High-Resolution Ultrasound Platform for Infant Meningitis Detection: An In Vitro Demonstration.

Infant meningitis remains a severe burden on global health, particularly for young infants. Traditional ultrasound imaging techniques are limited in spatial resolution to visualize white blood cells (WBCs) in the cerebrospinal fluid (CSF), which is considered a well-established marker for meningitis detection. This work presents a novel platform that uses high-resolution ultrasound to detect the backscatter signals from microscopic CSF WBCs through the anterior fontanelle of neonates and young infants. The whole system was built around a custom probe that allows for a 20 MHz focused transducer to be mechanically controlled to map the area of interest in the CSF. Data processing can be performed internally in the device without the need to extract the images for further analysis. The in vitro feasibility of the proposed solution was evaluated in imaging 7 µm particle suspensions at different concentrations relevant to meningitis diagnosis ranging from 7- to 646-particles (pp)/µL. The experimental tests were conducted from a simple setup using a sample container to a more realistic setup based on an anatomical phantom of the neonatal head. The results show high-quality images, where 7 µm particles can be resolved for the different concentrations.

Comparison of international guidelines for CT prior to lumbar puncture in patients with suspected meningitis.

PURPOSE: To compare the performance of multiple international guidelines in selecting patients for head CT prior to lumbar puncture (LP) in suspected meningitis, focusing on identification of potential contraindications to immediate LP. METHODS: Retrospective study of 196 patients with suspected meningitis presenting to an emergency department between March 2013 and March 2023 and undergoing head CT prior to LP. UK Joint Specialist Society Guidelines (UK), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Infectious Diseases Society of America (IDSA) guidelines were evaluated by cross-referencing imaging criteria with clinical characteristics present at time of presentation. Sensitivity of each guideline for recommending neuroimaging in cases with brain shift on CT was evaluated, along with the number of normal studies and incidental or spurious findings. RESULTS: 2/196 (1%) patients had abnormal CTs with evidence of brain shift, while 14/196 (7%) had other abnormalities on CT without brain shift. UK, ESCMID and IDSA guidelines recommended imaging in 10%, 14% and 33% of cases respectively. All three guidelines recommended imaging pre-LP in 2/2 (100%) cases with brain shift. IDSA guidelines recommended more CT studies with normal findings (59 vs 16 and 24 for UK and ESCMID guidelines respectively) and CT abnormalities without brain shift (4 vs 1 and 2 respectively) than the other guidelines. CONCLUSION: UK, ESCMID and IDSA guidelines are all effective at identifying the small cohort of patients who benefit from a head CT prior to LP. Following the more selective UK/ESCMID guidelines limits the number of normal studies and incidental or spurious CT findings.

Management of a rare case of intraventricular ruptured dermoid cyst and chemical meningitis.

INTRODUCTION: Intraventricular dermoid cyst are very rare benign tumour. Due to benign nature, it may go un-noticed for years and might present with sudden rupture. Ruptured cyst can cause chemical meningitis, hydrocephalus, seizures etc. Due to lack of data, there are no defined guidelines about its management. We are reporting an interesting case of ruptured intraventricular dermoid cyst and chemical meningitis, who was managed successfully and will review the literature. CASE REPORT: A 48 years male patient was brought with complaint of sudden mental deterioration, irritability, headache, vomiting for 3 days. He had history of seizures for 1 year. On examination, his higher mental functions were deteriorated, had neck rigidity and left lower limb weakness. CT/MRI brain confirmed diagnosis of right frontal horn ruptured dermoid cyst with scattered fat droplets, hydrocephalus and ventriculitis. Excision of cyst was done via right trans-sulcal (superior frontal sulcus) approach. Patient recovered well. DISCUSSION: Intraventricular dermoid cyst are a rare benign lesion. Due to potential of rupture, it must be surgically treated. Steroids should be used to treat chemical meningitis. Various individual case reports have shown good outcome after surgical management. CONCLUSION: We recommend early surgery, thorough ventricular wash with ringer lactate, post-operative extraventricular drain and steroid cover to manage ruptured cyst and chemical meningitis.

IgG4-related hypertrophic pachymeningitis with chronic subdural haematoma.

