Syndrome of anterior neural stalk, vertebral abnormality, enteric duplication cyst, and diaphragmatic hernia related to persistent ventral neurenteric canal: report of two cases.

PURPOSE: Abnormalities in notochordal development can cause a range of developmental malformations, including the split notochord syndrome and split cord malformations. We describe two cases that appear related to unusual notochordal malformations, in a female and a male infant diagnosed in the early postnatal and prenatal periods, which were treated at our institution. These cases were unusual from prior cases given a shared constellation of an anterior cervicothoracic meningocele with a prominent "neural stalk," which coursed ventrally from the spinal cord into the thorax in proximity to a foregut duplication cyst. METHODS: Two patients with this unusual spinal cord anomaly were assessed clinically, and with neuroimaging and genetics studies. RESULTS: We describe common anatomical features (anterior neural stalk arising from the spinal cord, vertebral abnormality, enteric duplication cyst, and diaphragmatic hernia) that support a common etiopathogenesis and distinguish these cases. In both cases, we opted for conservative neurosurgical management in regards to the spinal cord anomaly. We proposed a preliminary theory of the embryogenesis that explains these findings related to a persistence of the ventral portion of the neurenteric canal. CONCLUSION: These cases may represent a form of spinal cord malformation due to a persistent neurenteric canal and affecting notochord development that has rarely been described. Over more than 1 year of follow-up while managed conservatively, there was no evidence of neurologic dysfunction, so far supporting a treatment strategy of observation.

Spontaneous intramedullary abscesses caused by Streptococcus anginosus: two case reports and review of the literature.

BACKGROUND: Intramedullary abscesses are rare infections of the spinal cord. Intramedullary abscesses often have a complex presentation, making a high index of suspicion essential for prompt diagnosis and management. CASE PRESENTATION: We present two cases of intramedullary abscesses referred to and ultimately managed at our institution. Delayed diagnosis occurred in both instances due to the rarity of intramedullary abscesses and their propensity to mimic other pathologies. For both patients, prompt surgical management and the rapid institution of broad-spectrum antibiotics were critical in preventing further neurological decline. CONCLUSIONS: Although rare, it is critical to consider intramedullary abscesses on the differential for any MRI lesions that are hyperintense on T2 and peripherally enhancing on T1 post-contrast sequences, as even short delays in treatment can lead to severe neurological damage.

"Recycling" A Failed Superficial Temporal Artery Indirect Bypass into a Double Barrel Direct Bypass in Moyamoya Disease.

OBJECTIVES: Moyamoya disease is an idiopathic cerebrovascular disorder in which patients experience recurrent transient ischemic attacks, ischemic or hemorrhagic strokes, headaches, and seizures from progressive stenosis of the vessels of the anterior circulation. The mainstay of treatment in symptomatic patients is surgical revascularization. Here, we present the case of a moyamoya patient in which a failed encephaloduroarteriosynangiosis, after new strokes, is recycled and converted into a combined "double barrel" direct superficial temporal artery to middle cerebral artery bypass with included video. CASE REPORT/RESULTS: We describe a 37-year-old woman with a history of hypertension, obstructive sleep apnea, celiac disease, and moyamoya disease complicated by multiple ischemic strokes who presented with progressive dysarthria, dysphagia, and new left-sided ischemic infarcts. The patient had previously undergone right-sided direct bypass and left-sided encephaloduroarteriosynangiosis in the setting of multiple ischemic strokes. After more strokes, the patient underwent a left-sided frontotemporoparietal craniotomy for conversion of the failed indirect bypass into a "double barrel" direct bypass. CONCLUSIONS: The literature is divided over which revascularization procedure should be preferred. Irrespectively, most failed bypass grafts are repaired via direct bypasses, to good effect. We highlight a case in which a failed indirect bypass is directly incorporated into a combined direct bypass with resulting restoration of blood flow. In the case of a failed indirect bypass in an adult patient with moyamoya disease, this method provides the operator with an additional option for restoration of perfusion, especially in patients without other viable vessels available for anastomosis.

Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once.

A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.

The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.

Genome-wide survey of copy number variants finds MAPT duplications in progressive supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy is a neurodegenerative tauopathy manifesting clinically as a progressive akinetic-rigid syndrome. In this study, we sought to identify genetic variants influencing PSP susceptibility through a genome-wide association analysis of a cohort of well-characterized patients who had participated in the Neuroprotection and Natural History in Parkinson Plus Syndromes and Blood Brain Barrier in Parkinson Plus Syndromes studies. METHODS: We genotyped single-nucleotide polymorphisms in 283 PSP cases from the United Kingdom, Germany, and France and compared these with genotypes from 4472 controls. Copy number variants were identified from genotyping data. RESULTS: We observed associations on chromosome 17 within or close to the MAPT gene and explored the genetic architecture at this locus. We confirmed the previously reported association of rs1768208 in the MOBP gene (P = 3.29 × 10-13 ) and rs1411478 in STX6 (P = 3.45 × 10-10 ). The population-attributable risk from the MAPT, MOBP, and STX6 single-nucleotide polymorphisms was found to be 0.37, 0.26, and 0.08, respectively. In addition, we found 2 instances of copy number variants spanning the MAPT gene in patients with PSP. These copy number variants include tau but few other genes within the chromosome 17 haplotype region, providing additional support for the direct pathogenicity of MAPT in PSP. CONCLUSIONS: Clinicians should also be aware of MAPT duplication as a possible genetic cause of PSP, especially in patients presenting with young age at onset. © 2019 International Parkinson and Movement Disorder Society.

Frequency of the TREM2 R47H Variant in Various Neurodegenerative Disorders.

OBJECTIVE: A rare variant in TREM2 (p.R47H, rs75932628) has been consistently reported to increase the risk for Alzheimer disease (AD), while mixed evidence has been reported for association of the variant with other neurodegenerative diseases. Here, we investigated the frequency of the R47H variant in a diverse and well-characterized multicenter neurodegenerative disease cohort. METHODS: We examined the frequency of the R47H variant in a diverse neurodegenerative disease cohort, including a total of 3058 patients clinically diagnosed with AD, frontotemporal dementia spectrum syndromes, mild cognitive impairment, progressive supranuclear palsy syndrome, corticobasal syndrome, or amyotrophic lateral sclerosis and 5089 control subjects. RESULTS: We observed a significant association between the R47H variant and AD, while no association was observed with any other neurodegenerative disease included in this study. CONCLUSIONS: Our results support the consensus that the R47H variant is significantly associated with AD. However, we did not find evidence for association of the R47H variant with other neurodegenerative diseases.

Treatment-refractory Escherichia coli subdural empyema caused by infection of a chronic subdural hematoma in an infant.

INTRODUCTION: Subdural empyema (SDE) is a neurosurgical emergency that is typically treated with surgical drainage, either by burr hole or by craniotomy. Escherichia coli is an uncommon cause of SDE and is associated with infection of a pre-existing subdural hematoma. CASE REPORT: We report the case of an otherwise healthy, immunocompetent 4-month-old infant girl with an E. coli-infected subdural hematoma. The infection persisted despite aggressive neurosurgical treatment that included drainage of the subdural space through burr holes and, subsequently, a wide craniotomy was performed. Ultimately, after 30 days, the SDE resolved with good neurological outcome. A review of prior literature indicates that infected subdural hematomas (including those caused by E. coli) are typically less aggressive and respond to burr hole drainage. CONCLUSION: We illustrate the fulminant progression of the SDE in the face of neurosurgical treatment. Our experience suggests lowering the threshold for wide craniotomy in these incompletely understood cases.

Gene Co-Expression Network Analysis Implicates microRNA Processing in Parkinson's Disease Pathogenesis.

