J Korean Dysphagia Soc 2021; 11(1): 82-86
Published online January 30, 2021 https://doi.org/10.34160/jkds.2021.11.1.012
© The Korean Dysphagia Society.
Department of Rehabilitation Medicine, Gangnam Severance Hospital, Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul, Korea
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Wilson’s disease (WD) is a genetic disease caused by an ATP7B gene mutation. Although dysphagia is known as a neurological manifestation of WD, clinical case reports with post-treatment long-term follow-up are scarce. A 17- year-old male was admitted to hospital complaining of general weakness and swallowing difficulty. He was diagnosed with WD by genetic confirmation. Assessment of the videofluoroscopic swallowing study (VFSS) determined an initial videofluoroscopic dysphagia scale (VDS) score of 48. After 11 months treatment with D-penicillamine and neuromuscular electrical stimulation therapy (NMES) with oromotor exercises, the VDS score improved to 23, especially in the following areas: mastication, apraxia, premature bolus loss, triggering of pharyngeal swallow, and laryngeal elevation. Dysphagia is an early neurological symptom of WD, and is reversible when properly treated with early diagnosis. Thus, since WD is treatable, patients presenting with dysphagia should be indicative of high probability of the disease, and evaluated at the earliest. NMES treatment in combination with D-penicillamine helps to improve the deglutition function in both oral and pharyngeal phases. To investigate the characteristics of dysphagia and the specific clinical efficacy of NMES in WD, further studies with larger number of patients are required.
Keywords: Wilson’s disease, Deglutition disorders, Electrical stimulation
Wilson’s disease (WD) is a genetic disease caused by an
A 17-year-old male with no specific medical or family history was admitted to the department of pediatrics in a tertiary hospital for chief complaints of general weakness, tremor in the toes of both feet, speech disorder, and swallowing difficulty that has been worsening over the course of a month. Kayser- Fleischer rings were seen in both eyes. The result of muscle strength testing using the Medical Research Council (MRC) scale was grade 2 in the upper ex-tremities and grade 3 in the lower extremities bi-laterally. The patient showed dysdiadochokinesia in both arms along with hand tremor. Motor aphasia with articulation disorder and dysphagia were also observed. Based on the clinical findings of an ap-preciably delayed oral phase in swallowing, a pa-renteral liquid diet was initiated via a nasogastric tube. Laboratory tests showed decreased serum con-centrations of copper (28.4 μg/dL; normal range: 75.0-145.0 μg/dL) and ceruloplasmin (<4 mg/dL; normal range: 16.2-35.6 mg/dL). The 24-hour urine col-lection test showed an increased urine copper ex-cretion (2993.5 μg/day; normal range: 15.0-60.0 μg/ day). Genetic testing, which was conducted under the clinical impression of WD, confirmed exon 8 duplication, and substitution mutations of the
Table 1 . One-year follow-up of videofluoroscopic swallowing study.
Parameters of VDS | Initial VFSS | Follow-up VFSS |
---|---|---|
Lip closure | 2 | 2 |
Bolus formation | 3 | 3 |
Mastication* | 4 | 0 |
Apraxia* | 3 | 0 |
Tongue-to-palate contact | 5 | 5 |
Premature bolus loss* | 4.5 | 3 |
Oral transit time* | 3 | 0 |
Triggering of pharyngeal swallow* | 4.5 | 0 |
Vallecular residue | 4 | 4 |
Laryngeal elevation* | 9 | 0 |
Pyriform sinus residue | 0 | 0 |
Coating on the pharyngeal wall | 0 | 0 |
Pharyngeal transit time | 0 | 0 |
Aspiration | 6 | 6 |
Total VDS score | 48 | 23 |
*Improved parameter in the follow-up VFSS.
VFSS: videofluoroscopic swallowing study, VDS: videofluoro-scopic dysphagia scale.
