|Year : 2020 | Volume
| Issue : 1 | Page : 96-99
Compressive myelopathy – An unusual presentation of extramedullary hematopoiesis in a known patient of thalassemia major
Rajesh Nair1, Debish Anand1, Girish Menon1, KV Kiran Acharya2, B Ananthakrishna Shastri3
1 Department of Neurosurgery, Kasturba Medical College, Manipal, Karnataka, India
2 Department of Orthopedics, Kasturba Medical College, Manipal, Karnataka, India
3 Department of General Medicine, Kasturba Medical College, Manipal, Karnataka, India
|Date of Submission||14-May-2020|
|Date of Decision||18-May-2020|
|Date of Acceptance||20-May-2020|
|Date of Web Publication||20-Jun-2020|
Dr. Rajesh Nair
Department of Neurosurgery, Kasturba Medical College, Manipal - 576 104, Karnataka
Source of Support: None, Conflict of Interest: None
Thalassemia presenting with compressive myelopathy secondary to extramedullary hematopoiesis (EMH) is rare. We report the rare case of spinal EMH with dorsal cord compression and myelopathy in a 28-year-old male with inadequately transfused beta thalassemia major who presented with paraparesis and acute sphincter disturbance.
Keywords: Compressive myelopathy, extramedullary hematopoiesis, thalassemia
|How to cite this article:|
Nair R, Anand D, Menon G, Kiran Acharya K V, Shastri B A. Compressive myelopathy – An unusual presentation of extramedullary hematopoiesis in a known patient of thalassemia major. Arch Med Health Sci 2020;8:96-9
|How to cite this URL:|
Nair R, Anand D, Menon G, Kiran Acharya K V, Shastri B A. Compressive myelopathy – An unusual presentation of extramedullary hematopoiesis in a known patient of thalassemia major. Arch Med Health Sci [serial online] 2020 [cited 2020 Oct 25];8:96-9. Available from: https://www.amhsjournal.org/text.asp?2020/8/1/96/287373
| Introduction|| |
Compressive myelopathy in the young occurs secondary to trauma, tumors, and craniovertebral junction anomalies. Rarely, do we encounter myelopathy as a complication of yet another entity that frequents the same age group. Thalassemia, also known as Cooley's disease, is a Mendelian hemoglobinopathy, characterized by insufficient or absent globin chain production. This ineffective erythropoiesis causes the expansion of extrahemotopoietic tissues (spine, liver, spleen, and dura mater) and leads to the entity, now understood as, extramedullary hematopoiesis (EMH).
Patients with cord compression secondary to adjacent EMH present with a myriad of symptoms such as para/quadriparesis, quadri/paraplegia, sphincter disturbances, sensory deficits, clonus, and spastic gait among other signs of spasticity. Treatment protocol remains controversial, with successful reports of radiotherapy, transfusions, surgery, alone or in combination being used in different cases.
We report a rare case of spinal EMH with dorsal cord compression and myelopathy in a 28-year-old male with inadequately transfused beta thalassemia major who presented with paraparesis and acute sphincter disturbance.
| Case Report|| |
A 28-year-old thalassemia major, transfusion-dependent (TDT) gentleman presented to the outpatient department with complaints of upper back pain radiating to the right lower limb for 1 month. He also complained of difficulty in getting up from bed and rising from a seated position. He felt a sense of tightness in both lower limbs (right > left) and interjected that he felt like “he was walking over a cloud” for the last 3 weeks. He observed these symptoms to worsen over the past 3 weeks and noticed an acute deterioration of this in the dark. He had trouble negotiating his feet into footwear and complained of slippage of footwear while walking and inability to walk fast, negotiate narrow alleys and difficulty in walking on uneven surfaces. He also complained of difficulty in maintaining his posture while washing his face, and since the last 4 days, he was unable to micturate freely and had an incomplete sense of voiding and infrequent bowel movements.
