1. Feigin VL, Vos T, Alahdab F, et al. Burden of neurological disorders across the US from 1990-2017. JAMA Neurol 2021;78:165. Available from: https://jamanetwork.com/journals/jamaneurology/fullarticle/2772579

This study presents the burden estimates of major neurological disorders in the US states by age and sex from 1990 to 2017 from a systematic analysis of the Global Burden of Disease (GBD) 2017 study. Fourteen major neurological disorders were analyzed: stroke, Alzheimer disease and other dementias, Parkinson disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.

The 3 most burdensome neurological disorders in the US in terms of absolute number of disability adjusted life-years (DALYs) were stroke (3.58 million DALYs), Alzheimer disease and other dementias (2.55 million DALYs), and migraine (2.40 million DALYs). The burden of almost all neurological disorders (in terms of absolute number of incidents, prevalent, and fatal cases, as well as DALYs) increased from 1990 to 2017, largely because of the aging of the population.

The study showed reductions in the age-adjusted rates of most burden metrics of stroke, AD and other dementias, TBI, spinal cord injuries, meningitis, and encephalitis.

Southeastern states and Arkansas had a relatively higher burden for stroke, while northern states had a relatively higher burden of multiple sclerosis and eastern states had higher rates of Parkinson disease, idiopathic epilepsy, migraine and tension-type headache, and meningitis, encephalitis, and tetanus. While confirming previous observations of the so-called stroke belt mortality in the southeastern United States, unlike previous estimates that identified North Carolina, South Carolina, and Georgia with a higher stroke mortality rate than the other states of the stroke belt, this 2017 GBD stroke mortality estimates show that the stroke belt is now in Alabama, Mississippi, and South Carolina.

3 large figures and 2 large tables

2. Habib A, Pease M, Kodavali CV, et al. A contemporary update on glioblastoma: molecular biology, current management, and a vision towards bio-adaptable personalized care. J Neurooncol 2021;151:103–12. Available from: https://doi.org/10.1007/s11060-020-03671-w

Despite the established survival benefits of Temozolomide plus concomitant radiation therapy for GBM patients, over the past decade, no profound additional therapy mediated survival advantage has been realized. This is likely due to GBM developing resistance to treatment and to significant intra and inter-tumoral heterogeneity, as well as the rapidly evolving and heterogeneous cellular cancer landscape. Following surgical resection and chemoradiation, the median survival rate is 18 months, while survival for patients with only supportive treatment is 4 months. Long term survivors represent 3–5% of patients surviving more than 3 years.

GBM employs numerous genetically driven treatment escape pathways that suppress the immune response. One of those pathways is the programmed cell death protein-1 ligand pathway (PD-L1); a potent immunosuppressive agent expressed in microglia which is highly expressed in normal brain tissue proximal to GBM. PD-L1 acts as a suppressor of cytotoxic T-cells proliferation and induces apoptosis in this cell population. Another immune evasion pathway is the activator of transcription 3 (STAT3) mediated pathway which is overexpressed in GBM leading to pro-inflammatory cytokine inhibition. Moreover, this pathway plays an essential role in the inappropriate GBM vascularization and excessive O2 consumption by GBM cells.

Many molecular therapeutic targets have been described in recent literature.  Although GBM prognosis remains bleak, several new avenues of treatment modalities, ranging from oncolytic viruses to targeted immunotherapy, hold promise to change the disease course of GBM. There likely is no single agent cure for GBM but rather a series of treatments based on intratumoral niche-based genetics.

1 figure and 2 tables including summaries of major oncolytic viral therapy trials

3. Krauss JK, Lipsman N, Aziz T, et al. Technology of deep brain stimulation: current status and future directions. Nat Rev Neurol 2021;17:75–87. Available from: http://dx.doi.org/10.1038/s41582-020-00426-z

In this Review, the authors provide a comprehensive overview of the technical development of DBS, from its origins to its future.

