Rare Pediatric Cerebellar High-Grade Gliomas Mimic Medulloblastomas Histologically and Transcriptomically and Show p53 Mutations.

Pediatric high-grade gliomas (HGG) of the cerebellum are rare, and only a few cases have been documented in detail in the literature. A major differential diagnosis for poorly differentiated tumors in the cerebellum in children is medulloblastoma. In this study, we described the histological and molecular features of a series of five pediatric high-grade gliomas of the cerebellum. They actually showed histological and immunohistochemical features that overlapped with those of medulloblastomas and achieved high scores in NanoString-based medulloblastoma diagnostic assay. Methylation profiling demonstrated these tumors were heterogeneous epigenetically, clustering to GBM_MID, DMG_K27, and GBM_RTKIII methylation classes. MYCN amplification was present in one case, and PDGFRA amplification in another two cases. Interestingly, target sequencing showed that all tumors carried TP53 mutations. Our results highlight that pediatric high-grade gliomas of the cerebellum can mimic medulloblastomas at histological and transcriptomic levels. Our report adds to the rare number of cases in the literature of cerebellar HGGs in children. We recommend the use of both methylation array and TP53 screening in the differential diagnoses of poorly differentiated embryonal-like tumors of the cerebellum.

Utilization, surgical populations, centers, coverages, regional balance, and their influential factors of deep brain stimulation for Parkinson's disease: a large-scale multicenter cross-sectional study from 1997 to 2021.

BACKGROUND: Deep brain stimulation (DBS) is an emerging and effective therapy for Parkinson's disease (PD). However, little is known about its utilization, surgical populations, centers, coverages, regional balance, and influential factors. MATERIALS AND METHODS: This large-scale multicenter cross-sectional study was conducted using a national census involving 74 Chinese centers. National DBS populations and centers for PD were investigated in 1997-2021, and regional sociodemographic features, surgical populations, related resources, and insurance policies in 2020 were explored. RESULTS: Since the first DBS surgery in 1997, a total of 38 122 PD patients from 349 centers underwent DBS by 2021, which covered 1.118% (1.108-1.129) of patients and 0.954% (0.933-0.976) of centers. Significant upward trends in the annual surgical population and coverages were observed with rapid climbing rates, while the annual surgical centers and their coverage showed two growth peaks in 2002-2006 and 2010-2018, correlating with clinical approvals and new technologies. A total of 103 070 (51 165-154 975) PD patients [2.088% (1.351-2.825) coverage] and 603 (72-1134) centers [1.356% (1.126-1.586) coverage] are predicted to conduct DBS by 2030. The new remotely programmed DBS technology was recoded as the first application in 2015 and rapidly increased to 2771 (47.39%, 46.11-48.67) patients with 10 507 remote programming sessions annually in 2021. Provinces in the eastern and central regions had better economic status, more surgical patients, higher insurance affordability, and more related resources than those in the western and northeastern regions. Higher gross domestic product per capita ( ß =5.041, 3.324-6.758 and ß =0.008, 0.004-0.012; all P <0.001) and more functional neurosurgery doctors ( ß =3.596, 0.353-6.839; P =0.031 and ß =0.010, 0.002-0.017; P =0.013) positively influenced surgical populations and coverages, while higher insurance levels ( ß =128.888, 64.702-193.075; P <0.001) positively influenced surgical coverages. CONCLUSION: Although surgical populations, centers, and coverages of DBS for PD have rapidly improved and are predicted to show future increases, this is still insufficient to cover potential eligible patients. Regionally imbalanced health coverage should be given attention to promote coordinated development.

Intracranial nasofrontal dermoid cyst and a hair in the nose tip without a sinus tract identified with single-staged combined approach excision done.

This is the first reported case of intracranial nasofrontal dermoid without sinus tract, with complete excision done in single-staged combined approach frontal craniotomy and open rhinoplasty, and satisfactory nasal reconstruction.