A detailed history taking revealed that the patient was a diagnosed case of thalassemia major at 9 years of age and was fraught with fever, significant pallor, and deepening icterus. Stigmata of hemolytic facies with stunted growth and stature along with hepatosplenomegaly strengthened the clinical diagnosis of hemolytic anemia, possibly thalassemia. Blood workup and Hb electrophoresis revealed an elevated percentage of HbF which helped clinch the diagnosis. He was subjected to regular transfusions and iron chelation and after 2 years of his diagnosis, he developed hypersplenism. He underwent elective splenectomy soon after and failed to follow-up for the next 3 years.
His next hospital visit was with complaints of an apparent right lower limb shortening and gait disability and weakness in the right lower limb for 3 months. Hematological investigations revealed hemoglobin at 4.7 g/dL and HbF at 98.2%. He was reassured and advised for regular blood transfusions and failed to follow-up for the next few years.
On general examination, during the present consult, he was icteric, and there was an obvious length discrepancy between his lower limbs, with the left lower limb slightly longer than the right (by 6 cm). Neurological examination showed an asymmetric disproportionate ascending loss in sensation and power in both lower limbs with right > left. The tone was increased in both lower limbs (Modified Ashworth Grade 2). The power was 5/5 in both the upper limbs with no evidence of spasticity. Power in the lower limbs was noted to be 4/5 bilaterally in all joints except the right ankle which seemed to be weaker than its counterpart (3/5). Sensation to crude and fine touch was absent below the nipples on right side (T4) and T6 and below on the left side. The lower limb deep tendon reflexes were exaggerated (3+) in both lower limbs and 2+ in the upper limbs. Superficial reflexes were absent with upgoing plantars and cortical sensations were impaired (joint and position sense). Sphincters were affected, and there was no obvious skull or spine deformity.
Routine blood investigations revealed hemoglobin to be 8.2 g/dL with PCV of 27.8%, MCH 23.3 pg, RDW 28.5, and a serum total bilirubin 7.28 mg/dL. The patient had indirect hyperbilirubinemia with chronic anemia. Chest X-ray and computed tomographic scan of the spine revealed a lobulated soft-tissue mass in the paravertebral region extending from the 3rd to the 10th rib (posterior ends) along with dorsal spinal lesion extending from D3 to D7 with cord compression [Figure 1]e, [Figure 1]f, [Figure 1]g. Signs of extramedullary hematopoiesis in the form of medullary expansion and trabeculation were seen throughout the visualized spine in both axial and sagittal sections [Figure 1]e, [Figure 1]f, [Figure 1]g. The skull X-ray revealed no marrow expansion in the flat bones; however, frontal bossing was noted [Figure 1]i.
|Figure 1: Chest X-ray and computed tomographic scan of the spine showing a lobulated soft-tissue mass in the paravertebral region extending from the 3rd to the 10th rib (posterior ends) along with dorsal spinal lesion extending from D3 to D7 with cord compression (e-g). Plain X ray Chest PA view showing prominent bronchio alveolar markings and hilar shadows (h). Signs of extramedullary hematopoiesis in the form of medullary expansion and trabeculation are seen throughout the visualized spine in both axial and sagittal sections (e-g). The skull X-ray reveals no marrow expansion in the flat bones; however, frontal bossing is noted (i). Magnetic resonance imaging of the thoracic spine showing multiple lobulated paravertebral soft-tissue signal intensity lesions extending from D4 to D10 levels which were of intermediate intensity on T1- and T2-weighted images (a-d) and having postcontrast enhancement. Similar lesions are also seen in the posterior epidural space from D3-D7 levels (a-c)|
Click here to view
Magnetic resonance imaging (MRI) of the thoracic spine revealed multiple lobulated paravertebral soft-tissue signal intensity lesions extending from D4 to D10 levels which were of intermediate intensity on T1- and T2-weighted images [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d and having postcontrast enhancement. Similar lesions were also noted in the posterior epidural space from D3 to D7 levels [Figure 1]a, [Figure 1]b, [Figure 1]c. Multiple extramedullary hematopoietic deposits were noted in the paravertebral regions, and the epidural lesions were determined to be the cause of the severe cord compression. Similar lesions were found anterior to the sternum and along the ribs.
