Bishwanath Kumar

Central Poststroke Pain : A Review of Pathophysiology and Treatment

BACKGROUND: Central poststroke pain (CPSP) is a disabling morbidity occurring in 8%–14% of patients with stroke. It is infrequently recognized and difficult to manage. OBJECTIVE: We systematically reviewed the pathophysiology and treatment of CPSP. METHODS: We conducted a Medline search using the key words “central post-stroke pain,” “post-stroke pain,” “CPSP and basic studies,” “CPSP and clinical features,” “CPSP and pharmacological treatment,” “CPSP and nonpharmacological treatment” and “CPSP and treatment guideline.” The articles related to CPSP were categorized into clinical features, pathophysiology and treatment, and then systematically reviewed. RESULTS: Stroke along the spinothalamocortical pathway may result in CPSP after a variable period, usually after 1–2 mo. CPSP may be spontaneous or evoked, variable in intensity and quality. It tends to improve with time. CPSP is associated with mild motor symptoms with relative sparing of joint position and vibration sensations. The pathophysiology of CPSP is not well understood, but central disinhibition, imbalance of stimuli and central sensitization have been suggested. There are few class I and class II studies regarding its management. Amitriptyline and lamotrigine (class IIB) are recommended as first-line and mexiletine, fluvoxamine and gabapentin as second-line drugs. In pharmacoresistant patients, repetitive transcranial magnetic stimulation and deep brain stimulation have been beneficial. CONCLUSIONS: CPSP patients present with diverse sensory symptoms and its pathophysiology is still poorly understood. Amitriptyline and lamotrigine are effective treatments. Further studies are needed to understand the pathophysiology and investigate newer therapeutic modalities.

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

Background:u2002 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.

A Study of Clinical, Magnetic Resonance Imaging, and Somatosensory-Evoked Potential in Central Post-Stroke Pain

UNLABELLEDnThis study evaluates the clinical spectrum of central post-stroke pain (CPSP) and correlates it with magnetic resonance imaging (MRI) and somatosensory-evoked potential (SEP) changes. Thirty-one consecutive CPSP patients whose median age was 51 years were evaluated and subjected to quantitative sensory testing and median and tibial SEPs. Cranial MRI abnormalities were noted and correlated with clinical and SEP abnormalities. The majority of patients (n = 21) developed CPSP within 3 months of stroke, and CPSP was the presenting symptom in 7 patients. Five patients had focal symptoms and 26 had hemibody symptoms with or without facial involvement. Pain threshold was reduced in 12, and 3 did not have pain perception. Allodynia was present in 11, static in 4, dynamic in 5, and cold in 7 patients. Temporal summation was present in 14, punctate hyperalgesia in 11, and cold hyperalgesia in 3 patients. Cranial MRI revealed infarction in 23 and intracerebral hemorrhage in 8 patients; 16 had thalamic and 15 extrathalamic lesions. SEP was abnormal in 15 of 22 (68.2%) patients. There was no difference in symptoms and severity of CPSP, quantitative sensory testing, and SEP abnormalities in thalamic and extrathalamic stroke.nnnPERSPECTIVEnCPSP is a poorly recognized entity that can interfere with rehabilitation, reduce the quality of life, and interfere with the activities of daily living and recreational activities. This report concludes that the symptoms and severity of CPSP in thalamic and extrathalamic stroke do not differ significantly.

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

BACKGROUNDnPrimary spontaneous intracerebral hemorrhage (PSICH) is common in Asia and may have a genetic basis.nnnOBJECTIVEnTo report the role of angiotensin-converting enzyme (ACE) and a ADDUCIN (ADD1) gene polymorphisms in patients with PSICH.nnnSETTINGnTertiary care teaching referral hospital.nnnPATIENTS AND METHODSnStudy 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.nnnRESULTSnThe 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.nnnCONCLUSIONnACE DD genotype in isolation or in combination with ADD1 GW genotype is associated with PSICH, especially nonlobar hematoma.

A study of ACE and ADD1 polymorphism in ischemic and hemorrhagic stroke.

