Primary angiitis of the central nervous system.

Primary angiitis of the central nervous system (CNS) is an uncommon inflammatory disorder, with highly variable clinical presentation. It needs to be differentiated from several mimickers, such as CNS involvement in systemic vasculitides, connective tissue disorders, infectious disease, and leukodystrophy as well as neoplastic diseases. The diagnosis requires a combination of clinical and laboratory investigations, multimodal imaging, and histopathological examination, which should be available for confirmation. In the present paper, the histopathological features of primary angiitis of the CNS are described and highlighted to help pathologists avoid misdiagnosis of a treatable acquired disease.

Anti-Cyclic Citrullinated Peptide Antibody Index in the Cerebrospinal Fluid for the Diagnosis and Monitoring of Rheumatoid Meningitis.

Rheumatoid meningitis (RM) is a rare but often aggressive neurological complication of rheumatoid arthritis. The diagnosis of RM, besides the clinical, radiological, and laboratory criteria, usually requires a cerebral biopsy. Based on the two cases presented in this paper, we propose a new laboratory marker. Cerebrospinal fluid and serum anti-cyclic citrullinated peptide (CCP) IgG were measured, and the intrathecal synthesis of anti-CCP antibodies (anti-CCP antibody index) was calculated using the hyperbolic function. The anti-CCP antibody index was positive in both cases at first diagnosis and progressively decreased after treatments. Together with clinical and radiological criteria, the calculation of the anti-CCP intrathecal synthesis, more than the simple measurement of serum or cerebrospinal fluid anti-CCP antibody titers, may represent a useful tool for RM diagnosis and, possibly, for treatment response.

Neurovascular Perfusion Study With DynaPBV During Preoperative Balloon Test Occlusion: A Feasibility Study on Aneurysm and Tumor Lesions.

To report feasibility, safety, and technical advantages of flat-detector computed tomography perfusion (FD-CTP) during balloon test occlusion (BTO) angiography studies, 10 patients patients scheduled for BTO were evaluated. Cerebral blood volume maps were extracted from FD-CTP images acquired during the test. The FD-CTP perfusion combined with BTO is feasible and safe in intracranial tumor, and aneurysm cases in which vessel sacrifice should be considered.

Biopsy-proven primary angiitis of the central nervous system mimicking leukodystrophy: A case report and review of the literature.

Primary Angiitis of the Central Nervous System (PACNS) is a rare form of idiopathic CNS vasculitis. Neuroimaging is often abnormal and characterized by multifocal brain lesions, but brain biopsy definitely confirms the diagnosis. We report the rare case of a 45-year-old female presenting with symptoms of intracranial hypertension and leukodystrophy-like neuroimaging findings. A comprehensive diagnostic work-up led to the unexpected diagnosis of a definite PACNS which was successfully treated by immunosuppressive treatment. Although rarely, PACNS can present as diffuse leukoencephalopathy on neuroimaging, and mimic even an inherited leukodystrophy. Therefore, in adults with leukodystrophy-like neuroimaging findings, careful examination of clinical and non-clinical features is mandatory to avoid missing the diagnosis of a treatable acquired disease.

Microduplication of 15q13.3 and Microdeletion of 18q21.32 in a Patient with Moyamoya Syndrome.

Moyamoya angiopathy (MA) is a cerebrovascular disease determining a progressive stenosis of the terminal part of the internal carotid arteries (ICAs) and their proximal branches and the compensatory development of abnormal "moyamoya" vessels. MA occurs as an isolated cerebral angiopathy (so-called moyamoya disease) or in association with various conditions (moyamoya syndromes) including several heritable conditions such as Down syndrome, neurofibromatosis type 1 and other genomic defects. Although the mechanism that links MA to these genetic syndromes is still unclear, it is believed that the involved genes may contribute to the disease susceptibility. Herein, we describe the case of a 43 years old woman with bilateral MA and peculiar facial characteristics, having a 484-kb microduplication of the chromosomal region 15q13.3 and a previously unreported 786 kb microdeletion in 18q21.32. This patient may have a newly-recognized genetic syndrome associated with MA. Although the relationship between these genetic variants and MA is unclear, our report would contribute to widening the genetic scenario of MA, in which not only genic mutation, but also genome unbalances are possible candidate susceptibility factors.

