Drug-Coated Balloons for Treatment of Internal Carotid Artery Restenosis After Stenting: A Single-Center Mid-Term Outcome Study.

PURPOSE: Endovascular and surgical treatments of stenosis of the extracranial internal carotid artery (ICA) are common procedures, yet both introduce a risk of restenosis due to endothelial hyperplasia. Drug-coated balloons (DCBs) are designed to decrease neointimal hyperplasia, however rarely used in the neurovascular setting. This study retrospectively analyzes mid-term results of DCB-treated in-stent restenosis (ISR) of the ICA. MATERIALS AND METHODS: The medical history, comorbidities, and periprocedural data of patients receiving DCB treatment for > 50% ISR of the ICA after carotid artery stenting were analyzed. Follow-up after DCB treatment was performed with Doppler ultrasound. Suspicious cases were checked with CT- or MR-angiography and-if there was agreement between the modalities-validated with digital subtraction angiography. Potential risk factors for restenosis and differences in outcomes after PTA with three types of DCB balloons were evaluated. RESULTS: DCB treatment was performed in 109 cases, 0.9% of which involved in-hospital major stroke; no minor strokes occurred. A total of 17 patients (15.6%) had recurrent ISR after DCB treatment, after a mean time of 30.2 months (7-85 months). Tobacco use was significantly associated with a higher incidence of recurrent ISR. CONCLUSION: DCB angioplasty for ISR is an effective treatment that may delay and decrease restenosis. Treating comorbidities and adopting lifestyle changes may additionally help prevent ISR.

Cystatin C based estimation of chronic kidney disease and amyotrophic lateral sclerosis in the ALS registry Swabia: associated risk and prognostic value.

Kidney function as part of metabolic changes could be associated with amyotrophic lateral-sclerosis (ALS). We investigated the associations between estimated chronic kidney disease (CKD), based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation, and the risk at onset and prognostic value of CKD for ALS. Between October 2010 and June 2014, 362 ALS cases (59.4% men, mean age 65.7 years) and 681 controls (59.5% men, means age 66.3 years) were included in a population-based case-control study based on the ALS registry Swabia in Southern Germany. All ALS cases were followed-up (median 89.7 months), 317 died. Serum samples were measured for cystatin C to estimate the glomerular filtration rate (eGFR) according to the CKD-EPI equation. Information on covariates were assessed by an interview-based standardized questionnaire. Conditional logistic regression models were applied to calculate odds ratios (OR) for risk of ALS associated with eGFR/CKD stages. Time-to-death associated with renal parameters at baseline was assessed in ALS cases only. ALS cases were characterized by lower body mass index, slightly lower smoking prevalence, more intense occupational work and lower education than controls. Median serum cystatin-C based eGFR concentrations were lower in ALS cases than in controls (54.0 vs. 59.5 mL/min pro 1.73 m2). The prevalence of CKD stage ≥ 3 was slightly higher in ALS cases than in controls (14.1 vs. 11.0%). In the adjusted models, CKD stage 2 (OR 1.82, 95% CI 1.32, 2.52) and stage 3 (OR 2.34, 95% CI 1.38, 3.96) were associated with increased ALS risk. In this cohort of ALS cases, eGFR and CKD stage ≥ 3 (HR 0.94; 95% CI 0.64, 1.38) were not associated with prognosis. In this case-control study, higher CKD stages were associated with increased ALS risk, while in the prospective cohort of ALS cases, no indication of an association of CysC-based CKD on mortality was seen. In addition, our work strengthens the importance to evaluate renal function using a marker independent of muscle mass in ALS patients.

Use of the pCONus HPC as an adjunct to coil occlusion of acutely ruptured aneurysms: early clinical experience using single antiplatelet therapy.

