Jennifer Frankovich, MD, MS, dives into the intersection of infection, inflammation, and mental health. She discusses the increase in recognition of this critical overlap over the last decade, highlighting how systemic inflammatory conditions have the highest rate of co-occurring psychiatric disorders. The speaker outlines ten inflammatory diseases that frequently co-occur with mental health conditions, including spondyloarthritis, psoriasis/psoriatic arthritis, Behçet’s Syndrome, Sjögren’s disease, Scleroderma, CNS Vasculitis, Sydenhams’ Chorea, and Lupus. Frankovich underscores the connection of Streptococcal infections to many of these inflammatory conditions, noting their similarities to PANS and challenges with diagnosis. She provides thanks and acknowledgments before the Q&A. 

This is a follow-up to our June 12, 2024 webinar featuring Dr. Jennifer Frankovich, Ayan Mondal, Ph.D., and Noor A. Hussein, Ph.D.

In this Webinar

1:20 – Inflammation and mental health
3:50 – Spondyloarthritis (SpA)
11:00 – Psoriasis/Psoriatic Arthritis
16:05 – Behçet’s Syndrome
19:25 – Brain parenchymal disease
21:15 – Non-parenchymal disease
22:25 – Sjögren’s disease
24:05 – Scleroderma
25:50 – CNS Vasculitis
26:25 – Sydenhams’ Chorea
37:00 – Erythema Marginatum
38:50 – Strep infections and mental health
42:00 – Lupus
44:55 – Q&A

Inflammation and mental health

Over the last decade, recognition of the overlap between rheumatological/inflammatory disorders and mental health conditions has significantly increased. Frankovich notes common inflammatory diseases that co-occur with psychiatric symptoms, including those caused by small-vessel vasculitis, autoimmune encephalitis, basal ganglia inflammation, and white matter inflammation (1:20). Most commonly, she continues, systemic inflammatory conditions like psoriasis/psoriatic arthritis, and irritable bowel syndrome (IBS) have the highest rates of co-occurring psychiatric disorders (3:30). She outlines ten (10) specific disorders, how they present, and how clinicians/practitioners can test for them.

The odd couple?—Hardly: The emerging overlap between rheumatology and psychiatry (Taylor & Jain, 2017)

Spondyloarthritis 

Spondyloarthritis (SpA) can cause microscopic spinal inflammation that is not often perceptible on imaging until decades later. It is characterized by pain and stiffness in the morning and after prolonged stationary positions. Frankovich explains that 40% of patients with SpA also experience depression, anxiety, fatigue, and brain fog and that adults with SpA have a higher prevalence of OCD, anger/hostility, and deliberate self-harm versus controls (3:50). The speaker notes that children with psychiatric diagnoses may not be able to articulate pain and stiffness, so practitioners must look for clues such as stiffness walking, axial and peripheral stiffness, iliac pain and tenderness, and specific foot pains. Psoriasis and bowel inflammation also commonly co-occur with SpA. Frankovich underscores the high heritability of SpA and suggests observing parental symptoms when diagnosing children (7:15). 

Psoriasis/Psoriatic Arthritis

Psoriasis and psoriatic arthritis have significant overlap with psychiatric disorders, especially bipolar, depression, and anxiety. The speaker explains that pain from arthritis can seem out of proportion, so patients are often dismissed. Frankovich notes specific ultrasounds that can be used to identify inflammation in discrete areas of the body and reiterates how psychiatric conditions may keep patients, especially children, from complaining of their pain, making a diagnosis even more challenging (11:00). Common sites for psoriasis include behind the ears, on the scalp, around the belly button. She warns against mistaking Onycholysis for fungal nail infections and notes that streptococcal infections can trigger arthritis flares (13:35). 

Behçet’s Syndrome

The speaker describes Behçet’s Syndrome as a multisystem inflammatory disease where 10% of patients have neurological diseases perceptible on an MRI and 40% have psychiatric disorders. Other symptoms can include recurrent oral ulcers, ocular inflammation in the anterior portion of the eye, and potential scarring from genital ulcers. Behçet’s Syndrome is a type of transient arthritis where flareups, often triggered by intense immune responses to infection, can last from one to three weeks (16:05). Frankovich notes that when vascular inflammation is present in both arteries and veins, this nearly always indicates Behçet’s Syndrome. Pathergy, or blistering at the blood draw site, is also a strong indicator (18:25). 

