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.

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.

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.

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.

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.

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.

VEGF and its receptors in dengue virus infection.

Vascular permeability determines the severity of dengue virus infection. Vascular endothelial growth factor (VEGF) and its (receptor 1) R1 and (receptor 2) R2 receptors may provide insight about the neurological complications of dengue. We report VEGF and its R1 and R2 receptors level in dengue patients and correlate these with neurological complications. Consecutive patients with dengue were subjected to clinical and neurological evaluations. Their blood counts, serum chemistry, including liver and kidney function tests, serum creatine kinase (CK), and albumin were measured. VEGF, VEGFR1 and VEGFR2 were measured by ELISA in the patients and 16 matched controls. Twenty four patients with dengue were included whose ages ranged between 15 and 67 years, and nine of whom were females. Serum VEGF level was insignificantly lower in dengue patients whereas VEGFR1 was significantly higher (P = 0.01) and VEGFR2 was significantly lower (P = 0.005) compared to controls. VEGFR2 correlated with systolic blood pressure, coagulopathy, and serum CK levels. None of the other clinical and biochemical parameters correlated with VEGF and VEGFR1 levels. VEGFR1 and R2 normalized at 1 month. VEGFR2 correlates with the clinical severity of dengue and muscle dysfunction.

Neurological manifestations of scrub typhus.

OBJECTIVE: To evaluate the neurological manifestations of scrub typhus and correlate their clinical, EEG and MRI findings. METHODS: A cross-sectional study over 2 years included patients with scrub typhus diagnosed by solid phase immunochromatographic assay or Weil-Felix test. A detailed clinical evaluation including Glasgow Coma Scale (GCS) was documented. Blood counts, chemistry, ECG, chest radiograph, cerebrospinal fluid (CSF), EEG and cranial MRI were performed. Outcome on discharge and at 1 month were categorised into good and poor based on modified Rankin Scale. RESULTS: Thirty-seven patients with ages ranging between 3 and 71 years were included; 51% of whom were females. All patients had fever and myalgia. Thirty-one (84%) patients had impaired consciousness, and six were deeply comatose (GCS score ≤8). Eight patients presented with status epilepticus. MRI revealed meningeal enhancement in only 1/25 (4%) patient and EEG showed generalised slowing in 6/28 (21.4%). Among 31 patients with altered sensorium, CSF studies were conducted on 28. Nineteen patients had meningoencephalitis and 9 encephalopathy, but no significant differences were observed in clinical, laboratory, EEG and MRI findings. All patients responded within 48 h to doxycycline and had good recovery at 1 month. Patients with low GCS score had significantly more focal neurological deficit (r=0.5; p=0.002), longer hospital stay (r=-0.4; p=0.03) and more disability on discharge (r=-0.4; p=0.01). CONCLUSIONS: Meningoencephalitis/encephalopathy may be seen in two-third of patients with scrub typhus. Scrub typhus should be included in the differential diagnosis of febrile encephalopathy.

Safety and efficacy of levofloxacin versus rifampicin in tuberculous meningitis: an open-label randomized controlled trial.

OBJECTIVES: We report the efficacy and safety of levofloxacin versus rifampicin in tuberculous meningitis (TBM). PATIENTS AND METHODS: In this open-label, randomized controlled trial from India, patients with TBM diagnosed on the basis of clinical, MRI and CSF findings were included. Patients with hepatic or renal dysfunction, organ transplantation, malignancy, pregnancy, lactation, allergy, seizure, age <15 years and antitubercular treatment ≥1 month were excluded. Sixty patients each were randomized to levofloxacin (10 mg/kg, maximum 500 mg) or rifampicin (10 mg/kg, maximum 450 mg). They also received isoniazid, pyrazinamide, ethambutol, prednisolone and aspirin. The primary outcome was death and secondary outcome measures were 6 month disability, repeat MRI changes and serious adverse events (SAEs). RESULTS: The median age of the patients was 34.5 (16-75) years. The baseline clinical and MRI findings were similar between the two groups. At 6 months, 13 out of 60 (21.7%) patients in the levofloxacin arm and 23 out of 60 (38.3%) patients in the rifampicin arm had died (P = 0.07). On Cox regression analysis, survival in the levofloxacin group was significantly better than in the rifampicin group (hazard ratio 2.13, 95% CI 1.04-4.34, P = 0.04). The functional outcome (P = 0.47) was, however, not significantly different between the two groups. On intention-to-treat analysis, 10 out of 47 (21.3%) in the levofloxacin arm and 5 out of 37 (13.5%) in the rifampicin arm had poor recovery. Repeat MRI findings did not differ between the groups. Levofloxacin was discontinued more frequently than rifampicin due to SAEs (16 versus 4, P = 0.01). CONCLUSIONS: Levofloxacin is superior to rifampicin in reducing 6 month death in TBM but not disability. Levofloxacin may be used in TBM especially in those patients with hepatotoxicity and without seizure.

