Brainstem Cavernous Malformations Management: Microsurgery vs. Radiosurgery, a Meta-Analysis

Given the rareness of available data, we performed a systematic review and meta-analysis on therapeutic strategy microsurgical resection and stereotactic radiosurgery (SRS) for brainstem cavernous malformations (BSCMs) and assessed mortality, permanent neurological deficits (PNDs), rebleeding rate, and patients who require reintervention to elucidate the benefits of each treatment modality. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) were used for protocol development and manuscript preparation. After applying all inclusion and exclusion criteria, six remaining articles were included in the final manuscript pool. In total, this meta-analysis included 396 patients, among them 168 patients underwent microsurgical treatment and 228 underwent SRS. Findings of the present meta-analysis suggest that regarding the total group of patients, in terms of mortality, late rebleeding rate, and PNDs, there was no superiority of the one method over the other. Applying the leave-one-out method to our study suggests that with low robust of the results for the bleeding rate and patients who require reintervention outcome factor, there was no statistical difference among the surgical and SRS treatment. Microsurgical treatment of BSCMs immediately eliminates the risk of rehemorrhage; however, it requires complete excision of the lesion and it is associated with a similar rate of PNDs compared with SRS management. Apparently, SRS of BSCMs causes a marked reduction in the risk of rebleeding 2 years after treatment, but when compared with the surgical treatment, there was not any remarkable difference.

Blood-Spinal Cord Barrier: Its Role in Spinal Disorders and Emerging Therapeutic Strategies

The blood-spinal cord barrier (BSCB) has been long thought of as a functional equivalent to the blood-brain barrier (BBB), restricting blood flow into the spinal cord. The spinal cord is supported by various disc tissues that provide agility and has different local immune responses compared to the brain. Though physiologically, structural components of the BSCB and BBB share many similarities, the clinical landscape significantly differs. Thus, it is crucial to understand the composition of BSCB and also to establish the cause–effect relationship with aberrations and spinal cord dysfunctions. Here, we provide a descriptive analysis of the anatomy, current techniques to assess the impairment of BSCB, associated risk factors and impact of spinal disorders such as spinal cord injury (SCI), amyotrophic lateral sclerosis (ALS), peripheral nerve injury (PNI), ischemia reperfusion injury (IRI), degenerative cervical myelopathy (DCM), multiple sclerosis (MS), spinal cavernous malformations (SCM) and cancer on BSCB dysfunction. Along with diagnostic and mechanistic analyses, we also provide an up-to-date account of available therapeutic options for BSCB repair. We emphasize the need to address BSCB as an individual entity and direct future research towards it.

Genetic Genealogy Uncovers a Founder Deletion Mutation in the Cerebral Cavernous Malformations 2 Gene

Cerebral cavernous malformations (CCM) are vascular malformations consisting of collections of enlarged capillaries occurring in the brain or spinal cord. These vascular malformations can occur sporadically or susceptibility to develop these can be inherited as an autosomal dominant trait due to mutation in one of three genes. Over a decade ago, we described a 77.6 Kb germline deletion spanning exons 2-10 in the CCM2 gene found in multiple affected individuals from seemingly unrelated families. Segregation analysis using linked, microsatellite markers indicated that this deletion may have arisen at least twice independently. In the ensuing decades, many more CCM patients have been identified with this deletion. In this present study we examined 27 reportedly unrelated affected individuals with this deletion. To investigate the origin of the deletion at base pair level resolution, we sequenced approximately 10 Kb upstream and downstream from the recombination junction on the deleted allele. All patients showed the identical SNP haplotype across this combined 20 Kb interval. In parallel, genealogical records have traced 11 of these individuals to five separate pedigrees dating as far back as the 1600-1700’s. These haplotype and genealogical data suggest that these families and the remaining “unrelated” samples converge on a common ancestor due to a founder mutation occurring centuries ago on the North American continent. We also note that another gene, NACAD, is included in this deletion. Although patient self-reporting does not indicate an apparent phenotypic consequence for heterozygous deletion of NACAD, further investigation is warranted for these patients.

Large cavernous malformations in infant

Cavernous malformations are rare vascular malformations in the central nervous system. We present the case of a 2-month-old female patient who presented tonic-clonic seizures, with no previous history of seizures. Magnetic resonance imaging showed a 5.6 cm tumor in the left parieto-occipital region. The radiological aspect of the tumor initially suggested an anaplastic meningioma. After surgical treatment and anatomopathological analysis, it was found to be a cavernous malformation. Cavernous malformations, or cavernomas, are rare lesions and even more rare is the occurrence of large cavernomas. In the pediatric population, although still quite rare, they usually are presented as larger cavernomas. Surgical resection is considered the most effective treatment.

Displacement of Gray Matter and Incidence of Seizures in Patients with Cerebral Cavernous Malformations

Seizures are the most common presentation in patients with cerebral cavernous malformations (CCMs). Based on the hypothesis that the volume or proportion of gray matter (GM) displaced by CCMs is associated with the risk of seizure, we developed an algorithm by which to quantify the volume and proportion of displaced GM and the risk of seizure. Image analysis was conducted on 111 patients with solitary CCMs (divided into seizure and nonseizure groups) from our gamma knife radiosurgery (GKRS) database from February 2005 and March 2020. The CCM algorithm proved effective in quantifying the GM and CCM using T1WI MRI images. In the seizure group, 11 of the 12 patients exhibited seizures at the initial presentation, and all CCMs in the seizure group were supratentorial. The location of the limbic lobe within the CCM was significantly associated with the risk of seizure (OR = 19.6, p = 0.02). The risk of seizure increased when the proportion of GM displaced by the CCM exceeded 31%. It was also strongly correlated with the volume of displaced GM. The volume and proportion of displaced GM were both positively correlated with the risk of seizure presentation/development and thus could be used to guide seizure prophylaxis in CCM patients.