Original Paper Eur Neurol 2014;72:153–156 DOI: 10.1159/000361045
Received: December 24, 2013 Accepted: March 3, 2014 Published online: August 28, 2014
Uhthoff’s Phenomenon in Multiple Sclerosis and Neuromyelitis Optica Kwiyoung Park a Keiko Tanaka b Masami Tanaka a a
Multiple Sclerosis Center, Utano National Hospital, Kyoto, and b Department of Neurology, Kanazawa Medical University, Uchinada, Japan
Key Words Uhthoff’s phenomenon · Multiple sclerosis · Neuromyelitis optica · Aquaporin 4 · Optic neuritis · Hot bath test
Abstract To evaluate and compare the incidence and clinical features of Uhthoff’s phenomenon in Japanese patients with neuromyelitis optica (NMO) and those with multiple sclerosis (MS), we asked 135 consecutive patients with MS and an NMOrelated disorder (NMOrd) whether they experienced worse neurological symptoms after an increase in body temperature. Responses were obtained from 54 MS and 37 NMOrd patients. Uhthoff’s phenomenon was observed in 26 MS (48.1%) and 20 NMOrd patients (54.1%). Motor and sensory symptoms were more frequent than visual symptoms in both diseases. The incidence of Uhthoff’s phenomenon was similar in MS and NMOrd. © 2014 S. Karger AG, Basel
Introduction
Patients and Methods
© 2014 S. Karger AG, Basel 0014–3022/14/0724–0153$39.50/0
We used questionnaires to query 135 consecutive patients with MS at Utano National Hospital who fulfilled McDonald’s criteria [3] and had an NMO-related disorder (NMOrd), including NMO that fulfilled the criteria proposed by Wingerchuk et al. [4], the NMO spectrum disorder proposed by Wingerchuk et al. [5], and
Masami Tanaka Multiple Sclerosis Center, Utano National Hospital 8 Ondoyama Narutaki, Ukyo-ku, Kyoto 616-8255 (Japan) E-Mail tanaka @ unh.hosp.go.jp
Downloaded by: University of Tokyo 157.82.153.40 - 5/18/2015 6:45:41 PM
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system that involves demyelination and axonal degeneration. Neuromyelitis optica (NMO) mainly affects the optic nerves and spinal cord. It
E-Mail [email protected] www.karger.com/ene
is characterized with longitudinally extensive spinal cord lesions extending over 3 vertebral segments (LESCLs) and anti-aquaporin (AQP) 4 antibodies in sera. Uhthoff’s phenomenon, i.e. paroxysmal neurological deterioration induced by increased body temperature, is known to occur in up to 80% Western patients with MS [1]. Temperature-dependent central motor conduction blockage of partially demyelinated axons has been proposed as the main pathophysiological mechanism underlying clinical deterioration with increased body temperature. The incidence of Uhthoff’s phenomenon is unknown in patients with NMO. Initially, the presence of necrotic lesions but not demyelination was considered to be the main feature of the pathology of NMO, which is unlikely to block conduction. However, recent studies have detected demyelinating lesions in NMO [2]. We compared the incidence and neurological symptoms of Uhthoff’s phenomenon between MS and NMO patients.
