Spinal Arachnoid Web: A didactic report of two cases with clinical, radiological, surgical and pathological correlations.

BACKGROUND: Arachnoid web (AW) is a rare but probably underestimated cause of spinal cord injury that is complex to diagnose due to subtle MRI findings and similarities to other better-known diseases such as arachnoid cyst (AC) or transdural spinal cord herniation (TSCH). Increased recognition of AW is mandatory since delay in diagnosis can lead to potentially serious neurological sequelae. CASE PRESENTATIONS: We report two additional cases of AW for didactic purposes, with special emphasis on the distinctive MRI and intraoperative findings. Both patients presented with progressively worsening neurological symptoms, including proprioceptive ataxia, motor weakness, numbness and neuropathic pain. The diagnosis of AW was suspected on the basis of specific MRI criteria, especially the so-called "scalpel sign". Formal confirmation of the diagnosis was obtained in two patients that were managed surgically. Postoperative follow-up demonstrated significant functional recovery. DISCUSSION: There is a need for better recognition of AW by the medical community. Careful analysis of MRI semiology is crucial for the distinction between AW, AC and TSCH. Prompt and accurate diagnosis is mandatory to conserve functional prognosis, since appropriate surgical treatment with AW resection is curative, halting or even resolving the neurological symptoms.

Vagoglossopharyngeal neuralgia revealed through predominant digestive vagal manifestations. Case report and literature review.

Vagoglossopharyngeal neuralgia is a rare pathology whose atypical forms, dominated by syncopal manifestations, are still rarer. Although the territory of the vagus nerve involves, beyond the cardiovascular system, the respiratory and the digestive systems, there is no report in literature of atypical forms other than syncopal. Therefore, the authors were prompted to report the case of a patient whose vagoglossopharyngeal neuralgia was predominantly revealed by digestive symptoms. A 58-year-old patient presented with stereotypical severe digestive disturbances including nausea, vomiting and diarrhoea. High definition cranial MRI showed a neurovascular conflict between the posterior inferior cerebellar artery and the IXth and Xth nerves, on the right side. A microsurgical decompression was carried out which confirmed the vascular compression and successful transposition of the artery. One year after the surgery, the patient was free from all painful and digestive symptoms. A survey of the literature did not find any reference to digestive symptoms together with the neuralgia; only a syncopal type of cardiac symptoms related to the parasympathetic nervous system were described. The hypothesis was that the revealing digestive symptoms are linked to a similar parasympathetic mechanism, implying the visceral component of the Xth cranial nerve.

CSF Lumbar Drainage: A Safe Surgical Option in Refractory Intracranial Hypertension Associated with Acute Posttraumatic External Hydrocephalus.

INTRODUCTION: External lumbar drainage (ELD) of cerebrospinal fluid (CSF) in posttraumatic refractory intracranial hypertension (ICHT) is controversial. We report our experience of ELD in ICHT associated with acute disturbance of CSF flow within subarachnoid spaces (SASs). MATERIALS AND METHODS: Four adult patients admitted to the neurointensive care unit for severe TBI who presented with secondary ICHT are retrospectively reported. When refractory to second-tier therapy, if external ventricular drainage were not possible or failed, and in the absence of an indication for craniotomy to treat a mass lesion or decompressive craniectomy, we assessed the evolution of CSF volume within cranial SAS and checked the presence of basal cisterns and the absence of tonsillar herniation to evaluate interest in and the safety of ELD. RESULTS: As second-tier therapy failed to lower intracranial pressure (ICP; mean ICP 37 ± 5 mmHg), and computed tomography (CT) showed abnormally enlarged cranial SAS following traumatic subarachnoid hemorrhage, patients received ELD. ICP decreased, with immediate and long-term effect (mean ICP 5 mmHg ± 2 mmHg). There were no complications to report. DISCUSSION: Acute traumatic external hydrocephalus may explain some of the specific situations of secondary increased ICP, with a "normal" CT scan, that is refractory to medical treatment. In these situations, lumbar drainage should be considered to be a safe, minimally invasive, and effective surgical option.

Personalized mapping of the deep brain with a white matter attenuated inversion recovery (WAIR) sequence at 1.5-tesla: Experience based on a series of 156 patients.

