ORIGINAL ARTICLE
Current symptomatology in multiple sclerosis and neuromyelitis optica M. Mutoa, M. Moria, Y. Satob, A. Uzawaa, S. Masudaa, T. Uchidaa and S. Kuwabaraa Department of Neurology, Graduate School of Medicine, Chiba University, Chiba; and bClinical Research Center, Chiba University Hospital, Chiba, Japan
Keywords:
multiple sclerosis, neuromyelitis optica, paroxysmal symptoms, symptomatology Received 17 April 2014 Accepted 25 July 2014 European Journal of Neurology 2014, 0: 1–6 doi:10.1111/ene.12566
Background and objectives: Several symptoms and signs are characteristic of multiple sclerosis (MS) such as Lhermitte’s sign, Uhthoff’s phenomenon and painful tonic seizure. Neuromyelitis optica (NMO) is another inflammatory disease of the central nervous system, and most of the opticospinal form of MS is thought to be NMO. This study aimed to investigate the frequencies of symptoms and signs, previously regarded as characteristic of MS, in NMO and MS patients. Methods: Consecutive Japanese NMO-plus patients [NMO (n = 30) or partial NMO (n = 18)] and MS patients (n = 128) seen at Chiba University Hospital between 2011 and 2012 were investigated for the frequencies of symptoms and signs characteristic of MS. Logistic regression analyses were used to identify factors that distinguished NMO-plus from MS. Results: Univariate analyses revealed that tonic seizures, Lhermitte’s sign, persistent pain, fatigue and girdle sensation were more frequent in NMO-plus patients than in MS patients. Multivariate logistic regression analysis showed that paroxysmal itching, Uhthoff’s phenomenon, Lhermitte’s sign and girdle sensation were more characteristic of NMO-plus than of MS. Conclusions: Several classical MS symptoms and signs are more frequent in NMO patients than MS patients, which may be caused by the differences in the severity of inflammation, and localization and extensiveness of demyelinated lesions.
Introduction Both multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory diseases of the central nervous system. MS is primarily a disease of myelin and oligodendrocytes, and the major characteristic feature of MS pathology is demyelination [1]. Sensory signs, paresthesia, motor weakness, pyramidal sign, visual loss and sphincter disturbance are common clinical symptoms or signs of MS [2]. Several other symptoms and signs, including paroxysmal symptoms, Uhthoff’s phenomenon, Lhermitte’s sign, pain and fatigue, are also thought to be relatively characteristic of MS [3– 5], and most of these can be explained by the effects of demyelination. Correspondence: M. Mori, Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan (tel.: +81-43-222-2129; fax: +81-43-226-2160; e-mail: [email protected]).
© 2014 The Author(s) European Journal of Neurology © 2014 EAN
Historically, NMO has been considered to be an MS variant. In particular, the opticospinal form of MS (OSMS), which selectively affects the optic nerve and spinal cord, has been frequently found in Asia, with some clinical features that are different from those typically observed in western countries [6]. After the discovery of NMO-IgG, a biomarker for NMO [7], NMO was redefined as a specific clinical entity, and most OSMS patients are now considered to have NMO [7,8]. Moreover, accumulating evidence indicates that astrocyte injury due to NMO-IgG targeting of aquaporin-4 on the foot processes of astrocytes is key to the pathogenesis of NMO. Therefore, NMO is thought to be a disease that primarily involves astrocytes and is different from MS. Several symptoms and signs such as severe visual loss and severely sustained motor weakness, intractable vomiting and syndrome of inappropriate antidiuresis are known to be characteristic of OSMS/NMO,
1
EUROPEAN JOURNAL OF NEUROLOGY
a
2
M. MUTO ET AL.
not MS [8–12]. However, it is unclear whether the differences in symptoms and signs considered to be characteristic of MS or OSMS/NMO are based on the pathological differences between MS and OSMS/ NMO. Therefore, the frequencies of symptoms and signs which are known to be characteristic of MS and of OSMS in MS and NMO were compared in this study.
Patients and methods
brief duration (from a few seconds to a few minutes) and with repetitive and stereotypical features. Uhthoff’s phenomenon was also defined as paroxysmal deterioration induced by exercise and by other situations in which body temperature rises [21]. Lhermitte’s sign was defined as a brief, stabbing, electric-shocklike sensation that runs from the back of the head down the spine, brought on by bending the neck forward [17,18]. Girdle sensation was defined as vague or burning sensation, and was localized with a width of 3 or 4 dermatomes from the T3 to T11 level [22].