In view of the diagnostic findings and an acute involvement of the bowel and bladder, the patient was taken up for an emergent decompressive laminectomy. Wide laminectomy from D3 to D7 was done using high-speed drill, and the hematopoietic lesion was excised and tortuous epidural veins were coagulated to decompress the dorsal cord [Figure 2]a and [Figure 2]b]. No intraoperative dural injury [Figure 2]d was noted, and the resected laminae and hematopoietic tissue were subjected histopathological examination.
|Figure 2: Intraoperative picture following a wide laminectomy from D3 to D7 shows the hematopoietic lesion and tortuous epidural veins (a and b) in the epidural space (d). The hematopoetic tissue ( in circle) seen as vascular friable tissue (c)|
Click here to view
Grossly, the extradural lesion was noted to be friable gray-to-brown tissue [Figure 2]a, [Figure 2]b, [Figure 2]c, with gray white and gray brown areas on cut section. Microscopically, sheets of erythroid and myeloid precursors were seen, along with lymphocytes, megakaryocytes, and hemosiderin-laden macrophages. Congested blood vessels along with fibrocollagenous, adipose tissue, and bony spicules were also noted. Biopsy of laminae revealed gray-brown areas on cut section while microscopically the bony trabeculae were noted to contain hematopoietic elements within the marrow spaces. It was affirmative for extramedullary hematopoietic tissue.
Patient improved rapidly and uneventfully during his convalescence, with profound improvement in sphincteric function and reduction in spasticity. He was discharged after being ambulant with minimal support and was on regular follow-up.
| Discussion|| |
Thalassemia major is an Mendelian recessive anomaly with complete inability to produce beta chains. It affects individuals in the homozygous state for the defective gene. About 1.5% of the worldwide populations are carriers of the gene, from which 60,000 symptomatic individuals are born annually. These patients tend to be TDT thalassemics and suffer from all stigmata of chronic hemolytic anemia as seen in other blood dyscrasias. Nonetheless, they suffer from ineffective erythropoiesis, despite a compensatory increase in HbF and HbA. The other end of this spectrum is the seemingly benign thalassemia intermedia (TI) who are transfusion independent and this comes at a high price. The gradual “central retreat” of red marrow into the axial skeleton in adults is deferred and overproduction of blood elements by the pathologically expanded bone marrow occurs in TI.
EMH most commonly occurs in the liver and spleen where hematopoiesis normally takes place during the fetal development. The usual manifestations of EMH include hepatosplenomegaly; however, EMH may occur, rarely, in other locations, and present with multisystem involvement, as in the present case.
EMH is common in TI and inadequately transfused thalassemia major patients; however, its occurrence in paraspinal areas is extremely rare ,, and produces varied symptoms of cord compression. Fewer than 11%–15% of patients present with myelopathy and is usually asymptomatic in majority of them. The lesions most commonly involve the thoracic and lumbosacral regions due to the natural anatomic narrowing of the spinal canal. Diagnosis relies on a high degree of clinical suspicion, appropriate neurological examination along with adequate imaging.
Presenting complaints may vary depending on the underlying disorder with paraparesis more common in thalassemia, whereas paraplegia is more common in polycythemia vera and sickle cell anemia. Regardless, any neurological deficits in a known case of hemolytic anemia or hemoglobinopathy should raise a high degree of suspicion toward cord compression secondary to dural or extramedullary hematopoiesis. MRI scans show characteristic paravertebral soft-tissue lesions with varying degrees of spinal cord compression on T1- and T2-weighted series. Diagnosis may also be aided with a biopsy for histopathology; however, due to the obvious risks of cord injury, this is seldom performed unless surgery is also planned. Treatment in these cases can be a combination of, or any one of the following: low-dose radiotherapy with corticosteroids and hydroxyurea, hypertransfusion, and surgical decompressive laminectomy.,,,
Transfusions provide the advantage of reducing excessive extramedullary hematopoiesis sometimes leading to the regression of the lesions and perioperatively combatting bleeding. Transfusion-related complications include iron overload, alloimmunization, infections, and other such entities. Therefore, this modality is probably best reserved as an adjunct to surgery and radiation.
