Neurol Sci (2015) 36:173–174 DOI 10.1007/s10072-014-1872-8
LETTER TO THE EDITOR
Restless legs syndrome heralding an acute exacerbation of multiple sclerosis Takamichi Kanbayashi • Hisao Kamiya Keiichi Hokkoku • Yuki Hatanaka • Masahiro Sonoo
•
Received: 5 April 2014 / Accepted: 26 June 2014 / Published online: 5 July 2014 Ó Springer-Verlag Italia 2014
Dear Editor, Restless legs syndrome (RLS) is a neurological movement disorder characterized by a distressing urge to move the legs, usually accompanied by unpleasant sensations, paresthesia, and motor restlessness. These symptoms increase or appear during rest periods, mostly at night, with partial or total relief by movement. Several medical and neurological conditions have been reported to be related to RLS, such as iron deficiency, renal failure, pregnancy, diabetes, rheumatoid arthritis, neuropathies, myelopathies, and Parkinson’s disease. Increased incidence of RLS in patients with multiple sclerosis (MS) has also been reported [1], although there have been no reports of RLS development as an initial symptom of an acute attack of MS. Here, we describe a patient who presented with RLS as a prodromal symptom preceding an acute exacerbation of MS. A 40-year-old woman suffered from right optic neuritis, which was successfully treated with an oral corticosteroid. Brain, cervical spine and thoracic spine MRI at that time revealed no apparent lesions. Three months later, she presented at our clinic complaining of discomfort in both legs T. Kanbayashi H. Kamiya K. Hokkoku Y. Hatanaka M. Sonoo (&) Department of Neurology, Teikyo University School of Medicine, Kaga 2-11-1, Itabashi-ku, Tokyo 1738605, Japan e-mail: [email protected] T. Kanbayashi e-mail: [email protected] H. Kamiya e-mail: [email protected] K. Hokkoku e-mail: [email protected] Y. Hatanaka e-mail: [email protected]
associated with an urge to move the legs, which had persisted for 1 week and was mainly felt while lying down in the night. Neurological examinations showed no abnormalities. Her symptoms were consistent with the diagnostic criteria of RLS [2]. Following the diagnosis of idiopathic RLS, a dopamine agonist was administered, with no effect. One week later, difficulty in walking developed and she was admitted to our hospital. Neurological examinations revealed weakness of the left lower limb, increased left patellar and Achilles tendon reflexes, and the positive left Babinski sign. She noticed paresthesia in the left distal forearm and right lower limb, and pain and temperature sensations were lost on the right side below the T11 level. Urination became difficult, although the symptoms of RLS remained the same. Routine laboratory tests showed no abnormalities, including serum iron and ferritin. Autoantibodies such as anti-nuclear antibody and anti-SSA/SSB antibodies were negative. Cerebrospinal fluid cell count, protein, and IgG index were normal, and oligoclonal band was negative, whereas myelin basic protein was elevated at 416 pg/ml (normal \109). Aquaporin-4 (AQP4) antibody, which was measured by a cell-based assay using HEK-293 cells stably transfected with the M23 isoform of AQP4, was negative. Cervical and thoracic spine MRI at the time of admission revealed T2 high-intensity lesions in the dorsal medulla, C1–2, left T1–2, and left T10 levels of the spinal cord (Fig. 1), of which those at C1–2 and T1–2 levels were enhanced by Gadolinium. Gadolinium enhancement was not performed in the thoracic spine MRI. Brain MRI showed a very small T2 high-intensity lesion compatible with a demyelinating plaque in the right periventricular while matter. Visual-evoked potentials (VEPs) at the time of admission revealed a prolonged latency of the right P100
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Fig. 1 Cervical and thoracic spine MRI revealed T2 high-intensity lesions in the dorsal medulla, C1–2, T1–2 (left) and T10 (right, arrow-head) levels
component (peak latency of P100: left 89 ms, right 126 ms). Neuromyelitis optica (NMO) was considered as a differential diagnosis, although the patient did not satisfy the diagnostic criteria for NMO [3] because the spinal cord lesion did not extend over three vertebral segments and the AQP4 antibody was negative. In contrast, she satisfied the McDonald’s criteria for MS (2 attacks, each being supported objectively by MRI lesions in the spinal cord and by the VEP abnormality, respectively). We diagnosed her as MS because other autoantibodies were negative and there was no better explanation. Her symptoms were confined to those caused by the spinal cord and optic nerve lesions, and therefore it would be appropriate to classify her as the opticospinal form of MS (OSMS). Following this diagnosis, methylprednisolone pulse therapy was started (1,000 mg/day, 3 days), which caused rapid disappearance of RLS symptoms and gradual improvement of other signs. Methylprednisolone pulse therapies were completed twice during hospitalization, followed by introduction of IFNb1a for relapse prevention.
