Meningeal Changes Research Articles

Explorations about the correlation between biological changes of meninges in periodontitis mice and cognitive impairment via single-cell RNA sequencing

Objective: To clarify the potential correlation between biological changes of meninges in periodontitis mice and cognitive impairment by analyzing the biological changes of meninges in periodontitis mice using single-cell RNA sequencing. Methods: Thirty C57BL/6 mice were divided into two groups by using random number table method (15 mice in each group). Mice in the control group were locally administered 2% carboxyl methyl cellulose (CMC) without Porphyromonas gingivalis (Pg) on both buccal sides. A mixture of Pg W83 and 2% CMC was applied on both buccal sides in the experimental group mice three times a week, lasting for 16 weeks in total. The absorption of alveolar bone, locomotor activity and cognitive function, the activation of microglia and astrocytes in the cortex were observed and assessed. The mRNA expression levels of Occludin in meninges and brain were detected in two groups. Single-cell RNA sequencing data of meninges were processed by uniform manifold approximation and projection (UMAP). Differential genes expressions of endothelial cells were processed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In addition, real-time fluorescence quantitative PCR (RT-qPCR) was used to verify the expressions of transcription activating factor 3 (Atf3) and apolpoprotein L domain-containing 1 (Apold 1). Results: Methylene blue staining found the distances of buccal and palatal cement-enamel junction-alveolar bone crest in experimental mice [(185.60±17.60), (206.90±13.37) μm] increased significantly compared with the control group [(135.33±9.57), (163.05±14.98) μm] (t=5.02, P=0.002; t=4.37, P=0.005). Open field experiment showed the total distance and average speed of mice in the experimental group [(971.88±164.57) cm, (3.25±0.55) cm/s] were not statistically significant compared with the control group [(914.24±278.81) cm, (3.05±0.93) cm/s] (t=0.65, P=0.525; t=0.65, P=0.520). The recognition index of the experimental group [(48.02±16.92) %] was lower than the control group [(66.27±17.90) %] (t=2.40, P=0.027) by novel object recognition tests. Compared with the control group [(63.56±11.88) %], the alternation of experimental group [(50.99±14.17) %] was significantly decreased in Y maze tests (t=2.33, P=0.030). Immunohistochemistry results showed microglia and astrocytes were activated in the cortex of experimental mice. Compared with the control group (1.02±0.25, 1.04±0.31), the relative mRNA expressions of Occludin decreased significantly in the meninges and brain of periodontitis mice, respectively (0.61±0.10, 0.64±0.20) (t=3.47, P=0.010; t=2.66, P=0.024). By single-cell RNA sequencing, meninges cells were divided into 11 types, such as endothelial cells, fibroblasts, immune cells and so on. Endothelial cells were the main cell types in meninges [the control group: 26.47% (1 589/6 004), the experimental group: 26.26% (807/3 073)]. Compared with the control group [5.56% (334/6 004)], the percentage of granulocytes increased in the periodontitis mice [11.65% (358/3 073)]. Using clustering analysis to further focus on endothelial cells, GO enrichment analysis revealed differential genes were mainly related to angiogenesis, cell adhesion, apoptosis and so on. KEGG enrichment analysis revealed that differential genes were related to signaling pathways of interleukin-17, relaxin and so on. The relative mRNA expressions of Atf3 and Apold1 in meninges of periodontitis mice (0.42±0.24, 0.54±0.27) were significantly lower than the control group (1.03±0.26, 1.02±0.23) (t=3.88, P=0.005; t=3.02, P=0.017). Conclusions: The mice chronically infected with Pg W83 occurred memory impairment, neuroinflammation and changes of barrier function. In the meninges of periodontitis mice, there were infiltration of immune cells and down-regulation expressions of Atf3 and Apold1 by single-cell RNA sequencing. Meningeal immunity and changes of barrier function may play an important role in the cognitive impairment caused by periodontitis.

