Neurol Sci (2015) 36:1925–1927 DOI 10.1007/s10072-015-2277-z
LETTER TO THE EDITOR
Severe aquaporin-4 IgG-positive neuromyelitis optica spectrum disorder with short myelitis lesion and favourable outcome Gianni Masi1 • Chiara Cioni1 • Umberto Arrigucci2 • Alfonso Cerase2 Pasquale Annunziata1
•
Received: 11 March 2015 / Accepted: 3 June 2015 / Published online: 7 June 2015 Ó Springer-Verlag Italia 2015
Keywords Neuromyelitis optica Neuromyelitis optica spectrum disorder Aquaporin-4 Aquaporin-4 IgG Transverse myelitis Autoimmunity Neuromyelitis optica spectrum disorders (NMOSD) refer to limited forms of neuromyelitis optica (NMO) including recurrent or simultaneous bilateral optic neuritis (ON) or longitudinally extensive transverse myelitis (LETM), extending three or more vertebral segments, unified by the seropositivity for anti-aquaporin-4 (AQP4) antibody [1]. Myelitis extending less than three vertebral segments in NMOSD has recently been recognized as a rare variant with not well-established clinical outcome. We here report a case of severe AQP4-IgG-positive NMOSD with short myelitis lesion and favourable outcome. A 24-year-old woman experienced in May 2011 sudden visual loss and ocular pain in left eye showing visual acuity \1/10 and significant P100 amplitude decrease and latency prolongation. Apart visual loss, neurological examination was unremarkable. Brain and orbits magnetic resonance imaging (MRI) revealed only an inflammatory injury to the left optic nerve. Left retrobulbar ON was diagnosed and
Electronic supplementary material The online version of this article (doi:10.1007/s10072-015-2277-z) contains supplementary material, which is available to authorized users. & Pasquale Annunziata [email protected] 1
Department of Medicine, Surgery and Neurosciences, Clinical Neuroimmunology Unit, University of Siena, Siena, Italy
2
Unit of Neuroimaging and Neurointervention, Medical School, Siena, Italy
treated with high-dose intravenous methylprednisolone (IVMP) for 5 days resulting in complete recovery of the visual acuity in several months. In October 2011, she presented with paresthesias affecting upper limbs, in the absence of any sensory level and motor impairment, and brain MRI showed three gadolinium-enhancing lesions located at left frontal horn periventricular white matter, genu of corpus callosum and within the cervical spinal cord C2–C3 (Fig. 1a, b). Cerebrospinal fluid analysis revealed no alterations including the absence of oligoclonal bands. Search for serum anti-AQP4 IgG with a commercial indirect immunofluorescence transfected cell-based assay, showing reliable sensitivity [1, 2, supplementary file], was positive. In May 2012, internuclear ophthalmoplegia (INO) and severe vertigo occurred, and brain MRI documented a slight FLAIR hyperintensity adjacent to the fourth ventricle floor (Fig. 1c, d). The clinical features reversed after an IVMP 5-day course. In July 2012, the patient experienced numbness and progressive weakness at both legs. Neurological examination revealed paraparesis with walking difficulty, rapidly evolving to paraplegia, as well as sensory loss below D5 thoracic level and urinary retention. TM was diagnosed, and spinal cord MRI showed a gadolinium-enhancing short lesion longitudinally extending only over two vertebral segments (Fig. 2a), as well as brain MRI revealed a large FLAIR hyperintensity adjacent to the fourth ventricle floor (Fig. 1e). The diagnosis of NMOSD was therefore supported [1]. Acute-phase treatment consisted of IVMP (1 g/day for 5 days) followed by two cycles of IV immunoglobulin (0.4 g/kg/day for 5 days) over 2 months. Motor, sensory and bladder dysfunctions greatly improved: at the end of August 2012, she was able to walk with bilateral assistance and, in October 2012, after an intensive physical rehabilitation, she was able to walk without aid. As maintenance therapy, oral azathioprine
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Fig. 1 Two gadolinium-enhancing lesions in genu of corpus callosum and in the cervical spinal cord C2–C3 (arrows, a) and another gadolinium-enhancing lesion in left frontal horn periventricular white matter (arrow, b). Brain FLAIR hyperintensity adjacent to the fourth ventricle floor with bilateral involvement of facial nerve colliculus Fig. 2 Spinal cord new swollen lesion longitudinally extending from D3 to D4 with gadolinium enhancement (arrow, a). Follow-up MRI revealed no gadolinium enhancement of the thoracic spinal cord lesion (b)
