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Biomedical subjects

Dieter Schmidt

Publications and source records attributed to Dieter Schmidt.

32 records · Page 2Linked to original sources
PubMed2003

How effective is surgery to cure seizures in drug-resistant temporal lobe epilepsy?

It is well recognized that two-thirds of patients with drug-resistant temporal lobe epilepsy will be free of disabling seizures with continued medical treatment after temporal resection. Seizure recurrence has been noted during a five-year follow-up in approximately one-third of these seizure-free patients mostly but not exclusively following planned complete discontinuation of antiepileptic drugs (AEDs). This leaves one-third of patients without disabling seizures and without AEDs several years after surgery. Despite improvements in seizure frequency or severity, seizures persist in another third of patients undergoing surgery. Although cure (five years without any seizures and off AEDs) is the ultimate aim of epilepsy surgery, the percentage of patients cured by surgery cannot be well defined at the moment. We need a long-term randomized controlled trial on AED discontinuation in seizure-free patients followed by long-term open extension to determine if only one in three adult patients with drug-resistant temporal lobe epilepsy is cured by surgical intervention.

Anticonvulsants↗
PubMed2003

[Unusual retinal anomaly: the double papilla].

BACKGROUND: It is not clear whether doubling of the papilla occurs in connection with congenital ocular malformations or whether there is a double anlage of a real papilla. A double optic nerve close to the globe has never been observed. PATIENT: A 87-year old woman had high-grade myopia and amblyopia of her right eye together with an esotropia from early childhood. The right eye had a cataract. Some time ago she experienced a bilateral incomplete infarction of the territory of the posterior cerebral artery. The visual acuity of her right eye was 1/50. The Goldmann visual field showed a concentric constriction with the V/4 test mark. RESULTS: The right fundus revealed a double configuration of a papilla, in addition to widespread myopic changes due to extension of the retina and choroid at the posterior eye pole. The two papillae were located one upon another and the slightly smaller pseudopapilla was found temporal beneath to the true papilla. The papillae had central vessels, well supplied with blood, and with distributions into temporal and nasal tributaries. The big vessels of both papillae were not connected. The MRI revealed only one optic nerve of normal appearance. CONCLUSION: The findings in our patient demonstrate that a double papilla occurs without a double optic nerve. The smaller papilla occurred in an area of widespread myopic changes of the retina and choroid that we assume the appearance of a pseudopapilla. The site beneath the true papilla in an colobomatous area points to a developmental failure due to an incomplete closure of the optic cleft of the embryo. A secondary ingrow of vessels could have developed into the pseudopapilla during the embryonal period.

Aged↗
PubMed2003

[Cranial arteritis - An Overview].

BACKGROUND: Cranial arteritis is one of the most important emergency situations in ophthalmology. METHOD: Recommendations of the literature how to diagnose and how to treat the disease are described. RESULTS: The basic diagnostic steps such as the "Five Criteria Classification" together with certain exceptions of the classification criteria and the recognition of different facets of the varying clinical picture are emphasised. Special arteritic appearances of the facial artery, the occipital artery and the vertebral artery should be noted and identified. It is pointed out that an arteritis without headache is of great clinical importance, known as occult arteritis, because of the lack of classical symptoms, often leading to a wrong diagnosis. Anterior ischaemic optic neuropathy (AION) is the most frequent cause of blindness. Differential diagnosis between non-arteritic and arteritic AION is emphasised. The different arguments concerning the performance of unilateral or bilateral arterial resection ("biopsy") and the findings of colour duplex ultrasonography in comparison to the histological results are discussed. It is also pointed out that some new diagnostic procedures such as the MRI examination with gadolinium and the PET-Scan examination may be helpful in supporting the diagnosis. CONCLUSIONS: Cranial arteritis is more often diagnosed in recent years. The diagnosis should be made in cooperation by the ophthalmologist and internists and neurologists. Blindness caused by cranial arteritis is preventable in the majority of patients if diagnosed early and treated properly. For decades of clinical experience it has been well established that early diagnosis and systemic treatment with high doses of systemic corticosteroids are essential in preventing blindness in one or both eyes.

Anti-Inflammatory Agents↗
PubMed2003

[Amiodarone treatment and visual prognosis].

