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Dieter Schmidt

Publications and source records attributed to Dieter Schmidt.

At least 19 recordsLinked to original sources

Central retinal artery occlusion: findings in optical coherence tomography and functional correlations.

BACKGROUND: Visual prognosis in central retinal artery occlusion (CRAO) is poor and not predictable in individual patients. There may be a correlation between visual acuity and extent of initial macular edema. METHODS: Central retinal thickness of eleven patients with subtotal CRAO was measured with optical coherence tomography (OCT). Patients' acute-stage macular thicknesses were compared to those of later stages. Values are given as mean (+/-standard error; range). RESULTS: The mean age of the eleven patients was 68.8 years (62-75). Eight men and three women were examined. The mean initial duration of CRAO was 24.7 (+/- 5.0; 4-77) hours. Initial central thickness was 372.5 (+/- 27.1; 258-522) microm. After 5.7 (+/- 1.5; 1-17) months, mean reduction in macular edema was 197 (+/- 31.3; 63-391) microm. Visual acuity (VA) improved from 0.0125 (+/- 0.2; blindness -0.6) to 0.035 (+/- 0.2; blindness - 0.8) namely 4.5 lines. This difference was significant (p= 0.023). 6/11 patients (55 %) initially had a pronounced central retinal edema (>380 microm). No correlation was found between the initial macular edema height and visual improvement. CONCLUSIONS: The extent of macular edema differs widely and does not affect visual prognosis in CRAO eyes.

Aged↗

Preserved vision despite distinct retinal edema in central retinal artery occlusion.

BACKGROUND: In subtotal central retinal artery occlusion (CRAO), distinct retinal edema with acute onset irreversible visual loss is common. - METHODS: Clinical observation, fluorescein angiogram. - PATIENT: A 69-year-old patient presented with acute visual loss of his right eye. Risk factors for CRAO were arterial hypertension and diabetes mellitus. A further factor was a 60% stenosis of the right and a 90% stenosis of the left internal carotid arteries. - RESULT: Visual acuity at initial examination was 20/32 despite pronounced central retinal edema with characteristic cherry red spot of the macula. Fluorescein angiography demonstrated early filling of retinal vessels, only perfusion of the inferior macular vessels was delayed. Two months later retinal edema resolved and central visual acuity was 20/25. - CONCLUSION: In this patient, retinal edema most likely resulted from a transient retinal ischemia. Spontaneous reperfusion occurred early enough to allow functional recovery in the ischemic retina.

Aged↗

Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study.

It is not well known how often drug resistance, a major clinical problem, occurs early or late in the course of epilepsy and how often epilepsy follows a continuous, remitting or relapsing-remitting pattern. To provide evidence if, in fact, different patterns of evolution of drug resistance and remission exist, a prospective, long-term population-based study of 144 patients followed on the average for 37.0 years (SD 7.1, median 40.0, range 11-42) since their first seizure before the age of 16 years was performed. At the end of follow-up, 67% of 144 patients were in terminal remission, on or off antiepileptic drugs. Early remission, starting within the first year of treatment, was seen in 45 patients (31%). In 23 (16%) of them, first remission continued, uninterrupted by relapse, to terminal remission. Late remission with a mean delay of 9 years was achieved by a further 72 patients (50%), including 46 (32%) patients who achieved terminal remission without any relapse and suggested, together with 23 patients, a remitting course. Following a relapse after early or late remission, 28 (19%) patients achieved terminal remission, suggesting a remitting-relapsing pattern. Altogether 20 patients (14%) did not re-enter remission, indicating a worsening course of epilepsy. Twenty-seven (19%) patients were drug-resistant from the start to the end of follow-up. In conclusion, half the patients with childhood-onset epilepsy will eventually enter terminal remission without relapse and a fifth after relapse. One-third will have a poor long-term outcome in terms of persistent seizures after remission or without any remission ever.

Adolescent↗

New Horizons in the development of antiepileptic drugs: Innovative strategies.

