A Study of Catecholamine Levels in Acute ICH Patients and its Clinical Significance.

ICH is one of the most serious neurological emergency which can result in high mortality which may be related to catecholamine release. We aim to evaluate serum catecholamine levels in acute ICH and correlate their levels with clinical parameters of stress and outcome. MATERIAL: Consecutive patients with CT proven ICH within 7 days of ictus were included and their clinical finding, SIRS Parameters, GCS, NIH score, laboratory parameters (ESR, CRP) were evaluated. Serum Catecholamine (DA, NE, E) levels were measured by LCMS. The patients were followed up at discharge and one month, the outcome was defined by mortality and 1 month modified Rankin scale (good 0-2, poor >2). OBSERVATION: There were 31 patients of acute ICH. Patients were admitted 1 to 2 days after ictus. Among the patients 19 were male and 12 were female.Their age ranged from 31 to 86 with mean 53.3+- 16.7. History of hypertension was present in 27.3% of patients. Their average GCS was median 12 (6.0, 15.0) and NIHSS was 12.5 (8.5, 22) Their average ESR was 30 (13,56) and average CRP was 1.8 (1.1, 5.9). Almost all pateints had raised SIRS parameters. There was an increase in levels of Dopamine (63.2 pg/ml), Epinephrine (73.5 pg/ml) and Norepinephrine (390pg/ml) on admission as compared to their levels 1 week after ictus or on discharge (Dopamine 35.6, Epinephrine 52.1, and Norepinephrine 241 pg/ml). CONCLUSION: CA surge is common in ICH pateints and it correlates with severity and outcome of patient. 6 pateints died in the hospital 72 % of patients had poor outcome. Catecholamine levels were higher in poor outcome patients.

Safety and Efficacy of Sovateltide (IRL-1620) in a Multicenter Randomized Controlled Clinical Trial in Patients with Acute Cerebral Ischemic Stroke.

BACKGROUND: Sovateltide (IRL-1620, PMZ-1620), an endothelin-B receptor agonist, has been previously shown to increase cerebral blood flow, have anti-apoptotic activity and produce neurovascular remodeling when administered intravenously following acute cerebral ischemic stroke in rats. Its safety and tolerability were confirmed in healthy human volunteers (CTRI/2016/11/007509). OBJECTIVE: Our objective was to determine the safety, tolerability and efficacy of sovateltide as an addition to standard of care (SOC) in patients with acute cerebral ischemic stroke. METHODS: A prospective, multicentric, randomized, double-blind, placebo-controlled study was conducted to compare the safety (primary objective) and efficacy (secondary objective) of sovateltide in patients with acute cerebral ischemic stroke. Adult males or females aged 18-70 years who had experienced a radiologically confirmed ischemic stroke within the last 24 h were included in the study. Patients with intracranial hemorrhage and those receiving endovascular therapy were excluded. Patients randomized to the sovateltide group received three doses of sovateltide (each dose 0.3 µg/kg) administered as an intravenous bolus over 1 min at an interval of 3 ± 1 h on day 1, day 3 and day 6 (total dose of 0.9 µg/kg/day). Patients randomized to the placebo group received an equal volume of saline. Every patient in both groups received SOC for stroke. Efficacy was evaluated using neurological outcomes based on National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI) scores from day 1 through day 90. Quality of life was measured using the EuroQoL-5 Dimensions (EQ-5D) and Stroke-Specific Quality of Life (SSQoL) at 60 and 90 days of follow-up. RESULTS: A total of 40 patients with acute cerebral ischemic stroke were enrolled in this study, of whom 36 completed the 90-day follow-up. Patients received saline (n = 18; 11 male and 7 female) or sovateltide (n = 18; 15 male and 3 female) within 24 h of onset of stroke. The number of patients receiving investigational drug within 20 h of onset of stroke was 14/18 in the saline group and 10/18 in the sovateltide group. The baseline characteristics and SOC in both cohorts was similar. Sovateltide was well-tolerated, and all patients received complete treatment with no incidence of drug-related adverse events. Hemodynamic, biochemical or hematological parameters were not affected by sovateltide. Sovateltide treatment resulted in improved mRS and BI scores on day 6 compared with day 1 (p < 0.0001), an effect not seen in the saline group. Sovateltide increased the frequency of favorable outcomes at 3 months. An improvement of ≥ 2 points on the mRS was observed in 60 and 40% of patients in the sovateltide and saline groups, respectively (p = 0.0519; odds ratio [OR] 5.25). An improvement on the BI of ≥ 40 points was seen in 64 and 36% of the sovateltide and saline groups, respectively (p = 0.0112; OR 12.44). An improvement of ≥6 points on the NIHSS was seen in 56% of patients in the sovateltide group versus 43% in the saline group (p = 0.2714; OR 2.275). The number of patients with complete recovery (defined as an NIHSS score of 0 and a BI of 100) was significantly greater (p < 0.05) in the sovateltide group than in the saline group. An assessment of complete recovery using an mRS score of 0 did not show a statistically significant difference between the treatment groups. Sovateltide treatment resulted in improved quality of life as measured by the EQ-5D and SSQoL on day 90. CONCLUSION: Sovateltide was safe and well-tolerated and resulted in improved neurological outcomes in patients with acute cerebral ischemic stroke 90 days post-treatment. TRIAL REGISTRATION: The study is registered at CTRI/2017/11/010654 and NCT04046484.

