1. Takami H, Perry A, Graffeo CS, et al. Comparison on epidemiology, tumor location, histology, and prognosis of intracranial germ cell tumors between Mayo Clinic and Japanese consortium cohorts. J Neurosurg 2020;134(February):1–11
CNS germ cell tumors (GCTs) are rare neoplasms predominantly arising in adolescent and young-adult male patients. Standardized treatment protocols using chemoradiation have demonstrated durable tumor control in 90% of germinomas. By contrast, nongerminomatous GCTs (NGGCTs) have proven resistant to a wide array of chemotherapy, radiation, and combined protocols, resulting in a generally poor prognosis.
GCTs demonstrate characteristic racial-geographic distributions, with gonadal GCTs predominating in Western countries, whereas CNS GCTs arise more frequently in East Asian populations. Within the US, the frequency of intracranial GCTs was highest in Asian/Pacific islanders, followed by White and Black populations. More specifically, while CNS GCTs account for only 5% of primary brain tumors in Western children younger than 14 years of age, in a comparable Japanese cohort CNS GCTs account for 14%, a nearly 3-fold increase in incidence.
In 2015, utilizing whole-genome germline sequencing a key association was identified between a genetic variant of JMJD1c and Japanese CNS GCT, in whom it was 4.8-fold more prevalent, as compared to a matched Western cohort. JMJD1c is a Jumonji domain-containing protein, which encodes the histone H3K9 demethylating enzyme (Sound familiar? H3K27M in Diffuse midline glioma).
Intracranial Germ Cell Tumor Genome Analysis Consortium (iGCT Consortium) was established in 2011. At present, the iGCT Consortium has enrolled more than 200 cases including tumor specimens and clinical data, via the National Cancer Center (NCC) in Japan. In parallel, the Mayo Clinic in the US has prospectively registered, biobanked, and followed 98 cases of CNS GCT, including metastatic cases from other organs, that underwent neurosurgical management during the study period (1988–2017).
The goal of the present study was to perform a direct comparison between these large, prospective CNS GCT registries—with particular attention to characteristic differences in demographics, clinical presentation, and treatment response.
There was no significant difference in age and sex distributions between the databases. However, there was a significant difference in the tumor locations; specifically, the frequency of basal ganglia was higher in the NCC database compared with the Mayo Clinic (8.4% vs 0%), and bifocal location (neurohypophysis and pineal gland) was higher at the Mayo Clinic than at the NCC (18.8% vs 5.8%). There was no difference in histological subdivisions between the databases. There was no difference in progression-free survival (PFS) and overall survival (OS) of germinoma cases and OS of nongerminomatous GCT (NGGCT) cases treated with chemotherapy and radiation therapy covering whole ventricles. However, PFS of NGGCTs differed significantly, and was better in the NCC cohorts.
In conclusion, there appears to be a differential distribution of GCTs by neuroanatomical location between major geographic and national groups.
5 figures, 1 table, no images
2. Hardy TA. Spinal cord anatomy and localization. Continuum (Minneap Minn) 2021;27:12–29. Available from: http://www.ncbi.nlm.nih.gov/pubmed/33522735
This is a very nice review of spinal cord anatomy including some basic clinical findings and the different types of cord injury. Highly recommended for residents and fellows.
For example, some clues to a spinal cord lesion from the history:
-Bilateral greater than unilateral sensory and/or motor symptoms
-Bladder, bowel, and/or sexual dysfunction
-Stiffness in the legs
-Neck and/or back pain in association with neurologic symptoms, particularly if the patient had preceding trauma or if pain is exacerbated by neck flexion or extension
-Sensory level across the trunk (often more reliable as a symptom than a sign)
-Tight band around the trunk or torso
-Neurogenic claudication (suggests cauda equina pathology rather than a lower cord lesion)
-Sensory ataxia (can also occur with peripheral nervous system disorders)
-Dyspnea when lying flat (C3-C5 lesion)
-Lhermitte or Uhthoff phenomenon
The Uhthoff phenomenon occurs when patients with a demyelinating disease (such as multiple sclerosis) develop a recrudescence of symptoms attributable to a CNS demyelinating lesion with an increase in body temperature, such as when febrile, during exercise, or when ambient temperatures are hot (eg, in the shower).
The Lhermitte phenomenon (defined as an electrical pain or tingling brought on by neck flexion that runs from the neck down the back and sometimes into the arms or legs) is a clue to cervical myelopathy most commonly due to a demyelinating lesion, but it may be encountered with other etiologies, including cervical spondylotic myelopathy.
