CNS demyelination associated with immune dysregulation and a novel CTLA-4 variant.

BACKGROUND: The cytotoxic T-lymphocyte antigen-4 (CTLA-4) pathway acts as a negative immune regulator of T-cell activation and promotes self-tolerance. CASE: We report the first case of biopsy-proven central nervous system inflammatory demyelination in the context of primary immunodeficiency and a novel CTLA-4 variant. CONCLUSION: This case has significant implications for the development of novel treatments for autoimmune conditions including multiple sclerosis and further emphasises the need for caution with clinical use of CTLA-4 immune checkpoint inhibitors in those with a history of inflammatory demyelination.

Internal Carotid Artery Test Balloon Occlusion Using Single Photon Emission Computed Tomography Scan in the Management of Complex Cerebral Aneurysms and Skull Base Tumors: A 20-Year Review.

BACKGROUND: Test balloon occlusion (TBO) is important in the management of complex cerebrovascular and skull base lesions when permanent occlusion (PO) of a parent artery may be indicated. Several adjuncts may be used to increase the sensitivity of TBO to predict whether PO will be tolerated. This is an observational study to evaluate the utility of internal carotid artery (ICA) TBO using single photon emission computed tomography (SPECT) scan in the management of complex vascular pathology and skull base tumors. METHODS: All TBO procedures performed over a 20-year period were analyzed. Clinical assessment and angiographic collateral flow were combined with semi-quantitative cerebral blood flow analysis using 99mTc hexamethylpropylene-amine oxime SPECT scan during ICA TBO. Evaluation of collateral circulation after TBO, and the complications of TBO and the safety of PO after successful TBO were evaluated. RESULTS: Eighty-three patients underwent TBO without complication. Of 45 patients with satisfactory TBO, 28 proceeded to PO. Three patients developed transient ischemic symptoms thought to be embolic in origin. Thirty-eight patients had unsatisfactory TBO, of whom 15 required PO accompanied by a bypass procedure. Forty patients in the series did not undergo permanent vessel occlusion. CONCLUSIONS: SPECT scan-enhanced TBO is an important component of the management of complex vascular pathology and skull base tumors, permitting safe PO of the parent vessel and definitive treatment of the main pathology.

The negative predictive value of CT angiography in the setting of perimesencephalic subarachnoid hemorrhage.

BACKGROUND: Perimesencephalic subarachnoid hemorrhage (PMSAH) is only rarely associated with a ruptured cerebral aneurysm and CT angiography (CTA) has very good sensitivity and specificity for aneurysm detection. The necessity for invasive imaging with digital subtraction angiography (DSA) is therefore debatable. We chose to assess the negative predictive value (NPV) of CTA in a series of patients with PMSAH treated at our institution over a 9-year period. METHODS: We retrospectively assessed the diagnostic yield of DSA after initial negative CTA in patients with a PMSAH pattern defined as blood centered anterior to the midbrain and/or pons within the pre-pontine or interpeduncular cistern with possible quadrigeminal or ambient cistern extension; possible extension into the basal parts of the sylvian fissures but not the lateral sylvian fissures; possible extension to the cisterna magna but not centered on the cisterna magna; and possible extension into the fourth ventricle and occipital horns of the lateral ventricles. RESULTS: Using this definition of PMSAH, of 72 patients, one patient showed a potentially significant finding on DSA that was not demonstrated on initial CTA (NPV 98.61% (95% CI 92.47% to 99.77%)). However, when cisterna magna extension was excluded from the definition of PMSAH, no false negative CTAs in 56 patients were encountered (NPV 100% (95% CI 93.56% to 100.00%)). CONCLUSIONS: The NPV of normal CTA for an arterial abnormality in patients with PMSAH is high and our results therefore question the role of invasive imaging. The findings also suggest that a prospective study designed to clarify the necessity of performing DSA in this population would be feasible.

Tumefactive demyelination presenting during bevacizumab treatment.

We report the emergence of tumefactive demyelination during treatment with intravitreal bevacizumab (Avastin). This is of particular significance given that bevacizumab is currently being assessed as a potential treatment option for neuromyelitis optica, another demyelinating condition.

Is long-term follow-up of adequately coil-occluded ruptured cerebral aneurysms always necessary? A single-center study of recurrences after endovascular treatment.

