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Nature Communications Jan 2022Meningeal lymphatic vessels have been described in animal studies, but limited comparable data is available in human studies. Here we show dural lymphatic structures...
Meningeal lymphatic vessels have been described in animal studies, but limited comparable data is available in human studies. Here we show dural lymphatic structures along the dural venous sinuses in dorsal regions and along cranial nerves in the ventral regions in the human brain. 3D T2-Fluid Attenuated Inversion Recovery magnetic resonance imaging relies on internal signals of protein rich lymphatic fluid rather than contrast media and is used in the present study to visualize the major human dural lymphatic structures. Moreover we detect direct connections between lymphatic fluid channels along the cranial nerves and vascular structures and the cervical lymph nodes. We also identify age-related cervical lymph node atrophy and thickening of lymphatics channels in both dorsal and ventral regions, findings which reflect the reduced lymphatic output of the aged brain.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Case-Control Studies; Cranial Sinuses; Epilepsy; Female; Glymphatic System; Humans; Lymph Nodes; Magnetic Resonance Imaging; Male; Meninges; Middle Aged; Phantoms, Imaging; Retrospective Studies; Sex Factors
PubMed: 35017525
DOI: 10.1038/s41467-021-27887-0 -
Neurology India 2022Hypertrophic pachymeningitis (HPM) is a unique disorder characterized by thickening and fibrosis of the dura mater. Clinically it presents with headache, cranial nerve... (Observational Study)
Observational Study
BACKGROUND
Hypertrophic pachymeningitis (HPM) is a unique disorder characterized by thickening and fibrosis of the dura mater. Clinically it presents with headache, cranial nerve palsies, and other focal neurological deficits. Two forms exist, one is primary, where all other causes have been excluded and the other is secondary where an identifiable cause exists. It is important to recognize these secondary causes as treatment depends on the etiology.
OBJECTIVE
To elucidate the various characteristics of HPM. To delineate clinical-radiological features that help differentiate secondary from primary causes and to understand treatment response and disease outcomes of HPM.
METHODS
This retrospective observational study included 33 patients who presented with radiological diagnosis of HPM from January 2014 to July 2019. Spontaneous intracranial hypotension patients were excluded. All patients were extensively evaluated for secondary causes and treatment outcomes were analyzed on follow-up.
RESULTS AND CONCLUSIONS
Secondary causes of HPM were present in 48% cases. The clue for primary causes is an associated Tolosa-Hunt syndrome. Secondary causes in our series are immunological, infection, and malignancy. Clues to differentiate primary from these secondary causes are clinical like myelopathy, seizures, poor response to immunosuppression; radiological like hypertrophic cranial nerves, infarcts, bony erosion, and leptomeningeal involvement. There are case reports in literature but large Indian studies are lacking. This manuscript presents a large cohort of cases with HPM, which helps differentiate primary from secondary causes, as management and prognosis depend on etiology. An algorithm depicting the approach to the management of HPM has been presented.
Topics: Humans; Magnetic Resonance Imaging; Meningitis; Cranial Nerve Diseases; Headache; Treatment Outcome; Hypertrophy; Dura Mater
PubMed: 36537427
DOI: 10.4103/0028-3886.364052 -
Cell Reports Nov 2022The trigeminal sensory innervation of the cranial meninges is thought to serve a nociceptive function and mediate headache pain. However, the activity of meningeal...
The trigeminal sensory innervation of the cranial meninges is thought to serve a nociceptive function and mediate headache pain. However, the activity of meningeal afferents under natural conditions in awake animals remains unexplored. Here, we used two- and three-dimensional two-photon calcium imaging to track the activity of meningeal afferent fibers in awake mice. Surprisingly, a large subset of afferents was activated during non-noxious conditions such as locomotion. We estimated locomotion-related meningeal deformations and found afferents with distinct dynamics and tuning to various levels of meningeal expansion, compression, shearing, and Z-axis motion. Further, these mechanosensitive afferents were often tuned to distinct directions of meningeal expansion or compression. Thus, in addition to their role in headache-related pain, meningeal sensory neurons track the dynamic mechanical state of the meninges under natural conditions.