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and likely, of medial longitudinal fasciculus (arrows, c) as well as median raphe (arrow, d). Brain large FLAIR hyperintensity adjacent to the fourth ventricle floor (arrows, e). Follow-up MRI revealed disappearance of the fourth ventricular lesion (f)
Neurol Sci (2015) 36:1925–1927
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patients with STM respect to those with LETM has been reported suggesting lower clinical severity [3]. Conversely, our patient with STM was paraplegic at nadir although resulting in a favourable outcome, characterized by complete recovery of the motor autonomy maintained after 29-month follow-up. The major severity of clinical features in our patient at the time of STM could depend on the underlying inflammatory process even though we cannot exclude that early MRI might miss a longer medullar lesion. In conclusion, our report highlights the need of searching for serum anti-AQP4 antibody not only in the presence of LETM, but also when a STM is detected and suggests that NMOSD with STM may have a favourable prognosis even with a severe clinical manifestation at nadir. Fig. 3 Progression over time (months) of the impairment assessed with modified Rankin scale score, clinical features and related treatment. IV MP intravenous methylprednisolone, IV Igs intravenous immunoglobulins
(100 mg daily) and prednisone (0.5 mg/kg daily) were started. The patient did not experience new relapses (Fig. 3). In December 2012, an MRI scan demonstrated atrophic evolution of the thoracic spinal cord lesion with no gadolinium enhancement (Fig. 2b) and disappearance of the fourth ventricular lesion (Fig. 1f) as well as anti-AQP4 seropositivity was still detected. At the last follow-up, in December 2014, neurological examination was normal and spinal cord lesion further reduced at MRI (data not shown). In our case, after a monophasic ON, NMOSD diagnosis was supported by AQP4 IgG seropositivity associated with a short myelitis lesion as well as a brain lesion in a periependymal area, very rich in AQP4 and atypical for multiple sclerosis (MS) [1, 2]. INO, due to demyelination of medial longitudinal fasciculus, has frequently been reported in MS but seldom in NMO and NMOSD [3, 4, supplementary file]. LETM is the typical myelitis in NMOSD, but short medullar lesions, not extending three vertebral segments, can occur in NMOSD with frequency ranging from 5.5 % [4] to 14 % [3]. In our patient, short transverse myelitis (STM) occurred 14 months after monophasic ON lacking in any clinical predictor of AQP4 IgG seropositivity identified in STM such as older age, personal history of autoimmunity and tonic spasms [3]. In LETM, a correlation between serum anti-AQP4 antibody levels and number of segments of spinal cord involved has recently been found [5]. Less need of aid to walk at nadir in
Conflict of interest of interest.
The authors declare that they have no conflict
Research involving human participants and/or animals All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with 1964 Helsinki declaration and its later amendments or comparable ethical standards. However, for this case report, formal consent is not required. Informed consent
Informed consent was obtained from the patient.
References 1. Jacob A, McKeon A, Nakashima I, Sato DK, Elsone L, Fujihara K, de Seze J (2013) Current concept of neuromyelitis optica (NMO) and NMO spectrum disorders. J Neurol Neurosurg Psychiatry 84:922–930 2. Pittock SJ, Lennon VA, Krecke K, Wingerchuk DM, Lucchinetti CF, Weinshenker BG (2006) Brain abnormalities in neuromyelitis optica. Arch Neurol 63:390–396 3. Flanagan EP, Weinshenker BG, Krecke KN, Lennon VA, Lucchinetti CF, McKeon A, Wingerchuk DM, Shuster EA, Jiao Y, Horta ES, Pittock SJ (2015) Short myelitis lesions in aquaporin4-IgG-positive neuromyelitis optica spectrum disorders. JAMA Neurol 72:81–87 4. Sato DK, Nakashima I, Takahashi T, Misu T, Waters P, Kuroda H, Nishiyama S, Suzuki C, Takai Y, Fujihara K, Itoyama Y, Aoki M (2013) Aquaporin-4 antibody-positive cases beyond current diagnostic criteria for NMO spectrum disorders. Neurology 80:2210–2216 5. Wang J, Li X, Zhang DQ, Yang CS, Qi Y, Li MS, Shi FD, Yang L (2014) Quantitative analysis of aquaporin-4 antibody in longitudinally extensive transverse myelitis. J Neuroimmunol 278:26–29