BACKGROUND: Amiodarone is currently regarded as the most effective antiarrhythmic drug available for the treatment of tachyarrhythmias. Up to now, no recommendations exist concerning ophthalmological follow-up examinations at regular intervals of patients treated with amiodarone. METHODS AND PATIENTS: We examined six patients with a mean age of 71.7 years (five men, one woman) who were treated with amiodarone. RESULTS: One patient had no visual disturbances and a second patient had no permanent change of the optic nerve because treatment with amiodarone was discontinued in time. In one patient an abnormal blue colour vision was noticed. Swelling of the optic disc completely disappeared in five patients after discontinuing the drug. One patient revealed a posterior ischaemic optic neuropathy (PION). In two patients a unilateral change of the optic disc occurred. In three patients a severe irreversible lesion of the optic nerve was found at follow-up examination. CONCLUSIONS: An insidious visual loss can occur with amiodarone treatment. A swelling of the optic disc without visual deterioration can occur as the first sign of a defect of the optic nerve. An abnormal blue colour vision can also be detected. After discontinuation of amiodarone either a visual improvement or a permanent deterioration may result. We recommend that every patient being treated with amiodarone should be observed by opthalmoscopy and colour vision examination at regular intervals (approximately every 3 months). Treatment with amiodarone should be discontinued after exclusion of life-threatening situations by a cardiologist, as soon as the first changes of the optic disc occur.

Aged↗
PubMed2002

New horizons in the development of antiepileptic drugs.

Significant advances have been made in the treatment of epilepsy over the past decades. However, despite the development of various novel antiepileptic drugs, about one third of patients with epilepsy is resistant to current pharmacotherapies. Even in patients in whom pharmacotherapy is efficacious, current antiepileptic drugs do not seem to affect the progression or underlying natural history of epilepsy. Furthermore, there is currently no drug available which prevents the development of epilepsy, e.g. after head trauma. Thus, there are at least three important goals for the future. (1) Better understanding of processes leading to epilepsy, thus allowing to create therapies aimed at the prevention of epilepsy in patients at risk; (2) improved understanding of biological mechanisms of pharmacoresistance, allowing to develop drugs for reversal or prevention of resistance; and (3) development of disease-modifying therapies, inhibiting the progression of epilepsy. The ultimate goal would be a drug combining these three properties, thus resulting in a complete cure for epilepsy. In this review, the current status of antiepileptic therapies is critically assessed, and innovative approaches for future therapies are highlighted.

Animals↗
PubMed2002

The clinical impact of new antiepileptic drugs after a decade of use in epilepsy.

The introduction of numerous effective, well tolerated and safe new antiepileptic drugs (AEDs) in the last decade of the 20th century has widened the choice of treatment options in epilepsy and improved the tolerability and the ease of use of treating patients with epilepsy. Nevertheless, significant safety and efficacy deficits continue to exist. Severe idiosyncratic reactions and organ toxicity have hampered the wide use of some of the newer AEDs. As a decade before, about one third of patients with chronic epilepsy is resistant to current pharmacotherapy. Even in patients in whom pharmacotherapy is efficacious, current AED do not seem to affect the progression or the underlying natural history of epilepsy. In addition, there is currently no drug available which prevents the development of epilepsy, e.g. after head trauma. Thus, there is an unmet need for safer and more effective drugs, especially for chronic, drug-resistant epilepsy. To stimulate the development of even better compounds, the demonstrated benefits and risks of current new AEDs are reviewed.

Anticonvulsants↗
PubMed2002

New strategies for the identification of drugs to prevent the development or progression of epilepsy.

During the last decade, several new antiepileptic drugs (AEDs) have been introduced in Europe, the United States, or other parts of the world. Although the antiepileptic efficacy of these drugs is not superior to that of older AEDs, some of the new drugs offer advantages in terms of improved tolerability, ease of use, and reduced interaction potential with other drugs. However, the new AEDs have only a modest impact on patients with refractory epilepsies, so that about one third of patients with epilepsy continue to have seizures with current pharmacotherapies. Thus, there is a continuing need for new medical therapies in epilepsy. During the Workshop on "New Horizons in the Development of Antiepileptic Drugs" (November 28-29, 2001, Philadelphia, PA), one topic dealt with the critical re-evaluation of previous preclinical strategies for the discovery and the development of new AEDs. The discussion of this session, which was chaired by the authors, is summarized in this article. Main issues of the discussion were whether epilepsy is a progressive disease and whether refractory epilepsy is preventable, the use of acute versus chronic animal models in the discovery and development of new AEDs, models for drug-resistant epilepsy, mechanisms of drug resistance, alterations in adverse effect potential of AEDs by epilepsy, and advances in pharmacogenomics and our understanding of pharmacologic responsiveness in epilepsy. Overall, it was felt that the current preclinical strategies for the discovery and development of new AEDs have to be redefined in order to identify agents that are clearly superior to current medications.

Animals↗
PubMed2002

Pharmacological overtreatment in epilepsy: mechanisms and management.

