The Impact of Hyponatremia on the Severity of Childhood Tuberculous Meningitis

Introduction: Hyponatremia and/or hypoglycorrhachia are commonly encountered biochemical derangements during the acute stage of childhood tuberculous meningitis (TBM). Few studies have explored the correlation between these derangements and the staging of TBM disease (severity), or explored their role as biomarkers for vascular ischemic events, hydrocephalus, or seizures.Methods: We aimed to identify the prevalence and the correlation between serum hyponatremia (mild, moderate and severe) and/or hypoglycorrhachia in relation to clinical TBM features such as stage of disease, seizures and stroke in children diagnosed with definite and probable TBM, between 1985 and 2015, at Tygerberg Hospital, Cape town, South Africa.Results: The prevalence of hyponatremia was 344 out of 481 (71.5%) patients; 169 (49.1%) had mild hyponatremia, 146 (42.4%) moderate hyponatremia and 29 (8.4%) severe hyponatremia. Children with severe hyponatremia had higher frequency of stroke [odds ratio (OR) 4.36, 95% confidence interval (CI) 1.24–15.35; p = 0.01], brainstem dysfunction (OR 7.37, 95% CI 2.92–18.61; p < 0.01), cranial nerve palsies (OR 2.48, 95% CI 1.04–5.91; p = 0.04) and non-communicating hydrocephalus (OR 2.66, 95% CI 1.09–6.44; p = 0.03). Children with moderate hyponatremia and mild hyponatremia compared to those without hyponatremia similarly were more likely to exhibit signs of brainstem dysfunction (OR 1.91, 95% CI 1.11–3.28; p = 0.02) and hydrocephalus (OR 3.18, 95% CI 1.25–8.09; p = 0.01), respectively. On multivariable analysis only brainstem dysfunction was significantly associated with severe hyponatremia [adjusted odds ratio (aOR) 4.46, 95% CI 1.62–12.30; p < 0.01]. Children with hypoglycorrhachia compared to normoglycorrhachia were more likely to have had longer symptom duration prior to admission (OR 1.87, 95% CI 1.09–3.20; p = 0.02), non-communicating hydrocephalus (OR 1.64, 95% CI 0.99–2.71; p = 0.05), higher cerebrospinal white cell counts (OR 3.00, 95% CI 1.47–6.12; p < 0.01) and higher CSF protein concentrations (OR 2.51, 95% CI 1.49–4.20; p < 0.01). On multivariable analysis raised CSF protein concentration >1 g/L was significantly associated with hypoglycorrhachia (aOR 2.52, 95% CI 1.44–4.40; p < 0.01). Death rates did not differ by sodium level category or presence of hypoglycorrachia, however an increasing trend of children that had demised was noted the more severe the sodium category.Conclusion: Hyponatremia and/or hypoglycorrhachia occur in more than two-thirds of children with TBM. Severe TBM disease complications such as brainstem dysfunction was associated with moderate hyponatremia, while severe hyponatremia was associated with brainstem dysfunction, stroke, cranial nerve palsies and non-communicating hydrocephalus. Cerebrospinal fluid (CSF) glucose depletion correlated with non-communicating hydrocephalus and increased CSF inflammation.

Multifocal spinal glioblastoma and leptomeningeal carcinomatosis in an elderly male with hydrocephalus and myelopathy

Background: Primary spinal glioblastoma multiforme with multifocal leptomeningeal enhancement is rarely diagnosed or documented. We describe a rare case of multifocal spinal isocitrate dehydrogenase (IDH) wild type glioblastoma with leptomeningeal carcinomatosis in an elderly male presenting with a chronic subdural hematoma, progressive myelopathy, and communicating hydrocephalus. Case Description: A 77-year-old male with a medical history of an acoustic schwannoma, anterior cranial fossa meningioma, and immune thrombocytopenic purpura presented with right-sided weakness after repeated falls. Magnetic resonance imaging of the brain and spine demonstrated a left-sided subdural hematoma, leptomeningeal enhancement of the brain and skull base, ventricles, and the cranial nerves, and along with florid enhancement of the leptomeninges from the cervicomedullary junction to the cauda equina. Most pertinent was focal thickening of the leptomeninges at T1 and T6 with mass effect on the spinal cord. A T6 laminectomy with excisional biopsy of the lesion was planned and completed. Findings were significant for glioblastoma the World Health Organization Grade IV IDH 1 wild type of the thoracic spinal cord. Subsequently, his mental status declined, and he developed progressive hydrocephalus which required cerebrospinal fluid diversion. Unfortunately, the patient had minimal improvement in his neurological exam and unfortunately died 2 months later. Conclusion: In a review of the limited literature describing similar cases of primary spinal glioblastoma, the prognosis of this aggressive tumor remains unfavorable, despite aggressive treatment options. The purpose of this report is to increase awareness of this rare condition as a potential differential diagnosis in patients presenting with multifocal invasive spinal lesions.