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LETTER TO THE EDITOR
Severe aquaporin-4 IgG-positive neuromyelitis optica spectrum disorder with short myelitis lesion and favourable outcome Gianni Masi1 • Chiara Cioni1 • Umberto Arrigucci2 • Alfonso Cerase2 Pasquale Annunziata1
•
Received: 11 March 2015 / Accepted: 3 June 2015 / Published online: 7 June 2015 Ó Springer-Verlag Italia 2015
Keywords Neuromyelitis optica Neuromyelitis optica spectrum disorder Aquaporin-4 Aquaporin-4 IgG Transverse myelitis Autoimmunity Neuromyelitis optica spectrum disorders (NMOSD) refer to limited forms of neuromyelitis optica (NMO) including recurrent or simultaneous bilateral optic neuritis (ON) or longitudinally extensive transverse myelitis (LETM), extending three or more vertebral segments, unified by the seropositivity for anti-aquaporin-4 (AQP4) antibody [1]. Myelitis extending less than three vertebral segments in NMOSD has recently been recognized as a rare variant with not well-established clinical outcome. We here report a case of severe AQP4-IgG-positive NMOSD with short myelitis lesion and favourable outcome. A 24-year-old woman experienced in May 2011 sudden visual loss and ocular pain in left eye showing visual acuity \1/10 and significant P100 amplitude decrease and latency prolongation. Apart visual loss, neurological examination was unremarkable. Brain and orbits magnetic resonance imaging (MRI) revealed only an inflammatory injury to the left optic nerve. Left retrobulbar ON was diagnosed and
Electronic supplementary material The online version of this article (doi:10.1007/s10072-015-2277-z) contains supplementary material, which is available to authorized users. & Pasquale Annunziata [email protected] 1
Department of Medicine, Surgery and Neurosciences, Clinical Neuroimmunology Unit, University of Siena, Siena, Italy
2
Unit of Neuroimaging and Neurointervention, Medical School, Siena, Italy
treated with high-dose intravenous methylprednisolone (IVMP) for 5 days resulting in complete recovery of the visual acuity in several months. In October 2011, she presented with paresthesias affecting upper limbs, in the absence of any sensory level and motor impairment, and brain MRI showed three gadolinium-enhancing lesions located at left frontal horn periventricular white matter, genu of corpus callosum and within the cervical spinal cord C2–C3 (Fig. 1a, b). Cerebrospinal fluid analysis revealed no alterations including the absence of oligoclonal bands. Search for serum anti-AQP4 IgG with a commercial indirect immunofluorescence transfected cell-based assay, showing reliable sensitivity [1, 2, supplementary file], was positive. In May 2012, internuclear ophthalmoplegia (INO) and severe vertigo occurred, and brain MRI documented a slight FLAIR hyperintensity adjacent to the fourth ventricle floor (Fig. 1c, d). The clinical features reversed after an IVMP 5-day course. In July 2012, the patient experienced numbness and progressive weakness at both legs. Neurological examination revealed paraparesis with walking difficulty, rapidly evolving to paraplegia, as well as sensory loss below D5 thoracic level and urinary retention. TM was diagnosed, and spinal cord MRI showed a gadolinium-enhancing short lesion longitudinally extending only over two vertebral segments (Fig. 2a), as well as brain MRI revealed a large FLAIR hyperintensity adjacent to the fourth ventricle floor (Fig. 1e). The diagnosis of NMOSD was therefore supported [1]. Acute-phase treatment consisted of IVMP (1 g/day for 5 days) followed by two cycles of IV immunoglobulin (0.4 g/kg/day for 5 days) over 2 months. Motor, sensory and bladder dysfunctions greatly improved: at the end of August 2012, she was able to walk with bilateral assistance and, in October 2012, after an intensive physical rehabilitation, she was able to walk without aid. As maintenance therapy, oral azathioprine
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1926
Fig. 1 Two gadolinium-enhancing lesions in genu of corpus callosum and in the cervical spinal cord C2–C3 (arrows, a) and another gadolinium-enhancing lesion in left frontal horn periventricular white matter (arrow, b). Brain FLAIR hyperintensity adjacent to the fourth ventricle floor with bilateral involvement of facial nerve colliculus Fig. 2 Spinal cord new swollen lesion longitudinally extending from D3 to D4 with gadolinium enhancement (arrow, a). Follow-up MRI revealed no gadolinium enhancement of the thoracic spinal cord lesion (b)