Table 1. Symptoms of Uhthoff’s phenomenon in MS and NMOrd
patients
Visual symptoms Motor symptoms Sensory symptoms Sensory + motor symptoms Urinary incontinence Stiffness Dizziness Unsteady gait Difficulty moving
NMOrd4
33 (19 – 56) 35.4 ± 10.9
39 (6 – 66) 39.0 ± 15.4
8 (0.7 – 43) 9.7 ± 7.8
7 (0.5 – 24) 8.7 ± 5.8
1.5 (0 – 8) 1.9 ± 1.7
4.3 (0 – 7.5) 4.4 ± 2.4
19.2 11.5 30.8 42.3 80.8
15 0 25 70 90
79.2 24.5 7.7 3.8 3.8 3.8 3.8
30 5.0 20
Results 90 55 40 5.0
7 7 13 19 2 2 1 0 2
5 7 10 13 0 3 1 1 0
Uhthoff’s phenomenon was observed in 26 (48.1%) and 20 (54.1%) patients with MS and NMOrd, respectively. Some patients experienced 2 or more kinds of symptoms. EDSS = Expected disability status scale by Kurtzke [14]; Cbr = cerebrum; Cbll = cerebellum; BS = brainstem; ON = optic nerve; SC = spinal cord; IFN = interferon; FTY = fingolimod; MITX = mitoxantrone; NTZ = natalizumab; GA = glatiramer acetate; PSL = oral prednisolone; TCR = tacrolimus; AZT = azathioprine; RITX = rituximab. 1 Not on the market in Japan. 2 Administered during clinical trials. 3 We administered IFN-β to NMO patients before the publication of the use of anti-AQP 4 antibodies [14] and found a severe relapse in a patient with anti-AQP 4 antibodies after fingolimod treatment during a Japanese clinical trial [16]. 4 Includes NMO, NMOsd, and anti-AQP 4 syndrome (monophasic optic neuritis or acute myelitis without LESCLs).
154
Eur Neurol 2014;72:153–156 DOI: 10.1159/000361045
Responses were obtained from 91 patients (67.4%) as follows: 54 with MS (59.3%; 20 men and 34 women) aged 21–72 years (mean ± SD: 45.3 ± 11.0) and 37 patients with NMOrd (40.7%; 4 men and 33 women) aged 21–74 years (47.9 ± 15.1). NMOrd included 17 cases of NMO, 10 cases of NMOsd, and 10 cases of anti-AQP 4 syndrome. Uhthoff’s phenomenon was observed in 26 (48.1%) and 20 (54. 1%) patients with MS and NMOrd, respectively (not significant, p = 0.671). In the MS patients, motor (7 patients) and sensory (13 patients) symptoms (19/26; 73.1%) were more frequent than visual symptoms (7/26, 26.9%; p = 0.002). In the NMOrd patients, motor (7 patients) and sensory (10 patients) symptoms (13/20; 65.0%) were more frequent than visual symptoms (5/20; 25%; p = 0.025) (table 1). The other symptoms included urinary incontinence (2 MS patients), stiffness (2 MS and 3 NMOrd patients), dizziness (1 each), unsteady gait (1 NMOrd patient), and difficulty moving (2 MS patients) (table 1). The causes of increased body temperature included: bathing (17 MS and 17 NMOrd patients), showering (5 MS and 6 NMOrd patients), going outside in the summer (4 MS and 5 NMOrd patients), exercising (3 MS and 2 NMOrd patients), sitting near a heater (5 MS patients), and being heavily clad (2 MS patients). Most of the symptoms lasted less than 30 min (e.g. visual symptoms in 6/7 MS patients and 4/5 NMOrd paPark /Tanaka /Tanaka
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Age at onset, years Median (range) Mean ± SD Disease duration, years Median (range) Mean ± SD Disability score (EDSS) Median (range) Mean ± SD Clinically estimated lesions, % Cbr Cbll BS ON SC Treatment history, % IFN-β3 FTY3 MITX NTZ1,2 ONO46412 GA2 None PSL TCR AZT RITX
MS
anti-AQP 4 syndrome without NMO or NMO spectrum disorder (NMOsd) features (monophasic optic neuritis or acute myelitis without LESCLs). The patients participated in the 2012 national survey of MS/NMO in Japan (May 1, 2012, to July 31, 2012) and were asked whether they experienced worse neurological symptoms after an increase in body temperature (see Appendix). The patients freely responded to the questionnaire in their own words, and they could provide multiple answers to each question. We excluded 2 patients (1 with NMO and 1 with MS) with Uhthoff’s phenomenon because their symptoms had continued for >12 h (NMO patient) or 4–5 days (MS patient). We included typical patients with Uhthoff’s phenomenon. Their symptoms were classified as follows: motor symptom (weakness), sensory symptoms (hypesthesia, pain, and numbness), and visual symptoms (blurred vision and visual loss). Anti-AQP 4 antibodies were analyzed in patient sera using a cell-based assay, as reported previously [6]. Differences in frequency between the two groups were analyzed using Fischer’s exact test. The Mann-Whitney U test was used to analyze differences between the periods of visual and sensorimotor impairment after body heating. The Ethics Committee at our hospital approved this study.
