Radiology case reports · 2024
Марбургский вариант множественного склероза: отчет о деле молодых женщин.
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Jameel Mohammed Alaa, Jamel Wameth Alaa, Hasan Alaa Jameel, Hammood Alkhuzaie Riyam Amer
Аннотация
Болезнь Марбурга (мягкий множественный склероз, MS) представляет собой редкий, острый вариант MS, который встречается преимущественно среди молодежи. Поскольку эта болезнь характеризуется редкостью, высокой заболеваемостью и смертностью, она нуждается в дальнейшей оценке, и опыт врачей играет определенную роль в лечении. Мы сообщаем о случае 15-летней женщины с прогрессивной слабостью по отношению к конечностям, гиперрефлексией и потерей ощущения в результате физического осмотра, лабораторных тестов и радиологических исследований. После лечения в ходе клинического посещения неулучшенность была признана в ходе анализа симптомов после IV кортикостероидов, габапентина и клоназепама. IV кортикостероиды, Габапентин и Клоназепам не являются достаточным лечением для Марбургского варианта заболевания множественным склерозом. Поэтому для дальнейшего подавления подстрекательского процесса можно использовать агрессивную терапию, чтобы предотвратить дальнейшие неврологические повреждения.
Оригинал публикации
Marburg variant of multiple sclerosis: A young women case report.
Marburg disease (malignant multiple sclerosis, MS) is a rare, acute MS variant, predominantly occurring among young adults. Because it is characterized by rarity, high morbidity and mortality rates, the disease needs to be further characterized, and the experience of the physicians play a role in treatment regimens. We report the case of a 15-years-old female presenting with progressive weakness over the limbs, hyperreflexia and loss of sensation by physical examination, lab tests and radiological investigations (MRI). After treatment, nonimprovement was recognized by symptoms review after IV corticosteroids, Gabapentin and Clonazepam intake during a clinical visit. IV corticosteroids, Gabapentin and Clonazepam are not sufficient treatment for Marburg's variant of multiple sclerosis disease. Therefore, aggressive therapies can be used to further suppress the inflammatory process to prevent further neurological damage.
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https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
Marburg's variant of multiple sclerosis (MS) was first identified by the Austrian neurologist Otto Marburg in 1905 [ 1 ]. MS is the most prevalent cause of nontraumatic impairment in young adults and is a chronic inflammatory demyelinating disease of the central nervous system (CNS) that affects over 1 million individuals globally [ 2 ]. It is an extremely uncommon demyelinating illness that often results in severe impairment or death within weeks to months [ [3] , [4] , [5] ].
The location and degree of lesions within the CNS affect the symptoms of multiple sclerosis. A few symptoms include ataxia, vertigo, bladder involvement, epilepsy, ocular and facial paralysis that may resemble idiopathic Bell's palsy, and sensory symptoms such as Lhermitte's sign [ 6 ]. The Marburg variant is more likely to cause sudden-onset confusion or altered consciousness, which typically brings people to the urgent care. Other symptoms may include: headache, vomiting, vision and speech problems, loss of sensation and seizures [ 7 ].
Due to its rarity, it is still not fully described, and treatment is influenced by the experiences of the doctors. However, the use of modern imaging modalities aids in establishing the diagnosis. Early identification of MS may delay progression to death.
Case report
A 15 years old female, with a free medical and surgical history, presented with abnormal body movements, tongue biting and incontinence. The patient presented with a progressive weakness over the left upper limb and lower limb for 3-5 days, hyperreflexia and loss of sensation over the left side of the face and upper limb. The patient had no history of cranial and spinal traumatic injury.
On physical examination, the patient was alert, conscious and oriented to place person and time with complete loss of power on left upper limb and both lower limbs. In sensory examination, the patient loss her sensation over the left side of face and upper limb only.
The plantar reflexes on both sides were extensor. In the upper limbs, deep tendon reflexes were present in right upper limbs. The patient frequently broke down in tears, a sign of emotional liability.
Patient lab results, renal function test, liver function test, lipid profile and complete blood count, were normal.
