Training-induced brain plasticity in aphasia.

It has long been a matter of debate whether recovery from aphasia after left perisylvian lesions is mediated by the preserved left hemispheric language zones or by the homologous right hemisphere regions. Using PET, we investigated the short-term changes in the cortical network involved in language comprehension during recovery from aphasia. In 12 consecutive measurements of regional cerebral blood flow (rCBF), four patients with Wernicke's aphasia, caused by a posterior left middle cerebral artery infarction, were tested with a language comprehension task. Comprehension was estimated directly after each scan with a modified version of the Token Test. In the interval between the scans, the patients participated in brief, intense language comprehension training. A significant improvement in performance was observed in all patients. We correlated changes in blood flow measured during the language comprehension task with the scores achieved in the Token Test. The regions which best correlated with the training-induced improvement in verbal comprehension were the posterior part of the right superior temporal gyrus and the left precuneus. This study supports the role of the right hemisphere in recovery from aphasia and demonstrates that the improvement in auditory comprehension induced by specific training is associated with functional brain reorganization.

QEEG in hemophiliacs with HIV infection.

Conventional visual analysis of the EEG was performed on 320 hemophiliacs infected with HIV, who spanned the range of the Walter Reed (WR) system for classifying clinical stage of HIV infection, and on 50 HIV seronegative hemophiliac controls. Intermittent or paroxysmal slowing was the conventional EEG abnormality most commonly seen in early stages of HIV infection (stages WR1 and 2), with increased focal epileptiform activity and generalized slowing appearing in patients with the full clinical syndrome of AIDS (WR6). Slowing of the manually measured alpha rhythm was noted in stages WR2 and above. Quantitative EEG (qEEG) was obtained in a subset of 103 male HIV seropositive male hemophiliacs and 35 male HIV seronegative hemophiliac controls. The principal findings were a progressive relative increase in theta power with a tendency towards an anterior topographic distribution, and a progressive decline of spectral power in fast alpha relative to slow alpha with increasing severity of HIV disease. Significant qEEG differences from controls were apparent in WR2 subjects (seropositive with lymphadenopathy and without other constitutional symptoms), and were relatively greater in WR3-6 subjects. These results suggest sensitivity of qEEG to early CNS involvement with HIV infection.

[Interaction of epileptic seizures and biological rhythms]. / Wechselwirkung von epileptischen Anfällen und biologischen Rhythmen.

Circadian modulation of seizure threshold is subjected to a multitude of periodical, aperiodical and stochastical influences. Epilepsies on the other hand influence the biological rhythms themselves. Epileptic seizures are activated during transient sleep stages. Nocturnal seizures lead to severe sleep disorders and therefore to hypersomnia. Partial and generalized epilepsies have a different sleep profil even without seizure manifestation. Finally antiepileptic drugs may interfere with circadian rhythms. Knowing the chronobiological context a differentiation of epileptic seizures from nonepileptic parasomnias may succeed more easily. To ensure the appropriate diagnostical proceeding multichannel EEG should be used in every polysomnography with neurological topics.

[Validating rehabilitation after stroke]. / Validierung der Rehabilitation nach Schlaganfall.

Evaluation of therapeutic efficacy in neurologic rehabilitation is methodologically limited by the well established polypragmasia and the lack of untreated controls. Controversial discussion is generated by the following topics: superiority of specific therapy versus spontaneous recovery, higher efficacy of in-patient-setting versus out-patient-setting and the value of neurorehabilitation treatment in latency of more than 1 year after the event. To develop a practicable method for the evaluation of efficacy, we surveyed retrospectively 30 patients after stroke in a sequential study design on 4 scheduled visits: first admission to in-patient rehabilitation, discharge to out-patient treatment, admission and discharge of second in-patient rehabilitation. Impairment, disability and handicap were documented by NIH-Stroke Scale, Barthel-Index, CGI, WWK-Pflegeskala N and Risk-Profile. A descriptive data-analysis implies a therapeutic gain of stroke rehabilitation in-patient setting which is apparently superior to out-patient treatment. A measurable therapeutic effect was evident even more than one year after the stroke.

Early signs of cognitive deficits among human immunodeficiency virus-positive hemophiliacs.

A total of 181 human immunodeficiency virus (HIV)-seropositive hemophiliacs and 28 hemophilic controls were evaluated by psychometric tests and by electroencephalogram (EEG). Patients were classified from stages 1-6 according to the immunological criteria of the Walter Reed staging system. Statistical analysis of psychometric data showed an effect of the stage of the disease on test performances, indicating a decline in attention, accumulation of perceptual interferences, decline in visuoperceptual speed and visuomotor response speed and reduced verbal memory performance, especially in stage 6 patients. Comparison of performance levels with normative test data already revealed cognitive deficits in about 20-30% of the patients in stages 2-5. As regards verbal memory, especially learning and recognition of new verbal information were impaired. In contrast, there was no significant deficit for nonverbal memory processing. Compared with the controls, patients exhibited an increasing number of abnormal EEG findings in stages 2-6. As a conclusion, in the stages before acquired immunodeficiency syndrome (AIDS) develops, EEG findings as well as psychometric findings indicate central nervous system involvement of AIDS in about 20-30% of cases, whereas in full-blown AIDS there is a marked increase to 80%. Besides a more general deficit of attention and psychomotor speed as is seen in subcortical dementia, there is evidence for a particular verbal learning disorder, suggesting additional selective impairment of the brain.