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Neurol Sci (2015) 36:173–174
The relationship between MS and RLS has been discussed by many authors [1, 4]. However, there have been no reports of RLS occurring as a heralding symptom of an MS attack except for one case report where an isolated RLS episode was considered to be an MS exacerbation [5]. In the present case, RLS symptoms did not improve after treatment with a dopamine agonist, but rapidly disappeared following methylprednisolone pulse therapy, which supports our contention that her RLS was caused by the MS lesions, possibly in the cervical or thoracic cord. RLS was the initial and sole manifestation of an acute exacerbation of MS in this case. MS, especially the spinal form of MS [4], should be considered as a differential diagnosis in patients who acutely present with RLS. Acknowledgments We would like to thank Dr.Toshiyuki Takahashi (Department of Neurology, Tohoku University School of Medicine) for the measurement of the AQP4 antibody. Conflict of interest
No conflict of interest.
References 1. Deliu M, Cossu G, Morali A et al (2009) Restless legs syndrome in multiple sclerosis: a case-control study. Mov Disord 24:697–701 2. Allen RP, Picchietti D, Hening WA et al (2003) Restless legs syndrome diagnosis and epidemiology workshop at the national institutes of health; International restless legs syndrome study group. restless legs syndrome: diagnostic criteria, special considerations and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 4:101–119 3. Wingerchuk DM, Lennon VA, Pittock SJ et al (2006) Revised diagnostic criteria for neuromyelitis optica. Neurology 66:1485– 1489 4. Manconi M, Rocca MA, Ferini-Strambi L et al (2008) Restless legs syndrome is a common finding in multiple sclerosis and correlates with cervical cord damage. Mult Scler 14:86–93 5. Bernheimer JH (2011) Restless legs syndrome presenting as an acute exacerbation of multiple sclerosis. Mult Scler Int. doi:10. 1155/2011/872948
LETTER TO THE EDITOR
Restless legs syndrome heralding an acute exacerbation of multiple sclerosis Takamichi Kanbayashi • Hisao Kamiya Keiichi Hokkoku • Yuki Hatanaka • Masahiro Sonoo
•
Received: 5 April 2014 / Accepted: 26 June 2014 / Published online: 5 July 2014 Ó Springer-Verlag Italia 2014
Dear Editor, Restless legs syndrome (RLS) is a neurological movement disorder characterized by a distressing urge to move the legs, usually accompanied by unpleasant sensations, paresthesia, and motor restlessness. These symptoms increase or appear during rest periods, mostly at night, with partial or total relief by movement. Several medical and neurological conditions have been reported to be related to RLS, such as iron deficiency, renal failure, pregnancy, diabetes, rheumatoid arthritis, neuropathies, myelopathies, and Parkinson’s disease. Increased incidence of RLS in patients with multiple sclerosis (MS) has also been reported [1], although there have been no reports of RLS development as an initial symptom of an acute attack of MS. Here, we describe a patient who presented with RLS as a prodromal symptom preceding an acute exacerbation of MS. A 40-year-old woman suffered from right optic neuritis, which was successfully treated with an oral corticosteroid. Brain, cervical spine and thoracic spine MRI at that time revealed no apparent lesions. Three months later, she presented at our clinic complaining of discomfort in both legs T. Kanbayashi H. Kamiya K. Hokkoku Y. Hatanaka M. Sonoo (&) Department of Neurology, Teikyo University School of Medicine, Kaga 2-11-1, Itabashi-ku, Tokyo 1738605, Japan e-mail: [email protected] T. Kanbayashi e-mail: [email protected] H. Kamiya e-mail: [email protected] K. Hokkoku e-mail: [email protected] Y. Hatanaka e-mail: [email protected]