Predictors of outcome of myasthenic crisis.

There is paucity of study on predictors of myasthenic crisis (MC), prolonged ventilation and their outcome, a reason why this study was undertaken. Sixty-four patients with myasthenia gravis (MG) were included whose median age was 45 (6-84) years. Their clinical treatment, presence of thymoma, anti-acetylcholine receptor antibody (AchRAb), thymectomy, comorbidities, offending drugs and occurrence of MC were noted. Patients needing prolonged ventilation (>15 days) were noted. Hospital mortality, MG quality of life (QOL) at discharge and thereafter annual hospital visit, admission, expenditure and work day loss were enquired. Fourteen (21.9 %) patients had MC within 1-120 (median 8.5) months of disease onset within a median follow-up of 48 (3-264) months. The precipitating factors were infection in six, surgery in five, tapering of drugs in two and reaction to iodinated contrast in one patient. Male gender, bulbar weakness, AchRAb, thymoma, surgery and comorbid illnesses were related to MC. Eight of them (57.1 %) needed prolonged ventilation. Half the patients with MC had recurrent crisis (2-4 attacks). Death was not related to MC although MC patients had worse QOL, higher annual treatment expenditure with frequent hospital visit and hospitalization. In conclusion, association of comorbid illness with MC and prolonged ventilation highlights the need of close follow-up and appropriate management.

Beware of parotitis induced by iodine-containing contrast media.

Carotid stenting is being increasingly used for revascularization of the moderate to severe carotid stenosis and thus its complications are increasingly being recognized. We report a rare complication of induced by iodine contrast in a patient undergoing carotid stenting. s. A 51 year old man after the second stenting developed multiple small infarcts in spite of the distal device. He also had painful parotid swelling which improved within a week. One should be aware of iodine parotitis s in the patients undergoing iodinated contrast study.

Stimulus-sensitive myoclonus and cerebellar ataxia following chikungunya meningoencephalitis.

Chikungunya virus was initially thought to be a non-neurotropic virus, but recently neurological complications have been reported in patients with chikungunya virus infection. Here, we report a rare case of stimulus-sensitive myoclonus following chikungunya meningoencephalitis. The cranial MRI scan of the patient was normal, the cerebrospinal fluid contained 200 lymphocytes/mm(3), and the serum immunoglobulin M ELISA was positive for chikungunya. The patient improved completely after 1 month of treatment. This case study illustrates that chikungunya virus should also be considered in a febrile patient with myoclonus, especially in an endemic area.

Amitriptyline vs divalproate in migraine prophylaxis: a randomized controlled trial.

OBJECTIVE: This study compares efficacy and safety of divalproate extended release (DVA-ER) and amitriptyline (AMT) in migraine. MATERIALS AND METHODS: Three hundred migraineurs having >4 attacks monthly were randomized into DVA-ER or AMT. The primary end points were >50% reduction in frequency, ≥1 grade improvement in the severity, and >50% improvement in a visual analogue scale (VAS). Secondary end points were functional disability, rescue medication, and adverse events. RESULTS: The median age was 32 years, and 241 were women. 150 patients each received DVA-ER and AMT. At 3 months, 74.7% in DVA-ER and 62% patients in AMT group improved in headache frequency (P = 0.02) and at 6 months, 65.3% and 54%, respectively (P = 0.90). At 3 months, the VAS score improved by >50% in 80.7% in DVA-ER and 64% in AMT (P = 0.005). At 6 months, there was no significant difference between the two groups in VAS score (69.3% vs 56%; P = 0.47) and other outcome parameters. The composite side effects were also not different between the two groups (68% vs 81%); however, hair fall, menstrual irregularity, polycystic ovary, and weight gain were commoner in DVA-ER group. CONCLUSION: Divalproate extended release is more effective at 3 months than AMT; however, at 6 months, both are equally effective in migraine prophylaxis.

