Pearls:

Motor impersistence or the inability to sustain a motor command, like sticking your tongue out or holding something in your hand is a symptom of chorea. This can cause a darting tongue or “milk-maids grip”.

As of 2015 Sydenham’s chorea cannot be used as single isolated criteria to make the diagnosis of acute rheumatic fever. Two major, or one major and two minor, must be present on initial presentation. Echocardiographic findings of carditis have been added to the criteria.

Post streptococcal glomerulonephritis can happen after skin or throat infections but acute rheumatic fever occurs only after throat infections.

Case

An eight-year-old previously healthy female presents with abnormal movements and difficulty speaking for the last two months.

Mom first noticed some spasms and some flailing of the patient's left arm roughly two to three months prior to presentation. The patient would have twitching of her arm and rapid retraction of the arm when she was attempting to use her hand. She had some difficulty writing and was unable to draw in a straight line. She also had some associated wrist and elbow pain, but there was not any redness or swelling of any of her joints. This came along with restlessness. In the last two weeks these movements began to progress to uncontrolled movements of all of her extremities, trunk and face. Her facial movements were described as moving her lower jaw from side to side, sticking out her tongue and the occasional lip smacking. She was able to speak in short phrases, but unable to speak in complete sentences and that speaking kind of waxed and waned. She had difficulty eating and chewing and she always felt like she was going to bite her tongue, because she couldn't control her tongue. She was having difficulties walking and keeping her balance. When she was focused on an activity the symptoms improved she got excited they got worse.

She had URI symptoms during the course of the illness but was not having any fevers, chest pain, palpitations or rash. She healthy, development was normal and she was not taking any medications.

On exam she was afebrile and vitals were normal.

She just appeared very restless and was constantly moving. Her exam was normal including the absence of any heart murmur or tachycardia, no arthritic joints and no rash. Her neurological exam was normal except for dysarthria, uncoordinated gait, and the presence of choreiform movements throughout involving all 4 extremities.

What is chorea? Think about dancing, writhing movements. In children this can look like restlessness. Finger movements can look like playing piano. They can be unable to maintain a motor movement and this is called motor impersistence. For example trying to stick the tongue out will look like it is coming back in and out. With the handgrip this is called “milk maids grip”.

Chorea can be differentiated from other movements.



Myoclonus, which can be single or clustered with rapid, jerky movements. Imagine the motions people make when falling asleep which is common and called hypnogogic myoclonus.





Motor tics which unlike chorea can be suppressed.





Dystonia is a movement disorder that is slower and a more twisting, writhing and posturing

Case Continuation

If asked her to stick her tongue out, she couldn't control it whatsoever. She could not sustain a grip on both hands at the same time. She had dysarthric speech and was unable to get out more than 1 or 2 words at a time. She had orofacial movements, including some lip smacking and some jaw thrusts. Her gait was really uncoordinated and she was stumbling after every few steps.

Brief Case Summary: An 8-year-old previously healthy girl who now has two to three months of worsening choreiform movements, in addition to dysarthria and clumsy walking, without any history of preceding illness.

Differential diagnosis:

Sydenham's chorea related to rheumatic fever is what we think of as the most common cause of chorea in kids. Even though she does not have the history of pharyngitis, emotional lability, along with all of these choreiform movements point in that direction. She is also the right age for having group A Strep infections. Depending on the age somewhere between 20 to 70% of kids who do have acute rheumatic fever do not remember the preceding pharyngitis.



Juvenile Huntington's chorea would lower on the differential, given there is no family history. Usually when kids present with Huntington's chorea, it is more of a slower movement, more Parkinsonian than the choreiform movements we see in adults.



Paraneoplastic conditions like opsoclonus myoclonus due to neuroblastoma.



Hyperthyroidism.



Neuropsychiatric lupus can also be associated with abnormal movements.



Cerebrovascular accident, like a stroke would be a consideration though it is hard to explain the generalized chorea. If she had something stroke, it would probably be more focal or unilateral at least.



Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) which is sometimes a controversial diagnosis. It is something to remember with anyone with neuropsychiatric symptoms and movements like this.



Tourette's syndrome in which you usually have symptoms ongoing for at least six months and you also need to have the presence of focal tics, which this patient does not.