BACKGROUND: Coil occlusion has become the standard treatment for many ruptured aneurysms. However, specific aneurysm structures pose technical difficulties and may require the use of adjunctive neck-bridging devices, which necessitate the use of dual antiplatelet therapy. The hydrophilic polymer coating (pHPC, phenox) is a surface modification that inhibits platelet adhesion. OBJECTIVE: To present initial experience with the pCONUS HPC device as an adjunct to coil embolization for ruptured aneurysms using single antiplatelet therapy (SAPT). METHODS: All patients who were treated with the pCONUS HPC for ruptured aneurysms using SAPT were retrospectively identified. The occurrence of thromboembolic and hemorrhagic complications was recorded together with the angiographic and clinical follow-up details. RESULTS: Fifteen patients were identified (nine female) with a median age of 54 years (range 27-81). Six aneurysms were located at the anterior communicating artery, five at the middle cerebral artery bifurcation, two at the basilar artery bifurcation, one at the posterior communicating artery, and one involving the intradural internal carotid artery. Ten patients (66.6%) achieved modified Raymond-Roy classification I or II at post-treatment angiography, with 45.5% of patients having adequate occlusion (defined as complete occlusion or neck remnant) at follow-up. All patients received acetylsalicylic acid (ASA) as SAPT before and after the procedure. Intraprocedural thrombus formation was seen in three patients (20%), resolving in two patients after a bolus dose of eptifibatide, and one treated with mechanical aspiration. No clinical or radiological consequences were seen. There were no recurrent aneurysm ruptures. One patient died owing to cerebral vasospasm. CONCLUSION: This initial clinical experience highlights the possibility and limitations of using the pCONUS HPC device in the treatment of complex ruptured aneurysm with ASA as SAPT. Randomized trials with longer follow-up in larger cohorts are underway.

The value of whole lesion ADC histogram profiling to differentiate between morphologically indistinguishable ring enhancing lesions-comparison of glioblastomas and brain abscesses.

BACKGROUND: Morphologically similar appearing ring enhancing lesions in the brain parenchyma can be caused by a number of distinct pathologies, however, they consistently represent life-threatening conditions. The two most frequently encountered diseases manifesting as such are glioblastoma multiforme (GBM) and brain abscess (BA), each requiring disparate therapeutical approaches. As a result of their morphological resemblance, essential treatment might be significantly delayed or even ommited, in case results of conventional imaging remain inconclusive. Therefore, our study aimed to investigate, whether ADC histogram profiling reliably can distinguish between both entities, thus enhancing the differential diagnostic process and preventing treatment failure in this highly critical context. METHODS: 103 patients (51 BA, 52 GBM) with histopathologically confirmed diagnosis were enrolled. Pretreatment diffusion weighted imaging (DWI) was obtained in a 1.5T system using b values of 0, 500, and 1000 s/mm2. Whole lesion ADC volumes were analyzed using a histogram-based approach. Statistical analysis was performed using SPSS version 23. RESULTS: All investigated parameters were statistically different in comparison of both groups. Most importantly, ADCp10 was able to differentiate reliably between BA and GBM with excellent accuracy (0.948) using a cutpoint value of 70 × 10-5 mm2 × s-1. CONCLUSIONS: ADC whole lesion histogram profiling provides a valuable tool to differentiate between morphologically indistinguishable mass lesions. Among the investigated parameters, the 10th percentile of the ADC volume distinguished best between GBM and BA.

The Medina Embolic Device: early clinical experience from a single center.

OBJECTIVE: To report our initial experience with the Medina Embolic Device (MED) in unruptured intracranial aneurysms either as sole treatment or in conjunction with additional devices. METHODS: 15 consecutive patients (6 women, 9 men) with unruptured aneurysms were treated between September 2015 and April 2016. The aneurysm fundus measured at least 5 mm. We evaluated the angiographic appearances of treated aneurysms at the end of the procedure and at follow-up, the clinical status, complications, and requirement for adjunctive devices. RESULTS: The MED was successfully deployed in all but one case and adjunctive devices were required in 10 cases. Aneurysm locations were middle cerebral artery bifurcation (n=3), internal carotid artery (ICA) bifurcation (n=1), supraclinoid ICA (n=5), posterior communicating artery (n=1), anterior communicating artery (n=2), cavernous ICA (n=2), distal basilar sidewall (n=1), basilar tip (n=1). Three patients had complications although none could be attributed to the MED. Immediate angiographic results were modified Raymond-Roy classification (mRRC) I=1, mRRC II=5, mRRC IIIa=3, mRRC IIIb=5, and one patient showed contrast stasis within the fundus of the aneurysm. Follow-up angiography was available in 11 patients, with four showing complete aneurysm exclusion, six with stable remnants and one patient with an enlarging neck remnant. CONCLUSIONS: The MED represents a major step forward in the treatment of intracranial aneurysms. It can result in rapid exclusion of an aneurysm from the circulation and has a good safety profile. We believe that the true value of the MED will be in combining its use with adjunctive devices such as endoluminal flow diverters that will result in rapid aneurysmal exclusion.

