m grateful for their willingness to share their knowledge, especially considering how busy they were.

At NYPQ, we encountered a wide range of cases, many of which were textbook presentations of diseases we studied during our didactic year. There is still so much to learn, but overall, my experience in NYPQ Internal Medicine was excellent. I hope to return once I become a PA because it’s an incredible learning environment. This rotation also helped me identify areas of weakness that I need to address, but I view this as an integral part of the learning experience. I am confident that my time in this rotation has prepared me well for the remaining rotations during my clinical year.

Diagnostic Accuracy of Probe to Bone to Detect Osteomyelitis in the Diabetic Foot: A Systematic Review

Kenrick Lam ¹, Suzanne A V van Asten ², Tea Nguyen ¹, Javier La Fontaine ¹, Lawrence A Lavery ¹

The probe-to-bone (PTB) test is a commonly used clinical tool for diagnosing osteomyelitis (OM), particularly in diabetic foot infections (DFI). However, its utility has been questioned in clinical settings. Diabetic foot infections can occur in up to 60% of patients with diabetic foot ulcers, making it crucial for clinicians to differentiate between soft tissue infections and osteomyelitis.

While bone culture is the standard for diagnosing OM, the PTB test offers a simpler and quicker alternative that requires fewer resources. This test involves inserting a sterile, metal surgical probe into the ulcer and identifying a positive result if a hard, gritty surface is felt inside.

A systematic review was conducted to evaluate the accuracy of the PTB test in diagnosing diabetic foot osteomyelitis. Seven studies met the inclusion criteria, and the recommendation is to utilize the PTB test to diagnose OM in high-risk patients with DFI and to rule out OM in those with a low risk of DFI.

The findings from this meta-analysis demonstrate that the PTB test is an effective tool in diagnosing diabetic foot OM. The pooled sensitivity, specificity, and diagnostic odds ratio were 0.87, 0.83, and 32 (range, 1.95–630), respectively, for the PTB test, which is similar to reported values for MRI (0.90, 0.83, and 42) and the erythrocyte sedimentation rate (0.81 and 0.90).

However, it’s important to note that the reliability of the PTB test may vary with clinician experience and ulcer location. Nonetheless, the PTB test offers a valuable diagnostic tool for clinicians managing diabetic foot infections, allowing for timely and accurate identification of osteomyelitis.

Reference:

Lam, K., van Asten, S. A., Nguyen, T., La Fontaine, J., & Lavery, L. A. (2016). Diagnostic Accuracy of Probe to Bone to Detect Osteomyelitis in the Diabetic Foot: A Systematic Review. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 63(7), 944–948. https://doi.org/10.1093/cid/ciw445

Diagnostic-Accuracy-of-Probe-to-Bone-to-Detect-Ostepmyelitis

For the first evaluation, I presented a case involving a female patient who visited the emergency department for gallstone pancreatitis. As I was writing up this case, I had to do some background research on pancreatitis, including relearning what it was. This really helped me expand my knowledge in the area. Before completing this evaluation, there was still so much about pancreatitis that I didn’t know. After researching, I learned a lot, not only about pancreatitis but also about gallbladder diseases. During the didactic phase, I honestly didn’t know enough to distinguish between gallbladder diseases, but now I would say I finally feel comfortable and knowledgeable enough. To enhance my understanding, I watched a helpful video on Osmosis that clinically discussed pancreatitis. I also used UpToDate to learn about management and the differential diagnosis for pancreatitis.

For my second evaluation, I discussed a male patient who had osteomyelitis. I saw an ulcer that went straight to the bone. This was another topic that I didn’t fully understand during the didactic phase, and it was astonishing how much can be learned by researching a topic related to the case. I learned the importance of managing diabetes to prevent foot ulcers, especially because they are so linked to osteomyelitis. To my surprise, I didn’t know that so much was involved with osteomyelitis; I thought of it as more of an independent disease. But to prevent ulcers, you need to keep the area clean and manage diabetes at the very least. Therefore, it is important to make sure that everything is controlled to prevent future ulcers. I made the mistake of focusing too much on osteomyelitis only and not thinking about the big picture, which includes controlling risk factors. Therefore, management involves not only the disease in question but also everything else that surrounds it, and that’s a lesson I will take with me into future rotations.

In the second evaluation, I also presented an article related to bone probing and its accuracy for diagnosing osteomyelitis. I learned that it is a useful part of the physical exam because it has sensitivities and specificities similar to MRI and ESR measures.

This evaluation was a good learning experience because I made several mistakes that are worth learning from. First, I need to work on my H&P flow, making sure it includes the relevant information and doesn’t become too repetitive. Second, I really need to make improvements to my plan, ensuring it includes all necessary steps, including consultations that need to be made. The plan also involves managing everything else that needs attention regarding the patient’s health, whereas before, I thought the plan was only for the patient’s chief complaint and related diagnosis. There was plenty I was unaware of and need to improve on in the future to be a competent physician assistant. But I am glad I am learning and finding out now while I’m still a student. I look forward to the next rotations to continue learning and improving my skills.