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 the 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 four important goals for the future: (1) development of better antiepileptic ("anti-ictal") drugs with higher efficacy and tolerability to stop seizures compared to current medications; (2) better understanding of processes leading to epilepsy, thus allowing to create therapies aimed at the prevention of epilepsy in patients at risk; (3) development of disease-modifying therapies, interfering with progression of epilepsy, and (4) improved understanding of neurobiological mechanisms of pharmacoresistance, allowing to develop drugs for reversal or prevention of drug resistance. The third Workshop on New Horizons in the Development of Antiepileptic Drugs explored these four goals for improved epilepsy therapy, with a focus on innovative strategies in the search for better anti-ictal drugs, for novel drugs for prevention of epilepsy or its progression, and for drugs overcoming drug resistance in epilepsy. In this conference review, the current status of antiepileptic therapies under development is critically assessed, and innovative approaches for future therapies are highlighted.

Animals↗

Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment with antiepileptic drugs.

Development of tolerance (i.e., the reduction in response to a drug after repeated administration) is an adaptive response of the body to prolonged exposure to the drug, and tolerance to antiepileptic drugs (AEDs) is no exception. Tolerance develops to some drug effects much more rapidly than to others. The extent of tolerance depends on the drug and individual (genetic?) factors. Tolerance may lead to attenuation of side effects but also to loss of efficacy of AEDs and is reversible after discontinuation of drug treatment. Different experimental approaches are used to study tolerance in laboratory animals. Development of tolerance depends on the experimental model, drug, drug dosage, and duration of treatment, so that a battery of experimental protocols is needed to evaluate fully whether tolerance to effect occurs. Two major types of tolerance are known. Pharmacokinetic (metabolic) tolerance, due to induction of AED-metabolizing enzymes has been shown for most first-generation AEDs, and is easy to overcome by increasing dosage. Pharmacodynamic (functional) tolerance is due to "adaptation" of AED targets (e.g., by loss of receptor sensitivity) and has been shown experimentally for all AEDs that lose activity during prolonged treatment. Functional tolerance may lead to complete loss of AED activity and cross-tolerance to other AEDs. Convincing experimental evidence indicates that almost all first-, second-, and third-generation AEDs lose their antiepileptic activity during prolonged treatment, although to a different extent. Because of diverse confounding factors, detecting tolerance in patients with epilepsy is more difficult but can be done with careful assessment of decline during long-term individual patient response. After excluding confounding factors, tolerance to antiepileptic effect for most modern and old AEDs can be shown in small subgroups of responders by assessing individual or group response. Development of tolerance to the antiepileptic activity of an AED may be an important reason for failure of drug treatment. Knowledge of tolerance to AED effects as a mechanism of drug resistance in previous responders is important for patients, physicians, and scientists.

Animals↗

Spontaneous regression of retinal angiomatous lesions in v. Hippel-Lindau disease (VHL).

BACKGROUND: Very little documentation of spontaneous regression of an angiomatous retinal lesion in v. Hippel-Lindau disease (VHL) exists. It is commonly believed that a spontaneous change of hemangiomas into fibrotic lesions occurred. PATIENTS/METHODS: Follow-up examinations of four patients with VHL in the Freiburg VHL study were carried out. RESULTS: A 16-year-old girl revealed a vascular lesion at the border of the optic disc. Control examination nine years later revealed complete spontaneous regression of the retinal vascular changes. A slight retinal vascular change at the superior border in her right eye was found in a 36-year-old woman. A control examination 20 years later revealed regression of the lesion. A 41-year-old woman showed in the retinal periphery a small fibrotic white hemangioma with a pigmented feeder vessel as sign of spontaneous tumor regression. A 12-year-old boy had a retinal microaneurysm inferior to the optic disc that disappeared several years later. CONCLUSION: Documentations of spontaneous regression of minor angiomatous retinal lesions in VHL exist. Such vascular changes are rare. Every retinal lesion should be controlled by follow-up examination and documentation. In case of retinal lesion growth, treatment is necessary.

Adolescent↗

Retinal arterial occlusion due to embolism of suspected cardiac tumors -- report on two patients and review of the topic.