Pre-operative cognitive burden as predictor of motor outcome following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

INTRODUCTION: The interrelationship between neurocognitive impairments and motor functions was observed in patients with advanced Parkinson's disease (PD). This study was conducted to identify pre-operative neurocognitive and clinical predictors of short-term motor outcome following subthalamic nucleus deep brain stimulation (STN-DBS). METHODS: All consecutive PD patients who were eligible for bilateral STN-DBS from 2009 to 2019 were evaluated before and at 1 year following surgery. Standard motor evaluation and neurocognitive tests including global cognition, memory, executive functions (attention and category fluency), confrontational speech, visuospatial abilities, and mood were conducted at baseline. The post-operative STN-DBS effects were assessed at 1 year following the surgery. Multiple regression analysis was applied to identify baseline independent predictors of post-operative STN-DBS effect. RESULTS: A total of 82 patients were analyzed. It was found that younger age at operation, higher levodopa responsiveness at baseline based on UPDRS-III total score, and better baseline verbal delayed memory and category fluency predicted post-operative motor outcome at 1 year following STN-DBS (F = 9.639, p < 0.001, R2 = .340). CONCLUSION: Our findings demonstrated the role of baseline cognitive burden, especially cognitive processes related to frontostriatal circuits, was significant clinical predictors of short-term motor outcomes following STN-DBS. Profile analysis of neurocognitive functions at baseline is recommended.

Deep brain stimulation in a young child with GNAO1 mutation - Feasible and helpful.

Background: GNAO1 is an emerging disorder characterized with hypotonia, developmental delay, epilepsy, and movement disorder, which can be potentially life threatening during acute exacerbation. In the USA, deep brain stimulation (DBS) has been licensed for treating children with chronic, treatment-resistant primary dystonia, who are 7 years old or older. Case Description: A 4-year-old girl diagnosed to have GNAO1-related dyskinesia and severe global developmental delay. She had severe dyskinesia precipitated by intercurrent infection, requiring prolonged intensive care for heavy sedation and related complications. Her dyskinesia improved dramatically after DBS implantation. Technical difficulties and precautions of DBS in preschool children were discussed. Conclusion: DBS should be considered early in the treatment of drug-resistant movement disorders in young children with GNAO1, especially after dyskinetic crisis, as they tend to recur. Presurgical counseling to parents and close monitoring of complications is also important in the process.

Radiological Latency in Pineal Germinoma: A Case Report and Literature Review.

Suprasellar germinomas can present with non-diagnostic, or even normal results on imaging. The spectrum of reported cases ranges from normal imaging, thickened pituitary stalks, to discrete tumour growths. This similar phenomenon is less commonly seen in the pineal region, or bifocal germinomas, and the literature is sparse with only a few case series or reports mentioning a similar presentation of signs and symptoms preceding radiological evidence of diagnosis. We report a case of pineal germinoma presenting with dorsal midbrain syndrome with no evidence of tumour growth on initial imaging despite symptoms. For patients presenting with this clinical radiological latent period, follow-up imaging is useful to identify interval development of germinomas. This applies to patients with dorsal midbrain syndrome, or even other unexplained ophthalmoplegia, as the initial sign of pineal region germinoma, despite normal imaging.

Case Report: Novel Biallelic Variants in the COL18A1 Gene in a Chinese Family With Knobloch Syndrome.

Knobloch syndrome is a rare collagenopathy characterized by severe early onset myopia, retinal detachment, and occipital encephalocele with various additional manifestations due to biallelic changes in the COL18A1 gene. Here we reported a Chinese family with two affected siblings presented with antenatal occipital encephalocele, infantile onset retinal detachment, and pronounced high myopia at early childhood. Quartet whole exome sequencing was performed in this family and identified that both siblings carried novel compound heterozygous variants in the COL18A1 gene (NM_001379500.1): the maternally inherited variant c.1222-1G>A at the consensus acceptor splice site of intron 8, and the paternally inherited frameshift variant c.3931_3932delinsT p.(Gly1311Serfs*25) in the last exon. Both patients had successful surgical treatment for the occipital encephalocele soon after birth. They had normal neurocognitive outcome and good general conditions examined at the age of 7 years old for the elder sister and 4 years old for the younger brother. The younger brother developed infantile onset retinal detachment at 7 months of age while the sister had high myopia without signs of retinal detachment until 7 years old. This report expands the phenotype and genotype spectrum of Knobloch syndrome with antenatal and postnatal findings.

