Correspondence.

(Letters to the Editor are welcomed. They may report new clinical or laboratory observations and new developments in medical care or may contain comments on recent contents of the Journal. They will be published, if found suitable, as space permits. Like other material submitted for publication, letters must be typewritten, double-spaced, and submitted in duplicate. They must not exceed two typewritten pages in length. No more than five references and one figure or table may be used. See "Information for Authors" for format of references, tables, and figures. Editing, possible abridgment, and acceptance remain the prerogative of the Editors.)

Conservative Management of Lumbar Disk Herniations in Adolescents

To the Editor: We have taken an interest in the case report by Hood-White et al (1) that was published in your journal recently. They described an adolescent patient with a central lumbar disk herniation who had been treated conservatively. Although we agree with their conservative handling of the patient, we would like to comment on certain aspects of the management of this case.

The authors mentioned that, in the very first examination of the patient, only back pain was present during the straight leg raising test (SLRT), 70[degrees] on the right and 45[degrees] on the left. Having initially diagnosed the patient as having lumbar strain, they seem not to have considered that finding to be relevant with any lumbar root irritation (LRI). We admit that the SLRT is generally accepted to be positive if the patient describes pain radiating toward the leg; however, this is not always what we encounter in daily practice. Thus, the diagnosis of LRI should have been suspected and ruled out with other confirmative tests (eg, Kernig's sign, Milgram's test, or Naffziger's test), or the patient could have been questioned regarding any radiating pain during straining, coughing, or sneezing. These clinical hints would have implied the necessity of an earlier magnetic resonance imaging (MRI) study for the likely diagnosis of herniation. We also wonder if the patient was prescribed a reasonable period of strict rest in the first 5 days, before the second visit and the results of the SLRT done at that time. It could have been very instructive if the authors had reported the patient's consecutive SLRT results in subsequent visits (as they did for the blood analysis), since this simple test is quite informative regarding the degree of spinal root irritation and its response to the applied treatment.

The authors declare that the radiographs, which would have been performed during the first visit, were noncontributory for the diagnosis, but they do not mention any likely structural differences, such as facet joint asymmetry or transitional vertebrae, that usually accompany disk herniations in children and adolescents. (2, 3)

The task of alleviating pain in these patients is genuinely difficult. Although the known cascade of inflammatory cytokines may play a role in the discogenic pain, (4) its unresponsiveness to the anti-inflammatory agents cannot easily be elucidated. The authors also had difficulty in managing the patient's pain. Adjusted doses of diazepam would be beneficial in such cases, since diazepam is also a strong muscle relaxant.

We are also curious about the details of physical therapy, such as the type of traction, duration of therapy, medical professional in charge, the effect of levothyroxine therapy on the patient's pain relief, the duration of subsequent bed rest (sick leave), and the frequency of control visits. These details are not mentioned in the case report.

Overall, we do agree that conservative treatment is a very appropriate alternative for these patients. Surgery should be considered as a last resort in children and adolescents, since its results have a tendency to deteriorate between short-term and long-term follow-up. (5) We do believe that all other alternatives should be tried before young patients are faced with surgery. Last, but not least, the conservative management of patients with disk herniations should definitely be executed by specialists experienced in physical medicine an rehabilitation practice.

Levent Ozcakar, MD

Department of Physical Medicine and Rehabilitation 

Hacettepe University Medical School

48.sok. 15/1 Bahcelievler

Cankaya, Ankara, Turkey

Z. Birsin Ozcakar, MD

Gazi University Medical School

Ankara, Turkey

References

(1.) Hood-White R, Lowdon JD: Herniated nucleus pulposus with radiculopathy in an adolescent: successful nonoperative treatment. South Med J 2002; 95:932-933

(2.) Ishihara H, Matsui H, Osada R, et al: Facet joint asymmetry as a radiological feature of lumbar intervertebral disc herniation in children and adolescents. Spine 1997; 22:2001-2004

(3.) Lee JY, Ernestus RI, Schroder R, et al: Histological study of lumbar intervertebral disc herniation in adolescents. Acta Neurochir (Wien) 2000; 142:1107-1110

(4.) Miyamoto H, Saura R, Harada T, et al: The role of cyclooxygenase-2 and inflammatory cytokines in pain induction of herniated lumbar intervertebral disc. Kobe J Med Sci 2000; 46:13-28

