What Is Sandifer Syndrome

Introduction

Sandifer Syndrome (SS) is a paediatric condition and a rare complication of gastroesophageal reflux disease (GERD). This is manifested by abnormal muscle spasms of the head, neck, trunk, and involuntary eye movements, also described as similar to epileptic seizures.^1,2 

The epidemiology of the disease has yet to be fully studied; therefore, prevalence and occurrence are currently unknown. However, it has been estimated that 1% of children with gastroesophageal reflux also manifest muscle spasms. The disease can affect both genders, and it occurs mainly during the first months after birth, with a peak registered at 4 months of age. The symptoms tend to gradually improve in nearly 90% of infants after one year of life.² Children and adolescents can both be affected by this syndrome.³

Symptoms and presentation

SS is associated with GERD in children, and this connection is supported by the resolution of symptoms when children are successfully treated for  GERD. The symptoms are abnormal and can cause spastic movements of the limbs and head. This includes nodding and twisting, neck contortion (torticollis) accompanied by vomit, gurgling sounds, and a decrease in muscle tone. The child will also tend to flex and arch their back during a typical attack. The posture assumed by the baby is possibly an attempt to find relief from discomfort generated by acid reflux in GERD.^2,4 

Not all children have the same neurological symptoms, and while the reason is unknown,  some children with GERD do not have muscle spasms.¹ In young children, GERD can be fatal if respiratory symptoms such as apnoea (when breathing is stopped and started during sleep) and choking occur. Anaemia, irritability, and lack of appetite can also be signs of gastroesophageal reflux disease.⁵

Diagnosis and evaluation

Often, the symptoms are not easily detected as the syndrome manifests in infants. This can lead to an incorrect or missed evaluationresulting in the misinterpretation of the condition. SS can be wrongly identified as epilepsy, trauma, congenital torticollis, and other pathologies with similar signs. 

An incorrect diagnosis means an incorrect approach and therapy. This can cause delays in finding a successful treatment which will then require greater expenses to the patient’s family.³ 

Laboratory exams are often required to diagnose SS. Electroencephalograms (tests to record brain activity) can help to understand whether the symptoms are related to epilepsy. Testing the child for cow’s milk protein allergy (CPMA) will identify the acid reflux as oesophagitis, secondary to the allergy. Metabolic diseases and congenital neurological conditions should also be analysed.² 

A case study reported a 9-month-old  child vomiting for 2 months. Before admission to the hospital, the baby had abnormal head and neck contortion, which manifested only after feeding and stopped once asleep. Laboratory exams, electroencephalograms (EEG) taken at different times of the day while the infant was awake and asleep, and other subspecialty tests all appeared as normal. However, an oesophageal biopsy showed the presence of acid reflux, which was confirmed after monitoring the pH levels in the oesophagus for 24 hours.¹  

Causes and risk factors

Sandifer syndrome is a sign associated with the presence of GER disease.  GERD  is sometimes associated with the presence of a hiatal hernia. There can be a primary reflux caused by a weak lower oesophageal sphincter (bands of muscle at the top and bottom of the oesophagus), as the pressure coming from the stomach can lead to the relaxation of the sphincter, letting the gastric content to travel up the oesophagus. 

The reflux can also be secondary and associated with either medical conditions that affect the upper gastrointestinal (GI) tract, oesophagitis caused by CPMA,  or conditions outside the GI l tract, such as intracranial hypertension (build-up of pressure around the brain).⁵ 

The backflow of the gastric content is usually a common phenomenon in infants and it does not represent a real concern even when it occurs a few times a day. However, it can be considered pathological when the retrograde reflux becomes severe and starts to affect the oesophageal mucosa (a barrier protecting the underlying muscle layer).² 

Despite the information we have on the correlation between GERD and the syndrome, currently, the exact pathophysiology of SS has not been fully identified. Neurological signs of the medical disorder can be linked to the vagal reflex to seek relief from discomfort the child experiences.³ 

