Unilateral deep brain stimulation (DBS) of nucleus ventralis intermedius thalami (Vim) for the treatment of post-traumatic tremor in children: a multicentre experience.

PURPOSE: Deep brain stimulation (DBS) of nucleus ventralis intermedius thalami (Vim) is a validated technique for the treatment of essential tremor (ET) in adults. Conversely, its use for post traumatic tremor (PTT) and in paediatric patients is still debated. We evaluated the efficacy of Vim-DBS for lesional tremor in three paediatric patients with drug-resistant post-traumatic unilateral tremor. METHODS: We retrospectively collected data regarding three patients with unilateral tremor due to severe head injury, with no MRI evidence of basal ganglia lesions. The three patients underwent stereotactic frame-based robot-assisted DBS of Vim contralateral to the tremor side. RESULTS: Mean follow-up was 48 months (range: 36-60 months). Tremor was reduced in all patients with a better control of voluntary movements and improvement of functional status (mean FIM scale improvement + 7 points). No surgical complications occurred. CONCLUSION: Unilateral contralateral DBS of Vim could be efficacious in post-traumatic tremor, even in paediatric patients and should be offered in PTT drug-resistant patients.

Rare Onset of Erdheim-Chester Disease in Children and Young Adults: A Case Series and Review of the Literature.

INTRODUCTION: Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm that affects patients, predominantly males aged 40-70 years, with very heterogeneous clinical presentation and prognosis. In 2020, Goyal et al. proposed consensus recommendations for the management of patients with ECD, remarking on the exceptional presentation of the disease in the pediatric population. CASE PRESENTATION: The first patient, a 20-year-old male, underwent cervical laminectomy and partial removal of a cervical spine lesion, initially apparently consistent with cervical schwannomas. The second patient, a 9-year-old female, received surgery for an extra-axial lesion of the greater sphenoid wing, radiologically consistent with a meningioma. CONCLUSION: At present, 15 pediatric cases have been reported in the literature with involvement of the central nervous system, with no consensus on the diagnostic and therapeutic management, as Pegoraro et al. evidenced in their pediatric multicenter case series. The present article adds two new cases of ECD with onset in childhood and young adulthood, who received the diagnosis after neurosurgical procedures.

Clostridium septicum infection complicating Hemolytic-Uremic Syndrome: a case report and review of the literature.

Clostridium septicum (C. septicum) is a zoonotic bacillus found in 2.8% of healthy human stools. In humans, it can cause serious infections such as bacteremia, myonecrosis, and encephalitis by spreading through the bloodstream. Reports of Shiga toxin-producing Escherichia Coli-related hemolytic-uremic syndrome complicated by C. septicum superinfection are rare, likely because colonic microangiopathic lesions by Shiga toxin-producing Escherichia Coli facilitate bacterial dissemination. Only 13 cases of Shiga toxin-producing Escherichia Coli-related hemolytic-uremic syndrome with C. septicum superinfection have been reported to date, according to our litterature review, with a 50% mortality rate. The lack of clinico-laboratory clues suggesting this condition makes the diagnosis challenging. For these reasons C. septicum superinfection usually goes undiagnosed in patients with Shiga toxin-producing Escherichia Coli-related hemolytic-uremic syndrome, and results in unfavorable outcomes. In this paper, we describe the case of a 5-year-old girl admitted for Shiga toxin-producing Escherichia Coli-related hemolytic-uremic syndrome who developed C. septicum coinfection leading to a fatal outcome. We carried out a review of the available literature on C. septicum infection complicating Shiga toxin-producing Escherichia Coli-related hemolytic-uremic syndrome and we compared the clinical features of the observed cases with those of an historical cohort of uncomplicated Shiga toxin-producing Escherichia Coli-related hemolytic-uremic syndrome. The mechanisms of superinfection are still unclear and clinical features are indistinguishable from those of uncomplicated Shiga toxin-producing Escherichia Coli-related hemolytic-uremic syndrome. However, rapid deterioration of clinical conditions and evidence of neurological involvement, associated with abnormal radiological findings, require immediate management. Although therapeutic approaches have not been directly compared, neurosurgical treatment of amenable lesions may improve the clinical outcome of patients with C. septicum-hemolytic-uremic syndrome.

Robot-assisted transcerebellar stereotactic approach to the posterior fossa in pediatric patients: a technical note.