Painful cramping or weakness in the legs that presents after walking a set distance and improves with rest (neurogenic claudication) is a feature of clinically significant lumbar spinal canal stenosis causing intermittent compression of cauda equina nerve roots; patients may report doing better when the spine is in flexion, which widens the lumbar canal (eg, when bent forward leaning over a shopping cart).
7 figures, 2 tables
3. Machino M, Ando K, Kobayashi K, et al. Postoperative changes in spinal cord signal intensity in patients with spinal cord injury without major bone injury: comparison between preoperative and postoperative magnetic resonance images. J Neurosurg Spine 2021;34:259–66
In some patients with SCI without major bone injury, resolution or decrease in increased signal intensity has been observed after surgery, but few studies have evaluated alterations in increased signal intensity between pre- and postoperative MRI sequences. Alterations in increased signal intensity have not been evaluated fully, and no relationship between postoperative ISI and surgical outcomes in patients with SCI without major bone injury has been clearly established. The aim of this study was to determine if the postoperative classification of and alterations in increased signal intensity on MRI of the spinal cord reflect the postoperative symptom severity and surgical outcomes in patients with SCI without major bone injury.
One hundred consecutive patients with SCI without major bone injury (79 male and 21 female) with a mean age of 55 years (range 20–87 years) were included. All patients were treated with laminoplasty and underwent MRI pre and postoperatively (mean 12.5 months). ISI was classified into three groups on the basis of sagittal T2-weighted MRI: grade 0, none; grade 1, light (obscure); and grade 2, intense (bright).
The postoperative JOA scores and recovery rate (RR) decreased significantly with increasing postoperative increased signal intensity grade. The postoperative grade tended to increase with the postoperative spinal injury impairment grade. Postoperative grade 2 was observed in severely paralyzed patients. The postoperative ISI grade improved in 23 patients (23%), worsened in 25 (25%), and remained unchanged in 52 (52%). Patients with an improved ISI grade had a better recovery rate than those with a worsened ISI grade.
They conclude that postoperative increased signal intensity reflected postoperative symptom severity and surgical outcomes. Alterations in ISI were seen postoperatively in 48 patients (48%) and were associated with surgical outcomes.
4 figures, 4 tables with MR images
4. Mariano R, Messina S, Roca-Fernandez A, et al. Quantitative spinal cord MRI in MOG-antibody disease, neuromyelitis optica and multiple sclerosis. Brain 2021;144:198–212
The most well-described inflammatory demyelinating CNS disease is multiple sclerosis, a T-cell predominant immunological disorder of unknown etiology. More recently, two further diseases caused by antibodies have been described. Aquaporin-4 antibodies (AQP4-Ab) target the AQP4 water channels situated on astrocyte foot processes and cause a primary astrocytopathy with secondary demyelination and the clinical phenotype of neuromyelitis optica spectrum disorders (NMOSD). Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) target myelin and are associated with a primary demyelinating disease with a wider clinical phenotype.
Spinal cord involvement is a hallmark feature of all three conditions and spinal cord lesions are important because they are a major driver of clinical symptoms and may cause substantial disability. The classically described MRI findings are short, asymmetrical lesions in multiple sclerosis and longitudinally extensive central lesions (greater than or equal to 3 vertebral segments) in both NMOSD and MOG-Ab disease with involvement of the conus being noted particularly in those with MOG-Abs. However, short lesions are being reported more commonly in MOG-Ab disease and both short and asymptomatic lesions have been reported in patients with AQP4-Ab disease.
In this study the authors used multimodal MRI (routine, measurements, MT, DTI) to study spinal cord involvement in AQP4-Ab-positive NMOSD and MOGAb disease and compared it to multiple sclerosis and healthy volunteers. MRI sequences that have shown clinical relevance were selected and clinical data were collected using established measures. They aimed to assess if these markers can be used to differentiate these conditions, provide a better understanding of the underlying condition outside of an acute episode, and if they are clinically relevant.
Myelitis with AQP4-Abs shows the most severe, localized damage in areas involved during the acute episode. In multiple sclerosis, metrics show significant change in comparison to healthy volunteers; however, the relationship with lesion location is not as pronounced. Finally, in MOG-Ab disease, metrics are comparable with healthy volunteers in all measures except that there is significant localized grey matter atrophy in affected areas of the cord. MOG-Ab disease is also moderately discriminated from AQP4-Ab disease and multiple sclerosis based on these quantitative metrics due to good recovery.
