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Biomedical subjects

L J Hirsch

Publications and source records attributed to L J Hirsch.

At least 19 recordsLinked to original sources
PubMed2003

Predictors and clinical impact of epilepsy after subarachnoid hemorrhage.

OBJECTIVE: To determine the frequency, predictors, and impact on outcome of epilepsy developing during the first year after subarachnoid hemorrhage (SAH). METHODS: The authors prospectively analyzed 247 of 431 patients with SAH treated over a period of 5 years who were alive with follow-up at 12 months. Epilepsy was defined as two or more unprovoked seizures after hospital discharge. RESULTS: New-onset epilepsy occurred in 7% (n = 17) of patients; an additional 4% (n = 10) had only one seizure after discharge. Independent predictors of epilepsy included subdural hematoma (OR 9.9, 95% CI 1.9 to 52.8) and cerebral infarction (OR 3.9, 95% CI 1.4 to 11.3). Unlike those without seizures, patients who developed epilepsy failed to experience functional recovery on the modified Rankin Scale (mRS) between 3 and 12 months after SAH. At 12 months epilepsy was independently associated with severe disability (score >/= 3) on the mRS (OR 10.3, 95% CI 2.5 to 42.0), increased instrumental disability on the Lawton Instrumental Activities of Daily Living scale (OR 4.9; 95% CI 1.1 to 22.2), reduced quality of life on the Sickness Impact Profile (OR 4.5; 95% CI 1.1 to 18.0), and increased state anxiety on the Spielberger Anxiety Inventory (OR 4.8; 95% CI 1.1 to 20.4). Epilepsy was not associated with cognitive impairment, depression, or subjective life satisfaction. CONCLUSION: Epilepsy occurred in 7% of patients with SAH, was predicted by subdural hematoma and cerebral infarction, and was associated with poor functional recovery and quality of life. Our findings indicate that focal pathology, rather than diffuse injury from hemorrhage, is the principal cause of epilepsy after SAH.

Activities of Daily Living↗
PubMed2001

Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus.

BACKGROUND: Although cIV-MDZ has emerged as a popular alternative to barbiturate therapy for refractory status epilepticus (RSE), experience with its use for this indication is limited. OBJECTIVE: - To evaluate the efficacy of continuous intravenous midazolam (cIV-MDZ) for attaining sustained seizure control in patients with RSE. METHODS: The authors reviewed 33 episodes of RSE treated with cIV-MDZ in their neurologic intensive care unit over 6 years. All patients were monitored with continuous EEG (cEEG). MDZ infusion rates were titrated to eliminate clinical and EEG seizure activity; cIV-MDZ was discontinued once patients were seizure-free for 24 hours. Acute treatment failures (seizures 1 to 6 hours after starting cIV-MDZ), breakthrough seizures (after 6 hours of therapy), post-treatment seizures (within 48 hours of discontinuing therapy), and ultimate treatment failure (frequent seizures that led to treatment with pentobarbital or propofol) were identified. RESULTS: All patients were in nonconvulsive SE at the time cIV-MDZ was started; the mean duration of SE before treatment was 3.9 days (range 0 to 17 days). In addition to benzodiazepines, 94% of patients had received at least two antiepileptic drugs (AED) before starting cIV-MDZ. The mean loading dose was 0.19 mg/kg, the mean maximal infusion rate was 0.22 mg/kg/h, and the mean duration of cIV-MDZ therapy was 4.2 days (range 1 to 14 days). Acute treatment failure occurred in 18% (6/33) of episodes, breakthrough seizures in 56% (18/32), post-treatment seizures in 68% (19/28), and ultimate treatment failure in 18% (6/33). Breakthrough seizures were clinically subtle or purely electrographic in 89% (16/18) of cases and were associated with an increased risk of developing post-treatment seizures (p = 0.01). CONCLUSIONS: Although most patients with RSE initially responded to cIV-MDZ, over half developed subsequent breakthrough seizures, which were predictive of post-treatment seizures and were often detectable only with cEEG. Titrating cIV-MDZ to burst suppression, more aggressive treatment with concurrent AED, or a longer period of initial treatment may reduce the high proportion of patients with RSE who relapse after cIV-MDZ is discontinued.

Adult↗
PubMed2001

The ontogeny of partial seizures in infants and young children.