Radiation therapy on the other hand is based on the principle that hematopoietic tissue is especially vulnerable to even low doses of radiation and has proven a reliable treatment avenue because of quick resolution of symptoms. It carries with it however, the unavailability of a tissue biopsy and the risk of tissue edema which can worsen the cord compression. Corticosteroids and hydroxyurea  are supplemented with radiation to reduce edema and recurrences, respectively. There is report of radiotherapy as the sole modality of treatment in a patient presenting with paraplegia.
Surgery involves performing a decompressive laminectomy with excision of the hematopoietic lesion and is an interesting option for the treatment as it provides almost immediate symptomatic relief with neurological recovery. The risks include intraoperative blood loss which can worsen the anemia, hemodynamic instability due to the underlying anemia, potential damage to dura mater, difficulty in excising a diffuse and large lesion, and a slight risk of recurrence.
Surgical decompression is not the first line of treatment in TIT (TI). They are often treated with regular transfusions and low-dose radiotherapy with steroids and hydroxyurea. EMH is not often encountered in thalassemia major; however, in the absence of regular transfusions, this subset of patients may have extramedullary hemopoiesis. Spinal EMH is very rare in thalassemics, and surgery is often considered in conjunction with transfusions and or low-dose radiotherapy.
Emergent decompression was quintessential in view of sphincteric failure and postoperative neurological improvement was remarkable. The large number of patient in the developing nations would make us assume that a protocol is in place; however, no such gold standard of treatment has been formulated. Whether transfusions have an added advantage over surgical decompression is a daunting question. With no algorithm or standard operating procedure in place over the past few decades, each case has been approached and treated on an individual basis. Larger trails would have to be globally instituted to put a protocol in place. Until then, each patient's treatment relies on his physicians experience and expertise.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Galanello R, Origa R. B-thalassemia. Orphanet J Rare Dis 2010;5:11.
Salehi SA, Koski T, Ondra SL. Spinal cord compression in beta thalassemia: Case report and review of the literature. Spinal Cord 2004;42:117-23.
Taher A, Isma'eel H, Cappellini MD. Thalassemia intermedia: Revisited. Blood Cells Mol Dis 2006;37:12-20.
Logothetics J, Constantoulakis M, Exonomidou J, Stefanis C, Hakas P, Augoustaki O, et al
. Thalassaemia major (homozygous eta thalassemia). A survery of 138 cases with emphasis on neurologic and muscular aspects. Neurology 1972:22:249-304.
Prabhakar S, Chopra JS, Khosla VK, Dash S, Banerjee AK. Spinal cord compression in homozygous beta thalassaemia. Surg Neurol 1980;13:351-4.
Parsa K, Oreizy A. Nonsurgical approach to paraparesis due to extramedullary hematopoiesis. Report of two cases. J Neurosurg 1995;82:657-60.
Kaufmann T, Coleman M, Giardina P, Nisce LZ. The role of radiation therapy in the management of hematopoietic neurologic complications in thalassemia. Acta Haematol 1991;85:156-9.
Cario H, Wegener M, Debatin KM, Kohne E. Treatment with hydroxyurea in thalassemia intermedia with paravertebral pseudotumors of extramedullary hematopoiesis. Ann Hematol 2002;81:478-82.
Malik M, Pillai LS, Gogia N, Puri T, Mahapatra M, Sharma DN, et al
. Paraplegia due to extramedullary hematopoiesis in thalassemia treated successfully with radiation therapy. Haematologica 2007;92:e28-30.
Cianciulli P, Sorrentino F, Morino L, Massa A, Sergiacomi GL, Donato V, et al
. Radiotherapy combined with erythropoietin for the treatment of extramedullary hematopoiesis in an alloimmunized patient with thalassemia intermedia. Ann Hematol 1996;72:379-81.
Karimi M, Cohan N, Pishdad P. Hydroxyurea as a firstline treatment of extramedullary hematopoiesis in patients with beta thalassemia: Four case reports. Hematology 2015;20:537.
Angastiniotis M, Modell B. Global epidemiology of hemoglobin disorders. Ann N
Y Acad Sci 1998;850:251-69.
[Figure 1], [Figure 2]