Complications of tuberculous meningitis and their effect on outcome in a tertiary care cohort.

BACKGROUND: To report the frequency and severity of complications, and their effect on the outcome of tuberculous meningitis (TBM).METHODS: In this retrospective cohort study, the following TBM complications were observed: status epilepticus (SE), hydrocephalus, paradoxical clinical worsening (PCW), hyponatremia, drug-induced hepatitis (DIH), infarction and mechanical ventilation (MV). These were recorded and correlated with stage of meningitis and outcome.RESULTS: A total of 144 patients with TBM (median age 26 years, range 12-75) were included. There were 76 (52.8%) females. The patients were in Stage I (n = 33), Stage II (n = 82) and Stage III (n = 29); 58 had definite TBM. Complications occurred in 128 (88.9%); complications included hydrocephalus (n = 58, 40.3%), hyponatremia (n = 70, 48.6%), infarction (n = 48, 33.3%), DIH (n = 42, 29.2%), SE (n = 16, 18.0%), MV (n = 43, 29.9%) and PCW (n = 24, 16.7%), with variable overlap. By 6 months, 33 patients had died. Death was related to PCW (P = 0.016), hyponatremia (P = 0.03), MV (P = 0.02), infarction (P = 0.03) and the number of complications. Except PCW, most complications occurred during the first month.CONCLUSIONS: In TBM, complications occurred in 128 (88.9%) patients, mainly in the early stages, with variable overlap. Infarction, PCW, hyponatremia and MV were predictive of poor outcome.

Impaired Autophagy Flux is Associated with Proinflammatory Microglia Activation Following Japanese Encephalitis Virus Infection.

Role of autophagy in Japanese encephalitis viral (JEV) infection is not well known. In the present study, we reported the role of autophagy flux in microglia activation, neurobehavioral function and neuronal death using a mouse model of JEV. Markers for autophagy (LC3-II/I, SQSTM1/P62, phos-Akt, phos-AMPK), and neuronal death (cleaved caspase 12, H2Ax, polyubiquitin) were investigated by western blot at 1, 3 and 7 days post inoculation. Cathepsin D was measured in cerebral cotex of JEV infected mice spectrophotometrically. Microglia activation and pro-inflammatory cytokines (IL1ß, TNF-α, IFNγ, IL6) were measured by immunohistochemistry, western blot and qPCR analysis. In order to determine the neuroinflammatory changes and autophagy mediated neuronal cell death, BV2-microglia and N2a-neuronal cells were used. Autophagy activation marker LC3-II/I and its substrate SQSTM1/P62 were significantly increased while cathepsin D activity was decreased on day 7 post inoculation in cerebral cortex. Microglia in cortex were activated and showed higher expression of proinflammatory mRNA of IL1ß, TNF-α, IFNγ and IL6, with increased DNA damage (H2AX) and neuronal cell death pathways in hippocampus and neurobehavioral dysfunction. Similar observations on JEV infection mediated autophagy flux inhibition and neuronal cell death was found in N2a neuronal cell. Collectively, our study provides evidence on the role of autophagy regulation, microglial activation and neurodegeneration following JEV infection.