1 table, 6 figures, 1 with MR
5. Vogrig A, Muñiz-Castrillo S, Joubert B, et al. Cranial nerve disorders associated with immune checkpoint inhibitors. Neurology 2021;96:e866–75. Available from: http://www.neurology.org/lookup/doi/10.1212/WNL.0000000000011340
Immune checkpoint inhibitors (ICIs) are novel drugs that have revolutionized oncologic practice by increasing survival in patients with advanced tumors, including melanoma, non–small cell lung cancer, and kidney cancer. ICIs are able to potentiate T-cell activation and consequently lead to an immune attack against cancer cells. Given their mechanism of action, ICIs may unleash a number of immune-related toxicities.
Among 67 cases with ICI-related neurologic toxicities diagnosed in the authors reference center, 9 patients with Cn-ICI were identified (7 men, 78%, median age 62 years). Patients were receiving a combination of anti–cytotoxic T-lymphocyte antigen 4 and anti–programmed cell death 1 (PD-1)/PD-1 ligand (n = 5, 56%) or anti–PD-1 antibodies alone (n = 4, 44%). Cn-ICI involved optic (n = 3), vestibulocochlear (n = 3), abducens (n = 2), facial (n = 2), and oculomotor (n = 1) nerves. Two patients had involvement of 2 different cranial nerves. Treatment comprised corticosteroids (n = 8, 89%), ICI permanent discontinuation (n = 7, 78%), plasma exchange (n = 2, 22%), and IV immunoglobulin (n = 1, 11%). Median follow-up was 11 months (range 1–41 months). In 3 cases (33%), neurologic deficit persisted/worsened despite treatment: 2 optic and 1 vestibulocochlear. Among cases from the literature and the present series combined (n = 39), the most commonly affected cranial nerves were facial (n = 13, 33%), vestibulocochlear (n = 8, 21%), optic (n = 7, 18%), and abducens (n = 4, 10%). Trigeminal, oculomotor, and glossopharyngeal nerves were less frequently affected (total n = 7).
The present study found that CN disorders represent a possible complication of ICI treatment. An immune-mediated involvement of CNS unleashed by ICIs is supported in the cases reported herein by the association with other neurologic and non-neurologic immune-related adverse events, the occurrence of Cn-ICI along with a favorable oncologic response, and the possible positive effect of corticosteroids and other first-line immunotherapies, but also the improvement or resolution of neurologic disorders that was achieved in two thirds of the cases that was maintained after a median followup of ≈1 year.
2 figures, 1 table, with 1 MR
6. Boyke AE, Bader ER, Naidu I, et al. Medical malpractice and meningiomas: an analysis of 47 cases. Neurosurg Focus 2020;49:1–8
The online legal database Westlaw was utilized to query public litigation cases related to the medical management of meningiomas between December 1985 and May 2020. Variables extracted included the following: plaintiff and defendant demographics, litigation category, plaintiff medical complaints, and trial outcomes. The authors compared these characteristics between cases with decisions in favor of the defendant and those with decisions in favor of the plaintiff.
A total of 47 cases met the inclusion criteria. Failure to diagnose (68.1%) was the most common type of malpractice claim, and surgical complications (19.1%), motor weakness (33%), and financial loss (33%) were cited as the most common postoperative complaints. Individual specialties that most often required defense due to malpractice claims were radiology (21.7%) and neurosurgery (19.6%). The jury verdict was in favor of the defense in 51.1% of cases and in favor of the plaintiff in 27.7% of cases. A settlement was reached in 19.1% of cases. The mean payout for a verdict in favor of the plaintiff was $3,409,650.22, while the mean payout for settlements was $867,555.56. The greatest average payout for specialties was in neurosurgery at $3,414,400, followed by radiology at $3,192,960.
2 figures, 3 tables, with no imaging
7. Dengler J, Rüfenacht D, Meyer B, et al. Giant intracranial aneurysms: natural history and 1-year case fatality after endovascular or surgical treatment. J Neurosurg 2019;134:1–9. Available from: https://thejns.org/view/journals/j-neurosurg/aop/article-10.3171-2019.8.JNS183078/article-10.3171-2019.8.JNS183078.xml
Since aneurysm size has been shown to be the most dominant risk factor for rupture, unruptured intracranial aneurysms at highest risk of rupture are those categorized as unruptured giant intracranial aneurysms (GIAs). This group comprises all unruptured intracranial aneurysms with diameters of at least 25 mm. Since unruptured GIAs only account for about 5% of all unruptured intracranial aneurysms, limited data are available on long-term rupture rates and treatment outcomes. Due to this lack of evidence, decisions on unruptured GIA management remain subject to debate.