(5.) Parisini P, DiSilvestre M, Greggi T, et al: Lumbar disc excision in children and adolescents. Spine 2001; 26:1997-2000

Reply

To the Editor: The evaluation of an adolescent presenting with low back pain can be a challenging problem, and we agree that thorough, timely, and sequential physical examinations are necessary. Statistically, however, the likelihood that an adolescent patient will actually have central lumbar disk herniation is quite low, with patients aged < 25 years comprising only 2.3% of all patients with herniated nucleus pulposus (HNP). (1)

We concur that tabulated serial straight leg raising tests would provide valuable information, but because there were different examiners, we could not supply this information. While it is true that nerve root irritation can develop in the lumbar spine and present as sciatica, thus suggesting the diagnosis of a herniated disk, it is unlikely that, upon initial examination, a physician would suspect lumbar disk herniation as a first diagnosis in an adolescent.

Radiographs traditionally have a low yield in the diagnosis of patient with little or no acute trauma. Magnetic resonance imaging (MRI) should not be used as the first diagnostic tool for patients with acute low back pain in patient groups where medical treatment, "tincture-of-time," or other diagnostic tools exist for the statistically more likely conditions. The MRIs are costly, and frequently necessitate deep sedation or general anesthesia in the younger child or adolescent. In this case, an MRI was not obtained earlier since there was no indication of HNP.

It has also been demonstrated that, for patients with acute low back pain, normal activity is therapeutically at least equivalent to bed rest. (2,3) In fact, it has been shown that there are potentially harmful effects of prolonged bed rest in patients with acute low back pain. (3)

Indeed, diazepam ia a remarkably good, even underutilized, muscle relaxant. In these times, when so many individuals are taking other agents that are active in the central nervous system (especially selective serotonin reuptake inhibitors) with which traditional muscle relaxants may interact, diazepam may often be the muscle relaxant of first choice.

Regarding physical therapy, water traction was used, and actually exacerbated the pain. Exercises seemed to work best, with the backward-bending position being the most useful. Ice was also applied routinely, which helped control the pain. Use of a corset was attempted, but this yielded no positive results, since the patient was reluctant to use it on a long-term basis.

Low back pain is a major health problem in developed countries, and is most commonly treated in the primary health care setting. (4) We believe that many experienced primary care physicians are adequately equipped to handle the diagnosis, treatment, and management of adolescents presenting with HNP. Specialists trained in physical medicine and rehabilitation should certainly be considered for consultation and to perform more invasive nonsurgical treatments as indicated.

Ramona Hood-White

J. Devon Lowdon, MD

PG Box 6222

Charlottesville, VA 22906-6222

References

(1.) Pietila TA, Stendel R, Kombos T, et al: Lumbar disc hernition in patients up to 25 years of age. Neurol Med Chir (Tokyo) 2001; 41:340-344

(2.) Rozenberg S, Delval C, Rexvani Y, et al: Bed rest or normal activity for patients with acute low back pain: a randomized controlled trial. Spine 2002; 27:1487-1493

(3.) Hagen K, Hilde C, Camtvedt C, et al: The Cochrane Review for bed rest for acute low back pain and sciatica. Spine 2000; 25:2932-2939

(4.) Koes B, van Tulder M, Ostelo R, et al: Clinical guidelines for the management of low back pain in primary care: an international comparison. Spine 2001; 26:2504-2513

Adult T-Cell Leukemia/Lymphoma Presenting as Obstructive Jaundice With Complete Resolution of Jaundice After Chemotherapy

To the Editor. Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoproliferative malignancy associated with the human T-cell leukemia virus-I (HTLV-l). It is characterized by the proliferation of abnormal lymphocytes with deeply indented or lobulated nuclei and post-thymic/mature CD4+ phenotype. In addition to skin involvement and hypercalcemia, which are known to be common in ATLL, these patients show a higher incidence of hepatic involvement compared with patients with non-Hodgkin's lymphomas (NHLs). There is more frequent hepatomegaly, and higher levels of total bilirubin, alanine amino transferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) in patients with ATLL than in patients with NHL. We describe a patient with ATLL who had severe obstructive jaundice that completely resolved with combination chemotherapy. To our knowledge, this has not previously been reported in the literature.

