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PubMed2001

MRI of neurologic complications in end-stage renal failure patients on hemodialysis: pictorial review.

End-stage renal disease patients who have been on long-term hemodialysis tend to develop central nervous system complications. The most common neurologic complications in this patient group include white matter changes, cerebral atrophy, osmotic demyelination syndrome, dialysis encephalopathy, hypertensive encephalopathy, intracranial hemorrhage, infarct, sinus thrombosis, and infection. Clinical evaluation of these patients is somehow complicated and MRI is important before establishment of the therapy. The purpose of this article is to illustrate the range of MRI findings of neurologic complications in end-stage renal failure patients on hemodialysis with etiologic factors.

Atrophy↗

PubMed2002

Subdural haematoma and non-accidental head injury in children.

PATIENTS AND METHODS: In this retrospective study, 36 children referred to paediatric neurology and neurosurgery during April 1995-June 1998 with a diagnosis of subdural haematoma (SDH) were studied. Nine were accidental secondary to witnessed trauma and 4 were iatrogenic. Non-accidental head injury (NAHI) was suspected in the remaining 23 children. RESULTS: After a full clinical, radiological and social assessment, NAHI was diagnosed in 14, lateral sinus thrombosis in 1, 2 were accepted as accidental and 6 remained unexplained. In the NAHI group (n=14), 12 were between 4 and 16 weeks of age, 12 (85%) had retinal haemorrhages and skeletal surveys showed evidence of additional injury in 8. Computerised tomography (CT) brain scans showed bilateral SDH in 11, and 6 had inter-hemispheric bleeding along with loss of grey-white differentiation. Eleven had magnetic resonance imaging (MRI), which yielded additional information in 7. Seven required intensive care, and 2 died. Twelve had surgical aspiration. In the group with no satisfactory explanation for SDH ( n=6); 5 had neonatal problems, all except 1 were older than 5 months of age and not as ill with bilateral, old SDH. All but 1 had skeletal surveys, which were normal, and eye examination showed no retinal haemorrhages. A social services enquiry was non-contributory. CONCLUSIONS: SDH is frequently traumatic whether accidental or non-accidental. SDH due to NAHI tends to present before 4 months of age with an inconsistent history; the patients are more seriously ill and have other findings, such as fractures and retinal haemorrhages. A small subgroup of patients was identified who had isolated, old SDH and in whom full investigation remained inconclusive. A consistent, comprehensive approach needs to be maintained in all cases with the essential backup of detailed neuro-imaging including MRI.

Brain Injuries↗

PubMed2000

Unusual clinical manifestations of disturbed CSF dynamics in hydrocephalic children.

OBJECTS: Clinical symptoms and signs of increased intracranial pressure (ICP) may be nonspecific and unreliable, or even entirely absent, in hydrocephalic infants and children. Even with a radiological examination, it is often difficult to distinguish between "arrested hydrocephalus" and slowly progressive hydrocephalus requiring treatment. METHODS: We present two cases with unusual and initially misleading clinical manifestations of increased ICP. In both cases, the disturbed cerebrospinal fluid (CSF) dynamics, i.e. raised ICP, were not recognised until demonstrated by a long-term ICP monitoring. In a 5-month-old boy with normal head circumference and normal psychomotor development, the sudden onset of episodes of torticollis and screaming were the only symptoms. No pathology underlying the developing hydrocephalus and the raised ICP could be established, but the boy's condition improved after a shunt operation. In the other case, symptoms and signs consisted primarily in a slowly progressive dilatation of the facial veins with onset at the age of 2-3 years. As the girl also presented a congenital subvalvular aortic stenosis, the venous congestion was initially thought to reflect a vena cava superior syndrome. Further radiological examinations, however, revealed an extensive sinus thrombosis underlying the raised ICP. The girl underwent shunt insertion, and the venous congestion was reduced. CONCLUSIONS: The cases illustrate that though clinical and radiological findings may be very doubtful, or unusual for increased ICP, direct diagnostic long-term ICP monitoring should always be contemplated. Only ICP monitoring can reveal with certainty whether disturbed CSF dynamics are involved, requiring a CSF diverting operation to treat and stabilise the condition.

Child, Preschool↗

PubMed1998

Behçet's disease and the nervous system.