Topics: Animals; Mice; Meninges; Neurons, Afferent; Headache; Locomotion
PubMed: 36384109
DOI: 10.1016/j.celrep.2022.111648 -
Seizure Apr 2023Central nervous system (CNS) tuberculosis is a life-threatening condition that usually presents with seizures, particularly in children and HIV-infected patients.... (Review)
Review
Central nervous system (CNS) tuberculosis is a life-threatening condition that usually presents with seizures, particularly in children and HIV-infected patients. Tuberculous meningitis (TBM) and tuberculomas are the two forms of CNS tuberculosis that can present with seizures. Seizures usually resolve after successful treatment of the underlying infection. However, the success of the treatment is usually based on an early diagnosis. Delay in the treatment of CNS tuberculosis increases the risk of its associated complications, such as stroke. This would lead to the development of epilepsy. Early seizures may be related to meningeal irritation and cerebral edema, whereas late seizures are often associated with structural brain lesions that generally require more advanced and prolonged treatment. Risk factors associated with the development of epilepsy include young age, refractory seizures, tuberculoma, cortical involvement, epileptiform discharges, and residual lesions. Treatment of CNS tuberculosis is based on early initiation of appropriate anti-tuberculous drugs, antiseizure medications, and correction of associated predisposing factors. Finally, further research into the mechanisms of seizures and the development of epilepsy in CNS tuberculosis could help improve management of these conditions.
Topics: Child; Humans; Tuberculosis, Central Nervous System; Tuberculosis, Meningeal; Epilepsy; Seizures; Risk Factors
PubMed: 36963243
DOI: 10.1016/j.seizure.2023.03.006 -
Medicine Nov 2022Diagnosis of viral meningitis (VM) is uncommon practice in Sudan and there is no local viral etiological map. We therefore intended to differentiate VM using... (Review)
Review
Diagnosis of viral meningitis (VM) is uncommon practice in Sudan and there is no local viral etiological map. We therefore intended to differentiate VM using standardized clinical codes and determine the involvement of herpes simplex virus types-1 and 2 (HSV-1/2), varicella zoster virus, non-polio human enteroviruses (HEVs), and human parechoviruses in meningeal infections in children in Sudan. This is a cross-sectional hospital-based study. Viral meningitis was differentiated in 503 suspected febrile attendee of Omdurman Hospital for Children following the criteria listed in the Clinical Case Definition for Aseptic/Viral Meningitis. Patients were children age 0 to 15 years. Viral nucleic acids (DNA/RNA) were extracted from cerebrospinal fluid (CSF) specimens using QIAamp® UltraSens Virus Technology. Complementary DNA was prepared from viral RNA using GoScriptTM Reverse Transcription System. Viral nucleic acids were amplified and detected using quantitative TaqMan® Real-Time and conventional polymerase chain reactions (PCRs). Hospital diagnosis of VM was assigned to 0%, when clinical codes were applied; we considered 3.2% as having VM among the total study population and as 40% among those with proven infectious meningitis. Two (0.4%) out of total 503 CSF specimens were positive for HSV-1; Ct values were 37.05 and 39.10 and virus copies were 652/PCR run (261 × 103/mL CSF) and 123/PCR run (49.3 × 103/mL CSF), respectively. Other 2 (0.4%) CSF specimens were positive for non-polio HEVs; Ct values were 37.70 and 38.30, and the approximate virus copies were 5E2/PCR run (~2E5/mL CSF) and 2E2/PCR run (~8E4/mL CSF), respectively. No genetic materials were detected for HSV-2, varicella zoster virus, and human parechoviruses. The diagnosis of VM was never assigned by the hospital despite fulfilling the clinical case definition. Virus detection rate was 10% among cases with proven infectious meningitis. Detected viruses were HSV-1 and non-polio HEVs. Positive virus PCRs in CSFs with normal cellular counts were seen.
Topics: Humans; Child; Infant, Newborn; Infant; Child, Preschool; Adolescent; Cross-Sectional Studies; Meningitis, Viral; Herpesvirus 2, Human; Herpesvirus 1, Human; Herpesvirus 3, Human; Enterovirus; Viruses; Parechovirus; Nucleic Acids
PubMed: 36401437
DOI: 10.1097/MD.0000000000031588 -
Frontiers in Immunology 2023To describe the clinical and neuroimaging characteristics of rheumatoid meningitis (RM) in Chinese patients.