Hypovolemia due to cerebral salt wasting may contribute to stroke in tuberculous meningitis.

BACKGROUND: Both stroke and cerebral salt wasting (CSW) are common in tuberculous meningitis (TBM), but there is paucity of studies evaluating their combined effect. AIM: The present study has been undertaken to evaluate the spectrum of stroke in TBM and its relation to CSW. DESIGN: Hospital-based prospective cohort study. METHODS: Eighty-one patients with TBM diagnosed on the basis of clinical, cerebrospinal fluid and magnetic resonance imaging (MRI) criteria were prospectively included. Stroke was diagnosed on the basis of clinical, MRI findings or both. Stroke risk factors were noted. Patients with hyponatremia were categorized into CSW and other causes. Three and 6 months outcome was defined using modified Rankin Scale (mRS) as good (<2) or poor (≥2). RESULTS: Out of 81 patients with TBM, 32 (39.5%) had ischemic stroke. CSW was the commonest cause of hyponatremia and occurred in 34 (42%) patients. Stroke occurred in tubercular zone in 10, ischemic zone in 15 and both in 7 patients. The patients with ischemic zone infarction were older and had stroke risk factors such as diabetes mellitus, hypertension and hyperlipidemia. Out of 16 (47%) patients with CSW, 10 (62.5%) had stroke during the polyuric phase. The patients with CSW had more frequent deep white matter infarcts (P = 0.01) which were in internal border zone in 4 (40%). CONCLUSION: In TBM, stroke occurred in 39.5% of the patients, 50% of whom had CSW. Volume contraction due to CSW may contribute to stroke.

A study of atrial and brain natriuretic peptides in tuberculous meningitis and acute encephalitis.

OBJECTIVE: To report atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels in patients with tuberculous meningitis (TBM) and acute encephalitis syndrome (AES), and evaluate their relationship with hyponatraemia. METHODS: Consecutive patients with TBM and AES were included in the study. Hyponatraemia was categorised as cerebral salt wasting (CSW), syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and a miscellaneous group based on clinical and laboratory criteria. Serum ANP and BNP levels were measured upon hospital admission, at the time of diagnosis of hyponatraemia and upon correction of hyponatraemia. Outcome at 3 months was assessed using the modified Rankin scale (mRS) as good (mRS 2) and poor (mRS >2). RESULTS: There were 67 patients with TBM and 77 with AES. Hyponatraemia was more common in TBM than in AES (65.7% vs. 27%, P < 0.01). Forty-one (63.1%) patients had CSW, 6 (9.2%) SIADH and 18 (27.7%) had miscellaneous causes of hyponatraemia. During hyponatraemia, ANP (180 ± 45 vs. 106 ± 32 pg/ml, P < 0.01) and BNP (263 ± 118 vs. 163 ± 91 pg/ml, P  0.01) levels were significantly increased compared with baseline, and remained high even after Na+ correction. CONCLUSION: ANP and BNP levels were increased during hyponatraemia and remained high even after correction of hyponatraemia in TBM and AES, especially in patients with CSW. However, ANP and BNP levels could not be used to differentiate CSW from SIADH.

Multifocal Balo's Concentric Sclerosis in Children: Report of a Case and Review of Literature.

Balo's concentric sclerosis (BCS) is a rare demyelinating lesion considered to be a variant of multiple sclerosis (MS). On magnetic resonance imaging (MRI) Balo's concentric sclerosis shows the typical concentric pattern. We report a case of 10 year old child with BCS who presented as post infectious acute disseminated encephalomyelitis (ADEM). He is asymptomatic and had no relapse after 6 years of follow-up.

