1. Dittrich TD, Sporns PB, Kriemler LF, et al. Mechanical Thrombectomy Versus Best Medical Treatment in the Late Time Window in Non-DEFUSE-Non-DAWN Patients: A Multicenter Cohort Study. Stroke. 2023;54(3):722-730. doi:10.1161/STROKEAHA.122.039793
The authors assessed the efficacy and safety of mechanical thrombectomy (MT) in adult stroke patients with anterior circulation large vessel occlusion presenting in the late time window not fulfilling the DEFUSE-3 (Thrombectomy for Stroke at 6 to 16 Hours With Selection by Perfusion Imaging trial) and DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct trial) inclusion criteria. This was a cohort study of adults with anterior circulation large vessel occlusion admitted between 6 and 24 hours after last-seen-well at 5 participating Swiss stroke centers between 2014 and 2021. Mismatch was assessed by CT or MR perfusion with automated software (RAPID or OLEA). They excluded patients meeting DEFUSE-3 and DAWN inclusion criteria and compared those who underwent MT with those receiving best medical treatment alone by inverse probability of treatment weighting using the propensity score. The primary efficacy end point was a favorable functional outcome at 90 days, defined as a modified Rankin Scale score shift toward lower categories. The primary safety end point was symptomatic intracranial hemorrhage within 7 days of stroke onset; the secondary was all-cause mortality within 90 days.
Among 278 patients with anterior circulation large vessel occlusion presenting in the late time window, 190 (68%) did not meet the DEFUSE-3 and DAWN inclusion criteria and thus were included in the analyses. Of those, 102 (54%) received MT. In the inverse probability of treatment weighting analysis, patients in the MT group had higher odds of favorable outcomes compared with the best medical treatment alone group (modified Rankin Scale shift: acOR, 1.46) and lower odds of all-cause mortality within 90 days (aOR, 0.59). There were no significant differences in symptomatic intracranial hemorrhage (MT versus best medical treatment alone: 5% versus 2%, P=0.63).
They conclude that two out of 3 patients with anterior circulation large vessel occlusion presenting in the late time window did not meet the DEFUSE-3 and DAWN inclusion criteria. In these patients, MT was associated with higher odds of favorable functional outcomes without increased rates of symptomatic intracranial hemorrhage. These findings support the enrollment of patients into ongoing randomized trials on MT in the late window with more permissive inclusion criteria.
Both DEFUSE-3 and DAWN trials had very restrictive inclusion criteria. In this MT group, the main reasons for DEFUSE-3 ineligibility were distal occlusion site (ie, isolated occlusion of the M2 segment), low baseline NIHSS score (ie, <6 points), premorbid functional disability (ie, mRS score >2 points), and treatment with intravenous tissue-type plasminogen activator >4.5 hours after last known-well. Main reasons for DAWN ineligibility were the absence of clinical-imaging-mismatch, low baseline NIHSS score (ie, <10 points), and premorbid functional disability (ie, mRS score >1 point).
2 figures, 4 tables
2. Puetz V, Lutsep HL, Nguyen TN. Endovascular Therapy for Basilar Artery Occlusion: Among the First to Conceptualize, Last to Prove. Stroke. 2023;(March):905-908. doi:10.1161/strokeaha.122.041645
Nice summary of the current state of endovascular therapy for BAO.
The BASICS (Basilar Artery International Cooperation Study) and BEST (Basilar Artery Occlusion: Endovascular Interventions vs Standard Medical Treatment) trials were 2 seminal randomized trials comparing EVT to best medical management (BMM) in patients with BAO presenting up to the 6 and 8 hour window of estimated time of BAO. Both trials were neutral in demonstrating superiority of EVT for BAO despite a direction of treatment effect in favor of EVT. Several concepts emerged from the BASICS trial in the selection of BAO patients that now define the care and benchmark for future study. In contrast to the traditional concept of time since last known well in the acLVO trials, the BASICS registry and BASICS trial defined the notion of estimated time of onset. Patients who had transient or minor neurological symptoms prior to the estimated time of acute BAO could be candidate for intravenous thrombolysis (IVT) and enrollment in the BASICS trial, hence broadening inclusion of patients who may have otherwise been excluded. We also learned from BASICS that patients with minor deficits, defined as a NIHSS score below 10, had equivocal outcomes of EVT compared to BMM.
ATTENTION (Endovascular Treatment for Acute Basilar-Artery Occlusion) was a randomized trial comparing endovascular versus best medical management in patients with BAO presenting within 12 hours of estimated time of BAO, with moderate to severe symptoms as defined by NIHSS score ≥10, and posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) ≥6. (pc-ASPECTS reference -https://doi.org/10.1161/STROKEAHA.107.511162). The primary end point of good functional outcome defined as modified Rankin Scale score 0 to 3 was 2-fold greater in the EVT compared to MM group.
