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Recurrent pseudotumoral relapses in multiple sclerosis: a case report
Author’s Accepted Manuscript RECURRENT PSEUDOTUMORAL RELAPSES IN MULTIPLE SCLEROSIS: A CASE REPORT Lucía Lebrato Hernández, María Díaz Sánchez, María Prieto León, Nuria Alicia Cerdá Fuertes, Antonio José Uclés Sánchez, José Luis Casado Chocán www.elsevier.com/locate/msard
PII: DOI: Reference:
S2211-0348(18)30092-0 https://doi.org/10.1016/j.msard.2018.03.006 MSARD801
To appear in: Multiple Sclerosis and Related Disorders Received date: 22 August 2017 Revised date: 18 February 2018 Accepted date: 4 March 2018 Cite this article as: Lucía Lebrato Hernández, María Díaz Sánchez, María Prieto León, Nuria Alicia Cerdá Fuertes, Antonio José Uclés Sánchez and José Luis Casado Chocán, RECURRENT PSEUDOTUMORAL RELAPSES IN MULTIPLE SCLEROSIS: A CASE REPORT, Multiple Sclerosis and Related Disorders, https://doi.org/10.1016/j.msard.2018.03.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
RECURRENT PSEUDOTUMORAL RELAPSES IN MULTIPLE SCLEROSIS: A CASE REPORT. Lucía Lebrato Hernández, María Díaz Sánchez*, María Prieto León, Nuria Alicia Cerdá Fuertes, Antonio José Uclés Sánchez, José Luis Casado Chocán 1
Unidad de Gestión Clínica de Neurociencias, Servicio de Neurología del Hospital Universitario Virgen del
Rocío, Seville, Spain *Corresponding Author's Institution: Unidad de Gestión Clínica de Neurociencias, Servicio de Neurología del Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Seville, Spain; Tel.: +34955012593. [email protected].
Abstract: Objetives: Multiple sclerosis (MS) is the most common chronic disabling disease of the central nervous system (CNS) in young adults. It is characterized by the presence of multiple demyelinating inflammatory lesions disseminated in the CNS. Pseudotumoral lesions (PL) are rarely observed in patients with MS. Methods: These atypical lesions can pose a diagnostic problem, especially when they are present at disease onset. Results: Most MS patients with PLs only have a single episode throughout their disease course, which reflects its low tendency of recurrence. Conclusions: We report the rare case of a 34-year-old MS patient who suffered from recurrent pseudotumoral episodes during follow-up.
Keywords: Multiple Sclerosis; Pseudotumoral lesion; Pseudotumoral relapse.
1. BACKGROUND
Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system and exhibits a variety of clinical and radiological manifestations. Demyelinating lesions observed in MS are typically ovoid and do not commonly exceed 0.6cm in diameter. However, atypical MS lesions showing an unusual size, morphology or pattern of contrast uptake are occasionally identified1,2. Pseudotumoral lesions (PL) represent one of these atypical manifestations. These lesions normally present as a large mass located in the cerebral hemispheres with perilesional oedema, mass effect and an incomplete ring contrast enhancement1-5]. Their clinical picture also includes atypical neurological symptoms which
distinguish them from conventional MS relapses, such as: headache, effects on cognitive functions, mental confusion, hemiparesis, visual disorders and epileptic seizures3-5]. PLs have been described not only at disease onset but also during follow-up, typically as an isolated event. Recurrent pseudotumoral episodes are considered a rare condition in MS 4,5]. We will describe the case of a patient diagnosed with MS who suffered from two pseudotumoral episodes.