Brain parenchymal disease

Brain parenchymal disease (BPD) is characterized by a subacute onset of multi-focal inflammatory legions, which an MRI can miss if it is not conducted at the time of a new deficit. In many cases, the MRI reflects non-specific white matter changes that do not rule out BPD in and of themselves. Some patients also suffer from headaches, behavior changes, and cognitive dysfunction, which can lead to temporary encephalopathy, seizures, and psychosis. The presenter underscores the importance of early diagnosis and treatment but notes that BPD is difficult to diagnose because legions are temporary and appear in different places each time (19:25). 

Non-parenchymal disease

Non-parenchymal diseases involve the brain’s venous systems. Cerebral venous thrombosis, or severe headaches, must be assessed using imaging that highlights the venous system (e.g., MRV). Non-parenchymal diseases often co-occur with fibromyalgia (18 – 37%), parietal cell autoantibodies, vitamin deficiencies (especially B,) and bowel ulcers or IBS (21:15). 

Sjögren’s disease

Frankovich defines Sjögren’s disease as a systemic rheumatologic condition that often presents with dry eyes and mouth and a lot of autonomic nervous system dysfunction such as altered vascular tone, esophageal contractility (trouble swallowing), cardiac rhythm abnormalities, and neuropathic symptoms (i.e., burning, tingling, or numbness). Co-occurring psychiatric disorders make it challenging to self-advocate. The speaker suggests running a mucosal biopsy of the lip to assess salivary gland inflammation if Sjögren’s disease is suspected (22:25). 

Scleroderma

Scleroderma is a systemic sclerosis that causes widespread vascular dysfunction and progressive fibrosis of the skin and internal organs. Over many years, the speaker explains, a person’s skin starts to harden. Early signs in children include Raynauds (cold, white hands) and abnormal nail fold capillaroscopic. She highlights that manifestation may precede the full disease by years, so it is critical to follow patients closely (24:05). 

Personality structure disturbances and psychiatric manifestations in primary Sjögren’s syndrome (Drosos et al., 1989)

CNS Vasculitis

CNS vasculitis is a very rare type of inflammation focused on the brain. It is perceptible on MRI scans and should be considered when children present with new-onset headaches and behavior changes (25:50). 

The spectrum of CNS vasculitis in children and adults (Twilt & Benseler, 2012)

Sydenhams’ Chorea

Sydenhams’ Chorea (SC) presents with three critical components: emotional lability, hypotonia (weak muscles), and chorea (involuntary, brief, random, and irregular movements of the limbs and face). In children, this can look like continuous restlessness (26:25). Frankovich explains that accompanying psychiatric symptoms are similar to what we see in PANS. For example, 60% of patients with SC have OCD at onset, and 100% have it at relapse. Other symptoms include outbursts of inappropriate behavior or mismatched emotions (easy crying or inappropriate laughing), irrational fears that can lead to delusions, anxiety, personality changes, and night terrors (28:08). Other presentations include difficulty keeping arms up or hyperactive reflexes (33:40). 

The presenter notes that the line between what is and is not SC is very blurry, making it hard to detect and diagnose. One of the earliest studies (1926) notes that, in children, nuanced chorea is always Sydenhams, so practitioners should always treat for strep infection and clear it out of the house. According to the study, emotional lability is the most constant observation, along with extreme personality changes where individuals become aggressive and irritable, which is very similar to how PANS presents (30:00). 

Children often cover up their chorea, so clinicians must actively look for muscle use abnormalities. Simple tests for chorea include the milkmaid’s grip and darting tongue. Because psychiatric symptoms like OCD can start two to four weeks before chorea, children who present with acute-onset OCD should be re-evaluated over at least one month (31:25). The onset of chorea can occur anywhere between one and eight months after a strep infection, meaning that ASO and DNASE titers may be normal during assessments (33:40). 

The presence of acute rheumatic fever can also support an SC diagnosis, but it is not necessary. However, the speaker warns that mild cases of SC without other manifestations of acute rheumatic fever may be mistakenly ascribed to behavior or emotional disorders, restlessness, or clumsiness. She reiterates the need for careful evaluation (36:10). 

