In memory of Leonard T. Kurland, the father of neuroepidemiology.
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Biomedical subjects
Publications and source records attributed to K Radhakrishnan.
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Eighty-five women with epilepsy were followed up for reproductive functions under the registry of epilepsy and pregnancy. 32 of them had completed the pregnancy. Their mean age was 26 years and mean seizure frequency was 0.7 during current pregnancy. Nineteen of them (59.4%) had generalized epilepsy. Nine of them were not on any anti epileptic drugs (AED), 23 women were on various AEDs, 19 being on monotherapy. Only 40% of the women were taking folic acid during pregnancy. Pregnancy ended as spontaneous abortion in one patient. Nearly one third required cesarean section. Majority (87.5%) had term babies. Three (10.7%) babies had birth asphyxia. Six babies (21.4%) had low birth weight. Congenital malformations were detected in four cases (12.5%). Malformations included neural tube defects, talipes equinovarus and other minor anomalies. These babies were exposed to sodium valproate, carbamazepine or phenobarbitone. The risk of malformation was significantly greater (p<0.05) when the mother had generalized epilepsy. The odds ratio for risk of malformation was much higher with sodium valproate (6) than that with carbamazepine (1.2) or phenobarbitone (0.8). Majority of women with epilepsy had safe pregnancy and childbirth without any aggravation of epilepsy.
The safety and efficacy of selective intraarterial administration of urokinase in five male patients, (age range 30 to 65 years, mean 41.2 years), with occlusive stroke involving the carotid territory and a normal cranial computed tomography scan was evaluated. The time elapsed before treatment ranged from one to 10 hours. Digital subtraction angiography disclosed distal internal carotid artery occlusion in one patient and occlusion of the middle cerebral artery or its branches in the others. The urokinase dose ranged from 120,000 to 500,000 units. In two patients who received thrombolytic treatment within three hours of the onset of symptoms, there was a 100% recanalisation associated with excellent neurological recovery. In the remaining three patients, recanalisation rate varied from 0 to 50% with partial recovery in two and no recovery in one patient. None had a haemorrhagic transformation of the infarct. Although no firm conclusions can be drawn because of the small number of patients studied, selective intraarterial urokinase therapy appears to be safe and useful in patients with carotid territory stroke if undertaken early. Only through a multicenter, randomized, controlled trial, enough number of patients can be recruited to verify these observations.
Quantitative analysis of vascular generational branching demonstrated that transforming growth factor-beta1 (TGF-beta1), a multifunctional cytokine and angiogenic regulator, strongly inhibited angiogenesis in the arterial tree of the developing quail chorioallantoic membrane (CAM) by inhibition of the normal increase in the number of new, small vessels. The cytokine was applied uniformly in solution at embryonic day 7 (E7) to the CAMs of quail embryos cultured in petri dishes. After 24 h the rate of arterial growth was inhibited by as much as 105% as a function of increasing TGF-beta1 concentration. Inhibition of the rate of angiogenesis in the arterial tree by TGF-beta1 relative to controls was measured in digital images by three well-correlated, computerized methods. The first computerized method, direct measurement by the computer code VESGEN of vascular morphological parameters according to branching generations G(1) through G(>/=5), revealed that TGF-beta1 selectively inhibited the increase in the number density of small vessels, N(v>/=5) (382 +/- 85 cm(-2) for specimens treated with 1 microg TGF-beta1/CAM for 24 h, compared to 583 +/- 99 cm(-2) for controls), but did not significantly affect other parameters such as average vessel length or vessel diameter. The second and third methods, the fractal dimension (D(f)) and grid intersection (rho(v)), are statistical descriptors of spatial pattern and density. According to D(f) and rho(v), arterial density increased in control specimens from 1.382 +/- 0.007 and 662 +/- 52 cm(-2) at E7 (0 h) to 1.439 +/- 0.013 and 884 +/- 55 cm(-2) at E8 (24 h), compared to 1. 379 +/- 0.039 and 650 +/- 111 cm(-2) for specimens treated with 1 microg TGF-beta1/CAM for 24 h. TGF-beta1 therefore regulates vascular pattern and the rate of angiogenesis in a unique "fingerprint" manner, as do other major angiogenic regulators that include VEGF, FGF-2 (bFGF), and angiostatin. TGF-beta1 did not stimulate angiogenesis significantly at low cytokine concentrations, which suggests that this quail CAM model of angiogenesis is not associated with an inflammatory response.