A 71-year-old Jamaican woman presented with hypercalcemia, itching, and jaundice. Physical examination showed a maculopapular rash on the chest, moderate hepatomegaly, and small, bilateral, axillary lymphadenopathy. Laboratory studies showed a white blood cell count of 19 x [10.sup.3]/[micro]L (70% lymphcytes) with normal hematocrit level and platelet count. Other significant laboratory values included: ALT, 82 U/L; AST, 70 U/L; LDH, 1,071 U/L; calcium, 12.4 mg/dL. Over a period of 4 weeks, there was progressive elevation in the levels of serum bilirubin (to a peak of 23.9 mg/dL with > 75% direct bilirubin), ALP (to a peak of 952 U/L), and gamma-glutaryl transferase (GGT) (to a peak of 898 U/L). Examination of the peripheral blood smear was remarkable for lymphocytosis, with 10% atypical lymphocytes that were flower-shaped, polylobulated, and compatible with ATLL (Figure). Bone marrow biopsy revealed a focal T-cell aggregate with an apparently aberrant phenotype (CD5+, CD3+) compatible with T-cell leukemia. C hromosomal analysis showed a normal karyotype. Test for HTLV-l antibody was positive. Bone scan showed diffusely increased uptake. Ultrasonography of the abdomen showed moderate hepatomegaly without intrahepatic or extrahepatic biliary dilatation. Serologic tests for hepatitis A, B, and C were negative. Computed tomography of the abdomen revealed a borderline enlarged spleen and mediastinal and retroperitoneal lymphadenopathy. Based on these findings, the patient was diagnosed as having ATLL and treatment with cyclophosphamide, adriamycin, yincristine, and prednisone (CHOP) chemotherapy was begun. After 2 cycles of CHOP chemotherapy given over a period of 3 weeks, liver function tests completely normalized. Eventually, 6 weeks after the second cycle of CHOP chemotherapy, the patient relapsed with meningeal leukemia and died. Post-mortem needle biopsy of the liver revealed portal and periportal fibrosis with residual lymphoid cells. Fatty degeneration of the hepatocytes at the periphery of the portal triads an d mild liver atrophy were also noted.

Adult T-cell leukemia/lymphoma was first recognized in 1977 in patients born in southwestern Japan and has since been diagnosed in American-born blacks from the southeastern United States and in West Indian immigrants to the United States and Britain. (1) It is characterized by a leukemic or lymphomatous proliferation of hyperlobulated peripheral T-cells, and is associated with infection by a type C retrovirus. (1) The HTLV-l virus is transmitted by blood transfusion, needle sharing, sexual intercourse, and from mother to child through breast milk. Less than 5% of infected persons have ATLL, a process that typically has a latent period of 20 to 30 years. The clinical course is variable, and can be comprised of acute, lymphoma, chronic, or smoldering forms.' The acute form is the most common presentation (55% to 60% of cases), and consists of lymphadenopathy, organomegaly, skin infiltration, leukocytosis, hypercalcemia, and increased LDH level; lytic bone lesions and pulmonary lesions are common. It has a rapi dly fatal course. The lymphoma form (20% to 25% of cases) presents mainly with lymphadenopathy. Extranodal lymphatic sites, including skin, Waldeyer's ring, gastrointestinal tract, sinuses, and pleura, can be affected.

Adult T-cell leukemia/lymphoma is invariably fatal. Poor prognostic features include a high leukocyte count ([greater than or equal to]20 x [10.sup.3] [micro]L), hypercalcemia, and elevated LDH level. The median survival time for patients with these poor prognostic features is approximately 3 months, while those without any of these factors have a median survival time of about 8 months. (2) The treatment strategy for ATLL has not been established. Combination chemotherapy regimens derived from CHOP, such as vincristine, cyclophosphamide, prednisone, and doxorubicin (VEPA) and VEPA plus methotrexate (VEPAM), have failed to yield high complete remission rates or long survival times. (3) A multi-institutional trial attempting to increase dose intensity, supported by treatment with granulocyte colony-stimulating factor, has shown improved remission rates and survival times. (4)

Our patient presented with an acute, progressive obstructive jaundice, most likely due to liver infiltration by leukemic cells (as shown by postmortem liver biopsy). Other causes of jaundice, including medications, hepatitis, and gallstones, were ruled out. Hepatic involvement, with high levels of total bilirubin, transaminases, LDH, and ALP, is more common in patients with ATLL than in those with NHL, (5) but complete resolution of obstructive jaundice after chemotherapy, as in this case, has not been described in the literature. Therefore, combination chemotherapy might be an option in patients with ATLL and hepatic involvement, though it may not significantly improve the survival rate.