Drug resistant epilepsy with mesial temporal sclerosis as possible late neurological complication in two AML survivors after stem cell transplantation.

•Mesial temporal sclerosis (MTS) is a potential late complication of hematological malignancies.•Seizures are usually drug resistant with MTS yet seizure freedom may be achieved by surgery.•Early evaluation for epilepsy surgery is warranted for drug resistant seizures due to AML.

Early versus Late Application of Subthalamic deep brain Stimulation to Parkinson's disease patients with motor complications (ELASS): protocol of a multicentre, prospective and observational study.

INTRODUCTION: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established surgical treatment for Parkinson's disease (PD). However, there is currently no consensus on the best timing for this surgery. The aim of our study is to compare the therapeutic efficacy of bilateral STN DBS in patients with PD with early and late motor complications. METHODS AND ANALYSIS: 200 patients with PD will be enrolled in this multicentre, prospective, observational study, and will be followed up for 4 years. Patients with PD who meet the criteria for STN DBS surgery will be allocated to either the early stimulation group or the late stimulation group based on the duration of their motor complications. The primary outcome will be changes in quality of life from baseline to 4 years, measured using the 39-item Parkinson's Disease Questionnaire Summary Index. The secondary outcomes include changes in motor function measured using Movement Disorder Society-revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, self-reported experiences of daily living measured using MDS-UPDRS Part I B and Part II, good 'on' time recorded by the patients using a diary and safety profile of both groups. ETHICS AND DISSEMINATION: The study received ethical approval from the Medical Ethical Committee of the First Affiliated Hospital, Sun Yat-sen University. The results of this study will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT01922388; Pre-results.

Phase I/II randomized controlled trial of autologous bone marrow-derived mesenchymal stem cell therapy for chronic stroke.

AIM: To examine the safety and efficacy of mesenchymal stem cell (MSC) therapy for intracerebral haemorrhage with neurological dysfunctions for a year. METHODS: MSC were ex vivo expanded from 29 mL (17-42 mL) autologous bone marrow. Patients were randomized to have two intravenous injections of autologous MSC or placebos in four weeks apart. Neurological functions and clinical outcomes were monitored before treatment and at 12th, 16th, 24th, 36th and 60th week upon completion of the treatment. RESULTS: A mean of 4.57 × 107 (range: 1.43 × 107-8.40 × 107) MSC per infusion was administered accounting to 8.54 × 105 (2.65 × 105-1.45 × 106) per kilogram body weight in two occasions. There was neither adverse event at time of administration nor sign of de novo tumour development among patients after monitoring for a year post MSC therapy. Neuro-restoration and clinical improvement in terms of modified Barthel index, functional independence measure and extended Glasgow Outcome Scale were evident among patients having MSC therapy compared to patients receiving placebos. CONCLUSION: Intravenous administration of autologous bone marrow-derived MSC is safe and has the potential of improving neurological functions in chronic stroke patients with severe disability.

Incidence and mortality of spontaneous subarachnoid hemorrhage in Hong Kong from 2002 to 2010: a Hong Kong hospital authority clinical management system database analysis.

BACKGROUND: Ninety-five percent of the Hong Kong population is Chinese, and no previous epidemiological study has focused on spontaneous subarachnoid hemorrhage (SAH) in Hong Kong. These data would have significant public health implications and can guide future resource allocations and service development in Hong Kong. The aim of this study was to investigate the local incidences of spontaneous SAH and 1-year mortality rates in Hong Kong, with the respective time trends in recent years. METHODS: Data from the Clinical Management System database of the Hong Kong Hospital Authority were used to examine the incidence of SAH and 1-year mortality rates among the Hong Kong population for the 2002-2010 period. Age-standardized incidence rates were calculated by the direct method using the standard population given in World Health Organization World Standard Population 2000-2025. RESULTS: Crude SAH incidences increased from 5.5 per 100,000 person-years in 2002 to 7.5 in 2010. Standardized SAH incidences increased from 4.1 per 100,000 person-years in 2002 to 5.6 in 2010. Crude 1-year mortality rates decreased from 43% in 2002 to 19% in 2010, and the standardized 1-year mortality rate decreased from 38% in 2002 to 19% in 2010. CONCLUSION: The Hong Kong SAH incidence was 7.5 per 100,000 person-years in 2010, and an increasing trend over time was noted. The 1-year mortality rates decreased from 43% in 2002 to 19% in 2010, in accordance with the worldwide trend.