BAOCHE (Basilar Artery Occlusion Chinese Endovascular) was a randomized trial also comparing EVT versus best medical management in patients with BAO presenting from 6 to 24 hours since symptom onset, NIHSS score ≥6, and pc-ASPECTS ≥6. As the enrollment window was extended, approximately 18% of patients received IVT. The trial was halted after interim analysis demonstrated a nearly 2-fold greater proportion of patients achieving the primary outcome (modified Rankin Scale score 0 to 3) in the EVT compared to MM group.
The “good-scan-occlusion” paradigm, which has been applied in the acLVO EVT trials by selection of patients based on the detection of an acLVO and an ASPECTS score of 5 to 6 or above, has now been shown to work for identifying patients with BAO who benefit from EVT. ATTENTION and BAOCHE were the first BAO trials which applied imaging scores, including pc-ASPECTS ≥6 and the pons-midbrain index. The good news is that in patients with BAO, this principle works for late-window patients until 24 hours without requiring advanced imaging.
3. Chandra R, Saini HS, Palmer KN, Cerejo R. The link between reversible cerebral vasoconstriction syndrome and transient global amnesia. Headache: The Journal of Head and Face Pain. 2023;63(1):168-172. doi:10.1111/head.14432
RCVS is a cerebrovascular phenomenon that presents clinically as recurrent TCHs predominantly affecting females. Although RCVS is a self-limited entity, significant complications of subarachnoid hemorrhage, cerebral infarction and seizures have been reported leading to disability and poor functional outcomes. According to recent literature, the frequency of TCH is the most predictive diagnostic factor for RCVS with a sensitivity and specificity of 74% and 98%, respectively. Definite TGA is characterized by a sudden onset of anterograde amnesia without clouding or loss of consciousness, lack of epileptic features, head trauma and focal neurologic deficits witnessed by a reliable observer during the attack, furthermore the amnestic event must resolve within 24 h. RCVS and TGA are rare disorders with an annual incidence of three and 3–10 cases per million, respectively, in the general population. The patient described in this case was given an RCVS2 score of 8 (recurrent TCH, vasoconstrictive trigger present) indicating sensitivity and specificity of 90% and 99%, respectively for diagnosis of RCVS. He also met the criteria for definite TGA as he had witnessed clear anterograde amnesia during the attack without head trauma, epileptic features, and focal neurologic deficits with resolution of amnesia within 12 h from onset. Interestingly, the MRI findings in this patient correlated with symptom onset in that it suggested an acute/subacute timeframe. Given the chronology of events that led to the patient’s hospital admission, it is likely that RCVS led to his presentation of TGA. RCVS and TGA are two acute and reversible intra-cerebral conditions whose coexistence has been reported in a total of six cases worldwide (see table). The authors report the seventh case, linking RCVS to TGA and propose a common pathophysiologic link.
1 table, 1 figure
4. Gilligan M, McGuigan C, McKeon A. Paraneoplastic Neurologic Disorders. Curr Neurol Neurosci Rep. 2023;(January). doi:10.1007/s11910-023-01250-w
Paraneoplastic neurologic disorders are heterogeneous autoimmune diseases occurring in the context of a non-nervous system cancer (solid organ or hematologic). They can arise as the clinical presentation for a previously undiagnosed cancer (e.g., a woman who presents with ataxia in whom ovarian adenocarcinoma is subsequently detected). Paraneoplastic neurological disorders can also arise during treatment for a recently diagnosed cancer, or can be the clinical presentation alerting the treating providers to a cancer relapse. These disorders can target any part of the neuraxis, rostrocaudally, from cerebral cortex to neuromuscular junction, though certain classical syndromes, now known as “high risk phenotypes,” have the highest risk for accompanying cancer (Limbic encephalitis, Encephalomyelitis, Rapidly progressive cerebellar syndrome, Subacute sensory neuronopathy, Gastro-intestinal pseudo-obstruction, Lambert Eaton myasthenic syndrome, Opsoclonus myoclonus, Dermatomyositis).