To date, very few studies have investigated patients' views on the information they receive from the doctor concerning epilepsy and its management. Little information is available about the influence of doctor-patient communication and locus of control on the compliance of persons with epilepsy. We investigated, through a questionnaire-interview design, among patients attending the epilepsy clinic of a tertiary referral center in South India, their views about the provision of information by the doctor, and their compliance and locus of control. We also determined the interrelation between doctor-patient communication, compliance and locus of control. Our subjects comprised 200 adult persons with epilepsy, 113 males and 87 females, mean age 30.5 (range 18-67) years. Over one-third of the subjects received from the doctor insufficient information about epilepsy and its treatment. There was a significant positive correlation between effective doctor-patient communication and compliance. A majority of our patients had an external locus of control, which negatively influenced the compliance. Even in a comprehensive epilepsy clinic of a model tertiary referral center in a developing country, a significant proportion of patients do not receive optimal information about epilepsy from the doctor. Knowledge about their disease will encourage people with epilepsy to make informed choices, and achieve better compliance and personal control of their problems. Educating primary and secondary care physicians about the importance of doctor-patient communication in the management of epilepsy and educating the public about the positive aspects of life in epilepsy cannot be overemphasized.
PURPOSE: To ascertain the prevalence and pattern of epilepsy and to characterize and quantify knowledge, attitude, and practice (KAP) toward epilepsy among the people of the state of Kerala, which is distinguished from the rest of India by a high level of literacy and health awareness of its population. METHODS: We conducted a door-to-door survey covering the entire population of 238,102 people residing in 43,681 households in a semiurban area of central Kerala. The screening questionnaire administered by medical social workers had a sensitivity of 100% for identifying persons with epilepsy. Neurologists examined all the individuals suspected of having epilepsy. We evaluated KAP toward epilepsy among 1,118 subjects (439 males and 679 females; mean age, 33.3 years; age range, 15-85 years) from households without epilepsy in the study area. RESULTS: Through a three-phased survey, we ascertained 1,175 cases (616 males and 559 females) with active epilepsy, providing a crude point prevalence ratio of 4.9 cases per 1,000 people and an age-adjusted prevalence ratio of 4.7 cases per 1,000 population. The highest age-specific prevalence rate of 6.5 per 1,000 occurred in the 10- to 19-year-old age group. Sex-specific prevalence rates did not significantly differ. The proportion of generalized and localization-related epilepsies was 58.8% and 30.6%, respectively. Ninety-nine percent of the KAP respondents had read or heard about epilepsy. Thirty-one percent and 27% thought epilepsy was a hereditary disorder and a form of insanity, respectively. About 40% of the respondents felt that individuals with epilepsy could not be properly educated or employed. Eleven percent would object to their children having contact with epileptic children. CONCLUSIONS: The prevalence and pattern of epilepsy in central Kerala, South India, do not differ from that of developed countries. Although the awareness of epilepsy among the people of Kerala was comparable to that of developed countries, the attitudes were much more negative. The need for educating the people of Kerala on epilepsy and for incorporating an adequate knowledge of epilepsy in the school curricula cannot be overemphasized.
This study illustrates the outcome and cost-effectiveness of anterior temporal lobectomy (ATL) among patients with medically refractory temporal lobe epilepsy (TLE) treated in an epilepsy center in Kerala, South India. Patients for ATL were selected on the basis of a noninvasive protocol comprising clinical, interictal scalp electroencephalogram (EEG), magnetic resonance imaging, and ictal video-EEG data. The authors compared the outcome and direct cost of 119 patients (mean age, 25.6 years; mean duration of epilepsy before ATL, 16.1 years) who have completed at least 1 year follow-up after ATL with 71 refractory TLE patients (mean age, 27.1 years; mean duration of epilepsy, 15.4 years) who did not undergo ATL. Patients in the study who underwent ATL had a 70% likelihood of becoming seizure-free after ATL and a 30% chance of being completely off of antiepileptic drug treatment within 3 years after ATL. The out-of-pocket one-time payment for ATL (including presurgical evaluation) in this setup is Indian Rupees (INR) 47,000 (US$ 1,200). The total direct medical cost of caring for TLE patients aged 26 to 60 years would be INR 200,000 (US$ 5,000). Patients freed from seizures often can be better employed and achieve an improved quality of life. It is concluded that ATL for refractory TLE is a more cost-effective option than continued medical treatment. Epilepsy surgery is not only possible in a developing country but can also be undertaken in a cost-effective way.
