Restless Legs Syndrome as an Atypical Case of PANDAS?

Special Article - Clinical Case Reports

Austin J Clin Med. 2017; 4(1): 1030.

Restless Legs Syndrome as an Atypical Case of PANDAS?

Tromba V1*, Spalice A2, Lambiase C1, Favoriti A1 and Tancredi G1

¹Childhood Cardiology Division, Department of Pediatrics and Childhood Neuropsychiatry, Sapienza University of Rome, Rome, Italy

²Childhood Neurology Division, Department of Pediatrics and Childhood Neuropsychiatry, Sapienza University of Rome, Rome, Italy

*Corresponding author: Valeria Tromba, Childhood Cardiology Division, Department of Pediatrics and Childhood Neuropsychiatry, Umberto I Hospital, Sapienza University of Rome, Rome, Italy

Received: March 14, 2017; Accepted: April 20, 2017; Published: April 28, 2017

Abstract

Background: restless legs syndrome, also known as Willis-Ekbom disease or Wittmaack-Ekbom syndrome, is a neurological disorder characterized by an irresistible urge to move the body to stop uncomfortable or odd sensations. Moving the affected body part modulates the sensations, providing temporary relief. PANDAS is an acronym for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections, a hypothetical subset of conditions in which children are thought to exhibit an extremely abrupt onset of obsessive-compulsive disorder and/or tic disorders symptoms following Group A Beta-Hemolytic Streptococcal (GABHS) infections, with a relapsing-remitting (not waxing-waning) course. Our data highlight the close clinical similarity between Restless Legs Syndrome and PANDAS; in our opinion these two disorders may be distinguishable using laboratory test with the aim of identifying the etiologic agents of PANDAS. This case report presentation could be useful for the pediatrician that may chance upon a similar case.

Case Presentation: our objective is to describe clinical features of an atypical presentation of PANDAS in an Italian boy presenting restless leg syndrome. A 7 year-old boy that suffered for about one year from intense itching, forcing him to make continuous movements and stereotyped patterns of rotation of the limbs in order to find relief. The patient undergone in another hospital routine and specific laboratory data, including anti-streptolysin O titer. In addition he was investigated with neurologic and cardiologic assessment with EEG, SEP, MEP, polysomnography and medullary MRI, cardiologic examination, ECG and echocardiography: these were all normal. Blood tests showed only mild hypereosinophilia, elevated Antistreptolysin O antibody titers (ASO 329IU/ml) and low iron levels. He was discharged with the diagnosis of “Restless Legs Syndrome” (RLS) and began therapy with gabapentin 100mg twice daily and iron, without benefit. Suspecting movement disorders associated with GABHS infection, we started, after previous ineffective therapy, administration of benzyl penicillin every 20 days, until the next follow-up. After three months of follow-up the boy’s disorders had disappeared and the ASO titer was stable. The boy was in good clinical condition and no other movement disorders had appeared.

Conclusions: our data confirm that patients with suspected restless leg syndrome could present PANDAS.

Keywords: Group-A beta hemolytic streptococcal infection; PANDAS; Obsessive-compulsive symptoms; Autoimmunity; Restless legs syndrome

Background

Restless Legs Syndrome (RLS), also known as Willis-Ekbom Disease (WED) or Wittmaack-Ekbom syndrome is a neurological disorder characterized by an irresistible urge to move the body to stop uncomfortable or odd sensations. It most commonly affects the legs, but can affect the arms, torso, head, and even phantom limbs. Moving the affected body part modulates the sensations, providing temporary relief.

RLS sensations range from pain or an aching in the muscles, to "an itch you can't scratch", an unpleasant "tickle that won't stop", or even a "crawling" feeling. The sensations typically begin or intensify during quiet wakefulness, such as when relaxing, reading, studying, or trying to sleep. Additionally, most individuals with RLS suffer from periodic limb movement disorder (limbs jerking during sleep), which is an objective physiologic marker of the disorder and is associated with sleep disruption.

RLS can be caused by low iron levels. Treatment is often with levodopa or a dopamine agonist such as pramipexole. Some controversy surrounds the marketing of drug treatments for RLS. It is a "spectrum" disease, with some people experiencing only a minor annoyance and others suffering major sleep disruption and impaired quality of life.