Behçet's disease is a multisystem inflammatory disorder with unknown aetiology. It is a disease of young adults with a more severe course in males subjects. Its prevalence is high in the Mediterranean basin and Japan and has been linked with human leucocyte antigen B5 (HLA-B5) in those countries. According to the diagnostic criteria formed by the International Study Group, recurrent oral ulceration is a prerequisite, with two more typical symptoms or signs. Neurological involvement is one of the most devastating manifestations of Behçet's disease. The involvement is either caused by primary neural parenchymal lesions (neuro-Behçet) or secondary to major vascular involvement (vasculo Behçet). The course is relapsing-remitting, secondary progressive or primary progressive. The most commonly involved area is the brain stem, with additional symptoms or signs, hemispherical involvement with mental changes being the most common. Intracranial hypertension, usually owing to dural sinus thrombosis, has a special place in Behçet's disease. The most common clinical findings are pyramidal signs. Sensory symptoms or signs are much less frequent, and hemianopia and higher cortical function disturbances as well as pure cerebellar syndrome are rare features. Cerebrospinal fluid usually has a high protein content and/or pleocytosis. Notably, in the acute period most patients have lesions shown by magnetic resonance imaging (MRI) extending from the brain-stem to diencephalic structures. Differential diagnosis from multiple sclerosis can be difficult in patients with hemispheric white matter MRI hyperintensities. Immunosuppressives are used in treatment.

Adult↗

PubMed2001

Behçet's disease: diagnostic and prognostic aspects of neurological involvement.

This study was conducted to describe clinical and prognostic aspects of neurological involvement in Behçet's disease (BD). Patients referred for neurological evaluation fulfilled the criteria of the International Study Group for Behçet's Disease. We analyzed disability and survival by the Kaplan-Meier method, using Kurtzke's Extended Disability Status Scale (modified for BD) and the prognostic effect of demographic and clinical factors by Cox regression analysis. We studied 164 patients; of the 107 diagnostic neuroimaging studies: 72.1% showed parenchymal involvement, 11.7% venous sinus thrombosis (VST) and the others were normal. CSF studies were performed in 47 patients; all with inflammatory CSF findings (n = 18) had parenchymal involvement. An isolated increase in pressure was compatible with either VST or normal imaging. The final diagnoses were VST (12.2%), neuro-Behçet syndrome (NBS) (75.6%), isolated optic neuritis (0.6%), psycho-Behçet syndrome (0.6%), and indefinite (11%). VST and NBS were never diagnosed together. Ten years from onset of BD 45.1% (all NBS) reached a disability level of EDSS 6 or higher, and 95.7 +/- 2.1% of the patients were still alive. Having accompanying cerebellar symptoms at onset or a progressive course is unfavorable. Onset with headache or a diagnosis of VST is favorable. Two major neurological diagnoses in BD are NBS and VST. These are distinct in clinical, radiological, and prognostic aspects, hence suggesting a difference in pathogenesis.

Behcet Syndrome↗

PubMed2001

Rhinocerebral zygomycosis in childhood acute lymphoblastic leukaemia.

The hazards associated with invasive candidiasis and aspergillosis in oncology patients are well recognised. These conditions typically present late in treatment, often after prolonged or recurrent episodes of neutropenia. We report the occurrence of Absidia corymbifera infection causing rhinocerebral zygomycosis in two children with acute lymphoblastic leukaemia, early in the induction phase of treatment and within a 3-month interval, in the same oncology unit. The initial presentation of facial pain was rapidly followed by the development of cranial nerve palsies, cavernous sinus thrombosis, diabetes insipidus, seizures and death within 9 days of symptom onset, despite aggressive management with high-dose liposomal amphotericin (Ambisome), surgical debridement and local instillation of amphotericin solution. These cases highlight the need for awareness of zygomycosis as a potentially lethal fungal infection that can present even with short duration exposure to the usual risk factors. Their occurrence within a limited time period raises questions as to the relative importance of environmental exposure. The failure of medical and surgical intervention to impact on the course illustrates the need to develop appropriate preventative strategies which may have to incorporate measures to reduce the environmental exposure of susceptible patients.

Absidia↗

PubMed2005

Simultaneous multiple hypertensive intracerebral haemorrhages.