OBJECTIVE: Deep brain mapping has been proposed for direct targeting in stereotactic functional surgery, aiming to personalize electrode implantation according to individual MRI anatomy without atlas or statistical template. We report our clinical experience of direct targeting in a series of 156 patients operated on using a dedicated Inversion Recovery Turbo Spin Echo sequence at 1.5-tesla, called White Matter Attenuated Inversion Recovery (WAIR). METHODS: After manual contouring of all pertinent structures and 3D planning of trajectories, 312 DBS electrodes were implanted. Detailed anatomy of close neighbouring structures, whether gray nuclei or white matter regions, was identified during each planning procedure. We gathered the experience of these 312 deep brain mappings and elaborated consistent procedures of anatomical MRI mapping for pallidal, subthalamic and ventral thalamic regions. We studied the number of times the central track anatomically optimized was selected for implantation of definitive electrodes. RESULTS: WAIR sequence provided high-quality images of most common functional targets, successfully used for pure direct stereotactic targeting: the central track corresponding to the optimized primary anatomical trajectory was chosen for implantation of definitive electrodes in 90.38%. CONCLUSION: WAIR sequence is anatomically reliable, enabling precise deep brain mapping and direct stereotactic targeting under routine clinical conditions.

Robot-guided neuronavigated rTMS as an alternative therapy for central (neuropathic) pain: Clinical experience and long-term follow-up.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) appears as a useful tool to alleviate neuropathic pain but only few data are available for the long-term benefit of this treatment. METHODS: Here we report the effects of rTMS sessions, considered as a possible therapy for pain relief after a failure of different medications in patients with central (neuropathic) pain. We review here the prospectively collected data of the first forty patients treated as follow: 20 Hz stimulation delivered over the contralateral primary motor cortex (M1), each 3-4 weeks. RESULTS: A total of 440 rTMS sessions was collected (mean sessions number: 11, range: 1-37, follow-up 312 days on average, maximum 2.8 years). After four sessions, nine patients (22.5%) discontinued rTMS because of a lack of efficiency (<10% pain-relief). The other 31 patients (77.5%) had a cumulative effect across sessions leading to a mean pain relief of 41% for a duration of 15.6 days. A correlation was observed between pain relief in the first session and long-term pain relief (R = 0.649. p = 5.6*10(-6) ). Both intensity and duration of pain relief were significantly better for patients with persistent laser evoked potentials (LEPs, p = 0.049 and 0.0018). We did not observe any adverse-effects. CONCLUSION: These results suggest that repeated sessions of 20 Hz rTMS over M1 are interesting in clinical practice for the treatment of selected patients with central pain. Both the cumulative effects across the first sessions and the long duration of pain-relief should impact further randomized trials that are warranted to conclude formally on rTMS efficiency in central pain.

Presurgical Assessment of the Sensorimotor Cortex Using Resting-State fMRI.

BACKGROUND AND PURPOSE: The functional characterization of the motor cortex is an important issue in the presurgical evaluation of brain lesions. fMRI noninvasively identifies motor areas while patients are asked to move different body parts. This task-based approach has some drawbacks in clinical settings: long scanning times and exclusion of patients with severe functional or neurologic disabilities and children. Resting-state fMRI can avoid these difficulties because patients do not perform any goal-directed tasks. MATERIALS AND METHODS: Nineteen patients with diverse brain pathologies were prospectively evaluated by using task-based and resting-state fMRI to localize sensorimotor function. Independent component analyses were performed to generate spatial independent components reflecting functional brain networks or noise. Three radiologists identified the motor components and 3 portions of the motor cortex corresponding to the hand, foot, and face representations. Selected motor independent components were compared with task-based fMRI activation maps resulting from movements of the corresponding body parts. RESULTS: The motor cortex was successfully and consistently identified by using resting-state fMRI by the 3 radiologists for all patients. When they subdivided the motor cortex into 3 segments, the sensitivities of resting-state and task-based fMRI were comparable. Moreover, we report a good spatial correspondence with the task-based fMRI activity estimates. CONCLUSIONS: Resting-state fMRI can reliably image sensorimotor function in a clinical preoperative routine. It is a promising opportunity for presurgical localization of sensorimotor function and has the potential to benefit a large number of patients affected by a wide range of pathologies.

[Young French neurosurgeons: Working conditions and outlook]. / Jeunes neurochirurgiens français: conditions de travail et perspectives.

