Continuing Education Activity

Sandifer syndrome is rare paroxysmal dystonia of the back and neck that is often associated with gastroesophageal reflux in children. This activity reviews the evaluation and management of patients with this condition.

Objectives:

• Identify the typical and atypical presentation of a patient with Sandifer syndrome.
• Review the appropriate evaluation of Sandifer syndrome.
• Summarize the appropriate management of Sandifer syndrome.
• Describe some strategies for improving care coordination for these patients, to avoid inappropriate referrals, diagnostic tests, and treatments in patients with Sandifer syndrome.

Introduction

Sandifer syndrome (SS) is a type of movement disorder that constitutes paroxysmal spasms of head, neck, and back arching but spares the limbs. SS is often associated with gastroesophageal reflux (GERD) in children. In addition, due to the abnormal posturing, parents may describe the dystonic episodes of SS as possible seizures. Therefore this causes great concern among parents and poses a diagnostic dilemma to the physicians.

An increased number of these patients may obtain a referral to a pediatric neurologist for management of this condition leading to expensive diagnostic tests like MRI or EEG and antiepileptic medication management. Kotagal, et al. studied patients in an epileptic unit with an established diagnosis of an epileptic disorder and found that around 16% of them presented with GERD as the underlying cause, also, the average time of duration of symptoms and the length of treatment before a correct diagnosis was about one year.[1] The primary care providers are urged to keep Sandifer syndrome in the differential diagnosis of nonepileptic paroxysmal dystonic events and abnormal posturing. A correct and timely diagnosis of SS leads to the complete resolution of the symptoms.[2]

Etiology

In most healthy infants, the retrograde movement of gastric content into the esophagus is a normal physiological phenomenon occurring many times a day. The main factors contributing to this phenomenon include a liquid-based diet, recumbent position, and immaturity of the gastro-esophageal junction.[3] However, it becomes pathologic when the GERD is severe and the esophageal mucosa gets eroded. The patients present with symptoms of discomfort, mainly fussiness in infants and extraesophageal manifestations of abnormal posturing.

To date, the exact etiology of the muscle dystonia in Sandifer syndrome remains unidentified. It may be associated with the diaphragm and the head and neck area sharing common innervation. Frankel was able to prove the direct relationship between dystonic movements and low pH, and he measured the pH in a patient with SS. He recorded 83 episodes of posturing, and none of these episodes occurred during a period of pH >5 for ≥30 seconds.[4]

Epidemiology

Sandifer syndrome incidence and prevalence are unknown, and the epidemiology has not been well studied. However, estimates are that 7% of infants can present with typical GERD symptoms like spitting up, and 1% of them can present as associated muscular dystonia.[2] Knowing the natural history of GERD is very important to understand the outcome of Sandifer Syndrome since once GERD resolves, the dystonic movements dramatically improve. GERD is more prevalent in the first months of life with a peak age of 4 months; symptoms improve in almost 80% of infants during the first month of life and in 90% by 1-year-old.[5] There is not an established gender preference described; however, in the literature review for this article, there were more published cases in boys than in girls.

Pathophysiology

It is unclear why GERD leads to neck and back dystonia, some authors have postulated the movements and abnormal postures are a learned behavior to relieve abdominal discomfort and improve esophageal motility. In 1964 Dr. Kinsbourne published a series of five cases of patients with muscle dystonia and hiatal hernia; in three of them, head positioning was able to relieve abdominal discomfort. However, central neurological pathways could be involved; further investigation is necessary in this area.[6]

History and Physical

History and careful observation of an episode are valuable in evaluating a patient with dystonic movements as part of an uncommon presentation of GERD. The initial symptoms are vital in making a correct diagnosis. One of the presentations of Sandifer syndrome is the exacerbation of the abnormal posturing immediately after eating and improvement in between feeds. Some parents describe intermittent episodes of torticollis that change from one side to another with feeds. It is important to note that the sternocleidomastoid muscle is normal, unlike true torticollis, where the muscle has spasms and has shortened. Hence these episodes of torticollis with GERD will not respond to physical therapy. This clinical picture can be easily confusing as seizures; however, during the paroxysmal events, patients are conscious, and these positions and movements do not occur during sleep.[6][7]

The neurological exam is usually normal in these patients, making Sandifer syndrome a more likely diagnosis than epilepsy.

