Cerebral Salt Wasting Syndrome (CSW): An unusual cause of hypovolemia after spontaneous cerebral hemorrhage successfully treated with fludrocortisone
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SUBMITTER: Bouchlarhem A
PROVIDER: S-EPMC8577092 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceTuberculous meningitis is associated with high frequency of cerebral salt wasting. There is a paucity of objective information regarding the best method of treatment of this condition.ObjectiveTo evaluate the efficacy and safety of fludrocortisone in the treatment of cerebral salt wasting in patients with tuberculous meningitis.Design, setting, and participantsThis is a single-center, open-label, randomized clinical trial conducted from October 2015 to April 2017 in India. Patients were randomized in a 1:1 ratio to arms receiving saline only or saline plus fludrocortisone, in addition to a standard treatment of 4 antitubercular drugs, prednisolone, and aspirin. The 2 arms were matched for demographic, clinical, and magnetic resonance imaging findings. The patients were followed up for at least 6 months.InterventionsPatients were randomized to a 0.9% solution of intravenous saline with 5 to 12 g per day of oral salt supplementation, with or without the addition of 0.1 to 0.4 mg of fludrocortisone per day.Main outcomes and measuresThe primary end point was the time needed to correct serum sodium levels; secondary end points were in-hospital deaths, disability at 3 months, disability at 6 months, occurence of stroke, and serious adverse reactions.ResultsNinety-three patients with suspected tuberculous meningitis were recruited; 12 did not meet the inclusion criteria, including 4 with alternate diagnoses. A total of 37 patients with cerebral salt wasting were eligible for the study. One refused to participate, and therefore 36 patients were included, with 18 randomized to each group. The median (range) age was 30 (20-46) years, and 19 were male (52.8%). Those receiving fludrocortisone regained normal serum sodium levels after 4 days, significantly earlier than those receiving saline only (15 days; P = .004). In an intention-to-treat analysis, hospital mortality, disability at 3 months, and disability at 6 months did not differ significantly, but fewer infarcts occurred in the deep border zone in the group receiving fludrocortisone (1 of 18 [6%]) vs those in the control arm (6 of 18 [33%]; P = .04). Fludrocortisone was associated with severe hypokalemia and hypertension in 2 patients each, and pulmonary edema occurred in 1 patient. These adverse reactions necessitated discontinuation of fludrocortisone in 2 patients.Conclusions and relevanceFludrocortisone results in earlier normalization of serum sodium levels, but did not affect outcomes at 6 months. Fludrocortisone had to be withdrawn in 2 patients because of severe adverse effects. This study provides class II evidence on the role of fludrocortisone in treatment of hyponatremia associated with cerebral salt wasting in patients with tuberculous meningitis.Trial registrationClinical Trials Registry of India (ctri.nic.in) Identifier: CTRI/2017/10/010255.
| S-EPMC6248117 | biostudies-literature
Project description:BackgroundGenetic variants in SEC61A1 are associated with autosomal dominant tubulointerstitial kidney disease. SEC61A1 is a translocon in the endoplasmic reticulum membrane and variants affect biosynthesis of renin and uromodulin.MethodsA patient is described that presented at 1 year of age with failure-to-thrive, kidney failure (glomerular filtration rate, GFR, 18 ml/min/1.73m2), hyperkalemia and acidosis. Genetic evaluation was performed by whole genome sequencing.ResultsThe patient has a novel de novo heterozygous SEC61A1 variant, Phe458Val. Plasma renin was low or normal, aldosterone was low or undetectable and uromodulin was low. Kidney biopsy at 2 years exhibited subtle changes suggestive of tubular dysgenesis without tubulocystic or glomerulocystic lesions and with renin staining of the juxtaglomerular cells. The patient experienced extreme fatigue due to severe hypotension attributed to hypoaldosteronism and at 8 years of age fludrocortisone treatment was initiated with marked improvement in her well-being. Blood pressure and potassium normalized. Biopsy at 9 years showed extensive glomerulosclerosis and mild tubulointerstitial fibrosis, as well as tubular mitochondrial abnormalities, without specific diagnostic changes. Her GFR improved to 54 ml/min/1.73m2.ConclusionsAs the renin-angiotensin system promotes aldosterone release, and the patient had repeatedly undetectable aldosterone levels, the SEC61A1 variant presumably contributed to severe hypotension. Treatment with a mineralocorticoid had a beneficial effect and corrected the electrolyte and acid-base disorder. We suggest that the increased blood pressure hemodynamically improved the patient's kidney function.