BACKGROUND: Recent advances in genetics have provided insights into important inherited causes of Parkinson's disease (PD), but the underlying biological mechanisms are still incompletely understood. Gene expression studies have pointed toward the dysregulation of neuroinflammation, mitochondrial function, and protein degradation pathways. OBJECTIVE: We aimed to identify groups of dysregulated genes in PD. METHODS: In order to increase statistical power and control for potential confounders, we re-analyzed transcriptomic data from PD patients and model systems, integrating additional genomic data using a systems biology approach. Using weighted gene co-expression network analysis, we partitioned genes into co-expressed modules. RESULTS: One co-expression module, M13, had an expression trajectory that was highly correlated with PD, was not characterized by any specific cell type markers, and was enriched in PD genes identified by genome-wide association studies. Genes within M13 seemed to be related to global microRNA biogenesis, and DICER1 and AGO3 were highly connected within the module. The NUCKS1 gene, previously identified as part of the PARK16 locus, was also a hub gene within M13. CONCLUSION: These results suggest that microRNA processing and function may play a role in the pathogenesis of PD, and thus may represent a useful target for future drug development.

An epigenetic signature in peripheral blood associated with the haplotype on 17q21.31, a risk factor for neurodegenerative tauopathy.

Little is known about how changes in DNA methylation mediate risk for human diseases including dementia. Analysis of genome-wide methylation patterns in patients with two forms of tau-related dementia--progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD)--revealed significant differentially methylated probes (DMPs) in patients versus unaffected controls. Remarkably, DMPs in PSP were clustered within the 17q21.31 region, previously known to harbor the major genetic risk factor for PSP. We identified and replicated a dose-dependent effect of the risk-associated H1 haplotype on methylation levels within the region in blood and brain. These data reveal that the H1 haplotype increases risk for tauopathy via differential methylation at that locus, indicating a mediating role for methylation in dementia pathophysiology.

SIRT1 deficiency in microglia contributes to cognitive decline in aging and neurodegeneration via epigenetic regulation of IL-1ß.

Aging is the predominant risk factor for neurodegenerative diseases. One key phenotype as the brain ages is an aberrant innate immune response characterized by proinflammation. However, the molecular mechanisms underlying aging-associated proinflammation are poorly defined. Whether chronic inflammation plays a causal role in cognitive decline in aging and neurodegeneration has not been established. Here we report a mechanistic link between chronic inflammation and aging microglia and a causal role of aging microglia in neurodegenerative cognitive deficits. We showed that SIRT1 is reduced with the aging of microglia and that microglial SIRT1 deficiency has a causative role in aging- or tau-mediated memory deficits via IL-1ß upregulation in mice. Interestingly, the selective activation of IL-1ß transcription by SIRT1 deficiency is likely mediated through hypomethylating the specific CpG sites on IL-1ß proximal promoter. In humans, hypomethylation of IL-1ß is strongly associated with chronological age and with elevated IL-1ß transcription. Our findings reveal a novel epigenetic mechanism in aging microglia that contributes to cognitive deficits in aging and neurodegenerative diseases.

Machine learning for large-scale wearable sensor data in Parkinson's disease: Concepts, promises, pitfalls, and futures.

For the treatment and monitoring of Parkinson's disease (PD) to be scientific, a key requirement is that measurement of disease stages and severity is quantitative, reliable, and repeatable. The last 50 years in PD research have been dominated by qualitative, subjective ratings obtained by human interpretation of the presentation of disease signs and symptoms at clinical visits. More recently, "wearable," sensor-based, quantitative, objective, and easy-to-use systems for quantifying PD signs for large numbers of participants over extended durations have been developed. This technology has the potential to significantly improve both clinical diagnosis and management in PD and the conduct of clinical studies. However, the large-scale, high-dimensional character of the data captured by these wearable sensors requires sophisticated signal processing and machine-learning algorithms to transform it into scientifically and clinically meaningful information. Such algorithms that "learn" from data have shown remarkable success in making accurate predictions for complex problems in which human skill has been required to date, but they are challenging to evaluate and apply without a basic understanding of the underlying logic on which they are based. This article contains a nontechnical tutorial review of relevant machine-learning algorithms, also describing their limitations and how these can be overcome. It discusses implications of this technology and a practical road map for realizing the full potential of this technology in PD research and practice. © 2016 International Parkinson and Movement Disorder Society.