BACKGROUND: Simultaneous occurrence of multiple intracerebral haemorrhages (ICHs) in different arterial territories is a rare clinical event which has been reported to be associated with cerebral amyloid angiopathy, venous sinus thrombosis, coagulopathy, vasculitis, haemorrhagic transformation of cerebral infarcts and multiple intracranial pathologies such as vascular anomalies or tumours. Although hypertension is the most common etiological factor for the development of spontaneous single intracerebral bleeding, its role in simultaneous multiple ICHs is not clear. METHODS: The authors have reviewed all patients with non-traumatic ICH admitted to Kaohsiung Medical University Hospital from 1993 to 2002. Ten hypertensive patients with simultaneous multiple ICHs were found. For the purpose of comparison, another 600 cases with solitary hypertensive ICH were also reviewed as a control group. Computerized tomographic scans and medical records concerning patients' histories, clinical presentations, locations of haematomas, associated risk factors, and outcome were analyzed. FINDINGS: The mean age and sex distribution were similar in both patient groups. Bilateral putaminal or thalamic haemorrhages were the most common combinations of simultaneous bleedings. As for the individual location of haematoma, there was a strong preponderance for the supratentorial space with the thalamus being the most preferable site. The duration of hypertension was longer and the percentage of previous stroke was higher in patients with multiple ICHs. Other associated risk factors were similar in both groups except for higher incidence of hypercholesterolemia in multiple ICHs group. Patients with simultaneous multiple ICHs had a much worse outcome compared to those with solitary ICH. CONCLUSIONS: As with solitary ICH, hypertension is still the most important etiological factor for simultaneous multiple ICHs. The widespread and prolonged degeneration of intracerebral arterioles predispose patients to the development of multiple ICHs, which could be justified by the longer history of hypertension and higher incidence of former strokes. Only hypercholesterolemia was identified to be significantly associated with this unusual brain event in our study. The mechanism underlying the development of simultaneous multiple ICHs is not clear although structural and haemodynamic changes of first haemorrhage may be responsible for the second one. Poorer outcome in patients with multiple ICHs can be explained by the concomitant destruction of crossing and non-crossing fiber tracts and bilateral diaschisis phenomenon.

Aged↗

PubMed2005

Clinical evaluation of bone-subtraction CT angiography (BSCTA) in head and neck imaging.

Fifty-one patients were examined with bone subtraction CT angiography (BSCTA). Data were acquired on 4-and 64-slice spiral CT systems. The post-processing method is based on fully automatic registration of non-enhanced and contrast-enhanced CT data and subsequent selective bone removal. Vascular structures and brain tissue are retained with the original CTA noise level. Image quality and delineation of the pathologic process were assessed and artifacts introduced by the bone removal process recorded. The bone subtraction algorithm worked successfully in all examinations. The processing time was 6 min on average. Image quality was rated excellent in 20 (39%), good in 26 (51%) and acceptable in 5 (10%) patients. Ophthalmic arteries were visible in 12 (24%) patients bilaterally, in 13 (25%) patients unilaterally and in 26 (51%) patients at least at the origin. BSCTA improved visualization of the infraclinoid ICA and the vertebral arteries. The depiction of stenosis of the extracranial ICA and supraclinoid aneurysms was not significantly improved. In patients with suspicion of sinus thrombosis, BSCTA and conventional CTA yielded similar results. To conclude, BSCTA improves the visualization of vessels with close contact to bone and can improve the diagnostic accuracy and therapy planning of infraclinoid aneurysms.

Adult↗

PubMed2026

PHACE syndrome: a systematic literature review and illustrative case report of a patient with severe cerebrovascular and neurodevelopmental sequelae.