| S-EPMC11317836 | biostudies-literature
Project description:BackgroundSpontaneous cerebellar-intracerebral hemorrhage (ICH) can be associated with both cerebral amyloid angiopathy (CAA) and hypertensive small vessel disease (HTN-SVD, i.e. arteriolosclerosis). To better understand the underlying microangiopathy of cerebellar-ICH, we aimed to evaluate the spatial distribution of supratentorial cerebral microbleeds (CMBs) and neuropathologic profiles in these patients.MethodsWe enrolled consecutive cerebellar-ICH patients. Clinical variables and MRI markers specific for CAA and HTN-SVD were assessed. Patients were classified into categories according to the topography (strictly-lobar, strictly-deep, and mixed) of supratentorial CMBs and comparisons were performed. Available neuropathological material was reviewed to evaluate the presence and severity of arteriolosclerosis and CAA.ResultsNinety-eight cerebellar-ICH patients were enrolled. Fifty patients (51%) had at least one supratentorial CMB. Twelve patients (12%) had strictly lobar-CMBs, 12 patients (12%) showed strictly deep-CMBs and mixed-CMBs (lobar and deep CMBs) were present in 26 cerebellar-ICH patients (27%). In multivariable analysis, cerebellar-ICH patients with mixed-CMBs were associated with higher prevalence of hypertension (OR 4.9, 95% confidence interval [CI] 1.2-20, p = 0.017) but with lower prevalence of severe centrum-semiovale enlarged perivascular spaces (OR 0.2, CI 0.05-0.8, p = 0.024) when compared to cerebellar-ICH patients with strictly lobar-CMBs. Vascular risk factors and neuroimaging characteristics were similar between strictly deep-CMBs and mixed-CMBs. Six patients had available neuropathological material for analyses and they all showed some degree of arteriolosclerosis.ConclusionsCerebellar-ICH patients frequently show supratentorial CMBs. The mixed-CMBs pattern appears to be the most common. Our radiological and pathological results suggest that the majority of cerebellar-ICH patients harbor HTN-SVD as dominant microangiopathy.
| S-EPMC9422345 | biostudies-literature
Project description:In patients with spontaneous intracerebral hemorrhage caused by different vasculopathies, cerebral microinfarcts have the same aspect on MRI and the same applies to cerebral microbleeds. It is unclear what pathological changes underlie these cerebral microinfarcts and cerebral microbleeds. In the current study, we explored the histopathological substrate of these lesions by investigating the brain tissue of 20 patients (median age at death 77 years) who died from ICH (9 lobar, 11 non-lobar) with a combination of post-mortem 7-T MRI and histopathological analysis. We identified 132 CMIs and 204 CMBs in 15 patients on MRI, with higher numbers of CMIs in lobar ICH patients and similar numbers of CMBs. On histopathology, CMIs and CMBs were in lobar ICH more often located in the superficial than in the deep layers of the cortex, and in non-lobar ICH more often in the deeper layers. We found a tendency towards more severe CAA scores in lobar ICH patients. Other histopathological characteristics were comparable between lobar and non-lobar ICH patients. Although CMIs and CMBs were found in different segments of the cortex in lobar ICH compared to non-lobar ICH patients, otherwise similar histopathological features of cortical CMIs and CMBs distant from the ICH suggest shared pathophysiological mechanisms in lobar and non-lobar ICH caused by different vasculopathies.