Hypertrophic pachymeningitis is a rare disorder of the dura mater of the spine or brain. It can be caused by inflammatory, infective or neoplastic conditions or can be idiopathic. We report a man with hypertrophic pachymeningitis and bilateral chronic subdural haematoma caused by IgG4-related disease. We highlight the diagnostic challenges and discuss possible underlying mechanisms of subdural haematoma formation in inflammatory conditions. Isolated IgG4-related hypertrophic pachymeningitis with chronic subdural haematoma is very rare; previously reported cases have suggested a possible predilection for men in their sixth decade, presenting with headache as the dominant symptom. Given the rarity and complexity of the condition, it should be managed in a multidisciplinary team setting.

Evaluation of the epidemiologic, clinical, radiologic, and treatment methods of patients with subacute and chronic meningitis.

BACKGROUND: Meningitis is known as a meningeal inflammation accompanied by pleocytosis in the cerebrospinal fluid (CSF), and can be classified into acute, subacute, and chronic meningitis based on symptoms duration of ≤ 5 days, ≥ 5 days and ≥ 4 weeks, respectively. Subacute and chronic meningitis are caused mainly by indolent infectious agents and noninfectious causes such as autoimmune, and neoplastic. In this study, we investigated the characteristics, diagnosis, and treatment of subacute and chronic meningitis. METHODS: We extracted the medical records of patients with chronic and subacute meningitis who were referred to three tertiary centers from Jun 2011 to Jun 2021. Initially, 2050 cases of meningitis were screened, and then 79 patients were included in the study. RESULTS: Headache (87.3%), nausea and vomiting (74.7%), fever (56.4%), and visual impairments (55.7%) were the most prevalent symptoms. The most common signs were nuchal rigidity (45.3%), altered mental status (26.9%), and papillary edema (37.5%). Brain computed tomography (CT) was normal in 68.6% of the patients while 22.9% of the cases had hydrocephalus. Brain magnetic resonance imaging (MRI) was normal in 60.0% of the patients. The most common abnormal MRI findings were leptomeningeal enhancement (16.0%) and hydrocephalus (16.0%). We had a 44.3% definite diagnosis with bacterial (n:25, 31.6%) and neoplastic (n:8, 10.1%) being the most prevalent etiologies. Mycobacterium tuberculosis (60%) and Brucella spp. (12%) were the most prevalent bacterial pathogens. CONCLUSIONS: The most common etiologies include infectious, neoplastic, and immunologic. Due to insidious presentation and uncommon etiologies, establishing a proper diagnosis, and providing timely targeted treatment for patients with subacute and chronic meningitis remains a challenge for clinicians.

Hypertrophic Pachymeningitis Development in Eosinophilic Granulomatosis with Polyangiitis at Relapse of Disease: A Case-Based Review.

Hypertrophic pachymeningitis (HP) presents with thickening of the dura mater in the cerebrum and spine, and its symptoms vary depending on the affected location. The association of HP with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis has been recognized, and most cases are complicated by granulomatosis with polyangiitis. We report the case of a 47-year-old man who presented with HP upon relapse of eosinophilic granulomatosis with polyangiitis (EGPA), with literature review. He presented with disturbance of consciousness, and magnetic resonance imaging (MRI) revealed thickening of the dura mater around the left parietal lobe. Although myeloperoxidase (MPO)-ANCA was positive on EGPA diagnosis, the elevation of MPO-ANCA was not documented at the onset of HP. Brain perfusion scintigraphy showed an increase in blood flow in the left parietal lobe and temporal lobe, and electroencephalogram (EEG) revealed slow waves in the left parietal lobe. He was treated with a high dose of corticosteroid and rituximab, and the slow waves on EEG and brain perfusion were normalized. Although the most frequent symptom of HP is headache, disturbance of consciousness can be the manifestation of HP, and inflammation of HP could affect the cerebral parenchyma, which can be documented as abnormal EEG and perfusion scintigraphy. Literature review revealed that most of the HP in EGPA developed when EGPA relapsed, and was observed in patients with MPO-ANCA positivity. HP develops without evidence of other clinical features of EGPA; therefore, adequate imaging, including contrast-enhanced MRI, is necessary. Rituximab may be effective for treating HP complicated with EGPA.

Magnetic resonance imaging in dogs with neuroangiostrongyliasis (rat lungworm disease).