Pawan K. Rao, MD

University of Texas Health Science Center at San Antonio 

Department of Medicine

7703 Floyd Curl Dr, Mail Code 7882

San Antonio, TX 78229-3900

Parag Mehta, MD

Muthuswamy Krishnamurthy, MD

New York Methodist Hospital

Department of Medicine

506 6th St

Brooklyn, NY 11215

References

(1.) Uchiyana T, Yodoi J, Sagawa K, et al: Adult T-cell leukemia: clinical and hematological features of 16 cases. Blood 1977; 50:481-492

(2.) Tamura K, Nagamine N, Araki Y, et al: Clinical analysis of 33 patients with adult T-cell leukemia-diagnostic criteria and significance of high and low risk ATL. Int J Cancer 1986; 37:335-341

(3.) Taguchi H: Treatment of adult T-cell leukemia. Gan To Kagaku Ryoho 1995; 22:16-22

(4.) Taguchi H, Kinoshita KI, Takatsuki K, et al: An intensive chemotherapy of adult T-cell leukemia/lymphoma CHOP followed by etoposide, vindesine, ranimustine, and mitoxantrone with granulocyte colony-stimulating factor support. J Acquir Immune Defic Syndr Hum Retrovirol 1996; 12:182-186

(5.) Yamada Y, Kamihira S, Murata K, et al: Frequent hepatic involvement in adult T-cell leukemia: comparison with non-Hodgkin's lymphoma. Leuk Lymphoma 1997; 26:327-335

Hematoma and Enoxaparin Use

To the Editor: Although intracranial hemorrhage and retroperitoneal hematoma are serious complications known to be associated with enoxaparin use, the list of potential bleeding complications is expanding as the use of this low molecular weight (LMW) heparin continues to grow. In addition to the rare complication of spontaneous hemothorax recently reported, (1) enoxaparin use has been linked to other potentially life-threatening conditions. For example, spontaneous rupture of a pathologically normal spleen has been reported in a patient treated solely with enoxaparin for a presumed false-negative ultrasonographic evaluation of the legs for deep vein thrombosis (DVT). (2) That enoxaparin and other LMW Hepariris (3) could be associated with spontaneous splenic rupture is not totally surprising, since intravenous (4) and subcutaneous (5) unfractionated heparin have been associated with spontaneous splenic rupture in patients treated for cerebrovascular disease and DVT, respectively.

Although treatment with enoxaparin and other LMW heparins offers advantages over the use of unfractionated heparin, clinicians should remain vigilant in monitoring for bleeding complications, even in patients without risk factors (ie, recent trauma or surgery; use of aspirin or glycoprotein IIb/IIIa inhibitors; thrombolysis; and advanced age). Spontaneous hemothorax and nontraumatic splenic rupture are 2 complications now known to occur in patients treated with enoxaparin or other LMW heparins; these diagnoses should be included in the differential of patients presenting with shock and signs, symptoms, physical examination findings, laboratory tests, and imaging studies consistent with either condition. The early recognition and management of bleeding complications in patients treated with enoxaparin or other LMW heparins is of vital importance in the avoidance of significant morbidity, and possibly death.

James Bradley Summers, MS, MD

Department of Diagnostic Radiology

University of South Alabama Medical Center

PO Box 16343

Mobile, AL 36616.

Joseph M. Kaminski, MD

Philadelphia, PA 19111

References

(1.) Mrug M, Mishra PV, Lusane HC, et al: Hemothorax and retroperitoneal hematoma after anticoagulation with enoxaparin. South Med J 2002; 95:936-938

(2.) Burg MD, Dallara JJ: Rupture of a previously normal spleen in association with enoxaparin: an unusual cause of shock. J Emerg Med 2001; 20:349-352

(3.) Habek D, Cerkez Habek J: Spontaneous rupture of the spleen following abdominal hysterectomy. Zentralbl Gynakol 2001; 123:588-589

