Carmelo Lucio Sturiale

Single nucleotide polymorphisms associated with sporadic brain arteriovenous malformations: where do we stand?

Brain arteriovenous malformations are characterized by a tangle of abnormal vessels directly shunting blood from the arterial to venous circulation. They are known to occur either sporadically or in the context of well-defined genetic disorders. Haemorrhage represents the most severe clinical manifestation, whereas other common symptoms include headache, seizures and neurological deficits. Although sporadic forms do not recognize a specific genetic cause, in recent years, it has been hypothesized that genes involved in angiogenesis and inflammation or coding for proteins, such as fibronectins, laminins and integrins, may play a role in the pathophysiology of brain arteriovenous malformations. More recently, a new trend of genetic studies has investigated the association between sporadic arteriovenous malformations and single nucleotide polymorphisms, single base variations between genomes within members of a biological species or between paired chromosomes in an individual, which may determine the susceptibility to develop complex diseases and influence their natural history. Several polymorphisms in two different families of genes have been associated with disease susceptibly and increased haemorrhagic risk. These genes are mainly involved in the inflammatory cascade and in the regulation of angiogenesis. However, most of the investigated polymorphisms have been selected on the basis of candidate genes because of their potential functional role in the pathogenesis of brain arteriovenous malformations or in other cerebrovascular diseases. Only one hypothesis-free genome-wide association study in a small number of patients has been performed so far, but it was unable to identify significant associations between brain arteriovenous malformations and specific genetic loci. In this article, we review and analyse the polymorphisms investigated to date in association with sporadic brain arteriovenous malformations in the medical literature. We discuss the biological, pathophysiological and clinical implications of these studies, with particular attention to the prediction of haemorrhagic risk and the possibility of building genetic profiles capable of defining the architectural features of the malformations and predict their evolution and natural history. We also present a joint analysis of the risk estimates found by the studies in literature that have evaluated the association between single nucleotide polymorphisms and brain arteriovenous malformation susceptibility and risk of bleeding. This analysis shows a statistically significant association between the interleukin 6 -174G>C (odds ratio = 1.97; 95% confidence interval: 1.15-3.38) and the tumour necrosis factor α -238G>A (odds ratio = 2.19; 95% confidence interval: 1.25-3.83) gene polymorphisms and risk of intracranial haemorrhage and between the activin-like kinase 1 (also known as ACVRL1) intervening sequence 3 -35A>G (odds ratio = 2.42; 95% confidence interval: 1.54-3.8) gene polymorphism and disease susceptibility.

Endovascular Treatment of Intracranial Aneurysms in Elderly Patients A Systematic Review and Meta-Analysis

Background and Purpose— Use of endovascular coiling for treatment of ruptured and unruptured intracranial aneurysms (IAs) in the elderly is increasing. We performed a meta-analysis of the literature examining clinical and angiographic outcomes for treatment of IAs in the elderly. Methods— We performed a comprehensive review of the literature from 1995 to 2012, reporting series of patients ≥65 years of age with ruptured or unruptured IAs treated with endovascular approach. Event rates were pooled across studies using random effects meta-analysis. Results— A total of 21 studies reporting on 1511 patients were included. Long-term aneurysm occlusion rates were 79% (95% confidence interval [CI], 70%–85%). Perioperative stroke occurred in 4% (95% CI, 3%–6%), with similar rates between patients with ruptured (5%; 95% CI, 3%–7%) and unruptured aneurysms (4%; 95% CI, 1%–14%; P=0.68). Intraprocedural rupture occurred in 1% (95% CI, 0%–3%) and 4% (95% CI, 2–6%; P=0.04) of patients with unruptured and ruptured aneurysms, respectively. Perioperative mortality rate for patients with ruptured aneurysms was 23% (95% CI, 17%–30%) and 1% (95% CI, 0%–6%) for patients with unruptured aneurysms (P<0.01). Rates of good clinical outcome at 1 year were 93% (95% CI, 88%–96%) and 66% (95% CI, 59%–72%) in patients with unruptured and ruptured aneurysms, respectively. Conclusions— This study suggests that endovascular treatment of IAs in the elderly is associated with high long-term occlusion rates. Given the morbidity and mortality associated with endovascular treatment of IAs in the elderly, careful patient selection, especially in the case of patients with unruptured aneurysm, is recommended.