In paraneoplastic limbic encephalitis, T2 hyperintensity of the mesial temporal lobes is typical, occasionally with contrast enhancement. In extra-limbic paraneoplastic encephalitides, MRI may demonstrate extratemporal lobar abnormalities that can resemble infectious or neoplastic processes. Linear, radial enhancement extending from the lateral ventricles is a characteristic MRI imaging finding in GFAP astrocytopathy. Distinctive radiological features also arise in GABAA-R encephalitis characterized by multi-lobar deep white matter and juxtacortical lesions on FLAIR imaging (without enhancement). In many instances, MRI of the brain can be entirely normal, including most patients with anti-NMDA receptor encephalitis.
3 tables, 1 figure
5. Tochigi S, Isoshima A, Ohashi H, et al. Preoperative assessment of dominant occipital sinus in patients with Chiari malformation type I: anatomical variations and implications for preventing potentially life-threatening surgical complications. J Neurosurg. 2023;138(2):540-549. doi:10.3171/2022.5.JNS212973
The surgical treatment of Chiari malformation type I (CM-I) frequently involves dural incision at the posterior cranial fossa. In cases of persistent patent occipital sinus (OS), the sinus is usually obliterated and divided. However, there are some patients whose OS is prominent and requires crucial modification of the operative planning to avoid potentially life-threatening massive hemorrhage and disturbance of cerebral venous circulation. In the present study, the anatomical variations of the dominant OS in patients with CM-I were analyzed and the authors attempted to develop treatment recommendations for patients with CM-I with dominant OS. The study included 213 patients with CM-I who underwent MR venography (MRV) prior to surgical treatment. OS dominance was assessed using 2D time-of-flight MRV or 3D phase-contrast MRV. Particular attention was paid to the pattern of venous outflow channels. The characteristics of the patients with dominant OS and the surgical outcomes were retrospectively reviewed. Dominant OS was identified in 7 patients (3.3%). The age in those with dominant OS was significantly younger than in those without. The incidence of concurrent scoliosis in the patients with dominant OS was significantly higher than in those without. All the dominant OSs were found to be of the oblique type. Multiple variations of venous drainage are described, with a helpful graphic. Bilateral OOSs with bilateral hypoplastic TSs were found in 2 patients (0.9%). Instead of performing Y-shaped dural incision and duraplasty, surgical procedures were modified depending on the types of the OOSs to preserve their venous drainage routes. Although massive bleeding from the dominant OS during dural incision occurred in 1 patient, none suffered neurological deterioration. The syrinx volume decreased in all but 1 of the patients postoperatively.
Considering the potentially devastating outcomes after obliterating a dominant OS resulting from Y-shaped duraplasty for CM-I, evaluating the venous drainage pattern prior to surgery is indispensable for safe surgical treatment. Even though the additional evaluation is costly and time-consuming, obtaining MRV prior to surgery is recommended, especially for the young and for patients with concurrent scoliosis.
4 figures, 2 tables, with MRI and MRV
6. Cools MJ, Wellons JC, Iskandar BJ. The Nomenclature of Chiari Malformations. Neurosurg Clin N Am. 2023;34(1):1-7. doi:10.1016/j.nec.2022.08.003
Nice review, particularly of the less commonly described Chiari 0, 0.5, and 1.5.
Regarding Chiari 0, in 1998, Iskandar and colleagues described five patients who presented with syringomyelia without tonsillar herniation who responded to posterior fossa decompression, which came to be known as a Chiari 0 malformation. Their patients all had improvement in clinical symptoms and a decrease in syrinx size. In a subsequent article with 10 additional patients, the authors showed similar findings, showing postoperative syrinx improvement in 9 patients, and stabilization in 1. Kyoshima and colleagues similarly described their experience with four patients with syringomyelia without tonsillar descent that improved after posterior fossa decompression, which they termed “tight cisterna magna.” It later became evident that patients with a Chiari type 0 malformation, whereas they lack tonsillar herniation, seem to have MRI evidence of other more subtle posterior fossa structural abnormalities, including the location of the obex below the level of the foramen magnum, indicating caudal descent of the brainstem, an enlarged anterior-posterior brainstem diameter at the level of the foramen magnum on sagittal imaging, an increase in the basion to opisthion distance compared with normal controls.
The challenge with the Chiari 0 diagnosis, which keeps it controversial, is the inability to distinguish Chiari 0 from true idiopathic syringomyelia. Although a lower position of the obex and other structural variations noted above, along with crowding of the subarachnoid spaces at the foramen, may be suggestive of Chiari 0 –the only reliable distinguishing feature is the response to posterior fossa decompression (postoperative resolution of the syrinx indicates Chiari 0 pathophysiology). This means that at least for now, Chiari 0 is a postoperative diagnosis, and remains a diagnosis of exclusion, in that all other causes of syringomyelia and symptoms need to be carefully ruled out, including tumor, arachnoiditis, tethered cord, and trauma.