Sacral dural arteriovenous fistulas: a diagnostic and therapeutic challenge - single-centre experience of 13 cases and review of the literature.

BACKGROUND: Sacral dural arteriovenous fistulas (DAVFs) are rare vascular abnormalities of the spine characterised by slowly progressive symptoms that can mimic different myelopathy disorders. OBJECT: To report our single Institution experience with sacral DAVFs. METHODS: We retrospectively reviewed the clinical records of patients admitted from 1 January 2006 to 31 December 2016 with a diagnosis of sacral DAVFs, treated by endovascular embolisation or surgical clipping. Clinical presentation, imaging characteristics, treatment results and follow-up were analysed. RESULTS: We identify 13 patients with sacral DAVFs supplied by lateral sacral arteries. Clinical presentation was characterised by different degrees of motor weakness and sphincter disturbances. In all patients, spinal MRI showed spinal cord hyperintensities with enhancement and prominent perimedullary vessels. Selective internal iliac angiography was mandatory to identify the exact location of the fistula. A complete embolisation was achieved in eight patients performing a single endovascular embolisation and in three patients performing a single surgical disconnection: two patients required combined procedures. Follow-up imaging showed a complete resolution of the spinal cord hyperintensities in 81% of patients and a reduction of the intramedullary enhancement in 91%. Gait improvement was observed in 73% of patients, while remaining stable in 27%. Sphincter disturbances improved in 36% of patients and remained stable in 64%. CONCLUSION: Awareness of sacral location of DAVFs is critical because standard spinal angiography will not identify sacral supplies, unless internal iliac arteries are properly examined. In our experience, the endovascular treatment show results comparable to surgery when the fistula point is correctly disconnected.

The semisitting position: analysis of the risks and surgical outcomes in a contemporary series of 425 adult patients undergoing cranial surgery.

OBJECTIVE The objective of this study was to analyze the incidence of the primary complications related to positioning or surgery and their impact on neurological outcome in a consecutive series of patients undergoing elective surgery in the semisitting position. METHODS The authors prospectively collected and retrospectively analyzed data from adult patients undergoing elective surgery in the semisitting position for a cranial disease. Patients were managed perioperatively according to a standard institutional protocol, a standardized stepwise positioning, and surgical maneuvers to decrease the risk of venous air embolism (VAE) and other complications. Intraoperative and postoperative complications were recorded. Neurointensive care unit (NICU) length of stay (LOS) and hospital LOS were the intermediate endpoints. Neurological outcome was the primary endpoint as determined by the modified Rankin scale (mRS) score at 6 months after surgery. RESULTS Four hundred twenty-five patients were included in the analysis. VAE occurred in 90 cases (21%) and it made no significant statistical difference in NICU LOS, hospital LOS, and neurological outcome. No complication was directly related to the semisitting position, although 46 patients (11%) experienced at least 1 surgery-related complication and NICU LOS and hospital LOS were significantly prolonged in this group. Neurological outcome was significantly worse for patients with complications (p < 0.0001). CONCLUSIONS Even in the presence of intraoperative VAE, the semisitting position was not related to an increased risk of postoperative deficits and can represent a safe additional option for the benefit of specific surgical and patient needs.

Carotid Artery Stenting With Proximal Embolic Protection via a Transradial or Transbrachial Approach: Pushing the Boundaries of the Technique While Maintaining Safety and Efficacy.