PURPOSE: During the last decade, there has been renewed interest in stereotactic approaches to diffuse intrinsic pontine gliomas (DIPGs) in children, due to the development of new concepts in molecular biology and management, and subsequent need for tissue sampling. Stereotactic frame-based and robot-assisted techniques are associated with reduced target error and have been incorporated into standard practice at our institution. METHODS: Four children (age 2-7 years) underwent a robot-assisted frame-based transcerebellar approach using the Leksell G frame coupled with Renishaw's neuromate® stereotactic robot. The procedures included 3 biopsies (two brainstem tumors and one cerebellar hemispheric lesion) and 1 depth electrode implantation into a low-grade tumor remnant (ganglioglioma) of the middle cerebellar peduncle causing drug-resistant epilepsy in a young girl. Targeting was based on MRI, and in one case, 18F-FET-PET was coregistered to MRI to improve sampling accuracy. The frame was applied 180° rotated compared to standard orientation, and patients were positioned prone during surgery and stereotactic preoperative CT scan. Postoperative CT scan ruled out complications and was coregistered to preoperative MRI to check the target accuracy. RESULTS: No complications occurred, and targeting was accurate in all cases. All tissue samplings provided proper histology; depth electrode EEG exploration was diagnostic and led subsequent resective surgery. CONCLUSIONS: According to our experience, the transcerebellar frame-based robotic stereotactic approach to the cerebellum and the brainstem is feasible, safe, and effective even in young children.

SMARCE1-related meningiomas: A clear example of cancer predisposing syndrome.

We report the case of a 16-year-old girl presenting with spinal clear-cell multiple meningiomas (CCMs). In view of this presentation, we sequenced a bioinformatic panel of genes associated with susceptibility to meningioma, identifying a germline heterozygous variant in SMARCE1. Somatic DNA investigations in the CCM demonstrated the deletion of the wild-type allele (loss of heterozygosity, LOH), supporting the causative role of this variant. Family segregation study detected the SMARCE1 variant in the asymptomatic father and in the asymptomatic sister who, nevertheless, presents 2 spinal lesions. Germline heterozygous loss-of-function (LoF) variants in SMARCE1, encoding a protein of the chromatin-remodeling complex SWI/SNF, have been described in few familial cases of susceptibility to meningioma, in particular the CCM subtype. Our case confirms the role of NGS in investigating predisposing genes for meningiomas (multiple or recurrent), with specific regard to SMARCE1 in case of pediatric CCM. In addition to the age of onset, the presence of familial clustering or the coexistence of multiple synchronous meningiomas also supports the role of a genetic predisposition that deserves a molecular assessment. Additionally, given the incomplete penetrance, it is of great importance to follow a specific screening or follow-up program for symptomatic and asymptomatic carriers of pathogenic variants in SMARCE1.

Loculated hydrocephalus: is neuroendoscopy effective and safe? A 90 patients' case series and literature review.

INTRODUCTION: Loculated hydrocephalus is a complex condition in which different non-communicating compartments form within the ventricular system due to different etiology, mainly intraventricular hemorrhage and infection. Since the end of the twentieth century, neuroendoscopy has been explored as a therapeutic option for loculated hydrocephalus with non-univocal results. METHODS: We performed a retrospective analysis of 90 patients who underwent endoscopic treatment for loculated hydrocephalus from January 1997 to January 2021 (mean age: 2 years, range 7-21). We included 37 (41.1%) children with multiloculated hydrocephalus, 37 (41.1%) with isolated lateral ventricle, 13 (14.4%) with excluded temporal horn, and 3 (3.3%) with isolated fourth ventricle. We compared our results with those available in literature. RESULTS: A mean of 1.91 endoscopic procedure/patient were performed (only one endoscopy in 42.2% of cases). Complications of neuroendoscopy and of shunt surgeries were recorded in 17 (18.9%) and 52 (57.8%) children, respectively. Twenty-six (28.9%) children were shunt-free at the last follow-up, 47.8% have only one shunt. DISCUSSION: The first goal of neuroendoscopy is to increase the rate of shunt-free patients but, when it is not possible, it aims at simplifying shunt system and reducing the number of surgical procedures. In our series, neuroendoscopy was able to achieve both these goals with an acceptable complication rate. Thus, our results confirmed neuroendoscopy as a valid tool in the long-term management of loculated hydrocephalus. Neuronavigation and intraoperative ultrasound could increase the success rate in cases with distorted anatomy.

Pediatric neurosurgery AC-after COVID-19: What has really changed? A review of the literature.

The COVID-19 outbreak has dramatically changed the organization of Pediatric Neurosurgery all over the world. The departments involved developed similar plans to maintain emergency surgeries without reducing clinical activities. The Association of Pediatric Neurosurgeons wrote different memoranda to detail the surgical procedures not to be postponed with special attention given to high-risk pathology for COVID-19 contamination, like trans-naso-sphenoidal surgery. On this basis, we have conducted a complete literature review focusing on many topics: hospital organization, patients and parents screening, surgical indication criteria, outpatient clinic and teleconsultation, telematic conference and meeting, fellowship and training, and virtual multidisciplinary meeting.

