1. Boulenoir N, Turc G, ter Schiphorst A, et al. Should Patients With Acute Minor Ischemic Stroke With Isolated Internal Carotid Artery Occlusion Be Thrombolysed? Stroke. 2022;(November):3304-3312. doi:10.1161/strokeaha.122.039228
Isolated cervical or intracranial internal carotid artery occlusion (iICAo), without associated occlusion of the circle of Willis (ie, without T-shaped, L-shaped, or tandem occlusions), is observed in ≈5% of acute stroke patients admitted in an early time window, with atherosclerosis as the leading cause followed by dissection and cardioembolism. Clinical severity is highly variable, in part as a function of collateral circulation, and patients with iICAo frequently present with minor neurological deficits. Given the lack of evidence derived from randomized controlled trials, the management of acute iICAo remains unclear. The early clinical course of acute iICAo treated or not with reperfusion therapies has been reported in few observational studies, all with small samples, and remains little known. In the 4.5-hour window, international guidelines recommend intravenous thrombolysis (IVT) in the context of disabling ischemic minor stroke in general, whereas an expert consensus from the European Stroke Organization suggests using IVT in nondisabling minor stroke with large vessel occlusion. Regarding iICAo, the authors recently reported a worrying 30% rate of early neurological deterioration (END) occurring within 24 hours following IVT in a multicentric cohort of patients with minor stroke iICAo, which occurred mostly within the first 2 hours from IVT start and was ascribed to artery-to-artery embolism in 3/4th of the cases. These observations led the authors to propose that IVT may foster carotid thrombus fragmentation and subsequent distal embolism and could therefore be deleterious in this situation. However, this study lacked a control group (ie, nonthrombolysed acute minor stroke with iICAo), which limited interpretation. In this paper, the authors tested the above hypothesis by comparing the incidence and mechanisms of early neurological deterioration within 24 hours (END24h), END within 7 days, and 3-month outcome of patients with acute minor stroke iICAo treated with IVT or antithrombotics only.
189 patients were included (IVT=95; antithrombotics=94 [antiplatelets, n=58, anticoagulants, n=36]) from 34 centers.
Four key findings emerged: (1) END was a frequent event in this population— occurring in 1 of 3 patients within the first week, predominantly in case of nonatheromatous cause—and was strongly associated with poor 3-month outcome; (2) END was of thromboembolic origin in two-thirds of the cases; (3) the rate of END within the first 24 hours was 2-fold higher following IVT, driven by higher odds of thromboembolic END; and (4) however, the rate of END occurring within 7 days did not significantly differ between the 2 treatment groups, and 3-month outcome was similar.
The higher END24h incidence following IVT, together with the lack of better 3-month functional outcome as found here, may suggest that the benefit/risk ratio may not favor IVT at least in case of nondisabling symptoms, a situation where the benefit of IVT is unproven. Apart from IVT alone, 3 other therapeutic options may be considered in this population. First, adding early post-IVT antiplatelet administration may be an attractive approach to prevent thromboembolic ENDs. A post hoc analysis of ARTIS, a randomized trial comparing early (within 90 minutes of IVT start) addition of aspirin after IVT versus IVT alone in an unselected acute stroke population, found that aspirin increased the risk of END24h due to intracranial hemorrhage, and had no effect on incidence of nonhemorrhagic END24h. However, this approach could still be of interest in populations at high risk of post-IVT thromboembolic END and low risk of intracranial hemorrhage, such as nonatheromatous iICAo with minor symptoms, and should be further tested, perhaps with later antiplatelet agent administration. Second, in patients with non-IVT–treated iICAo, more intensive antithrombotic strategies than aspirin alone may be of interest. An observational study focusing on patients with non-IVT–treated iICAo admitted within 24 hours from symptom onset suggested that, as compared to standard antiplatelet therapy, anticoagulation was associated with lower END7d rate. More intensive antiplatelet therapies such as dual antiplatelet therapy plus argatroban may reduce END risk, as reported in branch atherosclerosis disease. Last, direct—as opposed to rescue—endovascular therapy may be considered to prevent END. Two case series in acute iICAo suggested that immediate endovascular therapy including angioplasty and stenting may afford high rates of successful recanalization, although appeared to be associated with a substantial rate of intracranial embolism.
