H. H. Kornhuber

Increased serum glutamate in depressed patients

SummaryGlutamate concentration was determined in serum from endogenous and neurotic depressive patients, in persons with schizophrenia or schizoaffective disorder, and in normal subjects.The mean serum glutamate level in the endogenous and neurotic depressive patients was found to be significantly higher than in any of the other groups. No other statistically significant differences were found. Statistical analysis revealed that the elevated serum glutamate concentration in the endogenous and neurotic depressive patients was probably caused by medication. These results are discussed in view of the effect of antidepressants upon the serum glutamate in the affective disorders.ZusammenfassungDer Serum-Glutamatgehalt wurde bei endogen depressiven, neurotisch depressiven, schizophrenen und schizoaffektiven Patienten sowie gesunden Kontrollpersonen bestimmt.Hierbei zeigte sich, daß die Serumglutamatspiegel bei endogen und neurotisch Depressiven signifikant höher waren als bei den anderen Gruppen. Zwischen schizophrenen und schizoaffektiven Patienten sowie Kontrollen zeigten sich dagegen keine signifikanten Unterschiede. Die weitere Analyse der Daten erbrachte die Hypothese, daß die erhöhten Serum-Glutamat-Konzentrationen bei endogen und neurotisch Depressiven eine Folge der antidepressiven Medikation sind. Diese Ergebnisse werden im Hinblick auf die Wirkung der Antidepressiva auf das Serum-Glutamat bei affektiven Störungen diskutiert.

Acquired pendular nystagmus with oscillopsia in multiple sclerosis: a sign of cerebellar nuclei disease

In an unselected series of 644 cases of multiple sclerosis, 25 cases with acquired pendular nystagmus were found. Ten additional cases of pendular nystagmus in multiple sclerosis were investigated, and four cases from the literature are analysed. Acquired pendular nystagmus is purely sinusoidal in form, ceases with eye closure, is accompanied by oscillopsia, often monocular and vertical in direction, and never accompanied by optokinetic inversion. This is different from congenital nystagmus. Acquired pendular nystagmus in multiple sclerosis shows a high correlation with holding tremor of head and arm and with trunk ataxia, and must therefore be viewed as a result of lesions of cerebellar nuclei or their fibre connections with the brain-stem. Supporting evidence is discussed. The results fit into a theory of cerebellar function according to which the cerebellar nuclei are involved in the maintenance of positions.

Treatment of multiple sclerosis with mitoxantrone

SummaryTen multiple sclerosis patients, all with a rapid deteriorating disease profile, were treated with 12 mg/m2 of the cytostatic agent mitoxantrone, administered every 3 months. This dosage is only 25% of what a patient with a solid tumour would normally receive during the same time period. In all treated patients the deterioration was stopped following the initial dosage; in four out of ten patients there was even an immediate improvement of the neurological status. Eight out of nine patients showed an improvement after 1 year as compared with their enrolment status; the other one remained stabile. In correlation with the clinical improvement, the mean P100 latencies of visual evoked potentials showed a reduction after 1 year. However, the changes identified through magnetic resonance imaging were even clearer than those seen clinically. At admission, this group of patients presented with a total of 169 gadolinium (Gd)-enhancing lesions. Only 10 lesions were enhancing in nine patients 12 months after the initiation of treatment. It appears that mitoxantrone accelerates the disappearance of Gd-enhancing lesions and prevents the development of new ones. Minimal side effects such as mild nausea and a slight faintness were evident in six patients and then for only 1–2 days.

Efficient Treatment of Neurogenic Bladder Disorders in Multiple Sclerosis with Initial Intermittent Catheterization and Ultrasound-Controlled Training

Out of 350 multiple sclerosis (MS) patients, 197 had residual urine (RU), on average 113 ml on admission. Treatment with initial intermittent catheterisation and bladder training normalized the neurogenic bladder disorders (NBD) in most patients; the RU was 28 ml on average at discharge. Continence improved with the reduction of RU. Even in those 37 patients with a RU of over 200 ml on admission, this management reduced the average RU to 83 ml on discharge. Patients with a RU of over 50 ml had bacteriuria 3 times more often than patients with a lower RU. In patients admitted with a long-term catheter, the catheter was removed; these patients had an average RU of 166 ml on admission, 23 ml on discharge. There was a highly significant correlation between high RU and the degree of cerebral atrophy. Patients with more than 50 ml RU at discharge were those with severe cerebral atrophy, tetraplegia and dementia. The different patterns of NBD were merely different states of the same NBD under different training conditions. Since NBD occurs about a 1,000 times more often than bowel incontinence with the same lesions in MS, it is not the cerebrospinal lesions per se, but the peripheral vicious circle they trigger, which leads to detrusor hyperactivity and dyssynergy. The peripheral pathogenetic mechanism is urinary retention leading to bladder overextension. Urodynamic investigations beyond the measurement of RU (by ultrasound) are not necessary for the treatment of NBD in most MS patients. The noninvasive and inexpensive therapy described here is effective.

