Marc*’s Story: Feeling like an Outsider, Alone with PANDAS Disorder

by Assunta Ginanneschi

Apparently our blog is getting popular, and we are very happy about that!

This time we’ve got a request from Paula*, a former classmate of mine, who asked me to blog on PANDAS . Her neighbor Marc* is affected by this rare disease; as a result, his entire family has been on a therapeutic odyssey of epic proportions.

At the age of 3,  Marc had a severe case of strep throat, that worsened into Mononucleosis. He was hospitalized. After an antibiotic treatment, he recovered well and was discharged from hospital as a healthy child.  A few weeks later he developed some tics, which he had never had before.  

Disease description

PANDAS— Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections — is a subgroup of childhood-onset obsessive-compulsive disorder (OCD)The Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) states that obsessive-compulsive and related disorders include body dysmorphic disorder and body-focused repetitive behavior. Common obsessions in children include preoccupations with contamination, harm to self or others, symmetry, as well as fear that a bad outcome will occur if a ritual is not completed in just the right way. Common compulsions in children include washing, checking, and ordering rituals.

In Marc’s case the physical tics appeared suddenly: his leg were restless, he would involuntarily shrug and throw his head back. His condition worsened after his first growth spurt, around eight years old. The tics increased in number and frequency and became debilitating, with preferential lateralization on the left hand side of his body. In addition to these symptoms, Marc developed new disorders: strong intolerance to light and loud noises, somnambulism, a nervous cough and an affected gait. He began to find it difficult to concentrate and his handwriting changed for the worse.

Diagnosis

The situation was not longer tolerable and the symptoms worsened each time Marc was put under emotional stress. The pediatrician kept on trivializing the symptoms until Marc’s mother showed him a tape of her son. Marc had problems even keeping quiet enough to watch TV.  She read about a similar case on the Internet, where the child was improperly hospitalized as schizophrenia patient. Marc’s mum recognized almost all the symptoms that boy had in her own son. So she realized she was not over-protecting him, he had a real disease and needed a real treatment.

Unfortunately, PANDAS is not yet universally recognized as a real disease, and this makes access to the necessary support structures very difficult. Marc’s mother had problems even finding someone who could run the analysis in order to get a proper diagnosis, and her son was too young to explain how he felt. PANDAS can be diagnosed by a very simple throat swab and the “Antistreptolysin O Titer” ASLOT. The first test was negative for Marc, but the ASLOT revealed a value twice as high as the normal threshold.

Finally, again using the Internet, Marc’s mother found a physician in Rome who treats people with PANDAS. She sent him an email on Saturday evening, just after Christmas. He replied on Sunday morning to fix an appointment. That was the best Santa gift she got that year.

Disease Origin

So how is it possible that a child with a common strep infection a few week later develops neuro-psychiatric symptoms? This depends on how our body works.  When we come in contact with bacteria, our body reacts to protect us. Scientists call this an antigen-antibody reaction, a specific chemical interaction between the antibodies produced by our natural defenses, the B cells, and the antigens, produced by the bacterial invaders.

As the old saying goes: “The best defense is a good offense .”

immune reaction nrmicro3415-f2 This “best defense” is also known as immune reaction, the fundamental reaction in the body by which the body is protected from complex foreign molecules, such as GABHS and their chemical toxins. In the blood, the antigens are bound by antibodies to form an antigen-antibody complex and then transported to cellular systems where it can be destroyed or deactivated, as explained in this video.

Group A β-hemolytic streptococcus (GABHS, Streptococcus pyogenes), also known as GAS is one of the most common human pathogens. Several pathologies have been associated with acute GABHS infections, i.e. strep throat and scarlet fever. GABHS produces M protein as antigen, the major surface protein on the cell wall. 

NESTER  et alMicrobiology 2-28602-01 Figure 23.7

NESTER et al Microbiology 2-28602-01 Figure 23.7

The tricky thing is that the part of protein M the antibody binds to, mimics part of the brain receptorsIn other words, children with PANDAS apparently develop antibodies against the GABHS that work also as anti-neuronal (anti-brain) antibodies. The result is an uncommon behavioral or movement alteration, as shown in this video.

Incidence

In general Obsessive-Compulsive Disorder (OCD) affects 1%–2% of children and adolescentsAt puberty, the sex ratio of affected individuals switches from predominantly males to predominantly females. Boys are more commonly affected by childhood-onset OCD than girls, and the ratio of occurrence is 2–3:1. This ratio reverses in those diagnosed with the disorder during or after puberty, with a male-to-female ratio of 1:1.35. Both adult- and childhood-onset OCD were once thought to be a rare condition affecting less than 1 in 1,000 individuals; however, advances in diagnosis and treatment of have led to increased identification of the disorder.

