Symptomatic intracranial haemorrhage in acute nonlymphoblastic leukaemia: analysis of CT and autopsy findings

We studied the CT and autopsy findings in patients with symptomatic intracranial haemorrhage (ICH) in acute nonlymphoblastic leukaemia (ANLL). From 1982 to 1994, 38 (20%) of 194 patients with ANLL were diagnosed as having ICH, by CT in 17 patients, by autopsy in 11 and by both examinations in 10. Intracerebral haemorrhage occurred in 30 patients. Twenty-four patients with subcortical haemorrhage were classified into three types: a single haematoma (7), clustered multifocal haematomas (11), and separated multifocal haematomas (6). Subarachnoid haemorrhage (SAH) occurred in 22 patients; 15 with subcortical haemorrhage, 1 with subdural haemorrhage (SDH) and 6 without any other ICH. SDH was also found in 4 patients with parenchymal haemorrhage or SAH or both. Concurrent, multiple haemorrhages consisting of various combinations of intracerebral haemorrhage, SAH and SDH are characteristic of ICH in ANLL. Multiple or confluent haematomas occur preferentially in subcortical brain. Received: 7 May 1996 Received in revised form: 30 July 1996 Accepted: 26 August 1996     

Neuromuscular complications after allogeneic bone marrow transplantation

Neuromuscular syndromes following allogeneic bone marrow transplantation (BMT), although occasionally described,were not the focus of studies concerning neurologic complications following bone marrow transplantation. In this study,we summarize different polyneuropathy syndromes following BMT and report on patients with myasthenia gravis and inflammatory neuromuscular disorders such as myositis or fasciitis.Concerning the etiology of neuropathies, a neurotoxicity of immunosuppressants,a preexisting disorder due to the underlying disease as well as an association with graft-versus-host disease (GVHD) is discussed.GVHD-associated polyneuropathies as well as muscular complications have been found to occur during the early BMT phase, while myasthenia gravis is a late neurologic complication of GVHD.     

Intracerebral haemorrhage during surgery for chronic subdural haematoma.

Although intracerebral haemorrhage occurring after surgery for chronic subdural haematoma has been reported as a rare complication, intracerebral haemorrhage occurring during surgery has not been described previously. A case of bilateral chronic subdural haematomas, with a small motor area haemorrhage occurring intra-operatively, is described here.     

Evaluation of the efficiency of intracranial volume compensation before and after surgical treatment of intracranial hematoma

On the ground of the clinical status and indicators of intracranial pressure instability and cerebral arterial reactivity the authors evaluated the efficiency of intracranial volume compensatory mechanisms in 21 patients before and after operations for epidural and subdural haematomas and spontaneous intracerebral haematomas. The epidural haematomas in a greater degree but less permanently exhausted the efficiency of the compensatory mechanisms than subdural haematomas and after their removal these mechanisms regained easier their efficiency than after removal of subdural haematomas. In cases of spontaneous intracerebral haematomas the efficiency of the compensatory mechanisms is only slightly decreased.     

Spontaneous intracerebral haemorrhage following evacuation of chronic subdural hematomas.

Spontaneous intracerebral haematoma (ICH) is an extremely unusual complication following the evacuation of a chronic subdural haematoma (CSDH). Good outcome is expected after the drainage of the CSDH and neurological deterioration is a cause for serious concern. Authors report three cases of spontaneous ICH away from the site of surgery following evacuation of a CSDH with a review of literature. Changes in cortical blood flow following decompression of a long standing CSDH may be responsible for the ICH.     

Increased incidence of neurological complications in patients receiving an allogenic bone marrow transplantation from alternative donors

OBJECTIVE: To compare the frequency and type of neurological complications after bone marrow transplantation (BMT) with an HLA identical unrelated donor or a mismatched related donor (alternative donors) to the neurological complications after matched sibling BMT for standard and high risk leukaemia or myelodysplastic syndromes. METHODS: Retrospective analysis of consecutively treated patients with (a) BMT from alternative donors (n=39), (b) treated with matched sibling BMT for standard risk leukaemia, myelodysplastic syndromes, or aplastic anaemia (n=53), and (c) treated with matched sibling BMT for high risk leukaemia, myelodysplastic syndromes, or aplastic anaemia (n=49). RESULTS: A total of 72 neurological complications were found. Most of these occurred within the first 6 months after transplant. Thirty six patients developed a severe neurological complication: 17 Alternative donor patients (44%) by contrast with six standard risk patients (11%) and 13 high risk patients (27%; p<0.005). The most frequent complication was a metabolic encephalopathy occurring in 18% of patients. Most of the encephalopathies were caused by either the transplant procedure, cyclosporin, systemic infections, microangiopathic thrombopathy, or by complications induced by graft versus host disease. Infections of the CNS developed in 9% of patients, cerebrovascular lesions in 3%. CONCLUSIONS: Severe neurological complications are more frequent after BMT from alternative donors. This is mainly due to increased treatment related morbidity and to more profound immunosuppression after BMT from alternative donors.     