OBJECTIVE
To describe the clinical and neuroimaging characteristics of rheumatoid meningitis (RM) in Chinese patients.
METHODS
The patients admitted to our hospital with the diagnosis of RM in the past 8 years were retrospectively analyzed.
RESULTS
Six patients with RM were identified among 933 patients admitted with rheumatoid arthritis (RA). The symptoms of meningitis occurred after onset of arthritis in five patients and before onset in one. Headache (n=6), hyperacute focal neurological deficits (n=4) and seizures (n=3) were the most prevalent symptoms. The nadir modified Rankin Scale score was ≥3 in five patients. Rheumatoid factor was elevated in all patients, and interleukin-6 levels in cerebrospinal fluid were dramatically elevated in three of four tested patients. Magnetic resonance imaging of the brain revealed that the meninges were affected in all patients and the cerebral parenchyma was affected in one patient. The lesions were generally located in the frontoparietal region and showed restricted diffusion along the adjacent subarachnoid space. RM occurred during disease-modifying therapy in four patients. In the acute episode, three patients improved on tocilizumab and the other three improved on pulse corticosteroids. For maintenance therapy, two patients received combined therapy of tocilizumab and other immunosuppressive agents, one received adalimumab and methotrexate, and two received low-dose oral corticosteroids with an immunosuppressive agent. Five patients had a good outcome, and one died of pneumonia after stabilization of his neurologic conditions. No relapse of RM occurred on immunotherapy during follow-up.
CONCLUSIONS
Chinese patients with RM share some remarkable clinical and neuroimaging features and respond well to appropriate immunotherapy. Tocilizumab could be a treatment option for this severe complication of RA.
Topics: Humans; Retrospective Studies; Arthritis, Rheumatoid; Meningitis; Methotrexate; Adrenal Cortex Hormones
PubMed: 37350975
DOI: 10.3389/fimmu.2023.1065650 -
Annals of Medicine Dec 2023Tuberculous meningitis is an infectious disease of the central nervous system caused by Mycobacterium tuberculosis (M. tuberculosis). It mainly involves the meninges... (Review)
Review
Tuberculous meningitis is an infectious disease of the central nervous system caused by Mycobacterium tuberculosis (M. tuberculosis). It mainly involves the meninges and brain parenchyma, as well as the spinal cord and meninges; Disability and mortality rates are high. In recent years, due to the increase of drug-resistant tuberculosis patients, population mobility and the prevalence of acquired immune deficiency syndrome, the incidence rate of tuberculosis has increased significantly, and tuberculous meningitis has also increased. At present, tuberculosis is still a worldwide infectious disease that seriously threatens human health, especially in underdeveloped and developing countries. China is the largest developing country in the world with a large population. The situation of tuberculosis prevention and control is grim. Its disability rate is the highest in tuberculosis infection. In addition to the common non-specific manifestations, tuberculous meningoencephalitis may also have rare manifestations of stroke, hearing loss and visual loss. Understanding and timely improvement of corresponding examinations and targeted treatment will help improve the prognosis of patients.
Topics: Humans; Tuberculosis, Meningeal; Mycobacterium tuberculosis; Brain; Meningoencephalitis; China
PubMed: 36598144
DOI: 10.1080/07853890.2022.2164348 -
Frontiers in Immunology 2021The differential diagnosis between tuberculous meningitis (TBM) and bacterial meningitis (BM) remains challenging in clinical practice. This study aimed to establish a...
BACKGROUND
The differential diagnosis between tuberculous meningitis (TBM) and bacterial meningitis (BM) remains challenging in clinical practice. This study aimed to establish a diagnostic model that could accurately distinguish TBM from BM.
METHODS
Patients with TBM or BM were recruited between January 2017 and January 2021 at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort). The detection for indicators involved in cerebrospinal fluid (CSF) and T-SPOT assay were performed simultaneously. Multivariate logistic regression was used to create a diagnostic model.