Low molecular weight heparin versus unfractionated heparin in cerebral venous sinus thrombosis: a randomized controlled trial.

BACKGROUND: There is no randomized controlled trial (RCT) evaluating the efficacy and safety of low molecular weight heparin (LMWH) compared to unfractionated heparin (UFH) in cerebral venous sinus thrombosis (CVST). In this RCT, we have evaluated the efficacy and safety of LMWH versus UFH in CVST. METHODS: Consecutive patients with CVST diagnosed on the basis of MR venography (MRV) who was free of bleeding diathesis, malignancy, hepatic or renal failure were prospectively enrolled. History, clinical findings and risk factors were evaluated. MRI and MRV findings were recorded. The patients were randomized to LMWH and UFH groups for 14 days followed by oral anticoagulant. The hospital mortality and 3 months outcome as assessed by Barthel index (BI) score were noted. RESULTS: 32 patients received UFH and 34 received LMWH. The baseline demographic, clinical and radiological parameters were similar in both the groups. Six patients died and all were in UFH group (P = 0.01). At 3 months, insignificantly higher number of patients recovered completely in LMWH compared to UFH group (30 vs. 20). There was no serious side effect needing withdrawal of drugs except one was withdrawn from UFH because of heparin-induced thrombosis. CONCLUSION: Low molecular weight heparin resulted in significantly lower hospital mortality in CVST compared to UFH.

Dengue-associated transient muscle dysfunction: clinical, electromyography and histopathological changes.

BACKGROUND: Dengue is commonly associated with myalgia, but there is paucity of studies on the frequency, severity, and basis of muscle involvement. The aim of this study was to document the clinical, electromyographic, and histological changes in dengue-associated muscle dysfunction. MATERIALS AND METHODS: Seropositive dengue patients admitted to the neurology ward during 2010 were enrolled in this study. Detailed medical history, including bleeding diathesis and organomegaly, were noted. Muscle power on a 0-5 scale, muscle tone, reflex, sensations and coordination were tested. Blood counts, hemoglobin, and serum chemistry, including creatine kinase (CK) evaluations, were carried out. Concentric needle electromyography (EMG) and muscle biopsy were performed when clinical conditions were suitable. RESULTS: The study cohort comprised 39 patients with dengue, with a median age of 28 years. Of these, 31 patients showed evidence of muscle involvement-16 with clinical and 15 with subclinical muscle involvement. Eight of these patients had severe weakness and five had hyporeflexia. Thrombocytopenia was present in 26 patients, elevated serum creatinine in three patients and liver dysfunction in 31 patients. The median CK level was 837 (range 194-3,832) U/L. The EMG revealed polyphasic normal to short duration motor unit potentials, but spontaneous activity was absent. Muscle biopsy in three patients revealed interstitial hemorrhage with occasional necrosis and myophagocytosis. There was no vasculitis, but subtle inflammatory changes were present in one patient. The severity of muscle weakness correlated with the platelet count and CK level. All patients improved by 15 days of treatment initiation. CONCLUSION: Dengue commonly results in benign and self-limiting transient muscle dysfunction.

Loss of cell surface TFII-I promotes apoptosis in prostate cancer cells stimulated with activated α2 -macroglobulin.

Receptor-recognized forms of α2 -macroglobulin (α2 M) bind to cell surface-associated GRP78 and initiate pro-proliferative and anti-apoptotic signaling. Ligation of GRP78 with α2 M also upregulates TFII-I, which binds to the GRP78 promoter and enhances GRP78 synthesis. In addition to its transcriptional functions, cytosolic TFII-I regulates agonist-induced Ca(2+) entry. In this study we show that down regulation of TFII-I gene expression by RNAi profoundly impairs its cell surface expression and anti-apoptotic signaling as measured by significant reduction of GRP78, Bcl-2, and cyclin D1 in 1-Ln and DU-145 human prostate cancer cells stimulated with α2 M. In contrast, this treatment significantly increases levels of the pro-apoptotic proteins p53, p27, Bax, and Bak and causes DNA fragmentation. Furthermore, down regulation of TFII-I expression activates agonist-induced Ca(2+) entry. In plasma membrane lysates p-PLCγ1, TRPC3, GRP78, MTJ1, and caveolin co-immunoprecipitate with TFII-I suggesting multimeric complexes of these proteins. Consistent with this hypothesis, down regulating TFII-I, MTJ1, or GRP78 expression by RNAi greatly attenuates cell surface expression of TFII-I. In conclusion, we demonstrate that not only does cell surface GRP78 regulate apoptosis, but it also regulates Ca(2+) homeostasis by controlling cell surface localization of TFII-I.

