Amino acid abnormalities in cerebrospinal fluid of patients with parkinsonism and extrapyramidal disorders.

Free amino acid determinations in the cerebrospinal fluid of patients with Parkinson's disease or other extrapyramidal disorders showed that in both groups most amino acids were increased. Significantly increased amino acids were neutral and basic amino acids. Amino acid clusters were present and corresponded with the grouping of amino acids in accordance with amino acid transport systems. The amino acids within the clusters showed a remarkable degree of correlation, and there was a notable correlation between the clusters both in the parkinsonian group and in the group of extrapyramidal disorders, but not in a control group. Our data suggest that in a number of extrapyramidal disorders, Parkinson's disease included, a more generalized abnormality exists than neuronal loss only and, in addition, that patients with these neurologic conditions have a common biochemical defect in their amino acid transport systems.

Low-dose bromocriptine therapy in Parkinson's disease: double-blind, placebo-controlled study.

Twenty-one de novo parkinsonian patients in stage I to III of the Hoehn and Yahr scale completed a 6-month, double-blind, placebo-controlled study. Low-dose bromocriptine (15 mg daily) was effective. Rigidity improved more than tremor or bradykinesia. Sustained satisfactory benefit was seen only in patients with mild Parkinson's disease.

Rapid decarboxylation of carbon-11 labelled DL-DOPA in the brain: a potential approach for external detection of nervous structures.

The cerebral distribution of the positron-emitting agent [1-11C]beta-(3,4-dihydroxyphenyl)-D,L-alpha-alanine ([11C]DOPA) was studied after intravenous injection in rats pretreated with the peripheral decarboxylase inhibitor, carbidopa. Within 15 min of injection the accumulation of carbon-11 was almost twice as high in cortical areas and cerebellum as in the striatum and the brain stem. After destruction of catecholamine-containing nerve endings with 6-hydroxydopamine, the level of carbon-11 in the striatum was higher than in rats not treated with this neurotoxin. Pretreatment of rats with haloperidol or L-DOPA did not change the distribution pattern of carbon-11. Without pretreatment with carbidopa a uniform distribution of the label in the brain was observed. We suggest that [11C]DOPA is a potentially useful agent for external detection with positron imaging systems in patients and large animals of brain regions rich in the enzyme dopa-decarboxylase. (EC 4.1.1.26).

Bilateral ballism: a rare syndrome. Review of the literature and presentation of a case.

Ballism rarely occurs as a bilateral phenomenon and only 12 such cases have been reported so far in the literature. A further case is reported in the present paper. The definition of bilateral ballism is discussed, its movements described and the differences from chorea outlined. The most important difference from hemiballism is in the pathological substrate where, in most bilateral cases, diffuse lesions have been reported on both sides of the basal ganglia, without preferential involvement of the subthalamic nucleus. In our case, a fronto-temporal infarction was found. In the cases reported to date, the outcome had varied from death to complete recovery, partly depending on the aetiology, which is most frequently vascular. Although relevant data are scarce, dopamine antagonists appear to be the treatment of choice. We stress the role of the dopaminergic system and co-existing factors influencing the abnormal involuntary movements.

Axial apraxia in Parkinson's disease.

Attention is drawn to certain disorders of posture and movement such as kneeling, turning around in the recumbent position, arising and walking which form a separate group of motor disabilities in Parkinson patients. Levodopa therapy is far less effective for these axial motor abnormalities than for hypokinesia, tremor, rigidity and manual dexterity. Inappropriate function of the axial musculature leads to debilitating situations. It is argued that the disordered axial movements are not the result of an akinetic mechanism but share the criteria applied to apraxic phenomena and the term axial apraxia is proposed. Thus far axial apraxia has resisted conventional physiotherapeutic treatment, but some patients overcome their apraxic disability using alternative motor strategies.

Tracing of dopamine receptors in hemiparkinsonism with positron emission tomography (PET).