Wilson's disease (a disease of copper metabolism) can present with new onset neurologic symptoms, which can also include behavioral changes.



Infections such as Human Immunodeficiency Virus and syphilis can present very atypically and if they're not on your list in cases like this, you'll miss them.

Case Continuation

Initial workup included a CBC and Complete metabolic profile, which were unremarkable. Erythrocyte sedimentation rate was 15 mm/h and C-reactive protein was 1.6 mg/L. Serum copper and ceruloplasmin were normal. Thyroid studies were normal. We also did some thyroid studies. HIV and rapid plasma reagin (RPR) were negative. ASO titer to evaluate for possible streptococcal infection in the past and that was elevated at 514 units.

How can we interpret an ASO in this situation? An ASO response after an infection usually is positive during the second or third week after the episode of infection and peaks around 4 to 5 weeks and then can actually be positive for a few months. Often this is combined with an Anti-DNase B. The sensitivity of say just a throat culture for acute rheumatic fever may be as low as 25%, the sensitivity of an ASO titer is about 80%. When you combine the ASO titer and the Anti-DNase B, you get a sensitivity of around 95%.

Guidelines for the diagnosis of rheumatic fever. Jones Criteria, 1992 update.

Special Writing Group of the Committee on Rheumatic Fever, Endocarditis, and

Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the

American Heart Association. JAMA. 1992 Oct 21;268(15):2069-73. PMID: 1404745



Another thing to remember is that Sydenham's chorea being a relatively late finding of rheumatic fever, your ASO titer and Anti-Dnase could actually be negative by the time that you develop chorea, so these tests are not always reliable.







Case continuation

An Anti-Nuclear Antibody(ANA) was weakly positive. They also did a lumbar puncture did not show white blood cells and had a normal protein and glucose. An encephalitis panel was negative as well.

Given concern for possible rheumatic fever and echocardiogram was done and showed a normal left ventricular size and systolic function, with mild mitral valve insufficiency and no pericardial effusion. An EKG showed normal sinus rhythm. We also did an MRI brain, which was unremarkable. MRI spectroscopy of the brain, showed some abnormality of the left basal ganglia, with evidence for reduced neuronal density and neuronal damage.

What were you looking for in the EKG? Specifically, we were looking for PR interval (for which there are age related norms) prolongation which can be criteria for rheumatic fever.

What are the Jones criteria? The Jones Criteria are used to make the diagnosis of acute rheumatic fever. To meet the criteria, you need either 2 major, 1 major and 2 minor to be present.

Editor’s note: In recurrent rheumatic fever, the presence of 3 minor criteria alone can fulfill diagnostic criteria.

There is a mnemonic for the major criteria that spells the name: J, O, N, E and S.



J stands for joints as in migratory polyarthritis (in high risk populations mono-arthritis or poly-arthralgia)





O you can make into the shape of a heart, which stands for carditis and this can commonly manifest as valvulitis of the mitral or the aortic valves.





N stands for subcutaneous nodules, usually on the extensor surfaces or surfaces where you'd expect there to be a lot of pressure, such as the elbows or the knees.





E stands for erythema marginatum





S for Sydenham's chorea.



The minor criteria include a prolonged PR interval, arthralgias, fever and elevated acute phase reactants.

What do these criteria does this patient meet? S in the Jones criteria with the Sydenham's chorea. Mild mitral valve insufficiency is not criteria for carditis. If this patient was living in a high risk population the polyarthralgia would be a second major criteria.

Can you meet criteria for with only one major and no minor criteria? No. Previously you could meet criteria with a streptococcal infection and Sydenham’s chorea alone but as of 2015 this is no longer the case. Additionally in the update in 2015 ultrasound findings were added to the diagnostic criteria for carditis as previously it was based on physical exam.

Depending on the incidence of rheumatic fever in a population, you have slightly different criteria. In high risk populations, instead of the migratory polyarthritis, you can have a monoarthritis or a polyarthralgia to meet a major criteria, so if she had been in a place like Australia that has a high incidence of rheumatic fever, her Sydenham's chorea and having 2 joints with arthralgia would count as 2 major criteria and would be enough for the diagnosis, but because she lives in the United States with a much lower incidence of rheumatic fever, she doesn't quite meet that cutoff.