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Neurol Sci (2015) 36:1925–1927
and likely, of medial longitudinal fasciculus (arrows, c) as well as median raphe (arrow, d). Brain large FLAIR hyperintensity adjacent to the fourth ventricle floor (arrows, e). Follow-up MRI revealed disappearance of the fourth ventricular lesion (f)
Neurol Sci (2015) 36:1925–1927
1927
patients with STM respect to those with LETM has been reported suggesting lower clinical severity [3]. Conversely, our patient with STM was paraplegic at nadir although resulting in a favourable outcome, characterized by complete recovery of the motor autonomy maintained after 29-month follow-up. The major severity of clinical features in our patient at the time of STM could depend on the underlying inflammatory process even though we cannot exclude that early MRI might miss a longer medullar lesion. In conclusion, our report highlights the need of searching for serum anti-AQP4 antibody not only in the presence of LETM, but also when a STM is detected and suggests that NMOSD with STM may have a favourable prognosis even with a severe clinical manifestation at nadir. Fig. 3 Progression over time (months) of the impairment assessed with modified Rankin scale score, clinical features and related treatment. IV MP intravenous methylprednisolone, IV Igs intravenous immunoglobulins
(100 mg daily) and prednisone (0.5 mg/kg daily) were started. The patient did not experience new relapses (Fig. 3). In December 2012, an MRI scan demonstrated atrophic evolution of the thoracic spinal cord lesion with no gadolinium enhancement (Fig. 2b) and disappearance of the fourth ventricular lesion (Fig. 1f) as well as anti-AQP4 seropositivity was still detected. At the last follow-up, in December 2014, neurological examination was normal and spinal cord lesion further reduced at MRI (data not shown). In our case, after a monophasic ON, NMOSD diagnosis was supported by AQP4 IgG seropositivity associated with a short myelitis lesion as well as a brain lesion in a periependymal area, very rich in AQP4 and atypical for multiple sclerosis (MS) [1, 2]. INO, due to demyelination of medial longitudinal fasciculus, has frequently been reported in MS but seldom in NMO and NMOSD [3, 4, supplementary file]. LETM is the typical myelitis in NMOSD, but short medullar lesions, not extending three vertebral segments, can occur in NMOSD with frequency ranging from 5.5 % [4] to 14 % [3]. In our patient, short transverse myelitis (STM) occurred 14 months after monophasic ON lacking in any clinical predictor of AQP4 IgG seropositivity identified in STM such as older age, personal history of autoimmunity and tonic spasms [3]. In LETM, a correlation between serum anti-AQP4 antibody levels and number of segments of spinal cord involved has recently been found [5]. Less need of aid to walk at nadir in
Conflict of interest of interest.
The authors declare that they have no conflict
Research involving human participants and/or animals All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with 1964 Helsinki declaration and its later amendments or comparable ethical standards. However, for this case report, formal consent is not required. Informed consent
Informed consent was obtained from the patient.
References 1. Jacob A, McKeon A, Nakashima I, Sato DK, Elsone L, Fujihara K, de Seze J (2013) Current concept of neuromyelitis optica (NMO) and NMO spectrum disorders. J Neurol Neurosurg Psychiatry 84:922–930 2. Pittock SJ, Lennon VA, Krecke K, Wingerchuk DM, Lucchinetti CF, Weinshenker BG (2006) Brain abnormalities in neuromyelitis optica. Arch Neurol 63:390–396 3. Flanagan EP, Weinshenker BG, Krecke KN, Lennon VA, Lucchinetti CF, McKeon A, Wingerchuk DM, Shuster EA, Jiao Y, Horta ES, Pittock SJ (2015) Short myelitis lesions in aquaporin4-IgG-positive neuromyelitis optica spectrum disorders. JAMA Neurol 72:81–87 4. Sato DK, Nakashima I, Takahashi T, Misu T, Waters P, Kuroda H, Nishiyama S, Suzuki C, Takai Y, Fujihara K, Itoyama Y, Aoki M (2013) Aquaporin-4 antibody-positive cases beyond current diagnostic criteria for NMO spectrum disorders. Neurology 80:2210–2216 5. Wang J, Li X, Zhang DQ, Yang CS, Qi Y, Li MS, Shi FD, Yang L (2014) Quantitative analysis of aquaporin-4 antibody in longitudinally extensive transverse myelitis. J Neuroimmunol 278:26–29
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