JNS-13548; No of Pages 2 Journal of the Neurological Sciences xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Neuromyelitis optica spectrum disorder initiated with hemiageusia and pruritus: A case report Keywords: Neuromyelitis optica spectrum disorder Hypogeusia Pruritus
1. Introduction Neuromyelitis optica (NMO) is a severe inflammatory and demyelinating disorder of the central nervous system. The traditional concept of NMO restricted involvement to the optic nerve and spinal cord. The discovery of neuromyelitis optica immunoglobulin G (NMO-IgG), a specific antibody to aquaporin 4 (AQP4) [1], has greatly changed the traditional concept of NMO. Based on the seropositivity of NMO-IgG, the term “neuromyelitis optica spectrum disorders (NMOSD)” evolved. NMOSD includes definitive NMO, monophasic or recurrent longitudinally extensive transverse myelitis, bilateral simultaneous or recurrent neuromyelitis optica, brainstem disorders and hypothalamic disorders [2]. Now it's well recognized that brainstem involvement is common in NMO/NMOSD. Some NMO/NMOSD patients may initiate with brainstem symptoms; the most common of them are intractable hiccup and vomiting. Compared with these two symptoms, pruritus is less frequent [3]. Furthermore, some rare symptoms may be seen in NMO/ NMOSD. For example, hypogeusia was first described in a case of NMOSD in 2013 [4]. Here, we describe a case of NMOSD presenting with hemiageusia and pruritus before myelitis developing. We aim to emphasize that hypogeusia, a well-described symptom in multiple sclerosis and other disorders, might be under-recognized in NMO/NMOSD. Furthermore, hypogeusia may coexist with other brainstem symptom. 2. Case report A previously healthy 20-year-old woman presented with hypogeusia on the entire left side of the tongue and continuous pruritus on the left face without rash. Two weeks later, she developed transient diplopia lasting for 4 to 5 days. Three weeks later, she developed numbness and weakness in all four limbs. She was admitted to our hospital one month after onset. Neurological examination revealed diminished sensation to four fundamental tastes in both anterior and posterior left side of the tongue, a thoracic (T4) sensory level to pinprick, decreased vibratory and proprioceptive sensation in all limbs. Muscle strength was grade four out of five in all limbs with hyperreflexia and bilateral positive Babinski sign.
Brain MRI revealed hypointense lesions on T1 weighted image and hyperintense lesions on T2 weighted image in the right side of medulla oblongata, left midpontine tegmentum, and periaqueduct without contrast enhancement (Fig. 1). Spinal cord MRI showed a longitudinally extensive hyperintense lesion on T2 weighted image involving C1 to C5 (Fig. 1). Routine blood test and chemistry analysis including liver and renal function were unremarkable. Autoimmune markers including antinuclear antibody, anti-dsDNA, and rheumatoid factor were negative. Thyroid function was normal. A cerebrospinal fluid analysis (CSF) showed 3 white blood cells, normal protein and glucose level, and normal IgG index. No oligoclonal bands were detected. All indicators of bacteria and viruses were negative. AQP4 antibodies were detected in the serum but not in CSF using a cell-binding assay. A diagnosis of NMOSD was made. The patient was treated with intravenous methylprednisolone 1 g/day for 5 days, then oral prednisone and azathioprine. She had full recovery, and was discharged. At six-month follow-up, she remained well and experienced no relapse. Repeat brain MRI was not performed. Repeat spinal cord MRI showed obvious resolution of the lesion (Fig. 1).