Continuous growth of remote intracerebral haematoma following angiographically successful endovascular embolisation of ruptured cerebral aneurysms

We describe a poorly recognised and rare complication following the endovascular embolisation of ruptured cerebral aneurysms. Three patients with dense focal subarachnoid haemorrhage (SAH) developed continuous growth of remote intracerebral haematoma (ICH) following endovascular embolisation of a ruptured aneurysm. All endovascular procedures were conducted within less than 6 hours after the onset of SAH with systemic anticoagulation and were completed uneventfully; external ventricular drainage was subsequently inserted. Repeated CT scans revealed continuous growth of ICH remote from the aneurysm without aneurysmal rebleeding. The authors suggest that endovascular embolisation for a ruptured aneurysm under systemic anticoagulation within 6 hours after SAH onset may increase the risk of expanding haematomas, especially in patients with dense focal SAH.     

Intracerebral haemorrhage after thrombolysis for acute ischaemic stroke: an update

Intracerebral haemorrhage (ICH) still represents the most feared complication of thrombolysis. Our aim was to review the literature regarding clinical, biological and imaging predictors of ICH following thrombolysis for acute ischaemic stroke. Relevant studies were identified through a search in Pubmed, using the following key words: "intracerebral", "haemorrhage", "stroke" and "thrombolytic". The query was limited to studies published in the English literature. The reference lists of all relevant articles were reviewed to identify additional studies. The main predictors of clinically significant ICH were age, clinical stroke severity, as assessed by the National Institute of Health Stroke Scale score on admission, high blood pressure, hyperglycaemia, early CT changes, large baseline diffusion lesion volume and leukoaraiosis on MRI. The contribution of biomarkers in the prediction of the ICH risk is currently under evaluation. Available data on patients with limited number of microbleeds on pretreatment gradient echo MRI sequences suggest safe use of thrombolysis. ICH after stroke thrombolysis is a complex and heterogeneous phenomenon, which involves numerous parameters whose knowledge remains partial. To minimise the risk of tissue plasminogen activator (tPA) related symptomatic ICH, careful attention must be given to the pre-therapeutic glycaemia value, and a strict protocol for the control of elevated blood pressure is needed during the first 24 h. Future research should focus on predictors of severe intracerebral haemorrhagic complications (parenchymal haematomas type 2 according to the European Cooperative Acute Stroke Study (ECASS) classification). The input of multimodal MRI and biological predictors of ICH deserves further investigation.     

Neurological complications of anticoagulants (author's transl)]

During a course of therapy by anticoagulants, 16 intracranial haemorrhages and 10 cerebral infarctions, were observed over a period of seven years. The intracranial haemorrhages include 11 subdural haematomas (four acute, seven chronic) and ive intracerebral haemorrhages, one of which resulted from the rupture of an arterial aneurysm. The anticoagulant therapy lasted in 12 cases for more than two years, and in four cases between twenty-four hours and two months. Monocoumarinics are most often the cause of the haemorrhages. The subdural haematomas are unpredictable and a traumatism was only observed in four cases. Three out of four patients with acute haematomas died, as well as two out of seven patients with chronic haematomas. Three out of four intracerebral haemorrhages occurred after ischemic cerebral accidents. The existence of a cerebral infarction counter-indicates the use of anticoagulants. The cerebral infarctions occurred five times during the anticoagulation therapy, and five times after stopping the treatment (from within a few days to a few weeks). Anticoagulation therapy, apart from infarction, is in general well supported and well supervised during the first weeks. Used for a long time, it may lead to very serious and often fatal complication, and must therefore be weighed against the advantages of the treatment.     

Anticoagulation-related intracranial extracerebral haemorrhage.

From January 1981 to June 1986 116 patients with anticoagulation-related intracranial haemorrhage were referred to hospital. Seventy six of these haemorrhages were extracerebral, 69 were in the subdural and seven in the subarachnoid space. No epidural haemorrhages were identified. Compared with non-anticoagulation-related haematomas, the risk of haemorrhage was calculated to be increased fourfold in men and thirteenfold in women. An acute subdural haematoma, mostly due to contusion, was more frequently accompanied by an additional intracerebral haematoma than a chronic subdural haematoma. Trauma was a more important factor in acute subdural haematomas than in chronic. Almost half of the patients (48%) had a history of hypertension, more than a third (35%) had heart disease and about one fifth (18%) were diabetic. Headache was the most frequent initial symptom. Later decreased level of consciousness and focal neurological signs exceeded the frequency of headache. Three patients with subarachnoid haemorrhage and nine patients with acute subdural haematomas died, while those with chronic subdural haematomas all survived and had at the most mild, non-disabling sequelae. Myocardial infarction (22%), pulmonary embolism (20%), and arterial disease (20%) were the most frequent reasons for anticoagulant treatment. Critical review based on established criteria for anticoagulation treatment suggests there was no medical reason to treat a third of these patients. The single most useful measure that could be taken to reduce the risk of anticoagulation-induced intracranial haemorrhage would be to identify patients who are being unnecessarily treated and to discontinue anticoagulants.     

