Neurococcidiomycosis in children with hydrocephalus: assessment of functional outcome, quality of life and survival in relation to neuroimaging findings.

PURPOSE: Coccidioidal meningitis (CM) is an uncommon disease frequently misdiagnosed. Neuroimaging and mortality are not considered in detail in previous pediatric CM series. Our objective is to evaluate outcome of pediatric neurococcidiomycosis in relation to neuroimaging findings. METHODS: We performed a prospective, observational, cross-sectional study in children with hydrocephalus and CM treated at Specialties Hospital in Torreon, Mexico (between 2015 and 2020). The outcome was evaluated by Hydrocephalus Outcome Questionnaire (HOQ) and the modified Rankin Scale (mRS). Follow-up was established at the first shunt surgery and survival since CM diagnosis confirmation. Neuroimaging was analyzed in relation to clinical data, outcome and survival. Kaplan-Meier analysis was performed with IBM-SPSS-25. RESULTS: Ten pediatric cases with CM and hydrocephalus were reported. Aged 6-228 months, 60% were female. Mean number of surgeries was 4.3 SD ± 3 (range 1-15). Asymmetric hydrocephalus was the most common neuroimaging finding (70%), followed by cerebral vasculitis (20%) and isolated fourth ventricle (IFV) (20%). The mean HOQ overall score was 0.338 SD ± 0.35. A minimum follow-up of 18 months was reported. Mean survival was 13.9 SD ± 6.15 months (range 3-24). Poor survival was correlated with asymmetric hydrocephalus (p = 0.335), cerebral vasculitis (p = 0.176), IFV (p < 0.001), bacterial superinfection (p = 0.017), lower mRS scores at hospital discharge (p = 0.017) and during follow-up (p = 0.004). The mortality rate was 20%. CONCLUSIONS: We report the largest series in Latin America of pediatric CM and hydrocephalus. Asymmetric hydrocephalus, IFV and cerebral vasculitis are complications that increase mortality and must be early diagnosed for a timely surgical and medical treatment. HOQ and mRS could be alternative scales to evaluate outcome in these patients. After a long follow-up (18 months), survival remained poor after diagnosis confirmation in our series.

A Rare Complication of Sarcoidosis.

BACKGROUND: Cerebral vasculitis is a serious, but uncommon inflammatory condition of the blood vessel walls, with an annual incidence of 1-2 per million. A variety of disorders including encephalopathy, stroke, seizure, acute or subacute focal deficits should be considered as a differential diagnosis. CLINICAL CASE: A 56-year old male with a past history of pulmonary sarcoid presented with a unilateral facial numbness and loss of balance arising during sleep. His computed tomography scan of the brain was normal but brain magnetic resonance imaging with gadolinium demonstrated scattered infarcts in mixture of stroke topography not purely in keeping with embolism nor intrinsic small vessel disease. Further investigations including carotid ultrasound, transthoracic echo and 24-hour electrocardiogram were within normal limits. However, computed tomography angiography showed evidence of a widespread intracranial vasculopathy, as well as evidence of dissection of the left common carotid artery. His elevated calcium was consistence with a sarcoidosis relapse and cerebrospinal fluid analysis was in keeping with a central nervous system inflammatory process. Treatment was commenced with high dose steroids with additional pulsed intravenous cyclophosphamide together with antiplatelet therapy and a statin. CONCLUSIONS: This case illustrates the intracranial vasculopathy as a rare complication of sarcoidosis. Although sarcoid is well recognized to affect the central nervous system, it is unusual in the form of cerebral vasculitis.

Cerebrospinal fluid findings in reversible cerebral vasoconstriction syndrome: a way to differentiate from cerebral vasculitis?

