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Bilateral refractory subdural hygromas following intrathecal methotrexate injections for B-Cell Acute Lymphocytic Leukemia
Interdisciplinary Neurosurgery 19 (2020) 100608
Contents lists available at ScienceDirect
Interdisciplinary Neurosurgery journal homepage: www.elsevier.com/locate/inat
Technical notes & surgical techniques
Bilateral refractory subdural hygromas following intrathecal methotrexate injections for B-Cell Acute Lymphocytic Leukemia
T
⁎
Salman Assad , Katherine O' Connell, Justin Nolte, Abdul Rana, Dharampreet Singh Department of Neurology, Marshall University School of Medicine, WV, USA
A R T I C LE I N FO
A B S T R A C T
Keywords: Hygroma Subdural Leukemia Chemotherapy
Background: Subdural hygroma (SDG) is an important complication after intrathecal injections of medications. SDG develops because of a cerebrospinal fluid leak into subdural space. Case description: We report a case of 69 years old male who presented to the hospital with changes in mental status and hemodynamic instability. The patient was a known case of B-Cell Acute Lymphoblastic Leukemia (BALL) and was undergoing intrathecal injections of methotrexate (MTX) and intensive chemotherapy. Patient focal neurological deficits were correlated with the neuroimaging findings which showed bilateral subdural hygromas. He has received intrathecal injections of MTX almost 6 weeks ago. Surgical drainage of subdural hygroma was done but the refractory nature of hygroma left the patient with residual mass effects and neurological deficits. Conclusion: As physicians, we should be aware of a fatal but rare complication of intrathecal injections and one of them this patient developed as SDG.
1. Introduction Subdural hygromas (SDG) are different from acute and chronic subdural hematomas in clinical features and pathogenic mechanism [1]. The different mechanisms have been proposed to explain the pathogenesis of SDG, include an arachnoid flap, blood-brain barrier (BBB) failure, arachnoid rupture, and brain atrophy [2]. 2. Case report We present a case of 69-year-old male who presented with intractable nausea, vomiting, altered mental status, and dehydration, for nearly one week. He was hypotensive on admission and was transferred to the intensive care unit for intravenous fluids, empiric antibiotics, and further care. On laboratory investigation, blood cultures were negative but acute kidney injury and hyperkalemia were found. The patient was diagnosed with B-Cell Acute Lymphoblastic Leukemia (B-ALL) with the positive oncogene, Breakpoint Cluster Region- Abelson Murine Leukemia (BCR-ABL) about 4 months prior to admission. He received induction chemotherapy with Dasatinib (tyrosine kinase inhibitor) 100 mg tablet orally daily, Vincristine intravenous (IV) weekly for 2 weeks, intrathecal Methotrexate (MTX) weekly for 4 weeks (missed one dose of MTX) and 4 cycles of Dexamethasone 40 mg for 2 days
⁎
(Table 1). His last dose of MTX was nearly six weeks prior to presentation. The patient had a remission as per flow cytometry analysis and negative cerebrospinal fluid (CSF) cytology. The patient to be oriented to person only with features of inattention but he was able to follow some simple commands. The muscle strength examination revealed him to be 3/5 in left lower extremities and 3/5 in left upper extremities, 4/5 and symmetric in the right upper and lower extremities; deep tendon reflexes (DTR 3+) left patellar, left Achilles, biceps and triceps, DTR 2+ in right patella, Achilles, biceps, and triceps. Plantar responses were extensor on the left and silent on the right. Moderate dysmetria was present on finger-to-nose in the left hand, cannot do heel-to-shin left lower extremity (LLE), no tremor, decreased to light touch left upper extremity (LUE) and left lower extremity (LLE) compared to right side. Sensations were intact to vibration in all extremities and patient could stand with assistance with a negative Romberg. Magnetic resonance imaging (MRI) brain showed large bilateral extra-axial fluid collections, most suggestive of SDGs see (Fig. 1). SDG was differentiated from chronic subdural hematoma based on MRI findings as a crescentic nearCSF density/signal accumulation in the subdural space that does not extend into the sulci without causing significant mass-effect. Diagnostic spinal tap was done at the time of diagnosis and post-tap MRI lumbar spine did not show any CSF leak contributing to recurrent subdural
Corresponding author at: 1600 Medical Center Drive, Huntington, WV, USA. E-mail address: [email protected] (S. Assad).
https://doi.org/10.1016/j.inat.2019.100608 Received 6 June 2019; Received in revised form 5 September 2019; Accepted 13 October 2019 2214-7519/ © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Interdisciplinary Neurosurgery 19 (2020) 100608
S. Assad, et al.
Table 1 Oncological history and treatment of B-ALL. Oncological History and Treatment 1. 2. 3. 4. 5. 6. 7. 8.