INTRODUCTION: Due to the increase in the number of French neurosurgeon residents the neurosurgical workforce is changing. The main objective of this survey was to assess working conditions and perspectives for young French neurosurgeons. METHOD: An on-line survey was sent to young French neurosurgeons based on a mailing-list (219 mail addresses of Residents and Fellows obtained during previous meetings). The form contained questions about career, amount of work, salary, quality of life, teaching and university work. RESULTS: We received 78 replies from January to March 2014. A total of 56% from fellows saying they had undergone difficulties in obtaining a fellowship, although 78% were satisfied. Fellows considered a private career more often than residents. Overall, young neurosurgeons were worried about future employment. Some 33% admitted contemplating a different career from one they originally wanted. The average weekly working time of 76.8 hours was deemed to be excessive. Security rests after overnight shifts were lacking or incomplete in 91% of cases. The work atmosphere was good overall (3.7/5), and so was the quality of life (3.2/5). Theoretical teaching was unsatisfactory (2.43/5) as well as the time allowed for academic work (approximately 1.58 half-days per month). However, practical teaching was considered rewarding (3.63/5). CONCLUSION: This study provides some guidance for upcoming reforms, and should be considered again at a later date to evaluate progress.

Isolated primary central nervous system lymphoma arising from the optic chiasm.

A 58-year-old previously healthy woman rapidly developed progressive bilateral visual loss. Magnetic resonance imaging revealed a bulging appearance of the optic chiasm, with homogeneous enhancement after gadolinium administration, which suggested an optic glioma or inflammatory disease. In the absence of (para)clinical clues for a specific diagnosis despite extensive investigation, a biopsy of one optic nerve was performed, resulting in a diagnosis of non-Hodgkin B-cell lymphoma. There was no evidence of any other ocular or systemic involvement, therefore the conclusion was that this immunocompetent patient had a primary central nervous system lymphoma isolated in the anterior visual pathway. Treatment included two cycles of polychemotherapy (rituximab, methotrexate, carmustine, etoposide, methylprednisolone), followed by autologous peripheral blood stem cell transplantation and rituximab plus cytarabine consolidation therapy. Subsequently, the patient exhibited significant improvement in vision, and was still disease-free at the 1-year follow-up examination. The aim of the present paper was to provide well-documented clinical, radiological, and intraoperative features of isolated primary malignant lymphoma arising from the anterior visual pathway. A better recognition of this rare pathological entity is necessary for clinicians who may encounter similar presentations, as prompt management is crucial for both a visual and vital prognosis.

Electrical modulation of neuronal networks in brain-injured patients with disorders of consciousness: a systematic review.

Six clinical studies of chronic electrical modulation of deep brain circuits published between 1968 and 2010 have reported effects in 55 vegetative or minimally conscious patients. The rationale stimulation was to activate the cortex through the reticular-thalamic complex, comprising the tegmental ascending reticular activating system and its thalamic targets. The most frequent intended target was the central intralaminar zone and adjacent nuclei. Hassler et al. also proposed to modulate the pallidum as part of the arousal and wakefulness system. Stimulation frequency varied from 8Hz to 250Hz. Most patients improved, although in a limited way. Schiff et al. found correlations between central thalamus stimulation and arousal and conscious behaviours. Other treatments that have offered some clinical benefit include drugs, repetitive magnetic transcranial stimulation, median nerve stimulation, stimulation of dorsal column of the upper cervical spinal cord, and stimulation of the fronto-parietal cortex. No one treatment has emerged as a gold standard for practice, which is why clinical trials are still on-going. Further clinical studies are needed to decipher the altered dynamics of neuronal network circuits in patients suffering from severe disorders of consciousness as a step towards novel therapeutic strategies.

Intraoperative use of diffusion tensor imaging-based tractography for resection of gliomas located near the pyramidal tract: comparison with subcortical stimulation mapping and contribution to surgical outcomes.