Herpes simplex virus 2 meningitis: a retrospective cohort study

Herpes simplex virus 2 is a leading cause of viral meningitis and the most commonly recognized infectious cause of benign, recurrent meningitis. We report a retrospective, observational cohort study of patients with herpes simplex virus type 2 (HSV-2) meningitis, confirmed by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF). The terms "herpes simplex," "meningitis," or "encephalitis" were searched in the medical records system of the Mayo Clinic in Rochester, Minnesota (1995-2008). Patients were included if they had a clinical diagnosis of meningitis and HSV-2 detected by PCR in the CSF. There were 28 patients with 33 episodes identified (83 % female; mean age at presentation of meningitis 36 years, range 17-53; mean time to HSV2 detection from symptom onset 3 days, range 0-6; history of genital herpes 23 %). No patient took oral antiviral treatment at the time of presentation. Episodes were most likely to include headache (100 %), photophobia (47 %), self-reported fever (45 %), meningismus (44 %), and nausea and/or vomiting (29 %). CSF at the time of meningitis was notable for elevated protein (mean 156 g/dL, range 60-258) and white cell count (mean 504 cells/μL, range 86-1,860) with normal glucose (mean 54 mg/dL, range 32-80). Mollaret cells were never detected. Neuroimaging was most often normal (83 %) when performed, although some cases showed nonspecific (14 %) or meningeal changes (3 %). There was no consistent relationship to genital herpes. The duration of treatment with intravenous acyclovir ranged from 3 to 14 days for the first meningitic episode (daily dose range from 500 to 1,000 mg and total dose range from 500 mg q8h for 3 days to 800 mg q8h for 14 days). For subsequent episodes, the duration of treatment of intravenous acyclovir ranged from less than 1 to 14 days (total dose range from 1,390 mg for 1 day to 900 mg q8h for 10 days). The dose of valacyclovir ranged from 500 mg once daily to 500 mg four times daily. The median duration of valacyclovir treatment following the first episode was 10 days (range 3 to 14 days, n = 13). The median duration of valacyclovir treatment following a subsequent meningitic episode was 9 days (range 7 days to indefinite period, n = 9). No patient was reported to have seizures, neurological disability, or death in extended follow-up (mean follow-up 3.4 years). Recurrence of meningitic symptoms was not universal.

Hypertrophic pachymeningitis in systemic sclerosis sine scleroderma

Dear Editor, Hypertrophic pachymeningitis is a clinical disorder characterized by chronic refractory headache with or without neurologic manifestations, resulting from localized or diffuse thickening of the dura mater.1, 2 These meningeal changes can be found in various autoimmune, neoplastic and infective conditions.1, 3 Idiopathic hypertrophic pachymeningitis is the diagnosis of exclusion. Systemic sclerosis sine scleroderma is a condition characterized by vasculopathy, visceral manifestations and serologic findings similar to systemic sclerosis in absence of skin sclerosis. Here we describe a patient with systemic sclerosis sine scleroderma and hypertrophic pachymeningitis. To the best of our knowledge there has been no previous report of pachymeningitis in a patient with systemic sclerosis. A 45-years-old woman, a diagnosed case of systemic sclerosis sine scleroderma, presented to us with a 4-month history of severe, throbbing, holocranial headache associated with nausea. There was no other significant medical history. General physical and systemic examination was unremarkable except for basal crackles in both lungs. Hemogram and biochemical parameters were within normal limits. Antinuclear antibody titre was 1 : 320 homogenous pattern and anti-Scl-70 was positive. Tests for syphilis, hepatitis B surface antigen, anti-hepatitis C virus and human immunodeficiency virus were negative. The levels of serum angiotensin-convertase enzyme were normal. Urinalysis and 24-h urinary calcium was within normal limits. Cerebrospinal fluid (CSF) examination showed normal opening pressure, no cells, protein 18 mg/dL, blood sugar 70 mg/dL (random blood sugar 96 mg/dL). Tuberculosis polymerase chain reaction, India ink stain and malignant cytology on CSF were negative. Chest radiograph was normal. High-resolution computed tomography (HRCT) chest scan revealed features of early interstitial lung disease. Pulmonary function tests were suggestive of restrictive lung disease and echocardiography was normal with no evidence of pulmonary arterial hypertension. Gadolinium-enhanced magnetic resonance imaging (MRI) revealed diffuse pachymeningeal thickening with enhancement throughout cerebral and cerebellar hemispheres, suggestive of hypertrophic pachymeningitis (Fig. 1). Subsequently, bronchoscopy with transbronchial lung biopsy was performed. Bronchoscopic alveolar lavage revealed alveolar macrophages (82%), lymphocytes (10%) and polymorphs (8%) and lung biopsy had normal histology. The patient did not give consent for meningeal biopsy. She was started on 50 mg oral corticosteroids daily. She showed marked clinical improvement with complete resolution of headache. Follow-up gadolinium-enhanced MRI of the brain performed in September 2010 revealed marked regression in dural enhancement (Fig. 2). Hypertrophic pachymeningitis is a rare clinical disorder which commonly presents with chronic headache with or without neurological manifestations. Neuroimaging is essential in making correct diagnosis. Gadolinium-enhanced MRI is superior to contrast-enhanced computed tomography (CT) scan for diagnoses. Corticosteroid therapy has been effective in alleviating symptoms and in arrest of clinical progression. In refractory cases, immunomodulators such as azathioprine, methotrexate and cyclophosphamide can be used.3, 4 Connective tissue diseases such as Wegener's granulomatosis, rheumatoid arthritis, mixed connective tissue disease, undifferentiated connective tissue disease, sarcoidosis, Behçet's disease and Sjögren syndrome have been reported to be associated with hypertrophic cranial pachymeningitis.1, 5-8 To conclude, hypertrophic pachymeningitis is a rare association with connective tissue diseases and it should always be suspected when a patient presents with chronic refractory headache in which other etiologies have been ruled out. To the best of our knowledge this is the first case of pachymeningitis with scleroderma.