Patients
Clinical and laboratory data for MS and NMO-plus patients who were seen at the Chiba University Hospital between 2011 and 2012 were collected. MS patients fulfilled the revised McDonald criteria of 2005 [13]. NMO-plus patients were defined as those who fulfilled either of the following two criteria using seropositivity for an anti-aquaporin-4 antibody in place of NMOIgG: (1) NMO criteria of Wingerchuk et al. [9] or (2) partial NMO (pNMO) criteria of Mandler et al. [14] defined as anti-aquaporin-4 antibody-positive optic neuritis and/or transverse myelitis. This study was approved by the Ethics Committee of the Chiba University School of Medicine, Chiba, Japan. Because this was a retrospective review of medical records, the requirement for informed consent was waived. Analyses of neurological symptoms and signs
Although various paroxysmal symptoms and signs have been reported with MS, our focus was on those that occur relatively frequently in MS patients, including tonic seizure, paroxysmal dysarthria and ataxia, paroxysmal pain and paroxysmal itching [15,16]. The frequency of symptoms and signs in MS and NMOplus patients was also analyzed, including those relatively characteristic of MS, such as Uhthoff’s phenomenon, Lhermitte’s sign [17,18], persistent pain [5] and fatigue, [19] and those relatively characteristic of OSMS, including painful tonic seizures and girdle sensation [4,6,20]. Since the symptoms and signs of MS and NMO were of interest, the history of those symptoms and signs was taken from all the patients via face-to-face encounter independently of this study. Definitions of symptoms and signs
Paroxysmal symptoms and signs were defined as sudden-onset, briefly lasting and stereotypical symptoms thought to be caused by MS or NMO-plus. Tonic seizures were defined as transient extensor or flexor spasms in one or more limbs with abrupt onset and
Laboratory results
All patients had undergone brain magnetic resonance imaging (MRI) and whole spinal cord MRI at least once. A lesion that extended over more than three vertebral segments on spinal cord MRI was defined as a long, extended spinal cord lesion (LESCL). Serum samples were obtained from all NMO-plus and MS patients at the time of relapse and were tested for antiaquaporin-4 antibody, as described previously [23]. Statistical analysis
Group comparisons for the results of categorical and continuous variables were made by Fisher’s exact probability test and the Mann–Whitney U test, respectively. Logistic regression analysis was used to assess categorical outcome variables. Univariate regression analyses were first used to identify the possible factors related to NMO-plus or MS. Then, if two or more factors showed significant correlations with outcomes, multivariate logistic regression analyses were used to identify independent factors for distinguishing between NMO-plus and MS. Statistical analyses were conducted using SPSS statistical software, version 11.0.1J (SPSS Japan Inc., Tokyo, Japan). A P value of
Current symptomatology in multiple sclerosis and neuromyelitis optica M. Mutoa, M. Moria, Y. Satob, A. Uzawaa, S. Masudaa, T. Uchidaa and S. Kuwabaraa Department of Neurology, Graduate School of Medicine, Chiba University, Chiba; and bClinical Research Center, Chiba University Hospital, Chiba, Japan
Keywords:
multiple sclerosis, neuromyelitis optica, paroxysmal symptoms, symptomatology Received 17 April 2014 Accepted 25 July 2014 European Journal of Neurology 2014, 0: 1–6 doi:10.1111/ene.12566
Background and objectives: Several symptoms and signs are characteristic of multiple sclerosis (MS) such as Lhermitte’s sign, Uhthoff’s phenomenon and painful tonic seizure. Neuromyelitis optica (NMO) is another inflammatory disease of the central nervous system, and most of the opticospinal form of MS is thought to be NMO. This study aimed to investigate the frequencies of symptoms and signs, previously regarded as characteristic of MS, in NMO and MS patients. Methods: Consecutive Japanese NMO-plus patients [NMO (n = 30) or partial NMO (n = 18)] and MS patients (n = 128) seen at Chiba University Hospital between 2011 and 2012 were investigated for the frequencies of symptoms and signs characteristic of MS. Logistic regression analyses were used to identify factors that distinguished NMO-plus from MS. Results: Univariate analyses revealed that tonic seizures, Lhermitte’s sign, persistent pain, fatigue and girdle sensation were more frequent in NMO-plus patients than in MS patients. Multivariate logistic regression analysis showed that paroxysmal itching, Uhthoff’s phenomenon, Lhermitte’s sign and girdle sensation were more characteristic of NMO-plus than of MS. Conclusions: Several classical MS symptoms and signs are more frequent in NMO patients than MS patients, which may be caused by the differences in the severity of inflammation, and localization and extensiveness of demyelinated lesions.
Introduction Both multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory diseases of the central nervous system. MS is primarily a disease of myelin and oligodendrocytes, and the major characteristic feature of MS pathology is demyelination [1]. Sensory signs, paresthesia, motor weakness, pyramidal sign, visual loss and sphincter disturbance are common clinical symptoms or signs of MS [2]. Several other symptoms and signs, including paroxysmal symptoms, Uhthoff’s phenomenon, Lhermitte’s sign, pain and fatigue, are also thought to be relatively characteristic of MS [3– 5], and most of these can be explained by the effects of demyelination. Correspondence: M. Mori, Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan (tel.: +81-43-222-2129; fax: +81-43-226-2160; e-mail: [email protected]).