Radiological investigations were carried out with a Magnetic Resonance Imaging (MRI) of brain and orbit. It revealed extensive white matter lesions. There are numerous hyper intense lesions on T1-weighted sequences, predominantly involving the periventricular and deep white matter, with some lesions extending into the subcortical U-fibers ( Fig. 1 ). Fig. 1 T1-weighted MRI sagittal section (done on May 11, 2024) of the brain showing hyperintensities involving multiple regions with prominent periventricular lesions (distributed perpendicular to the body of the lateral ventricle) giving a `Dawson fingers' appearance (red arrows). Fig 1:
T1-weighted MRI sagittal section (done on May 11, 2024) of the brain showing hyperintensities involving multiple regions with prominent periventricular lesions (distributed perpendicular to the body of the lateral ventricle) giving a `Dawson fingers' appearance (red arrows).
MRI also revealed ring-enhancing lesions. Multiple large, confluent ring-enhancing lesions are observed after gadolinium administration, suggestive of active demyelination ( Fig. 2 ). Fig. 2 T2-weighted MRI axial section (done on May 11, 2024) of the brain showing hyperintensities with central necrosis. Fig 2:
T2-weighted MRI axial section (done on May 11, 2024) of the brain showing hyperintensities with central necrosis.
Some of these lesions show central necrosis and hemorrhage, a finding more typical of the Marburg variant ( Fig. 3 ). MRI also showed mass effect. There is evidence of moderate-severe mass effect due to the size and number of lesions, with midline shift and compression of the lateral ventricles. Fig. 3 T1-weighted MRI axial section (done on May 11, 2024) of the brain showing hyperintensities involving multiple regions with prominent periventricular lesions (distributed perpendicular to the body of the lateral ventricle) giving a `Dawson fingers' appearance (red arrows). Fig 3:
T1-weighted MRI axial section (done on May 11, 2024) of the brain showing hyperintensities involving multiple regions with prominent periventricular lesions (distributed perpendicular to the body of the lateral ventricle) giving a `Dawson fingers' appearance (red arrows).
Treatment and follow-up
The patient was admitted 5 days and received corticosteroids (1 gram of intravenous methylprednisolone daily). After discharge, the patient received a starting dose of Gabapentin (300 mg, once daily at bedtime) and Clonazepam (0.5mg, once daily at bedtime). Then, maintenance dose of Gabapentin (300 mg, 3 times per day at bedtime) and Clonazepam (1 mg, once daily at bedtime) was received.
The patient revisited the clinic after a course of treatment. She was still suffering from same symptoms. On the follow-up visit, a proper clinical evaluation was carried out to establish the rate of progression of symptoms. The evaluation included neurological examination and symptoms review. Through the neurological examination, the assessment of changes in motor strength, sensory function, coordination, and cognitive abilities was done. Through the symptoms review, muscular weakness, failing vision, failing cognition, pain, and fatigue was monitored.
Discussion
In this case study, our patient presented abnormal body movements, tongue biting, incontinence, sensation over the left side of face, loss of and complete loss of power on left upper limb and both lower limbs. Deferential diagnosis was stroke, peripheral neuro-pathy, brain mass, encephalitis or MS. The results of the patient's lab, renal function test, liver function test, lipid profile, and complete blood count were all normal.
Then, MRI was done where it reported no brain masses, no sign of inflammation and ischemia of brain and revealed multiple large demyelinating lesions in the brain. This means that the patient suffers from MS, Marburg's disease.
Since Otto Marburg described the MS variant in 1905, the differentiation of fulminant demyelinating diseases remains challenging [ 1 ]. It is a very serious variant form of MS that requires a unique approach to management due to its aggressive nature, rapid progression and acuteness of symptoms. Unlike the more common forms characterized by remissions and slow progression, Marburg disease is liable to cause remarkable neurological decline within a very short period; therefore, timely and effective intervention is important. The treatment follows the purpose of slowing down the progressive course of the disease, managing the symptoms, and improving the quality of life.
In Marburg disease, treatment relies first and foremost on how rapidly the symptoms appear and on the severity of neurological impairment [ 7 ]. This condition is very aggressive, and hence more intensive therapeutic strategies are usually needed compared to other forms of MS.