Semicarbazide-sensitive amine oxidase (SSAO) inhibition ameliorates kidney fibrosis in a unilateral ureteral obstruction murine model.

Semicarbazide-sensitive amine oxidase (SSAO) is an enzyme known for its dual function in mediating inflammation and reactive oxygen species production. However, the role of SSAO inhibitors in limiting kidney fibrosis is unclear. We aimed to determine the effectiveness of a SSAO inhibitor (SSAOi; PXS4728A) as an antifibrotic agent using a 7-day unilateral ureteric obstruction (UUO) model of acute kidney fibrosis in 6- to 8-wk-old mice. The experimental groups were 1) Sham operated; 2) UUO; 3) UUO+SSAOi (2 mg/kg); 4) UUO+telmisartan, an angiotensin receptor blocker (3 mg/kg); and 5) UUO+SSAOi+telmisartan. Kidney tissue was analyzed for histological evidence of tubulointerstitial fibrosis, nitrotyrosine staining, and mRNA expression of markers associated with fibrosis and inflammation. Kidney SSAO activity was determined by radiometric [(14)C]benzylamine methodology. Our results show that SSAOi effectively suppresses UUO-mediated SSAO activity. Extracellular matrix markers, namely, fibronectin, collagen IV protein, and nitrotyrosine staining, were lower in UUO+SSAOi mice compared with untreated UUO mice. This was consistent with the attenuated mRNA expression of collagen IV and fibronectin. SSAOi effectively inhibited transforming growth factor-ß1 (TGF-ß1) and monocyte chemoattractant protein-1 (MCP-1) expression to a similar extent to that observed with telmisartan. Individually, SSAOi and telmisartan induced a reduction in interstitial leukocyte and macrophage accumulation. However, the combination of SSAOi and telmisartan was more effective at reducing inflammatory cell infiltration. These results demonstrate that SSAO inhibition significantly suppresses profibrotic and proinflammatory cytokine secretion, reduces oxidative stress, and limits inflammatory cell accumulation and extracellular matrix expression in an acute model of renal fibrosis.

Correction of Chiari malformation due to closure of a concomitant thoracic meningocele.

INTRODUCTION: Chiari malformations are characterized by hindbrain herniation. Historically, some types have been linked to neural tube defects, but the causal relationship between the two conditions is still unclear. CASE REPORT: We report on a full-term male neonate with a prenatally diagnosed posterior thoracic meningocele, whose MRI demonstrated Chiari malformation. The meningocele was closed in the second week of life. The Chiari-related symptoms rapidly improved following surgery. Postoperative MRI at 7 months of age showed ascent of the cerebellar tonsils to a normal position. DISCUSSION: This case suggests that the traction on the cerebellum by a fixed spinal cord may play a role in the pathogenesis of the multifaceted Chiari malformations.

Landmine Injury Resulting in Comminuted Lumbar Facet Fracture as a Cause of Lumbar Stenosis and Spondylolisthesis.