BACKGROUND: Ophthalmic complications due to heart tumors are rare. PATIENTS: This case report describes two patients with ocular complications, caused by a suspected cardiac tumor. A 56-year-old woman with arterial hypertension had a severe episode of headache coinciding with an acute loss of vision in her right eye and left-sided hemiparesis. A 20-year-old woman noticed sudden transient visual loss in her right eye. RESULT: The 56-year-old woman had an infarction on the right side of the middle and posterior cerebral arteries and, simultaneously, a central retinal artery occlusion (CRAO) in her right eye. Echocardiography revealed a tumor in the left atrium. The tumor disappeared after treatment with phenprocoumon within a few days. The diagnosis of a cardiac thrombus was made. The 20-year-old woman noticed recurrent episodes of sudden, transient visual loss in her right eye. A branch retinal arterial occlusion (BRAO) in her right eye was diagnosed. Echocardiography revealed a myxoma in the left atrium. The tumor was successfully excised surgically. CONCLUSION: In any vascular disturbance in the eye suspected to be embolic in origin, echocardiography should be carried out in order to exclude the presence of a heart disease.

Adult↗

Ocular ichemia syndrome - a malignant course of giant cell arteritis.

PURPOSE: To call attention to a malignant course of ocular ischemic syndrome in patients with giant cell arteritis (GCA). METHODS/PATIENT: A 84-year-old woman developed severe headache for about 3 (1/2) months prior to myocardial infarction and visual disturbances. RESULTS: An anterior ischemic optic neuropathy (AION) in the right eye with a distinct reduction in visual acuity was found. The retina revealed several cotton-wool spots in both eyes. Serologic examinations showed inflammatory signs. Despite treatment with prednisolone, eye pressure decreased to 2 mm Hg in the right eye and 4 mm Hg in the left eye in a few days. An ischemic iritis developed in the right eye. Visual acuity worsened to detection of hand motions in the right eye and to 0.1 in the left eye. Approximately 8 (1/2) months after her initial headache, a biopsy was carried out. The patient was treated continuously with corticosteroids. Histology of the superficial temporal artery indicated inflammatory cells in the vessel wall. - The patients daughter developed symptoms of GCA at the age of 54 years. CONCLUSION: An ocular ischemic syndrome points to a malignant course of the disease. A cardiac infarction can develop in GCA. A biopsy of the temporal artery can reveal inflammatory changes even after 8 (1/2) months.

Aged↗

Anxiety in patients with epilepsy: systematic review and suggestions for clinical management.

Up to 50 or 60% of patients with chronic epilepsy have various mood disorders including depression and anxiety. Whereas the relationship between epilepsy and depression has received much attention, less is known about anxiety disorders. It is now recognized that anxiety can have a profound influence on the quality of life of patients with epilepsy. The relationship between anxiety disorders and epilepsy is complex. It is necessary to distinguish between different manifestations of anxiety disorder: ictal, postictal, and interictal anxiety. Preexisting vulnerability factors, neurobiological factors, iatrogenic influences (antiepileptic drugs, epilepsy surgery), and psychosocial factors are all likely to play a role, but with considerable individual differences. Despite the high prevalence of anxiety disorders in patients with epilepsy, there are no systematic treatment studies or evidence-based guidelines for best treatment practice. Nevertheless, a practical approach based on the temporal relationship between anxiety and epileptic seizures allows clinicians to consider appropriate treatment strategies to reduce the psychiatric comorbidity in patients with epilepsy.

Anti-Anxiety Agents↗

Drug resistance in epilepsy: putative neurobiologic and clinical mechanisms.

Drug-resistant epilepsy with uncontrolled severe seizures despite state-of-the-art medical treatment continues to be a major clinical problem for up to one in three patients with epilepsy. Although drug resistance may emerge or remit in the course of epilepsy or its treatment, in most patients, drug resistance seems to be continuous and to occur de novo. Unfortunately, current antiepileptic drugs (AEDs) do not seem to prevent or to reverse drug resistance in most patients, but add-on therapy with novel AEDs is able to exert a modest seizure reduction in as many as 50% of patients in short-term clinical trials, and a few become seizure free during the trial. It is not known why and how epilepsy becomes drug resistant, while other patients with seemingly identical seizure types can achieve seizure control with medication. Several putative mechanisms underlying drug resistance in epilepsy have been identified in recent years. Based on experimental and clinical studies, two major neurobiologic theories have been put forward: (a) removal of AEDs from the epileptogenic tissue through excessive expression of multidrug transporters, and (b) reduced drug-target sensitivity in epileptogenic brain tissue. On the clinical side, genetic and clinical features and structural brain lesions have been associated with drug resistance in epilepsy. In this article, we review the laboratory and clinical evidence to date supporting the drug-transport and the drug-target hypotheses and provide directions for future research, to define more clearly the role of these hypotheses in the clinical spectrum of drug-resistant epilepsy.

