Clinical Neurology and Neurosurgery 112 (2010) 575577

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Clinical Neurology and Neurosurgery

journa l homepage: www.e lsev ier .com

Case report

Diagnosis of acute lymphoblastic leukemia fromblast cr ra

Matthew a, KrDaniel P.a Department o 0211b Department o , MA 0

a r t i c l

Article history:Received 28 MReceived in re18 NovemberAccepted 3 ApAvailable onlin

Keywords:Acute leukemiALLBlast crisisIntracerebral hemorrhageLeukocytosis

ibuteis ofultimrecurtheeukoudy o4:q11t cris

ology of ICH is pivotal in its management. This case demonstrates that the presence of hyperleukocytosisin a patient with intracerebral hemorrhage should raise clinical suspicion for acute leukemia as the causeof the ICH.

2010 Elsevier B.V. All rights reserved.

1. Introdu

Intracerenosed withof the moadvancemepharmacothabnormalitiity and morgeneral remdations forfactors assosis (i.e., grimmature [11,13,14].WICH in patieto encountediagnosis ofin the settin

CorresponHospital, 55 Frfax: +1 617 72

E-mail add

0303-8467/$ doi:10.1016/j.ction

bral hemorrhage (ICH) is common in patients diag-acute leukemia, accounting for approximately 20%

rtality associated with this disease [13]. Despitents in chemotherapeutic dosing regimens, targetederapy, and close monitoring of associated coagulationes, ICH continues to be a signicant cause of morbid-tality in leukemic patients [4]. Management for ICH inains controversial, while evidence-based recommen-ICH in the setting of leukemia are lacking [512]. Riskciated with ICH include the presence of a blast cri-eater than 30% of WBC in the circulating blood areblast forms), leukocytosis, and other coagulopathieshile there are several post-mortemstudies identifying

nts previously diagnosed with leukemia, it is unusualr ICH as the initial presenting sign that reveals a newacute leukemia [15,16,3]. Since themanagement of ICHg of newly diagnosed acute leukemia with blast crisis

ding author at: Department of Neurosurgery, Massachusetts Generaluit Street, Boston, MA 02114, United States. Tel.: +1 617 726 6156;4 7407.ress: lborges@partners.org (L.F. Borges).

is very uncommon and may need to focus on the management ofthe leukemia as well as the hemorrhage, we present such a patientwhowasmanagedwithout surgery andwith an excellent outcome.

2. Case report

A55-year-oldmalewith ahistoryofmyocardial infarction, coro-nary artery bypass graft, and no prior blood dyscrasias presentedin June 2007 with a chief complaint of dizziness after sustain-ing an unwitnessed syncopal fall in his kitchen. The patients wifestated that she found her husband lying on the oor, complain-ing of back pain. Initial physical examination in the emergencydepartment revealed him to be stable; he was alert, oriented,and neurologically intact. Probing further into his medical his-tory, it was learned that he complained of mid-scapular pain overthe previous two weeks. He also had a severe occipital headacheover the previous two days. Given the patients scapular painand known aortic root dilatation, attention was turned to inves-tigation of his aortic vasculature with a concern for dissection.A contrast-enhanced computerized tomography (CT) of the chestdemonstrated a 4.7 cm undissected ascending aortic aneurysmwithout evidence of acute pathology.While awaiting further evalu-ationbycardiothoracic surgery, thepatientdevelopedacutementalstatus changes and became unresponsive. Hewas emergently intu-bated and underwent a non-contrast head CTwhich revealedmany

see front matter 2010 Elsevier B.V. All rights reserved.clineuro.2010.04.001isis. A case report and review of the lite

R. Naunheima, Brian V. Naheda, Brian P. WalcottCahill a, Lawrence F. Borgesa,

f Neurosurgery, Massachusetts General Hospital & Harvard Medical School, Boston, MAf Hematopathology, Massachusetts General Hospital & Harvard Medical School, Boston

e i n f o

ay 2009vised form2009ril 2010e 20 May 2010

a

a b s t r a c t

Intracerebral hemorrhage (ICH) contrfering from acute leukemia.While ICHfor ICH to be the presenting sign thatwith previously undiagnosed acute pdiffuse encephalopathy due to ICH intially suspected, because of the hyperlmarrow biopsy and ow cytometry stPhiladelphia translocation t(9:22)(q3permitted targeted therapy of the blas/ locate /c l ineuro

intracerebral hemorrhage andture

istopher T. Kahlea, Chad P. Soupirb,

4, United States2114, United States

s signicantly to the morbidity and mortality of patients suf-ten identied in autopsy studies of leukemic patients, it is rareately leads to the diagnosis of leukemia. We report a patientsor B-cell lymphoblastic leukemia (ALL) who presented withsetting of an acute blast crisis. The diagnosis of ALL was ini-cytosis observed on presentation, then conrmedwith a bonef the peripheral blood. Furthermore, detection of the BCR/ABL) in this leukemic patient by uorescent in situ hybridizationis with imatinib (Gleevec). Understanding the underlying eti-

