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ObjectiveTo better understand the heterogeneous population of patients with new-onset refractory status epilepticus (NORSE), we studied the most severe cases in patients who presented with new-onset super-refractory status epilepticus (NOSRSE).MethodsWe report a retrospective case series of 26 adults admitted to the Columbia University Irving Medical Center neurologic intensive care unit (NICU) from February 2009 to February 2016 with NOSRSE. We evaluated demographics, diagnostic studies, and treatment course. Outcomes were modified Rankin Scale score (mRS) at hospital discharge and most recent follow-up visit (minimum of 2 months post discharge), NICU and hospital length of stay, and long-term antiepileptic drug use.ResultsOf the 252 patients with refractory status epilepticus, 27/252 had NORSE and 26/27 of those had NOSRSE. Age was bimodally distributed with peaks at 27 and 63 years. The majority (96%) had an infectious or psychiatric prodrome. Etiology was cryptogenic in 73%, autoimmune in 19%, and infectious in 8%. Seven patients (27%) underwent brain biopsy, autopsy, or both; 3 (12%) were diagnostic (herpes simplex encephalitis, candida encephalitis, and acute demyelinating encephalomyelitis). On discharge, 6 patients (23%) had good or fair outcome (mRS 0–3). Of the patients with long-term follow-up data (median 9 months, interquartile range 2–22 months), 12 patients (71%) had mRS 0–3.ConclusionAmong our cohort, nearly all patients with NORSE had NOSRSE. The majority were cryptogenic with few antibody-positive cases identified. Neuropathology was diagnostic in 12% of cases. Although only 23% of patients had good or fair outcome on discharge, 71% met these criteria at follow-up.

Objective: To evaluate the diagnostic accuracy of Magnetic Resonance spectroscopy (MRS) in distinguishing neoplastic from non-neoplastic ring enhancing brain lesions taking histopathological findings as gold standard. Study Design and Setting: The cross sectional study was conducted at Radiology department of Jinnah Postgraduate Medical Centre. Methodology: Total 102 patients with ring enhancing lesions detected on MRI brain contrast studies were selected for this study. Cases were referred from Outpatient Department of Neurology Clinics who were suspected of having space occupying lesions in brain. Full history, clinical examination and laboratory investigations (Complete Blood Count and ESR) were carried out. The patients having claustrophobia, metallic implants, cardiac pacemaker and having metallic foreign body in situ were excluded from the study. Informed consent was taken from the research and MRS was performed. On MRS, lesion was categorized and final diagnosis was taken based on histopathology results. All the information was recorded into predesigned proforma. Patients Data was scrutinized by using Statistical Package for Social Sciences (SPSS 21.0). Mean + SD was calculated for age, gender, duration of symptoms and size of the lesion. Results: The average age of the patients was 35.45±10.36 years. Sensitivity, specificity, PPV, NPV and accuracy of MRS was 87.5%, 93.3%, 95.5%, 89.7% and 92.1% respectively. Conclusion: Magnetic resonance spectroscopy can be effective in discerning neoplastic from non-neoplastic ring enhancing cerebral lesions, thus avoiding an invasive procedure like brain biopsy

International audience; Background and purpose: The rationale for performing a second brain biopsy after initial negativity is not well evaluated in the literature. This study was designed to 1) assess the efficacy of a second brain biopsy when the first biopsy was nondiagnostic, 2) identify possible factors associated with an increased diagnostic rate in the second biopsy, and 3) analyze additional morbidity induced by the second biopsy.Methods: We performed a retrospective cohort study from 2009 to 2019, during which 1,919 patients underwent a brain biopsy, including 30 who were biopsied twice (1.6%). The specific histological diagnosis rate, diagnosis-associated factors, and complication rate were assessed for the 30 twice-biopsied patients.Results: The second biopsy allowed a specific histological diagnosis in 86.7% of the patients who had initially undergone a nondiagnostic brain biopsy [odds ratio (OR)=7.5, 95% confidence interval (CI)=3.0-18.7, p

Gliomatosis Cerebri (GC) is a rareand rapidly progressive pattern of growth of diffusely infiltrating gliomas with limited treatment options. Imaging findings are usually nonspecific and can mimic other neurologic disorders, including demyelination, encephalitis, and multicentric/multifocal glioma. In this report, we describe a case of a 53-year-old female who presented with left hemiparesis, global headache, and gait ataxia with imaging features initially thought to represent demyelinating disease. A combination of conventional and advanced imaging findings with brain biopsy was utilized to make the diagnosis of GC. In patients with widespread abnormalities on brain imaging, GC should strongly be considered when cortical expansion, involvement of the septum pellucidum and elevated myoinositol levels are observed and the clinical and laboratory findings are atypical for demyelination or infection. Considering GC in such cases can facilitate early biopsy with prompt diagnosis and avoid delay in appropriate treatment.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by JC virus (JCV) and is difficult to diagnose. We report on a male HIV-positive patient with PML finally diagnosed by 3 times lumbar punctures and 2 times brain biopsies. Negative results of JCV-PCR in cerebrospinal fluid (CSF) do not rule out the diagnosis of PML when clinical manifestations and neuroimaging features suspected PML. It is necessary to obtain new CSF and make repeat tests and even perform brain biopsy.