PURPOSE: To describe the clinical manifestations of partial seizures in the pediatric population as a function of age. METHODS: Using the database of the pediatric epilepsy monitoring unit (Children's Hospital of New York), clinical and EEG characteristics of partial seizures were distributed by age groups 0-2, 2-6, and 6+ years for 123 patients who had at least one such seizure with a clear EEG correlate during their admission. chi2 tests for trend were used to examine clinical and EEG features as a function of age. RESULTS: The frequency of aura, limb automatisms, dystonic posturing, secondary generalization, and unresponsiveness increased with age, whereas asymmetric clonus and symmetric tonic posturing decreased with age. There were no clear changes in the types of EEG ictal patterns observed with age; however, partial seizures emanating from the anterior regions of the brain tended to increase with age, whereas those from the posterior regions tended to decrease with age. CONCLUSIONS: Important differences exist in the clinical expression of seizures between young children and adults. These findings will contribute to a better understanding of ictal ontogeny that will promote more accurate classification of seizures and of the epilepsies in young patients. Such efforts can be used to identify young patients for focal epilepsy surgery and to select appropriate anticonvulsive medications.

Age Factors↗
PubMed2001

Experience with the ketogenic diet in infants.

OBJECTIVE: To evaluate the effectiveness, tolerability, and adverse effects of the ketogenic diet in infants with refractory epilepsy. METHODS: A retrospective review of 32 infants who had been treated with the ketogenic diet at a large metropolitan institution. RESULTS: Most infants (71%) were able to maintain strong ketosis. The overall effectiveness of the diet in infants was similar to that reported in the literature for older children; 19.4% became seizure-free, and an additional 35.5% had >50% reduction in seizure frequency. The diet was particularly effective for patients with infantile spasms/myoclonic seizures. There were concomitant reductions in antiepileptic medications. The majority of parents reported improvements in seizure frequency and in their child's behavior and function, particularly with respect to attention/alertness, activity level, and socialization. The diet generally was well-tolerated, and 96.4% maintained appropriate growth parameters. Adverse events, all reversible and occurring in one patient each, included renal stone, gastritis, ulcerative colitis, alteration of mentation, and hyperlipidemia. CONCLUSION: The ketogenic diet should be considered safe and effective treatment for infants with intractable seizures.

Diet Therapy↗
PubMed1999

Effects of incorporating memory confidence ratings and language handicap modifications on intracarotid amobarbital procedure (Wada test) memory asymmetry scores.

PURPOSE: Intracarotid amobarbital procedure (IAP) memory asymmetry scores are often considered in determining lateralization of temporal lobe seizure foci. Additionally, these scores sometimes influence treatment plans for epilepsy surgery candidates. We examined the effects of two scoring modifications on IAP asymmetry scores: incorporating memory confidence ratings (MC), and use of a language handicap (LH) (i.e., adding a point to the memory score with anesthetization of the language-dominant hemisphere), both of which could be applied to most IAP protocols despite variations in testing methods among epilepsy surgery programs. METHODS: Sixty-nine consecutive unilateral temporal lobe epilepsy (TLE) patients with subsequent good surgical outcomes (Engel I or II) underwent bilateral IAP testing. Confidence ratings were obtained for all memory responses. The incorporation of confidence ratings and the application of a language handicap for dominant-hemisphere injections were applied to memory asymmetry scores in all combinations, resulting in four scoring methods. Results of the four methods were compared with respect to the proportion of patients lateralized accurately by each method. RESULTS: No patients were falsely lateralized with any method. Percentage of patients correctly lateralized with each scoring method is shown in Table 2. The results obtained with MC and with MC + LH (67% and 64% of patients accurately lateralized, respectively) were significantly better than results obtained with LH (55%, p<0.05). No other differences were significant. CONCLUSIONS: Although not statistically superior to standard methods, these results suggest that incorporating memory confidence ratings into IAP protocols may increase the likelihood of obtaining asymmetry scores that accurately lateralize to the hemisphere of seizure onset. In contrast, inclusion of a language handicap for scores obtained with the language-dominant ICA injection were not helpful and may even decrease the probability of obtaining clinically useful lateralizing data. These scoring modifications can be applied to most IAP protocols.

Adult↗
PubMed1998

Multivariable prediction of seizure outcome one year after resective epilepsy surgery: development of a model with independent validation.