Cysteine-sparing CADASIL mutations in NOTCH3 show proaggregatory properties in vitro.

BACKGROUND AND PURPOSE: Mutations in NOTCH3 cause cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common monogenic cause of stroke and vascular dementia. Misfolding and aggregation of NOTCH3 proteins triggered by cysteine-affecting mutations are considered to be the key disease mechanisms. However, the significance of cysteine-sparing mutations is still debated. METHODS: We studied a family with inherited small vessel disease by standardized medical history, clinical examination, MRI, ultrastructural analysis of skin biopsies, and Sanger sequencing of all NOTCH3 exons. In addition, we performed in vitro characterization of NOTCH3 variants using recombinant protein fragments and a single-particle aggregation assay. RESULTS: We identified a novel cysteine-sparing NOTCH3 mutation (D80G) in 4 family members, which was absent in a healthy sibling. All mutation carriers exhibited a CADASIL typical brain imaging and clinical phenotype, whereas skin biopsy showed inconsistent results. In vitro aggregation behavior of the D80G mutant was similar compared with cysteine-affecting mutations. This was reproduced with cysteine-sparing mutations from previously reported families having a phenotype consistent with CADASIL. CONCLUSIONS: Our findings support the view that cysteine-sparing mutations, such as D80G, might cause CADASIL with a phenotype largely indistinguishable from cysteine mutations. The in vitro aggregation analysis of atypical NOTCH3 mutations offers novel insights into pathomechanisms and might represent a tool for estimating their clinical significance.

Predictors of outcome after mechanical thrombectomy for anterior circulation large vessel occlusion in patients aged ≥80 years.

BACKGROUND: There is uncertainty about the role of endovascular recanalization procedures for the treatment of acute ischemic stroke in patients aged ≥80 years. Therefore, careful patient selection is mandatory. Our aim was to find valid predictors of clinical outcome after mechanical thrombectomy (mTE) based on the sparse information available in the emergency setting. METHODS: We included consecutive patients aged ≥80 years treated by mTE for anterior circulation thromboembolic vessel occlusion in our department between January 2008 and January 2013. Successful recanalization was defined as a thrombolysis in cerebral infarction (TICI) score of 2b or 3. The rates of parenchymal hemorrhage types I (PHI) and II (PHII) according to the ECASS definition and the rate of focal and diffuse subarachnoid hemorrhage (SAH) were reported. A modified Ranking scale (mRS) score of 0-2 at 90 days was defined as a favorable outcome. We evaluated the influence of gender, smoking habits, atrial fibrillation, diabetes, hypertension, hyperlipidemia, coronary artery and peripheral artery disease, National Institutes of Health Stroke Scale (NIHSS) score, Totaled Health Risks in Vascular Events (THRIVE) score, Alberta Stroke Program Early CT Score (ASPECTS), and duration of symptoms on favorable outcome. Significant predictors were then included in a stepwise logistic regression analysis. Odds ratios (OR), 95% confidence intervals (CI), and receiver operating characteristics (ROC) curves were calculated. p < 0.05 was considered statistically significant. RESULTS: In the defined period, we treated 109 patients aged ≥80 years with 116 occluded anterior circulation target vessels. Successful recanalization was achieved in 87.9% of the targets. The rates of PHI, PHII, and focal and diffuse SAH were 6.4, 5.5, 12.8, and 7.3%, with an overlap between PH and SAH. The combined rate of PHII and/or diffuse SAH was 9.2%. Despite good recanalization rates and reasonable rates of hemorrhage, only 19 patients (17.4%) were functionally independent at 90 days. An additional 12 patients (11.0%) suffered from moderate disability (mRS score 3), 26 (23.9%) were severely disabled (mRS score 4-5) and 52 (47.7%) were deceased. NIHSS, ASPECTS, and THRIVE scores significantly predicted a favorable outcome. Stepwise logistic regression identified NIHSS (OR 0.89; 95% CI 0.82-0.96; p = 0.009) and ASPECTS (OR 2.27; 95% CI 1.28-4.02; p = 0.005) as independent predictors. The ROC area was 0.81. CONCLUSION: ASPECTS and NIHSS were independent predictors of a favorable outcome in patients aged ≥80 years after mTE for anterior circulation large vessel occlusion and may support decision making with regard to the treatment modality. Since the chances of gaining functional independence are limited, careful consideration of each individual case is mandatory. Further studies comparing endovascular and standard treatment in octogenarians are warranted.