2. CASE REPORT
A 34-year-old healthy woman was admitted to our hospital because of a progressive episode of hypoesthesia of her four limbs and the left side of her face, and left hemiparesis. The patient had no preceding history of fever and had no signs of infection. She denied having had contact with animals or having recently received vaccinations. In addition, she denied having toxic habits or having received any treatment. Magnetic resonance imaging (MRI) of the brain showed two mass lesions greater than 2 cm in diameter, one in the subcortical white matter of the right fronto-parietal lobe and the other located in the periventricular area of the left parietal lobe. Both lesions were hyperintense on T2 with surrounding oedema and minimal gadolinium uptake. As well as these, nine typical demyelinating lesions were identified, scattered throughout the periventricular and juxtacortical regions. A peripheral blood examination that included blood count, biochemistry, thyroid hormones, anti-aquaporine-4 antibodies, immunological and serological examinations was normal. The cerebrospinal fluid analysis was also normal and oligoclonal IgG bands were absent. The patient recovered almost entirely after receiving a standard corticoid therapy regimen. No brain biopsy was performed because of the strong suspicion of an inflammatory demyelinating disease. Six months later, the patient suffered from a spinal cord relapse and the diagnosis of relapsing-remitting MS was established. At that time, she started glatiramer acetate treatment. However, the patient was readmitted to our hospital one year later with a subacute episode of inattention, mental confusion, right homonymous hemianopia and persistent headache. A new MRI revealed a new large demyelinating lesion located in the subcortical white matter of the left parieto-occipital lobe with extensive peripheral oedema and open ring enhancement at its centre (figures 1a- 1b). Once again, the patient received a regimen of high steroid doses, but she only experienced a partial recovery on this occasion. One month later, the patient was switched from glatiramer acetate to fingolimod and she has been relapse-free since then. During the follow-up, a control MRI scan showed a marked reduction in lesion size of the last PL with disappearance of contrast uptake.
3. DISCUSSION
PLs are infrequently observed in patients with MS. Due to their rarity, they have scarcely been described in literature, and their clinical behaviour and exact management remain unknown to
clinicians. Their frequency is uncertain but a prevalence of 3 cases per million inhabitants per year has been estimated3,4. The pseudotumoral episodes have been described more commonly in women, in the second and third decades of life4. The definition of PL comes from its imaging picture. Although a minimum diameter has not been rigorously defined, a limit has been conventionally established at 2cm3. These lesions are characterized by hyperintensity on T2-weighted images which often corresponds to hypointensity on T1-weighted images. They generally have a round shape, with regular borders, perilesional oedema and mild mass effect. PLs are mainly located in the subcortical regions of cerebral hemispheres. If active, they typically show contrast enhancement, the most common pattern being in the form of an incomplete ring3-5. Their clinical picture is variable in relation to the location of the lesion, but includes atypical features that differentiate them from conventional MS relapses. In this way, the appearance of persistent headache, cognitive dysfunction, mental confusion, hemiparesis and hemianopia has been described, as it occurred in our patient3,4,5]. PLs can represent a diagnostic challenge especially when they appear isolated at disease onset. Main differential diagnosis must include tumours and abscesses. However, acute disseminated encephalomyelitis must also be considered when several PLs are observed on the same scan, as was the case in our patient’s first relapse. Clinical evolution, cerebrospinal fluid analysis, nonconventional MRI techniques findings and radiological response to steroid treatment might allow us to determine the diagnosis more specifically4-5]. The presence of additional typical demyelinating plaques also assists in the diagnosis of MS4,5]. In this regard, our patient’s MRI scans showed other typical demyelinating lesions (figure 1c), apart from the PLs, which fulfilled MRI criteria for dissemination in space. Nevertheless, brain biopsy is occasionally needed to reveal the real nature of the lesion. In relation to its prognosis, good recovery after steroids therapy was reported by some authors1,4. The great inflammatory component of PLs, demonstrated in histopathologic studies1,4, could explain this good response. However, other authors observed that the cessation of PL activity was often incomplete and the response to steroids was modest4. Significant response to plasmapheresis has been described in some studies. In addition, most MS patients suffered from a unique pseudotumoral event which reflects its low tendency for recurrence4,5. Given this fact, what is really remarkable in our case is the appearance of recurrent PLs in the same patient during follow-up. In conclusion, PLs can pose a diagnostic challenge because their clinical and radiological manifestation overlaps with the findings of tumor and infectious processes. Pseudotumoral episodes have different neurological symptoms from conventional MS relapses. Although it is a rare condition, recurrent PLs can appear in MS patients like this case report illustrates.