INTRODUCTION: For gliomas, the goal of surgery is maximal tumour removal with the preservation of neurological function. We evaluated the contribution of the combination of diffusion tensor imaging-based fibre tracking (DTI-FT) of the pyramidal tract (PT) integrated to the navigation and subcortical direct electrical stimulations (DESs) to surgical outcomes. METHOD: Ten patients underwent surgery for gliomas located in close relationship with the subcortical course of the PT. Preoperative DTI was performed with a three-Tesla magnetic resonance scanner applying an echo-planar sequence with 20 diffusion directions. DTI-FT data were systematically loaded into the navigation for intraoperative guidance. When the resection closely approached the PT as illustrated on navigation images, subcortical DESs were used to confirm the proximity of the PT by observing motor responses. The location of all subcortically stimulated points with positive motor response was correlated with the illustrated PT. Motor deficits were evaluated pre- and postoperatively, and compared with the extent of tumour removal. RESULTS: DTI-FT of the PT was successfully performed in all patients. A total of fifteen positive subcortical DESs were obtained in 8 of 10 patients; in these cases, the mean distance from the stimulated point to the PT was 6.2 ± 3.6 mm. The mean tumoural volumetric resection was 90.8 ± 10.4%, with a gross total resection in four patients. At one month after surgery, only one patient had a slight impairment of motor function (decreased fine motor hand skills). CONCLUSIONS: DTI-FT is an accurate technique to map the PT in the vicinity of brain tumours. By combining anatomical (DTI-FT) and functional (subcortical DES) studies for intraoperative localization of the PT, the authors achieved a good volumetric resection of tumours located in eloquent motor areas, with low morbidity. Careful use of this protocol requires the knowledge of some pitfalls, mainly the occurrence of brain shift during removal of large tumours.

A comparative trial of a MAOI, iproniazide, and a polycyclic agent, mianserine, for the search of the most rapidly and frequently active treatment of depressive syndromes in an oncology service.

Many cancer patients of the "Service des Maladies Sanguines et Tumorales" of Hôpital Paul-Brousse, Villejuif, are psychologically studied by: the objective and quantified Szondi test, and in the case a depressive syndrome clinical diagnosis is confirmed, this state is quantified by a quintile questionnaire requiring 25 "yes or no" answers (determined by five grades and five stages), in case an inhibition or/and hysteric component is found, the subjects are submitted to the care of a psychoanalyst. A comparative trial of the MAOI, iproniazide, and the tetracyclic analog, mianserine, has been conducted for the search of the most frequently and rapidly active antidepressant agent among them both. The hypothesis that mianserine is less frequently and rapidly active than iproniazide was drawn from our previous experience of 20 years: thus patients presenting a score less than or equal to 12/25 were given mianserine (20 up to 30 mg/day to be possibly increased according to medical decision), while those presenting a score greater than or equal to 13/25 received iproniazide (50 up to 75 mg/day). The patients who failed with mianserine received iproniazide, while those who failed with iproniazide were supposed to receive mianserine. The registered results are the following: a) out of the 25 patients with major depressive syndromes (score greater than or equal to 13) submitted to iproniazide, 16 (61%) were in complete remission (score at 0/25) and five in partial regression (score decreased by more than half); this makes 21 responses in all, i.e. 80%, obtained between the 10th and the 30th days, which is superior to all placebo responses which have varied in the reliable literature from 13 to 70%; b) out of 18 depressive patients submitted to mianserine, only one had benefited of a complete remission and four of a partial regression at the 30th day, which makes 28% responses. Among the side effects of iproniazide, they were two colon meteorism syndromes, easily corrected by prostigmine, five hyposomnia cases corrected by dipotassium chlorazepate, four anejaculation or delay at ejaculation cases which needed eserine when the patients require their disappearance or attenuation. We did not register either hepatic or hyperthermic or hypertensive complications: this is in good agreement with the true incidences, especially that of hypertensive crisis which could be found in serious and scientifically documented articles, to be 0.3 to 0.5% for their appearance, and 1 per 100,000 for their fatal evolution. Among the side effects of mianserine, we have not registered any of the hepatic, renal and cardiac complications mentioned in the literature.(ABSTRACT TRUNCATED AT 400 WORDS)

An oriented phase II trial of THP-adriamycin in breast carcinoma.

THP-ADM is a new anthracycline with broad antitumor activity without cardiac toxicity or alopecia in experimental models. Phase I studies had established a proposed dose for phase II trials of 50 mg/m2 every three weeks. This modality gave an insignificant result in breast carcinoma. Cellular pharmacokinetics suggested that a longer time of administration could be more efficient. In this phase II trial oriented to advanced breast cancer, we have used 3 consecutive daily doses of 20 mg/m2/day in monthly cycles with dose escalation in each patient. We have observed 28% partial remissions (PR). Two patients previously treated with adriamycin had PR. Significantly less alopecia and no cardiac toxicity were observed.

Phase I-II study of aclarubicin for treatment of acute myeloid leukemia.