PURPOSE: To compare the feasibility and safety of proximal cerebral protection to a distal filter during carotid artery stenting (CAS) via a transbrachial (TB) or transradial (TR) approach. METHODS: Among 856 patients who underwent CAS between January 2007 and July 2015, 214 (25%) patients (mean age 72±8 years; 154 men) had the procedure via a TR (n=154) or TB (n=60) approach with either Mo.MA proximal protection (n=61) or distal filter protection (n=153). The Mo.MA group (mean age 73±7 years; 54 men) had significantly more men and more severe stenosis than the filter group (mean age 71±8 years; 100 men). Stent type and CAS technique were left to operator discretion. Heparin and a dedicated closure device or bivalirudin and manual compression were used in TR and TB accesses, respectively. Technical and procedure success, crossover to femoral artery, 30-day major adverse cardiovascular/cerebrovascular events (MACCE; death, all strokes, and myocardial infarction), vascular complications, and radiation exposure were compared between groups. RESULTS: Crossover to a femoral approach was required in 1/61 (1.6%) Mo.MA patient vs 11/153 (7.1%) filter patients mainly due to technical difficulty in engaging the target vessel. Five Mo.MA patients developed acute intolerance to proximal occlusion; 4 were successfully shifted to filter protection. A TR patient was shifted to filter because the Mo.MA system was too short. CAS was technically successful in the remaining 55 (90%) Mo.MA patients and 142 (93%) filter patients. The MACCE rate was 0% in the Mo.MA patients and 2.8% in the filter group (p=0.18). Radiation exposure was similar between groups. Major vascular complications occurred in 1/61 (1.6%) and in 3/153 (1.96%) patients in the Mo.MA and filter groups (p=0.18), respectively, and were confined to the TB approach in the early part of the learning curve. Chronic radial artery occlusion was detected by Doppler ultrasound in 2/30 (6.6%) Mo.MA patients and in 4/124 (3.2%) filter patients by clinical assessment (p=0.25) at 8.1±7.5-month follow-up. CONCLUSION: CAS with proximal protection via a TR or TB approach is a feasible, safe, and effective technique with a low rate of vascular complications.

The diagnostic challenge of Divry van Bogaert and Sneddon Syndrome: Report of three cases and literature review.

Divry van Bogaert Syndrome (DBS) is a familial juvenile-onset disorder characterized by livedo racemosa, white matter disease, dementia, epilepsy and angiographic finding of "cerebral angiomatosis". A similar syndrome including livedo racemosa and cerebrovascular disease, often associated with anticardiolipin antibodies, has been described as Sneddon Syndrome (SS) highlighting the question whether these two conditions have to be considered different entities or indeed different features of a unique syndrome. Herein, we report the clinical, neuroradiological, histopathological findings and follow up of three cases diagnosed as Divry-van Bogaert Syndrome, including an updated review of literature of both DBS and SS cases. Our findings support the assumption that DBS and SS are different disease entities. DBS is characterized by the typical angiographic feature of angiomatosis, a hereditary trait and a juvenile onset of cognitive impairment and leukoaraiosis, whereas SS has less severe manifestations of cerebrovascular disease associated with livedo racemosa but without the characteristic cerebral angiography. The report of our cases and the literature review underline the necessity of a detailed work-up and the collection of larger series to better clarify the DBS and SS phenotype and course.

Impaired regulation of thalamic pacemaker channels through an imbalance of subunit expression in absence epilepsy.

The role of hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channel isoforms and hyperpolarization-activated cation current (Ih) for seizure-related burst firing in thalamocortical (TC) neurons was investigated in a rat genetic model of absence epilepsy [Wistar Albino Glaxo rats, bred in Rijswijk (WAG/Rij)]. Burst discharges in TC neurons locked to seizure activity in vivo were prolonged during blockade of Ih by Cs+ and ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride). In vitro analyses revealed a hyperpolarizing shift of half-maximal Ih activation (Vh) in WAG/Rij (Vh = -93.2 mV) compared with nonepileptic controls [August x Copenhagen-Irish (ACI) (Vh = -88.0 mV)]. This effect is explained by a shift of the responsiveness of Ih to cAMP toward higher concentrations in TC neurons from WAG/Rij, as revealed by application of 8-bromo-cAMP and the phosphodiesterase inhibitor IBMX. During blockade of adenylyl cyclase activity, Ih activation was similar in the two strains, whereas the difference in cAMP responsiveness persisted, thereby voting against different ambient cAMP levels between strains. Increasing the intracellular cAMP level and shifting Ih activation led to a change from burst to tonic firing mode in WAG/Rij but not in ACI rats. Furthermore, HCN1 expression was significantly increased on mRNA and protein levels, with no changes in HCN2-4 expression. In conclusion, there is an increase in HCN1 expression in the epileptic thalamus, associated with a decrease in cAMP responsiveness of Ih in TC neurons and resulting impairment to control the shift from burst to tonic firing, which, in turn, will prolong burst activity after recruitment of Ih during absence seizures.