Status epilepticus: why, what, and how.

Status epilepticus (SE) is an important neurological emergency with high mortality and morbidity. The first official definition of SE was the product of 10 th Marseilles colloquium held in 1962 which was accepted by International League Against Epilepsy in 1964. There are as many types of SE as of seizures. SE is supposed to result from failure of normal mechanisms that terminate an isolated seizure. In half of the cases, there is no history of epilepsy and SE is precipitated by some intercurrent infection. In children, it is often infection, whereas in adults, the major causes are stroke, hypoxia, metabolic derangements, and alcohol intoxication or drug withdrawal. The treatment of SE aims at termination of SE, prevention of seizure recurrence, management of precipitating causes, and the management of complications. The extent of investigations done should be based on the clinical picture and cost benefit analysis. The first line antiepileptic drugs (AED) for SE include benzodiazepines, phenytoin, phosphenytoin, and sodium valproate. Mortality of SE ranges between 7 and 39% and depends on underlying cause and response to AEDs.

Epstein Barr virus encephalitis: clinical diversity and radiological similarity.

Clinico-radiological features of two patients with cerebrospinal fluid polymerase chain reaction-positive Epstein Barr virus (EBV) encephalitis have been reported. Both the patients presented with fever and altered sensorium, one had visual hallucination, decerebration followed by visual loss and the other had downward ocular deviation and orofacial and upper limb choreiform movement. Magnetic resonance imaging (MRI) revealed parieto-occipital involvement in both the patients. Follow-up MRI at one month was normal in one and revealed regression of lesion in the other. Both the patients, however, had severe neurologic sequelae at 18 months' follow-up. EBV encephalitis may have diverse clinical presentation with characteristic parieto-occipital involvement.

Angiotensin-converting enzyme (rs4646994) and α ADDUCIN (rs4961) gene polymorphisms' study in primary spontaneous intracerebral hemorrhage.

BACKGROUND: Primary spontaneous intracerebral hemorrhage (PSICH) is common in Asia and may have a genetic basis. OBJECTIVE: To report the role of angiotensin-converting enzyme (ACE) and a ADDUCIN (ADD1) gene polymorphisms in patients with PSICH. SETTING: Tertiary care teaching referral hospital. PATIENTS AND METHODS: Study subjects included 104 patients with PSICH diagnosed by computed tomography (CT) brain scan and 198 controls. The vascular risk factors of stroke were noted. The location and size of the hematoma on CT scan were recorded. ACE (rs4646994) and a ADDUCIN (rs4961) gene polymorphisms were analyzed by polymerase chain reaction (PCR). The genotype and allele frequency were compared between patients and controls and within the PSICH group. RESULTS: The median age of the PSICH group was 58 years, 17 (16.3%) patients were aged above 70 years and 40 (38%) were females. Ninety-three (91.2%) patients were hypertensive and 17 (16.5%) were diabetic. Hematoma was putaminal in 88 (84.5%), pontine in 5 (4.9%), cerebellar in 2 (1.9%), lobar in seven (6.8%) and multiple and primary intraventricular in one (1%) patient each. In the patients with PSICH, ACE DD genotype was present in 44 (42.8%) and ID in 40 (38.4%) whereas in controls these were 22 (11.1%) and 103 (52%) respectively. ADD1- WW genotype was found in two patients (1.9%), and GW in 44 patients (42.7%). In the controls these were found in nine (4.5%) and 65 (32.8%) respectively. DD genotype had 7.4 times higher risk of PSICH. ADD1 variant genotypes were not associated with increased risk but in association with ACE DD genotype resulted in significantly higher risk of PSICH. ACE and ADD1 variant genotypes were associated with nonlobar hematoma. CONCLUSION: ACE DD genotype in isolation or in combination with ADD1 GW genotype is associated with PSICH, especially nonlobar hematoma.