Started induction therapy with Dasatinib plus vincristine plus dexamethasone (9/27/2018) Intravenous Vincristine weekly x2 last 10/10/18 (held due to cytopenia) Intrathecal Methotrexate weekly x3 last 10/18/18. Patient missed his cycle 4 of intrathecal methotrexate which was supposed to be 10/24/2018 Dexamethasone 40 mg daily x2 10/20/18 Dexamethasone 40 mg daily x2 10/26/18 Dasatinib was held starting 10/29/18 due to severe weakness Repeat flow cytometry 10/26/18; Negative for B lymphoblast population. Minute population of myeloid blasts (0.08% of total events) On Dasatinib 100 mg once daily. May consider giving Rituxan as an outpatient later on. No additional chemotherapy or intrathecal treatments after palliative care measures applied
Fig. 1. Magnetic resonance imaging (MRI) brain showing large bilateral extra-axial fluid collections, most suggestive of SDGs.
complication that may occur after head trauma and secondary to decompressive craniectomy [2]. The etiology of the development of bilateral SDGs in most cases was documented as either traumatic or idiopathic [3]. The pathophysiology can be explained due to either an underlying alteration of the dynamics of CSF circulation or disturbance of normal CSF absorption. SDG can be seen in the first week after surgery or external factors like intrathecal injections, as in the present case, and this fluid collection may increase for up to 4 weeks [4]. Lewis et al. documented the development of SDGs after the intrathecal MTX injection [3]. Dillon et al. documented the intracranial and spinal manifestations of CSF hypovolemia [2]. The spontaneous intracranial hypotension (SIH) or post-lumbar puncture headache syndrome (PLPHS), comprise an interesting constellation of imaging findings
hygromas. Following burr hole placement, the patient continued to have confusion and headache. Post-procedure computed tomography (CT) head showed interval improvement in subdural hygroma but with residual mild mass effect see (Fig. 2). Oncology was consulted as well during this admission and after discussion by family with them regarding his poor prognosis with B-ALL and refractory SDG despite multiple interventions the decision was made to pursue palliative measures.
3. Discussion Refractory bilateral SDGs have been reported in the literature, particularly as a complication of neurosurgical intervention. SDG is a
Fig. 2. Post-procedure computed tomography (CT) head showed interval improvement in subdural hygromas but with residual mild mass effect. 2
Interdisciplinary Neurosurgery 19 (2020) 100608
S. Assad, et al.
Declaration of Competing Interest
reflective of underlying pathophysiology. It is now well established that reduced CSF volume and pressure in the presence of closed calvarial sutures result in dilatation of both brain and spinal venous and arterial structures. This occurs to maintain intracranial volume and the relationship between CSF, brain parenchyma, and brain vasculature [5]. The patient in this case presentation has a poor prognosis due to underlying malignancy and refractory subdural hygromas of unknown etiology. Although we have a reason to believe that it might be related to underlying intrathecal MTX injections that might have disturbed CSF absorption and drainage dynamics we cannot complete exclude the possibility of progression of his B-ALL causing leptomeningeal disease as a potential etiology as well. No case has been documented in literature where the progression of B-ALL can lead to refractory SDGs. As such, we postulate that this case presentation might offer an alternative etiology of SDG and may open further discussion into the possibilities of malignancy progression and subsequent neurological manifestations.
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. References [1] B. Aarabi, D. Chesler, C. Maulucci, T. Blacklock, M. Alexander, Dynamics of subdural hygroma following decompressive craniectomy: a comparative study, Neurosurg. Focus. 26 (2009) E8. [2] W.P. Dillon, R.A. Fishman, Some lessons learned regarding the diagnosis and treatment of spontaneous intracranial hypotension, AJNR: Am. J. Neuroradiol. 6 (1998) 1001–1002. [3] H. Lewis, A.J. Mahdi, C. Rowntree, Bilateral subdural hygromas following administration of intrathecal methotrexate chemotherapy, BMJ Case Rep. 22 (2015) 2015. [4] J.N. St John, C. Dila, Traumatic subdural hygroma in adults, Neurosurgery 9 (1981) 621–626. [5] C.J. Njiokiktjien, J. Valk, H. Ponssen, Subdural hygroma: results of treatment by ventriculo-abdominal shunt, Childs Brain 7 (6) (1980) 285–302.