associated with an urge to move the legs, which had persisted for 1 week and was mainly felt while lying down in the night. Neurological examinations showed no abnormalities. Her symptoms were consistent with the diagnostic criteria of RLS [2]. Following the diagnosis of idiopathic RLS, a dopamine agonist was administered, with no effect. One week later, difficulty in walking developed and she was admitted to our hospital. Neurological examinations revealed weakness of the left lower limb, increased left patellar and Achilles tendon reflexes, and the positive left Babinski sign. She noticed paresthesia in the left distal forearm and right lower limb, and pain and temperature sensations were lost on the right side below the T11 level. Urination became difficult, although the symptoms of RLS remained the same. Routine laboratory tests showed no abnormalities, including serum iron and ferritin. Autoantibodies such as anti-nuclear antibody and anti-SSA/SSB antibodies were negative. Cerebrospinal fluid cell count, protein, and IgG index were normal, and oligoclonal band was negative, whereas myelin basic protein was elevated at 416 pg/ml (normal \109). Aquaporin-4 (AQP4) antibody, which was measured by a cell-based assay using HEK-293 cells stably transfected with the M23 isoform of AQP4, was negative. Cervical and thoracic spine MRI at the time of admission revealed T2 high-intensity lesions in the dorsal medulla, C1–2, left T1–2, and left T10 levels of the spinal cord (Fig. 1), of which those at C1–2 and T1–2 levels were enhanced by Gadolinium. Gadolinium enhancement was not performed in the thoracic spine MRI. Brain MRI showed a very small T2 high-intensity lesion compatible with a demyelinating plaque in the right periventricular while matter. Visual-evoked potentials (VEPs) at the time of admission revealed a prolonged latency of the right P100
123
174
Fig. 1 Cervical and thoracic spine MRI revealed T2 high-intensity lesions in the dorsal medulla, C1–2, T1–2 (left) and T10 (right, arrow-head) levels
component (peak latency of P100: left 89 ms, right 126 ms). Neuromyelitis optica (NMO) was considered as a differential diagnosis, although the patient did not satisfy the diagnostic criteria for NMO [3] because the spinal cord lesion did not extend over three vertebral segments and the AQP4 antibody was negative. In contrast, she satisfied the McDonald’s criteria for MS (2 attacks, each being supported objectively by MRI lesions in the spinal cord and by the VEP abnormality, respectively). We diagnosed her as MS because other autoantibodies were negative and there was no better explanation. Her symptoms were confined to those caused by the spinal cord and optic nerve lesions, and therefore it would be appropriate to classify her as the opticospinal form of MS (OSMS). Following this diagnosis, methylprednisolone pulse therapy was started (1,000 mg/day, 3 days), which caused rapid disappearance of RLS symptoms and gradual improvement of other signs. Methylprednisolone pulse therapies were completed twice during hospitalization, followed by introduction of IFNb1a for relapse prevention.
123
Neurol Sci (2015) 36:173–174
The relationship between MS and RLS has been discussed by many authors [1, 4]. However, there have been no reports of RLS occurring as a heralding symptom of an MS attack except for one case report where an isolated RLS episode was considered to be an MS exacerbation [5]. In the present case, RLS symptoms did not improve after treatment with a dopamine agonist, but rapidly disappeared following methylprednisolone pulse therapy, which supports our contention that her RLS was caused by the MS lesions, possibly in the cervical or thoracic cord. RLS was the initial and sole manifestation of an acute exacerbation of MS in this case. MS, especially the spinal form of MS [4], should be considered as a differential diagnosis in patients who acutely present with RLS. Acknowledgments We would like to thank Dr.Toshiyuki Takahashi (Department of Neurology, Tohoku University School of Medicine) for the measurement of the AQP4 antibody. Conflict of interest
No conflict of interest.
References 1. Deliu M, Cossu G, Morali A et al (2009) Restless legs syndrome in multiple sclerosis: a case-control study. Mov Disord 24:697–701 2. Allen RP, Picchietti D, Hening WA et al (2003) Restless legs syndrome diagnosis and epidemiology workshop at the national institutes of health; International restless legs syndrome study group. restless legs syndrome: diagnostic criteria, special considerations and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 4:101–119 3. Wingerchuk DM, Lennon VA, Pittock SJ et al (2006) Revised diagnostic criteria for neuromyelitis optica. Neurology 66:1485– 1489 4. Manconi M, Rocca MA, Ferini-Strambi L et al (2008) Restless legs syndrome is a common finding in multiple sclerosis and correlates with cervical cord damage. Mult Scler 14:86–93 5. Bernheimer JH (2011) Restless legs syndrome presenting as an acute exacerbation of multiple sclerosis. Mult Scler Int. doi:10. 1155/2011/872948