Intracranial thrombectomy using the Solitaire stent: a historical vignette.

INTRODUCTION: The endovascular treatment of acute ischemic stroke has been revolutionized in the past years by the introduction of new devices for mechanical thrombectomy. Several tools were already available in 2008. The majority allowed the recanalization of acutely occluded intracranial arteries with acceptable levels of safety and efficacy, and with occasional failures. CASE PRESENTATION: On 3 March 2008, a 67-year-old woman was treated 3.5 h after the clinical onset of a right hemispheric stroke due to an embolic middle cerebral artery (MCA) M1 occlusion. The National Institutes of Health Stroke Scale (NIHSS) score prior to treatment was 10. Mechanical thrombectomy with a microbrush yielded a significant amount of thrombotic material without recanalization. Given the urgency of the situation, the uncertain outcome in the case of a persistent occlusion of the right M1 segment and the fact that no other device was available, a Solitaire stent was deployed within the occluded right M1 segment. After several minutes of incubation, the expanded stent was slowly withdrawn under continuous aspiration with instantaneous removal of the entire thrombus and complete recanalization of the right MCA with reperfusion of the whole MCA supply territory. Digital subtraction angiography showed neither peripheral emboli nor vasospasm. The patient made a complete clinical recovery with an NIHSS score of 0 at the 30 day follow-up. CONCLUSION: The Solitaire stent was initially developed for the endovascular treatment of wide necked intracranial aneurysms but has been demonstrated to be safe and efficacious for intracranial thrombectomy. This was the first successful human clinical use of a Solitaire stent for this purpose and the ignition spark for the development of a whole generation of new devices, now called stent retrievers.

Long-term clinical outcome in meige syndrome treated with internal pallidum deep brain stimulation.

Deep brain stimulation of the globus pallidus internus (GPi DBS) is effective in the treatment of primary segmental and generalized dystonia. Although limb, neck, or truncal dystonia are markedly improved, orofacial dystonia is ameliorated to a lesser extent. Nevertheless, several case reports and small cohort studies have described favorable short-term results of GPi DBS in patients with severe Meige syndrome. Here, we extend this preliminary experience by reporting long-term outcome in a multicenter case series, following 12 patients (6 women, 6 men) with Meige syndrome for up to 78 months after bilateral GPi DBS. We retrospectively assessed dystonia severity based on preoperative and postoperative video documentation. Mean age of patients at surgery was 64.5 ± 4.4 years, and mean disease duration 8.3 ± 4.4 years. Dystonia severity as assessed by the Burke-Fahn-Marsden Dystonia Rating Scale showed a mean improvement of 45% at short-term follow-up (4.4 ± 1.5 months; P < 0.001) and of 53% at long-term follow-up (38.8 ± 21.7 months; P < 0.001). Subscores for eyes were improved by 38% (P = 0.004) and 47% (P < 0.001), for mouth by 50% (P < 0.001) and 56% (P < 0.001), and for speech/swallowing by 44% (P = 0.058) and 64% (P = 0.004). Mean improvements were 25% (P = 0.006) and 38% (P < 0.001) on the Blepharospasm Movement Scale and 44% (P < 0.001) and 49% (P < 0.001) on the Abnormal Involuntary Movement Scale. This series, which is the first to demonstrate a long-term follow-up in a large number of patients, shows that GPi DBS is a safe and highly effective therapy for Meige syndrome. The benefit is preserved for up to 6 years.

