Reversible posterior leukoencephalopathy syndrome: experience in 3 cases]

We report 3 cases with reversible posterior leukoencephalopathy syndrome (RPLS) accompanied by eclampsia or hypertensive encephalopathy. RPLS may develop in patients who have eclampsia or hypertensive encephalopathy or who are immunosuppressed. The findings on neuroimaging are characteristic of subcortical edema without infarction. A 27-year-old primigravida developed eclampsia at 37 weeks of gestation. MRI was performed 4 hours after the onset. The FLAIR sequence delineated extensive hyperintense lesions in the temporal and occipital lobe bilaterally. MR angiography(MRA) performed 6 days after the onset of symptoms clearly demonstrated intracranial vasospasm. Follow up MRI and MRA were performed 3 weeks after the onset. The MRI showed slight residual hyperintensity in the occipital lobe. The MRA showed the disappearance of the vasospasm. A 39-year-old woman on the 8th postpartum day presented with thunderclap headache, which led to a search for SAH. She visited our hospital, whose high arterial blood pressure (220/110 mmHg) was observed. Both CT and MRA were normal. MRI revealed abnormalities in the parieto-occipital regions bilaterally. Treatment of hypertension led to resolution of the posterior leukoencephalopathy. A 38-year-old woman on the 11th postpartum day suddenly developed vertigo, visual disturbance and generalized convulsion. MRI was performed 7 days after the onset. The FLAIR sequence delineated extensive hyperintense lesions in the occipital lobe bilaterally. MRA clearly demonstrated diffuse intracranial vasospasm. MRA performed 3 weeks after the onset showed the disappearance of the vasospasm. In conclusion, our experience suggests that the MRI and MRA noninvasively provide valuable findings which are complementary in the diagnosis and follow-up examination of a brain edema and vasospasm in RPLS.     

Magnetic resonance angiography of experimental cerebral vasospasm

The purpose of this study was to observe spastic cerebral arteries by magnetic resonance angiography (MRA) and to establish acetazolamide reactivity of these vessels. After control studies using MRA and conventional angiography, subarachnoid haemorrhage (SAH) was induced on day 0 in 7 Japanese monkeys. MRA and conventional angiography were then repeated on day 7 to observe the development of cerebral vasospasm. Reactivity of cerebral vessels to acetazolamide was also studied in both control animals (angiography before SAH) and on day 7 after SAH. Cerebral vasospasm was detected by both conventional angiography and MRA on day 7. The arteries on the side of the clot were more spastic than those on the control side. MRA was superior to conventional angiography in demonstrating dilatation of both control arteries (before SAH induction) and vasospastic arteries (on day 7 after SAH) after administration of acetazolamide.     

Posterior reversible leukoencephalopathy due to “triple H” therapy

Posterior leukoencephalopathy syndrome is a rare complication of triple H therapy, which is the treatment for symptomatic vasospasm occurring following subarachnoid hemorrhage. This complication must be considered when neurological deterioration of a patient continues or worsens during triple H therapy. We report a patient diagnosed with posterior leukoencephalopathy syndrome during triple H therapy.     

Reversible carotid artery narrowing in morning glory disc anomaly.

A 14-year-old boy with morning glory disc anomaly (MGDA) and normal visual and neurologic function displayed marked carotid artery narrowing on magnetic resonance angiography (MRA). This narrowing disappeared on a follow-up MRA six months later. Optic coherence tomography and scanning laser polarimetry disclosed a normal retinal nerve fiber layer in the eye with MGDA. MGDA has been reported in association with irreversible carotid artery stenosis leading to moya moya disease. This case suggests that mild cases of MGDA may be associated with reversible carotid artery narrowing owing to vasospasm.     

CT and CT-Perfusion Findings of Reversible Leukoencephalopathy During Triple-H Therapy for Symptomatic Subarachnoid Hemorrhage-Related Vasospasm

BACKGROUND: Reversible leukoencephalopathy syndrome (RLS) is an acute neurological syndrome associated with altered mental status and visual disturbances described in patients with sudden elevations in systemic blood pressure and other medical conditions. In this process, neuroimaging studies usually demonstrate diffuse edema involving the subcortical structures of the posterior regions of the brain. Triple H (HHH) therapy is an established treatment for symptomatic vasospasm following subarachnoid hemorrhage (SAH). RLS has not been reported in the scientific literature as a complication of HHH therapy with perfusion computed tomography (CTP) imaging documentation. CASE: A 73-year-old woman developed iatrogenic RLS during HHH therapy for SAH-related vasospasm. The computed tomography (CT) revealed bilateral parieto-occipital hypodensities. The CTP study showed increased cerebral blood volume and blood flow as well as decreased mean transit time in both parietal-occipital regions, which is compatible with vasogenic edema. CONCLUSION: The induction of hypertension as part of HHH therapy for SAH-related cerebral vasospasm may result in RLS. Therefore, it should be considered as a potentially reversible cause in the differential diagnosis of neurological deterioration in SAH patients while on HHH therapy. CTP study can offer an alternative for the assessment of this cerebrovascular syndrome.     