Lumbar facet fractures are rarely reported and have been linked to sports and spine surgery. We describe the case of a 77-year-old patient who sustained an injury from multiple landmine blasts during the Vietnam War. He had low back pain since that time, which was initially managed conservatively. However, the pain progressed over decades to severe neurogenic claudication that greatly restricted his quality of life. Neuroimaging revealed the presence of bone fragments impinging on the spinal canal at the L5/6 level (transitional anatomy) that resulted from a comminuted fracture of the lumbar facet at the inferior articular process. We performed an L5/6 decompressive laminectomy, with removal of these fragments, and posterior instrumented fusion, with substantial improvement in symptoms. This case illustrates a unique mechanism of lumbar facet fracture and the biomechanic origination, natural history, and optimal treatment of this entity. We expand on the spectrum of lumbosacral injuries associated with the combat blast injury that have only increased in prevalence in recent conflicts.

Robot-assisted deep brain stimulation of the centromedian nucleus of the thalamus for generalized epilepsy: targeting and operative video.

The centromedian (CM) nucleus of the thalamus is a promising target for a range of brain diseases including drug-resistant generalized and multifocal epilepsy. CM is highly connected to cortical and subcortical regions including frontoparietal/sensorimotor cortex, striatum, brainstem, and cerebellum, which are involved in some generalized epilepsy syndromes like Lennox-Gastaut syndrome (LGS). In this video, the authors describe their methodology for targeting CM for deep brain stimulation (DBS). Delineation of an optimal and consistent target will expand the efficacy of neuromodulation of CM in intractable epilepsy. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID245.

Combination endovascular and microsurgical treatment of partially thrombosed ruptured ICA terminus aneurysm, with common carotid artery to MCA bypass via saphenous vein graft and parent vessel sacrifice after coil embolization.

A 63-year-old woman presented with ruptured giant ICA terminus aneurysm, temporized with coil embolization and definitively treated with parent vessel sacrifice and high-flow bypass.

Cavernous venous malformations in and around the central nervous system. Part 1: Dural and extradural.

Cavernous-type malformations are venous lesions that occur in multiple locations throughout the body, and when present in the CNS, they have canonically been referred to as cavernomas, cavernous angiomas, and cerebral cavernous malformations. Herein all these lesions are referred to as "cavernous venous malformations" (CavVMs), which is congruent with the current International Society for the Study of Vascular Anomalies classification system. Even though histologically similar, depending on their location relative to the dura mater, these malformations can have different features. In Part 1 of this review, the authors discuss and review pertinent clinical knowledge with regard to CavVMs as influenced by anatomical location, starting with the dural and extradural malformations. They particularly emphasize dural CavVMs (including those in the cavernous sinus), orbital CavVMs, and spinal CavVMs. The genetic and histopathological features of CavVMs in these locations are reviewed, and commonalities in their presumed mechanisms of pathogenesis support the authors' conceptualization of a spectrum of a single disease entity. Illustrative cases for each subtype are presented, and the pathophysiological and genetic features linking dural and extradural to intradural CavVMs are examined. A new classification is proposed to segregate CavVMs based on the location from which they arise, which guides their natural history and treatment.

Cavernous venous malformations in and around the central nervous system. Part 2: Intradural.

Cavernous venous malformations (CavVMs) account for a spectrum of lesions with a shared pathogenesis. Their anatomical location dictates their clinical features and surgical treatment. Extradural and dura-based CavVMs were discussed in Part 1 of this review. In this part, intradural CavVMs are discussed, encompassing malformations growing within the intradural space without direct dural involvement. In addition to classic intra-axial CavVMs, cranial nerve CavVMs, intraventricular CavVMs, and intradural extramedullary spinal CavVMs are discussed in this group, given the similar natural history and specific management challenges. Herein the authors focus on critical clinical aspects of and surgical management of these malformations based on their location and discuss optimal surgical approaches at each of these anatomical locations with illustrative cases. The commonalities of the natural history and surgical management that are dictated by anatomical considerations lend to a new location-based taxonomy for classification of CavVMs.

Craniocervical dural arteriovenous fistula: Microsurgical clipping and technical nuances with ICG.

A 48-year-old male with progressive congestive myelopathy had a craniocvervical DAVF treated with surgical clipping using ICG to confirm solitary inflow.