PURPOSE: To identify predictors of seizure-outcome after epilepsy surgery and validate the findings in an independent series of patients. To use the results to develop a predictive model. METHODS: Sequential patients undergoing resective surgery for medically intractable epilepsy were identified at Yale New Haven Hospital (1987-1990, group 1) and Columbia Presbyterian Hospital (1991-1994, group 2). Information about seizure outcome and predictors of outcome was obtained from medical chart review. Good seizure-outcome was defined as having been seizure-free for one year beginning with discharge from the hospital. Multiple logistic regression was used to develop a model of predictors in group 1. It was then validated in group 2. RESULTS: There were 133 patients in group 1 and 81 in group 2. In a multivariable analysis, independent predictors of outcome in group 1 were presence of mesial temporal sclerosis based on postsurgical pathological analysis (MTS) (relative risk (RR) = 1.47), having a known underlying etiology (RR = 1.32), and partial seizures only (RR = 1.17). In group 2, the findings for each factor were similar to those in group 1: MTS, RR = 1.49; etiology, RR = 1.32; and partial seizures, RR = 1.24. Used in combination, these three factors can identify patients with nearly a 100% chance of being seizure-free (all three factors present) versus less than a 50% chance (none of the three factors present). CONCLUSIONS: With independent validation of the findings, we can be reasonably certain that the three factors identified in this analysis are meaningful and generalizable predictors of seizure outcome following epilepsy surgery. Use of predictive models should be considered in future studies to convert study results into clinically relevant statements about a particular patient's likelihood of surgical success.

Adolescent↗
PubMed1998

Postictal nosewiping lateralizes and localizes to the ipsilateral temporal lobe.

PURPOSE: We observed many patients with temporal lobe epilepsy (TLE) wiping their nose postictally, usually with the hand ipsilateral to their seizure focus. We wished to determine if this had lateralizing or localizing significance. METHODS: We retrospectively studied 87 patients: 47 with unilateral TLE defined by successful surgical outcome [30 with medial TLE (MTLE) and 17 with neocortical TLE (neoTLE)]; and 40 with extratemporal epilepsy (ExTLE). Videotapes of 319 complex partial seizures (CPS) without generalization were reviewed by 1 neurologist, blinded to patient identity, who recorded each episode of nosewiping and the hand with which it was performed. RESULTS: With regard to localizing potential, postictal nosewiping (PINW) was significantly more common in patients with unilateral TLE than in those with ExTLE. In the TLE group, PINW within 60 s of electrographic seizure offset occurred in 60% of patients (28 of 47) and 43% of seizures (74 of 171). In the ExTLE group, PINW was noted in 33% of patients (13 of 40; p < 0.05 as compared with TLE) and 15% of seizures (22 of 148; p < 0.001). Similar results were obtained with PINW within 30 s of seizure offset. Although PINW was more frequent in MTLE than in neoTLE (67% of patients vs. 47%), this finding did not reach significance. With regard to lateralizing potential, in the TLE group, unilateral PINW (performed with a single hand only) within 60 s of seizure offset was observed in 53% of patients (25 of 47) and was performed with the hand ipsilateral to the seizure focus in 92% (23 of 25). Thirteen patients (9 with TLE) wiped their nose more than once with the same hand in a single seizure within 60 s of offset in 18 seizures; this was done with the hand ipsilateral to the seizure focus in all 18 instances (predictive value = 100%). CONCLUSIONS: PINW is more common in unilateral TLE, particularly MTLE, than in ExTLE. PINW performed exclusively with one hand occurs in approximately 50% of patients with TLE and is highly predictive (92%) of seizure onset ipsilateral to the hand used, especially when it occurs repetitively. We hypothesize that ictal activation of the central autonomic nervous system, particularly the amygdala, results in ictal nasal secretions and causes nosewiping as the patient regains awareness postictally. The ipsilateral hand is used due to contralateral neglect or weakness.

Amygdala↗
PubMed1997

Prevention of nonvertebral fractures by alendronate. A meta-analysis. Alendronate Osteoporosis Treatment Study Groups.

OBJECTIVE: To evaluate the effect of treatment with alendronate sodium, a potent aminobisphosphonate, on the incidence of nonvertebral fractures in postmenopausal women with osteoporosis. DATA SOURCES: Published data and data on file at Merck Research Laboratories. STUDY SELECTION: All completed prospective, randomized, placebo-controlled alendronate trials of at least 2 years' duration (5 studies). DATA EXTRACTION: All subjects were women with osteoporosis between the ages of 42 and 85 years, postmenopausal at least 4 years, with lumbar spine bone mineral density (measured using dual-energy x-ray absorptiometry) at least 2.0 SD below the mean for young adult women. All women randomized to treatment with placebo or alendronate at a dose higher than 1 mg per day for at least 2 years were included. DATA SYNTHESIS: In the placebo group (n=590), 60 women reported nonvertebral fractures during 1347 patient-years at risk (overall rate, 4.45 women with fractures per 100 patient-years at risk). In the alendronate group (n = 1012), 73 women reported nonvertebral fractures during 2240 patient-years-at risk (overall rate, 3.26 women with fractures per 100 patient-years at risk). The estimated cumulative incidence of nonvertebral fractures after 3 years was 12.6% in the placebo group and 9.0% in alendronate group. The relative risk for nonvertebral fracture estimated using the Cox proportional hazards model was 0.71 (95% confidence interval,0.502-0.997) (P=.048). A reduction in risk was consistent across each of the studies and at each major site of osteoporotic fracture, including the hip and wrist. CONCLUSION: In postmenopausal women with osteoporosis, treatment with alendronate reduces the risk of nonvertebral fractures over at least 3 years.