(4.) Jabbour M, Tohme C, Ingea H, et al: Spontaneous rupture of the spleen due to heparin. Case report and literature review [in French]. J Med Liban 1995; 43:107-109

(5.) Weiss SJ, Smith T, Laurin E, et al: Spontaneous splenic rupture due to subcutaneous heparin therapy. J Emerg Med 2000; 18:421-426

Volvulus of the Transverse Colon

To the Editor: Acute volvulus of the colon is a rare but potentially lethal cause of mechanical intestinal obstruction, accounting for 2% to 10% of cases in Western Europe and North America. Sigmoid volvulus is by far the most common type, accounting for about two thirds of all cases; cecal volvulus accounts for most of the remaining cases. A simultaneous volvulus of the sigmoid and right colon has been reported. Together, sigmoid and cecal volvulus represent more than 90% of cases of colonic volvulus. Volvulus of the transverse colon is extremely infrequent, ranging from 0% to 10% of collected series of colonic volvulus; however, an incidence of 3% seems more realistic.

Gibson (1) found that only 38 cases of transverse-colon volvulus had been described in the literature through 1970. Anderson et al, (2) in a similar review in 1980, concluded that only 59 cases had been described, but they added another 7 of their own. Gumbs et al (3) added 3 more case reports in 1983, and a further 15 cases are well described in the literature (based on a MEDLINE search), with the case presented here bringing the total number of reported cases to 85. According to Mercado-Deane et al, (4 9) cases of volvulus of the transverse colon in children have been described in the English medical literature, and they added i more case of their own. I believe it is important to report this case of transverse-colon volvulus to keep this rare but interesting anomaly in focus.

A 61-year-old woman was admitted to the hospital with a 10-day history of constipation and abdominal distention. The patient had a long history of drug therapy for epilepsy and depression. On physical examination, she was uncooperative, but a grossly distended abdomen was noted. No masses were palpated, and no bowel sounds were auscultated. Rectal examination revealed an empty ampulla. Plain radiograph was pathognomonic for volvulus of the transverse colon. At the time of surgery, a chronic volvulus of the transverse colon was found, and extended right hemicolectomy was done. The patient made a good postoperative recovery. Histologic examination of the surgical specimen showed melanosis coli without other abnormalities.

Volvulus of the transverse colon tends to be associated with other abnormalities, such as congenital bands and hypermobile colonic flexure. Other factors include chronic constipation, distal obstructing lesions, previous abdominal surgery, and pregnancy. Gases of volvulus of the transverse colon have been reported in association with other anomalies and with rare diseases. Clincial features are indistinguishable from other causes of large-bowel obstruction. McGowan et al (5) stated that there was a history of recurrent attacks in 50% of patients, but this was not the case in the series reported by Anderson et al. (2) Vomiting is thought to occur earlier than is the case in simple colonic obstruction, perhaps due to twisting of the root of the mesocolon, which compresses the duodenojejunal-junction flexure.

Radiologic examination has not been particularly useful in the diagnosis of this condition, and many cases are misdiagnosed as sigmoid volvulus. A review of the radiologic aspects of reported cases shows variable features dependent on the particular anatomic abnormalities, the extent of the colon involved in the volvulus, and the competence of the ileocecal valve. A plain radiograph taken with the patient supine usually shows a grossly dilated colonic loop with distention of the proximal right colon. The distal colon contains little or no gas. The small bowel may also show evidence of obstruction. An abdominal x-ray film taken with the patient erect usually shows 2 fluid levels in the twisted loop, and a third in the right colon. Occasionally, only i fluid level may be seen in the volvulus, and fluid levels may or may not be seen in the small bowel. The variable position of the transverse colon is responsible for the condition being mistaken for a sigmoid volvulus on radiologic examination.

