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Biomedical subjects

C L Harden

Publications and source records attributed to C L Harden.

18 recordsLinked to original sources
PubMed2005

An analysis of lifetime fractures in women with epilepsy.

OBJECTIVE: To clarify the relationship between fractures and antiepileptic drug (AED) use. METHODS: Menopausal women with epilepsy were interviewed at two clinics regarding site, year and circumstances of any fracture, duration of AED use and menopause. Fracture sites were analyzed according to AED use. RESULTS: Twenty-nine fractures occurred in 20 of the 50 interviewed subjects (mean age 54). Nine occurred prior to AEDs; seven attributed to accident and two to clumsiness. Twenty occurred on AEDs; 10 attributed to clumsiness (most in the leg and foot), eight to seizure (most in the arm or hand) and two to accident. Duration of AED exposure was similar in both groups and in osteoporotic vs non-osteoporotic sites. CONCLUSIONS: Epilepsy therapy may contribute more to the lifetime occurrence of fracture than seizures themselves. More screening for osteoporosis is required. While adjusting doses to prevent seizures, ongoing screening for neurotoxicity must be maintained in order to avoid fractures.

Adult↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy [RETIRED]: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide-reviewed in the order in which these agents received approval by the US Food and Drug Administration) in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until September 2002, with selected manual searches up until 2003. RESULTS: There is evidence either from comparative or dose-controlled trials that gabapentin, lamotrigine, topiramate, and oxcarbazepine have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. There is also evidence that lamotrigine is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. CONCLUSIONS: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Acetates↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy [RETIRED]: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome. CONCLUSIONS: The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Acetates↗
PubMed2003

Seizure frequency is associated with age at menopause in women with epilepsy.

OBJECTIVE: To determine whether the age at menopause in women with epilepsy is associated with seizure frequency. METHODS: Women with epilepsy ages 45 and older from urban epilepsy centers were surveyed by interview and chart review for reproductive and general health characteristics, as well as seizure history, including frequency and treatment. Women who were not menopausal (> or = 1 year since last menses) were excluded. Subjects were divided into low, high, and intermediate seizure frequency groups. Statistical analyses included a one-way analysis of variance along with post hoc analysis (Bonferroni approach) to calculate pairwise comparisons. RESULTS: Sixty-eight subjects had a mean age at last menses (menopause) of 47.8 years (SD +/- 4.1, range 37 to 59 years). The age at menopause was 49.9 years in the low seizure frequency group (n = 15), 47.7 years in the intermediate seizure frequency group (n = 25), and 46.7 in the high seizure frequency group (n = 28). The difference in age at menopause in the three groups spanned approximately 3 years (p = 0.042). There was a negative correlation between the age at menopause and seizure group based on estimated lifetime seizures (p = 0.014, r = -0.310). No confounding influences such as history of cigarette smoking, number of pregnancies, or use of enzyme-inducing antiepileptic drugs were present. CONCLUSIONS: Seizure frequency or lifetime number of seizures is associated with the timing of cessation of reproductive cycling. Seizures may disrupt hypothalamic and pituitary function or alter neurally mediated trophic effects on the ovary.

Adult↗
PubMed2001

Topiramate titration and tolerability.

OBJECTIVE: To evaluate the tolerability and efficacy of two titration rates for topiramate initiated as adjunctive therapy in adults with partial-onset seizures, with or without secondary generalization, in a multicenter, double-blindtrial. METHODS: After a two-week baseline phase, 188 patients were randomized to either a 50/50 titration schedule (initial dosage 50 mg/d increased in 50-mg/d increments at weekly intervals; n = 95) or to a 100/200 titration schedule (initial dosage 100 mg/d increased by 100-200 mg/d at weekly intervals; n = 93). The maximum dosage of 400 mg/d was therefore achieved in eight weeks or three weeks, respectively. RESULTS: Compared with the 100/200 titration rate, the 50/50 titration rate significantly reduced the cumulative incidence of treatment-emergent adverse events (TEAEs) leading to changes in topiramate therapy (ie., dosage reductions, interruptions or discontinuations of therapy) (p = 0.048) and significantly reduced treatment interruptions or withdrawals due to TEAEs (p = 0.040). Mild or moderate effects involving the central nervous system were the most frequent adverse events. At the final visit, therapeutic responses were comparable in the 50/50 and 100/200 titration groups: median percent seizure reduction was 42% vs. 33%, proportion of patients with 250% seizure reduction was 42% vs. 38%, and proportion of patients with no seizures during double-blind treatment was 14% vs. 10%, respectively. Seizure frequency was substantially reduced from baseline during topiramate titration. At day 22, with the 50/50 titration group receiving 150 mg/d and the 100/200 titration group receiving 400 mg/d, the mean percent seizure reduction was 51% and 54%, respectively. CONCLUSIONS: Gradual initiation of topiramate therapy can significantly enhance patient tolerability without delaying therapeutic response.