The magnetic resonance imaging (MRI) appearance of the brain and spinal cord in humans with neuroangiostrongyliasis (NA) due to Angiostrongylus cantonensis infection has been well reported. Equivalent studies in animals are lacking. This case series describes clinical and MRI findings in 11 dogs with presumptively or definitively diagnosed NA. MRI of the brain and/or spinal cord was performed using high-field (1.5 T) or low-field (0.25 T) scanners using various combinations of transverse, sagittal, dorsal and three-dimensional (3D) T1-weighted (T1W), transverse, sagittal and dorsal T2-weighted (T2W), T2W fluid-attenuated inversion recovery (FLAIR) and T2*-weighted (T2*W) gradient echo (GRE), dorsal T2W short tau inversion recovery (STIR) and post-gadolinium transverse, sagittal, dorsal and 3D T1W and transverse T2W FLAIR sequences. In 4/6 cases where the brain was imaged, changes consistent with diffuse meningoencephalitis were observed. Evidence of meningeal involvement was evident even when not clinically apparent. The spinal cord was imaged in 9 dogs, with evidence of meningitis and myelitis detected in regions consistent with the observed neuroanatomical localization. Pathognomonic changes of neural larva migrans, as described in some human patients with NA, were not detected. NA should be considered in the differential diagnosis of dogs with MRI evidence of focal or diffuse meningitis, myelitis and/or encephalitis, especially in areas where A. cantonensis is endemic. If not precluded by imaging findings suggestive of brain herniation, cerebrospinal fluid (CSF) collection for cytology, fluid analysis, real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) testing should be considered mandatory in such cases after the MRI studies.

Hypertrophic Pachymeningitis Related Brain Infarction in Synovitis-Acne-Pustulosis-Hyperostosis Osteomyelitis Syndrome.

A 50-year-old woman with a history of synovitis-acne-pustulosis-hyperostosis osteomyelitis (SAPHO) syndrome was admitted for left unilateral neglect, dysarthria, and left hemiparesis. Brain MRI showed multiple infarctions in the territory of the right middle cerebral artery and gadolinium enhancement of the thickened frontotemporal dura mater on the right side. MR angiography showed significant narrowing of the cavernous segment of the right internal carotid artery. The right internal carotid artery stenosis was thought to originate from hypertrophic pachymeningitis associated with SAPHO syndrome. This is the first report of brain infarction due to internal carotid artery stenosis caused by hypertrophic pachymeningitis associated with SAPHO syndrome.

[Autoimmune Encephalitis/Meningitis].

Less than half of the cases of autoimmune encephalitis have brain MRI abnormalities; however, some patterns of MRI findings help diagnosis. Usually, DWI and FLAIR images reveal hyperintensity lesions in the cortical or subcortical regions or the cerebellum and/or the brainstem. Hyperintensity lesions in the limbic cortex on DWI suggest NMDAR encephalitis. RA or polychondritis-related meningitis show bright dot or linear signals on the convexities on DWI. Area postrema syndrome is a typical form of neuromyelitis optica. These conditions need to be diagnosed promptly for effective treatment.

Neuroinflammation trajectories precede cognitive impairment after experimental meningitis-evidence from an in vivo PET study.