The results of colonoscopy in cases of transverse-colon volvulus are disappointing (3, 6, 7); however, this treatment may be used to promptly diagnose and detorsion. The definitive treatment of volvulus of the transverse colon is surgical. If the bowel is compromised, the involved segment should be resected with a proximal-end colostomy and a distal mucous fistula should be created. If the bowel is viable, detorsion is recommended, followed by elective bowel resection. Fixation without resection results in a high incidence of recurrence. (2)

Ahmed M. El-Tawil, MRCS 

Department of Surgery

Birmingham Heartlands Hospital

Bordesley Green East

Birmingham B9 5SS, United Kingdom

References

(1.) Parrish RA, Crook JA, Mortez WH: Coexistent volvulus of the transverse, sigmoid, and right colon. Am Surg 1964; 30:313

(2.) Gibson JY: Volvulus of the transverse colon. South Med J 1972; 65:1150-1151

(3.) Anderson JR, Lee D, Taylor TV, et al: Volvulus of the transverse colon. Br] Surg 1981; 68:179-181

(4.) Gumbs MA, Kashan F, Shumofsky E, et al: Volvulus of the transverse colon: reports of cases and review of the literature. Dis Colon Rectum 1983; 26:825-828

(5.) Mercado-Dean MG, Burton EM, Howell CG: Transverse colon volvulus in pediatric patients. Pediatr Radiol 1995; 25:111-112

(6.) McGowan JM, Soriano S, McCausland W: Volvulus of the transverse colon. Am J Surg 1957; 93:857-859

(7.) Zinkin LD, Katz LD, Rosin JD: Volvulus of the transverse colon: report of case and review of the literature. Dis Colon Rectum 1979; 22:492-496

Extreme Leukocytosis Without Hematologic Malignancy

To the Editor: The term leukemoid reaction is poorly defined, often used to describe a markedly increased white blood cell count (>50,000/[micro]L). In general, leukocyte counts >45,000/[micro]L have a strong association with malignancy but are rare even in severe infections. (1, 2) Treatment with medications such as corticosteroids and catecholamines can also increase the leukocyte count due to demargination. (2)

Most of the literature describing extreme leukocytosis (hyperleukocytosis) is related to the chronic leukemias, in which white blood cell counts >300,000/[micro]L have been reported. Few cases of nonmalignant hyperleukocytosis are mentioned, but benign and malignant leukocytosis have significantly different complications. Due to the size and morphology of leukocyte precursors of acute leukemia, patients with that disease have increased morbidity due to leukostasis, including intracranial hemorrhage, pulmonary infarction, and disseminated intravascular coagulation. In contrast, leukostasis due to a nonmalignant extreme leukocytosis is less common, since leukocytes maintain normal size and adhesion characteristics. Leukocyte counts >100,000/[micro]L due to an infectious process or drug administration are rare, (2) and there is a paucity of current literature dealing with this entity. This case is unique, since it describes a patient presenting with an extreme leukocytosis of up to 207,900/[micro]L without evide nce of hematologic malignancy.

A 74-year-old man with a history of chronic obstructive pulmonary disease, cor pulmonale, and rectal bleeding was admitted to the hospital because of progressive dyspnea. He was subsequently diagnosed with rectal carcinoma and had abdominoperineal resection without initial complications. On postoperative day 6, however, the patient had peritonitis and underwent surgery for repair of a presumed anastamotic leak. He had been chronically treated with corticosteroids for severe chronic obstructive pulmonary disease and had leukocyte counts of 15,000 to 20,000/[micro]L before admission. Leukocyte count increased to 72,900/[micro]L with a left shift in the initial postoperative period, and to 127,200/[micro]L when he had peritonitis. Blood cultures grew Enterococcus faecalis and coagulase-negative Staphylococcus. Despite broad spectrum antibiotic therapy, leukocyte count increased to a maximum of 207,900/[micro]L after surgical revision. Concomitantly, the platelet count dropped to 22,000/[micro]L and the prothromb in and activated partial thromboplastin times increased, consistent with early disseminated intravascular coagulation. Platelets and vitamin K were administered. The leukocyte count decreased to 92,000/[micro]L over several days and continued to trend downward. The leukocyte alkaline phosphatase (LAP) score was within normal limits, and daily peripheral blood smears revealed no evidence of leukemic process or leukoerythroblastic reaction. Clinical evidence of leukostasis was not observed at any time, and the patient's whole-blood viscosity at the peak of his leukocytosis was 2.3 cP. The patient was electively extubated but died of respiratory failure approximately 2 weeks after his surgery.