In this study, our case was supported as Marburg's disease by typical clinical and radiological analysis. MRI was used to identify the MS disease. After that, clinical examination and symptom review were used to reassess the progression of disease. Clinical judgment and symptom review must balance the need for rapid intervention against possible side effects and long-term outcomes of the treatment chosen [ 5 ], not least because Marburg's disease can affect patients of any age, predominantly young people [ 8 ].
High-dose corticosteroids are usually prescribed for Marburg disease at the beginning itself to reduce inflammation and stabilize the disease [ 9 , 10 ]. The idea is to rapidly reduce the acute phase of the disease. But since Marburg's MS is malignant, corticosteroids alone often cannot help in arresting the progress [ 11 ].
Thus, the first line of treatment was corticosteroids, Gabapentin and Clonazepam. The goal of corticosteroids was to reduce the acute central nervous system inflammation responsible for the rapid neurodegeneration. Gabapentin was primarily utilized for managing neuropathic pain, which could prove a considerable issue. Clonazepam was utilized to treat anxiety, muscle spasms, and sleeplessness.
In the case study patient, nonimprovement was recognized in the clinical condition. Therefore, aggressive therapies can be used to further suppress the inflammatory process to prevent further neurological damage. This may entail considerations for treatment with plasmapheresis or intravenous immunoglobulin. This can also include the following immunomodulatory therapies, such as with disease-modifying therapies like alemtuzumab, in the management of Marburg's disease [ 12 ].
Although these therapies reduce the frequency and severity of relapses, their efficiency seems more limited in this malignant variant of MS when compared with their application in more typical forms of the disease. Some studies documented fair success using these therapies to stabilize the disease course [ 9 ], but more research is warranted to understand their full long-term benefits in Marburg's disease.
In patients where classical treatments couldn't keep the illness under control, more aggressive forms of approaches have been explored, including hematopoietic stem cell transplantation. In this approach, high-dose chemotherapy is used and is followed by hematopoietic stem cell transplantation to reset the immune system. While hematopoietic stem cell transplantation has been quite promising in some cases, it is a very risky treatment and is usually given to patients with rapidly worsening symptoms who don't respond to other treatments.
Given the rarity and severity of Marburg, it is expected that there is much learning to be obtained regarding how one could best handle the condition. Each case needs to be highly individualized according to the general health of the subject, the velocity of the development of the illness, and the risks opposed against benefits for the available therapies.
The progression of symptoms in a patient with Marburg disease despite a course of treatment points to the failure of the initial therapeutic measures to control the most aggressive nature of this condition. This case illustrates that rapid evolution makes Marburg disease very difficult to treat and refractory to all standard therapies.
Conclusion
Very limited data are found in literature for Marburg's variant of MS because of its rarity. Its exact incidence is not known. Currently, several consensus are not available for the diagnostic criteria for Marburg's variant of MS. Our patient showed nonimprovement following IV corticosteroids, Gabapentin and Clonazepam, thus adjunct therapy has to be considered in the long run.
Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Patient consent
The authors confirm that written, informed consent for publication of her case was obtained from the patient.
Marburg's variant of multiple sclerosis (MS) was first identified by the Austrian neurologist Otto Marburg in 1905 [ 1 ]. MS is the most prevalent cause of nontraumatic impairment in young adults and is a chronic inflammatory demyelinating disease of the central nervous system (CNS) that affects over 1 million individuals globally [ 2 ]. It is an extremely uncommon demyelinating illness that often results in severe impairment or death within weeks to months [ [3] , [4] , [5] ].
The location and degree of lesions within the CNS affect the symptoms of multiple sclerosis. A few symptoms include ataxia, vertigo, bladder involvement, epilepsy, ocular and facial paralysis that may resemble idiopathic Bell's palsy, and sensory symptoms such as Lhermitte's sign [ 6 ]. The Marburg variant is more likely to cause sudden-onset confusion or altered consciousness, which typically brings people to the urgent care. Other symptoms may include: headache, vomiting, vision and speech problems, loss of sensation and seizures [ 7 ].