In 13 hemiparkinson patients possible changes in dopamine receptors were investigated in vivo with PET, using [11C]methylspiperone as the receptor labeling ligand. Though in individual patients the specific binding of the tracer differed between both striata, no consistent difference was found. However, the specific binding in the striatum of patients with longterm dopaminergic medication was significantly higher than in non-medicated patients, and close to normal. No correlation with the predominantly unilateral clinical pathology was found. Since the postsynaptic receptor changes in hemiparkinson patients appear not to be uniform, these results suggest that the clinical asymmetry is not only caused by a dysfunction of nigral dopaminergic cells, but by pathology in other cells and probably in other neurotransmitter systems as well. The observed bilateral increase in receptor binding during dopaminergic therapy most likely results from a symmetrical change in local pharmacokinetics or from alteration of the receptor binding. Further studies with PET are needed to determine the exact nature of this change.

CSF GABA levels in Parkinson's disease.

CSF levels of GABA were investigated in a group of Parkinson patients without drug treatment and a group of Parkinson patients under treatment with L-DOPA or anticholinergics. Probenecid results in an elevation of CSF GABA levels in healthy persons. The results indicate a significant decrease of GABA levels in CSF in untreated Parkinson patients. Parkinson patients treated with L-DOPA or anticholinergics show nearly normal CSF GABA levels. This may suggest that the altered GABA function in Parkinson's disease is secondary to changes in the dopamine system.

Wilhelm von Hboldt and James Parkinson. An appraisal of observation and creativity.

Wilhelm von Humboldt (1767-1835) was an educational reformer, a statesman serving Frederick William III, King of Prussia and a philologist, who influenced the contemporary linguist Chomsky. Moreover von Humbolt was a prolific writer, he kept up a substantial correspondence with family and a circle of acquaintances. His letters also contain references to his physical fitness. In the year of James Parkinson's death, 1824, von Humboldt mentioned difficulties with writing for the first time. From his correspondence during the last 11 years of his life we can reconstruct a classic development of the shaking palsy based on clever self-observations. Von Humboldt supplemented James Parkinson's description with micrographia, and dysdiadochokinesia. In addition, he observed, that turning over in bed was impeded, that after 9 years of misery his tremor subsided, and that writing was possible using Latin print lettering instead of his usual gothic handwriting, von Humboldt died on the 8th April 1835 of pneumonia, a complication of his illness; he kept his full intellectual and artistic capacities until the end.

[Postural scintimyelography of the cervical spine (author's transl)]. / Haltungsszintimyelographie des Zervikalkanals

This study discusses the clinical validity of 101 postural scintimyelograms as a screening method for cervical myelopathy. The RIHSA or Ytterbium isotope-examination are not an extra burden to the patient if the radiopharmacon is introduced into the dural sac following Queckenstedt's test. If there is a normal rise and fall of CSF pressure after bilateral jugular compression and postural scintimyelography is judged normal as well, a cervical subarachnoid obstruction may be excluded. If both examinations yield pathological results an obstructive process in the cervical spinal canal is made certain; and in cases of spondylotic myelopathy a positive contrast myelogrpahy may thus be superfluous. If the results of these two examinations are contradictory then further neuroradiolocal studies are indicated.

The black hole in Charley Toorop's "The three generations": a neuro-iconographic analysis and reconstruction.

The painting "The Three Generations" is considered one of the highlights in Charley Toorop's works. It essentially represents a self portrait of the artist herself, with John Rädeker's sculpture of her father Jan Toorop, and her son Edgar Fernhout. The completion of this painting took 9 years (1941-1950). However, the left lower corner of the canvas, sometimes referred to as "the black hole", Charley's left thumb with the palette and the conspicuously raised right arm with the brush can be considered structural imperfections. During the last 5 years of her life Charley Toorop suffered at least three cerebrovascular accidents, which raises the question whether the described pictorial inadequacies were of a neuropathological origin. Closer examination of the "black hole" area on the canvas disclosed a subtle ridge, as predicted and reconstructed by computer image manipulation. It is argued that Charley Toorop suffered multiple brain infarctions with subsequent partial visuo-spatial agnosia which prevented her from either recognizing and/or restoring the alleged imperfections in the painting "The Three Generations".