A large number of patients have shown the presence of either metabolic conditions or brain damage, and a higher occurrence has also been identified among children with Brachman-de Lange syndrome (a disorder leading to severe developmental deformities). As demonstrated by these findings, there could be a correlation between GERD and brain damage.⁴ 

Moreover, the diaphragm and neck muscles are controlled by the same nerves. The stimulation of the diaphragm can cause involuntary movements of the neck, showing a neurologic link between the GI tract and muscle spasms. However, this is not fully understood since the abnormal posture in SS stops when the child is asleep, even though acid reflux is commonly more frequent at night. herefore, this does not explain the real connection between GERD and SS inevitably leads to a more challenging identification of a possible treatment.⁵ 

Treatment and management

The main approach to resolve SS  is to intervene on the GERD  since studies have demonstrated that once GERD or hiatal hernia are successfully treated, the convulsions tend to disappear permanently.⁵ A prompt evaluation and therapy for GER disease also results in the resolution of SS in patients with no other conditions. Consequently, this improves the quality of life in those who have other comorbidities, such as brain damage.⁴

The Sandifer syndrome can be treated with three different approaches: non-pharmacological, pharmacological, and surgical.³ 

The non-pharmacologic intervention is usually advised for children generally healthy and are gaining weight according to their development. This approach requires thickening the formula or breast milk the child is fed with by using one teaspoon to a maximum of one tablespoon of plain rice cereal per ounce. ^2,3,5 After being fed, the baby should be upright, preventing the acid reflux from ascending into the oesophagus. Parents are also encouraged to feed the baby less frequently if overfed and avoid their children from cigarette smoke exposure.^2,5The non-pharmacologic intervention usually shows improvements in 80% of the infants after only two weeks. However, if changes in lifestyle do not lead to the expected outcome, medications can be used to treat the syndrome.⁵ 

The pharmacologic method involves the use of anti-reflux medicines. This includes proton pump inhibitors (PPIs), such as rabeprazole and esomeprazole, and H2 receptor antagonists (ranitidine and famotidine) as first options.^2,3 Domperidone or metoclopramide,  both prokinetic agents, represent a second-line treatment, although it is not recommended as the side effects can overcome the benefits of the treatment.^3,5 The PPIs not only maintain a correct pH for longer, but they also help with emptying the gastric content and reducing the reflux volume. Despite the benefits brought by the PPIs, a continued intervention with these can unbalance the bacterial environment in the gastrointestinal tract and therefore, affect the absorption of nutrients such as calcium and vitamin B12. Among these, omeprazole and lansoprazole have been approved for treatment in children older than 1 year of age. Esomeprazole has also been approved for use in infants between 1 month and 1 year of age.⁵

When medications are still not an effective treatment for SS, it is then possible to intervene with surgical correction. This pathway is strictly considered only in the presence of hiatal hernia when the previous methods are not successful.^2,3

Prognosis 

The prognosis for children with SS is overall positive. If a correct evaluation and diagnosis are made and signs of GER disease are promptly recognised, a correct therapy is then followed to resolve the related neurological and gastroesophageal symptoms, and most of the patients heal over time. Usually, the syndrome has no long-term complications once GERD is resolved. 

When the causes of the convulsions are not clear, the child is then referred to a paediatric neurologist to identify the pathophysiology.²

Summary

SS is a rare paediatric disease as well as one of the complications of gastroesophageal reflux disease (GERD). Convulsions, abnormal muscle spasms and movements of the neck, head, limbs, and trunk are often mistaken for epileptic seizures, when instead they are an attempt for the child to find relief from discomfort given by the acid reflux caused by GERD.

Prompt Identification of the signs linked to GERD  helps with recognising the symptoms manifested by children when they are affected by SS. This helps with finding the correct treatment based on the nature and severity of the syndrome. This can be pharmacologic, non-pharmacologic or surgical treatments. The resolution of GERD  is often strictly correlated to the positive outcome of the SS, and a delay in recognising the association could represent a slower healing process for the child as well as a financial burden for the patient’s family. 

From a future perspective, finding a way to quickly identify the pathophysiologic link between the gastroesophageal condition and the consequent syndrome will provide benefit to the patient’s quality of life.