Computerised brain electrical activity findings of parkinson patients suffering from hyperkinetic side effects (hypersensitive dopamine syndrome) and a review of possible sources.

Among 2,000 Park. pat. hospitalised during the years 1988 till 1990 we found 61 pat. with hyperkinetic side-effects in the sequence of a long-term L-dopa treatment. 43 (mean age 64y.) had a complete clinical data set and hyperkinesia ratings (AIMS scale). Compared to the system's data base--none of these patients showed a strickly normal CEEG. Our standard parkinson treatment was established in 1986: L-dopa as low as possible, dopamine agonists low, amantadines as high as necessary, L-deprenyl till 10 mg and anticholinergics--no, if possible. Our pat. group got initially a mean of 508 mg L-dopa, at the end of the study 296 mg. Conventional EEG (Picker-Schwarzer) and CEEG data were recorded (Dynamic Brain Mapping, Itil). Clinical and CEEG follow-up investigations were done after 2 weeks and 2 years. At follow-up, a reduction of the hyperkinesias was found in 43 patients (AIMS scale). 28 pat. received an additional treatment with nootropic drugs, 15 pat. were without this additional therapy. The visually evaluated CEEG at the latter group showed an acceleration ("response") in 33%, but among the patients with nootropic drugs the acceleration was seen in 66%. In patients without nootropics the mean delta power increased, patients additionally treated showed a reduction of delta. In cases of high L-dopa dosage--associated with severe hyperkinetic side effects--more slow waves were registered. The non-nootropic treated patients were divided into two groups--non-responders and the responders: a) Non-responders (n = 10) showed a significant reduction of alpha and a significant increase of delta and theta, b) Responders (5 pat.) without nootropics had a significant reduction of theta and a increase of alpha, but the acceleration is less pronounced than in the responder group with nootropics. Without co-medication a high L-dopa dosage may provoke/facilitate an organic cerebral dysfunction. The nootropic-treated but non-responder group showed no significant changes (n = 13). The best results were seen in the nootropic-treated responder group (n = 15): a significant diminution of delta and theta and an increase of alpha and beta. Summing-up documented by CEEG methods--high L-dopa dosages seemed to be one of the causes of cerebral dysfunctions. Nootropic drugs were able to ameliorate the pathological CEEG patterns.

Distribution of metabolism of the potential anti-parkinson drug memantine in the human.

GC-MS of tissue extracts obtained from a parkinsonian patient who died from secondary causes during memantine (1-amino-3.5-dimethyladamantane) treatment showed the drug to be largely unmetabolized. In the kidney and liver a second peak corresponded to less than 1% of the main temporal lobe, hypothalamus and pons. Thus treatment with 2 X 10 mg memantine/day reveals an accumulation of the drug in microM concentrations in the brain. This is probably high enough to explain the ameliorating effect of memantine treatment in patients suffering from Parkinson's disease.

A natural and broad spectrum nootropic substance for treatment of SDAT--the Ginkgo biloba extract.

The efficacy of the Ginkgo biloba extract was not only found clinically or in standardised ratings but also documented by objective data, obtained by a computerized EEG method, the DYNAMIC BRAIN MAPPING and BRAIN FUNCTION MONITORING SYSTEM (Dr. T. Itil, New York). A one year open trial comprise 25 parkinson patients with additional signs of SDAT. Data from 3 selected cases were given: The short time efficacy of the substance after the infusion and the long-term result after the oral medication. The maps showed less slower and more faster waves. Without any side effects the Ginkgo biloba extract seems to be a substance with a broad spectrum of influence. Our therapeutic findings in parkinsonian patients with SDAT and the data taken from healthy elderly volunteers revealed that the computerized EEG method may have another big advantage: It seems that the so-called anteriorisation of the Theta waves can be taken as a preclinical sign of an incipient change in brain metabolism. As a consequence--it might be that these changes are reversible by an adequate nootropic treatment. Further studies and treatment experiences must confirm these preliminary findings.

[Cerebral accidents, psychic manifestations, spinocerebellar disturbances and brain tumour (author's transl)]. / Zerebrale Anfälle, psychische Auffälligkeiten, spino-zerebelläre Störungen und Hirntumor. Kasuistisches Beispiel zum Nutzen einer psychiatrisch-neurologisch-neurochirurgischen Zusammenarbeit

At the age of 35 years the patient was affected by epileptic attacks. Two years later psychic changes, vomiting and unsteadiness of gait were noted and not only in the EEG but also in the angiogram, the suspicion of a right hemisphere tumour was expressed. The operation was postponed because the patient's husband was afraid of complications. In the following years other doctors who were concerned with the diagnostic problem, either missed the significance of the existing symptoms or did not attach enough importance to them. As a result of an operation (uterine fibroids) and also because of a slight head injury, an increase in the neurological and psychiatric symptoms was brought about and fortunately this prepared the way for the correct treatment. After the operation there was a significant improvement not only in the psychiatric, but also in the neurological state. As a result of the advanced state of the tumour growth (oligodendroglioma) it was only possible to carry out a sub-total removal. A review of the case indicates that a closer neuropsychiatric and neurosurgical co-operation might have led, at the earliest ten or at the latest five years previously, to a successful outcome of the operation.