Gewitz MH et al. Revision of the Jones Criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography: a scientific statement from the American Heart

Association. Circulation. 2015 May 19;131(20):1806-18. PMID: 25908771





Case Continuation

The case was a challenge as she did not meet criteria but after consultation with infectious disease and neurology it was decided to treat. This was done with three days of methylprednisolone and clonazepam, which seemed to improve her movements. She was also started treated with IM Penicillin G intramuscularly for the presumed recent strep infection and started on Penicillin V prophylaxis, which she will continue until she, is 21 years old.

Why does she need prophylaxis? Recurrence can come with high risk of valvular damage. As such patients are put on a long course of either daily oral or monthly IM penicillin to prevent recurrence. The length of therapy is dependent on age and if carditis is present on presentation.

Could this also have been from a skin infection? In terms of post Strep complications, with regards to skin infections and throat infections, you can get post Strep glomerulonephritis from them both, but you can only get rheumatic fever from throat infections.

What are some ways we can distinguish different hyperkinetic movement disorders on exam using descriptive words? It is all visual pattern recognition. In chorea, you know that they are random involuntary, non-rhythmic purposeless movements. One of the key features is that they are pretty constant. They occur at rest, with action throughout the time that the child is awake. That somewhat distinguishes it from other movement disorders like tics or stereotypies where they wax and wane throughout the day.

What other descriptive terms can we use to help describe chorea? It is often constant and going on throughout the day. Describing exactly where the movements are occurring will also help. Although they can occur in both the distal and proximal extremities, they most often occur in the distal extremities and they can also involve your face and most especially the oral and buccal areas.

What else can we look for on exam? There are a few key examination findings in chorea.

One of them is that children with chorea have motor impersistence this means that they have difficulty in maintaining constant motor or muscle contraction. If you tell the child to do one thing for a long time, like stick out their tongue, they have difficulty just maintaining that position and their tongue seems to go in and out of their mouths.If you ask a child to squeeze your fingers constantly, they have difficulty doing that and they grab and release, grab and release.

What differential should we consider with pediatric chorea?

Sydenham's chorea is the most common cause of secondary chorea. Another to consider would be ingestions as different medications and drugs are common causes of chorea.



Medications that can commonly cause chorea are anti-epileptics, Phenytoin or carbamazepine, psychiatric medications like neuroleptics or even SSRI's. Other potential medications are anticholinergics and antiemetics.



Electrolyte abnormalities, thyroid disease, are metabolic diseases.

What is the typical time course for acute rheumatic fever and Sydenham's chorea? Sydenham's chorea is a relatively benign disorder, because it does eventually resolve and children return back to their baseline. Most of the time children start having the chorea, weeks or months after they have that initial Streptococcus infection and usually it is a gradual onset, with the movements occurring in like one arm or one leg and then it sort of spreads to the body.

In most kids it is pretty mild and you do not necessarily have to intervene or give any treatments. Most experts feel like the movements should stop within 6 months by themselves.

What are the goals of treatment? There are 2 categories of treatment.

One is symptomatic treatment just to try to reduce the chorea and reduce the movements. In this case Clonazepam was used.



The second category is actually immunomodulatory treatments to try to decrease the underlying pathogenesis of the problem. We actually elected to do both in this situation. One of the reasons is because her chorea was so severe and because it had persisted for four months. In this case steroids were used. There actually are not a lot of studies in terms of immunomodulatory treatments for Sydenham's chorea maybe because many are not treated. One small double blind randomized controlled trial supports its use for the chorea.



Paz JA et al. Randomized double-blind study with prednisone in Sydenham's chorea. Pediatr Neurol. 2006 Apr;34(4):264-9. PMID: 16638499



*Editor’s note: Beyond the chorea there is not good evidence supporting immunomodulatory medications for carditis.



Cilliers A, et al. Anti-inflammatory treatment for carditis in acute rheumatic fever. Cochrane Database Syst Rev. 2015 May 28;(5) PMID: 26017576







Case Conclusion

After three days of methylprednisolone she had better control over her movements, her speech was much less dysarthric and she was speaking in full sentences. She still required outpatient rehabilitation as well as follow-up with infectious disease and neurology.