Background and importance Rasmussen's Encephalitis (RE) is a chronic and progressive childhood disease caused by an inflammatory disorder that affects a cerebral hemisphere. On the other hand, Gliomatosis Cerebri (GC) is a rare primary neoplastic glial process with a diffuse and infiltrative growth. Clinical presentation We present two clinical cases with a history of continuous focal epilepsy refractory to antiepileptic drugs. They share similar clinical and radiologic features, but a different histopathological diagnosis. A brain biopsy was needed to distinguish GC from a RE. Conclusion The debut of a drug-resistant epilepsy with focal seizures and an ipsilateral progressive hemiparesis suggests the diagnosis of RE. However, there are other entities such as GC, which, despite its rarity, should be considered in the differential diagnosis. So, in some cases, histological diagnosis is needed.

BackgroundCommon variable immunodeficiency (CVID) is a group of heterogeneous primary immunodeficiencies characterised by a dysregulated and impaired immune response. In addition to an increased susceptibility to infection, it is also associated with noninfectious autoimmune and lymphoproliferative complications. CVID is rarely associated with neurological complications. Pulmonary involvement is more common, and patients can develop an interstitial lung disease known as granulomatous-lymphocytic interstitial lung disease (GLILD).Case presentationA 50-year-old Caucasian female with a history of Evans syndrome (idiopathic thrombocytopaenic purpura and autoimmune haemolytic anaemia) and hypogammaglobulinaemia initially presented to the neurology clinic with marked cerebellar ataxia and headaches. Following extensive investigation (which included brain biopsy), she was diagnosed with neuro-sarcoidosis and her symptoms resolved following treatment with immunosuppressive therapy. Over the following 10 years, she was extensively investigated for recurrent pulmonary infections and abnormal radiological findings, which included pulmonary nodules, infiltrates and splenomegaly. Subsequently, she was referred to an immunology clinic, where immunoglobulin replacement treatment was started for what was ultimately considered to be CVID. Shortly afterwards, evaluation of her clinical, radiological and histological findings at a specialist interstitial lung disease clinic led to a diagnosis of GLILD.ConclusionCVID is a condition which should be suspected in patients with immunodeficiency and recurrent infections. Concomitant autoimmune disorders such as haemolytic anaemia and immune thrombocytopenia may further support the diagnosis. As illustrated in this case, there is a rare association between CVID and inflammatory involvement of the neurological system. Respiratory physicians should also suspect CVID with associated GLILD in patients with apparent pulmonary granulomatous disease and recurrent infections. In addition, this case also highlights the challenge of diagnosing CVID and its associated features, and how the definitive exclusion of other pathologies such as malignancy, mycobacterial infection and lymphoma is required as part of this diagnostic process.

Purpose The pathological diagnosis of primary central nervous system lymphoma (PCNSL) by stereotactic brain biopsy and craniotomy is not often applicable due to the high cost and associated complications. In recent years, some biomarkers in cerebrospinal fluid (CSF), including interleukin 10 (IL-10), microRNAs, CXC chemokine ligand 13 (CXCL13), have been reported to be associated with PCNSL. However, this conclusion was controversial. Therefore, this study was to test whether Th17 cell-related cytokines could be used to distinguish PCNSL from other brain tumors. Patients and methods Th17 cell-related cytokines in CSF were measured in 108 patients with intracranial tumors, which included 66 PCNSL patients and 42 patients with other types of brain tumors. A receiver-operating characteristic (ROC) curve was utilized to analyze the diagnostic value of the cytokines based on the area under the curve (AUC). Results The CSF IL-10 level and IL-10/IL-6 ratios were significantly higher in PCNSL than in the other brain tumors (58.2 pg/mL VS 1.5 pg/mL, p=0.001; 24.3 VS 0.6, p=0.001). When the cutoff level of IL-10 was set at 8.3 pg/mL, its sensitivity and specificity for diagnosing PCNSL were 59.0% and 98%, respectively. The CSF IL-10 levels over 5pg/mL (+LR 12.3) were of significant value for the diagnosis of PCNSL. These parameters are highly valuable in PCNSL diagnosis, but their sensitivity is less valuable. The sensitivity of IL-4 and IL-17A, the ratio of mature lymphocytes and the monocytes/macrophages ratio in CSF were relatively high. In combination, the sensitivity increased by 15% and the specificity remained above 85%. The best combination was IL-10 and IL-17A, whose sensitivity was 70% and specificity was 96%. Conclusion The CSF level of IL-10 is a useful diagnostic biomarker in patients with PCNSL. The CSF levels of IL-4, IL-17A, mature lymphocytes and monocytes/macrophages can be used to increase the diagnostic value of CSF IL-10 level and IL-10/IL-6 ratio.