tients and sensorimotor symptoms in 9/20 MS and 8/16 NMOrd patients), though the differences between the MS and NMOrd patients were not significant (p = 0.0788 and p = 0.135, respectively). Among those with a history of optic neuritis (MS: n = 21; 38.9%; NMOrd: 22; 59.5%), visual symptoms of Uhthoff’s phenomenon were observed in 5/21 (23%) and 4/22 (18.2%) patients with MS and NMOrd, respectively (p = 0.721). Two MS patients exhibited visual symptoms but had never developed optic neuritis previously. One had abnormal visual evoked potentials but a normal critical flicker frequency, while 1 NMOrd patient exhibited visual symptoms but never developed optic neuritis. His visual evoked potentials and critical flicker frequency were normal.
Previous studies have shown that exercise is the most common cause of Uhthoff’s phenomenon [1]. In our study, the most common cause of Uhthoff’s phenomenon was bathing, which might be attributable to the different lifestyle of Japanese people. ‘Taking a bath’ in Japan usually means soaking in the bathwater. The worsening of neurological symptoms after an increase in body temperature can be reduced by oral administration of 4-aminopyridine [13], which inhibits potassium channel activation, thereby prolonging the action potential, which can restore nerve conduction in demyelinated nerve fibers. Recent clinical trials of dalfampridine detected improvement in the gait disturbance of MS patients, and thus it may have beneficial effects on neurological symptoms in NMOrd patients.
Appendix Discussion
This study showed that NMOrd patients experience the same incidence of Uhthoff’s phenomenon as MS patients in Japan. To the best of our knowledge, this is the first report of the frequency of Uhthoff’s phenomenon in Asian MS patients. Previous studies reported that 149/256 (58.2%) [7], 12/20 (60.0%) [8], and 17/20 (85%) [9] MS patients exhibited Uhthoff’s phenomenon, although patients with optic neuritis may have experienced a lower incidence than MS patients because 41/125 (32.8%) [10], 10/24 (41.7%) [11], and 48/80 (52%) [12] exhibited visual symptoms of Uhthoff’s phenomenon. The incidence of visual symptoms may have been low because our study showed that motor and sensory disturbances, which were probably attributable to spinal cord lesions, were more frequent in MS and NMOrd (table 1).
– Have you ever had an episode of worsened neurological symptoms such as visual impairment, weakness, sensory disturbances, or others after an increase in body temperature? – What kinds of episodes of increased body temperature causing worsened neurological symptoms have you experienced? – How long did the worsened neurological symptoms last? – What were the symptoms? Please express concretely. – Thank you for your time.
Acknowledgement This study was supported in part by Health and Labor Sciences Research Grants for research on intractable diseases from the Ministry of Health, Labour, and Welfare of Japan.
Disclosure Statement None.
References
Uhthoff’s Phenomenon in MS and NMO
3 McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al: Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol 2001;50:121–127. 4 Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG: Revised diagnostic criteria for neuromyelitis optica. Neurology 2006;66:1485–1489.
5 Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG: The spectrum of neuromyelitis optica. Lancet Neurol 2007;6:805–815. 6 Tanaka K, Tani T, Tanaka M, Saida T, Idezuka J, Yamazaki M, et al: Anti-aquaporin 4 antibody in selected Japanese multiple sclerosis patients with long spinal cord lesions. Mult Scler 2007;13:850–855.
Eur Neurol 2014;72:153–156 DOI: 10.1159/000361045
155
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1 Guthrie TC, Nelson DA: Influence of temperature changes on multiple sclerosis: critical review of mechanisms and research potential. J Neurol Sci 1995;129:1–8. 2 Misu T, Höftberger R, Fujihara K, Wimmer I, Takai Y, Nishiyama S, Nakashima I, et al: Presence of six different lesion types suggests diverse mechanisms of tissue injury in neuromyelitis optica. Acta Neuropathol 2013; 125: 815–827.