BACKGROUND: Bacterial meningitis is a devastating central nervous system (CNS) infection with acute and long-term neurological consequences, including cognitive impairment. The aim of this study was to understand the association between activated microglia-induced neuroinflammation and post-meningitis cognitive impairment. METHOD: Meningitis was induced in male Wistar rats by injecting Streptococcus pneumoniae into the brain through the cisterna magna, and rats were then treated with ceftriaxone. Twenty-four hours and 10 days after meningitis induction, rats were imaged with positron emission tomography (PET) using [11C]PBR28, a specific translocator protein (TSPO) radiotracer, to determine in vivo microglial activation. Following imaging, the expression of TSPO, cardiolipin, and cytochrome c, inflammatory mediators, oxidative stress markers, and glial activation markers were evaluated in the prefrontal cortex and hippocampus. Ten days after meningitis induction, animals were subjected to behavioral tests, such as the open-field, step-down inhibitory avoidance, and novel object recognition tests. RESULTS: Both 24-h (acute) and 10-day (long-term) groups of rats demonstrated increased [11C]PBR28 uptake and microglial activation in the whole brain compared to levels in the control group. Although free from infection, 10-day group rats exhibited increased expression levels of cytokines and markers of oxidative stress, microglial activation (IBA-1), and astrocyte activation (GFAP) similar to those seen in the 24-h group. Acute meningitis induction also elevated TSPO, cytochrome c, and caspase-3 levels with no change in caspase-9 levels. Furthermore, upregulated levels of TSPO, cytochrome c, and caspase-3 and caspase-9 were observed in the rat hippocampus 10 days after meningitis induction with a simultaneous reduction in cardiolipin levels. Animals showed a cognitive decline in all tasks compared with the control group, and this impairment may be at least partially mediated by activating a glia-mediated immune response and upregulating TSPO. CONCLUSIONS: TSPO-PET could potentially be used as an imaging biomarker for microglial activation and long-term cognitive impairment post-meningitis. Additionally, this study opens a new avenue for the potential use of TSPO ligands after infection-induced neurological sequelae.

Ultrasound of acquired posterior fossa abnormalities in the newborn.

Neonatal brain sonography is part of routine clinical practice in neonatal intensive care units, but ultrasound imaging of the posterior fossa has gained increasing attention since the burden of perinatal acquired posterior fossa abnormalities and their impact on motor and cognitive neurodevelopmental outcome have been recognized. Although magnetic resonance imaging (MRI) is often superior, posterior fossa abnormalities can be suspected or detected by optimized cranial ultrasound (CUS) scans, which allow an early and bed-side diagnosis and monitoring through sequential scans over a long period of time. Different ultrasound appearances and injury patterns of posterior fossa abnormalities are described according to gestational age at birth and characteristics of the pathogenetic insult. The aim of this review article is to describe options to improve posterior fossa sequential CUS image quality, including the use of supplemental acoustic windows, to show standard views and normal ultrasound anatomy of the posterior fossa, and to describe the ultrasound characteristics of acquired posterior fossa lesions in preterm and term infants with effect on long-term outcome. The limitations and pitfalls of CUS and the role of MRI are discussed.

Contrast-enhanced modified 3D T1-weighted TSE black-blood imaging can improve detection of infectious and neoplastic meningitis.

OBJECTIVES: To evaluate the diagnostic value of a contrast-enhanced 3D T1-weighted-modified volumetric isotropic turbo spin-echo acquisition sequence (T1-mVISTA) in comparison with a conventional 3D T1-weighted magnetization-prepared rapid gradient-echo (T1-MP-RAGE) sequence for the detection of meningeal enhancement in patients with meningitis. METHODS: Thirty patients (infectious meningitis, n = 12; neoplastic meningitis, n = 18) and 45 matched controls were enrolled in this retrospective case-control study. Sets of randomly selected T1-mVISTA and T1-MP-RAGE images (both with 0.8-mm isotropic resolution) were read separately 4 weeks apart. Image quality, leptomeningeal and dural enhancement, grading of visual contrast enhancement, and diagnostic confidence were compared using the Kruskal-Wallis rank sum test. RESULTS: Image quality was rated to be good to excellent in 75 out of 75 cases (100%) for T1-mVISTA and 74 out of 75 cases (98.7%) for T1-MP-RAGE. T1-mVISTA detected significantly more patients with leptomeningeal enhancement (p = 0.006) compared with T1-MP-RAGE (86.7 vs. 50.0%, p < 0.001), each with specificity of 100%. Similarly, sensitivity of T1-mVISTA for the detection of dural and/or leptomeningeal enhancement was also significantly higher compared with that of T1-MP-RAGE (96.7 vs. 80.0%, p = 0.025) without significant differences regarding specificity (97.8 vs. 95.6%, p = 0.317). No significant differences were found for dural enhancement alone. Diagnostic confidence in T1-mVISTA was significantly higher (p = 0.01). Visual contrast enhancement was tendentially higher in T1-mVISTA. CONCLUSIONS: T1-mVISTA may be an adequate and probably better alternative to T1-MP-RAGE for detection of leptomeningeal diseases. KEY POINTS: • Black-blood T1-mVISTA showed a significant higher sensitivity for the detection of leptomeningeal enhancement compared with MP-RAGE without losses regarding specificity. • Diagnostic confidence was assessed significantly higher in T1-mVISTA. • T1-mVISTA should be considered a supplement or an alternative to T1-MP-RAGE in patients with suspected leptomeningeal diseases.