A 62-year-old healthy male presents with leg weakness and fever. Imaging revealed leptomeningeal enhancement (LE). After cerebrospinal fluid (CSF) cultures were negative, he was discharged with a diagnosis of aseptic meningitis, but was readmitted due to worsening symptoms. Brain biopsy suggested rheumatoid leptomeningitis associated with elevated serum rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). Following discharge, the New York State Department of Health (NYSDOH) reported a polymerase chain reaction (PCR) on CSF and brain DNA consistent with Naegleria fowleri (NF). After dramatic improvement on steroids, the patient declined antimicrobial treatment. Upon prednisone taper, symptoms recurred which responded to rituximab (RTX). This case highlights a possible association between rheumatoid leptomeningitis (RM) onset and infection, in a patient without a history of rheumatoid arthritis (RA). Our goal is to assess whether this association is present in 69 RM cases reported since 2000. We also describe diagnosis and treatment of 31 new cases (January 2017 to March 2020). We did not identify evidence of active/latent infection in patients with RM and previous RA; however, patients without RA history appeared to have a significantly higher rate. This finding could demonstrate the necessity of evaluating for infection in de novo RM cases without antecedent RA history. We also describe characteristic clinical patterns for each group. More studies are needed to corroborate these results and expand into a possible distinct natural history of RM in each group, which might have an impact upon the clinical outcome.

Background: Hereditary diffuse leukoencephalopathy with spheroids (HDLS), first described in 1984 is a rare disorder. Generally, it presents at adulthood with dementia, motor impairment, extrapyramidal abnormalities, and epilepsy. Definitive diagnosis is made by brain biopsy. Neuroimaging studies have revealed confluent white matter lesions predominantly in the frontal lobes, corpus callosum, and corticospinal tracts on conventional magnetic resonance imaging. Only a few reports showed diffusion restriction in the cerebral white matter; furthermore, rarer reports emphasized persistent foci of diffusion restriction as a diagnostic imaging marker. Objective: Herein, we have aimed to illustrate the first biopsy-proven Turkish HDLS pedigree consisting of 18 persons in 3 generations which contained 4 affected individuals. Materials and Methods: Four individuals in the pedigree of HDLS [two affected patients (patient III-1 and patient III-2) and two unaffected individuals (patient II-4 and patient III-5)] were investigated with conventional MRI and Diffusion-weighted imaging (DWI) using 1.5 Tesla (T) scanner. All four individuals were evaluated via neurological examinations and Mini-Mental State Examination. Brain biopsy study was performed on patient III-2. Finally, an extensive literature review involving pathology investigations and neuroimaging studies of HDLS patients was conducted. Results: DWIs of two investigated patients showed deep white matter lesions with persistent diffusion restriction. Computed tomography imaging showed punctate mineralization in the lesions. Biopsy specimens of patient III-2 demonstrated axonal spheroids which were typical for HDLS. Conclusions: Via the presentation of our pedigree and literature review, we suggest HDSL as a first-line differential diagnosis in patients with undiagnosed adult-onset familial leukoencephalopathy, in particular, those with MRI lesions of frontal white matter and centrum semiovale associated with foci of diffusion restriction and mineralization. Finally, we think that the persistence of the diffusion restriction in deep white matter lesions should be kept in mind as a crucial neuroimaging sign for HDLS.

Here we present a case of a 41-year old immunocompetent female from central Maryland, who presented with new onset seizures. Magnetic resonance imaging of brain revealed a solitary ring-enhancing lesion. Stereotactic brain biopsy confirmed Blastomyces dermatitidis brain abscess. Patient's clinical course was complicated by voriconazole-induced pancytopenia that prompted surgical resection and amphothericin-induced severe hypokalemia necessitating change to high dose fluconazole. Four months after surgical resection, patient remains in radiographic and clinical remission.