Extreme leukocytosis is most commonly caused by severe bacterial infection or underlying malignancy and can be of myeloid, monocytoid, or lymphoid lineage. In bacterial infection, a granulocytic hyperleukocytosis is most commonly observed, but the etiology may be multifactorial. Contributing factors to neutrophilia can include infection, inflammation, treatment with corticosteroids, pressors, or lithium, physiologic stress, ketoacidosis, burns, and endogenous or exogenous colony-stimulating factors. (1, 2) Laboratory evidence of a leukemoid reaction is often worrisome to physicians, since hematologic malignancy must be ruled out by examining the peripheral blood smear, using the LAP score, and possibly performing a bone marrow biopsy. Extreme elevation of the leukocyte count due to chronic myelogenous leukemia will reveal a low LAP score, while in severe bacterial infection or inflammation the LAP score is normal. A peripheral smear in acute leukemia may reveal a high percentage of blasts. In chronic myelogen ous leukemia, it will reveal basophilia and eosinophilia, with numerous early myeloid forms. (2) A leukoerythroblastic smear can indicate metastatic infiltration of the bone marrow. Cytogenetic tests may also be helpful if the diagnosis is in question.

The diagnosis and outcome of 100 patients with extreme granulocytic leukocytosis (white blood cell counts ranging from 25,000 to 183,400/[micro]L with at least 50% granulocytes) were reviewed in 1998.' Extreme granulocytic leukocytosis was found to be associated with infection in 48% of cases. Leukocyte counts >45,000/[micro]L were associated with malignancy and increased mortality rates. Hyperleukocytosis was also caused by hemorrhage (9%), treatment with glucocorticoids (8%), and "other" etiologies (22%). Although the degree of leukocytosis was predictive of the etiology, the leukocyte differential count was not. Profound benign neutrophilia with an elevated level of colony-stimulating factor has been reported in association with various solid tumors, including lung, gastrointestinal, and urogenital malignancies. (2) Our patient's leukocytosis cannot completely be attributed to his rectal cancer, since the leukemoid response appeared postoperatively. It may, however, have been a contributing factor.

Hyperleukocytic syndrome and leukostasis are feared hematologic emergencies in a patient with extreme leukocytosis. (3, 4) Extraordinarily high leukocyte counts can cause cells to obstruct the microvasculature. Commonly, this syndrome affects the pulmonary circulation and central nervous system. Factors that contribute to the development of this leukostasis include the fractional volume of leukocytes (leukocrit), leukocyte volume, and cell morphology. In most cases, overall blood viscosity does not increase because the platelet count and hematocrit level undergo a concomitant drop as the leukocyte count rises. (4, 5) Blast cells are predominant in the acute. leukemias, consuming higher levels of oxygen and glucose than mature cells and impairing blood flow, which can lead to vascular and end-organ damage. Alternatively, we were unable to find case reports of leukostasis due to benign hyperleukocytosis in the literature. Benign hyperleukocytosis poses a much smaller risk of leukostasis because the cells are mo rphologically normal with respect to shape, size, and volume, and also maintain their deformability. (3, 4)

Treatment modalities for leukostasis include leukophoresis, exchange transfusion, and radiation therapy. Pharmacologic interventions include aggressive hydration, alkalinization, and treatment with allopurinol, hydroxyurea, or chemotherapy. There is debate about what is the safest and most effective treatment of leukostasis. (3-5) A high index of suspicion and rapid treatment is required for this hematologic emergency, however, to prevent complications, such as intracranial hemorrhage or pulmonary infarction. It was not necessary to use any of these treatment modalities in our patient, since he did not exhibit signs or symptoms of leukostasis.

CAPT Kristina E. Orio, USAF, MC

Department of Emergency Medicine

CAPT Brian J. Heller, USAF, MC

LT COL Michael Osswald, USAF, MC

Department of Hematology/Oncology

Wilford Hall Medical Center

2200 Bergquist Dr, Suite 1

759 MDOS/MMIH

Lackland AFB, TX 78236-5300

References

(1.) Reding M, Hibbs J, Morrison V, et al: Diagnosis and outcome of 100 consecutive patients with extreme granulocytic leukocytosis. Am J Med 1998; 104:12-16

(2.) Peterson L, Hrisinko M: Benign lymphocytosis and reactive neutrophilia: laboratory features provide diagnostic clues. Clin Lab Med 1993; 13:863-875

(3.) Dabrow M, Wilkins J: Hematologic emergencies: management of hyperleukocytotic syndrome, DIC, and thrombotic thrombocytopenic pupura. Post grad Med 1993; 93:193-202