© 2014 The Author(s) European Journal of Neurology © 2014 EAN
Historically, NMO has been considered to be an MS variant. In particular, the opticospinal form of MS (OSMS), which selectively affects the optic nerve and spinal cord, has been frequently found in Asia, with some clinical features that are different from those typically observed in western countries [6]. After the discovery of NMO-IgG, a biomarker for NMO [7], NMO was redefined as a specific clinical entity, and most OSMS patients are now considered to have NMO [7,8]. Moreover, accumulating evidence indicates that astrocyte injury due to NMO-IgG targeting of aquaporin-4 on the foot processes of astrocytes is key to the pathogenesis of NMO. Therefore, NMO is thought to be a disease that primarily involves astrocytes and is different from MS. Several symptoms and signs such as severe visual loss and severely sustained motor weakness, intractable vomiting and syndrome of inappropriate antidiuresis are known to be characteristic of OSMS/NMO,
1
EUROPEAN JOURNAL OF NEUROLOGY
a
2
M. MUTO ET AL.
not MS [8–12]. However, it is unclear whether the differences in symptoms and signs considered to be characteristic of MS or OSMS/NMO are based on the pathological differences between MS and OSMS/ NMO. Therefore, the frequencies of symptoms and signs which are known to be characteristic of MS and of OSMS in MS and NMO were compared in this study.
Patients and methods
brief duration (from a few seconds to a few minutes) and with repetitive and stereotypical features. Uhthoff’s phenomenon was also defined as paroxysmal deterioration induced by exercise and by other situations in which body temperature rises [21]. Lhermitte’s sign was defined as a brief, stabbing, electric-shocklike sensation that runs from the back of the head down the spine, brought on by bending the neck forward [17,18]. Girdle sensation was defined as vague or burning sensation, and was localized with a width of 3 or 4 dermatomes from the T3 to T11 level [22].
Patients
Clinical and laboratory data for MS and NMO-plus patients who were seen at the Chiba University Hospital between 2011 and 2012 were collected. MS patients fulfilled the revised McDonald criteria of 2005 [13]. NMO-plus patients were defined as those who fulfilled either of the following two criteria using seropositivity for an anti-aquaporin-4 antibody in place of NMOIgG: (1) NMO criteria of Wingerchuk et al. [9] or (2) partial NMO (pNMO) criteria of Mandler et al. [14] defined as anti-aquaporin-4 antibody-positive optic neuritis and/or transverse myelitis. This study was approved by the Ethics Committee of the Chiba University School of Medicine, Chiba, Japan. Because this was a retrospective review of medical records, the requirement for informed consent was waived. Analyses of neurological symptoms and signs
Although various paroxysmal symptoms and signs have been reported with MS, our focus was on those that occur relatively frequently in MS patients, including tonic seizure, paroxysmal dysarthria and ataxia, paroxysmal pain and paroxysmal itching [15,16]. The frequency of symptoms and signs in MS and NMOplus patients was also analyzed, including those relatively characteristic of MS, such as Uhthoff’s phenomenon, Lhermitte’s sign [17,18], persistent pain [5] and fatigue, [19] and those relatively characteristic of OSMS, including painful tonic seizures and girdle sensation [4,6,20]. Since the symptoms and signs of MS and NMO were of interest, the history of those symptoms and signs was taken from all the patients via face-to-face encounter independently of this study. Definitions of symptoms and signs
Paroxysmal symptoms and signs were defined as sudden-onset, briefly lasting and stereotypical symptoms thought to be caused by MS or NMO-plus. Tonic seizures were defined as transient extensor or flexor spasms in one or more limbs with abrupt onset and
Laboratory results
All patients had undergone brain magnetic resonance imaging (MRI) and whole spinal cord MRI at least once. A lesion that extended over more than three vertebral segments on spinal cord MRI was defined as a long, extended spinal cord lesion (LESCL). Serum samples were obtained from all NMO-plus and MS patients at the time of relapse and were tested for antiaquaporin-4 antibody, as described previously [23]. Statistical analysis
Group comparisons for the results of categorical and continuous variables were made by Fisher’s exact probability test and the Mann–Whitney U test, respectively. Logistic regression analysis was used to assess categorical outcome variables. Univariate regression analyses were first used to identify the possible factors related to NMO-plus or MS. Then, if two or more factors showed significant correlations with outcomes, multivariate logistic regression analyses were used to identify independent factors for distinguishing between NMO-plus and MS. Statistical analyses were conducted using SPSS statistical software, version 11.0.1J (SPSS Japan Inc., Tokyo, Japan). A P value of