Well-circumscribed intra-axial CNS tumors encompass a wide variety of gliomas and glioneuronal tumors, usually corresponding to WHO grades I and II. Nonetheless, sometimes high-grade 'diffuse' gliomas such as gliosarcoma and giant cell glioblastoma can be relatively circumscribed but are often found to have foci of diffuse infiltration on careful examination, harboring distinct molecular alterations. These tumors are excluded from the discussion in this chapter with the current review emphasizing on lower-grade entities to include a brief description of their histology and associated molecular findings. Like elsewhere in brain biopsy evaluation, imaging is crucial and acts as a surrogate to gross examination. Given the circumscribed nature of these tumors, surgery alone is the mainstay treatment in most entities.

Simulation training improves technical skills in a safe environment. Stereotactic techniques are widely used in neurosurgery for different kinds of procedures. The objective of the study was to describe a combined cadaveric and synthetic low-cost stereotactic simulation model and its validation by neurosurgeons.The brain was made using self-supporting gel with solid and cystic lesions. We used imaging scans to calculate x, y, and z target coordinates. A standard frame needle biopsy was performed. We calculated the number of mistakes and time needed to accomplish the task, and we evaluated the frame assembly and biopsy performance. Wilcoxon signed rank was used to analyzed the data; we considered a P value0.05 as statistically significant.The median initial number of mistakes was 32 (interquartile range [IQR]: 27.5-37) and after repeated training and feedback the final median number was 3.5 (IQR: 2-6) (P0.001). The median time needed to finish the exercises before training was 1020.5 seconds (IQR: 908-1125.5) and after using the model the final median time was 479 seconds (IQR: 423-503) (P0.0001).We presented a stereotactic simulation model with immediate haptic feedback. The model can be easily handmade in any neurosurgical laboratory. This model allows neurosurgeons in training to acquire and improve stereotactic techniques, reducing the number of surgical mistakes and time needed to finish the task.

In this case report, we described a 15-year-old boy who presented with intermittent episodes of ataxia and diplopia since 6.5 years of age. Extensive workup done over several years was negative. Brain biopsy showed a neuroinflammatory disorder, and hence, differential diagnosis of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, central nervous system (CNS) lymphoma, and small vessel CNS vasculitis were considered. A final diagnosis of familial hemophagocytic lymphohistiocytosis was made when the patient developed episodes of prolonged fever with pancytopenia much later in the course of illness and genetic workup revealed pathogenic mutations in the PRF1 gene.

A 26-year-old woman presented for a routine contact lens evaluation but was found to have a subtle right sixth nerve paresis and adducting nystagmus of the left eye. She reported horizontal diplopia on far right gaze as well as subjective right-sided weakness and poor balance for 1 year. Brain and spinal MRI revealed multiple cystic lesions with variable enhancement throughout the posterior fossa and cervical spinal cord. These MRI findings were highly suspicious for an infectious central nervous system process, such as neurocysticercosis; however, primary or metastatic tumors were also important considerations. Tumor location and imaging characteristics were most helpful in differentiating among these etiologies. A brain biopsy ultimately established the diagnosis of a rosette-forming glioneuronal tumor.

Introduction Ribosomal protein SA pseudogene 52 (RPSAP52) has been characterized as an oncogenic lncRNA in pituitary tumors. Analysis of TCGA dataset revealed the upregulation of RPSAP52 in glioblastoma (GBM). We, therefore, investigated the roles of RPSAP52 in GBM. Methods A total of 50 GBM patients (33 males and 20 females; 54-75 years; mean age: 61.8±5.8 years) were selected from the 89 cases of GBM patients. Under the guidance of MRI, brain biopsy was performed to collect GBM tissues from each patient for the diagnosis of GBM. U-373 MG cells were employed and had transient transfections. qRNA, Western blot, and a series of experiments were performed to characterize their associations. Results The results showed that RPSAP52 was upregulated in GBM patients, and its high expression levels predicted poor survival. In GBM tissues, expression levels of RPSAP52 were significantly and positively correlated with that of TGF-β1. In GBM tissues, RPSAP52 positively regulated the expression of TGF-β1. Cell stemness assay showed that, compared to C and NC groups, overexpression of RPSAP52 and TGF-β1 led to increased, while silencing of RPSAP52 led to decreased CD133+ cells. Overexpression of TGF-β1 attenuated the effects of RPSAP52 siRNA silencing. Conclusion Therefore, RPSAP52 upregulates TGF-β1 to increase cancer cell stemness and predict postoperative survival in GBM.