Some anticipated advances in DBS technology include:

-Miniaturization and cranialization

-Large-scale production and modernized production techniques to reduce cost

-Multiple power sources within implantable pulse generators (IPGs) to enable multiple independent current control

-Improved battery life, recharging capacity or energy harvesting

Increased safety

-Improved MRI compatibility with ≥3 T systems

-Antibiotic impregnation to reduce infection

-Protection from hacking, including ‘brainjacking’

Neuroimaging advances to improve targeting

-Enhanced anatomical resolution through specialized sequences (for example, quantitative susceptibility mapping) or ultra- high- field (7 T) MRI

-Improved automatic electrode reconstruction and segmentation with image- processing software

-Identification of ‘sweet spots’ from large retrospective imaging studies

-Enhanced deep brain stimulation programming through prospective functional imaging (for example, functional MRI) to identify optimal ‘neural signatures’

6 figures and 1 table

4. D’Antona L, Jaime Merchan MA, Vassiliou A, et al. Clinical presentation, investigation findings, and treatment outcomes of spontaneous intracranial hypotension syndrome. JAMA Neurol 2021;78:329–37. Available from: https://jamanetwork.com/journals/jamaneurology/fullarticle/2774171

The authors provide an objective summary of the available evidence on the clinical presentation, investigations findings, and treatment outcomes for SIH in this systematic review and meta-analysis.

Spontaneous intracranial hypotension is a highly misdiagnosed and underdiagnosed disorder. Estimates suggest that SIH is not uncommon with an annual incidence of 5 per 100 000 individuals every year, half the incidence of subarachnoid hemorrhage. Despite the lack of objective evidence on the effect of SIH on patients’ quality of life, the orthostatic headache typical of this condition makes SIH debilitating, affecting patients during their most active hours. The exact pathogenetic mechanism of SIH is unknown, and this lack of knowledge has led to a series of misconceptions. Moreover, the ICHD diagnostic criteria for SIH have changed significantly throughout the last few decades, and alternative diagnostic criteria have been proposed. These factors have probably contributed to the current uncertainty on how to reliably diagnose SIH and effectively treat these patients.

Of 6878 articles, 144 met the selection criteria and reported on average 53 patients with SIH each (range, 10-568 patients).

The most common symptoms were orthostatic headache (92%), nausea (54%), and neck pain/stiffness (43%).

Brain magnetic resonance imaging was the most sensitive investigation, with diffuse pachymeningeal enhancement identified in 73% of patients.

Brain magnetic resonance imaging findings were normal in 19% of patients.

Spinal neuroimaging identified extradural cerebrospinal fluid in 48% to 76% of patients.

Digital subtraction myelography and magnetic resonance myelography with intrathecal gadolinium had high sensitivity in identifying the exact leak site. Lumbar puncture opening pressures were low 67%, normal 32% (60-200mm H2O), and high in 3%. Large epidural blood patches (>20 mL) had better success rates than small epidural blood patches.

The incidence of rebound intracranial hypertension after treatment of SIH (EBP, percutaneous, or microsurgical treatment) has been reported to be between 7% and 27.4%.

They conclude that spontaneous intracranial hypotension should not be excluded on the basis of a nonorthostatic headache, normal neuroimaging findings, or normal lumbar puncture opening pressure.

2 tables, 3 figures with MR

5. Murphy OC, Salazar-Camelo A, Jimenez JA, et al. Clinical and MRI phenotypes of sarcoidosis-associated myelopathy. Neurol Neuroimmunol Neuroinflamm 2020;7:e722

Patients diagnosed with sarcoid associated myelopathy (SAM) at a single center between 2000 and 2018 who met the established criteria for definite and probable neurosarcoidosis were included in a retrospective analysis to identify clinical profiles, CSF characteristics, and MRI lesion morphology.

Of 62 included patients, 33 (53%) were male, and 30 (48%) were African American. SAM was the first clinical presentation of sarcoidosis in 49 patients (79%). Temporal profile of symptom evolution was chronic in 81%, with sensory symptoms most frequently reported (87%). CSF studies showed pleocytosis in 79% and CSF-restricted oligoclonal bands in 23% of samples tested. Four discrete patterns of lesion morphology were identified on spine MRI: longitudinally extensive myelitis (n = 28, 45%), short tumefactive myelitis (n = 14, 23%), spinal meningitis/meningoradiculitis (n = 14, 23%), and anterior myelitis associated with areas of disc degeneration (n = 6, 10%). Postgadolinium enhancement was seen in all but 1 patient during the acute phase. The most frequent enhancement pattern was dorsal subpial enhancement (n = 40), followed by meningeal/radicular enhancement (n = 23) and ventral subpial enhancement (n = 12).

Although some patients with spinal meningitis/ meningoradiculitis had patchy or subtle T2 signal changes within the cord, the enhancement was strictly extramedullary. However, meningeal, or radicular enhancement was also observed in conjunction with subpial enhancement in another 9 patients (i.e., in association with a longitudinally extensive or short tumefactive myelitis lesion). An unusual and distinct pattern of anterior myelitis occurring at locations of disc degeneration was identified in 6 patients (10%, figure 2), all with ventral subpial enhancement.