BACKGROUND: PHACE syndrome is a rare neurocutaneous disorder defined by the association of large segmental infantile hemangiomas of the head and neck with malformations of the posterior fossa, cerebral and cervical arteries, heart, eyes, and ventral midline structures. Although facial hemangiomas are often the presenting feature, the cerebrovascular, neurodevelopmental, and airway manifestations are responsible for the greatest long-term morbidity. METHODS: A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Web of Science, EMBASE, and PsycINFO. After removal of duplicates and screening of 308 records, five studies meeting the inclusion criteria were retained for qualitative synthesis. We additionally present the case of a now 12-year-old girl with PHACE syndrome characterized by a left V1-distribution facial hemangioma, ocular abnormalities, multiple cerebrovascular venous and arterial malformations, neonatal intraventricular hemorrhage with hydrocephalus, and a subsequently diagnosed dural arteriovenous fistula requiring repeated embolization. RESULTS: The five included studies collectively describe epidemiology and early supportive care needs, long-term health outcomes and quality of life into adulthood, airway hemangioma prevalence and management, and the clinical spectrum of infantile hemangiomas with minimal or arrested growth (IH-MAG) as a cutaneous marker of PHACE syndrome. Across studies, cerebrovascular arteriopathy (72-91%) and facial hemangioma residua (> 90%) were the most consistent findings, while progressive arteriopathy, headaches, learning differences, and airway involvement emerged as the principal sources of long-term morbidity. The reported case illustrates an unusually severe cerebrovascular phenotype, including neonatal hemorrhagic hydrocephalus, dural venous sinus thrombosis, and a late dural arteriovenous fistula, culminating in ataxic cerebral palsy and mild intellectual disability. CONCLUSIONS: PHACE syndrome requires a multidisciplinary, lifelong follow-up strategy. The presented case underscores that cerebrovascular complications may evolve over years to decades after the initial diagnosis, reinforcing the need for long-term neuroradiological surveillance even after apparent clinical stability.

Humans↗

PubMed2002

Long-term Anticoagulation Therapy in Prevention of Stroke.

Long-term anticoagulation continues to be used and investigated as a means to prevent new or recurrent stroke. The best-established indications for long-term anticoagulation are cardiac abnormalities capable of producing intracardiac thrombi that may embolize into the brain or systemic circulation. The firmest cardiac indications are mechanical prosthetic heart valves, mitral stenosis with atrial fibrillation, and atrial fibrillation with additional features placing them at increased risk for stroke. These and other "major" cardiac potential sources of emboli should be considered as anticoagulation candidates unless the estimated risk of bleeding is prohibitive. A number of noncardiac potential causes of stroke are generally managed with long-term anticoagulation. These include arterial dissections, cerebral venous sinus thrombosis, the antiphospholipid antibody syndrome, and congenital and acquired coagulopathies. Recent randomized studies do not support the use of long-term anticoagulation for the prevention of recurrent stroke in patients with noncardioembolic stroke that is not due to the previously outlined disorders. Whether long-term anticoagulation is beneficial in the specific population of patients with major documented intracranial atherosclerotic stenosis is currently under investigation.

Journal Article↗

PubMed1989

Pseudotumor cerebri induced by danazol.

Intracranial hypertension with papilledema occurred in two patients receiving danazol therapy for either cyclic neutropenia or immune hemolytic anemia. Results of clinical, laboratory, and neuroradiologic studies showed no apparent cause for the condition in Case 1 and the papilledema resolved one month after discontinuing danazol. Carotid angiography in Case 2 demonstrated cerebral venous sinus thrombosis; the papilledema showed gradual improvement after cessation of danazol. An additional seven cases of pseudotumor cerebri presumed secondary to danazol therapy have been reported to the Food and Drug Administration. The papilledema resolved in all seven cases soon after discontinuing danazol. A drug-induced complication should be suspected, and alternative therapy sought, in patients who develop intracranial hypertension associated with administration of danazol.

Adult↗

PubMed1996

Antenatal care in pregnancies at risk of alloimmune thrombocytopenia: report of 19 cases in 16 families.