ATP Binding Cassette Transporter, Subfamily B↗

High-resolution MRI in giant cell arteritis: imaging of the wall of the superficial temporal artery.

OBJECTIVE: This study investigated the hypothesis that high-resolution MRI can reveal mural inflammatory changes of the superficial temporal artery in giant cell arteritis (GCA). SUBJECTS AND METHODS: MRI of the temporal artery of 20 patients with suspected GCA was performed on a 1.5-T scanner using a dedicated eight-element phased-array head coil. Contrast-enhanced multislice T1-weighted spin-echo sequences were acquired perpendicular to the orientation of the vessel, with a submillimeter spatial resolution of 0.2 x 0.3 mm and a slice thickness of 3 mm. Mural thickness and lumen diameter of the temporal artery were measured, and mural contrast enhancement was graded on a four-point scale by two radiologists. For all patients, the MRI results were compared with the findings of clinical examination and laboratory tests. In addition, biopsy samples of the temporal artery were taken from 16 of these patients. RESULTS: MRI sharply demonstrated the superficial temporal artery, allowing an evaluation of its lumen and wall. Seventeen patients were GCA-positive according to criteria of the American College of Rheumatology. Of these 17, 16 had true-positive MRI findings and one had false-negative MRI findings. The 3 patients who were GCA-negative according to the American College of Rheumatology criteria had true-negative MRI findings. The mean thickness of the vessel wall and the lumen diameter were 0.88 +/- 0.23 mm and 0.78 +/- 0.29 mm, respectively, in GCA-positive patients and 0.57 +/- 0.25 mm and 0.7 +/- 0.1 mm, respectively, in GCA-negative patients. CONCLUSION: High-resolution contrast-enhanced MRI of the temporal artery allowed visualization of the temporal artery and evaluation of possible inflammation of the vessel wall. Our initial results with this noninvasive technique agreed well with histologic results and with the clinical criteria of the American College of Rheumatology.

Aged↗

What is the evidence that oxcarbazepine and carbamazepine are distinctly different antiepileptic drugs?

Oxcarbazepine (OXC, Trileptal) is a modern antiepileptic drug (AED) used as both monotherapy and adjunctive therapy for the treatment of partial seizures with or without secondary generalization in adults and children above 4 years (USA) or 6 years (Europe) of age. Although OXC has been developed through structural variation of carbamazepine (CBZ) with the intent to avoid metabolites causing side effects, significant differences have emerged between the two drugs. The mechanism of action of OXC involves mainly blockade of sodium currents but differs from CBZ by modulating different types of calcium channels. In contrast to CBZ, which is oxidized by the cytochrome P-450 system, OXC undergoes reductive metabolism at its keto moiety to form the monohydroxy derivative (MHD), which is glucuronidated and excreted in the urine. The involvement of the hepatic cytochrome P-450-dependent enzymes in the metabolism of OXC is minimal. Although it does not prevent interaction with oral contraceptives, it explains why OXC can be more effectively combined with other AEDs such as valproate compared with CBZ. Switching from CBZ to OXC normalized CBZ-associated thyroid and sexual hormone abnormalities and pathological lipid values in small patient samples. OXC is often better tolerated than CBZ and causes fewer rashes than CBZ. Add-on or substitution treatment with OXC was effective in controlled trials even when CBZ did not achieve sufficient seizure control. This constitutes compelling clinical evidence that OXC and CBZ are distinctly different medications. From postmarketing experience in over 1,000,000 patient years, OXC had an advantageous risk-benefit balance also in comparison to other new AEDs. OXC should be preferred over CBZ and other older AEDs because of its proven efficacy and excellent side effect profile in children, adolescents, and adults with partial seizures.

Animals↗

Seizure recurrence after planned discontinuation of antiepileptic drugs in seizure-free patients after epilepsy surgery: a review of current clinical experience.