576 M.R. Naunheim et al. / Clinical Neurology and Neurosurgery 112 (2010) 575577

Fig. 1. (A) A non-contrast head CT taken at the time of initial presentation demonstrates a 0.9 cm left cemeasuring 1.1 cm at its greatest dimension. There are also two parenchymal hemorrhages, measuringhemorrhage. (B) A non-contrast head CT scan taken three weeks after patients initial presentation demshift now measuring 9mm (previously 1.1 cm).

intracranial lesions: a 9mm left subdural hematoma, two non-contiguous left frontal parenchymal hemorrhages (4.3 cm1.6 cmand 2.9 cm2.7 cm), and extensive left subarachnoid hemorrhage.The mass effect exerted from this hemorrhage resulted in a 1.1 cmleft-to-right midline shift.

The patient was then transferred to the Massachusetts GeneralHospital where he arrived intubated and sedated. His pupils wereequal, round, and reactive to light. His bilateral upper extremitiesexed to stimuli and his bilateral lower extremities withdrew tostimuli. The neurosurgical service was consulted for the evalua-tion of ICHhe sustainecal impresswas more etrauma asswent an intICH (Fig. 1aor vascularratory testsnotable forsis (92,000/of acute leu

Table 1Results of labo

Variable

White bloodHemoglobinHematocritPlatelet coun

DifferentialBlastsBand formLymphocyMonocyteEosinophiBasophilsPoly

ProthrombinPartial thromInternationa

SodiumPotassiumChlorideCO2BUNCreatinineGlucose

data and thexam imprand spontaadmitted towas closelycorrect hissis, he undeBID), allopuHis plateletfusion. Afte

ytosieninl hextub, andB-cematoanal(q34in ato inprod-up iation0/Ll resmorent

r as a

cussi, which was initially thought to be related to the falld from his syncopal episode. However, the neurosurgi-ion was that it seemed that the pattern of hemorrhagextensive than would be expected from the minor headociated with a syncopal episode. The patient under-erval non-contrast head CT which demonstrated stable). CT angiography revealed no evidence of aneurysmmalformation to account for the hemorrhage. Labo-obtained concurrent to the radiological workup weremarked thrombocytopenia (30,000/L) and leukocyto-L), with 86% blasts (Table 1). A presumptive diagnosiskemia was made following review of the laboratory

ratory tests on presentation.

Value Reference range

cell count (per mm3) 92 4.511.0 th/cmm(g/dl) 12.3 13.517.5 g/dl(%) 36.5 41.053.0%t (per mm3) 30 150350 th/cumm

count (%)86 0%

leukoceye opIntervasoon ebiopsycursorthe he(FISH)t(9;22)foundtinib)fusionFollowambul(13,00intervather heunderwbrothe

3. Diss 2 010%tes 5 2244%s 1 411%ls 0 08%

0 03%6 4070%

time (s) 12.6 10.313.2 sboplastin time (s) 21.6 22.134.0 sl normalized ratio 1.1

135 135145mmol/L5.5 3.44.8mmol/L

106 100108mmol/L22.9 23.031.9mmol/L45 825mmol/L1 0.61.5mg/dl

220 70110mg/dl

ApproxiMultiple pacerebrovascful medicadiagnosis osigns of ICfocal neurotates invesgrowth is aICH; correcapproximatdepartmenetiologic fain the settisymptoms orebral convexity subdural hematoma with left-to-right midline shift4.3 cm1.6 cm and 2.9 cm2.7 cm. There is extensive subarachnoidonstrating evolution of the previously seen hemorrhage with midline

e peripheral blood smear. The patients neurologicaloved as sedation was held; he opened his eyes to voiceneously moved all four extremities. The patient wasthe Intensive Care Unit where his neurological exammonitored. Exogenous platelets were administered tothrombocytopenia. To manage his robust leukocyto-rwent leukophoresis and a course of hydroxyurea (2 grinol (300mg BID) and dexamethasone (4m Q6 hours).count increased to 70,000/L after his platelet trans-r leukopheresis and pharmacological treatment of hiss, the patients neurological exam improved such thatg became spontaneous and he followed commands.ad CT scans revealed stable hemorrhages, and he wasated. Following review of the bone marrow aspirate,peripheral blood ow cytometry, a diagnosis of pre-ll acute lymphoblastic leukemia (ALL) was made bypathology service. Fluorescence in situ hybridizationysis identied a BCR/ABL Philadelphia translocation;q11), which is characteristic of CML but can also besubset of ALL. The patient started chemotherapy (ima-hibit the exuberant tyrosine kinase of the BCR/ABLuct. He was discharged to home in complete remission.n onemonth revealed improved cognitive function and.Hiswhite blood cell count andplatelet count improvedand 326,000/L, respectively). A head CT demonstratedolution of the original hemorrhage with no sign of fur-rhage (Fig. 1b). Twomonths after discharge, the patientsuccessful allogenic stem cell transplantation, with hisdonor.