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by an acute onset of severe headache and multi-focal segmental vasoconstriction of cerebral arteries resolving within 12 weeks. Diagnostic criteria include normal or near-normal findings in cerebrospinal fluid (CSF) analysis, especially leucocyte levels < 10/mm³. Distinguishing RCVS from primary angiitis of the central nervous system (PACNS) is essential to avoid unnecessary and sometimes unfavourable immunosuppressive treatment. We reviewed retrospectively the clinical and diagnostic data of 10 RCVS patients who presented in our neurological department from 1 January 2013 to February 2017. The main purpose was to verify whether CSF leucocyte counts < 10/mm³ serve to discriminate RCVS from PACNS. Five of six patients who underwent lumbar puncture presented with CSF leucocyte levels ≥ 10/mm³. Two patients had a history of misinterpretation of CSF pleocytosis as cerebral vasculitis and of immunosuppressive treatment. A complete restitution of cerebral vasoconstriction was evident in all. No patient had further cerebral strokes or bleedings without immunosuppressive treatment over more than 12 weeks. Despite the established diagnostic criteria, RCVS can manifest with CSF leucocyte levels > 10/mm³. Careful anamnesis and the response of 'vasculitis-like angiography' to nimodipine given as a test during angiography and as oral medication are key to differentiate RCVS from cerebral vasculitis.

Inhibition of cerebral vascular inflammation by brain endothelium-targeted oligodeoxynucleotide complex.

The present study generated a novel DNA complex to specifically target endothelial NF-κB to inhibit cerebral vascular inflammation. This DNA complex (GS24-NFκB) contains a DNA decoy which inhibits NF-κB activity, and a DNA aptamer (GS-24), a ligand of transferrin receptor (TfR), which allows for targeted delivery of the DNA decoy into cells. The results indicate that GS24-NFκB was successfully delivered into a murine brain-derived endothelial cell line, bEND5, and inhibited inflammatory responses induced by tumor necrosis factor α (TNF-α) or oxygen-glucose deprivation/re-oxygenation (OGD/R) via down-regulation of the nuclear NF-κB subunit, p65, as well as its downstream inflammatory cytokines, inter-cellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1). The inhibitory effect of the GS24-NFκB was demonstrated by a significant reduction in TNF-α or OGD/R induced monocyte adhesion to the bEND5 cells after GS24-NFκB treatment. Intravenous (i.v.) injection of GS24-'NFκB (15mg/kg) was able to inhibit the levels of phoseph-p65 and VCAM-1 in brain endothelial cells in a mouse lipopolysaccharide (LPS)-induced inflammatory model in vivo. In conclusion, our approach using DNA nanotechnology for DNA decoy delivery could potentially be utilized for inhibition of inflammation in ischemic stroke and other neuro-inflammatory diseases affecting cerebral vasculature.

Psychosis in primary angiitis of the central nervous system involving bilateral thalami: a case report.

OBJECTIVE: To report a case of primary angiitis of the central nervous system (PACNS), a rare inflammatory disease restricted to the central nervous system (CNS), with unusual clinical presentation mimicking schizophrenia. METHOD: Case report. RESULTS: A 45-year-old male presented with alteration of consciousness and confusion. Brain magnetic resonance imaging (MRI) scan showed a mass-like enhancing lesion involving bilateral thalami, and biopsy revealed findings compatible with PACNS. The patient was treated with corticosteroids. Psychotic symptoms crystallized over the initial 2 months after the diagnosis and persisted for over a year. Severity of his symptoms improved with gradual normalization of the radiologic findings and antipsychotic medication. CONCLUSION: Our case highlights the importance of considering PACNS as a differential diagnosis of a tumor-like mass lesion in the CNS and the significance of thalamic involvement in the pathogenesis of psychotic symptoms including delusions and hallucinations.

Cerebral Aspergillus arteritis with bland infarcts: a report of two patients with poor outcome.

Two patients with cerebrovascular aspergillosis, in the form of arteritis, thrombosis and bland infarcts are reported. One patient had systemic lupus erythematosus with disseminated aspergillosis in lungs, kidneys and brain. The other patient was immunocompetent and had sphenoid sinusitis. Both the patients were diagnosed at autopsy only, despite extensive imaging and laboratory studies. High index of clinical suspicion and early aggressive antifungal therapy are required since definite diagnostic modalities are not available.