Due to its rarity, it is still not fully described, and treatment is influenced by the experiences of the doctors. However, the use of modern imaging modalities aids in establishing the diagnosis. Early identification of MS may delay progression to death.
Case report
A 15 years old female, with a free medical and surgical history, presented with abnormal body movements, tongue biting and incontinence. The patient presented with a progressive weakness over the left upper limb and lower limb for 3-5 days, hyperreflexia and loss of sensation over the left side of the face and upper limb. The patient had no history of cranial and spinal traumatic injury.
On physical examination, the patient was alert, conscious and oriented to place person and time with complete loss of power on left upper limb and both lower limbs. In sensory examination, the patient loss her sensation over the left side of face and upper limb only.
The plantar reflexes on both sides were extensor. In the upper limbs, deep tendon reflexes were present in right upper limbs. The patient frequently broke down in tears, a sign of emotional liability.
Patient lab results, renal function test, liver function test, lipid profile and complete blood count, were normal.
Radiological investigations were carried out with a Magnetic Resonance Imaging (MRI) of brain and orbit. It revealed extensive white matter lesions. There are numerous hyper intense lesions on T1-weighted sequences, predominantly involving the periventricular and deep white matter, with some lesions extending into the subcortical U-fibers ( Fig. 1 ). Fig. 1 T1-weighted MRI sagittal section (done on May 11, 2024) of the brain showing hyperintensities involving multiple regions with prominent periventricular lesions (distributed perpendicular to the body of the lateral ventricle) giving a `Dawson fingers' appearance (red arrows). Fig 1:
T1-weighted MRI sagittal section (done on May 11, 2024) of the brain showing hyperintensities involving multiple regions with prominent periventricular lesions (distributed perpendicular to the body of the lateral ventricle) giving a `Dawson fingers' appearance (red arrows).
MRI also revealed ring-enhancing lesions. Multiple large, confluent ring-enhancing lesions are observed after gadolinium administration, suggestive of active demyelination ( Fig. 2 ). Fig. 2 T2-weighted MRI axial section (done on May 11, 2024) of the brain showing hyperintensities with central necrosis. Fig 2:
T2-weighted MRI axial section (done on May 11, 2024) of the brain showing hyperintensities with central necrosis.
Some of these lesions show central necrosis and hemorrhage, a finding more typical of the Marburg variant ( Fig. 3 ). MRI also showed mass effect. There is evidence of moderate-severe mass effect due to the size and number of lesions, with midline shift and compression of the lateral ventricles. Fig. 3 T1-weighted MRI axial section (done on May 11, 2024) of the brain showing hyperintensities involving multiple regions with prominent periventricular lesions (distributed perpendicular to the body of the lateral ventricle) giving a `Dawson fingers' appearance (red arrows). Fig 3:
T1-weighted MRI axial section (done on May 11, 2024) of the brain showing hyperintensities involving multiple regions with prominent periventricular lesions (distributed perpendicular to the body of the lateral ventricle) giving a `Dawson fingers' appearance (red arrows).
Treatment and follow-up
The patient was admitted 5 days and received corticosteroids (1 gram of intravenous methylprednisolone daily). After discharge, the patient received a starting dose of Gabapentin (300 mg, once daily at bedtime) and Clonazepam (0.5mg, once daily at bedtime). Then, maintenance dose of Gabapentin (300 mg, 3 times per day at bedtime) and Clonazepam (1 mg, once daily at bedtime) was received.
The patient revisited the clinic after a course of treatment. She was still suffering from same symptoms. On the follow-up visit, a proper clinical evaluation was carried out to establish the rate of progression of symptoms. The evaluation included neurological examination and symptoms review. Through the neurological examination, the assessment of changes in motor strength, sensory function, coordination, and cognitive abilities was done. Through the symptoms review, muscular weakness, failing vision, failing cognition, pain, and fatigue was monitored.
Discussion
In this case study, our patient presented abnormal body movements, tongue biting, incontinence, sensation over the left side of face, loss of and complete loss of power on left upper limb and both lower limbs. Deferential diagnosis was stroke, peripheral neuro-pathy, brain mass, encephalitis or MS. The results of the patient's lab, renal function test, liver function test, lipid profile, and complete blood count were all normal.