Unexpected neuropsychological improvement after cranioplasty: a case series study

Objective. Decompressive craniectomy is often emergently performed in an effort to reduce intracranial hypertension. After this urgent intervention, brain-injured patients often start rehabilitation programs but are left with a skull defect. Cranioplasty is often performed in these situations in order to repair this defect, mainly for cosmetic reasons and/or the patients safety. The possible effects of this breach on the patients’ neurological recovery are poorly understood and have been scarcely evaluated until now. The effect of cranioplasty on cognitive and motor functions in severely brain-injured individuals remains controversial. Methods and procedures. In order to further support evidence of the beneficial effects of cranioplasty on motor and cognitive function in severely brain-injured individuals, we discuss four cases, retrospectively selected among a cohort of several patients who underwent decompressive craniectomy after severe brain injury. The selected patients presented a biphasic pattern of recovery of cognitive and motor performance consisting of an initial improvement, followed by a progressive worsening of neurological signs and symptoms, and, ultimately, an unexpected recovery of function following cranioplasty. Main outcomes and results. In all four cases, we found a deterioration of motor and neuropsychological deficits prior to cranioplasty and a subsequent unexpected improvement in performance on a neuropsychological battery and a series of motor function tests immediately after cranioplasty. Conclusions. Results give clear evidence that a subset of patients are negatively affected by the persistence of a breach in skull integrity during the rehabilitation phase of brain injury. Moreover, they show that the repair of the cranial defect can trigger relevant neurological improvement in both motor and cognitive domains. This possibility should serve as a reminder to rehabilitation clinicians to give serious consideration to prompt performance of cranioplasty during the time allotted for the rehabilitation of these patients.

A comment on impaired peri-nidal cerebrovascular reserve in seizure patients with brain arteriovenous malformations

Sir, We read with great interest the article by Fierstra et al . (2011), recently published in your journal. This article reopens the debate regarding the unsolved problem of the origin of seizures in patients with brain arteriovenous malformations, the pathophysiology of which remains poorly understood. Although angiographic studies have shown some associations between different brain arteriovenous malformation angioarchitectural features and epilepsy, they have not elucidated the underlying pathophysiology (Turjman et al ., 1995 a , b ; Hoh et al ., 2002). Similarly, MRI studies have often shown gliosis and chronic ischaemic changes in peri-nidal tissue as well as in remote regions, but any significant correlation has been demonstrated between extent of gliosis and clinical symptoms (Essig et al ., 2000). The main pathophysiological hypotheses to date include: (i) focal cerebral ischaemia attributable to a steal phenomenon as described by Spetzler et al . (1992) and Taylor et al . (2002); (ii) gliosis, demyelination and haemosiderin deposits in peri-nidal tissue; and (iii) secondary epileptogenesis in ipsilateral temporomesial cortex (Yeh et al ., 1990), or at a distant site, attributable to a ‘kindling’ phenomenon, in which epileptic discharges are enhanced by excitatory synaptic connections from brain arteriovenous malformations (Hoh et al ., 2002). Bleeding was deemed responsible for triggering seizure activity by Turjman et al . (1995 a ) and Stein and Wolpert (1980); in contrast, in the study by Hoh et al . (2002), intracranial haemorrhage was not a statistically significant factor associated with epilepsy. Fierstra et al . (2011) studied in vivo the possible haemodynamic effect …

Are parenchymal AVMs congenital lesions

A long-held dogma in neurosurgery is that parenchymal arteriovenous malformations (AVMs) are congenital. However, there is no strong evidence supporting this theory. An increasing number of documented cases of de novo formation of parenchymal AVMs cast doubt on their congenital nature and suggest that indeed the majority of these lesions may form after birth. Further evidence suggesting the postnatal development of parenchymal AVMs comes from the exceedingly rare diagnosis of these lesions in utero despite the widespread availability of high-resolution imaging modalities such as ultrasound and fetal MRI. The exact mechanism of AVM formation has yet to be elucidated, but most likely involves genetic susceptibility and environmental triggering factors. In this review, the authors report 2 cases of de novo AVM formation and analyze the evidence suggesting that they represent an acquired condition.

Stereotaxic biopsy and radioactive implantation for interstitial therapy of tumors of the pineal region

Stereotaxic biopsy was performed in 10 patients with tumors of the pineal region. On the basis of intraoperative tissue diagnosis, low-energy radioactive sources (125I) were implanted in seven patients for interstitial irradiation during the same stereotaxic procedure. Results were good in five cases. This therapeutic modality appears to be indicated in cases of proven low-grade malignancy, inasmuch as the implantation of radioactive sources in a highly malignant lesion carries the risk of severe, often irreversible, damage to the surrounding brain, because of possible seed migration.

Decompressive craniectomy, interhemispheric hygroma and hydrocephalus: A timeline of events?