Clinical features of hypertrophic pachymeningitis in a center survey.

BACKGROUND: Hypertrophic pachymeningitis (HP) is characterized by cranial and/or spinal thickening of the dura mater with or without associated inflammation. Neuroimaging studies reveal dura mater thickening and focal or diffuse contrast enhancement. It is described in association with trauma, infections, tumors, autoimmune/inflammatory diseases, and cerebrospinal fluid hypotension syndrome, with some cases remaining idiopathic. METHODS: A retrospective study was conducted with patients' identification through a key terms search within MRI reports in the period of July 2008 to September 2015. Clinical files, MRI, laboratory, and pathology data were reviewed. RESULTS: Fifty-three patients were identified and 20 were excluded because they did not meet the inclusion criteria. Of the 33 included, 19 were female, with a mean age at symptoms onset of 51.2 ± 17.6 years. The most common presenting symptoms were headache and cranial nerves palsy, followed by seizures, delirium, lumbar pain, cognitive decline, motor deficit, and language impairment. In 17 patients, a neoplastic etiology was identified; in eight, inflammatory/autoimmune; in six, infectious; and two were classified as idiopathic. Of the eight patients with inflammatory/autoimmune etiology, four had possible IgG4-related disease (IgG4-RD) and the remaining had granulomatosis with polyangiitis, sarcoidosis, rheumatoid arthritis, and Tolosa-Hunt syndrome. Treatment was directed according to the underlying etiology. DISCUSSION: In the described series, a female predominance was identified, with symptoms' onset in the 5th decade. Although headache was the most common symptom, clinical presentation was varied, emphasizing the role of MRI in HP diagnosis. The underlying etiologies were diverse, with only a few cases remaining idiopathic, also reflecting the contribution of the recently described IgG4-RD.

The clinical and imaging features of hypertrophic pachymeningitis: a clinical analysis on 22 patients.

OBJECTIVE: To explore the clinical and imaging features of patients with hypertrophic cranial pachymeningitis (HCP). METHODS: A retrospective study was performed on 22 patients with HCP diagnosed at the Affiliated Hospital of Xuzhou Medical University from February 2014 to September 2017. RESULTS: A headache was present as an initial symptom in 18 patients. The headache was associated with the loss of vision (2 cases), facial pain (1 case), and unsteady walking (1 case). Other symptoms included cranial nerve dysfunction (15 cases), cerebellar ataxia (4 cases), and sinus thrombosis (3 cases). In the laboratory tests, 7 patients showed an increased number of white blood cells, higher levels of C-reaction protein (CRP), and erythrocyte sedimentation rate (ESR). An elevated level of immunoglobulin G4 (IgG4) and the presence of the anti-neutrophil cytoplasmic antibody (ANCA) were found in 3 and 2 patients respectively. There were 17 patients who had abnormalities in their cerebrospinal fluid (CSF) on lumbar puncture. On magnetic resonance imaging (MRI), a local or generalized thickening was observed in the cerebral falx, the tentorium of the cerebellum, the fronto-parietal lobe, the occipito-parietal lobe, and the dura of skull base. A dural biopsy obtained in one case showed a variety of inflammatory changes. An immunohistochemical analysis revealed the positivity of CD138, IgG, and IgG4 in some cells. All 22 patients had a good response to corticosteroids. CONCLUSION: HCP mainly leads to a headache and the paralysis of multiple cranial nerves. A biopsy and MRI are often required and serve as the basis for the diagnosis and effective therapy.

Computed tomography head scans prior to lumbar punctures in suspected meningitis.