[Implication of dexamethasone adjunctive therapy after the onset of cerebral vasculitis in Streptococcus pneumoniae meningitis]. / Implication du traitement adjuvant par dexaméthasone dans la survenue d'une artérite septique cérébrale au cours d'une méningite à Streptococcus pneumoniae.

Few adverse effects have been reported with adjunctive dexamethasone treatment in pneumococcal meningitis. Nevertheless, we report a case of cerebral vasculitis. A 49-year-old man was admitted for fever and altered mental status. Lumbar puncture revealed a high inflammatory response and Streptococcus pneumoniae was identified by culture. Antibacterial therapy and adjunctive dexamethasone treatment were initiated as recommended. The immediate outcome was favorable but due to the onset of focal cerebral abnormalities, a CT scan was performed on the ninth day showing cerebral vasculitis. The patient died on the thirteenth day despite antibacterial therapy and resuscitation. In our case, a secondary neurological worsening appeared when adjunctive dexamethasone treatment was stopped suggesting a rebound effect. Observation of similar cases may lead to modifying adjunctive dexamethasone treatment protocol in bacterial meningitis.

[Cerebral vasculitis as the initial manifestation of systemic lupus erythematosus]. / Zerebrale Vaskulitis als Erstmanifestation eines systemischen Lupus erythematodes.

HISTORY AND CLINICAL FINDINGS: A 41-year-old man was admitted to the hospital because of a series of seizures. History revealed increasing weakness and generalized myalgia following a severe respiratory tract infection three months previously. The clinical examination was dominated by reduced alertness and cognitive impairment. INVESTIGATIONS: Positive ANA titres pointed to an autoimmune disease; further laboratory tests revealed an antiphospholipid syndrome. The clinical diagnosis of systemic lupus erythematosus was supported by renal biopsy. Transcranial Doppler sono-graphy and magnetic resonance imaging with angiography revealed cerebral vasculitis with multiple intracerebral grey and white matter lesions. TREATMENT AND COURSE: In addition to an immunosuppressive therapy with corticosteroids and intravenous pulses of high-dose cyclophosphamide, oral anticoagulation was given in order to prevent thromboembolic complications. Seizures were treated with valproate. A follow-up MRI revealed multiple glial cell reactions and reduced vasculitic changes. CONCLUSIONS: Initial neuropsychiatric symptoms and seizures prompted the diagnosis of systemic lupus erythematosus with cerebral vasculitis in a 41-year-old patient. Approximately 20 % of all lupus patients initially present with neuropsychiatric disorders. Central nervous system involvement and renal complications determine the course and prognosis of the disease as well as therapeutic decisions. Particularly in young patients with neuropsychiatric symptoms systemic lupus erythematosus should be excluded routinely.

[The effect of tropoxin on the neurogenic and vasogenic inflammation of the dura mater vessels]. / Vliianie tropoksina na neirogennoe i vazogennoe vospalenie sosudov tverdoi mozgovoi obolochki.

Subchronic administration of tropoxin (in doses of 7.5 and 10 mg/kg) caused dose-dependent blocking of 131I-albumin plasma transudation from the dura mater vessels, induced by electrical stimulation of the trigeminal ganglion and intravenous infusion of the agonist of 5-HT2B/2C receptors metachlorophenylpiperazine. The antimigraine agent metisergid produced a similar effect. A single injection of metisergid and tropoxin did not block albumin transudation. A 3 mg/kg dose of mianserin prevented the blocking effect of tropoxin and metisergid on plasma exudation into the dura mater. It is suggested that the mechanism of the tropoxin antimigraine effect is realized through the presynaptic 5-HT1 receptors of afferent endings of the trigeminal nerve and the postsynaptic 5-HT2B/2C receptors of the dura mater vessels.