BACKGROUNDnStroke is a common cerebrovascular accident. ACE and ADD1 gene are known to be associated with vascular complications leading to stroke susceptibility. The present study was carried out to evaluate the relative frequency of ACE and ADD1 common polymorphisms in ischemic stroke and intracerebral hemorrhage (ICH).nnnMETHODSnA total of 386 CT or MRI proven stroke patients were included; 193 each had ischemic stroke and ICH. The locations and type of stroke were noted. ACE- I/D (rs4646994) and ADD1 (rs4961) gene polymorphisms were analyzed by polymerase chain reaction (PCR). The genotype and allele frequencies of ACE and ADD1 polymorphisms were compared between patients and controls as well as between ischemic stroke and ICH.nnnRESULTSnACE (DD) genotype was significantly higher in ischemic stroke (37.8%) and ICH (33.7%) compared to controls (11.7%). D allele was also more frequent in ischemic stroke (57.3%) and ICH (56.7%) compared to controls (38.3%). ADD1 (WW) genotype and W allele frequencies were not significantly different in ischemic stroke, ICH and controls. In contrast, we found a synergistic role of ACE (DD)*ADD1(GW) interaction showing a positive association in both ischemic and hemorrhagic strokes.nnnCONCLUSIONnOur study suggests that ACE (DD) genotype and D allele significantly increase the susceptibility to ischemic and hemorrhagic strokes.

Is beta-blocker (atenolol) a preferred antihypertensive in acute intracerebral hemorrhage?

The mortality in intracerebral hemorrhage (ICH) is mainly due to raised intracranial pressure, and its complications mediated by sympathetic overactivity. There is paucity of studies evaluating the role of beta-blockers in the outcome of ICH. This study reports the role of atenolol in reducing mortality, pneumonia, systemic inflammatory response syndrome (SIRS), and 3xa0months outcome in the patients with hypertensive ICH. 138 consecutive patients with hypertensive ICH were included and their stroke risk factors and clinical details were recorded. Consciousness was assessed by Glasgow Coma Scale and severity of stroke by Canadian Neurological Scale. Volume of hematoma was measures on CT scan and occurrence of SIRS and pneumonia were noted. 3xa0months outcome was categorized into good (Barthel index >12) and poor (BIxa0<xa012). The patients were categorized into those receiving atenolol and nonatenolol. The effects of atenolol on stroke outcome parameters were evaluated. Seventy-nine patients received atenolol and 59 did not and they mainly received amlodipine. There was no difference in the base line clinical characteristics between the two groups except smoking (Pxa0=xa00.01) and baseline blood pressure (Pxa0=xa00.007). Atenolol significantly reduced the mortality (11.4 vs 37.3xa0%, Pxa0<xa00.0001), SIRS (16.4 vs 40.9xa0%, Pxa0=xa00.007), and pneumonia (8.9 vs 30.5xa0%, Pxa0=xa00.002) compared to those not receiving atenolol. At 3xa0months, patients with atenolol had insignificantly better outcome compared to nonatenolol group (49.1 vs 31.9xa0%, Pxa0=xa00.11). Use of atenolol in hypertensive ICH results in reduction in mortality, SIRS, and pneumonia which may be due to its β-adrenergic blocking effect.

Central Post Stroke Pain: Clinical, MRI, and SPECT Correlation

OBJECTIVEnThe objective of this study was to report clinical spectrum of central post stroke pain (CPSP) and correlate these with magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) findings.nnnDESIGNnThe study was designed as a prospective study.nnnSETTINGnThe study was set in a tertiary care teaching hospital.nnnSUBJECT AND METHODnTwenty-three consecutive CPSP patients were included and their severity of pain, sensory threshold, allodynia, hyperalgesia, and temporal summation were assessed by quantitative sensory testing (QST). Cranial MRI and (99)Tc ethylene cystine dimmer SPECT findings correlated with QST.nnnRESULTSnThe duration of CPSP was 5 months (0.25-108). Allodynia was present in 12 patients, punctuate hyperalgesia in 11, and temporal summation in 12. SPECT was abnormal on visual analysis in 17 patients; hypoperfusion in corresponding thalamus in nine, and parietal cortex in 11 patients. Semiquantitative analysis revealed hyperperfusion of thalamus in four and parietal cortex in five patients. MRI revealed infarction in 14 and hematoma in nine patients. The QST findings were similar in thalamic and extrathalamic CPSP. The MRI and SPECT findings were also not different in CPSP patients with and without allodynia.nnnCONCLUSIONnThe QST findings in patients with CPSP were similar in patients with thalami and extrathalamic lesions. SPECT and MRI findings were also not different in CPSP patients with and without allodynia.

