Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course.

The "isomorphic subtype of diffuse astrocytoma" was identified histologically in 2004 as a supratentorial, highly differentiated glioma with low cellularity, low proliferation and focal diffuse brain infiltration. Patients typically had seizures since childhood and all were operated on as adults. To define the position of these lesions among brain tumours, we histologically, molecularly and clinically analysed 26 histologically prototypical isomorphic diffuse gliomas. Immunohistochemically, they were GFAP-positive, MAP2-, OLIG2- and CD34-negative, nuclear ATRX-expression was retained and proliferation was low. All 24 cases sequenced were IDH-wildtype. In cluster analyses of DNA methylation data, isomorphic diffuse gliomas formed a group clearly distinct from other glial/glio-neuronal brain tumours and normal hemispheric tissue, most closely related to paediatric MYB/MYBL1-altered diffuse astrocytomas and angiocentric gliomas. Half of the isomorphic diffuse gliomas had copy number alterations of MYBL1 or MYB (13/25, 52%). Gene fusions of MYBL1 or MYB with various gene partners were identified in 11/22 (50%) and were associated with an increased RNA-expression of the respective MYB-family gene. Integrating copy number alterations and available RNA sequencing data, 20/26 (77%) of isomorphic diffuse gliomas demonstrated MYBL1 (54%) or MYB (23%) alterations. Clinically, 89% of patients were seizure-free after surgery and all had a good outcome. In summary, we here define a distinct benign tumour class belonging to the family of MYB/MYBL1-altered gliomas. Isomorphic diffuse glioma occurs both in children and adults, has a concise morphology, frequent MYBL1 and MYB alterations and a specific DNA methylation profile. As an exclusively histological diagnosis may be very challenging and as paediatric MYB/MYBL1-altered diffuse astrocytomas may have the same gene fusions, we consider DNA methylation profiling very helpful for their identification.

First report of postoperative intracranial Weeksella virosa infection.

A 49-year-old female underwent multiple craniotomies for resection of recurrent malignant meningiomata (WHO grade III). She re-presented with sepsis due to a ventricular empyema. The craniotomy wound was urgently debrided, and isolates of the gram-negative rod, Weeksella virosa, were identified on 16S PCR. This species is most commonly found as a genitourinary commensal. We present the first documented intracranial infection by Weeksella virosa and its successful treatment with oral ß-lactam antibiotics.

Personalizing Deep Brain Stimulation Therapy for Parkinson's Disease With Whole-Brain MRI Radiomics and Machine Learning.

Background Deep brain stimulation (DBS) is a well-recognised treatment for advanced Parkinson's disease (PD) patients. Structural brain alterations of the white matter can correlate with disease progression and act as a biomarker for DBS therapy outcomes. This study aims to develop a machine learning-driven predictive model for DBS patient selection using whole-brain white matter radiomics and common clinical variables. Methodology A total of 120 PD patients underwent DBS of the subthalamic nucleus. Their therapy effect was assessed at the one-year follow-up with the Unified Parkinson's Disease Rating Scale-part III (UPDRSIII) motor component. Radiomics analysis of whole-brain white matter was performed with PyRadiomics. The following machine learning methods were used: logistic regression (LR), support vector machine, naïve Bayes, K-nearest neighbours, and random forest (RF) to allow prediction of clinically meaningful UPRDSIII motor response before and after. Clinical variables were also added to the model to improve accuracy. Results The RF model showed the best performance on the final whole dataset with an area under the curve (AUC) of 0.99, accuracy of 0.95, sensitivity of 0.93, and specificity of 0.97. At the same time, the LR model showed an AUC of 0.93, accuracy of 0.88, sensitivity of 0.84, and specificity of 0.91. Conclusions Machine learning models can be used in clinical decision support tools which can deliver true personalised therapy recommendations for PD patients. Clinicians and engineers should choose between best-performing, less interpretable models vs. most interpretable, lesser-performing models. Larger clinical trials would allow to build trust among clinicians and patients to widely use these AI tools in the future.

Human Immunodeficiency Virus in Adults Undergoing Surgery for Brain Tumors.

Introduction Early diagnosis and treatment of human immunodeficiency virus (HIV) can improve outcomes. HIV prevalence in brain tumor patients and the impact of an HIV diagnosis on patient outcomes are poorly understood. Materials and methods This was a prospective study of 100 consecutive brain tumor patients admitted to a Greater London Tertiary Neurosurgical center for surgery between January 2021 and October 2021. All brain tumors were included. All patients have appropriately consented. Blood was tested to detect HIV antibodies and p24 antigen. Outcomes were noted at 30-day postoperative follow-up. Results In 100 patients, there was one case of a known HIV-positive, seronegative patient, and no new diagnosis was made, giving a prevalence of 1%. The mean age of patients included was 61.7 ± 13.3, with 57% female. The patient with HIV suffered a postoperative pseudomonas infection, requiring intensive care, additional surgery, and antibiotics. This resulted in an inpatient stay of 55 days - an increase of 274% compared to patients without HIV. Conclusion Literature regarding the prevalence of HIV in glioma patients is inconclusive, of low quality, and primarily out-of-date. Our literature search found no similar study of rates of HIV in brain tumor patients in the United Kingdom. The incidence of both HIV and brain tumors, particularly glioblastomas, is low.