[The course of pregnancy and teratogenicity of antiepileptic agents in 66 patients with epilepsy]. / Untersuchungen zum Schwangerschaftsverlauf und zur Teratogenität der Antiepileptika bei 66 Epilepsie-Patientinnen.

We report on 79 pregnancies in 66 female outpatients with epilepsy. An increase of seizure frequency was significantly more frequent in complex partial seizures than in grand mal seizures and in absences. The reason for these disparities are not clear. In most patients a raised frequency of seizures during pregnancy decreased again after delivery. Carbamazepine was the antiepileptic drug prescribed most frequently followed by valproic acid. The course of the blood levels of carbamazepine and valproic acid was nonuniform during pregnancy. Total concentrations of carbamazepine in cord blood were on average 84.5% of those in maternal blood (n = 22). Valproic acid blood levels were on average 183% of those in maternal blood (n = 15). It is still unclear whether these differences are clinically relevant. During the last weeks of pregnancy we found an increase of the free fraction of carbamazepine and valproic acid. Simultaneously the total protein concentration decreased. Until now these findings are without clinical relevance. The course of labor did not differ from normal population concerning the ratios of spontaneous labor, cesarean section and delivery by forceps. Miscarriage and perinatal mortality were 2.7% each and outnumbered the risk in the general population. In 42.8% of the neonates one to three perinatal complications were observed. The ratio of perinatal complications is not different between patients with monotherapy and combined therapy respectively. There was a tendency to lower values of length, weight and head circumference in the male neonates but not in the female neonates. The risk of minor malformations was 26%, the risk of major malformations was 14% (including one case of suspected malformation) without a discernible correlation with a specific antiepileptic drug.

[Cardiac pacemaker implantation in unrecognized obstructive sleep apnea syndrome]. / Herzschrittmacher-Implantation bei nicht-erkanntem obstruktivem Schlafapnoe-Syndrom.

A cardiac pacemaker was implanted because of nocturnal sinus arrhythmia into a 53-year-old man with hypersomnia. After other patients had reported loud snoring and breathing pauses, which appeared to be dangerously long, polysomnography was performed. It indicated a marked obstructive sleep apnoea syndrome with an apnoea index of 55 and an average apnoea duration of 35 seconds. The nocturnal cardiac arrhythmias disappeared under continuous nasal raised pressure ventilation.

[EEG topography in HIV-positive hemophiliacs]. / EEG-Topogramm bei HIV-infizierten Hämophilen.

HIV-central nervous system manifestations, here the AIDS-Dementia complex, are at the moment of special interest owing to its unexpected development. With EEG-topography one can expect to gain more information about possible changes in frequency according to topographical location. We recorded 69 HIV-positive hemophiliacs (23 WR 2, 26 WR 3-5 and 6 patients) plus 50 HIV-seronegative controls with a 12 channel EEG-topography evaluation. During the critical examination we looked for the results of two parameters: a) alpha 1-3/alpha 4 and b) alpha 4-4/9. In comparison to the control group we found a statistical significance (p less than 0.05) for WR 2-6 in alpha 1-3/alpha 4 index. Concerning the alpha 1-4/9 index one can only recognize a statistical significance (p less than 0.05) for WR 3-6 patients in comparison to the controls.

EEG discharges in WR 1-5 HIV-seropositive hemophiliacs.

Human immunodeficiency virus (HIV)-seropositive patients show involvement of the central and/or peripheral nervous system. We present here the results of electroencephalographic (EEG) findings in stage WR 1-5 HIV-seropositive hemophiliacs from a total of 184 who attended our clinic prior to October 1987.

[HMPAO-SPECT in cerebral seizures]. / HMPAO-SPECT bei zerebralen Anfällen.

In nine patients with suspected psychogenic seizures and in three patients with proven epileptic seizures HMPAO-SPECT was performed prior to and during seizure. In the patients with later on-proven psychogenic seizures no, or only slight, changes of regional cerebral blood flow were found. Patients with proven epilepsy revealed partly normal findings interictally but during seizure a markedly increased circumscript blood flow was found in all patients. Even though PET is superior to SPECT with respect to spatial resolution, in the diagnosis of seizures HMPAO-SPECT has the advantage of enabling injection of the tracer during the seizure and the performance of the SPECT study subsequently.