(4.) Lichtman M, Rowe J: Hyperleukocytotic leukemias: rheological, clinical, and therapeutic considerations. Blood 1982; 60:279-283

(5.) Nelson S, Bruggers C, Kurtzberg J, et al: Management of leukemic hyperleukocytosis with hydration, urinary alkalinization, and allopurinol. Am L Pediatr Hematol Oncol 1993; 15:351-355

Paraneoplastic Gaze Palsies in a Patient With Negative Anti-Hu and Anti-Yo Antibody Tests

To the Editor: A 68-year-old woman was admitted for evaluation of progressive difficulties with vision and gait. Her problems began with diplopia, left leg weakness, and headaches. She began to have progressive gait difficulty, weakness of the right leg, and intention tremor of the arms. She had slurred speech, lost the urge to urinate, and had a pins-and-needles numbness in the feet. She had a 60 pack-year smoking history.

Physical examination revealed that the patient was dysarthric. Cranial-nerve testing showed severe difficulties with lateral gaze in both directions. She had a complete gaze paresis to the right and a partial gaze paresis to the left. Upward and downward pursuit was intact without nystagmus. She could not generate saccades in any direction, and pupillary and vestibulo-ocular responses were intact. She was weak and had areflexia in the arms and legs, with extensor plantar responses in both feet. Sensory examination revealed mild to moderate loss of pain sensation, temperature sensation, and proprioception in all limbs. Cerebellar neurologic examination revealed bilateral past-pointing, intention tremor, dysdiadochokinesis, and rebound. She displayed head titubation, truncal titubation, and a wide-based gait.

Lumbar puncture revealed a protein level of 119 mg/dL, glucose level of 76 mg/dL, and white blood cell count of 45/[mm.sup.3] (90% monocytes). Magnetic resonance imaging of the head revealed enhancement of the cerebellar peduncles on the T2-weighted image. Results of serum tests for human immunodeficiency virus, rheumatoid factor, and antinuclear antibodies were negative. Vitamin [B.sub.12] level, thyroid function tests, erythrocyte sedimentation rate, complete blood count, liver function tests, blood smear, and prothrombin time/partial thromboplastin time were all normal. Serum anti-Hu and anti-Yo antibodies were not present. Mammograms were negative. Computed tomography of the chest showed a right hilar lymph node measuring 2.1 cm. Transbronchial aspirate of the lymph node revealed small cell carcinoma of the lung. Neuropathologic examination revealed encephalitis, predominantly in the white matter tracts of the pons, medulla, and midbrain, with patchy, chronic inflammation with organizing and incomplete ne crosis.

Antibody reaction of the patient's serum and a control serum were tested against fresh temporal lobe specimens obtained from a recent anterior temporal lobectomy. This method ensured that there was no postmortem infiltration of the brain by proteins and antibodies, which may cross a damaged blood-brain barrier after death. The serum was labeled with anti-rabbit immunoglobulin G (IgG) and examined microscopically with indirect immunofluorescence. The patient's serum indicated the presence of an antibody reaction against brain, while the control serum showed no evidence of reaction. There were no antibodies present in the patient's serum that could be identified by conventional laboratory testing; however, there was a nonspecific protein identified by Western blot test.

Two new paraneoplastic syndromes that can present as a brainstem encephalitis have recently been described. These are the anti-Ma (testicular cancer) (1, 2) and anti-amphiphysin (breast cancer) (3-5) antibody syndromes. Discovery and characterization of other new paraneoplastic syndromes continues. Our case of bilateral gaze paresis with pancerebellar findings illustrates the importance of the history, physical examination, and search for an underlying tumor, even if serum antibody tests are negative. Specific identification of the causative antibody will provide useful information in further classifying this syndrome and developing an antibody test to facilitate diagnosis of syndromes with similar clinical presentations and serum tests that are negative for anti-Hu and anti-Yo antibodies.

Acknowledgement. We thank Jerome Posner, MD, and laboratory staff at Memorial Sloan-Kettering for their contribution to this case.

Michael S. Okun, MD

M. Tariq Bhatti, MD

Thomas Eskin, MD

Steven Eisenschenk, MD

Robert T. Watson, MD

Neurology Department

Emory University

Wesley Wood Health Center Building

1841 Clifton Road NE

Atlanta, GA 30329

References

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