异基因造血干细胞移植导致的可逆性后部白质脑病综合征

可逆性后部白质脑病综合征是异基因造血干细胞移植后常见并发症之一,病因主要是预处理方案中大剂量放化疗和免疫抑制剂的应用,另外与感染、抗感染治疗和移植后排斥反应有关。发病机制是脑血管自动调节障碍与内皮损伤、交感神经分布差异与高血压脑血管痉挛。临床表现多以抽搐为首发,多有视力下降、血压增高、头痛、意识和精神行为改变。 全身症状可有代谢紊乱、低镁血症、低胆固醇血症、肾功能衰竭。可逆性后部白质脑病综合征一个重要特点是其临床和影像学的可逆性,异基因造血干细胞移植后仅少数患者在数周内痊愈,长时间抽搐、伴缺血性改变者预后不良。     

A case of reversible postpartum cytotoxic edema in preeclampsia

We report on a 32-year-old woman who developed reversible cortical blindness and right-sided weakness after cesarean section at 36 weeks of gestation, due to preeclampsia. An initial brain MRI demonstrated high signal intensity lesions in the bilateral occipito-parietal and left frontal lobes on T2-weighted and diffusion-weighted imaging. All of the lesions showed low signal intensity on apparent diffusion coefficient (ADC) map, which were compatible with cytotoxic edema, and MR angiography (MRA) showed diffuse vasospasm of the intracranial vessels. A follow-up brain MRI showed that most of the lesions disappeared and the vasospasm also resolved. This case suggests that the cytotoxic edema in preeclampsia may evolve differently from the pattern in cerebral infarction and explains the relatively benign course of the neurological signs in preeclampsia.     

Sickle cell disease and posterior reversible leukoencephalopathy

Sickle cell disease can present with neurological manifestations. One such presentation is with posterior reversible leukoencephalopathy also known as reversible posterior leukoencephalopathy. The condition is classically described as reversible over time; it commonly presents with oedematous changes involving the white matter of the occipital and parietal regions. Only a few patients with the association between sickle cell disease and posterior reversible leukoencephalopathy have been described in the adult literature. We present two patients from our institutions to emphasise the association between the two conditions and summarise the published cases in the literature.     

动脉瘤性SAH后症状性脑血管痉挛与高凝状态相关性及防治研究

目的:探讨动脉瘤性SAH后症状性脑血管痉挛与病人外周血清高凝状态的相关性,同时观察应用丹参注射液对血液高凝状态的影响。方法:60例动脉瘤性蛛网膜下腔出血(SAH)病人,出现症状性脑血管痉挛38例,症状性脑血管痉挛组随机分为丹参治疗组和非丹参治疗组。所有病人分别在住院时、3天、7天、14天、21天,进行周围血中FDP和D-dimer含量的测定并进行动态观察。结果:症状性脑血管痉挛组病人FDP和D-dimer的含量在住院后各时间段明显高于非症状性脑血管痉挛组(P<0.01),住院后第14天、21天丹参治疗组FDP和D-dimer的含量明显低于非丹参治疗组(P<0.05)。症状性脑血管痉挛组中,丹参治疗组病人的预后明显优于非丹参治疗组。结论:动脉瘤性SAH引起症状性脑血管痉挛与血粘稠度增高有明显关系。丹参注射液可明显降低血粘稠度,促进脑血液循环对改善症状性脑血管痉挛的脑缺血症状有明显的治疗作用。     

Magnetic resonance imaging of suspected cervicocranial arterial dissections.

The authors propose that the optimal screening protocol for evaluation of suspected cervicocranial arterial dissections is magnetic resonance imaging (MRI) that includes three components: 1) contrast-enhanced three-dimensional time-of-flight magnetic resonance angiography (MRA) through the superior mediastinum, neck, and skull base; 2) three-dimensional multiple overlapping thin-section acquisition MRA of the skull base and Circle of Willis region; and 3) axial non-contrast, non-fat-suppressed T1-weighted, fat-suppressed T1-weighted, and T2-weighted spin-echo MRI from the level of the aortic arch through the level of the circle of Willis. MRA permits visualization of vascular luminal narrowing or obliteration, which can suggest vascular dissection but can also be caused by congenital variation, dysplasia, intraluminal thrombus, vasospasm, or extramural compression by tumor. By directly visualizing the blood vessel wall, axial T1-weighted and T2-weighted spin-echo MRI can identify the intramural hemorrhage of vascular dissection. This protocol is designed to maximize the sensitivity of a noninvasive technique and may eliminate the need for conventional endovascular angiography.     