The authors describe the results of an international multicenter registry aiming to document the natural history, as observed in patients selected for conservative management (CM) without aneurysmal repair, and outcomes of surgical management (SM) or endovascular management (EM) for both ruptured and unruptured GIAs.
The retrospective cohort comprised 219 patients with GIAs (21.9% ruptured GIAs and 78.1% unruptured GIAs) whose index hospitalization occurred between January 2006 and November 2016. The index hospitalization in the prospective cohort (362 patients with GIAs [17.1% ruptured and 82.9% unruptured]) occurred between December 2008 and February 2017. In the retrospective cohort, the risk ratio for death at a mean follow-up of 4.8 years after conservative management, compared with endovascular management and surgical management, was 1.63 in ruptured GIAs and 3.96 in unruptured GIAs. In the prospective cohort, the 1-year case fatality in ruptured GIAs/unruptured GIAs was 100%/22.0% during CM, 36.0%/3.0% after SM, and 39.0%/12.0% after EM. Corresponding 1-year rupture rates in unruptured GIAs were 25.0% during CM, 1.2% after SM, and 2.5% after EM.
In the prospective cohort of the registry, patients with CM of a ruptured or an unruptured GIA were in poorer condition at 1 year of follow-up than patients with SM or EM. In ruptured GIAs, the natural history was characterized by a 1-year case fatality of 100%, compared with 36% after SM and 39% after EM. In unruptured GIAs, the natural history displayed a 1-year case fatality of 22% for the entire cohort and 1-year rupture rates of 25%. The results after SM or EM of unruptured GIAs were significantly better: after SM, 1-year case fatality was 3% and rupture rates were 1%; the EM group exhibited a 1-year case fatality rate of 12% and rupture rates of 2%.
They conclude that the rupture rates for unruptured GIAs were high, and the natural history and treatment outcomes for ruptured GIAs were poor. Patients undergoing SM or EM showed lower case fatality and rupture rates than those undergoing CM.
1 figure, 5 tables, no images
8. CreveCoeur TS, Yahanda AT, Maher CO, et al. Occipital-cervical fusion and ventral decompression in the surgical management of Chiari-1 malformation and syringomyelia: analysis of data from the Park-Reeves Syringomyelia Research Consortium. Neurosurgery 2021;88:332–41. Available from: https://academic.oup.com/neurosurgery/advance-article/doi/10.1093/neuros/nyaa460/6031389
While posterior fossa decompression (PFD) is commonly accepted as the primary treatment for pediatric Chiari type I malformation (CM-1) with or without syringomyelia (SM), the indications for and use of occipital-cervical fusion (OCF) and/or ventral decompression (VD) are less clear. Studies have examined variations in craniovertebral anatomy and their relationship to instability with implications for management. Clivo-axial angle (CXA)(aka clival canal angle) less than 125◦, basilar invagination, medullary kinking, and a diagnosis of Chiari 1.5 malformation have been proposed risk factors associated with OCF treatment in a complex subset of CM-1 patients. The objective of this current study was to examine factors associated with the use of OCF and VD in a large group of pediatric CM-1/syrinx patients treated across the United States.
The Park-Reeves Syringomyelia Research Consortium registry was used to examine 637 subjects with cerebellar tonsillar ectopia ≥ 5mm, syrinx diameter ≥3mm, and at least 1 yr of follow-up after their index PFD.
All 637 patients underwent PFD, 505 (79.2%) with and 132 (20.8%) without duraplasty. A total of 12 subjects went on to have OCF at some point in their management (PFD + OCF), whereas 4 had OCF and ventral decompression (PFD + OCF/VD). Of those with complete data, a history of platybasia (3/10), Klippel-Feil (2/10), and basilar invagination (3/12) were increased within the OCF group, whereas only basilar invagination (1/4) was increased in the OCF/VD group. Clivo-axial angle (CXA) was significantly lower for both OCF (128.8 degrees) and OCF/VD (115.0◦) groups when compared to PFD-only group (145.3◦).
The vast majority of CM-1/syrinx patients do not undergo OCF or OCF/VD. Clinical symptoms and signs of lower cranial nerve dysfunction and ventral brainstem compression were common in patients undergoing OCF and OCF/VD. Patients with significantly greater radiological findings of tonsillar ectopia and lower clivo-axial angle more often received OCF/VD, and patients with genetic anomalies more frequently received OCF. However, most patient with a high degree of tonsillar herniation and a low CXA do not require fusion.
1 figure, 7 tables, no images
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