BACKGROUND Decompressive craniectomy (DC) is a known risk factor for the development of post-traumatic hydrocephalus. The occurrence of subdural hygroma (SH) was also reported in 23-56% of patients after DC and it seemed to precede hydrocephalus in more than 80% of cases. We analyzed the relationship among DC, SH and hydrocephalus. METHODS From 2007 to 2011, 64 patients underwent DC after head trauma. Variables we analyzed were: intaventricular hemorrhage, age, GCS, distance of craniectomy from the midline, evacuation of a hemorrhagic contusion (HC) and infection. Logistic regression was used to assess the independent contribution of the predictive factors to the development of hydrocephalus. RESULTS Nineteen patients (29.7%) developed hydrocephalus. Interhemispheric SH was present in 8/19 patients with hydrocephalus and temporally preceded the occurrence of ventricular enlargement. Moreover, most patients who developed a interhemispheric SH had been undergone DC whose superior margin was close to the midline. Logistic regression analysis showed that craniectomy closer than 25 mm to the midline was the only factor independently associated with the development of hydrocephalus. CONCLUSION Craniectomy close to the midline can predispose patients to the development of hydrocephalus. SH could be generated with the same mechanism, and these three events could be correlated on a timeline.

Angioarchitectural features of brain arteriovenous malformations associated with seizures: a single center retrospective series.

Epileptic seizures account for 24–40% of all clinical onsets in patients with brain arteriovenous malformations (AVMs).

Sewing Needles in the Brain: Infanticide Attempts or Accidental Insertion?

BACKGROUND:Placing of sewing needles in the brain through the anterior fontanelle was first described in Germany in 1914. Forty cases have been reported in the scientific literature; most of them were identified in Turkey and Iran, with only a few cases in the Far East, North and Eastern Europe, and the United States. The only case observed in Italy was recorded in 1987. In nonmedical literature, this practice was frequently described in Persian novels, and it has been thought that this ritual could have been diffused with the Persian Empire domination over the centuries. OBJECTIVE:We report on a new Italian case of an 82-year-old woman admitted for progressive right hemiparesis and gait disturbance. METHODS:Brain computed tomography scan showed a left frontoparietal chronic subdural haematoma and, surprisingly, three 4-cm-long sewing needles inserted through the region of the anterior fontanelle. The patient and her friends and family did not remember any event justifying their presence. RESULTS:Subdural collection was evacuated by craniotomic approach, and the sewing needles were left in place and followed up. CONCLUSION:The rare cases of intracranial needling reported in the literature may represent only the tip of the iceberg. The phenomenon is usually reported as an incidental finding in asymptomatic adults, whereas many babies could not have been diagnosed because they died. The therapy remains controversial, although many authors suggest only follow-up for asymptomatic patients. In this article, all the pertinent literature is reviewed and the most important clinical aspects are discussed, along with a historical assessment of the problem.

Association between the rs1333040 polymorphism on the chromosomal 9p21 locus and sporadic brain arteriovenous malformations.

Background Single nucleotide polymorphisms (SNPs) on chromosome 9p21 have been recently associated with intracranial aneurysms and stroke. In this study, we tested the association between the rs1333040C>T polymorphism on the 9p21 locus and sporadic brain arteriovenous malformations (BAVMs). Methods We studied 78 patients with sporadic BAVMs and 103 unaffected controls. Genomic DNA was isolated from peripheral blood and the rs1333040C>T polymorphism was assessed by PCR–restriction fragment length polymorphism using the BsmI restriction endonuclease. Results We found that the distribution of the three genotypes (TT/TC/CC) of the rs1333040 polymorphism was significantly different between cases and controls (p=0.02). Using dominant, recessive and additive genetic models, we found that the TT genotype and the T allele were significantly more common in the BAVM group than in controls. We also evaluated whether the rs1333040 polymorphism was associated with prototypical angio-architectural features of BAVMs (such as nidus size, venous drainage pattern and Spetzler–Martin grading) and with the occurrence of seizures and bleeding. We detected a significant association between the homozygous T allele in the recessive model and BAVMs with a nidus >4 cm in diameter. Deep venous drainage was significantly more frequent among subjects carrying at least one T allele in the dominant model. Patients with seizures showed a significant association with the TT genotype and the T allele in all genetic models examined whereas those who experienced intracranial bleeding showed a significant association with the T allele in the trend model. Conclusions This is the first study demonstrating an association between an SNP of the 9p21 region and sporadic BAVMs. Our results emphasise the relevance of this chromosomal locus as a common risk factor for various forms of cerebrovascular diseases.