AUTHOR DECLARATION
We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property.
We understand that the Corresponding Author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). She is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the Corresponding Author
REFERENCES 1. Seewann A, Enzinger C, Filippi M, Barkhof F, Rovira A, Gass A, et al. MRI
characteristics of atypical idiopathic inflammatory demyelinating lesions of the brain. A review of reported findings. J Neurol 2008; 255: 1–10. 2. Wallner-Blazek M, Rovira A, Fillippi M, Rocca MA, Miller DH, Schmierer K, et al. Atypical idiopathic inflammatory demyelinating lesions: prognostic implications and relation to multiple sclerosis. J Neurol 2013; 260: 2016–2022. 3. Altintas A, Petek B, Isik N, Terzi M, Bolukbasi F, Tavsanli M, et al. Clinical and radiologica characteristics of tumefactive demyelinating lesions: follow-up study. Mult Scler. 2012. 18: 1448-53. 4. Comi G. Multiple sclerosis: pseudotumoral forms. Neurol Sci 2004;25 (Suppl 4):S374-
S379. 5. Mauri Fábrega L, Díaz Sánchez M, Casado Chocán JL, Uclés Sanchez AJ.
Pseudotumoral forms of multiple sclerosis: report of 14 cases and review of the literature. Eur Neurol. 2014;72:72-78
Figure 1. MRI from the second pseudotumoral episode 1a: Axial FLAIR image showing a large hyperintense left occipito parietal pseudotumoral lesion. 1b: On T1-weighted image after the injection of Gadolinium it appears as a hypointense lesion with open ring enhancement at the centre. 1c: Axial FLAIR image showing other typical periventricular demyelinating lesions.
Highlights
-
Pseudotumoral demyelinating lesions have a minimal diameter greater than 2 cm. Their clinical picture includes atypical neurological symptoms. They represent a diagnostic challenge especially when they appear isolated. Recurrent pseudotumoral episodes are a rare condition in multiple sclerosis.
PII: DOI: Reference:
S2211-0348(18)30092-0 https://doi.org/10.1016/j.msard.2018.03.006 MSARD801
To appear in: Multiple Sclerosis and Related Disorders Received date: 22 August 2017 Revised date: 18 February 2018 Accepted date: 4 March 2018 Cite this article as: Lucía Lebrato Hernández, María Díaz Sánchez, María Prieto León, Nuria Alicia Cerdá Fuertes, Antonio José Uclés Sánchez and José Luis Casado Chocán, RECURRENT PSEUDOTUMORAL RELAPSES IN MULTIPLE SCLEROSIS: A CASE REPORT, Multiple Sclerosis and Related Disorders, https://doi.org/10.1016/j.msard.2018.03.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
RECURRENT PSEUDOTUMORAL RELAPSES IN MULTIPLE SCLEROSIS: A CASE REPORT. Lucía Lebrato Hernández, María Díaz Sánchez*, María Prieto León, Nuria Alicia Cerdá Fuertes, Antonio José Uclés Sánchez, José Luis Casado Chocán 1
Unidad de Gestión Clínica de Neurociencias, Servicio de Neurología del Hospital Universitario Virgen del
Rocío, Seville, Spain *Corresponding Author's Institution: Unidad de Gestión Clínica de Neurociencias, Servicio de Neurología del Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Seville, Spain; Tel.: +34955012593. [email protected].
Abstract: Objetives: Multiple sclerosis (MS) is the most common chronic disabling disease of the central nervous system (CNS) in young adults. It is characterized by the presence of multiple demyelinating inflammatory lesions disseminated in the CNS. Pseudotumoral lesions (PL) are rarely observed in patients with MS. Methods: These atypical lesions can pose a diagnostic problem, especially when they are present at disease onset. Results: Most MS patients with PLs only have a single episode throughout their disease course, which reflects its low tendency of recurrence. Conclusions: We report the rare case of a 34-year-old MS patient who suffered from recurrent pseudotumoral episodes during follow-up.