Despite considerable advances in the drug treatment of epilepsy in the last decade, pharmacoresistant epilepsy continues to occur today in as many as one in three patients with newly diagnosed epilepsy. These limitations of current drug treatment may result in the inadvertent overtreatment of patients with epilepsy. Overtreatment is defined here as unnecessary and excessive drug load in the management of epilepsy leading to a suboptimal risk-to-benefit balance. Pharmacological overtreatment is relatively common and may occur at all stages of epilepsy therapy. Scenarios for overtreatment include the unnecessary use of AEDs for prevention of epilepsy in patients at risk where current medications have not been shown to be effective or in patients with benign epilepsy syndromes with mild and rare partial seizures. Unnecessary rapid titration leading to overtreatment is a common occurrence in many patients. In addition, dose titration to the limit of tolerability and polytherapy are of limited utility and thus may cause overtreatment in many patients. As no markers currently exist for prediction of individual drug effect, trial and error still prevail in the pharmacotherapy of epilepsy. The increased drug load needs to be reversed once the risk-to-benefit balance worsens in the eye of the patient and in the assessment of the physician. Informing the patient about the benefit and the limitation of the planned change in medication is important. Because of emerging concern that drug overload may cause significant and even serious adverse effects without adequate benefit in seizure control, more data from rigorous scientific studies and new concepts for early recognition, reduction and prevention of overtreatment are needed.

Anticonvulsants↗
PubMed2002

Strategies to prevent overtreatment with antiepileptic drugs in patients with epilepsy.

Overtreatment is defined here as an unnecessary and excessive drug load in the management of epilepsy leading to a suboptimal risk-to-benefit balance. Pharmacological overtreatment can often be prevented by deciding and counselling carefully about the need for antiepileptic drugs (AEDs) given the limitations of current AEDs. Although AEDs will reduce the incidence of seizures, they have no demonstrated ability to prevent epilepsy in patients at risk or to modify the course of epilepsy in patients following the first seizure. In addition, starting AEDs may not be necessary for control of epileptic seizures induced by precipitation or predisposing factors or for benign epilepsies with rare or mild seizures. Start monotherapy with the chosen first-line AED, initially at low doses titrating up to the low maintenance dose. Avoid drug loading (except for emergency treatment). If seizures continue, titrate to the limit of tolerability which will however, achieve additional seizure control in approximately 20% of patients. If, as in many patients, dosing to the limit of tolerability is not beneficial, the dose should be reduced. Switching to an average dose of another first line AED is another option to prevent overtreatment. Avoid drug overload during add-on therapy by slowly reducing the dose of the first drug in patients having adverse effects, ideally by an amount that the patient does not experience any further adverse effects, if possible, before adding another drug. If the patient does not benefit unequivocally from two-drug therapy within 3 months (and approximately 75% will not benefit), slowly transfer to monotherapy of the second drug and start with a newly chosen AED for add-on. To counteract the propensity to overmedication in chronic epilepsy is not easy. Great benefits, without loss of seizure control, are often gained by slowly reducing the overall drug load.

Anticonvulsants↗
PubMed2002

[Ocular syphilis].

BACKGROUND: Syphilis has distinctly increased in the last decades. It is necessary to know the different eye changes in syphilis. PATIENTS: In four patients, between 34 and 71 years of age, typical as well as unusual syphilitic eye changes were found. In three patients diagnosis was made due to the inflammatory eye changes. RESULTS: An iritis was found in two patients (62 and 34 years old). In addition, the 62-year-old patient showed the unusual fundus picture of both vasculitis and neuroretinitis, with macular exudates and swelling of the optic disk. A venous occlusion, a rare sign in syphilis, was diagnosed in a 55-year-old patient. A 71-year-old patient revealed the characteristic finding of a placoid chorioretinitis. All four patients showed a swelling of the optic disk. CONCLUSION: Syphilis should be suspected even in older patients with an uncertain origin of uveitis, optic nerve disease, pupillary changes, or eye motility disturbances giving rise to carry out serologic tests in patients with the suspected diagnosis.

Adult↗
PubMed2000

Oxcarbazepine for Treatment of Partial Epilepsy: A Review and Recommendations for Clinical Use.