In stereotactic brain biopsy, operating the needle accurately and taking the biopsy specimen safely are two major challenges for ensuring the success of the surgical procedure. Considering this fact, surgical robots offering high accuracy and precision have been developed for neurosurgery including brain biopsy. Typical brain biopsy robots are only commanded to adjust the needle's pose before inserting the needle manually by a neurosurgeon. In the literature, there exists no robotic system that is competent to complete the needle insertion task autonomously. To move a step forward, a novel biopsy module for brain biopsy is first designed and fabricated in this paper. The biopsy module can be automated to complete a series of tasks such as inserting the needle, generating and controlling the aspiration pressure for specimen acquisition, and rotating the cannula for side-cutting. The biopsy module is further integrated with a cost-effective and lightweight UR5 robot and an optical tracking system to improve the autonomy, leading to a stereotactic neuronavigation system. Kinematic relationships of the involved elements are established via a calibration process. A quadratic programming based approach equipped with a virtual potential field method is implemented to safely control the robot with joint-limit avoidance and obstacle avoidance capabilities. The experimentation of the brain biopsy robot is performed, demonstrating that the developed robotic system has potential applicability in the brain biopsy surgery.

Brain tumors comprise a heterogeneous group of diseases, featuring different biology, prognosis, and treatment. The most known forms are malignant gliomas and metastases. Brain biopsy is a recognized technique in the management of intracranial space-occupying lesions and tumors in particular. Tumor heterogeneity of malignant brain lesions has been described and can lead to significant sampling errors in stereotactic biopsy. Different methods have been used to perform biopsies, including biopsy guided by CT or RMI, echoguided or stereotactic. The choice of the target with the help of PET and MRI with spectroscopy allows one to identify metabolically more active areas of the tumor, and in this way reduce the rate of negative results.

Background Thalamic aphasia is an unusual clinical presentation of brain neoplasm with few cases reported. Herein, we present a case of an adult woman with thalamic aphasia due to glioblastoma of the thalamus. Case presentation A 57-year-old female patient presented with difficulty walking, slow speech and cognition and altered mental status. At baseline, she was conversant and interactive. Physical examination showed right hemiparesis in addition to word finding difficulties, an impaired naming of objects and semantic paraphasia but preserved repetition and comprehension. The remaining neurological exam was otherwise unremarkable. Brain CT and brain MRI scans showed a left thalamic lesion that is centrally necrotic and peripherally enhancing suggestive of a high-grade neoplasm. Eventually, histopathological examination of brain biopsy confirmed the diagnosis of glioblastoma multiforme. Thalamic aphasia was proposed as an explanation for the neurological symptoms observed in this patient. Conclusions This patient demonstrates an unusual presentation of glioblastoma multiforme as thalamic aphasia. It may also point to the potential contribution of the understanding of how thalamic aphasia evolves to characterize the role of the thalamus in language functions.

Objectives: To evaluate the diagnostic value and clinical application of prenatal ultrasonography (US) and Magnetic Resonance Imaging (MRI) for different types of fetal Agenesis of the Corpus Callosum (ACC). Material and methods: There were 42 cases of fetal ACC discovered by routine US, including complete ACC 18 cases and partial ACC 24 cases, checked by MRI within 1 week. The results were confirmed by head ultrasound after birth or brain biopsy after labor induction. Results: From prenatal ultrasonic diagnosis, 18 cases were complete ACC and 24 cases were partial ACC. MRI was able to find complete ACC in 11 cases, partial ACC in 16 cases, and non-ACC in 15 cases. Labor induction or birth confirmed that, 11 cases were complete ACC, 14 cases were partial ACC, and 17 cases were non-ACC.The results of different types of ACC were detected by ultrasound and MRI were statistically significant (p < 0.05).MRI examination was superior to ultrasound in specificity, positive predictive value, negative predictive value, Youden index, and diagnostic index. Conclusions: MRI is high specific degrees, diagnostic performance is satisfactory, should be use as a necessary method for prenatal definitive diagnosis of ACC. However, prenatal ultrasound can be tested repeatedly and can be combined with blood flow imaging detection in real time, and it is still the preferred method for screening fetal structural malformation in a comprehensive way, which is suitable for general screening of ACC.

BACKGROUND/PURPOSE To report a case of serology-negative severe disseminated Bartonella neuroretinitis in an immunocompromised patient in which diagnosis was made by detection of B. henselae DNA by universal polymerase chain reaction of brain tissue. METHODS Case report. RESULTS A 57-year-old man with immunoglobulin A vasculitis on immunosuppressive therapy presented with lethargy, weight loss, and bilateral decreased vision. Fundus examination revealed bilateral mild vitritis, marked optic disc edema, vascular sheathing, and numerous white inner retinal and preretinal lesions. Brain magnetic resonance imaging revealed multiple foci of restricted diffusion and a ring-enhancing focus in the left parietal lobe. Serologies, cerebrospinal fluid, and vitreous biopsies were all negative for Bartonella. A brain biopsy was performed and B. henselae DNA was detected by universal polymerase chain reaction of the specimen. The patient demonstrated resolution of fundus findings with antibiotic treatment. Repeat serological testing demonstrated seroconversion. CONCLUSION In immunocompromised patients, infection by Bartonella henselae can present as severe disseminated disease. Establishing the diagnosis can be challenging as serologic testing is often unrevealing in the setting of a blunted immune response. Polymerase chain reaction has been used in select cases to establish the diagnosis.