Adult↗
PubMed1996

Esophagitis associated with the use of alendronate.

BACKGROUND: Alendronate, an aminobisphosphonate and a selective inhibitor of osteoclast-mediated bone resorption, is used to treat osteoporosis in postmenopausal women and Paget's disease of bone. Aminobiphosphonates can irritate the upper gastrointestinal mucosa. METHODS: We describe three patients who had severe esophagitis shortly after starting to take alendronate and also analyze adverse esophageal effects reported to Merck, the manufacturer, through postmarketing surveillance. RESULTS: As of March 5, 1996, alendronate had been prescribed for an estimated 475,000 patients worldwide, and 1213 reports of adverse effects had been received. A total of 199 patients had adverse effects related to the esophagus; in 51 of these patients (26 percent), including the 3 we describe in case reports, adverse effects were categorized as serious or severe. Thirty-two patients (16 percent) were hospitalized, and two were temporarily disabled. Endoscopic findings generally indicated chemical esophagitis, with erosions or ulcerations and exudative inflammation accompanied by thickening of the esophageal wall. Bleeding was rare, and stomach or duodenal involvement unusual. In patients for whom adequate information was available, esophagitis seemed to be associated with swallowing alendronate with little or no water, lying down during or after ingestion of the tablet, lying down during or after ingestion of the tablet, continuing to take alendronate after the onset of symptoms, and having preexisting esophageal disorders. CONCLUSIONS: Alendronate can cause chemical esophagitis, including severe ulcerations, in some patients. Recommendations to reduce the risk of esophagitis include swallowing alendronate with 180 to 240 ml (6 to 8 oz) of water on arising in the morning, remaining upright for at least 30 minutes after swallowing the tablet and until the first food of the day has been ingested, and discontinuing the drug promptly if esophageal symptoms develop.

Aged↗
PubMed1996

Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis.

To determine the effects of long-term daily oral alendronate sodium (ALN) on bone mass in postmenopausal women with osteoporosis, 19 centers enrolled 516 postmenopausal women aged 45-80 years with spine bone mineral density (BMD) at least 2.5 SD below the mean for young premenopausal women in a 3-year, double-blind, placebo-controlled study. Subjects were randomly allocated to one of four treatment groups: placebo; alendronate, 5 or 10 mg/day for 3 years; or alendronate, 20 mg/day for 2 years followed by 5 mg/day for the 3rd year. All patients received 500 mg/day of supplemental calcium to ensure adequate calcium intake. BMD was measured by dual-energy X-ray absorptiometry at several skeletal sites. Nonsignificant mean decreases in BMD of the spine, femoral neck, and trochanter of 0.6, 0.7, and 0.4%, respectively, occurred in the placebo group at 3 years. Relative to placebo-treated patients, spine BMD increased by 5.4%, 7.4%, and 8.4% in the 5, 10, and 20/5 mg ALN groups, respectively. Increases at the femoral neck were 3.5%, 5.5%, and 4.3%, and those at the trochanter were 5.1%, 7.2%, and 7.2%, respectively. Thus, efficacy of 10 and 20/5 mg ALN was similar, whereas the 5 mg dose was less effective. BMD continued to increase over the entire 3-year study duration in the ALN-treated groups and, compared with the other dosage groups, 10 mg ALN produced the largest gains in BMD during the 3rd year. Changes in biochemical markers of bone turnover and mineral homeostasis confirmed the effect of ALN to decrease bone turnover to a new steady-state level. The safety and tolerability of ALN were comparable with those of placebo. In summary, 10 mg daily oral ALN given for 3 years significantly and progressively increases bone mass and is a generally well-tolerated treatment for osteoporosis in postmenopausal women.

Administration, Oral↗