Case report Bilateral subdural haematomas following lumbar ... - Nature

Bone Marrow Transplantation, (1999) 24, 1033–1035  1999 Stockton Press All rights reserved 0268–3369/99 $15.00 http://www.stockton-press.co.uk/bmt

Case report Bilateral subdural haematomas following lumbar puncture in three haematopoietic stem cell transplant recipients P Hentschke1, H Ha¨gglund1,2, J Mattsson1, S Carlens1, B Lo¨nnqvist2, P Ljungman1,2, J Aschan1,2, S Fredrikson3 and O Ringde´n1 1

Centre for Allogeneic Stem Cell Transplantation, Departments of 2Haematology and 3Neurology, Huddinge Hospital, Stockholm, Sweden

Summary: Between 1990 and 1996, three patients (1.1%), all with CML, among 272 patients with haematological malignancies, developed bilateral subdural haematomas (SDH) after treatment with i.t. MTX before HSCT in our unit. Since October 1996, we have given i.t. MTX only to patients at increased risk of CNS leukaemia such as ALL and AML M4 or M5. We suggest that intrathecal treatment before HSCT should only be given to patients at increased risk of CNS leukaemia. Keywords: bone marrow transplantation; methotrexate; lumbar puncture; subdural haematoma; CML

Subdural haematomas have been observed after dural puncture and are normally a rare complication. However, they are more common in patients with leukaemia and after haematopoietic stem cell transplantation (HSCT).1 The reported incidences of SDH vary depending on the diagnosis and treatment.2–4 Post-puncture headache has been said to be caused by cerebrospinal fluid leakage, followed by decreased intracranial pressure, leading to traction of pain-sensitive vessels that also may rupture.5 Post-puncture headache that does not disappear is therefore an indication for computerized tomography (CT). Treatment for SDH may be conservative but surgical drainage is often necessary.6 Patients, methods and results Two of three patients with CML underwent conditioning with CY 60 mg/kg i.v. once daily for 2 days and TBI 10 Gy (9 Gy to the lungs). One patient received BU 4 mg/kg p.o. in divided doses daily for 4 days and CY 60 mg/kg i.v. once daily for 2 days.7 GVHD prophylaxis consisted of CYA, in combination with MTX.8 Two patients were also treated with heparin 100 U/kg/day from day −4 as Correspondence: Dr P Hentschke, Centre for Allogeneic Stem Cell Transplantation, Huddinge Hospital, B56, SE-141 86 Huddinge, Sweden Received 27 November 1998; accepted 13 May 1999

VOD prophylaxis.9 Intrathecal MTX was given on day −2 to one patient, on days −9 and −2 to one patient and on day −9 to another patient. Post-puncture headache developed immediately after i.t. MTX in all patients. Bilateral subdural haematomas were diagnosed by CT between days +11 and +27 after HSCT. Surgical drainage was performed in all three patients and two patients are alive and well 8. and 3 years after HSCT, respectively. One patient died of liver failure 5 months after HSCT. Case 1 A 34-year-old male with CML underwent BMT from an HLA-identical brother in October 1990 after treatment with BU and CY. I.t. MTX was given on day −2 before BMT and was followed by the immediate onset of headache that resolved spontaneously. At this time, his platelet count was 100 ⫻ 109/l, prothrombin time and partial thromboplastin time were normal. Ten days after HSCT, he again developed a bilateral frontal headache which was different from the initial headache. His platelet count at this time was 10 ⫻ 109/l. Five days later, he complained of nausea and vomiting and became somnolent. CT on day +20 revealed bilateral SDH about 1 cm wide on the left side and 0.5 cm on the right side with slight displacement of the septum pellucidum to the right. The plantar response was extensor. The platelet count at this time was 47 ⫻ 109/l. Surgical drainage of the left haematoma was performed on day +21 after transfusion of one unit of platelets. He improved initially, but his headache and nausea recurred 10 days after surgery and CT still showed SDH. The patient was observed for 3 days by neurosurgeons and re-operation was not considered to be indicated. The patient recovered spontaneously during the following weeks. He is alive and well 8. years after BMT. Case 2 A 49-year-old male with CML was transplanted with PBSC from an unrelated HLA-identical donor in February 1996 after treatment with CY and TBI. Heparin was given as a continuous infusion over 24 h from day −4 as prophylaxis against VOD. The partial thromboplastin time during this treatment was about 40 s (normal 28–38 s), the prothrombin

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time was normal and the platelet count was initially normal. On days −9 and −2, i.t MTX was given. Heparin treatment was stopped for 24 h at the time of lumbar puncture. He suffered a moderate post-puncture headache that resolved initially after the first lumbar puncture. After the second puncture he again immediately had a headache. Platelet counts were normal on both occasions. During the following 4 weeks he successively developed a severe, immobilizing headache, nausea and vomiting. CT on day +27 showed a bilateral SDH measuring 1.5 cm in thickness on the left and 1 cm on the right side with displacement of the septum pellucidum (see Figure 1). At this time, the platelet count was ⬎200 ⫻ 109/l. Heparin treatment was discontinued. Three days later, he successfully underwent surgical drainage. He is alive and well 3 years after HSCT. Case 3 A 44-year-old man with CML received i.t. MTX on day −9 prior to PBSC. He was conditioned with CY and TBI. The second i.t. MTX was not given, because of post-puncture headache that occurred immediately after the first puncture. His platelet count was normal at this time. As prophylaxis against VOD, heparin was given as a continuous infusion over 24 h from day −4. The prothrombin time and partial thromboplastin time were normal. On day +10 the headache had worsened and neurological examination showed ptosis of the left eye, and the plantar response was extensor on the right side. CT on day +11 showed bilateral SDH (0.5 cm wide). His platelet count at this time was 23 ⫻ 109/l. Heparin treatment was discontinued. Surgery was not considered to be immediately indicated. CT on day +18 was unchanged and the symptoms were less. The symptoms fluctuated, but on day +38 his balance became poor and he was confused. CT scan on the same day showed slight progression of the SDH bilaterally. His platelet count was 115 ⫻ 109/l. Surgical drainage was performed on day +40 and he recovered. However, he died of liver failure 5 months after HSCT.