3 figures including MR

6. Martens RM, Koopman T, Lavini C, et al. Multiparametric functional MRI and 18F-FDG-PET for survival prediction in patients with head and neck squamous cell carcinoma treated with (chemo)radiation. Eur Radiol 2021;31:616–28

The authors assessed correlations between diffusion-weighted (DWI), intravoxel incoherent motion (IVIM), dynamic contrast-enhanced (DCE) MRI, and 18F-FDG-PET/CT imaging parameters capturing tumor characteristics and also their predictive value of locoregional recurrence-free survival (LRFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy in 70 patients.

This is complicated, but essentially in the present study, the combination of HPV status, tumor volume (ADCGTV), high Ktrans, and high Ve (the fractional volume of extravascular extracellular space) showed more predictive potential for locoregional control than the clinically used risk stratification per T-stage. The more of these adverse factors, the worse the locoregional-free survival was. The previously described predictive value of Ktrans and Ve was confirmed in this study.

The combination of all modalities showed that N-stage, HPV negative status, hypopharyngeal location, and intoxication were risk factors for adverse overall survival. This was in line with other studies who found hypopharyngeal PT location, alcohol use, and HPV status as predictors.

1 figure, 2 big tables

7. Broocks G, Elsayed S, Kniep H, et al. Early prediction of malignant cerebellar edema in posterior circulation stroke using quantitative lesion water uptake. Neurosurgery 2021;88:531–37. Available from: https://academic.oup.com/neurosurgery/article/88/3/531/5920780

179 patients with posterior circulation stroke and multimodal admission CT were included. A total of 35 (19.5%) patients developed malignant cerebellar edema (MCE) defined by using an established 10-point scale in follow-up CT, of which ≥4 points are considered malignant. Posterior circulation net water uptake (pcNWU) was quantified in admission CT based on CT densitometry and compared with posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) as predictor of malignant cerebellar edema using receiver operating curve (ROC) analysis and logistic regression analysis.

Acute posterior circulation net water uptake within the early ischemic lesion was 24.6% for malignant and 7.2% for nonmalignant infarctions, respectively. Based on ROC analysis, posterior circulation net water uptake above 14.9% identified malignant cerebellar edema with high discriminative power.

They used a standardized procedure to quantify posterior circulation net water uptake at the time of admission imaging based on a previously published method (Broocks G, Flottmann F, Ernst M, et al. Computed tomography-based imaging of voxel-wise lesion water uptake in ischemic brain: relationship between density and direct volumetry. Invest Radiol. 2018;53(4):207-213.) The measurement of net water uptake is based on densitometric analysis of the ischemic core compared to physiological density determined in an automatically mirrored contralateral region of interest.

The quantification of lesion water uptake in acute PCS may serve as an important surrogate imaging marker for developing malignant cerebellar edema. Besides pc-ASPECTS, lesion water uptake measurements could help to identify patients at risk for MCE at an early stage indicating stricter monitoring is required.

4 figures with CT

8. Belakhoua SM, Rodriguez FJ. Diagnostic pathology of tumors of peripheral nerve. Neurosurgery 2021;88:443–56. Available from: https://academic.oup.com/neurosurgery/article/88/3/443/6133985

Neoplasms of the peripheral nervous system represent a heterogenous group with a wide spectrum of morphological features and biological potential. They range from benign and curable by complete excision (schwannoma and soft tissue perineurioma) to benign but potentially aggressive at the local level (plexiform neurofibroma) to the highly malignant (malignant peripheral nerve sheath tumors [MPNST]). In this review, the authors discuss the diagnostic and pathologic features of common peripheral nerve sheath tumors, particularly those that may be encountered in the intracranial compartment or in the spine and paraspinal region. The discussion covers schwannoma, neurofibroma, atypical neurofibromatous neoplasms of uncertain biological potential, intraneural and soft tissue perineurioma, hybrid nerve sheath tumors, MPNST, and the recently renamed enigmatic tumor, malignant melanotic nerve sheath tumor, formerly referred to as melanotic schwannoma. They also discuss the diagnostic relevance of these neoplasms to specific genetic and familial syndromes of nerve, including neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis.

9 figures, 1 table, lots of histology images

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