PURPOSE: Aneurysm recurrence following coil occlusion is well recognized. However, there is controversy as to how long these patients should be followed up after coiling to detect reopening. We aimed to identify the rate of late reopening and the risk factors for reopening in a large single-center cohort of ruptured aneurysms that appeared adequately occluded at 6 months. We also aimed to assess whether rates of recurrence have altered over time with improving coil and angiographic technology. METHODS: Patients treated between 1996 and 2010 were assessed and those with both 6-month initial and subsequent long-term follow-up with either digital subtraction angiography or magnetic resonance angiography were included. Aneurysms were stratified by features such as size, neck width, anatomical location and time of treatment: 1996-2005 (cohort 1) and 2006-2010 (cohort 2). ORs for risk of recurrence were calculated for aneurysm features and rates of recurrence in each cohort were compared using a χ(2) test. RESULTS: 437 patients with 458 adequately occluded aneurysms at 6 months had mean long-term follow-up of 31 months; 57 (12.4%) were large (≥ 10 mm) and 104 (22.7%) were wide-necked (>4 mm). Nine aneurysms (2%) showed significant late anatomical deterioration whereby retreatment was considered or undertaken. The risk was greater for large aneurysms (≥ 10 mm) (OR 15.61, 95% CI 3.79 to 64.33, p=0.0001) or wide-necked aneurysms (>4 mm) (OR 12.70, 95% CI 2.60 to 62.13, p=0.0017). The frequency of significant late anatomical deterioration and retreatment was also less common in those treated in cohort 2 (p<0.05). No completely occluded aneurysm at 6 months demonstrated significant late recurrence. CONCLUSIONS: Most aneurysms adequately occluded at 6 months did not show evidence of late recurrence. Large and wide-neck aneurysms are, however, at greater risk of later recurrence.

Trigeminal neuralgia caused by microarteriovenous malformations of the trigeminal nerve root entry zone: symptomatic relief following complete excision of the lesion with nerve root preservation.

OBJECT: Within a series of 341 consecutive patients who underwent posterior fossa surgery for trigeminal neuralgia (TN), in five the cause was found to be a microarteriovenous malformation (micro-AVM) located in the region of the trigeminal nerve root entry zone (REZ). The surgical management and clinical outcomes of these cases are presented. METHODS: Patients were identified from a prospectively collected database of all cases of TN treated at one institution between 1980 and 2000. Presentation was clinically indistinguishable from TN caused by vascular compression. Preoperative imaging, including computerized tomography scanning (two cases) and magnetic resonance (MR) imaging and MR angiography (three cases), failed to demonstrate an AVM except for one case in which multiple abnormal vessels were identified in the trigeminal REZ on an MR image obtained using a 1.5-tesla magnet. All patients underwent a standard retromastoid craniotomy. In all cases a small AVM embedded in the trigeminal REZ was identified and completely excised, with preservation of the trigeminal nerve. All patients experienced immediate relief of pain following surgery. Postoperatively, in one patient a small pontine hematoma developed, resulting in permanent trigeminal nerve anesthesia in the V2 and V3 divisions. All patients were free from pain at a mean follow-up period of 30 months. CONCLUSIONS: These rare lesions are usually angiographically occult, but may sometimes be identifiable on high-resolution MR images. Total microsurgical resection with nerve preservation is possible, although operative complications are relatively common, reflecting the intimate association between these lesions and the pons. Complete resection is advised not only for symptom relief, but also to eliminate the theoretical risk of pontine hemorrhage.

Thrombus length estimation in acute ischemic stroke: a potential role for delayed contrast enhanced CT.

PURPOSE: Thrombus length has been shown to be an important determinant of recanalization using intravenous thrombolysis in hyperacute ischemic stroke. Various studies have attempted to quantify thrombus based on non-contrast CT (NCCT) or CT angiography (CTA). However, thrombus may not be seen on NCCT, and CTA may fail to delineate the distal extent of the thrombus. Contrast enhanced CT (CECT) following CTA can be used to estimate infarct core, but we investigated whether the angiographic data available on these images provided reliable information on thrombus length. MATERIALS AND METHODS: 15 consecutive patients, mean age 81 years (range 63-93), with terminal internal carotid artery or M1-middle cerebral artery occlusions underwent NCCT, CTA (bolus tracked technique), and CECT (acquired 80 s post initial CTA injection). Three radiologists assessed thrombus length on thin slice NCCT, and CTA and CECT. RESULTS: CTA overestimated thrombus length relative to NCCT (p<0.001) and CECT (p<0.001). There was less difference between CTA and CECT estimation in patients with good collateral scores (p<0.05). There was good correlation between NCCT and CECT (Pearson's correlation coefficient=0.90, 95% CI 0.81 to 0.95, p<0.001). Inter-rater reliability assessed using intraclass correlation was 0.95 (95% CI 0.87 to 0.98) for NCCT and 0.98 (95% CI 0.94 to 0.99) for CECT. CONCLUSIONS: CTA regularly overestimates thrombus length as the distal end of the thrombus is not delineated. This can be overcome through the use of a CECT acquisition which can reliably be used to estimate thrombus length.