4 tables, 2 figures, no imaging
2. Siegler JE, Shu L, Yaghi S, et al. Endovascular Therapy for Cerebral Vein Thrombosis: A Propensity-Matched Analysis of Anticoagulation in the Treatment of Cerebral Venous Thrombosis. Neurosurgery. 2022;91(5):749-755. doi:10.1227/neu.0000000000002098
Definitive treatment of CVT includes recanalization of occluded cerebral vein or dural sinus with anticoagulation for 3 to 6 months. Endovascular treatment (EVT) in the form of thrombectomy is considered in patients for whom anticoagulation may be contraindicated, or symptoms progress despite anticoagulation, and is recommended with a low level of evidence by the American Heart Association (Class IIb, Level of Evidence C). Systematic review and meta-analyses indicate that EVT is reasonable and safe as a salvage treatment for CVT, with similar patient outcomes compared with medically managed patients. However, these data are limited by small patient populations, with the largest cohort comprising 63 patients. Furthermore, the adjunctive benefit of endovascular treatment in CVT was not proven in the TO-ACT multicenter randomized clinical trial. In Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis (TO-ACT), the likelihood of achieving a good functional outcome (modified Rankin Scale [mRS] 0-1) was no different between the endovascular and medically managed arms.
Of the 1025 patients from the original ACTION-CVT cohort, 987 (96%) had complete demographic and treatment data for this analysis and were included.
This analysis of the ACTION-CVT multicenter cohort study represents the largest observational cohort study of patients with CVT who underwent medical or EVT management.
The authors found no difference in excellent functional outcome (mRS 0-1) at 90 days and no difference in secondary clinical or radiographic outcomes with EVT over medical treatment of CVT. In a sensitivity analysis limiting inclusion of patients based on eligibility for the TO-ACT randomized clinical trial, there was no significant difference in the prespecified primary outcome based on treatment. Altogether, their findings provide real-world data supporting the TO-ACT trial results. It is possible that only a subgroup (or subgroups) of patients with CVT may benefit from EVT (eg, refractory intracranial hypertension, progressive venous infarction, or hemorrhage expansion), and this needs to be determined by future randomized clinical trials. Furthermore, among the few patients who underwent successful recanalization with EVT and had available recanalization and long-term follow-up data (n = 11), there was a suggestion of improved outcomes when compared with patients treated using medical management.
2 figures, 2 tables, no imaging
3. Jack MM, Smith BW, Capek S, et al. The spectrum of brachial plexopathy from perineural spread of breast cancer. J Neurosurg. 2022;137(November):1-10. doi:10.3171/2021.12.JNS211882
The differential diagnosis for breast cancer–related upper- extremity neurological issues is vast. The nerves can be damaged directly during surgery (especially with axillary lymph node dissections), compressed by local disease progression/recurrence, chemically damaged in a length dependent fashion from chemotherapy regimens, or injured – typically in a delayed fashion—as a complication of radiation treatments. One less common and thus less often recognized insult to the brachial plexus in patients with breast cancer is perineural spread.
The aim of this study was to describe the clinical, pathological, and radiological findings in the largest series of patients with pathologically verified perineural spread of breast cancer to the brachial plexus. A total of 19 female patients who all presented with evidence of brachial plexopathy, who had pathological evidence of perineural spread of breast cancer on fascicular nerve biopsy, and who were treated at the authors institution between 1999 and 2021 were included in the study.