3. Discussion Our case initiated with hypogeusia and pruritus, and then developed acute transverse myelitis. Brain MRI revealed multiple lesions in the brainstem. Spinal cord MRI showed a longitudinally extensive lesion involving C1 to C5. AQP4 antibodies were detected in the serum. The patient fulfilled the diagnostic criteria of NMOSD. Pruritus was previously described in patients with NMO. In a cohort of 44 NMO patients, 12 (27.3%) reported pruritus. In three patients, pruritus was the first symptom of a relapse. In one patient, pruritus was the very first symptom of the index episode of NMO. 5 out of 12 (41.67%) patients experienced continuous pruritus [5]. In a multicenter study of 258 patients with NMO or NMOSD, brainstem signs were observed in 81 patients. The most frequently observed signs were vomiting (33.1%), hiccups (22.3%), oculomotor dysfunction (19.8%), and pruritus (12.4%), followed by hearing loss, facial palsy, vertigo or vestibular ataxia, trigeminal neuralgia and other cranial nerve signs [3]. Hypogeusia, however, was rarely reported in NMO/NMOSD, although it was well described in multiple sclerosis [6] and other disorder. Fibers from the lingual nerve and the glossopharyngeal nerve (providing taste sensation from the anterior two thirds and the posterior third of the tongue, respectively) terminate in the nucleus solitarius. The second order gustatory fibers from the nucleus solitarius ascend ipsilaterally in the central tegmental tract before synapsing in the thalamus. Involvement of the nucleus solitarius or the central tegmental tract may cause ipsilateral taste disturbances. In our case, the lesion in the left midpontine tegmentum seen on MRI may be responsible for the ipsilateral hemiageusia. It was similar to the lesion described by Iones and Howard [4]. Compared with hypogeusia, pruritus was more common in NMO/ NMOSD. The first order pruritus-related neurons locate in the dorsal
http://dx.doi.org/10.1016/j.jns.2014.11.034 0022-510X/© 2014 Published by Elsevier B.V.
Please cite this article as: Wang R, et al, , J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.11.034
2
Letter to the Editor
horn of the spinal cord transmit through the spinothalamic tract and thalamus to the primary somatosensory cortex. Similar afferent pathways exist in the trigeminal sensory system. In NMO/NMOSD patients, involvement of the dorsal horn of the spinal cord, the spinal nucleus of trigeminal nerve or periaqueductal pathways could cause pruritus. In our case, it may be associated with involvement of the spinal nucleus of trigeminal nerve caused by the left midpontine tegmentum lesion. In conclusion, our case confirmed that hypogeusia as a rare brainstem symptom may occur in NMOSD. It also may coexist with other brainstem symptom. NMO/NMOSD should be considered in the diagnosis of hypogeusia. Conflict of interest The authors declare that there are no conflicts of interest. References [1] Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004;364:2106–12. [2] Jacob A, McKeon A, Nakashima I, Sato DK, Elsone L, Fujihara K, et al. Current concept of neuromyelitis optica (NMO) and NMO spectrum disorders. J Neurol Neurosurg Psychiatry 2013;84:922–30. [3] Kremer L, Mealy M, Jacob A, Nakashima I, Cabre P, Bigi S, et al. Brainstem manifestations in neuromyelitis optica: a multicenter study of 258 patients. Mult Scler 2014;20: 843–9. [4] Iones A, Howard J. Hypogeusia as a symptom of neuromyelitis optica spectrum disorder. Mult Scler 2013;19:1548–9. [5] Elsone L, Townsend T, Mutch K, Das K, Boggild M, Nurmikko T, et al. Neuropathic pruritus (itch) in neuromyelitis optica. Mult Scler 2013;19:475–9. [6] Combarros O, Sanchez-Juan P, Berciano J. Hemiageusia from an ipsilateral multiple sclerosis plaque at the midpontine tegmentum. J Neurol Neurosurg Psychiatry 2000;68:796. [7] Sun YG, Zhao ZQ, Meng XL, Yin J, Liu XY, Chen ZF. Cellular basis of itch sensation. Science 2009;325:1531–4.
RuiJin Wang⁎ Dong Qi YongBo Zhang Department of Neurology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-An Road, Xicheng District, Beijing 100050, People's Republic of China *Corresponding author. Tel.: +86 1063139810. E-mail address: [email protected]. Fig. 1. T1 hypointense and T2 hyperintense lesion in the right side of medulla oblongata (a, b); T1 hypointense and T2 hyperintense lesion in the left midpontine tegmentum (c, d); T1 hypointense and T2 hyperintense lesion in the periaqueduct (e, f); a longitudinally extensive hyperintense lesion on T2 involving C1 to C5 (g); obvious resolution of the spinal cord lesion (h).