Endovascular therapy in hyperacute ischaemic stroke: history and current status.

This is a literature review on to the use of endovascular therapy in hyperacute ischaemic stroke secondary to large vessel occlusion (LVO). The prognosis for LVO is generally poor and the efficacy of intravenous tissue plasminogen activator (IV TPA) in the treatment of this subtype of stroke is questionable. It is well documented that recanalisation is associated with improved outcomes but IV TPA has limited efficacy in LVO recanalisation and the complication rates are higher for IV TPA in this stroke subset. Improved recanalisation rates have been demonstrated with intra-arterial TPA and first and second generation mechanical techniques but the rate of favourable outcome has not overtly mirrored this improvement. Several controversial trials using these early techniques have recently been published but fail to reflect modern practice which centres on the use of stent-retriever technology. This has been proven to be superior to older techniques. Not only are recanalisation rates higher, but the speed of recanalisation is greater and clinical results are improved. Multiple observational studies demonstrate consistently high rates of LVO recanalisation; TICI 2b/3 in the order of 65-95% and, rates of favourable outcome (mRS 0-2) in the order of 55% (42.5-77%) in clinically moderate to severe stroke with complicating symptomatic haemorrhage in the order of 1.5-15%. A major factor determining outcome is time to treatment but success has been demonstrated using these devices with bridging therapy, after IV TPA failure or as a stand-alone treatment.

Endovascular treatment of children with cerebral venous sinus thrombosis: a case series.

BACKGROUND: Cerebral venous sinus thrombosis is a potentially serious condition affecting 0.56 to 0.67 per 100,000 children annually; adverse outcomes are common. The standard of care is anticoagulation with heparin. A proportion of patients, however, remain in a severe clinical condition and in these, endovascular therapy is an alternative treatment. There is little published literature on the use of endovascular treatments in children with cerebral venous sinus thrombosis. METHODS: We retrospectively reviewed case notes and imaging in a consecutive series of nine children treated using endovascular therapy after diagnosis of cerebral venous sinus thrombosis. Clinical presentation, decision to escalate therapy, methods of recanalization, and clinical outcome were assessed. RESULTS: Nine children were treated (age range 18 months to 16 years). Diagnosis was made by computed tomography, computed tomography venography, magnetic resonance imaging, or magnetic resonance venography. Seven children were in a coma; one had signs of raised intracranial pressure with progressive cranial nerve palsies; and one was drowsy with a fluctuating hemiparesis. Eight children had been treated with heparin without improvement. Several endovascular methods were used including local tissue plasminogen activator, microguidewire and catheter disruption, balloon angioplasty, and thromboaspiration using the Penumbra device. Eight children had good functional outcomes. One child died as a result of uncontrolled intracranial hypertension secondary to cerebral venous sinus thrombosis. CONCLUSION: Endovascular therapy may have a role in the treatment of cerebral venous sinus thrombosis in children when medical therapy has failed and the patient is in a poor clinical condition.

A rare cause of neural foraminal widening.

The differential diagnosis for lesions causing neural foraminal widening is vast. The majority are solitary benign peripheral nerve sheath tumours, such as neurofibromas or schwannomas. We present a case of a rare cause of neural foraminal expansion secondary to a posterior thoracic extradural angiolipoma. We describe the presence of chemical shift artefact on post gadolinium T1-weighted imaging as indirect evidence of a fatty component. This potentially important diagnostic sign may raise the suspicion of angiolipoma, especially in an isointense or hypointense dumbbell lesion on T1-weighted imaging, and has not been described previously in this context. Accurate radiological diagnosis of an angiolipoma is important to reduce unexpected haemorrhagic complications from biopsy or resection of the lesion.