Clinical Neuroscience

[The problem of the pathogenesis of amyotrophic lateral sclerosis]


APRIL 01, 1967

Clinical Neuroscience - 1967;20(04)

[The author bases his hypothesis on the pathogenesis of amyotrophic lateral sclerosis (ALS) on the following factors: 1. The fact that the disease process involves certain systems of the nervous system and is dystrophic in nature; 2. Analogies with the anatomic-clinical syndrome of tri-ortho-cresyl phosphate (TOCP) poisoning. 3. Certain biochemical data observed in both processes. Experimental subacute and chronic TOCP poisoning has been established in mice, rabbits and dogs. Histological, histochemical and biochemical studies were performed in brain tissue and serum. Changes in serum protein composition were also studied by electrophoresis. The results suggested that, in addition to irreversible inhibition of cholinesterase activity, several different, poorly studied factors are involved in the pathogenesis of TOCP intoxication. The pathophysio-clinical picture of TOCP intoxication represents an experimental model of neurological systemic lacrosis, the analogy of which with amyotrophic lateral sclerosis is undoubted. This analogy is not based on an exogenous toxic factor, i.e. ALS is not simply TOCP neurotoxicosis. We must assume a similar pathogenesis of the two processes. In the pathogenetic view of ALS, we can attribute a role to certain congenital enzyme biochemical abnormalities. Among these, perhaps those of cholinesterase nature or enzymes related to the biochemistry of acetyl-choline cholinesterase are of greatest importance. The decrease in cholinesterase activity observed in the serum of patients is in favour of the cholinesterase activity hypothesis. In analogy to the pathogenesis of TOCP poisoning, the pathogenesis of ALS is likely to involve a more complex perturbation of several enzyme chains, the most important of which are enzymopathic nature of the disease process.]


  1. Szófiai Neurológiai Klinika



Further articles in this publication

Clinical Neuroscience

Die ventrale Fusion im Bereich der Halswirbelsäule bei Bandscheibenschäden

W. Grote, P. Röttgen

Das so genannte Zervikalsyndrom, dessen häufigste Erscheinungsformen Schulter- und Armschmerzen, Nacken- und Kopfschmerzen, zervikale Migräne, vertebraler Schwindel und zervikale Myelopathie sind, ist wesentlich schwieriger zu diagnostizieren als das Lumbalsyndrom. Bei Vorliegen eines Zervikalsyndroms wurden folgende Operationen durchgeführt: La-Minektomie oder Hemilaminektomie mit oder ohne Entfernung der vorgefallenen Bandscheibe, Radikotomie nach Jackson oder Frykholn. 1962 führten Cloward (Honolulu) und Dereymaeker und Mulier (Belgien) die Operation ein, bei der die vorgefallene Bandscheibe durch ventrale Penetration entfernt und eine knöcherne Fusion zwischen den Wirbelkörpern hergestellt wurde. Nach Lindblom wird die chirurgische Indikation durch eine Diskographie mit 60 % Urographie ergänzt. Seit 1962 wurden 84 Patienten operiert (Tabelle 5). Die Myelographie wurde in 33 Fällen durchgeführt. Bei 37 Patienten wurde eine einzelne und bei 42 Patienten eine multiple Diskusläsion festgestellt. 28 Patienten wurden nicht fusioniert. Bei der Mehrzahl der Patienten wurde die Knochenfusion bei 8 Patienten mit autoplastischem Knochen, bei 42 Patienten mit homoplastischem Knochen und bei 6 Patienten mit heteroplastischem Knochen durchgeführt. Postoperative Ergebnisse (Tabelle 17): Von 29 Brachialgien zeigten 15 eine deutliche Besserung (wg), 10 eine deutliche Besserung (g), 4 hatten unveränderte Beschwerden (u). 17 Brachialgie und Zephalalgie postoperative Ergebnisse Verteilung: 11, 3 und 3. 8 Zephalalgie (C34): 5, 2 und 1. 30 Myelopathie: 7, 7 und 16. Wenige chirurgische Komplikationen: ein Fall von Ösophagusverletzung, ein Fall von Hämatom mit Atemnot, zwei Fälle von Abrutschen des Knochensplitters. Manchmal kann auf eine Knochenversteifung verzichtet werden, aber im Falle einer Versteifung ist das Operationsergebnis besser. Bei Myelopathie ist der Verzicht auf eine Indikation gerechtfertigt, aber auch in diesem Bereich können hervorragende Ergebnisse erzielt werden; ein Patient mit Tetraplegie war nach der Operation arbeitsfähig.

Clinical Neuroscience

[Ehlers-Danlos syndrome associated with neurological symptoms]


[The authors diagnosed a 43-year-old woman and her 8-year-old son with classic Ehlers-Danlos syndrome. In the mother, the underlying disease was accompanied by muscular atrophy and symptoms suggestive of spinal cord dorsal cord injury. The authors associate the onset of neurological symptoms with the underlying disease and attribute it to dysplastic vasculature.]