The patients in this series developed symptoms of brachial plexopathy on average 12 years after their initial diagnosis. This length of time makes a chemotherapy induced neuropathy much less likely. In this time frame, radiation plexopathy and perineural spread are two leading differential diagnoses. However, radiation-induced neuropathy and perineural spread can be difficult to distinguish clinically. Additionally, a long-term complication of breast cancer treatment such as lymphedema could be at play, given that there are many reports of compressive neuropathies in patients with cancer-related lymphedema. To this point, 42% of patients in this series received a carpal tunnel decompression, 11% received a cubital tunnel decompression, and 5% had a cervical decompression. One patient underwent all three types of procedures prior to the diagnosis of perineural spread. However, the true diagnosis remained elusive in all cases. Given its rarity and alternative diagnoses with similar presentations, perineural spread can be difficult to diagnose. This difficulty explains why patients had a mean time course of more than 2 years from the onset of brachial plexus symptoms until the diagnosis of perineural infiltration of the brachial plexus.
Patients with a history of breast cancer presenting with pain, weakness, or numbness should be evaluated for the possibility of perineural spread. In contrast to radiation injury, which is more severe regarding distal function, perineural spread can affect both the proximal and distal musculature in isolation. Imaging characteristics including a sugar-coating pattern on brachial plexus MRI and increased FDG uptake on PET imaging can be used to strengthen a diagnosis. Selective biopsy will help to make a clear diagnosis. Unfortunately, breast cancer with perineural spread is associated with high mortality, with nearly every patient in this cohort dying within 6 years.
5 tables, 3 figures, including MR, PET
4. Whiteley WN, MacRaild A, Wang Y, et al. Clinical Diagnosis and Magnetic Resonance Imaging in Patients With Transient and Minor Neurological Symptoms: A Prospective Cohort Study. Stroke. 2022;(November):3419-3428. doi:10.1161/strokeaha.122.039082
One strategy is to use magnetic resonance imaging (MRI) of the head for every patient with transient or minor neurological symptoms. MRI of the brain may detect diffusion- weighted imaging (DWI) lesions that are typical of acute brain ischemia or (rarely) may make a positive diagnosis of an alternative cause for symptoms such as multiple sclerosis or brain tumor. Where the diagnosis of TIA or stroke is secure, the pattern of ischemia seen on MRI may help to identify the underlying cause, such as multivascular-territory ischemia in cardioembolism.
To measure the benefits of an MRI strategy that scans all patients rather than a clinically targeted strategy, we need an estimate of the proportion of patients with positive DWI at different levels of clinical probability of a diagnosis of a TIA or minor stroke. For example, if the great majority of patients with a high clinical probability of TIA or stroke had DWI changes, or the great majority of patients with a low clinical probability had a negative MRI, then MRI could be targeted at those with intermediate clinical suspicion. However, if clinical probability did not identify a very high or low probability of DWI lesions, then a policy to scan all patients might be preferred.
Of the 272 participants, most had an MRI brain ≤2 days of symptom onset (157, 58%). Participants were mostly male (145, 53%); had a mean age of 60 (SD, 14); had only one episode of neurological symptoms (205, 75%); and had mild or no neurological signs (NIH Stroke Scale, 0: 247, 91%), which had either not resolved at presentation (118, 43%) or had resolved but lasted for ≥1 hour (94, 35%). In most participants, symptoms were monosymptomatic or all began simultaneously (156, 57%). Common non-focal symptoms were tiredness or fatigue (54%), headache (43%), and nausea or sickness. MRI evidence of acute brain ischemia was present in 61 (22%) participants. Of these 61 participants, 16 (26%) had one cortical infarct, 16 (26%) had one subcortical lacunar infarct, 11 (18%) had one cerebellar or brain stem infarct, and 18 (30%) had >1 infarct. The acute infarcts were all thought to be relevant to the participant’s symptoms.
MRI scanning in all patients presenting with transient or minor neurological symptoms is likely to identify some patients who would otherwise not receive a diagnosis of stroke or TIA because they were otherwise thought to be at low risk. However, whether this strategy is cost-effective, or how MRI scanning could best be targeted, is unclear.