Outcome after less-invasive decompression of lumbar spinal stenosis: a randomized comparison of unilateral laminotomy, bilateral laminotomy, and laminectomy.

OBJECT: Recently, limited decompression procedures have been proposed in the treatment of lumbar stenosis. The authors undertook a prospective study to compare the safety and outcome of unilateral and bilateral laminotomy with laminectomy. METHODS: One hundred twenty consecutive patients with 207 levels of lumbar stenosis without herniated discs or instability were randomized to three treatment groups (bilateral laminotomy [Group 1], unilateral laminotomy [Group 2], and laminectomy [Group 3]). Perioperative parameters and complications were documented. Symptoms and scores, such as visual analog scale (VAS), Roland-Morris Scale, Short Form-36 (SF-36), and patient satisfaction were assessed preoperatively and at 3, 6, and 12 months after surgery. Adequate decompression was achieved in all patients. The overall complication rate was lowest in patients who had undergone bilateral laminotomy (Group 1). The minimum follow up of 12 months was obtained in 94% of patients. Residual pain was lowest in Group 1 (VAS score 2.3 +/- 2.4 and 4 +/- 1 in Group 3; p < 0.05 and 3.6 +/- 2.7 in Group 2; p < 0.05). The Roland-Morris Scale score improved from 17 +/- 4.3 before surgery to 8.1 +/- 7, 8.5 +/- 7.3, and 10.9 +/- 7.5 (Groups 1-3, respectively; p < 0.001 compared with preoperative) corresponding to a dramatic increase in walking distance. Examination of SF-36 scores demonstrated marked improvement, most pronounced in Group 1. The number of repeated operations did not differ among groups. Patient satisfaction was significantly superior in Group 1, with 3, 27, and 26% of patients unsatisfied (in Groups 1, 2, and 3, respectively; p < 0.01). CONCLUSIONS: Bilateral and unilateral laminotomy allowed adequate and safe decompression of lumbar stenosis, resulted in a highly significant reduction of symptoms and disability, and improved health-related quality of life. Outcome after unilateral laminotomy was comparable with that after laminectomy. In most outcome parameters, bilateral laminotomy was associated with a significant benefit and thus constitutes a promising treatment alternative.

Supratentorial age-related white matter changes predict outcome in cerebellar stroke.

BACKGROUND AND PURPOSE: Little is known about the relevance of age related white matter lesions (WMLs) concerning outcome after first-ever territorial stroke. Based on an index patient, we hypothesized that age and pre-existent WMLs rather than infarct volume and topography determine outcome. PATIENTS AND METHODS: Thirty-four consecutive patients with magnetic resonance diffusion-weighted imaging-proven isolated acute cerebellar infarction were prospectively entered on our stroke data registry. Patients with pre-existent neurological deficits, hemorrhagic, or malignant cerebellar infarction were excluded. Patients were stratified using Rankin and Barthel disability scales into groups: I complete recovery, II moderate, and III significant disability 14 days after stroke onset. RESULTS: Initial neurological and functional scores were similar among all the groups with vertigo, nausea, unsteadiness, and limb ataxia being the most common. Infarct volume, vascular territories, and comorbidity did not predict clinical outcome. In contrast, presence and severity of supratentorial WMLs and age significantly determined outcome by functional tests. CONCLUSIONS: In patients with isolated cerebellar infarction functional outcome correlated with the coexistence of age-related WMLs rather than stroke volume and topography. This reflects the loss of compensatory network integrity as the equivalent of functional incapacity beyond local lesion disturbances.

Propriospinal myoclonus due to cervical disc herniation. Case report.

Propriospinal myoclonus is a rare form of spinal myoclonus. In most cases the cause has remained unclear. Secondary propriospinal myoclonus has been described secondary to various disorders including trauma, tumor, and infection. Thus far, propriospinal myoclonus caused by cervical disc herniation has not been reported. In the present report, the authors describe the case of a 53-year-old man who presented with radicular symptoms of the right C-6 nerve root and myoclonic twitches predominantly affecting the abdominal muscles but spreading to adjacent muscles. The spread was triggered and enforced by certain movements. Magnetic resonance imaging studies revealed a C-6 nerve root compression at the C5-6 level on the right side but no cervical myelopathy. Electromyography studies confirmed the diagnosis of propriospinal myoclonus. After discectomy and cage-augmented fusion via an anterior approach, the myoclonic movement disorder gradually subsided. To the authors' knowledge, this is the first report on successful treatment of propriospinal myoclonus by spinal disc surgery.