Clinical Neuroscience

[Eozinofil granulocytak a liquorban]

PÉTER Ágnes, KOVÁCS Ferenc

[Eosinophilic cells were detected in a small percentage of CSF in both bacterial and non-bacterial infections. Intense CSF eosinophilia was found only in bacterial processes. In these cases, an allergic pathomechanism was hypothesized. Unique in the literature, liquoreosinophilia accompanied by a leukocytic reaction was observed in our 1 case of meningitis in the setting of collagenosis and in our 3 cases of granulomatous menongoencephalitis. This specific CSF cytological reaction was highlighted in the group of diseases of the nervous system with immune-allergic syndrome. Immuno-allergic CSF syndromes with eosinophilic cell proliferation were divided into three groups according to the involvement of plasma cells. The factors determining the type of reaction response remain to be elucidated. Our patient with periarteritis nodosa with 26% eosinophils in his meningogram complements literature data. Of particular interest is our case No 4, who developed cerebroesinophilia after myelography.]

Clinical Neuroscience

[Data on the psychiatric use of chlormethiazole (Heminevrin)]


[Author reviews the literature on the pharmacological and clinical effects, side effects and complications of Heminevrin. He reports on 77 cases he has observed and treated. He confirms the excellent efficacy of Heminevrin in delirium tremens, where in 31 patients Heminevrin therapy led to recovery in a few days without mortality and without complications. He has used the drug praeventively in 27 cases of praedelirosus withdrawal syndrome, which he considers to be a beneficial combination for the treatment of endogenous and reactive psychogenic depressions (based on 13 cases). ]

Clinical Neuroscience

[The role of the limbic lobe in incentive production]


[Two cases of a midline tumour destroying limbic structures were described. In both cases, the clinical picture was characterized by a high degree of inducibility loss, which was already evident at the onset. We evaluate our cases as recent data on the role of limbic structures in the maintenance of incentin production. ]

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Clinical Neuroscience

Evaluation of the effectiveness of transforaminal epidural steroid injection in far lateral lumbar disc herniations

EVRAN Sevket, KATAR Salim

Far lateral lumbar disc herniations (FLDH) consist approximately 0.7-12% of all lumbar disc herniations. Compared to the more common central and paramedian lumbar disc herniations, they cause more severe and persistent radicular pain due to direct compression of the nerve root and dorsal root ganglion. In patients who do not respond to conservative treatments such as medical treatment and physical therapy, and have not developed neurological deficits, it is difficult to decide on surgical treatment because of the nerve root damage and spinal instability risk due to disruption of facet joint integrity. In this study, we aimed to evaluate the effect of transforaminal epidural steroid injection (TFESI) on the improvement of both pain control and functional capacity in patients with FLDH. A total of 37 patients who had radicular pain caused by far lateral disc herniation which is visible in their lumbar magnetic resonance imaging (MRI) scan, had no neurological deficit and did not respond to conservative treatment, were included the study. TFESI was applied to patients by preganglionic approach. Pre-treatment Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores of the patients were compared with the 3rd week, 3rd month and 6th month scores after the procedure. The mean initial VAS score was 8.63 ± 0.55, while it was 3.84 ± 1.66, 5.09 ± 0.85, 4.56 ± 1.66 at the 3rd week, 3rd month and 6th month controls, respectively. This decrease in the VAS score was found statistically significant (p = 0.001). ODI score with baseline mean value of 52.38 ± 6.84 was found to be 18.56 ± 4.95 at the 3rd week, 37.41 ± 14.1 at the 3rd month and 34.88 ± 14.33 at the 6th month. This downtrend of pa­tient’s ODI scores was found statistically significant (p = 0.001). This study has demonstrated that TFESI is an effective method for gaining increased functional capacity and pain control in the treatment of patients who are not suitable for surgical treatment with radicular complaints due to far lateral lumbar disc hernia.

Lege Artis Medicinae

[Second game, 37th move and Fourth game 78th move]