Then, MRI was done where it reported no brain masses, no sign of inflammation and ischemia of brain and revealed multiple large demyelinating lesions in the brain. This means that the patient suffers from MS, Marburg's disease.
Since Otto Marburg described the MS variant in 1905, the differentiation of fulminant demyelinating diseases remains challenging [ 1 ]. It is a very serious variant form of MS that requires a unique approach to management due to its aggressive nature, rapid progression and acuteness of symptoms. Unlike the more common forms characterized by remissions and slow progression, Marburg disease is liable to cause remarkable neurological decline within a very short period; therefore, timely and effective intervention is important. The treatment follows the purpose of slowing down the progressive course of the disease, managing the symptoms, and improving the quality of life.
In Marburg disease, treatment relies first and foremost on how rapidly the symptoms appear and on the severity of neurological impairment [ 7 ]. This condition is very aggressive, and hence more intensive therapeutic strategies are usually needed compared to other forms of MS.
In this study, our case was supported as Marburg's disease by typical clinical and radiological analysis. MRI was used to identify the MS disease. After that, clinical examination and symptom review were used to reassess the progression of disease. Clinical judgment and symptom review must balance the need for rapid intervention against possible side effects and long-term outcomes of the treatment chosen [ 5 ], not least because Marburg's disease can affect patients of any age, predominantly young people [ 8 ].
High-dose corticosteroids are usually prescribed for Marburg disease at the beginning itself to reduce inflammation and stabilize the disease [ 9 , 10 ]. The idea is to rapidly reduce the acute phase of the disease. But since Marburg's MS is malignant, corticosteroids alone often cannot help in arresting the progress [ 11 ].
Thus, the first line of treatment was corticosteroids, Gabapentin and Clonazepam. The goal of corticosteroids was to reduce the acute central nervous system inflammation responsible for the rapid neurodegeneration. Gabapentin was primarily utilized for managing neuropathic pain, which could prove a considerable issue. Clonazepam was utilized to treat anxiety, muscle spasms, and sleeplessness.
In the case study patient, nonimprovement was recognized in the clinical condition. Therefore, aggressive therapies can be used to further suppress the inflammatory process to prevent further neurological damage. This may entail considerations for treatment with plasmapheresis or intravenous immunoglobulin. This can also include the following immunomodulatory therapies, such as with disease-modifying therapies like alemtuzumab, in the management of Marburg's disease [ 12 ].
Although these therapies reduce the frequency and severity of relapses, their efficiency seems more limited in this malignant variant of MS when compared with their application in more typical forms of the disease. Some studies documented fair success using these therapies to stabilize the disease course [ 9 ], but more research is warranted to understand their full long-term benefits in Marburg's disease.
In patients where classical treatments couldn't keep the illness under control, more aggressive forms of approaches have been explored, including hematopoietic stem cell transplantation. In this approach, high-dose chemotherapy is used and is followed by hematopoietic stem cell transplantation to reset the immune system. While hematopoietic stem cell transplantation has been quite promising in some cases, it is a very risky treatment and is usually given to patients with rapidly worsening symptoms who don't respond to other treatments.
Given the rarity and severity of Marburg, it is expected that there is much learning to be obtained regarding how one could best handle the condition. Each case needs to be highly individualized according to the general health of the subject, the velocity of the development of the illness, and the risks opposed against benefits for the available therapies.
The progression of symptoms in a patient with Marburg disease despite a course of treatment points to the failure of the initial therapeutic measures to control the most aggressive nature of this condition. This case illustrates that rapid evolution makes Marburg disease very difficult to treat and refractory to all standard therapies.
Conclusion
Very limited data are found in literature for Marburg's variant of MS because of its rarity. Its exact incidence is not known. Currently, several consensus are not available for the diagnostic criteria for Marburg's variant of MS. Our patient showed nonimprovement following IV corticosteroids, Gabapentin and Clonazepam, thus adjunct therapy has to be considered in the long run.
Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Patient consent
The authors confirm that written, informed consent for publication of her case was obtained from the patient.