| S-EPMC9995541 | biostudies-literature
Project description:Background and purposeCerebral amyloid angiopathy (CAA) is a common cause of recurrent intracerebral hemorrhage in the elderly. Previous studies have shown that CAA induces inflammation and expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 (gelatinases) in amyloid-laden vessels. Here, we inhibited both using minocycline in CAA mouse models to determine whether spontaneous intracerebral hemorrhage could be reduced.MethodsTg2576 (n=16) and 5xFAD/ApoE4 knockin mice (n=16), aged 17 and 12 months, respectively, were treated with minocycline (50 mg/kg, IP) or saline every other day for 2 months. Brains were extracted and stained with X-34 (to quantify amyloid), Perls' blue (to quantify hemorrhage), and immunostained to examined β-amyloid peptide load, gliosis (glial fibrillary acidic protein [GFAP], Iba-1), and vascular markers of blood-brain barrier integrity (zonula occludins-1 [ZO-1] and collagen IV). Brain extracts were used to quantify mRNA for a variety of inflammatory genes.ResultsMinocycline treatment significantly reduced hemorrhage frequency in the brains of Tg2576 and 5xFAD/ApoE4 mice relative to the saline-treated mice, without affecting CAA load. Gliosis (GFAP and Iba-1 immunostaining), gelatinase activity, and expression of a variety of inflammatory genes (matrix metalloproteinase-9, NOX4, CD45, S-100b, and Iba-1) were also significantly reduced. Higher levels of microvascular tight junction and basal lamina proteins were found in the brains of minocycline-treated Tg2576 mice relative to saline-treated controls.ConclusionsMinocycline reduced gliosis, inflammatory gene expression, gelatinase activity, and spontaneous hemorrhage in 2 different mouse models of CAA, supporting the importance of matrix metalloproteinase-related and inflammatory pathways in intracerebral hemorrhage pathogenesis. As a Food and Drug Administration-approved drug, minocycline might be considered for clinical trials to test efficacy in preventing CAA-related intracerebral hemorrhage.
| S-EPMC4442054 | biostudies-literature
Project description:Introduction:In the setting of cerebral injury, cerebral salt wasting (CSW) is a potential cause of hyponatremia, which contributes to adverse effects and mortality. Objective:The primary objective of this study was to evaluate the clinical outcomes of severe traumatic brain injury (TBI) patients complicated by CSW. Methods:A retrospective data analysis was performed on data collected from patients with TBI with an abbreviated injury scale (AIS) greater than 3. Data was divided into 2 groups of patients with CSW and those without. The primary endpoint was incidence of adverse effects of CSW in regard to injury severity score (ISS), hospital length of stay (HLOS), ventilator days, ICU length of stay (ICU LOS) and survival to discharge. Data was analyzed using a one-way analysis of variance (ANOVA). Results:A total of 310 consecutive patients with severe head injury (anatomic injury score 3 or greater) were evaluated over a 3-year period. A total of 125 of the 310 patients (40%) were diagnosed with cerebral salt wasting as defined by hyponatremia with appropriate urinary output and salt replacement. Patients with CSW had poorer outcomes in regard to ISS (21.8 vs 14.2, p<0.0001), HLOS (14.1 vs 3.5, p<0.0001), ventilator days (5.0 vs 0.45, p<0.0001), ICU LOS (8.5 vs 1.6, p<0.0001), and survival to discharge (88% vs 99%, p<0.0001). Discussion:Common adverse effects of CSW were noted in this study. Patients with TBI have a predilection towards development of CSW and consequently have poorer outcomes including increased morbidity and mortality. Data is sparse on the duration of CSW and degree of hyponatremia over time. Larger, comparative studies need to be performed to investigate the hyponatremic patient population and the clinical outcomes of those who present with CSW.
| S-EPMC7104213 | biostudies-literature
Project description:IntroductionCerebral salt wasting syndrome (CSWS) is a cause of hyponatremia in the setting of intracranial pathologies such as Central Nervous System (CNS) trauma, infections, and tumors. It is important to differentiate CSWS from the syndrome of inappropriate antidiuretic hormone secretion (SIADH) as their management differs. CSWS leads to hypovolemia as opposed to euvolemia or hypervolemia in SIADH. SIADH is managed with fluid restriction and this could worsen CSWS which is managed with adminstration of intravenous crystalloids to correct hyponatremia.Case summaryA 42-year-old male was admitted after a week of low-grade fever with easy fatigability, hypersomnolence, and excessive thirst. He had polyuria which started 5 days before presentation, and unintentionally lost 3 kg of weight in the past month. He had orthostatic hypotension, and was dehydrated, but vital signs were normal with the exception of his temperature. Cerebrospinal fluid (CSF) analysis revealed a glucose of 42 mg/dl, protein 170 mg/dl, cell count 28/mm3 with 65% lymphocytes which was consistant with tubercular meningitis. CSF AFB culture was positive in addition to a positive CSF PCR for M. tuberculosis.DiscussionPresentation of CNS infection with tuberculosis may be non-specific and its insidious onset could lead to delayed or missed diagnosis; however persistent constitutional symptoms and signs with history of weight loss and a close contact with tuberculosis may raise the possibility of tuberculosis. Early diagnosis and treatment has an excellent prognosis, but any delay contributes to death and disability despite anti-tubercular drug therapy.CSWS should be managed with salt and volume replacement, but more importantly, the causative CNS insult should also be confirmed and addressed.