Background: Brain biopsy of intracranial lesions is often necessary to determine specific therapy. The cost of the currently used stereotactic rigid frame and optical tracking systems for brain biopsy in dogs is often prohibitive or accuracy is not sufficient for all types of lesion. Objectives: To evaluate the application accuracy of an inexpensive magnetic resonance imaging‐based personalized, 3D printed brain biopsy device. Animals: Twenty‐two dog heads from cadavers were separated into 2 groups according to body weight (20 kg). Methods: Experimental study. Two target points in each cadaver head were used (target point 1: caudate nucleus, target point 2: piriform lobe). Comparison between groups was performed using the independent Student's t test or the nonparametric Mann‐Whitney U Test. Results: The total median target point deviation was 0.83 mm (range 0.09‐2.76 mm). The separate median target point deviations for target points 1 and 2 in all dogs were 0.57 mm (range: 0.09‐1.25 mm) and 0.85 mm (range: 0.14‐2.76 mm), respectively. Conclusion and Clinical Importance: This magnetic resonance imaging‐based 3D printed stereotactic brain biopsy device achieved an application accuracy that was better than the accuracy of most brain biopsy systems that are currently used in veterinary medicine. The device can be applied to every size and shape of skull and allows precise positioning of brain biopsy needles in dogs.

This paper surveys both the clinical applications and main technical innovations related to steered needles, with an emphasis on neurosurgery. Technical innovations generally center on curvilinear robots that can adopt a complex path that circumvents critical structures and eloquent brain tissue. These advances include several needle-steering approaches, which consist of tip-based, lengthwise, base motion-driven, and tissue-centered steering strategies. This paper also describes foundational mathematical models for steering, where potential fields, nonholonomic bicycle-like models, spring models, and stochastic approaches are cited. In addition, practical path planning systems are also addressed, where we cite uncertainty modeling in path planning, intraoperative soft tissue shift estimation through imaging scans acquired during the procedure, and simulation-based prediction. Neurosurgical scenarios tend to emphasize straight needles so far, and span deep-brain stimulation (DBS), stereoelectroencephalography (SEEG), intracerebral drug delivery (IDD), stereotactic brain biopsy (SBB), stereotactic needle aspiration for hematoma, cysts and abscesses, and brachytherapy as well as thermal ablation of brain tumors and seizure-generating regions. We emphasize therapeutic considerations and complications that have been documented in conjunction with these applications.

This paper surveys both the clinical applications and main technical innovations related to steered needles, with an emphasis on neurosurgery. Technical innovations generally center on curvilinear robots that can adopt a complex path that circumvents critical structures and eloquent brain tissue. These advances include several needle-steering approaches, which consist of tip-based, lengthwise, base motion-driven, and tissue-centered steering strategies. This paper also describes foundational mathematical models for steering, where potential fields, nonholonomic bicycle-like models, spring models, and stochastic approaches are cited. In addition, practical path planning systems are also addressed, where we cite uncertainty modeling in path planning, intraoperative soft tissue shift estimation through imaging scans acquired during the procedure, and simulation-based prediction. Neurosurgical scenarios tend to emphasize straight needles so far, and span deep-brain stimulation (DBS), stereoelectroencephalography (SEEG), intracerebral drug delivery (IDD), stereotactic brain biopsy (SBB), stereotactic needle aspiration for hematoma, cysts and abscesses, and brachytherapy as well as thermal ablation of brain tumors and seizure-generating regions. We emphasize therapeutic considerations and complications that have been documented in conjunction with these applications.

Traumatic brain injury (TBI) is an extremely complex disease and current systems classifying TBI as mild, moderate, and severe often fail to capture this complexity. Neuroimaging cannot resolve the cellular and molecular changes due to lack of resolution, and post-mortem tissue examination may not adequately represent acute disease. Therefore, we examined the cellular and molecular sequelae of TBI in fresh brain samples and related these to clinical outcomes. Brain biopsies, obtained shortly after injury from 25 living adult patients suffering severe TBI, underwent immunohistochemical analysis. There were no adverse events. Immunostaining revealed various qualitative cellular and biomolecular changes relating to neuronal injury, dendritic injury, neurovascular injury, and neuroinflammation, which we classified into 4 subgroups for each injury type using the newly devised Yip, Hasan and Uff (YHU) grading system. Based on the Glasgow Outcome Scale-Extended, a total YHU grade of ≤8 or ≥11 had a favourable and unfavourable outcome, respectively. Biomolecular changes observed in fresh brain samples enabled classification of this heterogeneous patient population into various injury severity categories based on the cellular and molecular pathophysiology according to the YHU grading system, which correlated with outcome. This is the first study investigating the acute biomolecular response to TBI.