Quantitative gait analysis of long-term locomotion deficits in classical unilateral striatal intracerebral hemorrhage rat model.

Gait analysis is a systematic collection of quantitative information on bodily movements during locomotion. Gait analysis has been employed clinically in stroke patients for their rehabilitation planning. In animal studies, gait analysis has been employed for the assessment of their locomotive disturbances in ischemic stroke, spinal cord injury and Parkinson's disease. The aims of the work reported here were to identify the gait parameters, collected from the computer-generated CatWalk System, that change after unilateral intracerebral hemorrhage (ICH) in the acute stage and long term up to 56 days post-ICH. The results showed that with the collagenase-induced unilateral striatal lesion, the rats displayed a significant contralateral decrease in print and maximum contact area and paw intensity, a diagonal increase in the stance duration of the left front and right hind paws, a significant decrease in the stride length of all four limbs, and foot pattern instability as reflected by the base of support, support on styles, and cadence. These deficits, including those in print area, stance and pressure, were demonstrated throughout the long-term period following ICH. The correlations between the gait parameters, lesion volume and asymmetrical forelimb use were also reported in this paper. This work has provided a systematic description on gait parameters in the classical striatal ICH model, which might become an essential assessment tool in future studies of pathophysiology and the development of novel treatments for experimental unilateral intracerebral hemorrhage with gait deficits.

Single burr hole rigid endoscopic third ventriculostomy and endoscopic tumor biopsy: what is the safe displacement range for the foramen of Monro?

OBJECTIVE: To investigate the safe displacement range of the foramen of Monro (FM) during single burr hole rigid endoscopic third ventriculostomy (ETV) and endoscopic tumor biopsy (ETB). METHODS: Eleven patients who received ETV/ETB for third ventricular and pineal region tumor were reviewed. The burr-hole location, the size, and the virtual displacement of FM were measured using neuronavigation software. RESULTS: Hydrocephalus was resolved, and no subsequent cerebrospinal fluid (CSF) shunting was required in all cases. Histological diagnosis was established in 11 patients. Ten cases received instrumental cognitive and memory assessment postoperatively. The results were within the normal range for eight cases. The mean burr-hole location was 1.7 cm anterior to coronal suture and 3 cm from the midline. The mean diameters of FM measured on the axial, coronal, sagittal, and views were 5.7, 7.8, and 5.6 mm, respectively. The mean virtual displacements of the FM were 1.9±2.0 mm (range=0-4.8) for ETV and 2.4±2.1 mm (range=0-5.5) for ETB. The maximum displacements were 4.8 mm anteriorly for ETV and 5.5 mm posteriorly for ETB. CONCLUSION: Single burr hole rigid ETV/ETB is likely to be safe within maximum FM displacements of 4.8 mm anterior for ETV and 5.5 mm posterior for ETB. Preoperative trajectory planning using neuronavigation software is recommended.

A 45-year-old woman with reversible bilateral hearing loss.

A 45-year-old woman complained of a progressive 2-month history of bilateral hearing impairment and diplopia on upward gaze. She had a history of a recurrent pineal region ganglioglioma with repeated tumor excision, adjuvant radiotherapy, and a ventriculo-peritoneal shunt performed 12 years prior. Subsequent imaging studies 6 years ago showed a pineal region cyst with progressive increase in size and a Rickham reservoir (Codman; Johnson & Johnson, Raynham, MA) was placed for percutaneous cyst fluid aspiration. The size of the cystic lesion remained static upon follow-up CT scans for several years.

