The Golden Ratio (Phi, or Φ = 1.618…) is a potentially unifying quantity of structure and function in nature, as best observed in phyllotactic patterns in plants. For centuries, Φ has been identified ...in human anatomy, and in recent decades, Φ has been identified in human physiology as well. The anatomy and evolution of the human skull have been the focus of intense study. Evolving over millenia, the human skull embodies an elegant harmonization of structure and function. The authors explored the dimensions of the neurocranium by focusing on the midline calvarial perimeter between the nasion and inion (nasioiniac arc) and its partition by bregma into 2 sub-arcs. The authors studied 100 human skulls and 70 skulls of 6 other mammalian species and calculated 2 ratios: 1) the nasioiniac arc divided by the parieto-occipital arc (between bregma and inion), and 2) the parieto-occipital arc divided by the frontal arc (between nasion and bregma). The authors report that in humans these 2 ratios coincide (1.64 ± 0.04 and 1.57 ± 0.10) and approximate Φ. In the other 6 mammalian species, these 2 ratios were not only different, but also unique to each species. The difference between the ratios showed a trend toward convergence on Φ correlating with species complexity. The partition of the nasioiniac arc by bregma into 2 unequal arcs is a situation analogous to that of the geometrical division of a line into Φ. The authors hypothesize that the Golden Ratio (Φ) principle, documented in other biological systems, may be present in the architecture and evolution of the human skull.
To compare functional and seizure outcomes in children with vascular and dysplastic etiologies of cerebral palsy and medically intractable epilepsy following functional hemispherotomy or anatomic ...hemispherectomy.
Consecutive patients satisfying inclusion criteria from 07/01/2015 to 12/01/2019 were reviewed for demographic data and seizure (Engel classification) and functional (Functional Independence Measure for Children) outcomes.
After a mean follow-up of 2 years 8 months (1 year 2 months), 11 of 18 patients achieved post-operative seizure freedom without significant difference between vascular (5/7) and dysplastic (6/11) etiologies (P = 0.64). Functional assessments were completed for 15 of 18 of subjects, split comparably between groups. Mean change in the Functional Independence Measure for Children from pre-operative baseline to inpatient rehabilitation admission (vascular, −35.3 13.2; malformation of cortical development{MCD}, −34.5 25.0; P = 0.69), inpatient rehabilitation admission to discharge (vascular, 18.7 9.0; MCD, 20.8 11.4; P = 0.60), and pre-operative evaluation to clinic follow-up (vascular, −7.6 9.7; MCD, −3.6 19.3; P = 0.61) did not differ between groups.
Quantitative functional and seizure outcomes following functional hemispherotomy or anatomic hemispherectomy did not differ significantly between vascular and dysplastic etiologies of cerebral palsy and medically intractable epilepsy in this study. Hemispheric surgery resulted in minor functional declines from baseline following comprehensive multidisciplinary therapy.
Rasmussen encephalitis (RE) is a rare childhood neurological disease characterized by progressive unilateral loss of function, hemispheric atrophy and drug-resistant epilepsy. Affected brain tissue ...shows signs of infiltrating cytotoxic T-cells, microglial activation, and neuronal death, implicating an inflammatory disease process. Recent studies have identified molecular correlates of inflammation in RE, but cell-type-specific mechanisms remain unclear. We used single-nucleus RNA-sequencing (snRNA-seq) to assess gene expression across multiple cell types in brain tissue resected from two children with RE. We found transcriptionally distinct microglial populations enriched in RE compared to two age-matched individuals with unaffected brain tissue and two individuals with Type I focal cortical dysplasia (FCD). Specifically, microglia in RE tissues demonstrated increased expression of genes associated with cytokine signaling, interferon-mediated pathways, and T-cell activation. We extended these findings using spatial proteomic analysis of tissue from four surgical resections to examine expression profiles of microglia within their pathological context. Microglia that were spatially aggregated into nodules had increased expression of dynamic immune regulatory markers (PD-L1, CD14, CD11c), T-cell activation markers (CD40, CD80) and were physically located near distinct CD4+ and CD8+ lymphocyte populations. These findings help elucidate the complex immune microenvironment of RE.