BACKGROUND: The literature suggests that certain clinical criteria to determine raised intracranial pressure (ICP) should be met if a patient suspected of meningitis is to undergo a computed tomography (CT) head scan prior to having a lumbar puncture (LP). AIM: To evaluate whether these criteria were being used by the general medicine department of Auckland City Hospital when requesting CT scans prior to LPs in patients with suspected meningitis. METHODS: A total of 37 patients admitted under general medicine with suspected meningitis from 1 January to 31 July 2016 were retrospectively audited based on the clinical evidence justifying the decision to do a CT scan prior to a LP. RESULTS: Only 7 of 24 patients who underwent CT scans had met clinical criteria for raised ICP. There were no abnormalities found on any of the CT scans and approximately two-thirds of these patients had a final diagnosis of viral illness or headache. CONCLUSION: A large number of patients with suspected meningitis under general medicine at Auckland City Hospital are having CT scans without clinical evidence suggestive of raised ICP.

Increased Intracranial Pressure Attenuates the Pulsating Component of Cerebral Venous Outflow.

BACKGROUND: The underlying physiology of the intracranial pressure (ICP) curve morphology is still poorly understood. If this physiology is explained it could be possible to extract clinically relevant information from the ICP curve. The venous outflow from the cranial cavity is pulsatile, and in theory the pulsatile component of venous outflow from the cranial cavity should be attenuated with increasing ICP. In this study, we explored the relationship between ICP and the pulsatility of the venous outflow from the intracranial cavity. METHODS: Thirty-seven neuro-intensive care patients that had been examined with phase-contrast magnetic resonance imaging regarding cerebral blood flow (CBF) through the internal carotid and vertebral arteries and venous flow in the internal jugular veins were retrospectively included. The pulsatility of the jugular flow was determined by calculating the venous pulsatile index. The results were correlated to clinical data registered in the patient data monitoring system, including ICP and cerebral perfusion pressure (CPP). RESULTS: CBF was 996 ± 298 ml/min, and the flow in the internal jugular veins equaled 67 ± 17% of the CBF, with a range of 22-97%. The venous pulsatile index correlated negatively to ICP (R = - 0.47 p = 0.003). The lowest flow in the internal jugular veins over the cardiac cycle (Fmin) was not correlated to ICP. Temperature, end-tidal CO2, MAP, and CPP were not correlated to venous pulsatility. CONCLUSION: An increase in ICP correlates to a lower pulsatility of the venous outflow from the cranial cavity. A lower pulsatility could be due to increased pressure requirements to compress intracranial veins with increasing ICP.

Rheumatoid meningitis developed in patient with stable rheumatoid arthritis and myasthenia gravis-detailed analysis of intracranial inflammation using flow cytometry.

BACKGROUND: Rheumatoid meningitis (RM) is a rare disorder that often develops during a remission phase of rheumatoid arthritis (RA). This is the first study to demonstrate differences in regard to immunological disturbance between blood and cerebrospinal fluid (CSF) samples obtained from a patient with RM using flow cytometry. CASE PRESENTATION: A 36-year-old woman with RA and generalized myasthenia gravis (MG) developed RM during a remission phase. Although both RA and MG were stable and well controlled, she noticed fever, headache, and transient sensory disturbance. Blood and CSF examination findings suggested aseptic meningitis, while brain magnetic resonance imaging revealed restricted portions of meningitis and associated cortical lesions, compatible with a diagnosis of RM. The dose of oral prednisolone was increased, which ameliorated the symptoms within 1 week along with improvement in CSF findings. This patient exhibited features of RM that were manifested in a manner independent of the activity of RA. An investigation of cellular immunity using CSF specimens with flow cytometry showed differences in regard to the pathogenesis of inflammation in the CSF as compared to outside of the central nervous system. In contrast to results obtained with paired blood samples, CSF cells at the peak stage of RM showed a marked increase in CCR3+ Th2 cells and marked decrease in CD8+ cells, suggesting an immunoregulatory disturbance in the CSF. Those findings indicated a CSF-specific activation of humoral immunity, resulting in augmentation of meningeal inflammation, as shown by excess synthesis of intrathecal IgG and markedly elevated interleukin-6 level. Results of the present detailed investigation of lymphocyte subsets revealed a discrepancy regarding the process of inflammation in this RM patient between CSF and blood samples. CONCLUSIONS: RM is not a simple reflection of the immune status of RA, as the pathogenesis seems related to, at least in part, CSF-specific immunological dysregulation.

An unusual case of inflammatory meningitis in a young man with systemic lupus erythematosus.