OBJECTIVE: To assess accuracy of a management program in patients at risk for alloimmune thrombocytopenia (NAITP) and to describe perinatal outcomes. STUDY DESIGN: Nineteen fetuses at risk of thrombocytopenia were identified using obstetric history, HLA type of the mother and fetal phenotyping in cases where paternal heterozygozity for the offending antigen was present. Cordocentesis was timed according to obstetric history and performed with safety precautions to prevent haemorrhage. High dose intravenous gamma globulin (IVIG) was administered to the mother in cases with a fetal platelet count < 100 x 10(9)/l. RESULTS: The platelet antagonisms were distributed as follows: HPA-1a in 15 patients, HPA-5a in two, HPA-3a in one, with one further woman who had antibodies against a private antigen. All multigravidas (N = 18) had previously given birth to an infant with NAITP and two of those infants had experienced severe bleeding. Two fetuses were negative for the offending antigen. The median and mean platelet count at first cordocentesis was 26 and 75 x 10(9)/l respectively (range 3-276). A total of 46 cordocentesis were carried out, of which 37 were followed by platelet transfusions. Bleeding complications were not observed. IVIG was administered to eight mothers and two fetuses responded. Nine infants were delivered by caesarean section (CS) and 10 vaginally at a mean gestational age of 37 weeks (range 34-41). The median and mean platelet count at birth was 141.5 and 140 x 10(9)/l, respectively (range 36-314). Ultrasound examination, both ante- and postnatally, revealed no intracranial haemorrhages. There was one procedure related neonatal death and one infant suffered from convulsions in the neonatal period due to a sinus thrombosis, possibly related to the platelet transfusions. CONCLUSIONS: When obstetric history is taken into account cordocentesis in NAITP can be postponed. Safety recommendations described in this study allow cordocentesis without bleeding complications. However, our study does not support routine cordocentesis in patients with a history of NAITP. Both the risks of cordocentesis, and the lack of prospective data on the magnitude of the risk of intrauterine or peripartal bleeding, should be considered.

Blood Transfusion, Intrauterine↗

PubMedDate not supplied

Pseudotumor cerebri associated with obstructive nephropathy.

We report two infants with pseudotumor cerebri associated with renal disease. The pathogenesis of increased intracranial pressure in this clinical setting is unclear, but may be mediated by one or more of the conditions commonly associated with pseudotumor cerebri, including sinus thrombosis, increased intravascular fluid volume, anemia, and endocrine disturbances resulting in abnormal calcium and phosphorus metabolism. The onset of pseudotumor cerebri also may be related to changes in vasopressin levels that affect brain water permeability.

Acidosis, Renal Tubular↗

PubMed1995

Neurologic manifestations of pediatric systemic lupus erythematosus.

Central nervous system involvement is a common but rarely reviewed feature of pediatric systemic lupus erythematosus (SLE). We retrospectively reviewed the charts of 91 patients with pediatric SLE and using a standardized data abstraction form documented 40 patients with central nervous system (CNS-SLE) involvement. The mean age of onset of SLE was 13.3 years. In 19 patients the CNS manifestation was a presenting symptom, in 12 patients CNS involvement was present within the first year of diagnosis, and in 9 patients it took up to 7 years for CNS disease to become evident. Nineteen children (48%) manifested neuropsychiatric SLE, which included depression, concentration or memory problems, and frank psychosis. Seizures were present in 8 patients (20%), 6 had cerebral ischemic events (15%), 1 had chorea (3%), 2 had papilledema (5%), and 2 patients had a peripheral neuropathy (5%). Nine patients (22%) had severe headache consistent with lupus headache. Seven children had more than one CNS manifestation. In the investigation of CNS-SLE, computed tomography and/or magnetic resonance imaging scans were helpful in patients with focal ischemic lesions and venous sinus thrombosis. Electroencephalography was abnormal only in 33% of patients with seizure disorders and rarely helpful in patients with diffuse neuropsychiatric symptoms. Single-photon emission computed tomography scans were abnormal in most patients with neuropsychiatric SLE, especially in those with frank psychosis. The lupus anticoagulant was present in the patient with chorea and was frequently present in patients with cerebral vascular events. Long-term outcome was good: only 1 child died of cerebral hemorrhagic infarction and 3 others had significant persistent CNS deficits. The majority of patients (90%) had excellent recovery from CNS-SLE.

Adolescent↗

PubMedDate not supplied

Two consecutive cases of cerebrospinal fluid rhinorrhea after septoplasty operation.

Our aim in this work is to define the importance of anatomical knowledge in septoplasty operation and to prevent complications. Septoplasty is one of the most common operations in otorhinolaryngology to treat the nasal obstruction caused by septal deviation. During and after septoplasty, there are some recorded complications, such as hemorrhage, hematoma, septal abscess, septal perforation, saddle nose, infection, anosmia, visual disturbances, cavernous sinus thrombosis, meningitis, pneumoencephalos, subarachnoid hemorrhage, subdural empyma, brain abscess, periorbital emphysema, toxic shock syndrome, and cerebrospinal fluid (CSF) rhinorrhea. Some of the complications are rare, but their results are life threatening. We report a rare complication of septoplasty CSF rhinorrhea. Two consecutive cases of CSF fistulas after septoplasty operation are presented. Both of the cases were treated endoscopically. The possible mechanisms and different treatment options are discussed. Prevention of the CSF fistula in septoplasty is more important than its treatment. Realizing the anatomic variations and gentle manipulation at the ethmoid roof is essential.