Pontomesencephalic Atrophy and Postural Instability in Wilson Disease.

BACKGROUND AND PURPOSE: The MR Parkinsonism index helps in differentiating progressive supranuclear palsy from Parkinson disease and multisystem atrophy. Pontomesencephalic involvement is common in neurologic Wilson disease, but there is no prior study evaluating the MR Parkinsonism index and its indices in Wilson disease. We report the MR Parkinsonism index and its indices in Wilson disease and correlate these changes with clinical severity and postural reflex. MATERIALS AND METHODS: Thirteen individuals with neurologic Wilson disease were included, and their clinical details, including neurologic severity, postural reflex abnormality, and location of signal changes on MR imaging, were noted. The 3D BRAVO T1 sequence was used for measurement of the MR Parkinsonism index and its indices. The MR Parkinsonism index and its indices were also obtained in 6 age- and sex-matched controls. The morphometric parameters in Wilson disease were compared with those in with healthy controls and among the patients with and without abnormal postural reflex. RESULTS: The midbrain area was reduced in patients with Wilson disease compared with controls (112.08 ± 27.94 versus 171.95 ± 23.66 mm2, P = .002). The patients with an abnormal postural reflex had an increased MR Parkinsonism index and pons-to-midbrain ratio compared with controls, whereas these parameters were equivalent in patients with normal postural reflex and controls. The patients with abnormal postural reflex had more severe illness, evidenced by higher Burke-Fahn-Marsden scores (51.0 ± 32.27 versus 13.75 ± 12.37, P = .04) and neurologic severity grades (2.57 ± 0.53 versus 1.67 ± 0.82, P = .04). CONCLUSIONS: An increase in the MR Parkinsonism index in Wilson disease is mainly due to midbrain atrophy and it correlates with neurologic severity and abnormal postural reflex.

Spectrum of hyperosmolar hyperglycaemic state in neurology practice.

BACKGROUND & OBJECTIVES: Hyperosmolar hyperglycaemic state (HHS) is a medical emergency, but there is a paucity of studies reporting the spectrum of neurological manifestations of HHS. We, therefore, report the neurological spectrum, triggering factors and outcome of HHS in general neurology practice. METHODS: The records of the patients with HHS were extracted from computerized hospital information system and those managed currently were prospectively included. The demographic, clinical manifestations, duration of diabetes and precipitating events such as infection, stress and stroke were noted. Patients with HHS were categorized into seizure, movement disorder and encephalopathy groups. Their electroencephalography, magnetic resonance imaging (MRI) findings and outcome were noted. RESULTS: There were 17 patients with HHS (age range 40 and 75 yr) and seven were females. Seven patients were diabetic for five years, one for four years, one for one year and four were diagnosed after the occurrence of HHS. Four patients had epilepsia partialis continua persisting for 72-360 h, one patient had focal seizures and his MRI revealed T2 hyperintensity in frontal region in one patient and cerebellar vermian hyperintensity in another. All the five patients improved, but two had neurological deficits on discharge. Nine patients had encephalopathy which was precipitated by stroke in six patients, urinary infections in two and meningitis in one. Three females had hemichorea-hemiballismus syndrome, which was triggered by infections. Abnormal movements lasted 5-10 days and responded to correction of hyperosmolarity. Nine out of 17 patients improved completely whereas the remaining eight had partial recovery, these patients had stroke, ventilator-related complications or meningoencephalitis. INTERPRETATION & CONCLUSIONS: The most common presentation of HHS was encephalopathy (9) followed by seizure (5) and hemichorea-hemiballismus syndrome (3) which responded to the correction of hyperosmolar state.

Spectrum and outcome of acute infectious encephalitis/encephalopathy in an intensive care unit from India.