Neurosurgical aspects of sedimentation levels in acute intracerebral haematoma

We describe the neurosurgical aspects of sedimentation levels that are rarely found in acute intracerebral haematomas (ICH). We had four patients with acute ICH whose cerebral computed tomography revealed sedimentation levels. Two patients had received thrombolytic therapy for ischaemic heart disease and one for ischaemic stroke. Another patient, who was diagnosed later as having a coagulation disorder, did not have any medical history on admission. All patients had emergency ICH drainage under local anaesthesia. In the immediate postoperative period, we observed dramatic improvement in all the patients, without surgical complications. The sedimentation level in an ICH should be identified as a specific indicator of a coagulation defect and a thorough search for possible underlying coagulopathy is warranted. We believe that simple ICH drainage should be performed as the haematoma is in a liquid form.     

Prothrombin complex concentrates to reverse warfarin-induced coagulopathy in patients with intracranial bleeding

Prothrombin complex concentrates (PCCs) offer a means for the rapid reversal of warfarin, particularly in the setting of life-threatening bleeding. We evaluated the effectiveness and safety of a PCC-based protocol in patients with warfarin-associated intracerebral hemorrhage (ICH), subdural hematoma (SDH), or subarachnoid hemorrhage (SAH).     

Epileptic seizures in intracerebral haemorrhage.

Among 1402 patients with intracerebral haemorrhage (ICH), seizures occurred in 64 (4.6%) and epilepsy in 35 (2.5%). Seizure was the first manifestation of ICH in 19 patients (30%). Status epilepticus occurred in 11 patients (17%) and it was the initial presentation of ICH in six (9%). The majority had simple partial seizures that were predominantly focal and motor. There were 38 patients with early seizure and 26 patients with late seizure. Ninety per cent of seizures occurred within one year after ICH. Eleven patients (29%) with early seizure developed epilepsy, whereas 24 patients (93%) with late seizure developed recurrent seizures. The incidence of seizure was 32% for lobar haematoma, 2% respectively for putaminal, thalamic and pontine haemorrhages and 1% for cerebellar haemorrhage. Twenty-six (62%) out of 42 patients with lobar haematomas developed epilepsy. Thirteen patients (34%) with early seizure died within three months after the onset of seizures whereas three patients (12%) with late seizure died within the same period. The majority of patients who died had deep-seated haematomas.     

骨髓间充质干细胞移植治疗脑出血大鼠的实验研究

目的探讨骨髓间充质干细胞移植对脑出血大鼠的行为和血肿周围神经细胞凋亡的影响。方法全骨髓贴壁法分离培养大鼠骨髓间充质干细胞,使用立体定向纹状体注入胶原酶法制作大鼠脑出血模型。SD大鼠30只,随机分为对照组和移植组(各15只),对照组制作脑出血模型,不移植;移植组制作脑出血模型并于造模后48 h经立体定向脑内注射1×105个干细胞,并于移植后1 d、3 d、5 d、7 d、14 d进行神经功能缺损评分,对照组在相应时间点同样评分,各组再根据时间的不同随机分成五个亚组(每组3只),在相应时间点处死大鼠行免疫组织化学法检测细胞凋亡。结果在移植后1 d、3 d,两组大鼠评分及血肿周围脑组织内凋亡细胞的数量均较高,两组之间无显著性差异。在移植后第5 d、7 d,两组大鼠评分及血肿周围脑组织内凋亡细胞的数量开始下降,移植组下降幅度大于对照组,两组之间差异显著。移植后14 d,两组之间无显著性差异。结论骨髓间充质干细胞移植可明显促进大鼠脑出血后神经功能的恢复,其机制可能与下调血肿周围神经细胞凋亡有关。     

Cerebral involvement in graft-versus-host disease after murine bone marrow transplantation

Neurologic manifestation of graft-versus-host disease (GvHD) after allogeneic bone marrow transplantation (BMT) has until now been limited to rare neuromuscular syndromes. Investigating cerebral findings using a murine BMT model, the authors found parenchymal lymphocytic inflammation, microglia activation, and mild cerebral angiitis-like changes in allogeneic transplanted animals but not in syngeneic controls. These findings suggest that cerebral involvement during GvHD may be a new neurologic complication after BMT.     