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Contents lists available at ScienceDirect
Interdisciplinary Neurosurgery journal homepage: www.elsevier.com/locate/inat
Technical notes & surgical techniques
Bilateral refractory subdural hygromas following intrathecal methotrexate injections for B-Cell Acute Lymphocytic Leukemia
T
⁎
Salman Assad , Katherine O' Connell, Justin Nolte, Abdul Rana, Dharampreet Singh Department of Neurology, Marshall University School of Medicine, WV, USA
A R T I C LE I N FO
A B S T R A C T
Keywords: Hygroma Subdural Leukemia Chemotherapy
Background: Subdural hygroma (SDG) is an important complication after intrathecal injections of medications. SDG develops because of a cerebrospinal fluid leak into subdural space. Case description: We report a case of 69 years old male who presented to the hospital with changes in mental status and hemodynamic instability. The patient was a known case of B-Cell Acute Lymphoblastic Leukemia (BALL) and was undergoing intrathecal injections of methotrexate (MTX) and intensive chemotherapy. Patient focal neurological deficits were correlated with the neuroimaging findings which showed bilateral subdural hygromas. He has received intrathecal injections of MTX almost 6 weeks ago. Surgical drainage of subdural hygroma was done but the refractory nature of hygroma left the patient with residual mass effects and neurological deficits. Conclusion: As physicians, we should be aware of a fatal but rare complication of intrathecal injections and one of them this patient developed as SDG.
1. Introduction Subdural hygromas (SDG) are different from acute and chronic subdural hematomas in clinical features and pathogenic mechanism [1]. The different mechanisms have been proposed to explain the pathogenesis of SDG, include an arachnoid flap, blood-brain barrier (BBB) failure, arachnoid rupture, and brain atrophy [2]. 2. Case report We present a case of 69-year-old male who presented with intractable nausea, vomiting, altered mental status, and dehydration, for nearly one week. He was hypotensive on admission and was transferred to the intensive care unit for intravenous fluids, empiric antibiotics, and further care. On laboratory investigation, blood cultures were negative but acute kidney injury and hyperkalemia were found. The patient was diagnosed with B-Cell Acute Lymphoblastic Leukemia (B-ALL) with the positive oncogene, Breakpoint Cluster Region- Abelson Murine Leukemia (BCR-ABL) about 4 months prior to admission. He received induction chemotherapy with Dasatinib (tyrosine kinase inhibitor) 100 mg tablet orally daily, Vincristine intravenous (IV) weekly for 2 weeks, intrathecal Methotrexate (MTX) weekly for 4 weeks (missed one dose of MTX) and 4 cycles of Dexamethasone 40 mg for 2 days
⁎
(Table 1). His last dose of MTX was nearly six weeks prior to presentation. The patient had a remission as per flow cytometry analysis and negative cerebrospinal fluid (CSF) cytology. The patient to be oriented to person only with features of inattention but he was able to follow some simple commands. The muscle strength examination revealed him to be 3/5 in left lower extremities and 3/5 in left upper extremities, 4/5 and symmetric in the right upper and lower extremities; deep tendon reflexes (DTR 3+) left patellar, left Achilles, biceps and triceps, DTR 2+ in right patella, Achilles, biceps, and triceps. Plantar responses were extensor on the left and silent on the right. Moderate dysmetria was present on finger-to-nose in the left hand, cannot do heel-to-shin left lower extremity (LLE), no tremor, decreased to light touch left upper extremity (LUE) and left lower extremity (LLE) compared to right side. Sensations were intact to vibration in all extremities and patient could stand with assistance with a negative Romberg. Magnetic resonance imaging (MRI) brain showed large bilateral extra-axial fluid collections, most suggestive of SDGs see (Fig. 1). SDG was differentiated from chronic subdural hematoma based on MRI findings as a crescentic nearCSF density/signal accumulation in the subdural space that does not extend into the sulci without causing significant mass-effect. Diagnostic spinal tap was done at the time of diagnosis and post-tap MRI lumbar spine did not show any CSF leak contributing to recurrent subdural
Corresponding author at: 1600 Medical Center Drive, Huntington, WV, USA. E-mail address: [email protected] (S. Assad).
https://doi.org/10.1016/j.inat.2019.100608 Received 6 June 2019; Received in revised form 5 September 2019; Accepted 13 October 2019 2214-7519/ © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Interdisciplinary Neurosurgery 19 (2020) 100608
S. Assad, et al.
Table 1 Oncological history and treatment of B-ALL. Oncological History and Treatment 1. 2. 3. 4. 5. 6. 7. 8.