Adult↗

PubMedDate not supplied

Otogenic intracranial complications. a 7-year retrospective review.

OBJECTIVES: The objectives of this study were to review our experience on intracranial complications secondary to otitis media (OM), and to compare the results to those occurring 10-15 years ago. We also reviewed the timing of both otologic and neurosurgical treatments. MATERIAL AND METHODS: All patients with intracranial complications secondary to OM over a 7-year period were identified. A retrospective chart review was undertaken at Beaumont University Hospital, Dublin, Ireland. Clinical presentation, radiological findings, microbiology, surgical management, and antibiotic use were studied. We compare our findings to those of other international investigators. RESULTS: Twelve cases were identified. Five had brain abscesses, 4 had lateral sinus thrombosis, and 3 had petrous apicitis. Eight of these cases were secondary to chronic OM and 4 were secondary to acute OM. Malodorous otorrhea, otalgia, headache, fever, and vertigo were the primary symptoms. Anaerobic bacteria were the most commonly isolated organisms followed by Staphylococcus aureus, Proteus mirabilis, and Pseudomonas aeruginosa. Patients with cholesteatoma underwent modified radical or radical mastoidectomy, and those who did not have cholesteatoma underwent cortical mastoidectomy. Two brain abscesses were drained before mastoid surgery; 2 were drained after mastoid surgery and 1 at the same time as otologic surgery. All patients received broad-spectrum intravenous antibiotics targeted at individual culture and sensitivity results. The mortality rate was zero. CONCLUSION: Clinical presentation and the frequency of occurrence of intracranial complications are similar to those occurring 10 years ago. The choice of antibiotics should include adequate anaerobic cover. We recommend that otologic surgery be performed at the same time as intracranial surgery for patients with mature brain abscesses.

Adolescent↗

PubMed2005

Does use of hormonal contraceptives among women with thrombogenic mutations increase their risk of venous thromboembolism? A systematic review.

Because use of combined oral contraceptives (COCs) confers some risk of venous thromboembolism (VTE), there is concern that this effect may be greater among women with thrombogenic mutations. We searched the MEDLINE and EMBASE databases for all articles published from January 1966 through September 2004 for evidence relevant to hormonal contraception and thrombogenic mutations. Of 301 articles identified by the search strategy, 16 evaluated COCs, and no studies were found for other hormonal methods. We used standard abstract forms and grading systems to summarize and assess the quality of the evidence. A total of 10 studies together provided "good" evidence of a greater risk of VTE (risk ratios of 1.3-25.1) and cerebral vein or cerebral sinus thrombosis among COC users with factor V Leiden mutation when compared with nonusers who have the mutation. The evidence for prothrombin and other thrombogenic mutations was not as strong as for factor V Leiden mutation. It is unclear whether the type of COC or duration of use modifies the risk of VTE among women with thrombogenic mutations.

Contraceptives, Oral, Hormonal↗

PubMed2004

Central nervous system imaging in childhood leukaemia.

The aim of this study was to document the imaging abnormalities seen in the central nervous system (CNS) in cases of childhood leukaemia or as complications of its treatment. Magnetic Resonance (MR) images and Computed Tomographic (CT) scans were reviewed retrospectively in 22 children and adolescents with neurological manifestations/complications of leukaemia or its treatment. Among the 22 patients, nine had two or more different CNS abnormalities. The imaging abnormalities seen in 15 patients before or during treatment included sinus thrombosis, cortical vein thrombosis, cerebral haemorrhage, meningeal leukaemia, infections, skull leukaemic infiltration and treatment-related neurotoxicity. After therapy, seven patients had CNS abnormalities, including secondary brain tumours, skull tumour, mineralising microangiopathy, leucoencephalopathy, transient white matter abnormalities, spinal intradural haematoma, chronic subdural haematoma, radiation necrosis, meningeal leukaemia and leukaemic infiltration at the vertebral body. CNS complications are related to the inherent risk of leukaemia itself, to the treatment method and to the duration of survival.

Adolescent↗