Brain injury in children with sickle cell disease: prevalence and etiology

Our objective was to evaluate the relationship between brain injury by magnetic resonance imaging (MRI) and vasculopathy by magnetic resonance angiography (MRA) in children with hemoglobin SS, the most serious form of sickle cell disease. We reviewed imaging for all 146 SS patients imaged at St. Jude Children's Research Hospital since 1993. Standard MRI criteria were used to identify cystic infarction, leukoencephalopathy, encephalomalacia, or atrophy. Standard MRA criteria were used to identify arterial tortuousity (limited vasculopathy), and stenosis or occlusion (extensive vasculopathy). At an average age of 10 years, the estimated prevalence of infarction, ischemic damage, or atrophy in SS patients was 46%, and of vasculopathy was 64%. Only 28% of patients were normal by both modalities, and patients abnormal by MRA often were abnormal by MRI (p < 0.00001). Patients with cystic infarction had limited vasculopathy, whereas patients with encephalomalacia had stenosis or occlusion (p < 0.0001). Large arteries were affected in 31% of brain injury patients, whereas small arteries are inferred to be abnormal in up to 69% of patients with brain injury. The degree of vasculopathy is closely related to the degree of brain injury, implying that vasculopathy is prodromal to most forms of brain injury in hemoglobin SS.     

Focal monophasic demyelinating leukoencephalopathy in advanced HIV infection

A multiple sclerosis (MS)-like illness has been reported in human immunodeficiency virus (HIV)-infected patients, usually in the early stages of HIV infection. We report 3 patients with advanced HIV infection (CD4 lymphocyte count under 200/mm(3)) presenting with monophasic focal leukoencephalopathy, in whom biopsy demonstrated demyelinating lesions compatible with acute MS lesions. In 1 patient, recently started on highly active antiretroviral therapy, MS-like disease could represent an immune reconstitution syndrome. The lesions were reversible in 2 patients, but rapidly fatal in the third patient. These cases show that an MS-like disease may present in advanced HIV infection as focal monophasic leukoencephalopathy with either a reversible or fulminating course, mimicking progressive multifocal leukoencephalopathy.     

Megalencephalic leukoencephalopathy with subcortical cysts

Megalencephalic leukoencephalopathy with subcortical cysts is one of the newly described white-matter disorders for which recognition has been brought about by advances in imaging technology. The essential diagnostic features include megalencephaly noted in infancy, motor disability in the form of spasticity, ataxia, occasional seizures, mild cognitive decline, and slow progression. Magnetic resonance imaging (MRI) shows bilateral extensive white-matter changes with cysts in the temporal regions. Based on the clinical and MRI features, megalencephalic leukoencephalopathy with subcortical cysts can be distinguished from other conditions (ie, Alexander's disease, Canavan's disease, glutaricaciduria type I) that present in infancy with megalencephaly. Megalencephalic leukoencephalopathy with subcortical cysts is an autosomal recessive disorder, and mutations in the MLC1 gene have now been shown to cause this condition. Several genotypic and phenotypic variations have been described. In India, megalencephalic leukoencephalopathy with subcortical cysts occurs predominantly in the Agarwal community. A common mutation in the MLC1 gene has been seen in 31 Agarwal patients, which suggests a founder effect.     

Molecular mechanisms of cerebral vasospasm following aneurysmal SAH

Cerebral vasospasm following aneurysmal vasospasm has been the subject of intensive research. However the underlying pathophysiological mechanisms remain obscure. This article should summarize the present state concerning smooth muscle contraction, endothelial dysfunction, inflammatory changes, gene expression, in the genesis of vasospasm following aneurysmal subarachnoid hemorrhage.     

Delayed cerebral ischemia and spreading depolarization in absence of angiographic vasospasm after subarachnoid hemorrhage

It has been hypothesized that vasospasm is the prime mechanism of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Recently, it was found that clusters of spreading depolarizations (SDs) are associated with DCI. Surgical placement of nicardipine prolonged-release implants (NPRIs) was shown to strongly attenuate vasospasm. In the present study, we tested whether SDs and DCI are abolished when vasospasm is reduced or abolished by NPRIs. After aneurysm clipping, 10 NPRIs were placed next to the proximal intracranial vessels. The SDs were recorded using a subdural electrode strip. Proximal vasospasm was assessed by digital subtraction angiography (DSA). 534 SDs were recorded in 10 of 13 patients (77%). Digital subtraction angiography revealed no vasospasm in 8 of 13 patients (62%) and only mild or moderate vasospasm in the remaining. Five patients developed DCI associated with clusters of SD despite the absence of angiographic vasospasm in three of those patients. The number of SDs correlated significantly with the development of DCI. This may explain why reduction of angiographic vasospasm alone has not been sufficient to improve outcome in some clinical studies.     