The role of neuroinflammation in epileptogenesis is extensively investigated, but short-term effects of seizures on established CNS pathologies are less studied and less predictable. We describe the case of a woman with previous recurrent episodes of focal cerebral haemorrhage of unknown cause who developed a pseudo-tumoural oedema triggered by provoked focal status epilepticus. A brain biopsy revealed that the underlying condition was primary angiitis of the CNS. Ictal-induced blood-brain barrier dysfunction allows the entry of water and inflammatory molecules that, in the context of CNS inflammatory diseases, may trigger a self-reinforcing process. Caution should be observed when tapering antiepileptic drugs in patients with such conditions.

Background: Neurosurgical procedures are complex and require years of training and experience. Traditional training on human cadavers is expensive, requires facilities and planning, and raises ethical concerns. Therefore, the use of anthropomorphic phantoms could be an excellent substitute. The aim of the study was to design and develop a patient-specific 3D-skull and brain model with realistic CT-attenuation suitable for conventional and augmented reality (AR)-navigated neurosurgical simulations. Methods: The radiodensity of materials considered for the skull and brain phantoms were investigated using cone beam CT (CBCT) and compared to the radiodensities of the human skull and brain. The mechanical properties of the materials considered were tested in the laboratory and subsequently evaluated by clinically active neurosurgeons. Optimization of the phantom for the intended purposes was performed in a feedback cycle of tests and improvements. Results: The skull, including a complete representation of the nasal cavity and skull base, was 3D printed using polylactic acid with calcium carbonate. The brain was cast using a mixture of water and coolant, with 4 wt% polyvinyl alcohol and 0.1 wt% barium sulfate, in a mold obtained from segmentation of CBCT and T1 weighted MR images from a cadaver. The experiments revealed that the radiodensities of the skull and brain phantoms were 547 and 38 Hounsfield units (HU), as compared to real skull bone and brain tissues with values of around 1300 and 30 HU, respectively. As for the mechanical properties testing, the brain phantom exhibited a similar elasticity to real brain tissue. The phantom was subsequently evaluated by neurosurgeons in simulations of endonasal skull-base surgery, brain biopsies, and external ventricular drain (EVD) placement and found to fulfill the requirements of a surgical phantom. Conclusions: A realistic and CT-compatible anthropomorphic head phantom was designed and successfully used for simulated augmented reality-led neurosurgical procedures. The anatomic details of the skull base and brain were realistically reproduced. This phantom can easily be manufactured and used for surgical training at a low cost.

Background The preoperative preparation of the planning dataset for frame-based stereotactic brain biopsy is often associated with logistical effort and burden on the patient. Intraoperative imaging modalities need to be investigated to overcome these limitations. Objective The objective of the study was to develop and apply a new method for the intraoperative acquisition of the planning dataset with the multiaxial robotic C-arm system Artis zeego. Methods An indication-customized dose-reduced protocol for Artis zeego was developed and implemented into the workflow. A sample of 14 patients who had undergone intraoperative imaging with Artis zeego was analyzed. A sample of 10 patients with conventional preoperative imaging by cranial computed tomography (CT) was used as a control group. Outcomes were compared with regard to target deviation, diagnostic value of the biopsies, complications, and procedure time. Results In all patients, a suitable intraoperative planning dataset could be acquired with Artis zeego. Total procedure time was shorter for the Artis zeego group (p = 0.01), whereas time in the operating room area was longer in the Artis zeego group (p = 0.04). Biopsy results were diagnostic in 12 patients (86%) in the Artis zeego group and in 8 patients (80%) in the control group. There were no significant differences in target size, trajectory length, or target deviation. Conclusion Intraoperative imaging for frame-based stereotactic brain biopsy with Artis zeego is an easy and feasible method. Accuracy is comparable to conventional CT, whereas radiation exposure could be additionally reduced. It allows a significant reduction of the total procedure length and improves the comfort for the patient and staff.