Management outcome of NPC-related and non-NPC-related brain abscess in Hong Kong.

OBJECTIVES: (1) To review the patient profile, management outcome and prognostic factors of brain abscess; (2) To compare the neurological outcome of nasopharyngeal carcinoma (NPC)-related brain abscess with non-NPC related brain abscess. METHOD: Retrospective review of consecutive patients diagnosed (radiologically and/or microbiologically) with brain abscess in a regional neurosurgical center in Hong Kong over a nine year period. RESULTS: Fifty-four patients were recruited into this study. There were 37 male and 17 female patients. Eighteen (33%) patients had previous radiotherapy for nasopharyngeal carcinoma. Only 31 (57%) patients had fever on presentation. White cell count and/or C-reactive protein, was raised in 41 (76%) patients on admission. Surgical drainage was carried out in 49 (91%) patients, either by aspiration through a craniotomy, by drainage with corticotomy, or excision of the abscess. Abscess culture was positive in 45 (83%) patients. Common organisms isolated included Streptococcus species (35%) and Peptostreptococcus species (18%). Anaerobes were isolated in 50% of the NPC-related abscesses. The mean follow-up time was 34 months. At the 6 months interval, 24 (44%) patients had good recovery. Favorable outcome was achieved in 30 (55%) patients. NPC-related brain abscess was associated with unfavorable neurological outcome (33%, p = 0.04). There was also a trend towards higher in-patient mortality in patients with NPC-related brain abscess (22%, p = 0.08). CONCLUSION: Brain abscess carried a substantial morbidity and mortality despite aggressive surgical and medical treatment. Patients with NPC-related brain abscess had a higher mortality and unfavorable neurological outcome.

Neurological outcome in patients with traumatic brain injury and its relationship with computed tomography patterns of traumatic subarachnoid hemorrhage.

OBJECT: Traumatic subarachnoid hemorrhage (SAH) is a poor prognostic factor for traumatic brain injury. The authors aimed to further investigate neurological outcome among head injury patients by examining the prognostic values of CT patterns of traumatic SAH, in particular, the thickness and distribution. METHODS: The study was conducted using a database in a regional trauma center in Hong Kong. Data had been prospectively collected in consecutive trauma patients between January 2006 and December 2008. Patients included in the study had significant head injury (as defined by a head Abbreviated Injury Scale [AIS] score of 2 or more) with traumatic SAH according to admission CT. RESULTS: Over the 36-month period, 661 patients with significant head injury were admitted to the Prince of Wales Hospital in Hong Kong. Two hundred fourteen patients (32%) had traumatic SAH on admission CT. The mortality rate was significantly greater and a 6-month unfavorable outcome was significantly more frequent in patients with traumatic SAH. Multivariate analysis showed that the maximum thickness (mm) of traumatic SAH was independently associated with neurological outcome (OR 0.8, 95% CI 0.7-0.9) and death (OR 1.3, 95% CI 1.2-1.5) but not with the extent or location of hemorrhage. CONCLUSIONS: Maximum thickness of traumatic SAH was a strong independent prognostic factor for death and clinical outcome. Anatomical distribution per se did not affect clinical outcome.

Computed tomographic angiography and venography for young or nonhypertensive patients with acute spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: we compared the effectiveness of using computed tomographic angiography and venography (CTAV) with digital subtraction angiography (DSA) in young or nonhypertensive patients with acute spontaneous intracerebral hemorrhage. METHODS: we prospectively recruited 109 young (age between 18 and 45 years) or nonhypertensive patients with acute spontaneous intracerebral hemorrhage for this comparative study. All patients had CTAV using multidetector CT with 64 detectors. They were then scheduled to have catheter angiography the next day. Radiological data were collected for blinded analysis. RESULTS: DSA-positive pathologies causing hemorrhage were identified in 37 (33%) patients, which included cerebral arteriovenous malformation in 22 cases. The positive and negative predictive values of CTAV for DSA-positive pathologies causing hemorrhage were 97.3% (95% CI, 88.3%-99.9%) and 100% (95% CI, 95.9%-100%), respectively. CONCLUSIONS: CTAV was able to detect DSA-positive pathologies causing acute spontaneous intracerebral hemorrhage in young (age between 18 and 45 years) or nonhypertensive patients with high positive and negative predictive values.