Recent trials and extensive postmarketing use confirm the efficacy and safety of oxcarbazepine (OXC) as a first-line treatment for adults and children with simple partial seizures, complex partial seizures, and partial seizures evolving to secondarily generalized seizures. OXC undergoes reductive metabolism at its keto moiety to form 10-hydroxy-10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide (MHD), which is glucuronidated and excreted in the urine, with minimal involvement of the hepatic cytochrome P450-dependent enzymes. OXC has some drug interactions, and does not require titration, allowing for better tolerability. Titration for monotherapy and adjunctive therapy of OXC could begin at 150 mg/day and be increased by 150 mg every 2-3 days until the target dose of 900-1200 mg/day is reached. If necessary, one can go faster and start with up to 600 mg/day and titrate with weekly increments up to 600 mg/day if necessary for seizure control. Conversion to monotherapy can be done overnight or gradually. For gradual conversion, use the recommended titration of OXC and withdraw the baseline antiepileptic drugs gradually by 25%, starting at Day 14 or earlier in case of baseline tolerability issues. Consider reducing the dose of the primary antiepileptic drug during adjunctive therapy in case of adverse events or increase the dose of OXC in case of incomplete seizure control. In children OXC should be started at 8-10 mg/kg/day in two or three divided doses. If clinically indicated the dose can then be increased by 10 mg/kg/day in weekly intervals with final doses up to 30-46 mg/kg/day. Dose adjustment may be necessary in very young children (age 2-5 years) and in patients with renal dysfunction, based on renal clearance. However no adjustment of OXC dose is needed in patients with mild to moderate hepatic dysfunction. OXC has a number of advantages which include rapid titration, no need for safety monitoring (except for uncommon and mostly asymptomatic hyponatremia), a low potential for drug-drug interactions (except for those possibly impairing the effectiveness of oral contraceptives and increasing the serum concentration of phenytoin), a rash rate of less than 5%, similar efficacy and similar or better tolerability and safety compared with first-generation antiepileptic drugs. OXC is a valuable alternative to current treatment options.

Journal Article↗
PubMedDate not supplied

New horizons in the development of antiepileptic drugs: the search for new targets.

The past decades have brought many advances to the treatment of epilepsy. However, despite the continued development and release of new antiepileptic drugs, many patients have seizures that do not respond to drug therapy or have related side effects that preclude continued use. Even in patients in whom pharmacotherapy is efficacious, current antiepileptic drugs do not seem to affect the progression or underlying natural history of epilepsy. Furthermore, there is currently no drug available which prevents the development of epilepsy, e.g., after head trauma or stroke. Thus, there are at least three important goals for the future: (1) better understanding of processes leading to epilepsy, thus allowing to create therapies aimed at the prevention of epilepsy in patients at risk; (2) development of disease-modifying therapies, interfering with progression of epilepsy, and (3) improved understanding of neurobiological mechanisms of pharmacoresistance, allowing to develop drugs for reversal or prevention of drug resistance. The Second Workshop on New Horizons in the Development of Antiepileptic Drugs explored these three goals for improved epilepsy therapy, with a focus on the search for new drug targets for prevention of epilepsy, for interfering with progression of epilepsy, and for interfering with drug resistance in epilepsy. A special topic dealt with gene expression analysis for target identification. Furthermore, pharmacological and non-pharmacological targets for curing epilepsy were explored. In this conference review, the current status of antiepileptic therapies is critically assessed, and innovative approaches for future therapies are highlighted.

Animals↗
PubMedDate not supplied

The chance of cure following surgery for drug-resistant temporal lobe epilepsy. What do we know and do we need to revise our expectations?

Although surgery is often seen as a curative treatment for patients with drug-resistant temporal lobe epilepsy, little information is available how many cases can be considered cured after surgery, i.e. are seizure-free for several years without taking antiepileptic drugs (AEDs). In our review, 13 retrospective and five prospective clinical observations published since 1980 provided data on long-term seizure control off AEDs in a total of 1658 patients. No randomized studies were found. Following temporal lobe surgery, approximately one in four adult patients and approximately one in three children or adolescents can currently shown to be seizure-free for 5 years without AEDs (25%, mean of eight studies in adults, 95% CI: 21-30%, and 31%, mean of three studies in children, 95% CI: 20-41%). The rate of seizure control off AEDs seemed to be stable after 2 years of follow-up. However, as 55% of patients free of disabling seizures preferred not to discontinue their medication completely as late as 5 years after surgery, it is impossible to know if they are cured or not. No features predictive of surgical cure were detected except for better cure outcome in children versus adults with hippocampal sclerosis and in patients with typical versus atypical Ammonshorn's sclerosis or tumor in one small study each. In conclusion, the available evidence on seizure outcome off AEDs after temporal lobe surgery is based on non-randomized studies and, in part, data were collected retrospectively. A randomized controlled trial is needed to determine if, in fact only one in three to four patients with temporal lobe epilepsy undergoing surgery can be considered cured.

Adolescent↗