Aclarubicin (ACM) was administered as induction treatment to 40 patients with acute myeloid leukemia (AML) who were either refractory to initial induction chemotherapy or in relapse. Thirty-eight patients with AML, 2-80 years of age (mean +/- SE, 35.0 +/- 3.2), were evaluated during this study. Seventeen of these patients were given ACM after an unsuccessful attempt had been made to attain a complete remission (CR) with various regimens that included doxorubicin or daunorubicin; this group was considered resistant to these drugs. ACM was administered by rapid iv injection. Thirteen patients received a single course of ACM at a daily dose of 10-30 mg/m2 until a maximum total dose of 300 mg/m2 was reached or until unacceptable toxicity appeared. Of these patients, two (15%) attained a CR. The other 25 patients were given 10-day courses of ACM at a daily dose of 15 mg/m2 with 10-day intervals between courses; courses were repeated until the blast cells were cleared from peripheral blood and bone marrow or until progressive disease became evident. With this regimen, 11 patients (44%) attained a CR. The overall CR rate for the 38 patients was 34%. Total doses necessary to achieve a CR ranged from 150 to 600 mg/m2. A CR was attained by six patients who were previously resistant to a regimen containing moderate doses of doxorubicin. The incidence and severity of the toxic effects were related to the dose of ACM administered per course of therapy. The incidence of mucositis, diarrhea, vomiting, and infection in patients who received doses greater than 150 mg/m2/course was significantly higher than that observed in patients who received a dose of 150 mg/m2/course. In the latter patients, toxicity was within acceptable limits. Alopecia was not observed. Three patients had transient T-wave inversion, and reversible atrial flutter developed in one patient. Our results indicate that ACM is a major new drug for the treatment of AML.

Treatment of acute myeloid leukemia with a combination of intensive induction chemotherapy, early consolidation, splenectomy and long-term maintenance chemotherapy.

The authors developed a therapeutic regimen in which 33 patients aged 11 to 61 years (mean +/- SE, 35.9 +/- 2.3 years) with acute myeloid leukemia (AML) were given intensive induction chemotherapy with Adriamycin (doxorubicin) (ADM), vincristine (VCR) and cytosine arabinoside (ARA-C). Twenty-nine of these patients (88%) attained a complete remission (CR) after 1, 2, or 3 courses and were then subjected to an early consolidation course of chemotherapy, identical to that for induction. After consolidation, all patients in CR received a long-term continuous maintenance therapy in which 6-mercaptopurine (6-MP) and methotrexate (MTX) were alternated, associated with periodic reinforcements with daunorubicin (DNR) and VCR. Twenty-five of the 29 patients who achieved a CR were splenectomized soon after the consolidation course. Histologic sections of the spleens, liver biopsy specimens, and lymph nodes, stained routinely and with the naphthol AS-D chloroacetate esterase (NCA) method, showed mature granulocytes and a few NCA positive mononuclear cells, but no proved leukemic infiltrates. For the 25 splenectomized patients, the probability of remaining in CR at 36 and 54 months was 75% and 66%, respectively; the probability of survival at 36 and 54 months was 85% and 75%, respectively. Age older than 40 years and evidence of extramedullary involvement at presentation appeared to carry a bad prognosis for disease-free survival.

Phase I-II study of aclacinomycin for a treatment of acute myeloid leukemia.

Aclacinomycin A (ACM) was administered for induction treatment to 40 previously treated acute myeloid leukemia (AML) patients. 38 patients aged 2 to 80 years (mean +/- SE, 35.0 +/- 3.2 years) with overt AML were evaluated; of these, seventeen patients were given ACM after an unsuccessful attempt to obtain a complete remission (CR) with various regimens comprising adriamycin (ADM) or daunorubicin (DNR) and were considered resistant to these drugs. Thirteen patients received ACM at a daily dose of 10 to 30 mg/m2 IV bolus until the maximum total dose of 300 mg/m2 per course was reached or until unacceptable toxicity appeared; of these patients, 2 (15%) attained a CR. Twenty-five patients were given 10-day courses of ACM at the daily dose of 15 mg/m2 IV bolus with 10-day intervals between courses; with this regimen 11 patients (44%) attained a CR. The overall CR rate was 34%. Total doses necessary to attain a CR ranged from 150 to 600 mg/m2. CR was attained by 6 patients (35%) of the 17 who were previously resistant to ADM or DNR. The incidence and severity of the toxic effects such as mucositis, diarrhea, vomiting and infection were related to the dose of ACM administered during each course of therapy. However, in patients who received 150 mg/m2 per course the toxicity was within acceptable limits. Alopecia was not observed. Transient T-wave inversion was observed in 3 patients and atrial flutter developed in one patient. Therefore, we conclude that ACM is a new major drug in the treatment of AML.

