Initial Presentation

Mack was an 18-year-old college student who enjoyed sports and was doing well in his classes. He was socially engaged with no previous history of mental illness. Yet two months prior, things rapidly changed when he awoke with feelings of being persecuted and delusions about being under attack. He became convinced that the government was beaming microwaves into his body and was afraid he was going to be thrown in jail for inexplicable reasons.

With the onset of his symptoms, Mack also became severely depressed. His affect flattened and his responses became stiff and wooden. Of even more concern, his mind repeatedly returned to thoughts of suicide.

Due to the severity of his symptoms, Mack had been hospitalized. Several medications were administered without benefit. After three weeks, he was finally discharged with very modest improvements from the antipsychotic medication, risperidone. Yet due to lingering concerns, Mack’s family brought him to their family doctor who ran some additional blood work.

Upon questioning, one of Mack’s close friends had a case of strep throat one week prior to Mack’s symptom onset. The previous summer, Mack had also been bitten by a tick without medical follow-up. There was no history of drug use.

He tested positive for Lyme disease and was started on doxycycline. With the complexity of the case, the family doctor referred Mack for a more thorough integrative medicine workup to help identify other potential causes or underlying factors contributing to his symptoms.

Upon exam, Mack had involuntary muscle movements and muscle weakness. His left arm and hand twitched repeatedly. His left fingers would grasp and release without conscious control. His thyroid was mildly tender to palpation.

Initial Relevant Labs

The following were results from Mack’s hospital stay:

• TSH was elevated at 5.2
• Anti-thyroglobulin antibodies were elevated at 173
• Anti-thyroid peroxidase antibodies were elevated at 182
• Low vitamin D at 17.5

Additional labs

• Antistreptolysin O titers were negative
• Throat culture was attempted, but patient was not compliant with the sample collection procedure

Working Diagnosis

Post-infectious autoimmune encephalitis/pediatric acute-onset neuropsychiatric disorders associated with streptococcus (PANDAS)

Initial Treatment

• Amoxicillin, 500 mg every 12 hours for suspected strep
• Ibuprofen, 600 mg three times daily with food
• Vitamin C, 1000 mg three times daily
• Curcumin, 500 mg three times daily
• Probiotic, 1 cap twice per day
• Vitamin D, 5000 IU daily
• Continue doxycycline and risperidone

Explanation

Due to the sudden onset of symptoms without a prior history of mental illness, the likelihood of an underlying biochemical or physiological cause of Mack’s symptoms was quite high. With a positive Lyme disease test and recent exposure to strep, addressing the potentially infectious nature of his condition was paramount. Immune activation is a known component of schizophrenia and was a likely contributing factor to Mack’s sudden onset of symptoms (Mora 2020).

While Mack’s ASO titers—a test for strep exposure—were negative, up to 40% of children with strep infection may test negative (PANDAS 2024). A negative ASO test does not rule out the possibility of a strep infection. Due to the difficulty in getting a throat swab, and the severity of Mack’s symptoms, empiric treatment for strep was prescribed.

Amoxicillin is an effective choice to treat streptococcus, and antibiotics are generally recommended to treat PANDAS (Cooperstock 2017). Non-steroidal anti-inflammatory medications are also known to shorten the acute mental-emotional symptoms associated with the condition (Brown 2017). Rapid treatment targeting the infectious cause and underlying inflammation in cases of PANDAS can decrease the likelihood of chronic, disabling neurological symptoms (Lepri 2019).

Curcumin, probiotics, and vitamin C have well-documented immune-regulating and anti-inflammatory effects (Peng 2021, Maldonado Galdeano 2019, Jafari 2019). The supplements were included to further support Mack’s immune system, decrease inflammation, and improve the chances of recovery.

Hashimoto’s thyroiditis, with elevations of thyroid antibodies, can contribute to psychosis (Gondwal 2021). The condition can also originate from an infectious origin (Shah 2000).

Low vitamin D is commonly associated with psychosis. And while trials of vitamin D in schizophrenia have been mixed, evidence suggests the potential for improvements in symptoms with supplementation (Neriman 2021).

Follow-up Presentation

Follow-up one week later was marked by startling improvements. All psychotic symptoms, depression, and suicidal ideation were gone. Mack’s effect had returned to normal: he smiled and made jokes throughout the medical visit. While the patient’s insight about the severity of his experience was low, he understood that he had experienced a psychotic episode. Mack was adamant that he did not want to re-experience symptoms and was willing to continue treatment.

Upon physical exam, thyroid tenderness had resolved. All signs of uncontrolled twitching and weakness were dramatically improved with just a small hand tremor remaining.

Follow-up Testing

• Thyroid labs had fully normalized

Follow-up Treatment

• Continue previous treatments
• Fish oil, 1 gram daily

Explanation

Evidence for fish oil in the treatment of psychosis and schizophrenia is somewhat mixed. However, a meta-analysis from 2021 found significant benefits with fish oil supplementation (Goh 2021). In addition, a recent analysis found that fish oil may prevent the transition to psychosis in high-risk individuals (Chen 2024).

Case Summary

While PANDAS is usually thought to occur in children before puberty, case reports in adults exist (Deshmukh 2022, Jory 2024). In addition, psychosis due to Lyme disease with a delayed onset has also been reported (Peixoto 2020). Psychiatric symptoms as a consequence of an infection should be on any differential diagnosis, especially in cases with a rapid onset without a prior history of mental illness. Infections that contribute to a psychiatric condition can be “occult” or hidden (Mufaddel 2014). As a consequence, underlying infections can not be ruled out due to a lack of infectious-type symptoms.

Mack’s case highlights the complexity of mental health diagnoses, their relationship to physiological factors, and the resilience of the brain to recover when those underlying components are addressed properly. Evaluating and treating a patient’s unique biochemistry can yield powerful results. Symptom resolution is more often achievable through this type of comprehensive, whole-person approach. While Mack will need to be followed carefully to prevent relapse, his quick recovery bodes well. Rapid treatment likely prevented a lifetime of neurological problems and mental illness.

Learn more about PANS/PANDAS

If you are interested in learning more about PANS/PANDAS, join us for our virtual conference Psychiatry Reimagined, a Functional and Integrative Medicine event for mental health on June 22-23. Dr. Nancy O’Hara, MD, MPH, FAAP will be a keynote speaker.

She has dedicated her functional medicine practice to the integrative and holistic care of children with chronic illness and neurodevelopmental disorders such as ADHD, PANDAS/PANS, OCD, Lyme, and ASD.

She is also a leader in the training of clinicians in the United States and abroad. Dr. O’Hara has written a comprehensive guidebook, “Demystifying PANS/PANDAS: A Functional Medicine Desktop Reference on Basal Ganglia Encephalitis”

Click here to register for the conference.