The new antidepressant zimeldine in general practice. A surveillance study of 15,000 patients.

The safety and efficacy of zimeldine--the 5-HT reuptake blocker--was investigated in a 3-week open surveillance study of 15,000 out-patients with depressive illness. In general, a single daily dose of 200 mg of zimeldine was given to adults for a minimum of 3 weeks. Patients of 65 years or over received 100 mg. The drug was well tolerated and troublesome side-effects occurred in only a small percentage of patients. No previously unencountered side-effects or new pattern of side-effects emerged from this study. The general impression of the efficacy of zimeldine confirmed previous findings (i.e. that zimeldine is an effective antidepressant).

[Neuroleptic infusion therapy with high-dosed fluphenazine (author's transl)]. / Hochdosierte neuroleptische Infusionsbehandlung mit Fluphenazin.

19 chronic schizophrenics who had previously been resistant to various neuroleptic treatment regimens, were given extemely high doses (ca. 300-500 mg daily) of fluphenazine. 2 infusions were given in the morning and in the afternoon. Therapy results, possible side effects and the transition to oral and i.m. (depot) modes of application are discussed. The above-mentioned extemely high doses of fluphenazine appear to be contra-indicated in depressive states and in cases of latent organic brain changes. Psychiatric state hospitals would be able to carry out this form of treatment in a special unit for "intensive care" in connection with appropriate social rehabilitative methods.

Effects of a GABA-mimetic drug (sodium valproate) on visually evoked potentials in chronic schizophrenics.

Data were obtained from 14 chronically schizophrenic women (age 40-59) living in the same ward of a psychiatric hospital (Marburg, FRG), and having been treated with clozapine (450-600 mg/day) during the last 2 years. The uncontrolled study was initiated by the addition of sodium valproate (900 mg/day) for 3 months. The observation commenced after the discontinuation of the valproate medication with the evaluation of the symptoms (Brief Psychiatric Rating Scale, BPRS) and the visually evoked potentials (VEP). The VEP were recorded after 3, 12 and 30 days and the rating was repeated after 4 weeks. No significant changes in symptomatology were obtained with the BPRS in patients under combination therapy in comparison with the scores 30 days after discontinuation of the valproate medication. On the other hand, after single flash stimulation, the amplitudes of the components N110, P260, and N300 of the VEP were significantly (p less than 0.05) increased during the same time interval. These findings are interpreted as an expression of an inhibiting action of the GABA system on the reactivity of the visual system in chronic schizophrenics induced by the comedication of sodium valproate.

Double-blind study with phosphatidylserine (PS) in parkinsonian patients with senile dementia of Alzheimer's type (SDAT).

Experimental and clinical studies showed that Phosphatidylserine--special preparation from cow's brain by FIDIA, Abano Terme, Italy--is able to influence cerebral changes contributed to the symptoms of senile dementia of Alzheimer's type. The application of the computerized EEG method DYNAMIC BRAIN MAPPING (HZI Research Center, Tarrytown, New York) is able to proof the therapeutic effect of Phosphatidylserine: the acceleration of a slowed EEG in Parkinsonian patients with SDAT. These reactions were seen previous to the favourable clinical influence documented by the Sandoz Clinical Assessment Geriatric Scale (SCAG), which showed a significant amelioration in anxiety, motivation and affectivity by the verum drug. Acute and long-term CEEG results--till 18 months--showed that the so-called Theta anteriorisation can be reduced or even abolished; this is replaced by Alpha waves. Even in preclinical cerebral changes this method open the possibility to show incipient alterations of the brain metabolism. Preliminary therapeutic results leads to this and not prooven hypothesis that prevention or retardation of cerebral ageing might be possible.

[Effects of oral memantine administration on Parkinson symptoms. Results of a placebo-controlled multicenter study]. / Wirkungen oraler Memantin-Gaben auf die Parkinson-Symptomatik. Ergebnisse einer placebo-kontrollierten Multicenter-Studie.

The effectiveness of memantine on the symptoms of Parkinson's disease was investigated in 67 patients (39 males, 28 females) mostly between 55 and 75 years. The study was multi-center placebo-controlled with four treatment groups, i. e. patients with and without pre- and after-treatment with other anti-Parkinson medication receiving either placebo or memantine as sole or additional medication. The analysis of 61 evaluable cases showed a positive statistically significant influence on the single symptom tremor as well as on the neurological overall symptomatology (Webster-scale total score). Despite the inadequately ascertained mode of action memantine promises success particularly in milder and initial forms of the Parkinson syndrome either used as monotherapy or as an adjuvant.