Keywords: Multiple Sclerosis; Pseudotumoral lesion; Pseudotumoral relapse.
1. BACKGROUND
Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system and exhibits a variety of clinical and radiological manifestations. Demyelinating lesions observed in MS are typically ovoid and do not commonly exceed 0.6cm in diameter. However, atypical MS lesions showing an unusual size, morphology or pattern of contrast uptake are occasionally identified1,2. Pseudotumoral lesions (PL) represent one of these atypical manifestations. These lesions normally present as a large mass located in the cerebral hemispheres with perilesional oedema, mass effect and an incomplete ring contrast enhancement1-5]. Their clinical picture also includes atypical neurological symptoms which
distinguish them from conventional MS relapses, such as: headache, effects on cognitive functions, mental confusion, hemiparesis, visual disorders and epileptic seizures3-5]. PLs have been described not only at disease onset but also during follow-up, typically as an isolated event. Recurrent pseudotumoral episodes are considered a rare condition in MS 4,5]. We will describe the case of a patient diagnosed with MS who suffered from two pseudotumoral episodes.
2. CASE REPORT
A 34-year-old healthy woman was admitted to our hospital because of a progressive episode of hypoesthesia of her four limbs and the left side of her face, and left hemiparesis. The patient had no preceding history of fever and had no signs of infection. She denied having had contact with animals or having recently received vaccinations. In addition, she denied having toxic habits or having received any treatment. Magnetic resonance imaging (MRI) of the brain showed two mass lesions greater than 2 cm in diameter, one in the subcortical white matter of the right fronto-parietal lobe and the other located in the periventricular area of the left parietal lobe. Both lesions were hyperintense on T2 with surrounding oedema and minimal gadolinium uptake. As well as these, nine typical demyelinating lesions were identified, scattered throughout the periventricular and juxtacortical regions. A peripheral blood examination that included blood count, biochemistry, thyroid hormones, anti-aquaporine-4 antibodies, immunological and serological examinations was normal. The cerebrospinal fluid analysis was also normal and oligoclonal IgG bands were absent. The patient recovered almost entirely after receiving a standard corticoid therapy regimen. No brain biopsy was performed because of the strong suspicion of an inflammatory demyelinating disease. Six months later, the patient suffered from a spinal cord relapse and the diagnosis of relapsing-remitting MS was established. At that time, she started glatiramer acetate treatment. However, the patient was readmitted to our hospital one year later with a subacute episode of inattention, mental confusion, right homonymous hemianopia and persistent headache. A new MRI revealed a new large demyelinating lesion located in the subcortical white matter of the left parieto-occipital lobe with extensive peripheral oedema and open ring enhancement at its centre (figures 1a- 1b). Once again, the patient received a regimen of high steroid doses, but she only experienced a partial recovery on this occasion. One month later, the patient was switched from glatiramer acetate to fingolimod and she has been relapse-free since then. During the follow-up, a control MRI scan showed a marked reduction in lesion size of the last PL with disappearance of contrast uptake.