The medical therapy for cerebellar mutism syndrome: a case report and literature review.

PURPOSE: Cerebellar mutism syndrome (CMS) represents a major complication affecting many children that undergo surgery for posterior fossa lesions. Etiology and pathophysiology are still not fully understood. CMS deeply influences quality of life and recovery of these patients. An effective treatment has not been defined yet. This case-based review aims at analyzing the available evidence and knowledge to better delineate this phenomenon and to determine whether CMS can be successfully treated with pharmacological therapy. METHODS: Systematic research and retrieval of databases were conducted analyzing all papers where medical treatment of CMS was reported. A summary of the latest understanding and reports regarding definition, clinical manifestations, pathophysiology, management, and outcome of CMS has been conducted. RESULTS: Consensus on definition of this syndrome is lacking. CMS is the term accepted by the Posterior Fossa Society in 2016. Pathophysiology is still poorly understood but the most likely mechanism is injury along proximal components of the efferent cerebellar pathway. Nine papers describing positive effects of pharmacological therapy for CMS have been identified. Fluoxetine, zolpidem, bromocriptine, and midazolam are the drugs that seem to alleviate symptoms of CMS and improve recovery. To date, cognitive rehabilitation and physiotherapy are the only treatment options available. CONCLUSION: CMS has deep impact on affected children and their families. Despite attempts to identify preventive measures and treatment, cases still occur on a regular basis. Pharmacological treatments have been proposed to help reduce the symptoms of CMS with some promising results, but reports are limited; therefore, further studies are needed.

Complete section of the left vagus nerve does not preclude the efficacy of vagus nerve stimulation: illustrative case.

BACKGROUND: Vagus nerve stimulation (VNS) represents a valid therapeutic option for patients with medically intractable seizures who are not candidates for epilepsy surgery. Even when complete section of the nerve occurs, stimulation applied cranially to the involved nerve segment does not preclude the efficacy of VNS. Complete vagus nerve section with neuroma causing definitive left vocal cord palsy has never been previously reported in the literature. OBSERVATIONS: Eight years after VNS implant, the patient experienced worsening of seizures; the interrogation of the generator revealed high impedance requiring surgical revision. On surgical exploration, complete left vagus nerve section and a neuroma were found. Vocal cord atrophy was found at immediate postoperative laryngeal inspection as a confirmation of a longstanding lesion. Both of these events might have been caused by direct nerve injury during VNS surgery, and they presented in a delayed fashion. LESSONS: VNS surgery may be complicated by direct damage to the left vagus nerve, resulting in permanent neurological deficits. A complete section of the nerve also enables an efficacious stimulation if applied cranially to the involved segment. Laryngeal examination should be routinely performed before each VNS surgery to rule out preexisting vocal cord dysfunction.

Combined Technique of Temporal Muscle Augmentation for Muscle Reconstruction in Case of Small to Medium Anatomic Defects.

Inadequate temporal muscle (TM) reconstruction after surgery may hesitate in potentially severe functional and aesthetic sequelae, making it of paramount importance to carefully consider TM reconstruction even in case of small deformities.The authors describe the combined temporal muscle augmentation technique (CTMA), an innovative technique for TM augmentation for muscle reconstruction in case of small to medium substance loss.A cadaver study was conducted as preclinical validation of the technique for the assessment of CTMA coverage capability. CTMA consists in a combination of 2 techniques for muscle surface coverage (MSC) increase: the radial (RA) and the longitudinal augmentation (LA), which enables to harvest a radial (RF) and a longitudinal flap (LF), respectively.Each flap derives from a different muscle-bundle, spearing TM segmentation and functional performance, and are supplied by a specific neuro-vascular peduncle, which makes flaps functionally independent.A surgical case is reported to demonstrate the feasibility of the technique.Combined temporal muscle augmentation technique provides an overall coverage surface of 6.5 ± 0.6 cm, which corresponds to a gap distance of 2.5 ± 0.2 cm, with RF providing a statistically significant larger surface of coverage compared to LF (×2.1; P = 0.0001).Combined temporal muscle augmentation technique is easy and fast to perform displaying a good reconstructive capability with complete preservation of temporal muscle anatomic compartmentalization and segmental vasculature. It might be considered as a safe and effective alternative in the reconstruction of small-to medium TM defects.

Serum B-Type Natriuretic Peptide is Affected by Neoplastic Edema in Patients with a Brain Tumor.