Central and peripheral nervous system complications following allogeneic bone marrow transplantation

Although graft vs. host disease (GvHD) is a frequent complication of allogeneic bone marrow transplantation (BMT), involvement of the central and peripheral nervous systems (CNS and PNS, respectively) has not been demonstrated conclusively. Here, we report of a patient who, following allogeneic BMT for lymphoblastic T-cell lymphoma, suffered a syndrome characterized by self-remitting cerebellar and pyramidal signs associated with a progressive involvement of the peripheral nervous system (PNS). Clinical course and laboratory findings correlated with relapses of systemic GvDH, thus suggesting the possibility that involvement of CNS and PNS may be sustained by a similar pathogenic mechanism.     

Comparison of cerebral blood flow and injury following intracerebral and subdural hematoma in the rat

Subdural hematomas (SDH) can induce ischemia and neuronal damage in the underlying cortex. However, the extent to which intracerebral hematomas (ICH) produce reductions in cerebral blood flow (CBF) sufficient to cause ischemic damage is uncertain. Intracranial hemorrhage was induced by the injection of 100 or 200 microl of blood into the subdural space (SDH) or into the caudate nucleus (ICH) of the rat. CBF was measured using [14C]-iodoantipyrine autoradiography at 4 h. Brain damage was measured using 2,3, 5-triphenyl tetrazolium chloride (TTC) staining at 24 h and brain edema was measured using the wet/dry weight method. Brain ion contents were measured at 24 h using a flame photometer and chloridometer. In the CBF studies, the volume of tissue perfused below the ischemic threshold (<20 ml/100 g/min) for SDH was 122+/-35 mm3 (sham: 3.3+/-1.7 mm3). Following ICH, there was a small volume of tissue perfused below the ischemic threshold 50+/-11 mm3 (sham: 3. 3+/-2.5 mm3) but this volume corresponded closely to the volume of clot (71+/-5 mm3). The extent of brain damage, measured by TTC staining, in the cerebral cortex correlated with the increasing volume of the subdural blood clot (sham: 9+/-3 mm3; 200 microl: 81+/-19 mm3; P<0.01). Conversely, minimal brain damage was detected following ICH. The injection of blood into the subdural space or into the brain parenchyma induced blood volume-dependent increases in brain water content at 24 h. Increases in brain water content after SDH, were confined to the cerebral cortex (sham: 0.1+/-0.1 g/g dry weight; 200 microl: 0.8+/-0.3 g/g dry weight; P<0.001). In contrast, increases in brain water content after ICH were predominantly in the subcortical region (sham: 0.1+/-0.1 g/g dry weight; 200 microl: 0.4+/-0.2 g/g dry weight; P<0.01). The present investigations demonstrate differences in CBF, brain injury and edema formation following SDH and ICH indicating that these conditions may require different therapeutic interventions.     

Fatal Subdural Empyema Following Pyogenic Meningitis

Subdural empyema is a rare form of intracranial sepsis associated with high morbidity and mortality. The most frequent cause is extension of paranasal sinusitis through emissary veins or of mastoiditis through the mucosa, bone, and dura mater. Development of subdural empyema after pyogenic meningitis is known to be very unusual in adults. We report a rare case of fatal subdural empyema, an unusual complication of pyogenic meningitis. Our bitter experience suggests that subdural empyema should be borne in mind in patient with pyogenic meningitis who exhibit neurological deterioration.     

Interobserver agreement in the assessment of lobar versus deep location of intracerebral haematomas on CT

In patients with supratentorial intracerebral haemorrhage (ICH), it is important to discriminate superficial (lobar) and deep (basal ganglia) location, since this has consequences for research and prognosis. Haemorrhages at these sites have different causes and different risk factors. We studied the interobserver variation between three radiologists in classifying fifty large haematomas on CT as deep or lobar. The kappa values were almost perfect, ranging from 0.88 to 0.96. We conclude that the assessment of CT by radiologist is a reliable method to discriminate between lobar versus deep origin even for large intracerebral haematomas.     

Muscle-specific kinase antibody associated myasthenia gravis after bone marrow transplantation

Myasthenia gravis is a rare complication of bone marrow transplantation and graft versus host disease. We report a 30-year-old woman presented with oculobulbar and proximal limb weakness after allogeneic bone marrow transplantation for chronic myelogenous leukemia. Also, she developed graft versus host disease following bone marrow transplantation. Investigations led to the diagnosis of muscle specific kinase antibody related myasthenia gravis. There have been only two case reports of muscle specific kinase antibody positive myasthenia gravis after bone marrow transplantation in the literature, but none of the previously reported cases had graft versus host disease.