Adolescent↗
PubMed2000

Therapeutic safety monitoring: what to look for and when to look for it.

This review focuses on the safety problems associated with antiepileptic drugs (AEDs) as revealed by laboratory testing and clinical examination. There are two classes of side effects: (a) common and mild and (b) rare and severe. Allergic reactions to AEDs are common and usually mild. However, on rare occasions, they can progress to more severe cutaneous disorders, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Severe allergic reactions to AEDs range from immune responses with fever to multiorgan dysfunction. Allergic rashes may be genetically or immunologically determined. Laboratory abnormalities produced by AEDs are common and mild, and include hepatic enzyme elevation associated with phenytoin and mild elevation in ammonia associated with valproate. Serious, although rare, idiosyncratic side effects, such as aplastic anemia, hepatotoxicity, and thrombocytopenia, have also occurred with AEDs. These reactions are largely confined to the "classic" AEDs. With the exception of felbamate, AEDs approved in the past decade have not been plagued by severe idiosyncratic reactions. Subtle endocrine abnormalities, including variations in thyroid function tests and bone metabolism, and the often subclinical effects on peripheral nerve conduction produced by phenytoin and carbamazepine, are also examined.

Acetates↗
PubMed1999

A beneficial effect on mood in partial epilepsy patients treated with gabapentin.

PURPOSE: Antiepileptic drugs (AEDs) are frequently used for their beneficial psychoactive effects on affective disorders. We sought to demonstrate a psychoactive effect of gabapentin (GBP) when used as add-on AED therapy. METHODS: Forty adult patients with partial epilepsy were studied in a prospective, non-randomized fashion with interviewer-rated and self-rated scales of mood and anxiety: the Cornell Dysthymia Rating Scale (CDRS), Beck Depression Inventory (BDI), and Hamilton Depression (Ham-D) and Anxiety (Ham-A) Scales. After completion of baseline mood and anxiety scales (time 1), 20 of the 40 patients were prescribed add-on GBP (treated group). The remaining 20 patients served as a control group. Both groups were similar in age and sex distribution. Follow-up mood and anxiety scales were performed in all patients approximately 3 months later (time 2). The average GBP dose at time 2 was 1,615 mg/day. All patients were taking stable doses of one to four AEDs at baseline and throughout the study. Seizure frequency was monitored throughout. Statistical significance was assessed by analysis of variance (ANOVA) by using a two-factor repeated-measures model. RESULTS: The GBP-treated group had a significant decrease in CDRS score over time compared with the control group (p = 0.04). No significant differences between the control and the treated groups were found for any of the remaining mood scales (BDI, p = 0.58; Ham-D, p = 0.59; Ham-A, p = 0.93). There was no significant difference or change in seizure frequency between groups. CONCLUSIONS: GBP treatment is associated with mood improvement as measured by the CDRS. This improvement was not accounted for by seizure improvement.

Acetates↗
PubMed1999

The effect of menopause and perimenopause on the course of epilepsy.

PURPOSE: The purpose of this study was to obtain preliminary information about the effect of menopause and perimenopause on the course of epilepsy, and to determine whether seizure type, use of hormone-replacement therapy (HRT), or a history of catamenial seizure pattern would influence this course. METHODS: We performed a questionnaire study of women with epilepsy currently in menopause and perimenopause, requesting information regarding the course of their epilepsy and treatment. Statistical analysis was performed by using Pearson chi2 with 95% confidence limits. RESULTS: Forty-two menopausal women (ages 41-86 years) responded. Twelve subjects reported no change in seizures at menopause, 17 reported a decrease in seizure frequency, and 13 reported an increase. Sixteen (38%) took synthetic HRT. Sixteen (38%) additional subjects (having some overlap with the HRT group) reported having a catamenial seizure pattern before menopause. HRT was significantly associated with an increase in seizures during perimenopause (p = 0.001). A history of catamenial seizure pattern was significantly associated with a decrease in seizures at menopause (p = 0.013). Thirty-nine perimenopausal women (ages 38-55 years) responded. Nine subjects reported no change in seizures at perimenopause, five reported a decrease in seizure frequency, and 25 reported an increase. Eight (15%) subjects took synthetic HRT, and 28 (72%) reported having a catamenial seizure pattern before menopause. HRT had no significant effect on seizures; however, a history of catamenial seizure pattern was significantly associated with an increase in seizures at perimenopause (p = 0.02). CONCLUSIONS: These pilot data suggest that synthetic HRT may be associated with an increase in seizure frequency in menopausal women with epilepsy. A catamenial seizure pattern may be associated with seizure decrease during menopause but with an increase during perimenopause.