PANDAS is an acronym for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections, a hypothetical subset of conditions in which children are thought to exhibit an extremely abrupt onset of Obsessive-Compulsive Disorder (OCD) and/or tic disorders symptoms following Group A Beta-Hemolytic Streptococcal (GABHS) infections, with a relapsing-remitting (not waxing-waning) course [1]. The proposed link between the infection and these disorders is that an initial autoimmune reaction to a GABHS infection produces antibodies that continue to interfere with basal ganglia function, causing symptom exacerbation [2,3]. The PANDAS hypothesis was based on observations in clinical case studies at the US National Institute of Health and in subsequent clinical trials where children appeared to have dramatic and sudden OCD exacerbations and tic disorders following infection [4]. There is supportive evidence for the link between streptococcal infection and onset in some cases of OCD and tics, but proof of causality has remained elusive [5-7]. The PANDAS hypothesis is controversial; whether it is a distinct entity differing from other cases of Tourette Syndrome (TS)/OCD is debated [3,8-11]. It has not been validated as a disease entity [4] and is not listed as a diagnosis in the International Statistical Classification of Diseases and Related Health Problems (ICD) or the Diagnostic and Statistical Manual of Mental Disorders (DSM).

Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) was proposed in 2012 to describe another subset of acute-onset OCD cases including "not only disorders potentially associated with a preceding infection, but also acute-onset neuropsychiatric disorders without an apparent environmental precipitant or immune dysfunction" [12].

We report on a boy in whom restless leg syndrome was an atypical presentation of PANDAS.

Case Presentation

A 7 year-old boy came to our attention through a pediatric allergologic visit because for about a year he had suffered from intense itching localized predominantly in the feet and ankles, mainly occurring while falling asleep but that was still present throughout the day, forcing him to make continuous movements and stereotyped patterns of rotation of the limbs in order to find relief. His family history was unremarkable. Before coming to our attention, he had undergone cardiologic assessments (cardiologic examination, electrocardiogram test and echocardiography) and neurologic evaluations electroencephalogram, somatosensory evoked potential, motor evoked potentials, polysomnography and medullary magnetic resonance imaging) in another hospital: these were all normal. Blood tests showed only mild hypereosinophilia, elevated Antistreptolysin O antibody (ASO) titers (ASO 329IU/ml) and low iron levels. He was discharged with the diagnosis of “Restless Legs Syndrome” (RLS) and began therapy with gabapentin 100mg twice daily and iron, without benefit.

During our first check-up, the boy described his problem not as itchy but as a “deep discomfort” that compels him to move not only his ankles but also his wrists, with continuous nocturnal awakenings. Physical examination and skin prick tests were negative. Suspecting movement disorders associated with GABHS infection, we decide to repeat the blood tests, particularly ASO (525IU/ml) and neuronal antibodies (normal levels), and to prescribe azithromycin, first daily for 5 days, then weekly for 8 weeks. There was a clear improvement in symptoms during the first month of therapy, and then a new exacerbation. Blood tests showed an increase in ASO titer (678IU/ml) and physical examination showed hyperemia of the pharynx that was not present at the first examination. At this point we decide to change the therapeutic approach and started administration of benzyl penicillin every 20 days, until the next follow-up. After three months of follow-up the boy’s disorders had disappeared and the ASO titer was stable. The boy was in good clinical condition and no other movement disorders had appeared.

Discussion

The term PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections) describes a subset of pediatric conditions characterized by Obsessive-Compulsive Disorder (OCD) and/or tic disorders, in which symptoms worsen following a streptococcal infection such as “strep throat” and scarlet fever (NIH). They appear to be neurobiological disorders that potentially complicate GABHS infections in genetically susceptible individuals [13]. There has been extensive debate about whether or not PANDAS actually exist. Sufferers usually have a dramatic, “overnight” onset of signs and symptoms that include motor or vocal tics, obsessions and/or compulsions and remission of neuropsychiatric symptoms during antibiotic therapy [14]. This definition was formalized in 1998 by Swedo [15] and collaborators in a set of five criteria, of which the core feature was the association between newly diagnosed infections and tics and obsessive-compulsive symptoms (Table 1). While in Sydenham’s chorea (SC), the prototypical post-streptococcal neuropsychiatric disorder, anti-dopamine receptor antibodies might be relevant, in PANDAS this association is not found and the pathophysiological mechanism remains undefined [16]. Unlike SC, in PANDAS the latency between GABHS infection and neuropsychiatric onset seems shorter and so the immune-mediated mechanism probably differs partly from the mechanism of SC. The remission of symptoms during antibiotic therapy (generally with penicillin and azithromycin) is more frequent in PANDAS than in other acute obsessive-compulsive symptoms and tics. Over the years the need for a reappraisal of the definition of PANDAS has become evident, given the difficulties in consistently and reliably applying their diagnostic criteria in routine clinical practice [16]. For example, the main issue is differentiating a true “inciting” GABHS infection, whether clinical or subclinical, from GABHS carrier states [14]. In addition, streptococcal infections are common in childhood and could be just a trigger for the exacerbation of tics and obsessive-compulsive disorder.

Citation: Tromba V, Spalice A, Lambiase C, Favoriti A and Tancredi G. Restless Legs Syndrome as an Atypical Case of PANDAS?. Austin J Clin Med. 2017; 4(1): 1030.