156
10 Perkin GD, Rose FC: Uhthoff’s syndrome. Br J Ophthal 1975;60:60–63. 11 Lepore FE: Uhthoff’s symptom in disorders of the anterior visual pathways. Neurology 1994;44:1036–1038. 12 Fraser CL, Davagnanam I, Radon M, Plant GT: The time course and phenotype of Uhthoff phenomenon following optic neuritis. Mult Scler 2012;18:1042–1044. 13 van Diemen HA, van Dongen MM, Dammers JW, Polman CH: Increased visual impairment after exercise (Uhthoff’s phenomenon) in multiple sclerosis: therapeutic possibilities. Eur Neurol 1992;32:231–234. 14 Kurtzke JF: Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444– 1452.
Eur Neurol 2014;72:153–156 DOI: 10.1159/000361045
15 Tanaka M, Oono M, Motoyama R, Tanaka K: Longitudinally extensive spinal cord lesion after initiation, and multiple extensive brain lesions after cessation of fingolimod treatment in a patient with recurrent myelitis and anti-aquaporin 4 antibodies. Clin Exp Neuroimmunol 2013;4:239–240. 16 Kurtzke JF: Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444– 1452.
Park /Tanaka /Tanaka
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7 Flensner G, Ek A-C, Söderhamn O, Landtblom A-M: Sensitivity to heat in MS patients: a factor strongly influencing symptomologyan explorative survey. BMC Neurol 2011; 11: 27. 8 Humm AM, Beer S, Kool J, Magistris MR, Kesselring J, Rösler KM: Quantification of Uhthoff’s phenomenon in multiple sclerosis: a magnetic stimulation study. Clin Neurophysiol 2004;115:2493–2501. 9 Malhotra AS, Goren H: The hot bath test in the diagnosis of multiple sclerosis. JAMA 1981;246:1113–1114.
Received: December 24, 2013 Accepted: March 3, 2014 Published online: August 28, 2014
Uhthoff’s Phenomenon in Multiple Sclerosis and Neuromyelitis Optica Kwiyoung Park a Keiko Tanaka b Masami Tanaka a a
Multiple Sclerosis Center, Utano National Hospital, Kyoto, and b Department of Neurology, Kanazawa Medical University, Uchinada, Japan
Key Words Uhthoff’s phenomenon · Multiple sclerosis · Neuromyelitis optica · Aquaporin 4 · Optic neuritis · Hot bath test
Abstract To evaluate and compare the incidence and clinical features of Uhthoff’s phenomenon in Japanese patients with neuromyelitis optica (NMO) and those with multiple sclerosis (MS), we asked 135 consecutive patients with MS and an NMOrelated disorder (NMOrd) whether they experienced worse neurological symptoms after an increase in body temperature. Responses were obtained from 54 MS and 37 NMOrd patients. Uhthoff’s phenomenon was observed in 26 MS (48.1%) and 20 NMOrd patients (54.1%). Motor and sensory symptoms were more frequent than visual symptoms in both diseases. The incidence of Uhthoff’s phenomenon was similar in MS and NMOrd. © 2014 S. Karger AG, Basel
Introduction
Patients and Methods
© 2014 S. Karger AG, Basel 0014–3022/14/0724–0153$39.50/0
We used questionnaires to query 135 consecutive patients with MS at Utano National Hospital who fulfilled McDonald’s criteria [3] and had an NMO-related disorder (NMOrd), including NMO that fulfilled the criteria proposed by Wingerchuk et al. [4], the NMO spectrum disorder proposed by Wingerchuk et al. [5], and
Masami Tanaka Multiple Sclerosis Center, Utano National Hospital 8 Ondoyama Narutaki, Ukyo-ku, Kyoto 616-8255 (Japan) E-Mail tanaka @ unh.hosp.go.jp
Downloaded by: University of Tokyo 157.82.153.40 - 5/18/2015 6:45:41 PM
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system that involves demyelination and axonal degeneration. Neuromyelitis optica (NMO) mainly affects the optic nerves and spinal cord. It
E-Mail [email protected] www.karger.com/ene
is characterized with longitudinally extensive spinal cord lesions extending over 3 vertebral segments (LESCLs) and anti-aquaporin (AQP) 4 antibodies in sera. Uhthoff’s phenomenon, i.e. paroxysmal neurological deterioration induced by increased body temperature, is known to occur in up to 80% Western patients with MS [1]. Temperature-dependent central motor conduction blockage of partially demyelinated axons has been proposed as the main pathophysiological mechanism underlying clinical deterioration with increased body temperature. The incidence of Uhthoff’s phenomenon is unknown in patients with NMO. Initially, the presence of necrotic lesions but not demyelination was considered to be the main feature of the pathology of NMO, which is unlikely to block conduction. However, recent studies have detected demyelinating lesions in NMO [2]. We compared the incidence and neurological symptoms of Uhthoff’s phenomenon between MS and NMO patients.