Neuropsychiatric Aspects of Chorea in Children (Ebaugh, 1926)

The Prevalence of Neuropsychiatric Disorders in Sydenham’s Chorea (Ridel et al., 2010)

Obsessive compulsive behavior, hyperactivity, and attention deficit disorder in Sydenham chorea (Maia et al., 2005)

High prevalence of obsessive-compulsive symptoms in patients with Sydenham’s chorea. (Swedo et al., 1989)

Obsessive-Compulsive and Related Symptoms in Children and Adolescents With Rheumatic Fever With and Without Chorea: A Prospective 6-Month Study (Asbahr et al., 1998)

Sydenham’s Chorea: Physical and Psychological Symptoms of St Vitus Dance (Swedo et al., 1993)

The Emotional Correlates of Sydenham’s chorea (Freeman et al., 1963)

Mental Symptoms of Acute Chorea (Diefendor, 1912)

Rheumatic fever (Stollerman, 1997)

Erythema Marginatum 

Erythema Marginatum is a rash or skin lesion that occurs in SC and is brought out with heat (warm blankets or bath). Frankovich describes a case study of a 16-year-old with a long history of regressive behavior deterioration. He was initially diagnosed with SC; however, due to a lack of valve involvement, the diagnosis was removed. When he later presented with catatonia, clinicians wrapped him in warm blankets for 10 – 20 minutes and then observed his torso and limbs for rash patterns. The speaker notes that Erythema Marginatum patterns change every few minutes and that no other condition presents with such a rash (37:00). 

Streptococcal infections, inflammation, and mental health

A recent population-based study on the association of streptococcal infection and mental disorders found the primary outcome of strep infections was a diagnosis of mental disorders, OCD, or tics (38:50). The speaker says it can be difficult to know if strep played a role in any child’s behavior, so we must rely on epidemiologists continue educating practitioners about the link between strep and mental disorders, especially OCD. 

A smaller study that compared school strep swabs to behaviors found a high correlation between positive strep throat cultures and the presence of tics, adventitious movements, and problem behaviors. Further, if the strep was recurring, the risk for abnormal movements was increased (40:00). Many animal models have also shown this correlation. 

 Association of streptococcal throat infection with mental disorders (Orlovska et al., 2017)

Relationship of Movements and Behaviors to Group A Streptococcus Infections in Elementary School Children (Murphy et al., 2007)

CNS Autoimmune Disease after Streptococcus Pyogenes Infections: Animal Models, Cellular Mechanisms and Genetic Factors (Cutforth et al., 2016)

Lupus 

Lupus, though a common condition, is relatively rare in children. However, 25% of children with Lupus also have neuropsychiatric symptoms such as headaches (66%), psychosis (36%), and cognitive dysfunction (27%). Similar to PANS, Lupus patients commonly have arthritis, small vessel vasculitis, and high immune complexities. They are also 10 – 15 times more likely to have OCD compared to patients without Lupus (42:00). 

Resources

Frankovich thanks viewers and acknowledges research contributors. For more information on her research, visit med.stanford.edu/PANS. During the Q&A (44:55), the speaker answers questions about diagnosis, overlapping conditions, and much more.

Originally posted on October 1, 2024

Dr. Jennifer Frankovich reviews what we know about the underlying mechanisms, trajectories, and symptoms of Pediatric Acute Neuropsychiatric Syndrome (PANS). She discusses the role of the Basal Ganglia in PANS symptoms and cites contemporary research that highlights this connection. Frankovich touches on the disruption of the blood-brain barrier and auto-antibody regulation in PANS. 

Playback of Dr. Mondal’s presentation and Dr. Hussein’s presentation will be available at a future date.

In this webinar:

1:30 – PANS/PANDAS overview
3:10 – Underlying mechanisms
5:00 – Common symptoms
7:55 – PANS trajectories
9:35 – Basal Ganglia
13:12 – Antibodies and the blood-brain barrier

PANS/PANDAS

Frankovich outlines Pediatric Acute Neuropsychiatric Syndrome (PANS) and Pediatric Acute Neuropsychiatric Disorders Associated with Strep (PANDAS), underscoring the different triggers attributed to both conditions (1:30). Classification criteria for both PANS and PANDAS include a sudden onset of obsessive-compulsive disorder or eating restrictions along with at least two other co-occurring conditions like anxiety, sensory dysregulation, motor abnormalities, developmental regression, and deterioration of cognitive functioning (2:15). 