Adult↗
PubMed1997

Pseudoseizures and dissociative disorders: a common mechanism involving traumatic experiences.

Patients with psychogenic non-epileptic seizures (pseudoseizures) have been diagnosed as having conversion disorder or dissociative disorder. Pseudoseizure patients frequently report a history of physical and sexual abuse, and traumatic experience is considered part of the mechanism for producing dissociation. Pseudoseizures may be a manifestation of dissociative disorder, especially when a history of sexual or physical abuse is documented. A common mechanism involving traumatic experience may be present in both pseudoseizures and dissociative disorders. A complete neurodiagnostic evaluation along with an awareness of this relationship is needed to provide appropriate care for this patient population.

Adult↗
PubMed1996

Felbamate levels in patients with epilepsy.

The usefulness of felbamate (FBM) levels in managing epilepsy patients has not been determined. The purpose of the present study was to determine if FBM levels obtained at routine office visits correlated with side effects reported by patients. We determined FBM levels by high-pressure liquid chromatography (HPLC) of 46 epilepsy patient plasma specimens (41 patients) and assessed medication toxicity and seizure frequency by a questionnaire. Thirty-six patients were treated with other antiepileptic drugs (AEDs); concomitant AED levels not in ranges believed to cause toxicity. FBM levels ranged from 9 to 134 microgram/ml, and were divided into three groups for analysis, resulting in low-range (9-36 microgram/ml), midrange (37-54 microgram/ml), and high-level (44-134 microgram/ml) groups. Anorexia and complaints of severe side effects were reported significantly more often in the high-level group as compared with the low- and midrange groups. Significantly more patients in the high-level group (10/13) reported decreased seizure frequency, as compared with 12 of 30 patients in the low- and midrange groups combined. FBM levels correlated linearly with doses overall, but most closely in FBM monotherapy patients.

Adolescent↗
PubMed1993

Low amplitude EEGs in demented AIDS patients.

We have observed an unusual low amplitude, slow and featureless electroencephalogram (EEG) pattern in some human immunodeficiency virus (HIV) infected patients without focal lesions on computerized tomography (CT scan) of the head. Out of 17 cases, 13 with AIDS and 4 with HIV positive status, 6 had low amplitude EEGs with slowing, all in the AIDS group. Nine of the 13 AIDS patients were demented, and 4 of these demented patients had slow verbal responses and mutism, indicating advanced HIV-related dementia. All 4 had low amplitude, slow EEGs. The patients with low amplitude, slow EEGs also had atrophy on CT scan by visual assessment and by measurement of ventricular indices. Of 17 age-matched controls referred for non-specific complaints such as headache and dizziness or for psychiatric disorders, 3 had EEGs read as low amplitude with slowing; two had normal mental status and one was psychotic. Although this EEG pattern is not etiologically specific, it may correlate with advanced dementia and atrophy on CT scan in AIDS patients.

AIDS Dementia Complex↗
PubMedDate not supplied

Infantile spasms in COFS syndrome.

Cerebro-oculo-facial-skeletal (COFS) syndrome is a rare, autosomal recessive syndrome characterized by microcephaly, microphthalmia and/or cataracts, neurogenic arthrogryposis, and multiple congenital anomalies. A term female infant with COFS syndrome who developed infantile spasms at the age of 3 months is reported. The patient had a good response to intramuscular ACTH with disappearance of infantile spasms and resolution of the hypsarrhythmic pattern on electroencephalography succeeded by a slow, synchronous pattern. Modified hypsarrhythmia returned after ACTH therapy was discontinued. Infantile spasms have not previously been reported in association with COFS syndrome and are a potentially treatable aspect of the disease. This patient may add to the clinical spectrum of COFS syndrome or may have a variant.

Abnormalities, Multiple↗
PubMedDate not supplied

Hyperglycemia presenting with occipital seizures.

Seizures are common in hyperglycemia and are often the first manifestation, particularly in nonketotic hyperglycemia (NKH). Published reports emphasize partial motor seizures almost exclusively. In a 3-year period, we observed three patients in whom occipital seizures, documented by ictal EEG recording, were the initial symptom of hyperglycemia. One patient was mildly ketotic at first. Seizures were visual in two patients and visual and adversive in the third. Seizures regressed with correction of abnormal glucose levels and did not recur during follow-up of less than or equal to 1 year despite discontinuation of antiepileptic drugs (AEDs) in two. Computed tomography (CT) scans did not show correlative abnormalities. Although published reports suggest that frontal lobe structures are particularly susceptible to the epileptogenic effects of NKH, our experience indicates that in NKH epileptic foci may originate in other cortical areas, such as occipital.

Adult↗