Medically treated brainstem abscess in a 11 year old boy with tetralogy of Fallot is reported. There was a complete resolution of the lesion without any neurologic sequelae during parenteral antibiotic therapy with crystalline penicillin, chloramphenicol and metronidazole. The pathogenesis and management of cardiogenic brain abscesses in general and brainstem abscess in particular has been reviewed.
Following anterior temporal lobectomy performed to control intractable complex partial seizures (CPS), it is rare to find a symptomatic cyst at the lobectomy site causing increased intracranial pressure and neurological deterioration. We report a 24-year-old lady who underwent anterior temporal lobectomy with extended amygdalohippocampectomy for CPS of temporal lobe origin. Ten months following the procedure, she developed a large expanding cyst at the temporal lobectomy site manifesting with recurrence of CPS, progressive focal neurological deficit and increased intracranial pressure. The patient underwent a repeat craniotomy, decompression of the cyst along with wide excision of the wall and fenestration of the arachnoid membrane into the basal cisterns. Following the procedure, the features of increased intracranial pressure and focal neurological deficit promptly improved and her seizures became better controlled. Craniotomy and fenestration of a symptomatic iatrogenic cyst following temporal lobectomy results in clinical improvement, obviating the need for a permanent cystoperitoneal shunt.
The authors report three children who exhibited developmental learning disabilities (DLDs) associated with behavioral disturbances, such as attention deficit, hyperactivity, and autistic features. The thyroid function tests performed as a part of routine endocrinologic evaluation of children with DLDs revealed a hormonal profile consistent with hyperthyroidism. These children had no systemic signs of hyperthyroidism. Treatment with neomercazole resulted in good control of their hyperkinetic behavior and subsequent improvement in language function attributable to an increased attention span, thereby facilitating speech therapy. Although routine screening of all children with DLDs for thyroid dysfunction may not be cost-effective, selective screening of children with familial attention-deficit hyperactivity disorder and those with attention-deficit and hyperactivity in association with DLDs and pervasive developmental disorders appears to be justified.
No study has investigated the prevalence and pattern of benign epileptiform variants (BEVs) in the electroencephalograph (EEG) of subjects from a developing nation. We addressed this issue by ascertaining the BEVs among subjects referred for EEG to a comprehensive epilepsy program in South India. We identified BEVs in 326 out of 1778 subjects (18.3%) who had both awake and sleep EEG recordings. The frequency distribution of individual BEVs were as follows: benign sporadic sleep spikes 8.2%, wicket waves 1%, 14 and 6 Hz positive spikes 5.7%, 6 Hz spike-waves 2.8% and rhythmic temporal theta burst of drowsiness 0.8%. We conclude that the prevalence rates of BEVs among South Indian subjects are not different from those reported from developed countries. We have highlighted the consequences of misinterpretation of BEVs as epileptiform, which is more likely to occur in Third World countries because of the non-availability of qualified technologists and electroencephalographers.
We provide numerical evidence for the existence of a low-dimensional chaotic attractor in the rheology of dilute suspensions of slender bodies in a simple shear flow. The rheological parameters which characterize the stress deformation behavior of the suspension are calculated based on appropriate averages over the orientation vectors of the slender bodies. The system considered in this work, therefore, exhibits chaos in experimentally measurable averages over a large number of uncoupled chaotic oscillators. The numerical demonstration that these parameters may evolve chaotically may thus have important consequences for both chaos theory and suspension rheology. We also provide plausible explanations for the existence of a low-dimensional chaotic attractor in the rheological parameters in terms of the expressions for the rheological parameters and the coupling between individually chaotically evolving orientations and the expressions for the rheological parameters.
PURPOSE: To determine the factors associated with changes in seizure control during the postsurgical course of epilepsy surgery patients. METHODS: Evaluation of patients after consecutive temporal and frontal resection whose seizure frequency was scored for each year of postsurgical follow-up. In each cohort, patients with a change in their seizure control after the first postsurgical year were compared with control subjects to determine factors that may be responsible for the change. RESULTS: Thirty-three (15%) of 214 temporal lobectomy versus 12 (20%) of 59 frontal resection patients experienced a change in seizure control (p>0.05). Ten (5%) of 214 temporal lobectomy versus nine (15%) of 59 frontal resection patients experienced an improvement in seizure control (p = 0.009), but 23 (11%) of 214 temporal lobectomy versus three (5%) of 59 frontal resection patients had a worsening in seizure control (p>0.05). In temporal lobectomy patients, preoperative unilateral temporal epileptiform discharges were associated with improvement (p = 0.03), whereas older age at surgery was associated with worsening of seizure control (p = 0.007). In frontal resection patients, presence of a congenital central nervous system (CNS) anomaly was associated with late improvement in seizure control (p = 0.006). CONCLUSION: During the postsurgical course, an improvement in seizure control is more common after frontal resection than after temporal lobectomy. Factors associated with improvement are the presence of a congenital CNS abnormality in frontal resection patients, and the occurrence of preoperative unilateral epileptiform discharges in temporal lobectomy patients. Older age at temporal lobectomy may be associated with greater risk of worsening seizure control.