Underlying mechanisms

Children with PANS-related symptoms often have some form of immune predisposition. The speaker explains that PANS occurs after a person gets an infection, which, due to predisposition, causes a systemic inflammatory response. She notes that these inflammatory responses may lead to Basal Ganglia inflammation, altered neuronal signaling, microbial activation, and more (3:10). 

Common symptoms

The presenter describes classic PANS experiences, such as swelling in the knees, hips, and heel bones, back pain and inflammation, and evidence of psoriasis. She explains that children who experience their first case between the ages of five and ten will likely have arthritis by the time they are 14 (5:00). Frankovich highlights our bodies’ abilities to self-regulate inflammation, noting that in many cases, PANS symptoms are resolved on their own (7:15). 

PANS Trajectories

There are generally four different trajectories for PANS:

• Relapsing and remitting – returning to the same baseline
• Relapsing and remitting – worsening baseline across time
• Primary persistent – no return to baseline, remains in chronic episode
• Secondary persistent – multiple episodes with increasing baseline until it reaches a chronic episode. 

Frankovich asserts that the primary and secondary persistent trajectories are likely more related to autoimmune predispositions than the others. Therefore, she continues, these trajectories require the most intense treatments and assessments (7:55). 

Basal Ganglia

The Basal Ganglia (BG), a group of nuclei located beneath the cerebral cortex, has an inhibitory influence on motor and behavior systems. The speaker notes that inflammation, autoantibodies, and injury can disrupt the BG, affecting movements, mood, emotion, behavior, procedural learning, and cognition (9:35). 

Frankovich briefly presents four brain imaging studies suggesting BG inflammation in PANS. She also discusses three studies indicating that patients experience abnormal movements during REM sleep cycles. These REM movements predict Parkinson’s in adults, making this a critical area of research and care (10:25). 

Other physical signs of BG disruption include specific tongue and mouth movements. For example, a positive glabellar tap reflex is present in children with PANS, though it should disappear after infancy. Other abnormal tongue movements, like milkmaid grip, are discussed (11:55). The speaker notes that between 80 and 92% of patients in her clinic exhibit at least one sign of BG disruption (12:25).

19% of autistic youth also have a positive glabellar tap, and 27% have milkmaid grip tongue movements. The presenter, therefore, asserts that these BG signs are not unique to PANS and should be investigated carefully across groups (12:38). 

Antibodies and the blood-brain barrier

PANS autoantibodies target interneurons and have been found in healthy kids and children with PANDAS. Frankovich explains that if these antibodies are causing problems in the body, it is because they are crossing the blood-brain barrier (BBB) (13:12). She highlights that current research suggests local disruptions to the BBB are associated with PANS symptoms (13:50).

Originally published on June 14, 2024

This is a joint presentation by ARI and The World Autism Organisation.

Margaret Bauman, MD, discusses the many medical challenges those aging with autism face. She highlights the lack of medical training and research for adults and seniors with autism and underscores the need for increased education and advocacy. The speaker outlines challenges associated with preventative screenings, diagnosis of co-occurring conditions, primary care physicians, examination time constraints, and low government and health insurance reimbursement. Bauman speaks from her professional experiences and asserts the need for collaborative action to prepare for a better future. She closes with a question and answer session where she discusses guardian assignments and policy needs, disease prevalence in autism, and more.

Handouts are online HERE

In this webinar: 

0:00 – Petra Dilman – World Autism Organization
5:20 – Dr. Stephen Edelson – ARI
7:30 – Dr. Margaret Bauman – child psychologist and why she speaks on adult experiences
10:45 – Medical problems for aging autistic adults
12:00 – ER, hospitals and insurance providers
14:30 – Medical concerns for adults
18:20 – Provider limitations
21:20 – Incentives for primary care physicians
22:10 – Diagnostic challenges
24:30 – Atypical behaviors as signs of discomfort
27:14 – Behaviors that suggest GI discomfort
31:28 – Summary of diagnostic challenges
32:20 – Medical conditions
35:08 – Medically related conditions
38:10 – Mental health conditions
39:15 – Dementia surveys and queries
40:40 – Illnesses common in old age and lack of research
41:48 – Preventative screenings
43:34 – What needs to be done
46:33 – Parting words
48:20 – Q & A

Common medical challenges for autistic aging adults

Bauman emphasizes the importance of providing optimal – not minimal – medical care for adults and seniors with autism. She explains that due to the lack of medical care available to autistic adults, many pediatric practitioners have been obliged to carry on treating patients into adulthood (9:00). Presently, she continues, individual needs and proper support mechanisms for autistic adults and seniors remain largely unknown (7:30). Bauman lists some of the medical challenges faced by aging autistic adults (10:45) and discusses some in detail:

1. Finding primary care physicians (PCP) willing to accept adults with autism or who have any expertise or experience to do so. 