onmately 37,000 people develop an ICH each year [17].thological processes can cause ICH, including trauma,ular disease, and coagulation disorders [18,19]. A care-l history and non-contrast head CT often leads to af ICH, as was the case with our patient. PresentingH are headache, fatigue, mental status changes andlogical decits [15,16]. Once identied, ICH necessi-tigation to elucidate contributing factors. Hematomassociatedwith increasedmortality and poor outcome intable factorsmust therefore be treated expeditiously, asely30%ofpatientswith ICHpresenting toanemergencyt have ongoing intracerebral bleeding [20,21]. One suchctor is leukemic blast crisis, which should be suspectedng of ICH with marked leukocytosis. Thus, signs andf ICH should bemonitored closely in leukemic patients,

M.R. Naunheim et al. / Clinical Neurology and Neurosurgery 112 (2010) 575577 577

as fatal ICH ismost likely to occurwithin therst ten days followingthe initial blast crisis [22]. This case presents a unique situation inwhich ICHwas detected prior to the diagnosis of B-cell ALL, demon-strating that leukemia should be on the differential diagnosis forICH of unknown etiology, particularly in the setting of hyper-leukocytosis, and a characteristically abnormal peripheral bloodsmear.

The underlying pathophysiology of ICH in ALL is likelymultifac-torial. Graucommonlyin leukemiculopathy, orexact pathoof leukostadue to increleukocytes)topenia) likacute leukewhile 50 hathy as theexact pathois second opatientswit[2,1,16].

Surgeryan extant coof ICH is lathe Interna(STICH) triaevacuationadvantagewithin 1 cmfrom the Amgiving consis located wassociatedAlthough nminimally i[24].

Treatmethe underlycorrect theto reverse lhis recoverexcellent nICH have adural hemathe parenchcompressioabnormalitiwith thromtern of hemetiologies snosis drastioutcome.

Competing

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Funding

None.

Acknowledgements

None.

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derickthe mate: aociatiality oke 20ndelor Opinnetskcome5;102ers L.el MEiew. Nkey Geffec7;28(us F, Rcer. MH, Le

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tt T,ly hem7;28(erl S,blastindeloet al.ntaneal Tria5;365rgan Ts of thcuatioel PV,et al.aceres et al. [13] report that while hypertension is the mostassociated risk factor for ICH in the general population,patients other causes such as hyperleukocytosis, coag-emboli from infection aremore likely to cause ICH. Thegenesis of ICH in leukemia is unknown, but componentssis (i.e., stagnation of small cerebral vessel blood owased blood viscosity from high numbers of circulatingand/or coagulopathy (i.e., due to severe thrombocy-ely contribute. In an autopsy study of patients withmia and ICH, 19 of 69 demonstrated severe leukostasis,d no leukemic inltration, likely indicating coagulopa-primary etiology in this group [13]. Regardless of itsgenesis, ICH is a grave prognostic indicator in ALL andnly to infection as the most common cause of death inh either acutemyelogenous or lymphoblastic leukemia

has little role in the management of ICH in cases withagulopathy such as leukemic blast crisis. Managementrgely medical as a result of ndings generated fromtional Surgical Treatment in Intracerebral Hemorrhagel. This study demonstrated no benet to early surgicalof ICH [23]. However, subgroup analysis demonstratedto early surgical evacuation of hemorrhages located

of the cortical surface. Current recommendationserican Heart Association parallel these ndings, only

ideration to surgical evacuation of hemorrhage thatithin 1 cm of the cortical surface and those lesions

with marked mass effect, edema, or midline shift [7].ot completed, an ongoing trial may show benet fornvasive surgery for ICH in the absence of coagulopathy

nt in this case was immediately aimed at addressinging pathophysiology; platelets were administered tothrombocytopenia, and leukophoresis was performedeukostasis. These initial treatments were essential toy. This patient is fairly unique, as he survived witheurological outcome; most patients with blast crisishigh rate of mortality. In addition, patients with sub-toma and ICH fare considerably worse, likely due toymal injury caused by the hematoma and brainstemn [25]. Cases of ICH with associated hematologicales such as hyperleukocytosis, especially if associatedbocytopenia, particularly those with an unusual pat-orrhage, should raise clinical suspicion of uncommonuch as leukemic blast crisis. Accurate and rapid diag-cally impacts both the choice of treatment and patient

interests

ors do not have any conicts or competing interests.as not been previously published and is not under con-lsewhere for publication.

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Diagnosis of acute lymphoblastic leukemia from intracerebral hemorrhage and blast crisis. A case report and review of the ...IntroductionCase reportDiscussionCompeting interestsFundingAcknowledgementsReferences