INTRODUCTION:
MRI-guided laser interstitial thermal therapy for corpus callosotomy (MRIgLITT-CC) offers palliation of intractable drop events and atonic, tonic, and generalized tonic-clonic seizures.
...METHODS:
This multi-institutional retrospective study included pediatric patients with medically intractable epilepsy undergoing MRIgLITT-CC. Surgical details, post-operative radiographic results, and need for additional epilepsy surgery were recorded. Percent coverages of the intended ablation zones (anterior, complete, or posterior corpus callosotomy) were estimated from MRI. Data were summarized using descriptive statistics and compared using Chi-square tests.
RESULTS:
A total of 27 subjects (18 male, 9 female) with mean age 13 years +/- 5 years (4 years, 21 years) underwent planned complete (13, 48%), anterior (11, 41%), or posterior (3, 11%) MRIgLITT-CC. Planned complete MRIgLITT-CC entailed 2 (1/13, 8%), 3 (6/13, 46%), or 4 (6/13, 46%) trajectories with 100% (8/13, 62%) or 95-99% (5/13, 38%) coverage of the planned callosal ablation zone. Anterior MRIgLITT-CC cases included 1 (1/11, 9%), 2 (8/11, 73%), or 3 (1/11, 9%) trajectories to achieve 100% (7/11, 64%), 95-99% (2/11, 18%), 90-94% (1/11, 9%), or <90% (1/11, 9%) coverage of the planned callosal ablation zone. There were no significant differences in percent coverage of intended ablation zone as a function of trajectory number (p = 0.6). Three subjects (11%) required repeat callosal surgery while four subjects (15%) underwent additional vagus nerve stimulator (VNS) insertion during clinic follow-up (mean 11.7 months +/-10.6 months; 0.4 months, 37.1 months). The need for repeat callosal surgery differed significantly between subjects with 100% and less than 100% ablation coverage (0/16 vs. 3/11, p = 0.03).
CONCLUSION:
In this multi-institutional study, MRIgLITT-CC yielded 100% or 95-99% coverage of the intended callosal ablation zone in most subjects. Trajectory variation between centers did not impact percent coverage of the intended ablation zone. Few subjects required repeat callosal surgery, particularly those with less than 100% ablation zone coverage, or additional VNS insertion.
Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system (CNS) with synchronous or metachronous extra-CNS disease is a rare childhood malignancy with a dismal prognosis.
We report a ...7-week-old female with metastatic AT/RT and synchronous malignant rhabdoid tumor of the kidney who received an intensive multimodal approach combining surgical resection, intrathecal chemotherapy, and high-dose chemotherapy with autologous peripheral blood stem cell transplant (PBSCT). She is currently 24 months old without any evidence of disease. In addition, we completed an extensive literature review of cases with CNS AT/RT and synchronous or metachronous extra-CNS primary tumors. To date, 31 pediatric cases have been reported, and the median overall-survival was 6 months after diagnosis. The only 3 survivors received autologous PBSCT, and 2 of these patients had complete resection of their CNS tumor.
The rarity of CNS AT/RT with extra-CNS primary disease and the lack of standard treatment contribute to its reported dismal prognosis. We report a case of a long-term survivor with metastatic AT/RT and synchronous extra-CNS primary tumor. Maximal surgical resection, intrathecal chemotherapy, and consolidative autologous PBSCT may improve prognosis and avoid radiation.
Many genetic studies of intractable epilepsy in pediatric patients primarily focus on inherited, constitutional genetic deficiencies identified in patient blood. Recently, studies have revealed ...somatic mosaicism associated with epilepsy in which genetic variants are present only in a subset of brain cells. We hypothesize that tissue-specific, somatic mosaicism represents an important genetic etiology in epilepsy and aim to discover somatic alterations in epilepsy-affected brain tissue.
We have pursued a research study to identify brain somatic mosaicism, using next-generation sequencing (NGS) technologies, in patients with treatment refractory epilepsy who have undergone surgical resection of affected brain tissue.