The swallowing process is thought to be the result of a complex interaction between the cerebral cortex and brainstem motor or sensory nuclei. Thus, lesions that affect these structures may affect swallowing mechanisms and cause neurogenic dysphagia. In the present study, brainstem lesions of WD, including those that involve the pons and the midbrain, caused increased signal intensities on MRI due to copper accumulation. A significant increase in tissue copper content in the central nervous system causes damage to cellular structures, and it is thought that the site of copper deposition and the neurological symptoms may be correlated. The pons and midbrain constitute the ascending reticular activating system, which relays the signal produced in a central pattern generator (CPG), so that it functions to help rhythmic swallowing. In addition, the sensory feedback is believed to be conveyed to the cortical area via a first relay in the pons. In particular, pontine neurons, which play a role in transmitting sensory signals, are thought to be involved in the transfer of information from the oropharyngeal receptors to the higher centers in the central nervous system3. The ponto-corticomedullary loops might control the activity of the CPG swal-lowing neurons. If there is a problem with loop signal transmission, the swallowing process may get stuck at the oropharyngeal phase or at the early esophageal phase 4 . Based on these results, the improvement of dysphagia symptoms in this present study correlates the resolution of the anatomical lesion in neuro-imaging, which may have resulted from the medication. It was not clear whether the improvement of dysphagia at the follow-up session after 1 year was due to the effect of D-penicillamine treatment or the rehabilitation program for dysphagia, including NMES because these treatments were administered con-currently. However, the improvement of dysphagia symptoms despite the progressed weakness in lower limbs suggests that the rehabilitation program for dysphagia, including NMES, was specifically effective in treating dysphagia. This focal symptom improvement is more likely due to the specific dysphagia rehabilitation rather than a medication effect, which is a systemic treatment. This case suggests that dysphagia in WD can be selectively reversible with early detection and treatment. There have been no studies which showed improvement after NMES borne out by analyzing each detailed step of the swallowing process. The efficacy of NMES observed in this case is thought to be mediated by two mechanisms. First, sensory stimulation may increase local sensory input to the central nervous system via the CPG, which is located in the lower brainstem. It may also have a long-term effect in reorganization of the cerebral cortex, resulting in the enhancement of brain plas-ticity and recovery in control of swallowing 5 -7 . Second, motor stimulation may provoke contraction of pha-ryngeal muscles such as the suprahyoid muscle, which may improve laryngeal elevation and avoid disuse atrophy of muscle 8 -10 . Sensory stimulation and muscle contraction aided by NMES helps reconstruct the control function of the brainstem reflex center over the swallowing reflex and enhances pharyngeal muscle coordination 2 . In this present case, the oromotor exercise seems to have been effective in promoting tongue movement and mastication, shortening the OTT and allowing the bolus transition from the oral cavity to the pharynx. NMES may have helped improve the triggering of pharyngeal swallow and laryngeal elevation. From now on, no study has con-firmed improvement of the symptoms of dysphagia in WD after a long treatment period. This case report is meaningful in that it evaluated the scale of dys-phagia in detail and checked the symptoms of the patient for a prolonged time of 1 year. A high index of suspicion for dysphagia in WD is necessary since it is reversible when properly treated under early diagnosis. An active rehabilitation program for dys-phagia, including oromotor exercise and NMES, should be considered as a strong option for the treatment of dysphagia in patients with WD. Further studies with more cases are necessary to investigate the charac-teristics of dysphagia and the clinical efficacy of NMES in WD.
None of the authors had any funding to support this case report.
The authors declare that they have no competing interests. None of the authors have any conflicts of interest to disclose.
J Korean Dysphagia Soc 2021; 11(1): 82-86
Published online January 30, 2021 https://doi.org/10.34160/jkds.2021.11.1.012
Copyright © The Korean Dysphagia Society.
Doyoung Kim, M.D., Yoon Ghil Park, M.D., Ph.D., Jung Hyun Park, M.D., Ph.D., Jinyoung Park, M.D.