Movement disorders after intervertebral disc surgery: coincidence or causal relationship?

It is well known that brain injury or central traumatic lesions may result in the subsequent appearance of movement disorders such as dystonia or tremor. The concept that peripheral lesions to neural structures may be involved in the pathogenesis of movement disorders has been discussed controversely but has gained more widespread acceptance only recently. Here, we report on 6 patients who developed movement disorders after spinal disc surgery. The movement disorders became manifest with a delay of 1 day to 12 months after surgery. Of the six patients, 4 underwent cervical disc surgery, and 2 patients were operated on for lumbar disc herniation; 2 patients presented with paroxysmal kinesigenic segmental dystonia, 1 patient with focal dystonia, 2 with unilateral tremor, and 1 with bilateral tremor. The appearance of the movement disorder was associated with persistent dermatomal or segmental pain. In all patients, the anatomic distribution of the movement disorder was related to the nerve root or spinal segment of the corresponding disc level and the manifestation was in close temporal relation to the surgery. We conclude that spinal disc surgery may be another, thus far neglected, cause for movement disorders. The postoperative pain syndrome in all patients should be considered as an important factor of pathogenesis. Overall, movement disorders associated with disc surgery appear to be rare, yet they may cause significant discomfort to the affected individual.

Clinical and molecular findings in a patient with a novel mutation in the deafness-dystonia peptide (DDP1) gene.

The Mohr-Tranebjaerg syndrome (MTS) is a rare neurodegenerative disorder characterized by early-onset deafness, dystonia and further neurological abnormalities such as cortical blindness, spasticity, dementia and mental retardation. Causative mutations were identified within the deafness-dystonia peptide (DDP1/TIMM8a) gene on the X-chromosome. The DDP1 protein is located in the intermembrane space of human mitochondria. Here, it acts in a complex together with its partner protein Tim13 in a chaperone-like manner to facilitate the import of nuclear-encoded precursor proteins into the mitochondrial inner membrane. Thus, MTS is a novel type of mitochondrial disorder. To obtain more insight into the pathophysiology of this neurodegenerative disorder, we performed for the first time a comprehensive clinical and functional characterization of a patient suffering from MTS. This patient exhibited a typical combination of deafness, dystonia and visual loss. Sequence analysis of the patient's DDP1 gene revealed a G to C transversion at nucleotide position 38 of the first exon. The mutation affects the ATG start codon, thereby changing methionine to isoleucine (M1I), and leads to a complete absence of the DDP1 protein. In addition, the partner protein Tim13 was found to be significantly reduced, suggesting that Tim13 requires the presence of DDP1 for its stabilization. The assessment of mitochondrial functions showed the enzyme activities of the mitochondrial energy-generating systems to be normal in the muscle biopsy. Structural abnormalities or aggregations of mitochondria were absent. Electron microscopy revealed only a mild neurogenic atrophy. Neurophysiological investigations showed cochlear dysfunction and disturbance of visual pathways. PET and MRI studies revealed a multifocal pattern of neurodegeneration with hypometabolic areas predominantly located over the right striatum and parietal cortex and marked atrophy of the occipital lobes. Although the visual loss is caused predominantly by neurodegeneration of the visual cortex, degeneration of the retina and the optic nerve contributes to the visual impairment. The pathological changes in basal ganglia and sensory cortex demonstrate the disintegration of subcortico-cortical circuits and correlate well with the clinical presentation of multifocal dystonia. The data presented here showed that, in contrast to most of the known mitochondrial disorders, MTS appears not to be associated with a functional defect of the energy generation system of the mitochondria. Whereas the specific mitochondrial dysfunction leading to neuronal loss in MTS remains to be clarified, the electrophysiological and neuroimaging findings allowed the multifocal manifestation of neurodegenerative lesions in MTS to be characterized specifically.