Cerebral Glutamate, Neuroleptic Drugs and Schizophrenia: Increase of Cerebrospinal Fluid Glutamate Levels and Decrease of Striate Body Glutamate Levels following Sulpiride Treatment in Rats

Chronic (12 days) administration of sulpiride (50 mg/kg, i.p.) in rats resulted in a significant (12%) increase in the glutamate contents of cerebrospinal fluid. Sulpiride had no effect on the GABA content of the brain areas investigated (frontal cortex, striatum, hippocampus and substantia nigra). Sulpiride is a neuroleptic drug which is believed to block especially the non-adenylate cyclase dopaminergic receptors which are supposed to be inhibitory axoaxonic receptors on glutamatergic corticostriatal terminals. The results are compatible with the hypothesis that glutamatergic hypofunction might be the primary defect in schizophrenia rather than hyperactivity of the dopamine synapses.

Liquorpheresis (CSF-filtration): An effective treatment in acute and chronic severe autoimmune polyradiculoneuritis (Guillain-Barré syndrome)

SummaryIn recent years, plasmapheresis has become a well established treatment of acute and chronic polyradiculoneuritis (Guillain-Barré syndrome, GBS). Nervertheless, there are still non-responders and there are particular risks associated with this treatment. Despite all efforts, the duration of severe forms of Guillain-Barré syndrome is still considerable. Inflammation and demyelination start intrathecally. We therefore used liquorpheresis (cerebrospinal fluid filtration) as a new effective therapeutic approach. Our first patient, severely disabled with acute GBS, artificially ventilated, had undergone plasma exchange without effect. Plasma immunoadsorption led only to transient improvement. After several liquorphereses, the patient recovered completely. In three additional patients with acute and two with chronic GBS an improvement of clinical signs in close temporal relation to liquorpheresis was observed. Twice, liquorpheresis was combined with immunoadsorption of cerebrospinal fluid. Liquorpheresis was well tolerated in all cases. This procedure may be effective by eliminating humoral or cell-bound factors responsible for the onset or/and maintenance of inflammation. Further controlled studies are necessary and are in progress.

The measurement of residual urine by means of ultrasound (Sonocystography) in neurogenic bladder disturbances

SummaryThe measurement of residual urine is important for bladder training in cases with neurogenic bladder dysfunction, especially in multiple sclerosis and in non-neurogenic retention. It is possible to measure the bladder volume precisely enough for even small amounts of residual urine by means of the ultrasound B-mode technique. A sector scan was used since with a linear array scan, the caudal part of the bladder cannot be visualized in female patients because of the pubic bone. The 144 volume data taken by ultrasound from normal persons and from patients without residual urine and the 19 measurements made in patients with residual urine more than 20 ml were compared with the urine volume determined by micturation or catheterization. The bladder volume was calculated from the maximum sagittal and transversal planes using an ellipsoid formula. The regression coefficient was 0.75. The correlation coefficient was 0.94 for bladder volumes between 0 and 200 ml. The standard deviation of the calculated residual urine as compared to the measured urine was 10.5 ml for a volume between 0 and 100 ml and 16.2 ml for a volume between 101 and 200 ml. Thus, ultrasound determination of residual urine may be recommended as a simple and reliable method when using a sector scan.ZusammenfassungHarnwegsinfekte infolge von neurogenen Blasenstörungen sind eine häufige und schwerwiegende Komplikation zahlreicher Nervenkrankheiten, besonders der Multiplen Sklerose. Eine regelmäßige Restharnkontrolle bei diesen Patienten ist erforderlich, auch in der dezentralen symptomatischen Therapie und Rehabilitation. Es wird nachgewiesen, daß Restharnmessung mit Hilfe der Ultraschall-B-Mode-Technik möglich ist und auch beim Erwachsenen für kleine Blasenvolumina hinreichend exakte Meß werte ergibt. Da sich mit dem Linear-Array-Scan vor allem bei weiblichen Patienten der untere (caudale) Blasenrand aufgrund des vorgelagerten Schambeins oft nicht darstellen läßt, wurde ein Sektor-Scan verwendet. 144 Ultraschallmessungen bei gesunden Versuchspersonen und Patienten ohne Restharn bei verschiedenen Blasenfüllungen sowie 19 Messungen bei Patienten mit Restharn über 20 ml wurden mit dem Miktionsvolumen bzw. mit der durch Katheter bestimmten Restharnmenge verglichen. Das Blasenvolumen wurde aus den sagittalen und transversalen Schnittbildern in Anlehnung an die Rotationsellipsoidformel berechnet. Der empirische Regressionskoeffizient betrug mit unserem Gerät 0,75 (im Gegensatz zum theoretischen 0,52 für das Rotationsellipsoid). Der Korrelationskoeffizient ist 0,94 für Blasenvolumina zwischen 0 und 200 ml. Die Standardabweichungen der errechneten Blasenvolumina von der gemessenen Harnmenge betrug 10,5ml bei Harnvolumina zwischen 0 und 100 ml und 16,2 ml zwischen 101 und 200 ml.