Doxorubicin, vincristine, bleomycin, cytembena and cisplatin as combination chemotherapy for squamous cell lung cancer.

Thirty-nine evaluable patients with squamous cell lung carcinoma were treated with combination chemotherapy consisting of doxorubicin, oncovin, bleomycin, cytembena and cis-platin. Objective responses were seen in 46 per cent of the patients. Patients with limited disease had a response rate of 56 per cent. Two of the four complete responses were endoscopically and histologically verified. The median survival time was 37.6 and 26.3 weeks for patients with limited and extensive disease, respectively (p less than 0.05), and 29.9 weeks for the whole group. Hematologic and gastrointestinal toxicities were moderate. There was one drug-related death due to septicemia and 2 reversible acute renal failures. The chemotherapeutic combination appears to be relatively effective. It causes some tumor regression and may extend the survival of responding patients with acceptable quality of life. Maintenance chemotherapy with CCNU, cyclophosphamide, methotrexate, procarbazine alternating with vinblastine, nitrogen-mustard, methotrexate, procarbazine, frequently had to be discontinued because of severe toxicity.

The common acute lymphoid leukemia antigen on b cells of chronic lymphoid leukemia and non-Hodgkin's lymphoma.

Fourteen out of 21 non-Hodgkin lymphoma (NHL) and 3/11 chronic lymphoid leukemia cells (CLL) had the common acute lymphoid leukemia antigen (CALLA) All 32 patients had monoclonal B-cell proliferation. The CLL patients had 90% CALLA positive cells while the proportion of their leukemic elements was superior. Lymph-nodes or bone marrow invaded by a B monoclonal tumor cell population of NHL had significantly more CALLA positive cells (42.1 +/- 32.5%) than non-invaded tissues (11.4 +/- 10.3%). In NHL tissues with monoclonal B-cells, lymph-nodes had significantly more CALLA positive cells (56.0 +/- 29.9%) than marrow (23.5 +/- 27.7%). It is well known that the (CALLA) is not specific for ALL. It has been believed to be a differentiation antigen on pre B-cells. The present study confirms that it also occurs on B-cells (2,4,6,7,8,9,10,11).

[Treatment of acute myeloid leukemia with a protocol combining intensive induction chemotherapy, early consolidation treatment, splenectomy and long-term maintenance chemotherapy. Preliminary study]. / Traitement des leucémies aiguës myéloïdes par un protocole associant une chimiothérapie d'induction intensive, un traitement précoce de consolidation, une splénectomie et une chimiothérapie de maintien au long cours. Etude préliminaire.

Twenty-seven patients aged from 10 to 60 years (mean 34.4 +/- 13 years) in the first perceptible phase of acute myeloid leukemia were subjected to intensive induction chemotherapy consisting of adriamycin (ADM), vincristin (VCR) and cytosine arabinoside (ARA-C). Twenty-four patients (89%) attained complete remission (CR) after 1 to 3 cycles and were then given an early consolidation treatment with one of the previous cycles. This was followed by long-term continuous maintenance chemotherapy with 6-mercaptopurine (6-MP) and methotrexate (MTX) alternatively and 3-monthly reinforcement courses of donaurubicin (DNR) and VCR. Twenty of these 24 patients were splenectomized soon after the consolidation treatment. None of the spleens were enlarged, and histological sections of the spleens, liver biopsies and mesenteric lymph-nodes stained with routine dyes and by the naphthol AS-D chloroacetate esterase method revealed mature granulocytes but no demonstrable leukaemic cells. In the group of splenectomized patients, the probabilities of staying in complete remission at 27 and 44 months were 70 +/- 12.6% and 52 +/- 18.5% respectively, and the probabilities of remaining alive at 32 and 55 months were 79 +/- 11% and 57 +/- 19% respectively. Age over 40 and evidence of extramedullary infiltration at presentation appeared to leave little hope of disease-free survival. The rationale for the present therapeutic study is discussed.