OBJECTIVE: A positive correlation between serum B-type natriuretic peptide levels and the amount of dislodgement of intracranial structures (mass effect) produced by brain tumors has been demonstrated previously. The aim of our prospective observational study was to evaluate a possible relationship between serum B-type natriuretic peptide levels and the amount of neoplastic edema in patients affected by brain tumor. METHODS: We prospectively studied 110 patients with a supratentorial brain tumor. Serum N-terminal-pro B-type natriuretic peptide was measured and brain magnetic resonance images were analyzed to discriminate between neoplastic tissue and perilesional edema. A multivariate linear regression model predictive for serum N-terminal-pro B-type natriuretic peptide levels was generated. RESULTS: The radiologic diagnoses were meningioma in 45 patients (40.9%), glioma in 33 (30%), and metastasis in 32 (29.1%). A mass effect was present in 29 (26.4%) patients. Serum N-terminal-pro B-type natriuretic peptide was 125.61 ± 174.14 pg/mL (median 60 pg/mL, interquartile range 28-139 pg/mL). Four variables were entered into a multivariate linear regression model predictive for serum N-terminal-pro B-type natriuretic peptide values: age, neoplastic edema volume, metastatic lesion, and the presence of a mass effect (whole model P < 0.0001; R(2) = 0.5555; adjusted R(2) = 0.5294). CONCLUSIONS: Our data demonstrate that serum B-type natriuretic peptide levels are positively correlated to neoplastic brain edema in patients with a brain tumor and suggest a possible cerebral source for this phenomenon.

Clinical and immunological outcomes according to adherence to first-line HAART in a urban and rural cohort of HIV-infected patients in Burkina Faso, West Africa.

BACKGROUND: Aim of our study is to investigate the clinical and immunological outcomes according to first-line HAART adherence in a large cohort of HIV-infected patients in Burkina Faso. METHODS: A retrospective study was conducted between 2001 and 2009 among patients from two urban medical centers [St. Camille Medical Center (CMSC) and "Pietro Annigoni" Biomolecular Research Center (CERBA)] and 1 in the rural District of Nanoro (St. Camille District Hospital). Socio-demographical and clinical data were analyzed. Adherence was evaluated through a questionnaire investigating 5 key points related to drugs, consultations and blood exams, by assigning 0 to 2 points each up to 10 points overall. Data were collected at baseline and regularly thereafter. Adherence score was considered as a continuous variable and classified in optimal (8-10 points) and sub-optimal (0-7 points). Immunological outcome was evaluated as modification in CD4+ T-cell count over time, while predictors of death were explored by a univariate and multivariate Cox model considering adherence score as a time-varying covariate. RESULTS: A total of 625 patients were included: 455 (72.8%) were females, the median age was 33.3 (IQR 10.2) years, 204 (32.6.%) were illiterates, the median CD4+ T-cell count was 149 (IQR 114) cells/µl at baseline. At the end of the observation period we recorded 60/625 deaths and 40 lost to follow-up. The analysis of immunological outcomes showed a significant variation in CD4+ T-cell count between M12 and M24 only for patients with optimal adherence (Δ=78.2, p<0.001), with a significant Δ between the two adherence groups at M24 (8-10 vs 0-7, Δ=53.8, p=0.004). Survival multivariate analysis revealed that covariates significantly related to death included being followed at CERBA (urban area) or Nanoro (rural area), and receiving a regimen not including fixed dose combinations, (p=0.024, p=0.001 and p<0.001 respectively); conversely, an increasing adherence score as well as an optimal adherence score were significantly related to survival (p<0.001). CONCLUSIONS: Adherence to HAART remains pivotal to build up a good therapeutic outcome. Our results confirm that, according to our adherence system evaluation, less adherent patients have a higher risk of death and of inadequate CD4+ count recovery.

Epidemiology of malaria in endemic areas.

Malaria infection is still to be considered a major public health problem in those 106 countries where the risk of contracting the infection with one or more of the Plasmodium species exists. According to estimates from the World Health Organization, over 200 million cases and about 655.000 deaths have occurred in 2010. Estimating the real health and social burden of the disease is a difficult task, because many of the malaria endemic countries have limited diagnostic resources, especially in rural settings where conditions with similar clinical picture may coexist in the same geographical areas. Moreover, asymptomatic parasitaemia may occur in high transmission areas after childhood, when anti-malaria semi-immunity occurs. Malaria endemicity and control activities are very complex issues, that are influenced by factors related to the host, to the parasite, to the vector, to the environment and to the health system capacity to fully implement available anti-malaria weapons such as rapid diagnostic tests, artemisinin-based combination treatment, impregnated bed-nets and insecticide residual spraying while waiting for an effective vaccine to be made available.