3. DISCUSSION
PLs are infrequently observed in patients with MS. Due to their rarity, they have scarcely been described in literature, and their clinical behaviour and exact management remain unknown to
clinicians. Their frequency is uncertain but a prevalence of 3 cases per million inhabitants per year has been estimated3,4. The pseudotumoral episodes have been described more commonly in women, in the second and third decades of life4. The definition of PL comes from its imaging picture. Although a minimum diameter has not been rigorously defined, a limit has been conventionally established at 2cm3. These lesions are characterized by hyperintensity on T2-weighted images which often corresponds to hypointensity on T1-weighted images. They generally have a round shape, with regular borders, perilesional oedema and mild mass effect. PLs are mainly located in the subcortical regions of cerebral hemispheres. If active, they typically show contrast enhancement, the most common pattern being in the form of an incomplete ring3-5. Their clinical picture is variable in relation to the location of the lesion, but includes atypical features that differentiate them from conventional MS relapses. In this way, the appearance of persistent headache, cognitive dysfunction, mental confusion, hemiparesis and hemianopia has been described, as it occurred in our patient3,4,5]. PLs can represent a diagnostic challenge especially when they appear isolated at disease onset. Main differential diagnosis must include tumours and abscesses. However, acute disseminated encephalomyelitis must also be considered when several PLs are observed on the same scan, as was the case in our patient’s first relapse. Clinical evolution, cerebrospinal fluid analysis, nonconventional MRI techniques findings and radiological response to steroid treatment might allow us to determine the diagnosis more specifically4-5]. The presence of additional typical demyelinating plaques also assists in the diagnosis of MS4,5]. In this regard, our patient’s MRI scans showed other typical demyelinating lesions (figure 1c), apart from the PLs, which fulfilled MRI criteria for dissemination in space. Nevertheless, brain biopsy is occasionally needed to reveal the real nature of the lesion. In relation to its prognosis, good recovery after steroids therapy was reported by some authors1,4. The great inflammatory component of PLs, demonstrated in histopathologic studies1,4, could explain this good response. However, other authors observed that the cessation of PL activity was often incomplete and the response to steroids was modest4. Significant response to plasmapheresis has been described in some studies. In addition, most MS patients suffered from a unique pseudotumoral event which reflects its low tendency for recurrence4,5. Given this fact, what is really remarkable in our case is the appearance of recurrent PLs in the same patient during follow-up. In conclusion, PLs can pose a diagnostic challenge because their clinical and radiological manifestation overlaps with the findings of tumor and infectious processes. Pseudotumoral episodes have different neurological symptoms from conventional MS relapses. Although it is a rare condition, recurrent PLs can appear in MS patients like this case report illustrates.
AUTHOR DECLARATION
We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property.
We understand that the Corresponding Author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). She is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the Corresponding Author
REFERENCES 1. Seewann A, Enzinger C, Filippi M, Barkhof F, Rovira A, Gass A, et al. MRI
characteristics of atypical idiopathic inflammatory demyelinating lesions of the brain. A review of reported findings. J Neurol 2008; 255: 1–10. 2. Wallner-Blazek M, Rovira A, Fillippi M, Rocca MA, Miller DH, Schmierer K, et al. Atypical idiopathic inflammatory demyelinating lesions: prognostic implications and relation to multiple sclerosis. J Neurol 2013; 260: 2016–2022. 3. Altintas A, Petek B, Isik N, Terzi M, Bolukbasi F, Tavsanli M, et al. Clinical and radiologica characteristics of tumefactive demyelinating lesions: follow-up study. Mult Scler. 2012. 18: 1448-53. 4. Comi G. Multiple sclerosis: pseudotumoral forms. Neurol Sci 2004;25 (Suppl 4):S374-
S379. 5. Mauri Fábrega L, Díaz Sánchez M, Casado Chocán JL, Uclés Sanchez AJ.
Pseudotumoral forms of multiple sclerosis: report of 14 cases and review of the literature. Eur Neurol. 2014;72:72-78
Figure 1. MRI from the second pseudotumoral episode 1a: Axial FLAIR image showing a large hyperintense left occipito parietal pseudotumoral lesion. 1b: On T1-weighted image after the injection of Gadolinium it appears as a hypointense lesion with open ring enhancement at the centre. 1c: Axial FLAIR image showing other typical periventricular demyelinating lesions.
Highlights
-
Pseudotumoral demyelinating lesions have a minimal diameter greater than 2 cm. Their clinical picture includes atypical neurological symptoms. They represent a diagnostic challenge especially when they appear isolated. Recurrent pseudotumoral episodes are a rare condition in multiple sclerosis.