RESULTS
A total of 174 patients (76 TBM and 98 BM) and another 105 cases (39 TBM and 66 BM) were enrolled from Qiaokou cohort and Caidian cohort, respectively. Significantly higher level of CSF lymphocyte proportion while significantly lower levels of CSF chlorine, nucleated cell count, and neutrophil proportion were observed in TBM group when comparing with those in BM group. However, receiver operating characteristic (ROC) curve analysis showed that the areas under the ROC curve (AUCs) produced by these indicators were all under 0.8. Meanwhile, tuberculosis-specific antigen/phytohemagglutinin (TBAg/PHA) ratio yielded an AUC of 0.889 (95% CI, 0.840-0.938) in distinguishing TBM from BM, with a sensitivity of 68.42% (95% CI, 57.30%-77.77%) and a specificity of 92.86% (95% CI, 85.98%-96.50%) when a cutoff value of 0.163 was used. Consequently, we successfully established a diagnostic model based on the combination of TBAg/PHA ratio, CSF chlorine, CSF nucleated cell count, and CSF lymphocyte proportion for discrimination between TBM and BM. The established model showed good performance in differentiating TBM from BM (AUC: 0.949; 95% CI, 0.921-0.978), with 81.58% (95% CI, 71.42%-88.70%) sensitivity and 91.84% (95% CI, 84.71%-95.81%) specificity. The performance of the diagnostic model obtained in Qiaokou cohort was further validated in Caidian cohort. The diagnostic model in Caidian cohort produced an AUC of 0.923 (95% CI, 0.867-0.980) with 79.49% (95% CI, 64.47%-89.22%) sensitivity and 90.91% (95% CI, 81.55%-95.77%) specificity.
CONCLUSIONS
The diagnostic model established based on the combination of four indicators had excellent utility in the discrimination between TBM and BM.
Topics: Adult; Antigens, Bacterial; Biomarkers; Cerebrospinal Fluid; China; Cohort Studies; Diagnosis, Differential; Enzyme-Linked Immunospot Assay; Female; Humans; Interferon-gamma; Male; Meningitis, Bacterial; Middle Aged; Models, Biological; Mycobacterium tuberculosis; Tuberculosis, Meningeal
PubMed: 34867952
DOI: 10.3389/fimmu.2021.731876 -
Cellular and Molecular Life Sciences :... Oct 2023Meningeal lymphatic vessels (MLVs) help maintain central nervous system (CNS) homeostasis via their ability to facilitate macromolecule waste clearance and neuroimmune... (Review)
Review
Meningeal lymphatic vessels (MLVs) help maintain central nervous system (CNS) homeostasis via their ability to facilitate macromolecule waste clearance and neuroimmune trafficking. Although these vessels were overlooked for centuries, they have now been characterized in humans, non-human primates, and rodents. Recent studies in mice have explored the stereotyped growth and expansion of MLVs in dura mater, the various transcriptional, signaling, and environmental factors regulating their development and long-term maintenance, and the pathological changes these vessels undergo in injury, disease, or with aging. Key insights gained from these studies have also been leveraged to develop therapeutic approaches that help augment or restore MLV functions to improve brain health and cognition. Here, we review fundamental processes that control the development of peripheral lymphatic networks and how these might apply to the growth and expansion of MLVs in their unique meningeal environment. We also emphasize key findings in injury and disease models that may reveal additional insights into the plasticity of these vessels throughout the lifespan. Finally, we highlight unanswered questions and future areas of study that can further reveal the exciting therapeutic potential of meningeal lymphatics.
Topics: Mice; Animals; Lymphatic Vessels; Meninges; Central Nervous System; Lymphatic System; Models, Animal
PubMed: 37872442
DOI: 10.1007/s00018-023-04984-5 -
The Journal of Experimental Medicine Aug 2022A genuine network of lymphatic vessels can be found in the dural layer of the meninges that ensheathe the brain and spinal cord of mammalians. In this issue, Jacob et...
A genuine network of lymphatic vessels can be found in the dural layer of the meninges that ensheathe the brain and spinal cord of mammalians. In this issue, Jacob et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20220035) employ light sheet fluorescence imaging of intact mouse heads to provide a more comprehensive chart of the meningeal lymphatic vasculature and draw a parallel between lymphatic drainage of cerebrospinal fluid in mice and humans.
Topics: Animals; Brain; Lymphatic System; Lymphatic Vessels; Mammals; Meninges; Mice; Spinal Cord
PubMed: 35789368
DOI: 10.1084/jem.20220891