PURPOSE: To evaluate the spectrum of acute infectious encephalitis/encephalopathy syndrome (AIES) in intensive care unit (ICU) and the predictors of mechanical ventilation (MV) and outcome of these patients. METHODS: AIES patients diagnosed on the basis of fever, altered sensorium, seizure and cerebrospinal fluid pleocytosis admitted to the neurology ICU were prospectively included. The demographic and clinical details, hematological, biochemical, MRI and etiological findings of the patients were noted. Need of MV, death in hospital and 3-month functional outcome were analyzed. RESULTS: One hundred sixty-four out of 258 (64%) AIES patients needed ICU admission. Their median age was 35 (2-85) years and 71 (43%) were females. The etiology was viral in 44 (herpes and Japanese encephalitis in 12 each, dengue in 17, mumps, measles and varicella in 1 patient each), non-viral in 64 (scrub typhus in 48, falciparum malaria in 6, leptospira in 3 and bacterial in 7) and undetermined etiology in 56 (34%) patients. Sixty-nine (42%) patients needed MV. On multivariate analysis, Glasgow Coma Scale (GCS) score, Sequential Organ Failure Assessment (SOFA) score and raised intracranial pressure were independent predictors of MV. Forty-three (26%) patients died, and all were in the MV group. Higher SOFA score and untreatable etiology were independent predictors of mortality. At 3-month follow-up, 14% had poor and 86% had good outcome. Low GCS score, focal weakness and status epilepticus independently predicted poor outcome. CONCLUSION: Twenty-six percent patients with AIES died in ICU, and 86% had good recovery at 3 months. Admission SOFA scores and untreatable etiology predicted mortality.

Possible role of transforming growth factor ß in tuberculous meningitis.

BACKGROUND: Transforming growth factor ß (TGF-ß) is an anti-inflammatory cytokine and its role in hydrocephalus and stoke has been suggested. Tuberculous meningitis (TBM) is associated with exudates, stroke, hydrocephalus and tuberculoma, but the role of TGF-ß has not been evaluated in relation to these changes. AIM: To evaluate the cerebrospinal fluid (CSF) TGF-ß level in the patients with TBM, and correlate these with clinical findings, MRI changes, paradoxical response and outcome at 6months. METHODS: TBM patients diagnosed on the basis of clinical, CSF and MRI criteria were prospectively included. The clinical details including duration of illness, seizures, focal motor deficit, Glasgow Coma Scale (GCS) score and stage of TBM were noted. Presence of exudate, hydrocephalus, tuberculoma and infarction in MRI was also noted. MRI was repeated at 3months and presence of paradoxical response was noted. Cerebrospinal fluid TGF-ß was measured using ELISA on admission and repeated at 3months and these were compared with 20 controls. RESULTS: TGF-ß level was significantly higher in TBM compared to the controls (385.76±249.98Vs 177.85±29.03pg/ml, P<0.0001). TGF-ß correlated with motor deficit, infarction and tuberculoma on admission but did not correlate with CSF abnormalities, drug induced hepatitis, paradoxical response and outcome. TGF-ß level at 3months was significantly lower than the baseline but remained higher than the controls. CONCLUSION: CSF TGF-ß levels are elevated in TBM and correlate with infarction and tuberculoma.

Role of 18F-FDG PET in demonstrating disease burden in patients with tuberculous meningitis.

OBJECTIVE: To study the role of 18fluoro-deoxy glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan in documenting the disease burden in patients with tuberculous meningitis (TBM), and compare these findings with conventional imaging and magnetic resonance imaging (MRI). SUBJECTS AND METHODS: Ten patients with definite TBM were prospectively recruited. The severity of TBM was graded into stage I to III. The patients were subjected to whole body 18F-FDG PET/CT imaging and MRI brain. 18F-FDG PET/CT results were compared with the findings of brain MRI and other convectional imaging modalities (ultrasonography of abdomen and chest radiograph). RESULTS: There were ten patients with TBM whose median age was 27 (14-55) years, and the median duration of illness was 4 (0.5-8.0) months. Two patients were in stage I, six in stage II, and two in stage III meningitis. 18F-FDG PET/CT confirmed the cranial MRI findings in six patients, revealed additional brain lesion in one and did not detect the existing MRI lesions in three patients. 18F-FDG PET/CT however detected additional lesions in vertebrae, spinal cord and lymph nodes which were not seen on the conventional imaging. CONCLUSION: 18F-FDG PET/CT has a complementary role to MRI for detection of cranial lesions and is more sensitive in detecting the extra cranial tuberculosis burden in the patients with TBM.