Treatment of Nocardial Brain Abscess in a Patient With Systemic Lupus Erythematosus and Idiopathic Thrombocytopenic Purpura: Case Report and a Review of the Literature.

Brain abscesses due to Nocardia species account for 1-2% of all cerebral abscesses, often in immunosuppressed individuals, with a mortality three times higher than other cerebral abscesses. Early diagnosis and management are vital for good outcomes. We report a case of a right frontal Nocardia brain abscess in an immunosuppressed 38-year-old female. She presented with headaches, confusion, memory deficits, and personality change. She remained systemically well, with normal inflammatory markers. She underwent two open surgical drainages, with excision of the abscess wall. She made an excellent recovery with minimal edema and no contrast enhancement on imaging at eight weeks postoperatively. Management of Nocardia brain abscess includes a prompt diagnosis with direct microscopic examination and initiation of correct antibiotic therapy for good outcomes. We recommend open surgical resection, including excision of the abscess wall, followed by long-term antimicrobial therapy, to enhance the rate of recovery.

Pneumocephalus and air travel: an experimental investigation on the effects of aircraft cabin pressure on intracranial pressure.

This study investigates the effects of aircraft cabin pressure on intracranial pressure (ICP) elevation of a pneumocephalus patient. We propose an experimental setup that simulates the intracranial hydrodynamics of a pneumocephalus patient during flight. It consists of an acrylic box (skull), air-filled balloon [intracranial air (ICA)], water-filled balloon (cerebrospinal fluid and blood) and agarose gel (brain). The cabin was replicated using a custom-made pressure chamber. The setup can measure the rise in ICP during depressurization to levels similar to that inside the cabin at cruising altitude. ΔICP, i.e. the difference between mean cruising ICP and initial ICP, was found to increase with ICA volume and ROC. However, ΔICP was independent of the initial ICP. The largest ΔICP was 5 mmHg; obtained when ICA volume and ROC were 20 ml and 1,600 ft/min, respectively. The postulated ICA expansion and the subsequent increase in ICP in pneumocephalus patients during flight were successfully quantified in a laboratory setting. Based on the quantitative and qualitative analyses of the results, an ICA volume of 20 ml and initial ICP of 15 mmHg were recommended as conservative thresholds that are required for safe air travel among pneumocephalus patients. This study provides laboratory data that may be used by doctors to advise post-neurosurgical patients if they can safely fly.

Comparison of posterior subthalamic area deep brain stimulation for tremor using conventional landmarks versus directly targeting the dentatorubrothalamic tract with tractography.

OBJECTIVE: To compare posterior subthalamic area deep brain stimulation (PSA-DBS) performed in the conventional manner against diffusion tensor imaging and tractography (DTIT)-guided lead implantation into the dentatorubrothalamic tract (DRTT). PATIENTS AND METHODS: Double-blind, randomised study involving 34 patients with either tremor-dominant Parkinson's disease or essential tremor. Patients were randomised to Group A (DBS leads inserted using conventional landmarks) or Group B (leads guided into the DRTT using DTIT). Tremor (Fahn-Tolosa-Marin) and quality-of-life (PDQ-39) scores were evaluated 0-, 6-, 12-, 36- and 60-months after surgery. RESULTS: PSA-DBS resulted in marked tremor reduction in both groups. However, Group B patients had significantly better arm tremor control (especially control of intention tremor), increased mobility and activities of daily living, reduced social stigma and need for social support as well as lower stimulation amplitudes and pulse widths compared to Group A patients. The better outcomes were sustained for up to 60-months from surgery. The active contacts of Group B patients were consistently closer to the centre of the DRTT than in Group A. Speech problems were more common in Group A patients. CONCLUSION: DTIT-guided lead placement results in better and more stable tremor control and fewer adverse effects compared to lead placement in the conventional manner. This is because DTIT-guidance allows closer and more consistent placement of leads to the centre of the DRTT than conventional methods.

Pathological crying caused by high-frequency stimulation in the region of the caudal internal capsule.

BACKGROUND: Pathological crying has been rarely reported after deep brain stimulation. The exact neural substrate is unknown, but it is often assumed that pathological crying and the pseudobulbar syndrome result from disturbances of a common neural pathway. DESIGN: Case report. SETTING: Tertiary referral center for neurosurgery. Patient A 48-year-old woman with advanced Parkinson disease who received bilateral implantation of deep brain stimulators in her subthalamic nuclei. RESULTS: Stimulation in the region of the caudal internal capsule resulted in pathological crying but no other features of pseudobulbar palsy. CONCLUSIONS: At least 1 of the pathways controlling crying passes through the region of the caudal internal capsule, and this pathway is distinct from those involved with laughter and nonemotional facial movements. Moreover, different stimulation frequencies may elicit either crying or anxiety but not both.