First-in-human endovascular treatment of hydrocephalus with a miniature biomimetic transdural shunt

Surgical ventriculoperitoneal shunting remains standard treatment for communicating hydrocephalus, despite persistently elevated infection and revision rates. A novel minimally invasive endovascular cerebrospinal fluid (CSF) shunt was developed to mimic the function of the arachnoid granulation which passively filters CSF from the central nervous system back into the intracranial venous sinus network. The endovascular shunt is deployed via a femoral transvenous approach across the dura mater into the cerebellopontine angle cistern. An octogenarian with intractable hydrocephalus following subarachnoid hemorrhage underwent successful endovascular shunting, resulting in swift intracranial pressure reduction from 38 to <20 cmH2O (<90 min) and resolution of ventriculomegaly. This first successful development of a percutaneous transluminal venous access to the central nervous system offers a new pathway for non-invasive treatment of hydrocephalus and the potential for intervention against neurological disorders.

CS-5 A case of anaplastic pleomorphic xanthoastrocytoma in the pineal region

Tumors in the pineal gland are rare tumors that account for about 0.3% of all brain tumors and have various histological types of tumors develop with germinoma, pineocytoma, and pineoblastoma in that order. On the other hand, pleomorphic xanthoastrocytoma (PXA) is a rare tumor of less than 0.2% and frequently occurs in supratentorial cerebral surface of children and young adults.A case was a 61-year-old man whose pineal tumor was found due to visual disturbance. MRI showed a 23 mm-sized lesion with cysts and inhomogeneous enhancement in the pineal gland. Partial calcification was observed, but there was no non-communicating hydrocephalus, and no increase in HCG-β and AFP with blood sampling. A midline suboccipital craniotomy was performed in the sitting position, a head-up surgery was performed using a 4K / 3D video microscope system (ORBEYE exoscope, Olympus) by the infratentorial supracerebellar approach (ITSCA). The bridging veins and precentral cerebellar vein were dissected to expose the posterior surface of the tumor, and internal decompression was performed. For the complication of air embolism, artificial cerebrospinal fluid was sprayed, and the bilateral internal jugular veins were compressed to confirm the inflow point. There was strong adhesion to the Rt vein of Rosenthal, and the site was removed intracapsularly. Finally, subtotal resection was performed with remaining the upper part of the tumor, a blind lesion behind the Vein of Galen. Vertical gaze palsy occurred after this operation, but it gradually improved over time. Tumor showed pathologically remarkable polymorphism, poor microvascular proliferation and necrosis, but mitotic figures 4–5 / 10HPF, MIB-1 index 10%, GFAP positive, no BRAF V600E mutation. There are few reports of PXA occurring in the pineal gland, and this case is the sixth case. It is also the first report for pineal tumors using ORBEYE through ITSCA in the sitting position.

Proteomics and functional study reveal kallikrein-6 enhances communicating hydrocephalus

Background Communicating hydrocephalus (CH) is a common neurological disorder caused by a blockage of cerebrospinal fluid. In this study, we aimed to explore the potential molecular mechanism underlying CH development. Methods Quantitative proteomic analysis was performed to screen the differentially expressed proteins (DEPs) between patients with and without CH. A CH rat model was verified by Hoechst staining, and the co-localization of the target protein and neuron was detected using immunofluorescence staining. Loss-of-function experiments were performed to examine the effect of KLK6 on the synapse structure. Results A total of 11 DEPs were identified, and kallikrein 6 (KLK6) expression was found to be significantly upregulated in patients with CH compared with that in patients without CH. The CH rat model was successfully constructed, and KLK6 was found to be co-localized with neuronal nuclei in brain tissue. The expression level of IL-1β, TNF-α, and KLK6 in the CH group was higher than that in the control group. After knockdown of KLK6 expression using small-interfering RNA (siRNA), the expression levels of synapsin-1 and PSD95 in neuronal cells were increased, and the length, number, and structure of synapses were significantly improved. Following siRNA interference KLK6 expression, 5681 differentially expressed genes (DEGs) were identified in transcriptome profile. The upregulated DEGs of Appl2, Nav2, and Nrn1 may be involved in the recovery of synaptic structures after the interference of KLK6 expression. Conclusions Collectively, KLK6 participates in the development of CH and might provide a new target for CH treatment.

Neural Network Segmentation Algorithm-Based Magnetic Resonance Imaging to Explore the Relationship between Cerebrospinal Fluid Flow with Communicating Hydrocephalus after Decompressive Craniectomy for Craniocerebral Injury