Magnetic resonance imaging – unravelling the mystery

Magnetic resonance imaging – unravelling the mystery

Treatment of lumbosacral radiculopathy with epidural steroids.

Treatment of lumbosacral radiculopathy with epidural steroids.

Imaging techniques in neoplastic meningiosis.

Since the introduction of CT and MRI as diagnostic aids, it has been possible to obtain direct images of neoplastic meningiosis. After more than ten years experience, the combination of MRI with the administration of a paramagnetic contrast medium is now accepted as the method of choice for the sensitive detection of meningeal diseases and for monitoring their treatment. The almost uniform character of leptomeningeal or pachymeningeal enhancement in the presence of infective, inflammatory, neoplastic, vascular or reactive changes is the reason for the restricted specificity of MRI, so that with the imaging process alone only very limited information about the etiology is available. Clinical data, laboratory findings, examination of the CSF and histopathological examination are therefore essential for interpreting the meningeal changes and making a differential diagnosis. Various pathophysiological processes can lead to a single meningeal enhancement visualizable with MRI: 1. a genuine disturbance of the blood-brain barrier is found in the presence of infection or inflammation, 2. leptomeningeal structures can be directly infiltrated by sheets or nodules of tumors, the blood vessels of which possess no intact blood-brain barrier, 3. physical or chemical irritants may produce of local inflammatory reaction with vascular proliferation and its corresponding enhancement, a 4. a pseudoenhancement may follow reactive dilatation of the vessels. In the present article the various appearances of neoplastic invasion of the meninges in MRI and their differential diagnosis will be described.

Late meningeal changes after dimer-X-myelography in the absence of surgery (author's transl)

Myelography with Amipaque was carried out in a group of 28 patients who had had previous Dimer-X-myelography, but no surgery. In 12 cases there was radiological evidence of a meningeal reaction. In all these cases there were chronic changes in the lumbar subarachnoid space. The original myelograms showed no evidence of adhesive changes in the root pouches. It was not possible to correlate the radiological findings of the meningeal changes with the severity or type of neurological diseases.

Late meningeal changes due to water-soluble myelographic contrast medium (author's transl)

Late meningeal changes due to various contrast media of the water-soluble type used for radiculography were analysed and the causes for the changes are discussed. The osmotic properties of the substance are an important aspect of the contrast medium. Hints for avoiding late complications are given.

Difficulties of the differential diagnosis in a medulloblastoma. A casuistic contribution.

In a case developing the clinical picture of subacute-chronic meningitis, the difficulties of differential diagnosis in the recognition of a medulloblastoma with extensive infiltrating arachnoidal growth of tumour are presented. Only earlier and more certain evidence of tumour cells could have led to an earlier recognition of the malignancy of the meningeal changes, i.e., a diagnosis of meningitis carcinomatosa. Also, symptoms originating from the primary tumour may be missed to the very last, even though such massive sowing of the tumour is present.

A7. The Changes of Meninges in Cervical Syndrome

A7. The Changes of Meninges in Cervical Syndrome

DEGENERATION OF THE CEREBRAL CORTEX IN THE COURSE OF PERTUSSIS

A great variety of neurologic disturbances are known to occur in the course of pertussis. Among these the commonest are convulsions, cerebral palsies of various types and visual disturbances. These symptoms may be of brief duration or may persist. The older neurologists were accustomed to attribute such complications to cerebral hemorrhages resulting from the cerebral congestion which occurs during the paroxysms, but it is well known that hemorrhages may be absent in some cases and even when present may be insufficient to explain the clinical picture. This fact led to the theory that cerebral edema or serous meningitis was the pathologic basis of the nervous manifestations in pertussis, and Neurath 1 was able to demonstrate mild meningeal changes in fatal cases. In 1924, Husler and Spatz 2 published an article which threw new light on the subject. These investigators made a careful histologic study of the nervous system of two

Short Notes and Clinical Cases: A NOTE ON THE PRESENCE OF ENDARTERITIS OBLITERANS IN THE BRAIN OF A MONGOLIAN IMBECILE.

THE hypothesis that mongolism is a special form of congenital syphilis appears to be gaining ground, particularly in France, but it must be admitted that the pathological evidence for such a view remains extremely scanty. Indeed, with the solitary exception of a report by Babonneix(1) syphilitic lesions in the brain of the mongol do not appear to have been recorded. In the case of Babonneix, in addition to vascular and meningeal changes, a small tumour having the histological features of a gumma was found in the sulcus separating the right prefrontal and postfrontal gyri. To this case I am now able to add a second in which the outstanding feature was a syphilitic affection of the cerebral vessels.