The use of diffusion tensor tractography to measure the distance between the anterior tip of the Meyer loop and the temporal pole in a cohort from Southern China.

OBJECT: Anterior temporal lobe resection plus amygdalohippocampectomy can cause damage to the anterior portion of the optic radiation, also known as the Meyer loop, resulting in homonymous superior quadrantanopia. Magnetic resonance diffusion tensor tractography (DTT) of the Meyer loop can help in surgical planning. In this study, the distance of the anterior tip of the Meyer loop to the temporal lobe pole (ML-TP) in the Southern Chinese population was assessed. METHODS: The authors studied 16 Southern Chinese individuals (8 men and 8 women; mean age 45.6 years, range 21-60 years). Diffusion tensor images were obtained with a 3-T MR imaging system using a single-shot spin echo echo planar imaging sequence. Two trained operators, one neurosurgeon (Operator A) and one radiologist (Operator B), carried out the DTT analysis with software iPlan (BrainLAB) and FiberTrak (Philips). RESULTS: For the 32 temporal lobes, the intraclass correlation coefficient (ICC) of the 2 operators' results using iPlan was 0.96, while that of Operator A using iPlan and Operator B using FiberTrak was 0.75. The ICC of Operator B using iPlan and FiberTrak was 0.81. The ML-TP distance of normal lobes (30 lobes [2 lobes that previously underwent surgery were excluded]) was 36.3±5.5 mm (range 26.6-48.9 mm), 36.3±5.3 mm (range 26.8-48.2 mm), and 35.9±6.4 mm (range 20.8-48.4 mm) for Operator A using iPlan, Operator B using iPlan, and Operator B using FiberTrak, respectively (p>0.05). CONCLUSIONS: The 2 operators reached good agreement on ML-TP distance measurement using DTT. The DDT results can be more software dependent than operator dependent. The measurement with FiberTrak demonstrated larger range and standard deviation than measurement with iPlan.

Complications of deep brain stimulation: a collective review.

BACKGROUND: Since the first deep brain stimulation (DBS) performed for movement disorder more than a decade ago, DBS has become a standard operation for advanced Parkinson's disease. Its indications are expanding to areas of dystonia, psychiatric conditions and refractory epilepsy. Additionally, a new set of DBS-related complications have arisen. Many teams found a slow learning curve from this complication-prone operation. We would like to investigate complications arising from 100 DBS electrode insertions and its prevention. METHODS: We performed an audit in all DBS patients for operation-related complications in our centre from 1997 to 2008. Complications were classified into operation-related, hardware-related and stimulation-related. Operation-related complications included intracranial haemorrhages and electrode malposition. Hardware-related complications included fracture of electrodes, electrode migration, infection and erosion. Stimulation-related complications included sensorimotor conditions, psychiatric conditions and life-threatening conditions. RESULTS: From 1997 to the end of 2008, 100 DBS electrodes were inserted in 55 patients for movement disorders, mostly for Parkinsons disease (50 patients). There was one symptomatic cerebral haemorrhage (1%) and two electrode malpositions (2%). Meticulous surgical planning, use of microdriver and a reliable electrode anchorage device would minimise this group of complications. There were two electrode fractures, one electrode migration and one pulse-generator infection which contributed to the hardware-related complication rate of 5%. There were no sensorimotor or life-threatening complications in our group. However, three patients suffered from reversible psychiatric symptoms after DBS. CONCLUSION: DBS is, on the one hand, an effective surgical treatment for movement disorders. On the other hand, it is a complication-prone operation. A dedicated "Movement Disorder Team" consisting of neurologists, neurophysiologists, functional neurosurgeons, neuropsychologists and nursing specialists is essential. Liaison among team members in peri-operative periods and postoperative care is the key to avoiding complications and having a successful patient outcome.