4 tables, 2 figures, no imaging
5. Ayrignac X, Carra-Dallière C, Marelli C, Taïeb G, Labauge P. Adult-Onset Genetic Central Nervous System Disorders Masquerading as Acquired Neuroinflammatory Disorders: A Review. JAMA Neurol. 2022;79(10). doi:10.1001/jamaneurol.2022.2141
In this review, the authors provide a comprehensive description of the main genetic neuroinflammatory disorders that may be mistaken as acquired neuroinflammatory diseases and propose a diagnostic strategy to identify patients who may be proposed for targeted gene or next-generation sequencing (panel gene analysis or whole-exome/ whole-genome sequencing) and who may benefit from potential new therapies.
– Genetic leukodystrophies (X-ALD, MLD)
– Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a late-onset autosomal dominant inflammatory microangiopathy caused by TREX1 gene mutations
– Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an inhibitory receptor that is constitutively expressed on regulatory T cells. Its upregulation on effector T cells after activation inhibits their proliferation. Heterozygous germline CTLA4 mutations have been recently described in patients with immune dysregulation and immunodeficiency
-Alexander disease is a very rare leukodystrophy caused by dominantly inherited mutations in the GFAP gene, resulting in astrocyte dysfunction leading to abnormal cytoplasmic inclusions within astrocytes (Rosenthal fibers). Depending on the age at symptom onset, 3 main clinical forms have been identified: neonatal/infantile (birth to 2 years), juvenile (2-14 years), and adult.
CLIPPERS is a recently described neuroinflammatory syndrome of unknown origin. It is typically characterized by symptomatic pontine T2/FLAIR hyperintense lesions with punctate (diameter <3mm) and curvilinear gadolinium-enhancing lesions that are responsive to and require maintenance treatment with steroids to avoid symptom relapse. In addition to pontine and cerebellar gadolinium-enhancing lesions, involvement of juxtacortical areas and spinal cord has been described. The biopsy of these gadolinium-enhancing lesions reveals perivascular and parenchymal CNS infiltrates composed of T cells and macrophages. In the absence of a specific biomarker, according to the diagnostic criteria published in 2017, the definite diagnosis of CLIPPERS can be made when the clinical, radiological, and histological criteria are met, and probable CLIPPERS made in the absence of histological confirmation. Nevertheless, CLIPPERS diagnosis is difficult, and its mimics, including autoimmune gliopathies (ie,myelin oligodendrocyte glycoprotein–associated disorders and autoimmune GFAP astrocytopathy), primary angiitis of the CNS, histiocytosis (Erdheim- Chester disease), and CNS lymphoma, must be excluded by appropriate ancillary tests.
Importantly, one-third of the tested patients with probable or definite CLIPPERS carry mutations in genes implicated in familial HLH (hemophagocytic lymphohistiocytosis).
2 figures, 2 tables, with many MR images
6. Catapano JS, Rumalla K, Srinivasan VM, Lawrence PM, Larson Keil K, Lawton MT. A taxonomy for brainstem cavernous malformations: subtypes of pontine lesions. Part 1: basilar, peritrigeminal, and middle peduncular. J Neurosurg. 2022;136(6):1-15. doi:10.3171/2022.1.JNS212690
The 323 pontine BSCMs were classified into 6 distinct subtypes: basilar (6 [1.9%]), peritrigeminal (53 [16.4%]), middle peduncular (MP) (100 [31.0%]), inferior peduncular (47 [14.6%]), rhomboid (80 [24.8%]), and supraolivary (37 [11.5%]). Part 1 of this 2-part series describes the taxonomic basis for the first 3 of these 6 subtypes of pontine CM. Basilar lesions are in the anteromedial pons and associated with contralateral hemiparesis. Peritrigeminal lesions are in the anterolateral pons and are associated with hemiparesis and sensory changes. Patients with MP lesions presented with mild anterior inferior cerebellar artery syndrome with contralateral hemisensory loss, ipsilateral ataxia, and ipsilateral facial numbness without cranial neuropathies. A single surgical approach and strategy were preferred for each subtype: for basilar lesions, the pterional craniotomy and anterior transpetrous approach was preferred; for peritrigeminal lesions, extended retrosigmoid craniotomy and transcerebellopontine angle approach; and for MP lesions, extended retrosigmoid craniotomy and trans–middle cerebellar peduncle approach. Favorable outcomes were observed in 123 of 143 (86%) patients with follow-up data. There were no significant differences in outcomes between the 3 subtypes or any other subtypes.