Bluthochdruck und Alkoholkonsum

Erst in jungster Zeit wurde auch in der deutschen Hochdruckforschung erkannt, das Alkoholkonsum eine wesentliche Ursache vieler fruher als „essentiell“ klassifizierter Hypertoniefalle ist [35, 37]. Obwohl seit 1915 diskutiert [44c] und seit einem Jahrzehnt vermehrt belegt [5a, 17, 18, 23, 33, 49, 65], wurde ein ursachlicher Zusammenhang in Frage gestellt. Statt dessen wurde postuliert, das hoher Blutdruck und gesteigerter Alkoholkonsum auf einen dritten gemeinsamen Faktor zuruckzufuhren seien, z. B. Stres [7].

Treatment of neurogenic bladder dysfunction in multiple sclerosis by ultrasound-controlled bladder training

SummaryNeurogenic bladder dysfunction, the main cause of chronic urinary tract infections in multiple sclerosis (MS), is efficiently treated by bladder training with ultrasound control of the residual urine. However, the beneficial effects of bladder training in the hospital are often lost within a short time when the patient returns to his home. Reexamination at home of 97 MS patients with increased residual urine and/or chronic urinary tract infections showed that the group which claimed to continue bladder training at home had significantly less residual urine at home than the group which did not continue bladder training at home. The residual urine decreased from 210 ml on average to almost normal while the patients did bladder training in the hospital, but the volume nearly doubled within a short time at home. Thus, more decentralized rehabilitation by family members, volunteer personnel or local nurses is necessary. Decentralized symptomatic therapy is the most efficient treatment of MS at present. Family members, volunteers, and local nurses, however, need training. Without these improvements in decentralized rehabilitation the hospital treatment of MS is of little benefit because urinary tract infection quickly recurs at home. For efficient bladder training the patient needs feedback regarding the residual urine; this can be provided with minimum risk by ultrasound sonocystography. In those rare cases in which bladder training does not work, intermittent catheterization must be carried out by the patients or their families, volunteer personnel or a local nurse. A continuous indwelling catheter should not be used. Antibiotic treatment should be applied only on the basis of a precise bacteriological diagnosis.ZusammenfassungNeurogene Blasenstörungen sind die Hauptursache der chronischen Harnwegsinfekte bei der Multiplen Sklerose (MS); sie können wirksam behandelt werden durch Blasentraining mit Kontrolle des Restharns. Die günstige Wirkung des im Krankenhaus erlernten Blasentrainings geht jedoch oft binnen kurzer Zeit verloren, wenn der Patient nach Hause zurückkehrt. Eine Nachuntersuchung zu Hause von 97 MS-Patienten mit erhöhtem Restharn und/oder chronischem Harnwegsinfekt zeigte, daß jene MS-Krankengruppe, die bei der Aufnahme erhöhten Restharn hatte und angab, daheim das Blasentraining fortgesetzt zu haben, signifikant weniger Restharn hatte als jene Krankengruppe, die zugab, das Blasentraining zu Hause nicht fortgesetzt zu haben. In jener Gruppe von Kranken mit erhöhtem Restharn bei Aufnahme, die zu Hause das Blasentraining nicht fortgesetzt hatten, war der Restharn während der Krankenhausbehandlung durch Blasentraining von 210 ccm im Mittel auf fast normale Werte gesunken, aber zu Hause stieg der Restharn in kurzer Zeit wieder auf fast das Doppelte. Deshalb ist mehr dezentrale Rehabilitation unter Mithilfe von Familienmitgliedern, Gemeindeschwestern und freiwilligen Helfern nötig. Dezentrale symptomatische Therapie und Rehabilitation ist gegenwärtig das Wirksamste, was zur Besserung der Situation der MS-Kranken getan werden kann. Die Familienmitglieder, Helfer und Gemeindeschwestern brauchen aber praktische Ausbildung. Für wirksames Blasentraining bedarf der Patient einer Rückmeldung über den Restharn; diese ist risikofrei durch Ultraschall (Sonocystographie) zu erhalten. In denjenigen Fällen, in denen Blasentraining nicht ausreichend hilft, ist intermittierendes Katheterisieren durch den Patienten, Familienmitglieder oder die Gemeindeschwester angezeigt. Ein Dauerkatheter sollte vermieden werden. Antibiotische Behandlung ist nur auf Grund bakteriologischer Diagnose indiziert.