Started induction therapy with Dasatinib plus vincristine plus dexamethasone (9/27/2018) Intravenous Vincristine weekly x2 last 10/10/18 (held due to cytopenia) Intrathecal Methotrexate weekly x3 last 10/18/18. Patient missed his cycle 4 of intrathecal methotrexate which was supposed to be 10/24/2018 Dexamethasone 40 mg daily x2 10/20/18 Dexamethasone 40 mg daily x2 10/26/18 Dasatinib was held starting 10/29/18 due to severe weakness Repeat flow cytometry 10/26/18; Negative for B lymphoblast population. Minute population of myeloid blasts (0.08% of total events) On Dasatinib 100 mg once daily. May consider giving Rituxan as an outpatient later on. No additional chemotherapy or intrathecal treatments after palliative care measures applied
Fig. 1. Magnetic resonance imaging (MRI) brain showing large bilateral extra-axial fluid collections, most suggestive of SDGs.
complication that may occur after head trauma and secondary to decompressive craniectomy [2]. The etiology of the development of bilateral SDGs in most cases was documented as either traumatic or idiopathic [3]. The pathophysiology can be explained due to either an underlying alteration of the dynamics of CSF circulation or disturbance of normal CSF absorption. SDG can be seen in the first week after surgery or external factors like intrathecal injections, as in the present case, and this fluid collection may increase for up to 4 weeks [4]. Lewis et al. documented the development of SDGs after the intrathecal MTX injection [3]. Dillon et al. documented the intracranial and spinal manifestations of CSF hypovolemia [2]. The spontaneous intracranial hypotension (SIH) or post-lumbar puncture headache syndrome (PLPHS), comprise an interesting constellation of imaging findings
hygromas. Following burr hole placement, the patient continued to have confusion and headache. Post-procedure computed tomography (CT) head showed interval improvement in subdural hygroma but with residual mild mass effect see (Fig. 2). Oncology was consulted as well during this admission and after discussion by family with them regarding his poor prognosis with B-ALL and refractory SDG despite multiple interventions the decision was made to pursue palliative measures.
3. Discussion Refractory bilateral SDGs have been reported in the literature, particularly as a complication of neurosurgical intervention. SDG is a
Fig. 2. Post-procedure computed tomography (CT) head showed interval improvement in subdural hygromas but with residual mild mass effect. 2
Interdisciplinary Neurosurgery 19 (2020) 100608
S. Assad, et al.
Declaration of Competing Interest
reflective of underlying pathophysiology. It is now well established that reduced CSF volume and pressure in the presence of closed calvarial sutures result in dilatation of both brain and spinal venous and arterial structures. This occurs to maintain intracranial volume and the relationship between CSF, brain parenchyma, and brain vasculature [5]. The patient in this case presentation has a poor prognosis due to underlying malignancy and refractory subdural hygromas of unknown etiology. Although we have a reason to believe that it might be related to underlying intrathecal MTX injections that might have disturbed CSF absorption and drainage dynamics we cannot complete exclude the possibility of progression of his B-ALL causing leptomeningeal disease as a potential etiology as well. No case has been documented in literature where the progression of B-ALL can lead to refractory SDGs. As such, we postulate that this case presentation might offer an alternative etiology of SDG and may open further discussion into the possibilities of malignancy progression and subsequent neurological manifestations.
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. References [1] B. Aarabi, D. Chesler, C. Maulucci, T. Blacklock, M. Alexander, Dynamics of subdural hygroma following decompressive craniectomy: a comparative study, Neurosurg. Focus. 26 (2009) E8. [2] W.P. Dillon, R.A. Fishman, Some lessons learned regarding the diagnosis and treatment of spontaneous intracranial hypotension, AJNR: Am. J. Neuroradiol. 6 (1998) 1001–1002. [3] H. Lewis, A.J. Mahdi, C. Rowntree, Bilateral subdural hygromas following administration of intrathecal methotrexate chemotherapy, BMJ Case Rep. 22 (2015) 2015. [4] J.N. St John, C. Dila, Traumatic subdural hygroma in adults, Neurosurgery 9 (1981) 621–626. [5] C.J. Njiokiktjien, J. Valk, H. Ponssen, Subdural hygroma: results of treatment by ventriculo-abdominal shunt, Childs Brain 7 (6) (1980) 285–302.
3