Table 1. Symptoms of Uhthoff’s phenomenon in MS and NMOrd
patients
Visual symptoms Motor symptoms Sensory symptoms Sensory + motor symptoms Urinary incontinence Stiffness Dizziness Unsteady gait Difficulty moving
NMOrd4
33 (19 – 56) 35.4 ± 10.9
39 (6 – 66) 39.0 ± 15.4
8 (0.7 – 43) 9.7 ± 7.8
7 (0.5 – 24) 8.7 ± 5.8
1.5 (0 – 8) 1.9 ± 1.7
4.3 (0 – 7.5) 4.4 ± 2.4
19.2 11.5 30.8 42.3 80.8
15 0 25 70 90
79.2 24.5 7.7 3.8 3.8 3.8 3.8
30 5.0 20
Results 90 55 40 5.0
7 7 13 19 2 2 1 0 2
5 7 10 13 0 3 1 1 0
Uhthoff’s phenomenon was observed in 26 (48.1%) and 20 (54.1%) patients with MS and NMOrd, respectively. Some patients experienced 2 or more kinds of symptoms. EDSS = Expected disability status scale by Kurtzke [14]; Cbr = cerebrum; Cbll = cerebellum; BS = brainstem; ON = optic nerve; SC = spinal cord; IFN = interferon; FTY = fingolimod; MITX = mitoxantrone; NTZ = natalizumab; GA = glatiramer acetate; PSL = oral prednisolone; TCR = tacrolimus; AZT = azathioprine; RITX = rituximab. 1 Not on the market in Japan. 2 Administered during clinical trials. 3 We administered IFN-β to NMO patients before the publication of the use of anti-AQP 4 antibodies [14] and found a severe relapse in a patient with anti-AQP 4 antibodies after fingolimod treatment during a Japanese clinical trial [16]. 4 Includes NMO, NMOsd, and anti-AQP 4 syndrome (monophasic optic neuritis or acute myelitis without LESCLs).