This study aimed to explore the application value of magnetic resonance imaging optimized by neural network segmentation algorithm in analyzing the relationship between cerebrospinal fluid changes after decompressive craniectomy and the occurrence of communicating hydrocephalus. 100 patients with craniocerebral injury undergoing decompressive craniectomy in hospital were selected as research subjects. The collected MRI images were processed using the OTSU algorithm, the cerebrospinal fluid flow rate was calculated based on the observation results, and the MRI based on the neural network segmentation algorithm was used to analyze the relationship between the occurrence of communicating hydrocephalus with the cerebrospinal fluid flow after decompressive craniectomy for craniocerebral injury. Additionally, the dynamics of the flow of cerebrospinal fluid in the midbrain aqueduct was analyzed. After decompressive craniectomy for craniocerebral injury, of the 24 cases of cerebrospinal fluid accumulation, 23 cases had hydrocephalus; of the 55 cases of cerebrospinal fluid flow disorder, hydrocephalus occurred in 47 cases; and of the 21 cases of normal cerebrospinal fluid, no patients had hydrocephalus. For patients with communicating hydrocephalus, the cerebrospinal fluid flow at the aqueduct was obviously accelerated and the flow was increased. From this, the differential diagnosis of cerebrospinal fluid and communicating hydrocephalus can be further confirmed. The results showed that the third ventricle of the study group was significantly reduced, and the flow of cerebrospinal fluid was similar to that of normal people. It suggested that decompressive craniectomy can relieve communicating hydrocephalus. In patients with communicating hydrocephalus, the cerebrospinal fluid flow at the aqueduct was significantly accelerated, the flow amount was increased, and the blocked flow of cerebrospinal fluid can also lead to hydrocephalus, which further clarified the relationship between the occurrence of communicating hydrocephalus with the flow of cerebrospinal fluid. In short, the neural network segmentation algorithm-based magnetic resonance imaging demonstrated a good value in the analysis of craniocerebral injury, from which the doctor observed that the cerebrospinal fluid flow at the aqueduct was significantly accelerated. Its detection of brain complications after decompressive craniectomy was also effective.

INNV-01. THE CASE OF LEPTOMENINGEAL CARCINOMATOSIS RELATED HYDROCEPHALUS MANAGED WITH SYSTEMIC AND INTRATHECAL CHEMOTHERAPY

INTRODUCTION Leptomeningeal carcinomatosis (LC) is an end-stage sequela of metastatic cancer that commonly leads to severe neurological symptoms due to hydrocephalus and commonly treated with surgery or radiation. As these procedures are invasive and have associated risks, chemotherapy could be a great alternative. We report a case of a hydrocephalus related to LC in a patient with Stage IV breast cancer that resolved after the administration of HD-MTX and intrathecal cytarabine. CASE A 64-year-old right-handed woman with Stage IV ER positive, PR positive, HER2 negative invasive lobular carcinoma of the left breast on chemotherapy with palbociclib and alpelisib who presented with mild occipital headaches, diplopia and imbalance. Imaging revealed an extensive abnormal leptomeningeal enhancement withing the posterior fossa compatible with leptomeningeal carcinomatosis. CSF cytology was consistent with metastatic adenocarcinoma. Liquid biopsy detected circulating tumor cells. During the admission for the cycle 1 of systemic chemotherapy with HD-MTX and intrathecal cytarabine, neurological status deteriorated as she became stuporous due to the newly developed moderate obstructive and communicating hydrocephalus. Surgical innervation was considered but given her response to serial Ommaya taps and dexamethasone, we proceeded with observation. Symptomatic improvement was noted within few days and confirmed on imaging showing the resolution of previously seen hydrocephalus. DISCUSSION This case highlights the role of non-invasive combination of systemic and intrathecal chemotherapy in patients with LC-related hydrocephalus aimed to preserve patient’s quality of life. No relevant disclosures.

713. Coccidioidal Meningitis Among Children: A Case Series and Single Center Experience In Central California

Background Coccidioidal meningitis is a severe form of coccidioidomycosis associated with significant morbidity and mortality. Published literature in the pediatric population is limited, particularly on coccidioidal meningitis. Here we describe a large case series of pediatric coccidioidal meningitis followed at a tertiary care center in an endemic region. Methods We performed a retrospective case review of patients ≤21 years old followed at our facility with a diagnosis of coccidioidal meningitis from January 1, 2000, to December 31, 2018. Results Overall, 30 patients were identified during the study period. The median age was 10.8 years (IQR: 4.6-15). The majority of patients were previously healthy (93%) and all required hospitalization. Fever (90%), headache (70%), vomiting (53%), and fatigue (57%) were the most common clinical manifestations. More than one-third (40%) had concurrent pulmonary disease. Only 20 patients (67%) had initial Coccidioides complement fixation (CF) titers &gt;=1:16. The majority had extra-axial brain involvement (60%) and seven (23%) had associated spinal canal disease. Over two-third required shunt placement (70%) and almost half of them (43%) underwent revision. Neurological complications including paresis/paralysis, stroke, neuropathy, seizures, and cognitive delay were observed in 20% of patients. Two-thirds (73%) of patients received fluconazole as the initial drug. However, 37% of those had fluconazole failure, requiring alternative treatment. Due to refractory disease, two patients required a novel triazole, isavuconazole, while adjunctive therapy with steroids and interferon-gamma (IFNγ) was used in 20% of patients. Most cases (83%) stabilized, 13% experienced relapses and/or progressive disease, and 3% were fatal. Conclusion Pediatric coccidioidal meningitis is an uncommon and sometimes devastating complication of disseminated coccidioidomycosis. Many patients present with relatively low CF titers, and communicating hydrocephalus and long term neurologic complications are common. Fluconazole treatment failures are common, and management remains difficult despite recent advances in therapy. Most patients do well once the disease is stabilized and require lifelong therapy. Newer therapeutic agents are needed. Disclosures All Authors: No reported disclosures