Adult-onset tic disorders.

We report on 8 patients with adult-onset motor tics and vocalisations. Three had compulsive tendencies in childhood and 3 had a family history of tics or obsessive-compulsive behaviour. In comparison with DSM-classified, younger-onset Gilles de la Tourette syndrome, adult-onset tic disorders are more often associated with severe symptoms, greater social morbidity, a potential trigger event, increased sensitivity, and poorer response to neuroleptic medication.

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.

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.

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.

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".

Quantitative determination of the dopamine agonist lisuride in plasma using high-performance liquid chromatography with fluorescence detection.

An HPLC method for the determination of lisuride hydrogen maleate in plasma is described. After addition of ergotamine tartrate as internal standard, plasma is extracted with diethyl ether. Following evaporation of the solvent and redissolving in methanol the extract is injected on a silica HPLC column and lisuride is monitored by fluorescence detection using an excitation wavelength of 322 nm and an emission wavelength of 405 nm. The method is sufficiently accurate and precise with a detection limit of 20 pg/ml lisuride in plasma. The usefulness of the method is demonstrated by measurements of lisuride levels after oral intake of a 0.6 mg dose of the drug by a healthy male volunteer, showing a peak level of 1266 pg/ml, 45 min after intake.

Attenuation of haloperidol-induced catalepsy by noradrenaline and L-threo-DOPS.

In addition to impaired dopaminergic neurotransmission a dysfunctional noradrenergic system has been demonstrated in Parkinson's disease. L-threo-3,4-dihydroxyphenylserine (DOPS), a synthetic precursor of noradrenaline (NA), appears to be effective in the treatment of some akinetic symptoms in parkinsonian patients. In the present study the possible effect of DOPS was studied in rats, in which catalepsy was induced with haloperidol as a model for parkinsonian akinesia. Intravenous infusion of NA (1.5 and 15 micrograms/kg) or DOPS (2 and 4 mg/kg) in male Wistar rats (240-290 g) significantly decreased catalepsy. The effect of DOPS was abolished by pretreatment with the peripheral decarboxylase inhibitor benserazide (2 mg/kg). Pretreatment with Ro 40-7592, a catechol-O-methyltransferase inhibitor, potentiated and prolonged the anticataleptic effect of DOPS. The findings suggest a peripheral site of NA mediated anticataleptic action. Therapy with DOPS may be successful only without a peripheral decarboxylase inhibitor. Moreover, the therapeutic effect of DOPS may be potentiated by COMT inhibition.

Parlodel SRO in Parkinson's disease: a double-blind randomized comparison of Parlodel standard and Parlodel SRO.

In this study, we compared in an intent-to-treat analysis the tolerance and efficacy of Parlodel SRO with its standard galenic formulation in 34 patients with Parkinson's disease who received optimal levodopa therapy. The results suggest that Parlodel SRO was equally efficacious as Parlodel standard, but Parlodel SRO is better tolerated.

[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.

Catecholamine metabolism during additional administration of DL-threo-3,4-dihydroxyphenylserine to patients with Parkinson's disease.

DL-threo-3,4-dihydroxyphenylserine (DL-threo-DOPS) was administered during 10 days to 4 patients with longstanding Parkinson's disease in addition to their treatment with L-3,4-dihydroxyphenyl-L-alanine (L-DOPA)-carbidopa (Sinemet). All patients tended to improve in their symptoms freezing, all day life activity and mood. There were no improvements in rigidity, tremor, and akinesia (in general). During the DL-threo-DOPS-treatment cerebrospinal fluid (CSF), serum and urine concentrations of catecholamines were measured. The results show that DL-threo-DOPS is transported to the brain and CSF in a way comparable with L-DOPA. However, no measurable increase of 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG) in CSF could be demonstrated. This suggests that the synthesis of noradrenaline from DL-threo-DOPS in the brain is doubtful. In addition measurements in urine reveals that at the dose used Sinemet prevents peripheral decarboxylation of DL-threo-DOPS into noradrenaline. Other possible metabolic pathways of DL-threo-DOPS are discussed.

Meige syndrome: double-blind crossover study of sodium valproate.

A double-blind crossover study of sodium valproate and placebo was conducted in five patients with Meige syndrome. CSF neurotransmitter studies were performed at the end of each treatment period. GABA levels were not influenced by the administration of sodium valproate. An increase in HVA levels was observed in every patient, which may reflect an increase in central dopaminergic activity. This finding may explain the trend towards clinical deterioration which was observed during treatment with sodium valproate. Sodium valproate appears to be ineffective in Meige syndrome.

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.

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.

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.