| S-EPMC7677114 | biostudies-literature
Project description:The present study aimed to investigate the gene functions and expression profiles in perihematomal (PH) brain regions following spontaneous intracerebral hemorrhage. The gene expression profiles were downloaded from the Gene Expression Omnibus database under accession number GSE24265, which includes 11 brain samples from different regions, including four samples from PH areas, four from contralateral grey matter (CG) and three from contralateral white matter (CW). The gene expression profiles were pre-processed and the differentially expressed genes (DEGs) between PH and CG tissue, and PH and CW tissue were identified using R packages. The expression of genes in different tissues was analyzed by hierarchical clustering. Then, the interaction network between the DEGs was constructed using String software. Finally, Gene Ontology was performed and pathway analysis was conducted using FuncAssociate and Expression Analysis Systematic Explorer to identify the gene function. As a result, 399 DEGs were obtained between PH and CG, and 756 DEGs were identified between PH and CW. There were 35 common DEGs between the two groups. These DEGs may be involved in PH edema by regulating the calcium signaling pathway [calcium channel, voltage‑dependent, T-type, α1I subunit, Ca2+/calmodulin‑dependent protein kinase II α (CAMK2A), ryanodine receptor 2 (RYR2) and inositol 1,4,5-trisphosphate receptor, type 1 (ITPR1)], cell proliferation (sphingosine kinase 1), neuron differentiation (Ephrin-A5) or extracellular matrix-receptor interaction [collagen, type I, α 2, laminin B1 (LAMB1), syndecan 2, fibronectin 1 and integrin α5 (ITGA5)]. A number of genes may cooperate to participate in the same pathway, such as ITPR1-RYR2, CAMK2A-RYR2 and ITGA5-LAMB1 interaction pairs. The present study provides several potential targets to decrease hematoma expansion and alleviate neuronal cell death following spontaneous intracerebral hemorrhage.
| S-EPMC4148373 | biostudies-literature
Project description:Background Sarcoidosis is a systemic disorder of unknown origin characterized by noncaseating granulomas. Clinical symptoms due to central nervous system (CNS) involvement occur in 5 to 7% of all cases; subclinical involvement is more frequent. Sole CNS involvement is very rare. Case Report A 25-year-old man presented with increasing polyuria and polydipsia over 8 weeks. Magnetic resonance imaging (MRI) revealed a supra- and infra-chiasmatic pre-thalamic mass lesion 1.0 × 1.4 × 1.4cm in diameter. Microsurgical biopsy verified a necrotizing noncaseating epithelioid cell tumor indicative for neurosarcoidosis. All symptoms dissolved within 3 months under stringent corticoid therapy. Conclusion Intracranial mass lesions as the primary and only manifestation of neuronal sarcoidosis are rare. Because conservative treatment is safe and effective, surgery is limited to biopsy and the alleviation of pressure-related symptoms to preserve neurologic function.
| S-EPMC4520996 | biostudies-other
Project description:BackgroundMetabolic stroke is the rapid onset of lasting central neurological deficit associated with decompensation of an underlying metabolic disorder. Glutaric aciduria type I (GA1) is an inherited disorder of lysine and tryptophan metabolism presenting with metabolic stroke in infancy. The clinical presentation includes bilateral striatal necrosis and spontaneous subdural and retinal hemorrhages, which has been frequently misdiagnosed as non-accidental head trauma. The mechanisms underlying metabolic stroke and spontaneous hemorrhage are poorly understood.ResultsUsing a mouse model of GA1, we show that metabolic stroke progresses in the opposite sequence of ischemic stroke, with initial neuronal swelling and vacuole formation leading to cerebral capillary occlusion. Focal regions of cortical followed by striatal capillaries are occluded with shunting to larger non-exchange vessels leading to early filling and dilation of deep cerebral veins. Blood-brain barrier breakdown was associated with displacement of tight-junction protein Occludin.ConclusionTogether the current findings illuminate the pathophysiology of metabolic stroke and vascular compromise in GA1, which may translate to other neurometabolic disorders presenting with stroke.
| S-EPMC3940023 | biostudies-literature