PURPOSE: To study the current pharmacotherapy practices of epilepsy and its economics in a developing country by correlating the epidemiology and economics of antiepileptic drug (AED) treatment in general epilepsy care and comprehensive epilepsy care. METHODS: We compared the AED-use profiles, efficacy, and tolerability at entry and at last follow-up for 972 patients seen at a comprehensive epilepsy care program in South India from 1993 to 1995. The relative cost was expressed as the average percentage of the per capita gross national product (GNP/capita) each individual spent for AED treatment. RESULTS: At entry, 562 (57.8%) subjects were receiving polytherapy; at last follow-up, 743 (76.4%) patients were receiving monotherapy, an increase of 34.3% in the use of monotherapy. One or more adverse drug reactions were reported by 28.6% of patients at entry and by 19.8% at last follow-up. The proportion of patients who were seizure free increased from 29.0 to 44.8%. Carbamazepine (CBZ) was the most frequently used AED, followed by diphenylhydantoin (DPH), valproate (VPA), and phenobarbitone (PB). The relative cost (% GNP/capita) for standard AEDs were as follows: PB, 4.4%; DPH, 7.1%; CBZ, 16.8%; and VPA, 29.5%. The average annual cost of AED treatment per patient in U.S. dollars was $64.32 at entry and $47.73 at last follow-up. Reduction in polytherapy resulted in the net annual saving of $16,128 ($16.59 per patient, or 5.4% GNP/capita). CONCLUSIONS: The more frequent use of relatively expensive drugs like CBZ and VPA and the use of polytherapy-still quite prevalent in developing countries-has escalated the cost of AED therapy. Although in recent years AEDs have become more available in developing regions, primary and secondary care physicians have not been adequately educated about the current trends in the pharmacotherapy of epilepsy.
This is the first report of a case in which diagnosis of en-plaque tuberculoma on the basis of magnetic resonance imaging (MRI) findings was confirmed by a Mycobacterium tuberculosis complex-specific PCR assay of cerebrospinal fluid. The accuracy of the diagnosis was supported by good response to antitubercular drugs, which was shown by repeat MRI studies performed after treatment.
The neuropathological features of temporal lobe epilepsy were studied utilising 100 consecutive surgical specimens from patients with medically refractory complex partial seizures. A wide spectrum of neuropathological changes was recorded in 98 specimens. Fifty-eight specimens showed features of Ammon's horn sclerosis. Diffuse accumulation of corpora amylacea were demonstrated in the resected temporal lobes from 54 patients. Six patients had neoplastic lesions of temporal lobe. One unique case of dysembryoplastic neuroepithelial tumour showed a melanotic component within the tumour. The neuropathological features were regarded as nonspecific in 31% of cases. Our results indicate that a majority of patients with medically intractable epilepsy of temporal lobe origin reveal significant neuropathological features. Careful documentation of the neuropathological features and its correlation with radiological, electrophysiological and pre- and post-surgical clinical features will help in predicting the seizure outcome after temporal lobectomy for medically refractory epilepsy.
We report a 25-year-old female who developed clinical and electroencephalographic (EEG) features of subacute sclerosing panencephalitis (SSPE) at the age of 17 years. After almost 17 months of progressive neurological deterioration to a level where she was bedridden and incapable of self-care (Risk and Haddad stage 3a), she experienced a substantial spontaneous clinical and EEG remission (stage 4c) which she has maintained for the last 8 years. The measles antibody titer in the cerebrospinal fluid (CSF), however, progressively increased during follow-up. There are only very few patients with well documented diagnosis of SSPE who have maintained such a prolonged remission. The age at onset of SSPE of > or = 12 years, disappearance of periodic complexes and a tendency for normalization of the background activity in the EEG, and a progressive increase in the measles antibody titer in the CSF appears to predict a favourable outcome of SSPE.