Double-blind placebo-controlled trial with flunarizine in therapy-resistant epileptic patients.

The anticonvulsant efficacy and side-effect liability of flunarizine (15 mg/day) was investigated in a randomized, double-blind, placebo-controlled, crossover design in 30 outpatients with drug-resistant complex partial seizures. Flunarizine or placebo was added to the preexisting medication and each patient was followed up for 10 months. At the end of the study data from 22 patients were available for evaluation. In patients taking first flunarizine and then placebo, plasma levels of flunarizine were still detectable at the end of the 4 months' placebo phase. In the group of 13 patients starting therapy with placebo, a significant seizure frequency reduction was observed during the flunarizine period in 11 patients, whereas one patient showed no change and seizure frequency increased in another patient. Two patients had a 50% reduction in seizure frequency. Flunarizine was well tolerated and few side effects were noted.

Pharmacokinetics of oxcarbazepine and 10-hydroxy-carbazepine in the newborn child of an oxcarbazepine-treated mother.

Gaschromatography--mass spectrometry (GC/MS) was used to determine plasma levels of oxcarbazepine (OCB) and its main metabolite in a newborn girl and her OCB-treated mother during the first five post partum days. At delivery the maternal and neonatal plasma concentrations were in the same range, indicating considerable placental transfer of both substances. In spite of ingestion of both substances via breast milk, there was no accumulation in the baby. On the fifth post partum day OCB and 10-hydroxy-carbazepine (10-OH-CB) levels in plasma in the newborn were only 12 and 7%, respectively, of the values found on the first day after delivery.

[Fulminant liver failure in tuberculostatic therapy. A contribution to clinical aspects and pharmacokinetics]. / Fulminantes Leberversagen unter tuberkulostatischer Therapie. Ein Beitrag zur Klinik und Pharmakokinetik.

A 23-year old female patient on a prolonged regimen of tuberculostatic chemotherapy finally developed fulminant hepatic failure shortly after addition of hormonal contraception. The pathophysiology of this almost fatal drug reaction is described as a pharmacokinetic interaction: the inherent hepatotoxicity of prothionamide-the drug finally prescribed during convalescence-was significantly potentiated by the Cyt-P-450-inducing effect of the progestagen component of the hormonal contraceptive. Potentiation of hepatotoxicity in connection with tuberculostatic regimes containing rifampicin is well known and this pharmacokinetic phenomenon also pertains to the combination with other Cyt-P-450-inducing drugs such as, for instance, anticonvulsants. However, since the maximum of rifampicin-related Cyt-P-450-inducing effect is limited to the initial 2-3 weeks of therapy, the hepatotoxic risk triggered by this rifampicin-related induction may decline during continuation of therapy. This, unfortunately, does not pertain to the other Cyt-P-450-inducers, whose inductive effect is not time-limited. Progressive severe hepatic damage may follow from such interaction as demonstrated in this case report.

Influence of anticonvulsants and flunarizine on the metabolism of thyroid hormones: speculation about the possible role of calmodulin.

Interference of anticonvulsants with the metabolism of hormones may lead to side effects. Anticonvulsants influence the hypothalamic-pituitary-thyroid axis, in that lowering of thyrotropin [thyroid-stimulating hormone (TSH)] and thyroxine levels is observed. In the present study, flunarizine, a calcium ion blocker, administered as add-on medication, further lowered serum thyroxine but not TSH. The underlying biochemical principle may be an interference with the mediation of signals by calcium-calmodulin at the level of the thyroid follicle.

Effect of flunarizine on regional cerebral blood flow in common and complicated migraine. Pilot study.

Alterations of regional cerebral blood flow (rCBF) are at least epiphenomena of common and complicated migraine, but may lead to serious clinical complications. Since flunarizine seems to be effective in migraine prevention it may exert a beneficial influence on rCBF in migraine as well. rCBF was assessed using the 133Xe inhalation method in 5 patients with common and 8 patients with complicated migraine. Measurements were done interictally prior and after therapy with 15 mg flunarizine p.o. daily over a period of 4 weeks. Major abnormalities of grey matter flow were observed even interictally. Significant improvement of rCBF in initially hypoemic regions may be attributed to flunarizine therapy. These preliminary data suggest that calcium entry blockers may prevent the ischemic complications of migraine.

[Familial episodic ataxia]. / Familiäre episodische Ataxie.

5 members of a family with periodic cerebellar dysfunctions are described. This rare disorder occurred in the early childhood and is characterised by episodes lasting minutes to hours with severe cerebellar ataxia, dysarthria, diplopie, nystagmus, vertigo and vegetative symptoms. The examinations between attacks are almost normal. The inheritance appears to be autosomal dominant. An atrophy of the cerebellar vermis was found in two patients. Syndrome and investigation results were compared to the seven papers according this disorder, which were published until now.