Therapeutic Strategies

So far three different approaches have been identified for treating

1.Ataractics

Pharmacotherapy with serotonergic drugs (SSRI) combined with cognitive behavioral therapy (CBT) has proven efficacy against  OCD, whether the symptomatology is triggered by a GABHS infection or not. These drugs are currently thought to work by influencing structures in the caudate, but the specific details of the role of serotonin in OCD are not fully understood yet .

For the treatment of childhood OCD, only clomipramine, fluvoxamine and sertraline have been approved by the FDA for child and adolescent OCD. If one medication is found to be ineffective after an adequate test period, a different SSRI will usually be tried next.

Other therapies include Clonazepam (a benzodiazepine with anxiolytic properties), Risperidone (a neuroleptic with highly specific antidopaminergic activity) or Riluzole (a glutamate antagonist), but the benefit of these drugs in childhood-onset OCD still requires study. Many of these drugs have numerous side effects, some of which can be severe.

Marc never had SSRI, but he’s seeing a psychologist. His mother decided to submit him to a cognitive test. While the result showed Marc borderline for legasthenie, his performance in logical thinking and memory was much higher than the average.   

Integration in school was not easy for Marc, because even though he is young, he realizes there are differences between him and the others. This makes Marc an outsider; sometimes he feels alone and not able to manage the situation. His mum’s support is not enough, he needs some external care.

2.Plasma Exchange and IVIG

When symptoms are severe and disabling, children with PANDAS can also be treated with plasma exchange and IntraVenous ImmunoGlobulins (IVIG)This treatment reduces the OCD symptoms at 1-month follow-up.

This MRI shows significant enlargement of the basal ganglia (caudate, putamen and globus pallidus) among children with PANDAS symptoms and subsequent decrease in size after plasma exchange, compared with healthy volunteers.

JCI37563.f3

Basal ganglia are interconnected with the cerebral cortex, thalamus, and brainstem all of which are associated with functions such as motor control, cognition, emotions, and learning.

Plasma exchange and IVIG remove the pathogenic cross-reactive antibodies and confirm the involvement of the systemic immune system in the PANDAS disorder: the antibodies induce a dysfunction in the brain biochemistry and the result is an obsessive-compulsive disorder (OCD). The role of the immune system in the origin of OCD is still unclear, but parallels do exist. This treatment is quite complicated and has never been tried for Marc.

3.Antibiotics

The use of antibiotics is based upon on the idea that if OCD and/or tics are a consequence of the infection with GABHS.

Marc’s strep infection had first been treated with oral amoxicillin, which worked, but only partially. He described his head as getting lighter, but two weeks after the treatment everything was like before. Then they tried treating him with Azithromycin, just 3 days per week for 6 months, but the results were not satisfying. Now Marc’s treatment is Benzylpenicillin-retard, intramuscular injection, every three weeks. He limps for two days after each injection.

Sadly, the drug is not available where Marc lives and giving the injection itself requires some skills. Fortunately, Paula is always on business travel and can buy the drug in other European countries. Marc must be treated by the hospital in the next town, where the staff is willing to cooperate, give him the injection and complete the paperwork. For the follow up, it is necessary to fill out a form for comparing the symptoms before and after the therapy. The hospital just in front of Marc’s house door was not willing to assist.

Marc’s therapy should last six months, but may be extended if the symptoms don’t disappear. Of course, such long antibiotics treatment has side effects. Marc takes probiotics and follows rigid hygienic measures. Should he contract strep again, the worst case scenario would re-start all over again.  

It is Marc’s mother’s express wish to share her son experience and reach as many other mothers as possible. She has begun to call it her “crusade”: how difficult is to get the opportune attention from the pediatrician, have the analysis and diagnosis timely, make the pathology recognized as such, retrieve the drugs on the market, beg for the treatment and sustain all the costs by herself. The disease can be treated successfully if it’s addressed in time, but treatment becomes very difficult after puberty. We are glad to support her and Marc by sharing the story of their struggles with PANDAS, and we wait for your feedback and suggestions.
*Name changed to protect the patient’s identity

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One thought on “Marc*’s Story: Feeling like an Outsider, Alone with PANDAS Disorder

  1. Pingback: Working with Huntington’s Patients, Seizing the Damocles Sword | CheckOrphan

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