Quality of anticoagulation therapy in neurological patients in a tertiary care hospital in north India.

BACKGROUND & OBJECTIVES: There is paucity of studies on the quality of anticoagulation in neurological patients from India. This study evaluates the quality of oral anticoagulation therapy in neurology patients. METHODS: Consecutive patients attending a tertiary care neurology service in north India who were prescribed oral anticoagulant (OAC), were included. Their international normalized ratio (INR) values were prospectively monitored and the earlier INR values of the patients who were already on OAC were retrospectively analyzed. The patients with multi-organ dysfunction, pregnancy and those below 18 yr of age were excluded. The therapeutic INR range was defined as per standard recommendations. The level of anticoagulation, factors interfering with OAC and complications were noted. RESULTS: The results were based on 77 patients with median age 40 yr. Fifty one patients received OAC for secondary stroke prevention, 23 for cerebral venous sinus thrombosis (CVST) and three for deep vein thrombosis (DVT). A total 167.9 person-years of follow up was done with a median of 1.2 (0.3-9.3) years. of the 1287 INR reports, 505 (39.3%) reports were in the therapeutic range, 496 (38.5%) were below and 282 (21.91%) were above the therapeutic level. Stable INR was obtained in 33 (42.86%) patients only. INR level was improved by dose adjustment in 20 (26%), drug modification in two (2.6%), and dietary adjustment in six (7.8%) patients. Three patients were sensitive and five were resistant to OAC. Complications were noted in 28 instances; thromboembolic in 16 and haemorrhagic stroke in 12. The overall complication rate was 16.7 per 100 person-years. INTERPRETATION & CONCLUSIONS: It may be concluded that stable therapeutic INR is difficult to maintain in neurological patients. Optimal modification of diet, drug and dose of oral anticoagulant may help in stabilization of INR.

Safety and efficacy of additional levofloxacin in tuberculous meningitis: A randomized controlled pilot study.

BACKGROUND: Levofloxacin is an effective bactericidal category III antitubercular drug. There is paucity of studies comparing the role of additional levofloxacin to standard antitubercular regimen in the patients with tuberculous meningitis (TBM). AIMS: To compare the safety and efficacy of adding levofloxacin to standard four drug ATT regimen (RHZE). SUBJECTS AND METHODS: The patients with TBM diagnosed on the basis of clinical, cerebrospinal fluid (CSF) and MRI criteria were included. Children below 15 years, patients with pregnancy, seizures, liver failure, kidney failure and malignancy were excluded. The baseline clinical, CSF and MRI characteristics were noted and consciousness was evaluated by Glasgow Coma Scale (GCS). The patients were randomized to RHZE (rifampicin, isoniazid, pyrazinamide and ethambutol) and RHZEL (RHZE and levofloxacin) groups. Outcome was defined at 6 months. Primary outcome was death and secondary outcomes were disability as assess by Barthel Index score and adverse events. RESULTS: Out of 110 TBM patients screened, 57 fulfilled the inclusion criteria. Their median age was 35 (15-75) years. 29 patients received RHZEL and 28 RHZE. The baseline clinical, biochemical and MRI characteristics were similar in the two groups. At 6 months, 11 (19.3%) patients died, 38 (66.7%) had good and 7 (12.3%) poor outcome. There was insignificant survival benefit in RHZEL group compared to RHZE (HR-2.61, 95% CI 0.73-9.36, P = 0.14), 25% patients died in RHZE where as 13.8% in RHZEL group. The disability was not significantly different between the two groups. The composite side effects were also similar between the two groups except for a higher frequency of seizure in RHZEL group (5 Vs 0) which resulted in withdrawal of levofloxacin. CONCLUSION: There was insignificant survival benefit in RHZEL which was associated with high frequency of seizures.