Department of Rehabilitation Medicine, Gangnam Severance Hospital, Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul, Korea
Correspondence to:Jinyoung Park, Department of Rehabilitation Medicine, Gangnam Severance Hospital, Yonsei University, 20 Eonju-ro 63-gil, Gangnam-gu, Seoul 06229, Korea
Tel: +82-2-2019-3498, Fax: +82-2-2019-4881
E-mail: pjyblue511@gmail.com
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Wilson’s disease (WD) is a genetic disease caused by an ATP7B gene mutation. Although dysphagia is known as a neurological manifestation of WD, clinical case reports with post-treatment long-term follow-up are scarce. A 17- year-old male was admitted to hospital complaining of general weakness and swallowing difficulty. He was diagnosed with WD by genetic confirmation. Assessment of the videofluoroscopic swallowing study (VFSS) determined an initial videofluoroscopic dysphagia scale (VDS) score of 48. After 11 months treatment with D-penicillamine and neuromuscular electrical stimulation therapy (NMES) with oromotor exercises, the VDS score improved to 23, especially in the following areas: mastication, apraxia, premature bolus loss, triggering of pharyngeal swallow, and laryngeal elevation. Dysphagia is an early neurological symptom of WD, and is reversible when properly treated with early diagnosis. Thus, since WD is treatable, patients presenting with dysphagia should be indicative of high probability of the disease, and evaluated at the earliest. NMES treatment in combination with D-penicillamine helps to improve the deglutition function in both oral and pharyngeal phases. To investigate the characteristics of dysphagia and the specific clinical efficacy of NMES in WD, further studies with larger number of patients are required.
Keywords: Wilson’s disease, Deglutition disorders, Electrical stimulation
Wilson’s disease (WD) is a genetic disease caused by an
A 17-year-old male with no specific medical or family history was admitted to the department of pediatrics in a tertiary hospital for chief complaints of general weakness, tremor in the toes of both feet, speech disorder, and swallowing difficulty that has been worsening over the course of a month. Kayser- Fleischer rings were seen in both eyes. The result of muscle strength testing using the Medical Research Council (MRC) scale was grade 2 in the upper ex-tremities and grade 3 in the lower extremities bi-laterally. The patient showed dysdiadochokinesia in both arms along with hand tremor. Motor aphasia with articulation disorder and dysphagia were also observed. Based on the clinical findings of an ap-preciably delayed oral phase in swallowing, a pa-renteral liquid diet was initiated via a nasogastric tube. Laboratory tests showed decreased serum con-centrations of copper (28.4 μg/dL; normal range: 75.0-145.0 μg/dL) and ceruloplasmin (<4 mg/dL; normal range: 16.2-35.6 mg/dL). The 24-hour urine col-lection test showed an increased urine copper ex-cretion (2993.5 μg/day; normal range: 15.0-60.0 μg/ day). Genetic testing, which was conducted under the clinical impression of WD, confirmed exon 8 duplication, and substitution mutations of the
Table 1 . One-year follow-up of videofluoroscopic swallowing study.
Parameters of VDS | Initial VFSS | Follow-up VFSS |
---|---|---|
Lip closure | 2 | 2 |
Bolus formation | 3 | 3 |
Mastication* | 4 | 0 |
Apraxia* | 3 | 0 |
Tongue-to-palate contact | 5 | 5 |
Premature bolus loss* | 4.5 | 3 |
Oral transit time* | 3 | 0 |
Triggering of pharyngeal swallow* | 4.5 | 0 |
Vallecular residue | 4 | 4 |
Laryngeal elevation* | 9 | 0 |
Pyriform sinus residue | 0 | 0 |
Coating on the pharyngeal wall | 0 | 0 |
Pharyngeal transit time | 0 | 0 |
Aspiration | 6 | 6 |
Total VDS score | 48 | 23 |
*Improved parameter in the follow-up VFSS.
VFSS: videofluoroscopic swallowing study, VDS: videofluoro-scopic dysphagia scale.
