Introduction
Sandifer syndrome is defined as a rare complication of gastro-oesophageal reflux disease (GERD) when a patient presents with extraoesophageal symptoms, typically neurological [18]. These symptoms may be as severe as mimicking epileptic seizures or convulsions [23]. Although its pathophysiology is not completely understood, one possible explanation is that neurological manifestations are the consequence of vagal reflex with the reflex center in nucleus tractus solitarii [3]. The main difficulty with accurately diagnosing this clinical presentation is that often the overt gastro-intestinal symptoms, such as abdominal pain, vomiting or indigestion, are either absent, or the patient is too young to be able to communicate them. Thus, there is nothing to point the clinician to the direction of GI investigations, and as a result, the vast majority of patients with Sandifer syndrome are originally misdiagnosed with a neurological or a musculoskeletal disorder. This may lead to a range of unnecessary investigations, such as EEG, MRI and electromyographic studies, all of which come back normal. Moreover, this may result in the administration of unnecessary medications, such as anti-epileptic agents, which may have significant negative side effects. The aim of this study is to review the existing literature and describe a typical presentation and most appropriate investigations and management for the Sandifer syndrome, so that it can be considered early on in the differential diagnosis for children with intractable neurological symptoms.
Methodology
The literature search strategy included conducting a systematic review via Cochrane Library, PubMed and NHS Evidence databases. The search terms and the outcomes are listed below:
- Cochrane library: ‘Sandifer* syndrome’
- 1 controlled trial, not relevant
- PubMed search: ‘Sandifer* syndrome’
- 86 results in the English language, 27 were relevant
- The following publications were excluded:
- Case studies covering only adults
- Correspondence that did not include specific patient cases
- NHS Evidence: ‘Sandifer* syndrome’
- 8 results, 1 was relevant (NICE guideline)
Anzeige
Overall, 27 case reports and observational studies were available for analysis, covering 44 clinical cases in total.
Results
The detailed findings of the systematic review are provided in Table 1.
Table 1
Data collected from the literature review
Ref. no. | Reference | Study group size | Key results | Comments: prior misdiagnosis (e.g. neurological)? | |||
|---|---|---|---|---|---|---|---|
Extraoesophageal symptoms | Diagnostic investigation | Definitive treatment | Outcome: complete resolution of symptoms? | ||||
[1] | Bamji et al. (2015) | 2 | Abnormal body posturing, irritability | None, empirical treatment | Dietary | Yes | |
[20] | Nalbantoglu et al. (2013) | 1 | Abnormal posturing and movement of head and neck; ocular deviation | Oesophageal pH monitoring, oesophageal biopsy | Dietary | Yes | |
[30] | Tokuhara et al. (2008) | 1 | Growth retardation, abnormal neck movement, anaemia, hypoproteinaemia | Upper GI endoscopy with biopsy, 24-h pH monitoring | Surgical | Yes | |
[15] | Kostakis et al. (2008) | 1 | Abnormal head posturing | n/a1 | n/a1 | n/a1 | |
[16] | Lehwald et al. (2007) | 1 | Abnormal posturing and movement of head and neck | Upper GI endoscopy | Surgical | Near complete | Yes |
[9] | Firat et al. (2007) | 1 | Abnormal movements of head and neck, motor and speech delay | Oesophageal pH monitoring, upper GI fluoroscopy | Surgical | Yes | Yes |
[13] | Kabakuş, Kurt (2006) | 4 | Abnormal posturing and movements of head and neck, ocular deviation, irritability, growth retardation, anaemia | Gastro- oesophageal scintigraphies | Dietary and lifestyle, pharmacological | Near complete | Yes |
[5] | Corrado et al. (2006) | 1 | Abnormal posturing and movement of head, neck and trunk | 24-h gastro-oesophageal pH monitoring | Pharmacological | Yes | |
[10] | Frankel et al. (2006) | 1 | Abnormal head posturing, irritability | Oesophageal pHmetry, surface electromyography, split-screen videography | Surgical | Yes | Yes |
[7] | Demir et al. (2001) | 1 | Abnormal positioning and movements of neck, hand tremor, vomiting, stridor | Barium oesophagogram | Pharmacological | n/a1 | |
[6] | de Ybarrondo, Mazur (2000) | 1 | Cerebral palsy, severe developmental delay, asthma | n/a1 | n/a1 | n/a1 | |
[4] | Corrado et al. (2000) | 1 | Abnormal movements of head, neck, trunk | 24-h pH oesophageal monitoring | Dietary | Yes | |
[29] | Tekou et al. (1997) | 1 | Abnormal posturing of head and neck | n/a1 | Surgical | Yes | |
[2] | Cardi et al. (1996) | 1 | n/a1 | Real-time ultrasonography | n/a1 | n/a1 | |
[8] | Deskin (1995) | 1 | Abnormal neck posturing, irritability, cough, hoarseness | Barium swallow | Surgical | Yes | |
[11] | Gorrotxategi et al. (1995) | 8 | Abnormal neck posturing | Barium swallow, 24-h pH-metering, manometry, endoscopy, biopsy | Surgical (3 patients), pharmacological (5 patients) | Significant improvement | |