154
Eur Neurol 2014;72:153–156 DOI: 10.1159/000361045
Responses were obtained from 91 patients (67.4%) as follows: 54 with MS (59.3%; 20 men and 34 women) aged 21–72 years (mean ± SD: 45.3 ± 11.0) and 37 patients with NMOrd (40.7%; 4 men and 33 women) aged 21–74 years (47.9 ± 15.1). NMOrd included 17 cases of NMO, 10 cases of NMOsd, and 10 cases of anti-AQP 4 syndrome. Uhthoff’s phenomenon was observed in 26 (48.1%) and 20 (54. 1%) patients with MS and NMOrd, respectively (not significant, p = 0.671). In the MS patients, motor (7 patients) and sensory (13 patients) symptoms (19/26; 73.1%) were more frequent than visual symptoms (7/26, 26.9%; p = 0.002). In the NMOrd patients, motor (7 patients) and sensory (10 patients) symptoms (13/20; 65.0%) were more frequent than visual symptoms (5/20; 25%; p = 0.025) (table 1). The other symptoms included urinary incontinence (2 MS patients), stiffness (2 MS and 3 NMOrd patients), dizziness (1 each), unsteady gait (1 NMOrd patient), and difficulty moving (2 MS patients) (table 1). The causes of increased body temperature included: bathing (17 MS and 17 NMOrd patients), showering (5 MS and 6 NMOrd patients), going outside in the summer (4 MS and 5 NMOrd patients), exercising (3 MS and 2 NMOrd patients), sitting near a heater (5 MS patients), and being heavily clad (2 MS patients). Most of the symptoms lasted less than 30 min (e.g. visual symptoms in 6/7 MS patients and 4/5 NMOrd paPark /Tanaka /Tanaka
Downloaded by: University of Tokyo 157.82.153.40 - 5/18/2015 6:45:41 PM
Age at onset, years Median (range) Mean ± SD Disease duration, years Median (range) Mean ± SD Disability score (EDSS) Median (range) Mean ± SD Clinically estimated lesions, % Cbr Cbll BS ON SC Treatment history, % IFN-β3 FTY3 MITX NTZ1,2 ONO46412 GA2 None PSL TCR AZT RITX
MS
anti-AQP 4 syndrome without NMO or NMO spectrum disorder (NMOsd) features (monophasic optic neuritis or acute myelitis without LESCLs). The patients participated in the 2012 national survey of MS/NMO in Japan (May 1, 2012, to July 31, 2012) and were asked whether they experienced worse neurological symptoms after an increase in body temperature (see Appendix). The patients freely responded to the questionnaire in their own words, and they could provide multiple answers to each question. We excluded 2 patients (1 with NMO and 1 with MS) with Uhthoff’s phenomenon because their symptoms had continued for >12 h (NMO patient) or 4–5 days (MS patient). We included typical patients with Uhthoff’s phenomenon. Their symptoms were classified as follows: motor symptom (weakness), sensory symptoms (hypesthesia, pain, and numbness), and visual symptoms (blurred vision and visual loss). Anti-AQP 4 antibodies were analyzed in patient sera using a cell-based assay, as reported previously [6]. Differences in frequency between the two groups were analyzed using Fischer’s exact test. The Mann-Whitney U test was used to analyze differences between the periods of visual and sensorimotor impairment after body heating. The Ethics Committee at our hospital approved this study.
tients and sensorimotor symptoms in 9/20 MS and 8/16 NMOrd patients), though the differences between the MS and NMOrd patients were not significant (p = 0.0788 and p = 0.135, respectively). Among those with a history of optic neuritis (MS: n = 21; 38.9%; NMOrd: 22; 59.5%), visual symptoms of Uhthoff’s phenomenon were observed in 5/21 (23%) and 4/22 (18.2%) patients with MS and NMOrd, respectively (p = 0.721). Two MS patients exhibited visual symptoms but had never developed optic neuritis previously. One had abnormal visual evoked potentials but a normal critical flicker frequency, while 1 NMOrd patient exhibited visual symptoms but never developed optic neuritis. His visual evoked potentials and critical flicker frequency were normal.
Previous studies have shown that exercise is the most common cause of Uhthoff’s phenomenon [1]. In our study, the most common cause of Uhthoff’s phenomenon was bathing, which might be attributable to the different lifestyle of Japanese people. ‘Taking a bath’ in Japan usually means soaking in the bathwater. The worsening of neurological symptoms after an increase in body temperature can be reduced by oral administration of 4-aminopyridine [13], which inhibits potassium channel activation, thereby prolonging the action potential, which can restore nerve conduction in demyelinated nerve fibers. Recent clinical trials of dalfampridine detected improvement in the gait disturbance of MS patients, and thus it may have beneficial effects on neurological symptoms in NMOrd patients.