The swallowing process is thought to be the result of a complex interaction between the cerebral cortex and brainstem motor or sensory nuclei. Thus, lesions that affect these structures may affect swallowing mechanisms and cause neurogenic dysphagia. In the present study, brainstem lesions of WD, including those that involve the pons and the midbrain, caused increased signal intensities on MRI due to copper accumulation. A significant increase in tissue copper content in the central nervous system causes damage to cellular structures, and it is thought that the site of copper deposition and the neurological symptoms may be correlated. The pons and midbrain constitute the ascending reticular activating system, which relays the signal produced in a central pattern generator (CPG), so that it functions to help rhythmic swallowing. In addition, the sensory feedback is believed to be conveyed to the cortical area via a first relay in the pons. In particular, pontine neurons, which play a role in transmitting sensory signals, are thought to be involved in the transfer of information from the oropharyngeal receptors to the higher centers in the central nervous system3. The ponto-corticomedullary loops might control the activity of the CPG swal-lowing neurons. If there is a problem with loop signal transmission, the swallowing process may get stuck at the oropharyngeal phase or at the early esophageal phase 4 . Based on these results, the improvement of dysphagia symptoms in this present study correlates the resolution of the anatomical lesion in neuro-imaging, which may have resulted from the medication. It was not clear whether the improvement of dysphagia at the follow-up session after 1 year was due to the effect of D-penicillamine treatment or the rehabilitation program for dysphagia, including NMES because these treatments were administered con-currently. However, the improvement of dysphagia symptoms despite the progressed weakness in lower limbs suggests that the rehabilitation program for dysphagia, including NMES, was specifically effective in treating dysphagia. This focal symptom improvement is more likely due to the specific dysphagia rehabilitation rather than a medication effect, which is a systemic treatment. This case suggests that dysphagia in WD can be selectively reversible with early detection and treatment. There have been no studies which showed improvement after NMES borne out by analyzing each detailed step of the swallowing process. The efficacy of NMES observed in this case is thought to be mediated by two mechanisms. First, sensory stimulation may increase local sensory input to the central nervous system via the CPG, which is located in the lower brainstem. It may also have a long-term effect in reorganization of the cerebral cortex, resulting in the enhancement of brain plas-ticity and recovery in control of swallowing 5 -7 . Second, motor stimulation may provoke contraction of pha-ryngeal muscles such as the suprahyoid muscle, which may improve laryngeal elevation and avoid disuse atrophy of muscle 8 -10 . Sensory stimulation and muscle contraction aided by NMES helps reconstruct the control function of the brainstem reflex center over the swallowing reflex and enhances pharyngeal muscle coordination 2 . In this present case, the oromotor exercise seems to have been effective in promoting tongue movement and mastication, shortening the OTT and allowing the bolus transition from the oral cavity to the pharynx. NMES may have helped improve the triggering of pharyngeal swallow and laryngeal elevation. From now on, no study has con-firmed improvement of the symptoms of dysphagia in WD after a long treatment period. This case report is meaningful in that it evaluated the scale of dys-phagia in detail and checked the symptoms of the patient for a prolonged time of 1 year. A high index of suspicion for dysphagia in WD is necessary since it is reversible when properly treated under early diagnosis. An active rehabilitation program for dys-phagia, including oromotor exercise and NMES, should be considered as a strong option for the treatment of dysphagia in patients with WD. Further studies with more cases are necessary to investigate the charac-teristics of dysphagia and the clinical efficacy of NMES in WD.
None of the authors had any funding to support this case report.
The authors declare that they have no competing interests. None of the authors have any conflicts of interest to disclose.
Table 1 . One-year follow-up of videofluoroscopic swallowing study.
Parameters of VDS | Initial VFSS | Follow-up VFSS |
---|---|---|
Lip closure | 2 | 2 |
Bolus formation | 3 | 3 |
Mastication* | 4 | 0 |
Apraxia* | 3 | 0 |
Tongue-to-palate contact | 5 | 5 |
Premature bolus loss* | 4.5 | 3 |
Oral transit time* | 3 | 0 |
Triggering of pharyngeal swallow* | 4.5 | 0 |
Vallecular residue | 4 | 4 |
Laryngeal elevation* | 9 | 0 |
Pyriform sinus residue | 0 | 0 |
Coating on the pharyngeal wall | 0 | 0 |
Pharyngeal transit time | 0 | 0 |
Aspiration | 6 | 6 |
Total VDS score | 48 | 23 |
*Improved parameter in the follow-up VFSS.
VFSS: videofluoroscopic swallowing study, VDS: videofluoro-scopic dysphagia scale.