The aim of the present study was to evaluate the use of a novel intraoperative cone-beam computed tomography (CBCT)-based automated registration system for frameless stereotactic brain biopsy in companion animals. An experimental cadaveric study evaluated thalamic and piriform lobe target site needle placement error in three dogs and three cats without a history of intracranial disease. Diagnostic accuracy and diagnostic yield were prospectively evaluated in twenty-four client-owned dogs and four cats with intracranial disease. Twenty-one procedures were performed post mortem (eighteen dogs and three cats), and seven biopsy procedures were performed in alive patients (six dogs and one cat). Procedural duration was evaluated in ten post mortem and four living patients. Outcome was evaluated in six dogs and one cat. In dogs, the calculated median needle placement error was 1.8 mm (range 0.71–2.84 mm) and 1.53 mm (range 1.45–1.99 mm) for piriform lobe and thalamus target sites, respectively. In cats, the calculated median needle placement error was 0.79 mm (range 0.6–1.91 mm) for the piriform lobe target site and 1.29 mm (range 0.47–2.69 mm) for the thalamic target site. The diagnostic yield was 96.4% (95% CI 0.81–0.99), the diagnostic accuracy was 94.4% (95% CI 0.72–0.99). Median total procedural duration for post mortem biopsies was 57.5 min (range 41–69 min). Median total procedural duration for intra vitam biopsies was 122.5 min (range 103–136 min). Three dogs were discharged 1 day after biopsy and one dog after 6 days. Two dogs and one cat were euthanized 24 and 48 h after biopsy. Intraoperative CBCT-based automated image registration for frameless stereotactic biopsies in companion animals is capable of providing diagnostic brain biopsy specimens independent of skull size and morphology with diagnostic yield and accuracy comparable to published values for diverse frameless and frame-based stereotaxy systems used in veterinary medicine. Duration of the procedure is not negatively affected and within the published range with other systems. Mobile intraoperative CBCT-based registration combined with neuronavigation delivers diagnostic brain biopsies in companion animals.

CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is an inflammatory disorder of the central nervous system (CNS), predominantly involving the brainstem with a characteristic magnetic resonance imaging (MRI) appearance and clinical and radiological responsiveness to glucocorticosteroids. Yet diagnostic biomarkers are missing and other immune-mediated, (para-) infectious and malignant causes mimic CLIPPERS-like MRI presentations. We report the case of a 51-year-old male patient with CLIPPERS who repeatedly responded well to high-dose corticosteroids. After 7 months, however, treatment failed, and he had a biopsy-confirmed diagnosis of a CNS B-cell lymphoma. Clinical and MRI signs of CLIPPERS include a wide spectrum of differential diagnoses which often arise only later during the course of disease. Similar to the case presented here, delayed diagnosis and specific therapy may contribute to an unfavorable outcome. Hence, we propose that in the absence of other diagnostic markers, brain biopsy should be performed as early as possible in CLIPPERS patients.

Stereotactic brain biopsy (SBB) is used for establishing the histological diagnosis of intracranial lesions that are not amenable for a direct surgical approach.The objective of the study was to describe our experience having an evaluation of the biopsy sample by a neuropathologist during SBB.Retrospective analysis of 140 consecutive patients who underwent SBB between 2014 and 2018 in whom trans-operatory analysis of the sample was performed.There were 56% men. The mean age was 45 years. Histological diagnosis was performed in 131 of 140 patients (94% overall diagnostic yield). The presurgical radiological diagnosis was correct in 39%. Neoplastic lesions were reported in 108 cases, and 32 were non-neoplastic. We performed craniotomy and resection after biopsy in 14%. We found complications in 6% of patients.SBB continues to be a safe, useful, and inexpensive procedure. The diagnostic performance of SBB increases when intraoperative cytological evaluation by a neuropathologist is included in the study.la biopsia cerebral por estereotaxia (SBB) se utiliza para establecer el diagnóstico histológico de lesiones intracraneales que no son susceptibles de un abordaje quirúrgico directo.describir nuestra experiencia de tener una evaluación de la muestra de biopsia por un neuropatólogo durante el procedimiento.análisis retrospectivo de 140 pacientes consecutivos sometidos a SBB entre 2014-2018 en los que se realizó análisis transoperatorio de la muestra.El 56% fueron hombres. La edad promedio fue de 45 años. El diagnóstico histológico se realizó en 131 de 140 pacientes (rendimiento diagnóstico global del 94%). El diagnóstico radiológico prequirúrgico fue correcto solo en el 39%. Se identificaron lesiones neoplásicas en 108 casos, y en 32 se documentaron lesiones no neoplásicas. En el 14% de los casos se realizó posterior a la biospia craneotomía y resección de la lesión. Encontramos complicaciones en el 6% de los pacientes.SBB sigue siendo un procedimiento seguro, útil y económico. El rendimiento diagnóstico de SBB aumenta cuando se incluye la evaluación citológica intraoperatoria por un neuropatólogo.