[26] | Senocak et al. (1993) | 1 | Abnormal neck posturing | n/a1 | Surgical | Yes | |
[28] | Sommer (1993) | 13 | Developmental delay, abnormal behaviour, hoarse growling cry (all patients had Brachmann-de Lange syndrome) | 3 patients–barium swallow, 10 patients–pH probe monitoring of upper GI system, esophagoscopy, endoscopy | Pharmacological and dietary (5 patients), surgical (8 patients) | Significant improvement | |
[25] | Puntis et al. (1989) | 1 | Abnormal posturing and movements of head, neck, trunk, anaemia | Barium swallow, oesophageal pH monitoring, upper GI endoscopy and biopsy | Surgical | Yes | |
[17] | Mandel et al. (1989) | 3 | Abnormal posturing and movements of head and trunk, weight loss | 12-h lower oesophageal pH monitoring | Pharmacological | Yes | Yes |
[21] | Nanayakkara, Paton (1985) | 3 | Abnormal posturing and movements of head, neck and trunk | Barium study | Pharmacological, dietary | Yes | |
[12] | Hadari et al. (1984) | 1 | Abnormal posturing and movements of body and limbs, seizure-like episodes, hypotonia, developmental delay | Barium study | Pharmacological | Yes | Yes |
[21] | Nanayakkara, Paton (1985) | 3 | Abnormal movements of neck and trunk, irritability | n/a1 | Pharmacological | Yes | Yes |
[12] | Hadari et al. (1984) | 1 | Abnormal posturing and movements of head and neck | n/a1 | Surgical | Yes | |
[14] | Keren et al. (1983) | 1 | Abnormal posturing and movement of head and trunk | Barium study | n/a1 | n/a1 | |
[27] | Smallpiece, Deverall (1982) | 1 | Irritability, abnormal posturing and movements of head, neck, trunk, growth delay | Barium swallow | Surgical | Yes | |
[32] | Werlin et al. (1980) | 5 | Abnormal body posturing | n/a1 | n/a1 | n/a1 | |
[19] | Murphy, Gellis (1977) | 2 | Abnormal neck posturing | XR studies | Pharmacological | Yes | |
[24] | O’Donnell, Howard (1971) | 1 | Abnormal head and neck posturing, strabismus, anaemia | n/a1 | n/a1 | n/a1 | Yes |
The literature demonstrates that the presenting symptoms of Sandifer syndrome may include any combination of abnormal movements and/or positioning of head, neck, trunk and upper limbs, seizure-like episodes, ocular symptoms, irritability, developmental and growth delay and iron-deficiency anaemia. It is evident from the literature that many of the patients were originally misdiagnosed with various neuropsychiatric diagnoses that led to unnecessary testing and ineffective medications that may have caused significant side effects. Earlier diagnosis of Sandifer’s would have allowed to avoid them.
As Sandifer syndrome is caused by gastro-oesophageal reflux, its investigations and management should be consistent with those of GERD. In terms of diagnostic procedures, 24-h oesophageal pH monitoring was positive in all the cases of Sandifer’s where it was performed, while upper GI endoscopy ± biopsy and barium swallow were diagnostic only in a subset of cases.
Anzeige
A range of treatment options were applied in the reviewed literature, including dietary changes (cow’s milk exclusion, amino-acid-based formula), pharmacological management (alginates, proton pump inhibitors (PPIs)), enteral tube feeding, and surgical approach, when conservative management was ineffective (Nissen fundoplication is usually curative). The pharmacological treatment was often sufficient on its own to achieve the resolution of symptoms; however, further escalation of management was required in the cases of advanced disease. These treatment options are consistent with the 2015 NICE guideline on management of GERD in children and young people [22].
Successful treatment of the underlying gastro-oesophageal pathology led to a complete or near-complete resolution of the neurological symptoms in all of the reviewed cases.
Discussion
1.
Sandifer syndrome may be difficult to recognise due to its non-specific presentation; however, it is an important differential diagnosis to consider in children with neurological symptoms that remain unexplained by neurological investigations.
2.
When Sandifer syndrome is suspected, 24-h oesophageal pH monitoring is usually diagnostic; however, an empirical trial of pharmacological management (e.g., prescribing a PPI) is also appropriate without prior invasive investigation [31].
3.
Once diagnosed, it can be successfully managed by treating the underlying GERD/hiatus hernia which typically leads to a complete resolution of all associated symptoms.
4.
In the majority of patients, pharmacological management is sufficient for the resolution of symptoms. Other treatment options include dietary modifications, enteral tube feeding, and surgical management.
5.
The choice of a management plan in each case depends on the severity and duration of the underlying condition, as well as individual responsiveness to treatment.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.