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.

Phosphodiesterase 4 D gene polymorphism in relation to intracranial and extracranial atherosclerosis in ischemic stroke

In ischemic stroke, extracranial MR angiography (ECMRA) is more frequently abnormal in Caucasians and intracranial (ICMRA) in Asians which may have a genetic basis. We report phosphodiesterase (PDE4D) gene polymorphism and its correlation with MRA findings in patients with ischemic stroke. Consecutive patients with MRI proven ischemic stroke undergoing MRA were included in this study. The severity of atherosclerotic stenosis on MRA was categorized into moderate 50%–80%, severe 80%–99%, and total occlusion 100% using NASCET criteria. The polymorphism in SNP 32, SNP 83 and SNP 87 of PDE4D gene was analyzed by PCR both in the patients and in 188 controls. Among the 148 patients, MRA was abnormal in 77% patients; ECMRA in 53.8%, ICMRA in 66% and both were abnormal in 42% patients. The frequency of CC genotype of PDE4D83 was significantly higher in the patients with ischemic stroke compared to controls (OR 3.38, 95% CI 1.61–7.11, P = 0.001). The frequency of TT genotype of PDE4D87 was significantly higher ICMRA abnormalities (20%) compared to normal ICMRA (2%). The genotype and allele frequency of PDE4D83 and PDE4D32 were not significantly related to MRA abnormalities. The role of PDE4D87 in atherosclerosis needs confirmation in larger studies.

Do ACE (rs4646994) and αADDUCIN (rs4961) gene polymorphisms predict the recurrence of hypertensive intracerebral hemorrhage

This study was undertaken to evaluate the role of ACE and αADDUCIN polymorphisms in patients with recurrent and nonrecurrent hypertensive intracerebral hemorrhage (ICH). A total of 101 nonrecurrent and 33 recurrent hypertensive ICH patients underwent an ACE (rs4646994) and αADDUCIN (rs4961) gene polymorphism study. The risk factors, clinical findings, CT scan abnormalities and functional outcome of recurrent and nonrecurrent ICH were compared. ACE (rs4646994) and αADDUCIN (rs4961) gene polymorphisms were also compared in the two groups and with 198 controls. The patients with recurrent ICH were older compared to those with nonrecurrent ICH and the other stroke risk factors were found in the two groups. Ganglionic–ganglionic pattern of recurrence was the commonest (75.6%) and all had at least one ICH in the location of hypertensive ICH. ACE DD genotype (OR6.18, 95%CI 2.93–13.02) and D allele (OR 2.43, 95%CI 1.70–3.47) were associated with nonrecurrent ICH compared to controls. In patients with recurrent ICH, DD genotype (OR 7.46, 95%CI 2.8–19.4) and D allele (OR 3.16, 95%CI 1.83–5.46) of ACE, and GW (OR 3.49, 95%CI 1.47–8.28), WW (OR 2.9, 95%CI 1.40–4.30) genotypes and W allele (OR 7.46, 95%CI 2.80–19.40) of αADDUCIN were more frequent compared to controls. Recurrent ICH also had higher frequency of WW genotype (OR 9.43, 95%CI 1.49–59.50) and W allele (OR 2.19, 95%CI 1.11–4.03) compared to nonrecurrent ICH. The frequency of DDxa0+xa0WW (Pxa0=xa00.008) and DD/WWxa0+xa0ID/GW (Pxa0=xa00.0001) genotypes in the recurrent ICH was higher than in the nonrecurrent ICH and the controls. Variant genotype combinations of ACE and αADDUCIN render the hypertensive patient more vulnerable to recurrent ICH.