PURPOSE: Although epilepsy surgery, especially temporal lobe epilepsy surgery, is well established to control seizures in patients remaining on antiepileptic drug (AED) treatment, less information is available about how many seizure-free surgical patients will relapse after discontinuation of AEDs under medical supervision. METHODS: A literature review yielded six retrospective clinical observations. RESULTS: After planned discontinuation of AEDs in patients rendered seizure free after epilepsy surgery, most often various forms of temporal lobe surgery, the mean percentage recurrence rate in adults in four studies was 33.8%[95% confidence interval (CI), 32.4-35.2%], with maximum follow-up ranging from 1 to 5 years. Seizure recurrence increased during the follow-up of 1 to 3 years and occurred within 3 years of AED discontinuation. In one study of children with temporal lobe epilepsy, the recurrence rate was 20%. More than 90% of adult patients with seizure recurrence regained seizure control with reinstitution of previous AED therapy. Seizure recurrence was unaffected by the duration of postoperative AED treatment; as a consequence, delaying discontinuation beyond 1 to 2 years of complete postoperative seizure control seems to have no added benefit. The occurrence of rare seizures or auras after surgery did not eliminate the possibility of eventual successful AED discontinuation. CONCLUSIONS: AED discontinuation is associated with a seizure recurrence in one in three patients rendered seizure free by epilepsy surgery. These results will be useful in counseling patients about discontinuing AED treatment after successful epilepsy surgery.

Anticonvulsants↗

Color-coded sonography in suspected temporal arteritis-experiences after 83 cases.

Color-coded sonography is an interesting option for the diagnosis of temporal arteritis. We present our experiences regarding examination technique and diagnostic accuracy, comparing biopsy and clinical results in a series of 83 patients with suspected temporal arteritis. A dark halo around the vessel wall (representing inflammatory oedema), reduced or absent vessel wall pulsations (demonstrated by M mode), and vessel occlusions were used as diagnostic criteria. Forty-eight patients underwent biopsy of the temporal artery following ultrasound examination. Comparing these findings with biopsy yielded a sensitivity of 73%, specificity of 93%, positive predictive value (PPV) of 96%, and negative predictive value (NPV) of 58%. The halo sign alone had a lower sensitivity (67%). Comparison with overall clinical assessment (n = 83) yielded a sensitivity of 65%, specificity of 100%, PPV of 100%, and NPV of 73%. Irregular atherosclerotic vessel wall changes were the main differential diagnosis. Important pitfalls were false focus setting, too much/less color gain, and 'bifurcation halo'. In conclusion, a positive sonographic result in combination with typical clinical signs might replace the need for biopsy, while a negative result should not be used for exclusion of temporal arteritis. Considering the low PPV and high NPV of the clinical criteria defined by the American College of Rheumatology, color-coded sonography is a useful tool in the noninvasive diagnostic workup of temporal arteritis.

Aged↗

Comparison between color duplex ultrasonography and histology of the temporal artery in cranial arteritis (giant cell arteritis).

BACKGROUND: Duplex sonography of the temporal artery may be helpful in the diagnosis of cranial arteritis. PATIENTS AND METHODS: The superficial temporal arteries of 36 patients with cranial arteritis or suspected arteritis were examined using both duplex ultrasonography (US) and biopsy. The data of these patients were divided into two groups. Group A consisted of 24 patients (66.7%) with definite positive results using duplex (US) and Group B of 12 patients (33.3%) who showed a suspicious or negative ultrasonographic result. RESULT: In all patients of Group A, the histological findings corresponded with the ultrasonographic changes in the inflamed artery. - The characteristic ultrasonographic sign was a dark halo around the lumen of the temporal arteries. There was a high correlation between a bilateral halo found by US with an ocular involvement. Ten out of 14 patients with a bilateral halo (71.4%) showed a distinct involvement of the optic nerve or retina. - The characteristic histological signs were infiltration of the vessel wall by inflammatory cells, mainly lymphocytes. Group B: The biopsies of the superficial temporal arteries were positive in 8 patients (66.7 %), negative in 4 other patients (33.3%). CONCLUSION: Patients with a distinct halo, demonstrated by US, also showed corresponding pronounced inflammatory cell infiltration of the vessel wall. Patients with no ultrasonographic changes presented histological signs of initial inflammation such as isolated inflammatory cells around the vasa vasorum and/or in the adventitial layer.

Aged↗