We used an integrated combination of NGS techniques and conventional approaches (radiology, histopathology, and electrophysiology) to comprehensively characterize multiple brain regions from a single patient with intractable epilepsy. We present a 3-year-old male patient with West syndrome and intractable tonic seizures in whom we identified a pathogenic frameshift somatic variant in
, present at a range of variant allele fractions (4.2%-19.5%) in 12 different brain tissues detected by targeted sequencing. The proportion of the
variant correlated with severity and location of neurophysiology and neuroimaging abnormalities for each tissue.
Our findings support the importance of tissue-based sequencing and highlight a correlation in our patient between
variant allele fractions and the severity of epileptogenic phenotypes in different brain tissues obtained from a grid-based resection of clinically defined epileptogenic regions.
Spinal column metastatic disease clinically affects thousands of cancer patients every year. Local chemotherapy represents a new option in the treatment of metastatic disease of the spine. Despite ...the clinical impact of metastatic spine disease, the literature currently lacks an accurate animal model for the effective dosing of local chemotherapeutic agents within the vertebral column.
Female Fischer 344 rats, weighing 150 to 200 g each, were used in this study. After induction of anesthesia, a transabdominal approach to the ventral vertebral body of L-6 was performed. A small hole was drilled and 5 microL of ReGel (blank polymer), OncoGel (paclitaxel and ReGel) 1.5%, OncoGel 3.0%, or OncoGel 6.0% were immediately injected to determine drug toxicity. Based on these results, efficacy studies were performed by intratumoral injection of 5 microL of ReGel, OncoGel 3.0%, and OncoGel 6.0% on Day 6 in a CRL- 1666 breast adenocarcinoma metastatic spine tumor model. Hind limb function was tested pre- and postoperatively using the Basso-Beattie-Bresnahan rating scale. Histological analysis of the spinal cord and vertebral column was performed when the animal died or was killed.
There were no signs of toxicity observed in association with any of the agents under study. No increased benefit was seen in the blank polymer group compared with the control group (tumor only). OncoGel 3.0% and OncoGel 6.0% were effective in delaying the onset of paralysis in the respective study groups.
These findings demonstrate the potential benefit of OncoGel in cases of subtotal resections of metastatic spinal column tumors. OncoGel 6.0% is the most efficacious drug concentration and offers the best therapeutic option in this experimental model. These results provide promise for the development of local chemotherapeutic means to treat spinal metastases.
The aim of this study was to examine the feasibility and safety of ventriculoperitoneal (VP) shunt placement using a periumbilical approach for distal peritoneal access. By using this minimally ...invasive approach, the authors hypothesized that the cosmetic outcomes would be better than could be achieved by using a traditional minilaparotomy and that clinical results would be comparable.
A periumbilical approach was used for distal catheter insertion during a first-time VP shunt placement in 20 patients (8 males and 12 females). Median age at time of surgery was 3.0 months (range 7 days-11.9 years) and mean follow-up time was 17.8 months (range 1.2-28.0 months). The median weight of the patients was 3.99 kg (range 1.95-57.0 kg). A single incision was made along the natural crease inferior to the umbilicus. The linea alba was exposed and a 1-mm incision made while the patient was temporarily held in a Valsalva maneuver. A peritoneal trocar was then inserted through the fascial incision and the distal catheter was passed into the peritoneal space.
The incision line in all patients healed well, did not require operative revision, and was described as minimally visible by the patients' families. Mean operative time was 35 minutes. Eight patients required revision surgery. One distal failure occurred when the distal shunt tubing retracted and became coiled in the neck; this was repaired by conversion to a minilaparotomy for distal replacement. There was 1 shunt infection (5%) requiring shunt removal and replacement. One patient had significant skin thinning around the valve and proximal catheter, which required replacement of the entire shunt system, and another patient underwent a conversion to a ventriculoatrial shunt due to poor peritoneal absorption. In the remaining 4 patients who required operative revision, the peritoneal portion of the shunt was not involved.
The periumbilical approach for peritoneal access during VP shunt placement is technically feasible, has low infection rates, and has cosmetically appealing results. It may be considered as an alternative option to standard VP shunt placement techniques.
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