root ganglion. In the spinal cord, the gastrin-releasing protein receptorbearing neurons in the Lamina 1 of the dorsal horn seem highly specific for the transmission of pruritus [7]. Afferent impulses from the dorsal
Please cite this article as: Wang R, et al, , J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.11.034
12 October 2014 Available online xxxx
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Neuromyelitis optica spectrum disorder initiated with hemiageusia and pruritus: A case report Keywords: Neuromyelitis optica spectrum disorder Hypogeusia Pruritus
1. Introduction Neuromyelitis optica (NMO) is a severe inflammatory and demyelinating disorder of the central nervous system. The traditional concept of NMO restricted involvement to the optic nerve and spinal cord. The discovery of neuromyelitis optica immunoglobulin G (NMO-IgG), a specific antibody to aquaporin 4 (AQP4) [1], has greatly changed the traditional concept of NMO. Based on the seropositivity of NMO-IgG, the term “neuromyelitis optica spectrum disorders (NMOSD)” evolved. NMOSD includes definitive NMO, monophasic or recurrent longitudinally extensive transverse myelitis, bilateral simultaneous or recurrent neuromyelitis optica, brainstem disorders and hypothalamic disorders [2]. Now it's well recognized that brainstem involvement is common in NMO/NMOSD. Some NMO/NMOSD patients may initiate with brainstem symptoms; the most common of them are intractable hiccup and vomiting. Compared with these two symptoms, pruritus is less frequent [3]. Furthermore, some rare symptoms may be seen in NMO/ NMOSD. For example, hypogeusia was first described in a case of NMOSD in 2013 [4]. Here, we describe a case of NMOSD presenting with hemiageusia and pruritus before myelitis developing. We aim to emphasize that hypogeusia, a well-described symptom in multiple sclerosis and other disorders, might be under-recognized in NMO/NMOSD. Furthermore, hypogeusia may coexist with other brainstem symptom. 2. Case report A previously healthy 20-year-old woman presented with hypogeusia on the entire left side of the tongue and continuous pruritus on the left face without rash. Two weeks later, she developed transient diplopia lasting for 4 to 5 days. Three weeks later, she developed numbness and weakness in all four limbs. She was admitted to our hospital one month after onset. Neurological examination revealed diminished sensation to four fundamental tastes in both anterior and posterior left side of the tongue, a thoracic (T4) sensory level to pinprick, decreased vibratory and proprioceptive sensation in all limbs. Muscle strength was grade four out of five in all limbs with hyperreflexia and bilateral positive Babinski sign.
Brain MRI revealed hypointense lesions on T1 weighted image and hyperintense lesions on T2 weighted image in the right side of medulla oblongata, left midpontine tegmentum, and periaqueduct without contrast enhancement (Fig. 1). Spinal cord MRI showed a longitudinally extensive hyperintense lesion on T2 weighted image involving C1 to C5 (Fig. 1). Routine blood test and chemistry analysis including liver and renal function were unremarkable. Autoimmune markers including antinuclear antibody, anti-dsDNA, and rheumatoid factor were negative. Thyroid function was normal. A cerebrospinal fluid analysis (CSF) showed 3 white blood cells, normal protein and glucose level, and normal IgG index. No oligoclonal bands were detected. All indicators of bacteria and viruses were negative. AQP4 antibodies were detected in the serum but not in CSF using a cell-binding assay. A diagnosis of NMOSD was made. The patient was treated with intravenous methylprednisolone 1 g/day for 5 days, then oral prednisone and azathioprine. She had full recovery, and was discharged. At six-month follow-up, she remained well and experienced no relapse. Repeat brain MRI was not performed. Repeat spinal cord MRI showed obvious resolution of the lesion (Fig. 1).