Alanyl-tRNA Synthetase 2 ( AARS2 )-Related Ataxia Without Leukoencephalopathy

Mutations in the mitochondrial alanyl-tRNA synthetase gene, AARS2, have been reported to cause leukoencephalopathy associated with early ovarian failure, a clinical presentation described as “ovarioleukodystrophy.” We present a sibling pair: one with cerebellar ataxia and one with vision loss and cognitive impairment in addition to ataxia. Neither shows evidence of leukoencephalopathy on MRI imaging. Exome sequencing revealed that both siblings are compound heterozygous for AARS2 variants (p.Phe131del and p.Ile328Met). Yeast complementation assays indicate that p.Phe131del AARS2 dramatically impairs gene function and that p.Ile328Met AARS2 is a hypomorphic allele. This work expands the phenotypic spectrum of AARS2-associated disease to include ataxia without leukoencephalopathy.     

Folate-induced reversal of leukoencephalopathy and intellectual decline in methylene-tetrahydrofolate reductase deficiency: variable response in siblings

Homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency may present with variable neurological manifestations. Radiological features include white matter changes (leukoencephalopathy). Clinical, biochemical, and radiological response to treatment may again be variable. Here we present a 12-year follow-up of two siblings on the same treatment regimen, with contrasting long-term findings. The first patient, a female presenting at 15 years, showed a good clinical response, substantial intellectual gain, and complete reversal of leukoencephalopathy. Her brother presented at 13 years 9 months and showed limited clinical and cognitive improvement with persistence of the leukoencephalopathy. Both siblings showed a partial biochemical response to treatment.     

Cerebral vasospasm and ruptured intracranial aneurysm.

The literature concerning cerebral vasospasm associated with subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysm contains no definitive study of patients to determine whether there is (1) any clinical picture consistently present coincident with known cerebral vasospasm, (2) any relationship between mortality and known vasospasm, and (3) any relationship between serious brain damage (morbidity) and known vasospasm. To answer these important questions, experience with 198 consecutive acute SAH patients (every patient had a cerebral angiogram demonstrating one or more intracranial aneurysms) was studied. The experience with these 198 consecutive patients led to the conclusions that (1) there is no clinical picture consistently present coincident with known cerebral vasospasm; (2) cerebral vasospasm has no effect on the mortality from SAH due to ruptured aneurysm; and (3) there is no relationship between the frequency and severity of the complications from surgical or conservative treatment and the presence or absence of vasospasm.     

The vasorelaxant effect of dipyrone on an experimental cerebral vasospasm model in rabbits

Cerebral vasospasm is an important clinical phenomenon associated with a high mortality rate and therefore any promising findings in the laboratory deserve assessment in clinical practice. Dipyrone (Metamizol) has been in clinical use for its non-narcotic analgesic effect since 1922. In addition to its analgesic effect, dipyrone has been shown to possess spasmolitic activity in various smooth muscle organs. In our recent study, it was shown that dipyrone also has a relaxing effect in vascular smooth muscle preparations and that the smooth muscle relaxing effect on the rabbit thoracic aorta was produced by one of dipyrone's spontaneous degradation products. The present study was designed to examine the possible effects of dipyrone on the rabbit basilar artery in a model of cerebral vasospasm. Dipyrone was shown to have a clear spasmolitic effect in the rabbit basilar artery vasospasm produced by an intracisternal injection of autologous blood. This effect was apparent with either local or intravenous administration of dipyrone. These data suggest that dipyrone is potentially useful in the treatment of patients suffering from cerebral vasospasm in combination with other agents or alone.     

Cerebrospinal fluid membrane-bound tissue factor and myelin basic protein in the course of vasospasm after subarachnoid hemorrhage.

No marker that predicts accurately the time of occurrence of cerebral vasospasm due to subarachnoid hemorrhage (SAH) has been reported. In the present study, membrane-bound tissue factor (mTF) and myelin basic protein (MBP) concentrations in cerebrospinal fluid (CSF) were evaluated as a predictor of the time of occurrence of cerebral vasospasm. The mTF and MBP concentrations were measured in the CSF from 28 patients with SAH due to ruptured aneurysm. Serial assays were performed from day 4 to day 14 after SAH. CSF mTF and MBP concentrations from days 5 to 9 correlated with the volume of cerebral infarction due to vasospasm and outcome three months after SAH. From the serial assays, CSF mTF measurements predicted the time of occurrence and severity and irreversibility of symptoms due to vasospasm. In conclusion, CSF mTF is predictive of the occurrence and the recovery of cerebral vasospasm, while CSF MBP is only an indicator of severity of brain damage due to vasospasm.