Discussion The risk of SDH is increased in HSCT recipients.1 This may be due to several factors, such as malignancy, thrombocytopenia, heparin treatment and intrathecal treatment. It is difficult to say which risk factors are of importance, because SDH is a rare event. Due to several possible risk factors SDH may be present, and clinically silent, before lumbar puncture. To exclude this possibility CT scan prior to spinal tap could be conducted. In cases of a SDH, lumbar puncture should not be performed as this could cause a transtentorial herniation. In our patients CT scan was not performed prior to lumbar puncture. Therefore, we cannot exclude that SDH could have been present before dural puncture. However the patients only developed headache signifying cerebral bleeding after the puncture. In the first patient the post-puncture headache resolved and then recurred when the platelet count was 10 ⫻ 109/l. In this case the low platelet count may have contributed to the development of the SDH. The post-puncture headache indicates that the lumbar puncture may have initiated the development of SDH. Low platelet counts occur in all HSCT patients and are a risk factor that is difficult to avoid. The development of SDH is possibly multifactorial and risk factors should be minimised. Some patients may also have unknown predisposing factors. The second patient had headache for several weeks and CT was not performed until his symptoms had become worse. Although this case had a happy outcome, it indicates that one should not wait too long to perform CT scans in patients with post-puncture headache. All three patients with SDH were adults with CML. Pomeranz et al1 reported 13 patients with SDH out of 273 bone marrow transplanted patients. Their median age was 31 years (21–42). Five of them had CML. It is unlikely that CML is associated with an increased risk of developing SDH. The low incidence of SDH and the fact that CML is a common indication for HSCT make this difficult to verify. Two of our patients received prophylactic treatment for VOD with heparin, which may increase the risk of haemorrhage. We have stopped giving heparin as VOD prophylaxis, since a study from our centre showed that the incidence and mortality of VOD were not affected by heparin treatment.9 All three patients had a platelet count above 50 ⫻ 109/l at the time of operation, and surgical drainage of the haematomas was successful. Pomeranz et al reported that seven patients underwent neurosurgery without complications. Neurosurgery seems feasible after HSCT. Since we stopped giving i.t. MTX to all patients no SDH have been detected in over 100 stem cell transplant patients. As the incidence of SDH is low there is still too few patients to be statistically evaluable. However, based on these three cases, we suggest that intrathecal treatment before BMT should only be given to patients with ALL, AML M4 or M5 or a history of CNS leukaemia.10 References

Figure 1 Bilateral subdural haematoma with displacement of the septum pellucidum in a 49-year-old male with CML 27 days after HSCT.

1 Pomeranz S, Naparstek E, Ashkenazi E et al. Intracranial haematomas following bone marrow transplantation. J Neurol 1994; 241: 252–256.

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2 Wiznitzer M, Packer RJ, August CS, Burkey ED. Neurological complications of bone marrow transplantation in childhood. Ann Neurol 1994; 16: 569–576. 3 Patchell RA, White CL, Clark AW et al. Neurological complications of bone marrow transplantation. Neurology 1985; 35: 300–306. 4 Mohrmann RL, Mah V, Vinters HV et al. Neurological findings after bone marrow transplantation: an autopsy study. Hum Pathol 1990; 21: 630–639. 5 Wyble SW, Viswanathan S, Bayhi D, Webre D. Bilateral hematomas after dural puncture: delayed diagnosis after false negative computed tomography scan without contrast. Regional Anesthesia 1992; 17: 52–53. 6 Dent DL, Croce MA, Menke PG et al. Prognostic factors after acute subdural hematoma. J Trauma 1995; 39: 36–42. 7 Ringde´n O, Ruutu T, Remberger M et al. A randomized trial

comparing busulphan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia. A report from the Nordic Bone Marrow Transplantation Group. Blood 1994; 83: 2723–2730. 8 Ringde´n O, Pihlstedt P, Markling L et al. Prevention of graftversus-host disease with T cell depletion or cyclosporin and methotrexate. A randomized trial in adult leukemic marrow recipients. Bone Marrow Transplant 1991; 7: 221–226. 9 Ha¨gglund H, Remberger M, Klaesson S et al. Norethisterone treatment, a major risk-factor for veno-occlusive disease of the liver after allogeneic bone marrow transplantation. Blood 1998; 92: 4568–4572. 10 Greer JP, Baer MR, Kinney MC. Acute myelogenous leukemia. In: Lee GR, Forester J, Lukens J et al (eds). Wintrobe’s Clinical Hematology, 10th edn. William & Wilkins: Baltimore, 1999, pp 2272–2319.

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