We describe a man presenting with unusual neurological manifestations of systemic lupus erythematosus (SLE) including pachymeningitis, aseptic meningitis and encephalitis with grossly elevated cerebrospinal fluid protein, responding to immunosuppression. Initially he had intermittent dysarthria, dysphasia and unilateral upper limb weakness. One month later he experienced dysphasia, right-sided hemiparesis and confusion. Cerebrospinal fluid (CSF) analysis showed a white cell count of 70 x 106/litre and an unusually elevated protein level of 5.39 g/litre. An MRI brain showed dural and leptomeningeal enhancement compatible with a meningitic process. He improved with cefotaxime and aciclovir. On day seven of antimicrobials he developed left-sided weakness, sensory inattention and a left homonymous hemianopia. He responded well to intravenous methylprednisolone. On switching to oral prednisolone he developed expressive dysphasia, a right inferior quadrantanopia and seizures. His bloods were suggestive of macrophage activation syndrome. The patient improved with methylprednisolone and intravenous immunoglobulins, and the improvement was sustained on switching back to oral prednisolone. The prevalence of neuropsychiatric manifestations of SLE varies between 14 and 80% and according to the American College of Rheumatology includes 19 conditions. This case is unique because although some features were in keeping with aseptic meningitis the MRI appearances were also suggestive of pachymeningitis.

The mouse cortical meninges are the site of immune responses to many different pathogens, and are accessible to intravital imaging.

A wide range of viral and microbial infections are known to cause meningitis, and there is evidence that the meninges are the gateway to pathogenic invasion of the brain parenchyma. Hence observation of these regions has wide application to understanding host-pathogen interactions. Interactions between pathogens and cells of the immune response can be modified by changes in their environment, such as suppression of the flow of blood and lymph, and, particularly in the case of the meninges, with their unsupported membranes, invasive dissection can alter the tissue architecture. For these reasons, intravital imaging through the unperforated skull is the method of choice. We give a protocol for a simple method of two-photon microscopy through the thinned cortical skull of the anesthetized mouse to enable real-time imaging with sub-micron resolution through the meninges and into the superficial brain parenchyma. In reporter mice in which selected cell types express fluorescent proteins, imaging after infection with fluorescent pathogens (lymphocytic choriomeningitis virus, Trypanosoma brucei or Plasmodium berghei) has shown strong recruitment to the cortical meninges of immune cells, including neutrophils, T cells, and putative dendritic cells and macrophages. Without special labeling, the boundaries between the dura mater, the leptomeninx, and the parenchyma are not directly visualized in intravital two-photon microscopy, but other landmarks and characteristics, which we illustrate, allow the researcher to identify the compartment being imaged. While most infectious meningitides are localized mainly in the dura mater, others involve recruitment of immune cells to the leptomeninx.

Leptomeningeal form of Immunoglobulin G4-related hypertrophic meningitis with perivascular spread: a case report and review of the literature.

PURPOSE: Immunoglobulin G4 (IgG4)-related disease represents a spectrum of fibro-inflammatory disorders that affects various organ systems, including the central nervous system. METHODS: Here we present the case of lgG4-related hypertrophic meningitis with exclusively leptomeningeal involvement and spread via perivascular spaces. RESULTS: A 58-year-old male patient presented with complex partial seizures. Initial computed tomography examination showed left frontal sulcal hyperdensity. Subsequent magnetic resonance examination revealed FLAIR hyperintensity in the central sulcus, with post-contrast enhancement in the form of "dotted line." Physical examination, routine laboratory, and cerebrospinal fluid analyses were unremarkable. Meningeal biopsy confirmed IgG4-related meningitis. After corticosteroid treatment, a complete resolution of imaging findings was observed. Two months later, the patient presented with relapsing neurological symptoms and radiological findings in postcentral, precentral, and temporal sulci, resembling the form of "dotted line" contrast enhancement. In addition, linear intraparenchymal enhancement that followed perivascular spaces was seen in the left parietal lobe. After repeated steroid therapy, all lesions resolved completely. CONCLUSION: We reported the first case of isolated IgG4-related leptomeningeal involvement with a "dotted line" enhancement and perivascular intraparenchymal spread. Although IgG4-related meningitis represents a rare disease, both clinicians and radiologists should include this condition in the differential diagnosis of unclear leptomeningeal disease.