Focal childhood-onset, action induced primary hip dystonia treated with pallidal deep brain stimulation.

Focal proximal lower limb dystonias are rare. Unlike the adult form, focal lower limb dystonias in children usually become generalized. The condition is often unrecognized and the patient often receives orthopedic or psychiatric treatment for years before the diagnosis eventually made. Previously reported cases of isolated lower limb dystonias have been managed nonsurgically. We present a case of a childhood-onset action-induced primary hip dystonia that has remained focal even in adulthood and which responded successfully to pallidal deep brain stimulation. Additionally, our results suggest that neurons representing the leg lie within the most ventral aspect of the globus pallidus interna.

Isolated chorda tympani injury following petrous temporal fracture.

Petrous temporal fractures account for nearly a fifth of all skull base fractures but are associated with taste disturbance in only 2% of cases. Chorda tympani injuries almost invariably occur in association with other nerve injuries. We present a rare case of an isolated chorda tympani injury associated with a petrous temporal fracture. Our observations suggest that the gustatory fibres in this nerve are segregated into groups subserving different taste modalities.

Is There An Optimal Time for Performing Cranioplasties? Results from a Prospective Multinational Study.

BACKGROUND: The optimal timing of cranioplasty remains uncertain. OBJECTIVE: We hypothesized that the risk of infections after primary cranioplasty in adult patients who underwent craniectomies for non-infection-related indications are no different when performed early or delayed. We tested this hypothesis in a prospective, multicenter, cohort study. METHODS: Data were collected prospectively from 5 neurosurgical centers in the United Kingdom, Malaysia, Singapore, and Bangladesh. Only patients older than 16 years from the time of the non-infection-related craniectomy were included. The recruitment period was over 17 months, and postoperative follow-up was at least 6 months. Patient baseline characteristics, rate of infections, and incidence of hydrocephalus were collected. RESULTS: Seventy patients were included in this study. There were 25 patients in the early cranioplasty cohort (cranioplasty performed before 12 weeks) and 45 patients in the late cranioplasty cohort (cranioplasty performed after 12 weeks). The follow-up period ranged between 16 and 34 months (mean, 23 months). Baseline characteristics were largely similar but differed only in prophylactic antibiotics received (P = 0.28), and primary surgeon performing cranioplasty (P = 0.15). There were no infections in the early cranioplasty cohort, whereas 3 infections were recorded in the late cohort. This did not reach statistical significance (P = 0.55). CONCLUSIONS: Early cranioplasty in non-infection-related craniectomy is relatively safe. There does not appear to be an added advantage to delaying cranioplasties more than 12 weeks after the initial craniectomy in terms of infection reduction. There was no significant difference in infection rates or risk of hydrocephalus between the early and late cohorts.

The Impact of Deep Brain Stimulation on Sleep and Olfactory Function in Parkinson's Disease.

OBJECTIVE: Relatively little is known about the effects of deep brain stimulation on non-motor symptoms. The aim of this pilot study was to assess the impact of deep brain stimulation on sleep and olfactory function in Parkinson's disease. METHODS: Subjective sleep quality and olfactory testing were performed on 11 consecutive Parkinson's disease patients (eight men and three women) undergoing bilateral subthalamic nucleus stimulation. All patients consented to undergo clinical assessments prior to the procedure, and at regular intervals afterwards. RESULTS: Subjective sleep quality improved at six months following deep brain stimulation and this benefit was sustained in the majority of patients at later follow-up assessments. There was no significant change in olfactory function following deep brain stimulation. CONCLUSIONS: In addition to having beneficial effects on motor function and quality of life, bilateral subthalamic nucleus stimulation improves subjective sleep quality in Parkinson's disease.

Axotomized motoneurons can be rescued from cell death by peripheral nerve grafts: the effect of donor age.

Injury to neonatal nerves, unlike adult nerves, results in poor regeneration and extensive motoneuron death. We examined whether exposure to a more mature nerve environment could rescue axotomized motoneurons following neonatal injury. The sciatic nerve in 1 hindlimb of 3-day-old (P3) rats was transected and the cut end sutured to a nerve graft taken from donor rats, which ranged between P3 and P21. The extent of motoneuron survival and axon regeneration was established 7 days later. Since integrins play an important role in regeneration, we also examined the effect of manipulating integrin binding in nerve grafts. Following axotomy at P3 and implantation of nerve grafts from 3-day-old rats, approximately 38% of motoneurons survived. In contrast, grafts from rats aged 5 days and older resulted in an improvement in regeneration, and over 70% of motoneurons survived. This survival-promoting effect of P5 grafts was prevented by blocking beta1-integrins. In contrast, increasing beta1-integrin levels in grafts from P3 rats dramatically increased motoneuron survival. Thus, following neonatal nerve injury, exposure to a more mature nerve environment significantly increases motoneuron survival, an effect that is dependent upon beta1-integrin signaling. Therefore, pharmacological upregulation of beta1-integrins may significantly improve the outcome of neonatal nerve injuries.