VOKÓ Zoltán

[What has Go to do with making clinical decisions? One of the greatest intellectual challenges of bedside medicine is making decisions under uncertainty. Besides the psychological traps of traditionally intuitive and heuristic medical decision making, lack of information, scarce resources and characteristics of doctor-patient relationship contribute equally to this uncertainty. Formal, mathematical model based analysis of decisions used widely in developing clinical guidelines and in health technology assessment provides a good tool in theoretical terms to avoid pitfalls of intuitive decision making. Nevertheless it can be hardly used in individual situations and most physicians dislike it as well. This method, however, has its own limitations, especially while tailoring individual decisions, under inclusion of potential lack of input data used for calculations, or its large imprecision, and the low capability of the current mathematical models to represent the full complexity and variability of processes in complex systems. Nevertheless, clinical decision support systems can be helpful in the individual decision making of physicians if they are well integrated in the health information systems, and do not break down the physicians’ autonomy of making decisions. Classical decision support systems are knowledge based and rely on system of rules and problem specific algorithms. They are utilized widely from health administration to image processing. The current information revolution created the so-called artificial intelligence by machine learning methods, i.e. machines can learn indeed. This new generation of artificial intelligence is not based on particular system of rules but on neuronal networks teaching themselves by huge databases and general learning algorithms. This type of artificial intelligence outperforms humans already in certain fields like chess, Go, or aerial combat. Its development is full of challenges and threats, while it presents a technological breakthrough, which cannot be stopped and will transform our world. Its development and application has already started also in the healthcare. Health professionals must participate in this development to steer it into the right direction. Lee Sedol, 18-times Go world champion retired three years after his historical defeat from AlphaGo artificial intelligence, be­cause “Even if I become the No. 1, there is an entity that cannot be defeated”. It is our great luck that we do not need to compete or defeat it, we must ensure instead that it would be safe and trustworthy, and in collaboration with humans this entity would make healthcare more effective and efficient. ]

Clinical Neuroscience

[Effective therapy in highly active pediatric multiple sclerosis ]

MERÔ Gabriella, MÓSER Judit, LIPTAI Zoltán, DIÓSZEGHY Péter, BESSENYEI Mónika, CSÉPÁNY Tünde

[Multiple sclerosis (MS) is typically a disease of young adults. Childhood MS can be defined in patients under 18 years of age, although some authors set the limit un­der the age of 16 formerly known as “early-onset multiple sclerosis” or “juvenile multiple sclerosis”, seen in 3-5% of all MS patients. Nowadays, owing to ever-evolving, better diagnostic tools and well-traced, strictly defined diagnostic criteria, childhood MS is showing an increasing incidence worldwide (0.05-2.85/100 000). MS is characterized by recurrent episodes of the central nervous system with demyelination separated in space and time. In childhood almost exclusively the relapsing-remitting (RR) type of MS occurs. Based on experience in adults, the goal in the pediatric population is also the early diagnosis, to initiate adequate DMT as soon as possible and to achieve symptom relief and good quality of life. Based on efficacy and safety studies in the adult population, inter­feron β-1a and glatiramer acetate were first approved by the FDA and EMA for the treatment of childhood MS also. The increased relapse rate and rapid progression of childhood MS and unfavorable therapeutic response to nearly 45% of the first DMT necessitated the testing of more effective and second-line drugs in the population under 18 years of age (PARADIGMS, CONNECT). Although natalizumab was reported to be effective and well-tolerated in highly active RRMS in childhood, evidence based studies were not yet available when our patients’ treatment started. In this article, we report on the successful treatment of three active RRMS patients with individually authorized off-label use of natalizumab.]

Clinical Neuroscience

Matrix metalloproteinases and their tissue inhibitors in relapsing remitting multiple sclerosis: Possible markers and treatment agents


Matrix metalloproteinases (MMPs), which are synthesized by many cell groups and responsible for the destruction of matrix proteins, and endogen tissue inhibitors of MMPs (TIMPs) have a role in the pathogenesis of Multiple Sclerosis (MS) by affecting the blood-brain barrier. We aimed to investigate the role of MMPs and TIMPs in the immunopathogenesis and in the course of multiple sclerosis (MS). We enrolled 25 relapsing remitting MS patients, who had a definite MS diagnosis according to McDonald criteria and 25 healthy subjects similar for age and gender as control group. MMP-9- and TIMP-1 levels were measured twice in patient group (one time during an attack and one in remission) and once in healthy subjects. MMP-9- and TIMP-levels of patients during attack and remission period and MMP-9/TIMP-1 ratio were found significantly higher than in the control subjects. In patient group MMP-9 and TIMP-1 levels and MMP-9/TIMP-1 ratio during attacks were not significantly different than during remission period. However, when subdivided according to their number of attacks, patients with 2 attacks had significantly higher levels during attack period comparing to remission period (p<0.05); in case of patients with more than 2 attacks did not have a statistically significant difference in attack and remission periods. Matrix metalloproteinases are important actors in MS immunopathogenesis, particularly in the early period and inhibitor agents for these enzymes can be used as a treatment option.

Clinical Neuroscience

Chronic form of Pisa syndrome after prolonged exposure to low-dose amisulpride treatment

ERDEM Şimşek Nazan, ÖZKAYNAK Sibel Sehur

Pisa syndrome is a movement problem defined by tonic, sustained lateral flexion with a slight posterior rotation of the trunk. It seems to be a side effect of antipsychotic medicine in most cases. The clinical duration of Pisa syndrome can be acute, chronic, or recurrent. As far as we know, no reports are available in the literature on the chronic form of Pisa syndrome caused by low-dose amisulpride. A case of refractory tardive dystonia form of Pisa syndrome during treatment with stable low-dose amisulpride is presented in this report. Long-term, low-dosage amisulpride therapy may induce tardive dystonia even in patients with no other risk factors for dystonia.