Patients present with excessive crying, fussiness, irritability, emesis, gagging, or choking during and after feeding with these episodes. If the symptoms continue, patients can develop anemia, weight loss, failure to thrive, and dental erosions. Providers need to be aware of complications of GERD, not only SS, but BRUE, apnea, recurrent pneumonia, chronic stridor, or wheezing.[8]

Evaluation

Laboratory evaluation is usually not required to diagnose this syndrome. If the clinical examination and parents reported symptoms are not concerning epilepsy, clinicians should try a nonpharmacologic treatment and then pharmacologic treatment as needed. If symptoms improve, there is no need for further diagnostic tests. If symptoms are refractory to the non-pharmacologic or pharmacologic treatments, then a referral to a gastroenterologist is pertinent for further evaluation, such as continuous esophageal pH monitoring and other advanced studies. When the clinical picture is not clear for Sandifer syndrome, the clinician should tailor the diagnostic tools according to the physical exam and parental symptom report. In some cases, EEG will provide valuable clinical information to rule in or out seizure disorders. Metabolic conditions, infectious etiologies, and other congenital neuromuscular problems should be in the differential.

The evaluation of iron deficiency anemia with CBC and iron studies and referral to surgery in the assessment of hiatal hernia should be a part of the management of Sandifer syndrome.

Treatment / Management

There are two approaches to the treatment of Sandifer syndrome associated with GER, non-pharmacologic and pharmacologic. Sandifer syndrome resolves with GERD treatment. If the infant is gaining weight appropriately and developing well, nonpharmacologic interventions should be tried before the pharmacologic treatment.

The formula or expressed breast milk can be thickened with one teaspoon of rice cereal per ounce of formula to a maximum of 1 tablespoon per ounce. Parents should be counseled to avoid overfeeding and can decrease the volume of each feed. The importance of pacing in between feeds and keeping the infant in an upright position after every feed is a point of emphasis as an essential method to prevent GER. Some patients may require a change to a more elemental formula since one-third of the patients with GERD symptoms may have allergic esophagitis secondary to cow’s milk protein allergy (CPMA) as an underlying condition.

If all these lifestyle changes fail to improve GERD and, in turn, SS, pharmacologic treatment with anti-reflux medications should start. Proton pump inhibitors and H2 blockers are first-line therapy. In most cases, the paroxysmal events will resolve or dramatically decrease in frequency over time; furthermore, the anemic status will improve soon after the control of GERD.[9][10] Surgical interventions for possible hiatal hernia must be a consideration if pharmacologic and non-pharmacologic measures fail.[6]

Differential Diagnosis

The differential diagnoses for Sandifer syndrome include all the paroxysmal events in infancy, including epileptic syndromes, congenital muscular torticollis, metabolic and congenital conditions, CNS pathologies, trauma, and inflammatory or infectious conditions of the neck and head.

Prognosis

The prognosis for these infants is excellent. Once GERD is established as the etiology for Sandifer syndrome, timely and appropriate treatment of GERD decreases the dystonic episodes and, over time, resolves in the majority of patients. Also, iron deficiency anemia usually resolves after three months of established GERD treatment. In the literature review conducted for this article, there were no reported long-term complications or morbidity associated with Sandifer syndrome.

Complications

There are no complications of Sandifer syndrome; however, it may be diagnosed as a neurological condition and treated like it if it is not identified accurately on time. Antiepileptic medication management, though well tolerated, could be unnecessary, cause adverse effects and parental distress. Patients may receive incorrect treatment for prolonged periods until the diagnosis of GERD.

Enhancing Healthcare Team Outcomes

Sandifer syndrome is a condition that requires a high index of suspicion. Primary care providers (PCP) should be able to identify and treat SS. When the clinical picture is not clear, the PCP should refer the patient to a pediatric neurologist for further evaluation to determine the underlying etiology.

When GERD is established as a cause of Sandifer syndrome, and if the symptoms are refractory to treatment, a GI referral is pertinent for further treatment of GERD.