The spasmolytic properties of 5-chloro-4-(2-imidazolin-2-yl-amino)-2, 1,3-benzothiadiazole hydrochloride (DS 103-282): a pilot study.

The overall efficacy and tolerance of a new skeletal muscle relaxant DS 103-282 was evaluated by treating 10 patients with chronic spinal spasticity. Other agents such as baclofen, dantrolene sodium or diazepam had been only minimally beneficial in these patients. Treatment was started with DS 103-282 at a mean dosage of 7.4 mg. per day which was adjusted according to response up to 14.5 mg. per day at the end of the 8-week trial period. Objective rating assessments showed improvement in spasticity, medullary automatism and clonus. No changes were recorded in the reflex pattern nor improvement in disability scores. Only a few mild side-effects were reported, there was a noticeable absence of sedation, but reduction in systolic and diastolic blood pressure was noted in most patients. DS 103-282 appears to have demonstrable myotonolytic action and in view of its good tolerance it deserves further investigation.

Axial apraxia, a distinct phenomenon.

Three Parkinson patients who continued to have difficulties with turning in the horizontal plane despite adequate and therapeutically effective levodopa treatment are presented. The handicap of the disordered axial rotation, to be considered an elementary displacement of the body, could be alleviated by alternative motor strategies or overcome by specific extra stimuli or tactile guidance but not physiotherapeutically restored. On the basis of these clinical observations it is argued that these axial movement abnormalities are apraxic.

Abnormalities in postural reflexes and voluntarily induced automatic movements in Parkinson patients.

Postural abnormalities were systematically studied in 41 Parkinson patients in relation with the other Parkinson symptomatology. Evidence was collected that kinetic postural mechanisms, including turning in recumbant position, rising from the floor and walking, to be considered as volitional automatic movements, reacted differently on Levodopa therapy compared with static postural reflexes and the classical Parkinson symptoms. This suggests that the neuro-biochemical substrate of these postural movements may involve other than dopaminergic pathways as well.

Artful imaging of the brain. From logo to metaphor, about Michelangelo and Kiefer.

Michelangelo has painted the fresco 'Creation of Adam' for the Sistine Chapel. Recently it was discovered that he had an outline of the brain concealed in Gods cloud. As a renaissance artist he was not supposed to believe that the brain is the seat of the soul. Only when the concept of structure and function of the central nervous system had developed, artistic presentation of the brain did become possible. The conceptual painter Kiefer, who is possessed by Germany's recent and past history, expressed his apprehension using the philosopher Heidegger and his writings as symbol and a naked brain as metaphor.

[Physical symptoms of Parkinson's disease and the score on Beck's Depression Inventory]. / Lichamelijke symptomen van de ziekte van Parkinson en de score op Beck's Depression Inventory.

In patients with Parkinson's disease high prevalence of depression has been estimated. This prevalence may be overestimated since the commonly used assessment of depressive complaints neglects the correspondence with physical symptoms of Parkinson's disease and psychosomatic symptoms in depression. To evaluate the effect of this contamination, we presented a frequently used questionnaire for assessing depressive complaints, Beck's Depression Inventory (BDI), to eight neurologists specialized in Parkinson's disease. We asked them to select those items on which Parkinson patients might receive high scores merely because of the physical symptoms of their disease. Based on their consistent judgments, a BDI-version corrected for somatic items was constructed. Next, the scores of the original and the corrected version were computed for 27 outpatients with Parkinson's disease (from mild to very severe) and 52 psychiatric inpatients who were being treated for depression. Prevalence of depression were 74% (original BDI) and 48% (corrected BDI) for the Parkinson group and 75% and 81% respectively for the psychiatric group. Results indicate that great care should be taken in interpreting scores on depression inventories in patients with Parkinson's disease. In general, the results raise doubts on the validity of somatic complaints as indicators of depression in patients with Parkinson's disease.

Autopsy practises for brain dissections and Rembrandt's anatomy lesson of Dr. Deyman.

Illustrations, previous to the 19th century, provide evidence that brain dissections were executed on an isolated head, contrary to Rembrandt's anatomy lesson of Dr. Deyman. This paradox seems to be explained by clever biased composition.