9 figures and 1 table with multiple graphics
7. Dmytriw AA, Dibas M, Adeeb N, et al. The Pipeline Embolization Device: a decade of lessons learned in the treatment of posterior circulation aneurysms in a multicenter cohort. J Neurosurg. 2022;137(November):1-8. doi:10.3171/2021.12.JNS212201
This study is a retrospective review of consecutive posterior circulation aneurysms managed with the PED at four academic institutions in the US between January 1, 2011, and January 1, 2021. Factors related to case selection, rates of aneurysm occlusion, or complications were identified and evaluated. Angiographic outcomes as well as thromboembolic and hemorrhagic complications were investigated.
This study included 117 patients (median age 60 years). At a median follow-up of 12 months, adequate occlusion (> 90%) was attained in 73.2% of aneurysms. Aneurysm occlusion rates were similar over the study interval. Thromboembolic and hemorrhagic complications were reported in 12.0% and 6.0% of the procedures, respectively.
The authors observed a trend toward a decline in the rate of thromboembolic and hemorrhagic complications with improved operator experience in using the PED for posterior circulation aneurysms. The use of single-device PED flow diversion significantly increased, as did the tendency to treat smaller aneurysms and observe large unruptured fusiform/dolichoectatic lesions. These findings reflect changes attributable to evolving judgment with maturing experience in PED use.
4 tables, 2 figures with angiograms
8. Rezai Jahromi B, Niemelä M. “Dolichoectatic Vertebrobasilar Artery Aneurysms.” Neurosurg Clin N Am [Internet]. 2022 Oct;33(4):419–29. Available from: https://doi.org/10.1016/j.nec.2022.06.003
Intracranial artery dolichoectasia (IADE) is a heterogenous arterial disease that is underdiagnosed and identified mainly in stroke patients. The abnormal lengthening (dolicho) and enlargement (ectasia) of intracranial arteries are poorly defined, especially in anterior circulation arteries. IADE of the vertebrobasilar artery was defined by Smoker and colleagues as follows: (1) basilar artery diameter larger than 4.5 mm, (2) tortuous of basilar artery more lies laterally from margin of clivus or dorsum sellae, and (3) basilar artery is above the suprasellar cistern. No definitions or criteria currently exist for anterior circulation dolichoectasia. Accurate natural history and epidemiologic studies are lacking due to an undefined population and cohorts, and also because IADEs are seen as normal anatomic variations.
The lack of classification related to the outcome and progression of IADE, as well as its underdiagnosis by physicians, has resulted in inconsistent studies on its epidemiology, disease progression, definition, and pathophysiology. Most patients are diagnosed after stroke by a neurologist and referred for neurosurgical evaluation when disease progression has reached a level with cranial nerve palsies or other treatments requiring decompression. Most IADE occurs in posterior circulation, making such cases vertebrobasilar dolichoectasia; some develop separate aneurysms, or the whole arterial segment expands aneurysmatically.
Despite the apparently poor prognosis of VBADAs, there have been no randomized clinical trials on this aspect. VBADA patients also have concomitant= diseases that force clinicians to treat lesions conservatively. Individual vascular plasticity and collateral formation have brought hope that VBADAs can be treated conservatively: If the patient is lucky, the VBADA may stabilize, and the aneurysm will stop growing while the brain stem perforators are kept intact. After the BA has enlarged by 10 mm or more, the probability of rupture increases whereas enlargement also brings the possibility of the cranial nerve stretching and the brainstem compressing. There are contradictory reports on whether thrombosis formation stabilizes or promotes VBADA’s malignant activity. The risk of stroke increases much earlier at 4.5 mm BA diameter, which forces patients to be treated prophylactically with antithrombotic medication (ASA), statins, and hypertension medication. Clinicians should closely follow-up on patients when VBADA shows any signs of activity.
4 figures with CT, CTA, MR and catheter angiography
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