Is VEGF a marker of severity of scrub typhus infection?

Vascular endothelial growth factor (VEGF) and its receptors have been reported as severity markers of septicemia. Scrub typhus (ST) results in multi-organ dysfunction but the role of VEGF has not been evaluated. We report VEGF and its receptors in ST and its correlation with severity, outcome and laboratory findings. Thirty patients with ST diagnosed by solid phase immune chromatographic assay and Weil-Felix tests were included. Their clinical details, Glasgow Coma Scale (GCS), SOFA and modified Rankin Scale (mRS) scores and laboratory findings were noted. VEGF, VEGFR1 and VEGFR2 were done by ELISA at admission and repeated at 1 month. Outcome was defined at 1 month. Serum VEGF and VEGF-R1 levels were significantly higher and VEGFR2 was significantly lower in the ST patients compared to the controls. These levels significantly improved at 1 month. VEGF level correlated with SOFA score (p = 0.05) and SGPT (p = 0.04). VEGFR1 correlated with hemoglobin (p = 0.04), platelet count (p = 0.03), serum CK (p = 0.001), weakness (p = 0.04) and mRS score (p = 0.04). VEGFR2 did not correlate with any clinical or laboratory parameters. All the patients recovered with doxycycline. Serum VEGF and VEGFR1 levels increased in ST and suggest disease severity but do not predict outcome.

A Study on Apoptosis and Anti-apoptotic Status in Wilson Disease.

Wilson disease (WD) is characterized by hepatolenticular degeneration, but there is no report on apoptosis and anti-apoptotic markers in WD patients with neurological manifestation (WDN). The aim of this study was to evaluate active caspase-3 and X-linked inhibitors of apoptosis protein (XIAP) level in WDN and correlate these with disease severity and markers of death (tumor necrosis factor-alpha (TNF-α), interleukin (IL)-8, malondialdehyde (MDA), and Cu) and survival signals (glutathione). Fifty-four patients with WDN and 36 healthy matched controls were included. Their severity, Burke-Fahn-Marsden (BFM) scores, blood counts, hemoglobin, serum chemistry, ceruloplasmin, and free copper and 24-h urinary copper were measured. Cranial MRI findings were noted. Serum active caspase-3, XIAP, TNF-α, IL-8, and plasma glutathione and MDA were measured using enzyme-linked immunosorbent assay (ELISA), flow cytometry, and spectrophotometer respectively. In the patients with WDN, active caspase-3 (0.55 ± 0.11 vs 0.38 ± 0.06 ng/ml), TNF-α (76.05 ± 29.01 vs 36.05 ± 21.01 pg/ml), IL-8 (590.19 ± 89.19 vs 193.43 ± 71.01 pg/ml), and MDA (4.92 ± 0.39 vs 3.43 ± 0.21 nmol/ml) levels were increased whereas XIAP (84.66 ± 10.39 vs 95.76 ± 10.11 ng/ml) and glutathione (GSH) (2.03 ± 0.29 vs 2.98 ± 0.27 mg/dl) levels were decreased compared to controls. Active caspase-3 was correlated with neurological severity (r = 0.48), BFM score (r = 0.37), ceruloplasmin (r = -0.39), hemoglobin (r = -0.34), and serum Cu (r = 0.39). XIAP levels were correlated with neurological severity (r = -0.40), BFM (r = -0.51), serum Cu (r = -0.42), and ceruloplasmin (r = 0.34). The XIAP level positively correlated with survival (GSH) and inversely with death signals (TNF-α, IL-8, MDA and free serum Cu) whereas active caspase-3 positively correlated with death (TNF-α, IL-8, serum Cu, MDA) and inversely with survival signal (GSH). Serum active caspase-3 level increased in WDN and positively correlated with the severity of disease, death signals (TNF, IL-8, MDA, and free Cu) and inversely with GSH and XIAP.