Appendix Discussion
This study showed that NMOrd patients experience the same incidence of Uhthoff’s phenomenon as MS patients in Japan. To the best of our knowledge, this is the first report of the frequency of Uhthoff’s phenomenon in Asian MS patients. Previous studies reported that 149/256 (58.2%) [7], 12/20 (60.0%) [8], and 17/20 (85%) [9] MS patients exhibited Uhthoff’s phenomenon, although patients with optic neuritis may have experienced a lower incidence than MS patients because 41/125 (32.8%) [10], 10/24 (41.7%) [11], and 48/80 (52%) [12] exhibited visual symptoms of Uhthoff’s phenomenon. The incidence of visual symptoms may have been low because our study showed that motor and sensory disturbances, which were probably attributable to spinal cord lesions, were more frequent in MS and NMOrd (table 1).
– Have you ever had an episode of worsened neurological symptoms such as visual impairment, weakness, sensory disturbances, or others after an increase in body temperature? – What kinds of episodes of increased body temperature causing worsened neurological symptoms have you experienced? – How long did the worsened neurological symptoms last? – What were the symptoms? Please express concretely. – Thank you for your time.
Acknowledgement This study was supported in part by Health and Labor Sciences Research Grants for research on intractable diseases from the Ministry of Health, Labour, and Welfare of Japan.
Disclosure Statement None.
References
Uhthoff’s Phenomenon in MS and NMO
3 McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al: Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol 2001;50:121–127. 4 Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG: Revised diagnostic criteria for neuromyelitis optica. Neurology 2006;66:1485–1489.
5 Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG: The spectrum of neuromyelitis optica. Lancet Neurol 2007;6:805–815. 6 Tanaka K, Tani T, Tanaka M, Saida T, Idezuka J, Yamazaki M, et al: Anti-aquaporin 4 antibody in selected Japanese multiple sclerosis patients with long spinal cord lesions. Mult Scler 2007;13:850–855.
Eur Neurol 2014;72:153–156 DOI: 10.1159/000361045
155
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1 Guthrie TC, Nelson DA: Influence of temperature changes on multiple sclerosis: critical review of mechanisms and research potential. J Neurol Sci 1995;129:1–8. 2 Misu T, Höftberger R, Fujihara K, Wimmer I, Takai Y, Nishiyama S, Nakashima I, et al: Presence of six different lesion types suggests diverse mechanisms of tissue injury in neuromyelitis optica. Acta Neuropathol 2013; 125: 815–827.
156
10 Perkin GD, Rose FC: Uhthoff’s syndrome. Br J Ophthal 1975;60:60–63. 11 Lepore FE: Uhthoff’s symptom in disorders of the anterior visual pathways. Neurology 1994;44:1036–1038. 12 Fraser CL, Davagnanam I, Radon M, Plant GT: The time course and phenotype of Uhthoff phenomenon following optic neuritis. Mult Scler 2012;18:1042–1044. 13 van Diemen HA, van Dongen MM, Dammers JW, Polman CH: Increased visual impairment after exercise (Uhthoff’s phenomenon) in multiple sclerosis: therapeutic possibilities. Eur Neurol 1992;32:231–234. 14 Kurtzke JF: Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444– 1452.
Eur Neurol 2014;72:153–156 DOI: 10.1159/000361045
15 Tanaka M, Oono M, Motoyama R, Tanaka K: Longitudinally extensive spinal cord lesion after initiation, and multiple extensive brain lesions after cessation of fingolimod treatment in a patient with recurrent myelitis and anti-aquaporin 4 antibodies. Clin Exp Neuroimmunol 2013;4:239–240. 16 Kurtzke JF: Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444– 1452.
Park /Tanaka /Tanaka
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7 Flensner G, Ek A-C, Söderhamn O, Landtblom A-M: Sensitivity to heat in MS patients: a factor strongly influencing symptomologyan explorative survey. BMC Neurol 2011; 11: 27. 8 Humm AM, Beer S, Kool J, Magistris MR, Kesselring J, Rösler KM: Quantification of Uhthoff’s phenomenon in multiple sclerosis: a magnetic stimulation study. Clin Neurophysiol 2004;115:2493–2501. 9 Malhotra AS, Goren H: The hot bath test in the diagnosis of multiple sclerosis. JAMA 1981;246:1113–1114.