Few practitioners meet these parameters (11:30). Bauman describes this gap as a PCP shortage (18:25), noting the lack of medical education surrounding autism spectrum disorder. She states that, given the prevalence of autism, it is “inconceivable, regardless of what specialty somebody may eventually go into, that they aren’t going to come across one or more patients on the autism spectrum” (45:06). Further, time constraints on PCP visits (i.e., four 15-minute appointments per hour) do not allow enough time to assess many individuals with autism (19:00). Government medical records require thorough paperwork documentation as well, and there is relatively low Medicaid/Medicare reimbursement (20:40). Overall, she continues, incentives for PCP to take on patients with autism are minimal. Therefore, individuals needing such services often have to use academic hospitals where wait lists are three to six months long (21:20). 

2. ER and hospital staff (12:00) and insurance providers (13:30) are not prepared to deal with the complex multiplicity of care that accompanies autism.

3. Medical conditions often present differently in adults with autism, creating diagnostic challenges (22:10). 

For example, Bauman continues, autistic individuals often have difficulty verbalizing or pinpointing issues or discomfort (i.e., where it hurts, how it hurts, what the problem is) due to sensory processing differences and communication difficulties (23:40). She notes that atypical or disruptive behaviors may be signs of pain and discomfort, even if individuals cannot communicate their pain (24:30). The speaker shares personal experiences when she sent individuals with symptoms not generally associated with gastrointestinal (GI) issues to the gastroenterologist, where they were adequately diagnosed (24:50). She asserts that practitioners need to “… think beyond their own discipline” and consider unusual behaviors as interconnected. She reiterates that, due to the lack of education surrounding autism, even specialists may not know how to diagnose autistic adults and seniors (23:00) properly and urges viewers to “think beyond the obvious” (26:30). Bauman highlights the prevalence of GI issues in autism and asserts that practitioners and specialists must be trained on how differently symptoms present compared to the non-autistic population (30:30).  

Co-occurring conditions and mental health

The presenter lists medical conditions that commonly co-occur with autism, such as seizures, metabolic disorders, diabetes, and more (32:20). Bauman describes each condition and its relevance to autistic adults (33:30), noting the lack of routine screenings for adults and seniors with autism (41:48). She states that chronic pain, dental issues, sleep disorders, motor challenges, and even sensory processing issues can be significant factors that are part of, or contributing to, such medical conditions (35:08). Bauman touches on the acceleration of medical conditions with age, especially within the autistic population, and discusses gaps in research on diseases related to autistic adults and seniors (36:20). 

Bauman asserts that there should be more stress on the mental health conditions associated with autism, especially during and following the pandemic (38:10). Such conditions include frequent mental distress, anxiety, depression, PTSD, social isolation, and dementia (38:10). She discusses recent studies showing an increased diagnosis of dementia in adults with autism and questions how one defines such conditions in individuals with potential developmental delays (39:15). Bauman highlights the evident lack of research and publications on other illnesses common in old age (i.e., multiple sclerosis, Alzheimer’s) (41:00) and posits that we have little idea what these issues look like in adults with autism (40:40). 

Lifetime evaluation and care

The speaker reiterates the need to create methods by which we can begin to evaluate autistic seniors and adults in meaningful ways (44:10). She underscores that medical problems present in childhood often persist throughout the lifespan, along with other conditions that occur with aging (43:34). She tells of personal experiences consulting rehabilitation hospitals when autistic adults are admitted and notes how unprepared many are for communicating with and treating these patients (45:30). Bauman says that “family and professional advocacy for policy change is sorely needed” as it will take “several villages” to begin to understand how to effectively care for and assist autistic adults and seniors (46:18). She emphasizes preparing for the future and bringing greater awareness of the needs of aging autistic adults before opening the question and answer session (48:20).