1 table, 3 figures, with MRI
7. Chalif EJ, Morshed RA, Oh T, Dalle Ore C, Aghi MK, Gupta N. Neurosurgical Outcomes for Pediatric Central Nervous System Tumors in the United States. Neurosurgery. 2023;92(2):407-420. doi:10.1227/neu.0000000000002215
Limited data exist on pediatric central nervous system (CNS) tumors, and the results from the National Cancer Database, the largest multicenter national cancer registry, have not previously been comprehensively reported. The authors aimed to capture pediatric neurosurgical outcomes and investigate possible disparities of care. The National Cancer Database was queried for pediatric patients who were diagnosed with CNS tumors from 2004 to 2018. Primary outcomes included 30/90 days postoperative mortality (30M/90M), readmission within 30 days of discharge (30R), and length of inpatient stay (LOS). Twenty four thousand nine hundred thirty cases met the inclusion criteria, of which were 4753 (19.1%) juvenile pilocytic astrocytomas, 3262 (13.1%) medulloblastomas, 2200 (8.8%) neuronal/mixed neuronal-glial tumors, and 2135 (8.6%) ependymal tumors.
Patients aged 0 to 4 years had significantly poorer outcomes than patients in older age groups (90M: 3.5% vs 0.7%-0.9%). Tumor size was a strong predictor of poor outcomes with each additional cm in diameter conferring a 26%, 7%, and 23% increased risk of 90M, 30R, and prolonged LOS, respectively. Data over the study period demonstrated year over year improvements of 4%, 3%, and 2%, respectively, for 90M, readmission within 30 days of discharge, and prolonged LOS. Facilities with a high volume of pediatric tumor cases had improved 90M and LOS. Patients with private health insurance had better outcomes than patients with government insurance.
The authors demonstrate that treatments and outcomes differ by patient race, income, and insurance status. In addition, patients of lower socioeconomic status were more often treated at a low volume facility (LVF), and these were both risk factors for poorer outcomes. Although one might hypothesize that aggressive surgical intervention at LVFs was not as often pursued, thereby leading to worse outcomes, they found no statistically significant differences in extent of resection (EOR) between high volume facility and LVF or among socioeconomic groups. They also investigated these outcome differences by examining which patients were more likely to receive adjuvant treatment. Hispanic patients had reduced rates of radiation treatment compared with White patients, government-insured patients had reduced rates of chemoradiation than privately insured patients, and receipt of chemoradiation correlated negatively with lower income. Of note, many of the same socioeconomic groups that had less adjuvant treatment also had poorer outcomes.
They conclude that there is substantial variability in surgical morbidity and mortality of pediatric CNS tumors. Additional investigation is warranted to reduce outcome differences that may be based on socioeconomic factors.
3 tables, 5 figures, no imaging
8. Kashkoush AI, Whiting BB, Desai A, et al. Clinical Outcomes After Nonoperative Management of Large Acute Traumatic Subdural Hematomas in Older Patients: A Propensity-Scored Retrospective Analysis. Neurosurgery. 2023;92(2):293-299. doi:10.1227/neu.0000000000002192
The authors investigated inpatient mortality after conservative management of large aSDHs. Single-center retrospective review of adult patients with traumatic brain injury from 2018 to 2021 revealed 45 large aSDHs that met inclusion criteria. Inpatient outcomes included mortality, length of stay, and discharge disposition. Follow-up data included rate of surgery for chronic SDH progression. Patients with large aSDHs were 2:1 propensity score–matched to patients with small (<1 cm) aSDHs based on age, Injury Severity Scale, Glasgow Coma Scale, and Rotterdam computed tomography scale. Median age was (78 years), sex (male 52%), and race (Caucasian 91%) which were similar between both groups. Inpatient outcomes including length of stay (P = .32), mortality (P = .37), and discharge home (P = .28) were similar between those with small and large aSDHs. On multivariate logistic regression (odds ratio [95% CI]), increased in-hospital mortality was predicted by Injury Severity Scale , Rotterdam computed tomography scale 3 to 4, parafalcine, tentorial location, or presence of an intracranial contusion. Patients with large aSDHs trended toward higher progression on follow-up computed tomography of the head (36% vs 16%) and higher rates of chronic SDH surgery (25% vs 7%). They conclude that in conservatively managed patients with minimal symptoms and mass effect on computed tomography of the head, increasing SDH size did not contribute to worsened in-hospital mortality or length of stay. Patients with large aSDHs may undergo an initial course of nonoperative management if symptoms and the degree of mass effect are mild.
6 tables, 1 figure
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