3. Discussion Our case initiated with hypogeusia and pruritus, and then developed acute transverse myelitis. Brain MRI revealed multiple lesions in the brainstem. Spinal cord MRI showed a longitudinally extensive lesion involving C1 to C5. AQP4 antibodies were detected in the serum. The patient fulfilled the diagnostic criteria of NMOSD. Pruritus was previously described in patients with NMO. In a cohort of 44 NMO patients, 12 (27.3%) reported pruritus. In three patients, pruritus was the first symptom of a relapse. In one patient, pruritus was the very first symptom of the index episode of NMO. 5 out of 12 (41.67%) patients experienced continuous pruritus [5]. In a multicenter study of 258 patients with NMO or NMOSD, brainstem signs were observed in 81 patients. The most frequently observed signs were vomiting (33.1%), hiccups (22.3%), oculomotor dysfunction (19.8%), and pruritus (12.4%), followed by hearing loss, facial palsy, vertigo or vestibular ataxia, trigeminal neuralgia and other cranial nerve signs [3]. Hypogeusia, however, was rarely reported in NMO/NMOSD, although it was well described in multiple sclerosis [6] and other disorder. Fibers from the lingual nerve and the glossopharyngeal nerve (providing taste sensation from the anterior two thirds and the posterior third of the tongue, respectively) terminate in the nucleus solitarius. The second order gustatory fibers from the nucleus solitarius ascend ipsilaterally in the central tegmental tract before synapsing in the thalamus. Involvement of the nucleus solitarius or the central tegmental tract may cause ipsilateral taste disturbances. In our case, the lesion in the left midpontine tegmentum seen on MRI may be responsible for the ipsilateral hemiageusia. It was similar to the lesion described by Iones and Howard [4]. Compared with hypogeusia, pruritus was more common in NMO/ NMOSD. The first order pruritus-related neurons locate in the dorsal
http://dx.doi.org/10.1016/j.jns.2014.11.034 0022-510X/© 2014 Published by Elsevier B.V.
Please cite this article as: Wang R, et al, , J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.11.034
2
Letter to the Editor
horn of the spinal cord transmit through the spinothalamic tract and thalamus to the primary somatosensory cortex. Similar afferent pathways exist in the trigeminal sensory system. In NMO/NMOSD patients, involvement of the dorsal horn of the spinal cord, the spinal nucleus of trigeminal nerve or periaqueductal pathways could cause pruritus. In our case, it may be associated with involvement of the spinal nucleus of trigeminal nerve caused by the left midpontine tegmentum lesion. In conclusion, our case confirmed that hypogeusia as a rare brainstem symptom may occur in NMOSD. It also may coexist with other brainstem symptom. NMO/NMOSD should be considered in the diagnosis of hypogeusia. Conflict of interest The authors declare that there are no conflicts of interest. References [1] Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004;364:2106–12. [2] Jacob A, McKeon A, Nakashima I, Sato DK, Elsone L, Fujihara K, et al. Current concept of neuromyelitis optica (NMO) and NMO spectrum disorders. J Neurol Neurosurg Psychiatry 2013;84:922–30. [3] Kremer L, Mealy M, Jacob A, Nakashima I, Cabre P, Bigi S, et al. Brainstem manifestations in neuromyelitis optica: a multicenter study of 258 patients. Mult Scler 2014;20: 843–9. [4] Iones A, Howard J. Hypogeusia as a symptom of neuromyelitis optica spectrum disorder. Mult Scler 2013;19:1548–9. [5] Elsone L, Townsend T, Mutch K, Das K, Boggild M, Nurmikko T, et al. Neuropathic pruritus (itch) in neuromyelitis optica. Mult Scler 2013;19:475–9. [6] Combarros O, Sanchez-Juan P, Berciano J. Hemiageusia from an ipsilateral multiple sclerosis plaque at the midpontine tegmentum. J Neurol Neurosurg Psychiatry 2000;68:796. [7] Sun YG, Zhao ZQ, Meng XL, Yin J, Liu XY, Chen ZF. Cellular basis of itch sensation. Science 2009;325:1531–4.
RuiJin Wang⁎ Dong Qi YongBo Zhang Department of Neurology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-An Road, Xicheng District, Beijing 100050, People's Republic of China *Corresponding author. Tel.: +86 1063139810. E-mail address: [email protected]. Fig. 1. T1 hypointense and T2 hyperintense lesion in the right side of medulla oblongata (a, b); T1 hypointense and T2 hyperintense lesion in the left midpontine tegmentum (c, d); T1 hypointense and T2 hyperintense lesion in the periaqueduct (e, f); a longitudinally extensive hyperintense lesion on T2 involving C1 to C5 (g); obvious resolution of the spinal cord lesion (h).
root ganglion. In the spinal cord, the gastrin-releasing protein receptorbearing neurons in the Lamina 1 of the dorsal horn seem highly specific for the transmission of pruritus [7]. Afferent impulses from the dorsal
Please cite this article as: Wang R, et al, , J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.11.034
12 October 2014 Available online xxxx