Verbesserter Nachweis extracranieller Stenosen und Plaques der A. carotis durch Kombination von B-Bild Echo-Arteriographie und Doppler-Sonographie

SummaryInvestigations for carotid stenoses were performed in 850 patients suspected of having cerebrovascular insufficiency. Indirect and direct Doppler sonography as well as high resolution B-mode ultrasonic arteriography were used. Angiography was performed in 78 patients (138 carotid arteries). Carotid endarterectomy was carried out in 62 cases. While almost all high grade stenoses and occlusions were correctly detected by Doppler sonography, accuracy decreased to approximately 20% in lower grade stenoses of less than 40% diameter reduction. On the other hand ultrasonic arteriography showed the highest accuracy of approximately 85% in low grade stenoses, while less than 40% of high grade stenoses and occlusions were correctly identified. Overall sensitivity of the combination of both methods was 95% as compared with the angiographic findings, specifity 89%. Because X-ray-angiography often fails in the correct detection of low grade stenoses, and because ultrasonic arteriography has some advantages in estimating the morphology of plaques, the surgical findings rather than the X-ray findings should be the standard for evaluation of the ultrasonic findings. Combination of Doppler sonography and ultrasonic arteriography results in more specific indications for angiography and carotid endarterectomy in transient ischaemic attacks. The proposed method is suitable for detailed controls after carotid surgery, and is the method of choice for follow-up studies in asymptomatic carotid arteriosclerosis.Zusammenfassung850 Patienten mit Verdacht auf zerebrovaskuläre Durchblutungsstörungen wurden mit indirekter und direkter Doppler-Sonographie sowie anschließender Echo-Arteriographie mit einem hochauflösenden B-Bildgerät auf Carotisstenosen untersucht. 138 Carotiden von 78 Patienten dieses Kollektivs wurden angiographiert, in 62 Fällen wurde eine operative Ausschälung einer Carotisstenose vorgenommen. Während Doppler-sonographisch hochgradige Stenosen und Verschlüsse praktisch immer erkannt wurden, betrug die Treffsicherheit bei geringgradigen Stenosen unter 40% Lumeneinengung nur etwa 20%. Umgekehrt erreichte die Echo-Arteriographie ihre höchste Treffsicherheit von etwa 85% bei geringgradigen Stenosen, während weniger als 40% aller hochgradigen Stenosen und Verschlüsse erkannt wurden. Bei Kombination beider Verfahren betrug die Treffsicherheit bezüglich der Erkennung pathologischer Befunde im Vergleich zur Röntgen-Angiographie 95%, die Spezifität (richtig negative Diagnose) 89%. Da die Angiographie vor allem bei geringgradigen Stenosen selbst nur eine begrenzte Treffsicherheit im Vergleich zum anatomischen Substrat besitzt und die Echo-Arteriographie in manchen Fällen der Angiographie hinsichtlich der morphologischen Genauigkeit überlegen sein dürfte, wird für weitere Untersuchungen der Vergleich mit dem Operationsbefund empfohlen. Die kombinierte Doppler-Sonographie und Echo-Arteriographie ermöglicht eine gezieltere Indikationsstellung zur Angiographie und Gefäßrekonstruktion bei transitorischen ischaemischen Attacken, eignet sich für postoperative Kontrollen nach Carotis-Thrombendarteriektomien und bietet sich für Verlaufs- und Therapiekontrollen bei asymptomatischen Gefäßveraäderungen an.