Serological survey of Bartonella spp., Borrelia burgdorferi, Brucella spp., Coxiella burnetii, Francisella tularensis, Leptospira spp., Echinococcus, Hanta-, TBE- and XMR-virus infection in employees of two forestry enterprises in North Rhine-Westphalia, Germany, 2011-2013.

We initiated a survey to collect basic data on the frequency and regional distribution of various zoonoses in 722 employees of forestry enterprises in the German state of North Rhine-Westphalia (NRW) from 2011 to 2013. Exposures associated with seropositivity were identified to give insight into the possible risk factors for infection with each pathogen. 41.2% of participants were found to be seropositive for anti-Bartonella IgG, 30.6% for anti-Borrelia burgdorferi IgG, 14.2% for anti-Leptospira IgG, 6.5% for anti-Coxiella burnetii IgG, 6.0% for anti-Hantavirus IgG, 4.0% for anti-Francisella tularensis IgG, 3.4% for anti-TBE-virus IgG, 1.7% for anti-Echinococcus IgG, 0.0% for anti-Brucella IgG and anti-XMRV IgG. Participants seropositive for B. burgdorferi were 3.96 times more likely to be professional forestry workers (univariable analysis: OR 3.96; 95% CI 2.60-6.04; p<0.001); and participants seropositive for Hantavirus 3.72 times more likely (univariable analysis: OR 3.72; 95% CI 1.44-9.57; p=0.007). This study found a surprisingly high percentage of participants seropositive for anti-B. henselae IgG and for anti-F. tularensis IgG. The relatively high seroprevalence for anti-Leptospira IgG seen in this study could be related to living conditions rather than to exposure at work. No specific risk for exposure to C. burnetii and Echinococcus was identified, indicating that neither forestry workers nor office workers represent a risk population and that NRW is not a typical endemic area. Forestry workers appear to have higher risk for contact with B. burgdorferi-infected ticks and a regionally diverse risk for acquiring Hantavirus-infection. The regional epidemiology of zoonoses is without question of great importance for public health. Knowledge of the regional risk factors facilitates the development of efficient prevention strategies and the implementation of such prevention measures in a sustainable manner.

Distributed representations of the "preparatory set" in the frontal oculomotor system: a TMS study.

BACKGROUND: The generation of saccades is influenced by the level of "preparatory set activity" in cortical oculomotor areas. This preparatory activity can be examined using the gap-paradigm in which a temporal gap is introduced between the disappearance of a central fixation target and the appearance of an eccentric target. METHODS: Ten healthy subjects made horizontal pro- or antisaccades in response to lateralized cues after a gap period of 200 ms. Single-pulse transcranial magnetic stimulation (TMS) was applied to the dorsolateral prefrontal cortex (DLPFC), frontal eye field (FEF), or supplementary eye field (SEF) of the right hemisphere 100 or 200 ms after the disappearance of the fixation point. Saccade latencies were measured to probe the disruptive effect of TMS on saccade preparation. In six individuals, we gave realistic sham TMS during the gap period to mimic auditory and somatosensory stimulation without stimulating the cortex. RESULTS: TMS to DLPFC, FEF, or SEF increased the latencies of contraversive pro- and antisaccades. This TMS-induced delay of saccade initiation was particularly evident in conditions with a relatively high level of preparatory set activity: The increase in saccade latency was more pronounced at the end of the gap period and when participants prepared for prosaccades rather than antisaccades. Although the "lesion effect" of TMS was stronger with prefrontal TMS, TMS to FEF or SEF also interfered with the initiation of saccades. The delay in saccade onset induced by real TMS was not caused by non-specific effects because sham stimulation shortened the latencies of contra- and ipsiversive anti-saccades, presumably due to intersensory facilitation. CONCLUSION: Our results are compatible with the view that the "preparatory set" for contraversive saccades is represented in a distributed cortical network, including the contralateral DLPFC, FEF and SEF.

Three-dimensional cytoarchitectonic analysis of the posterior bank of the human precentral sulcus.

Studies employing functional magnetic resonance imaging have identified the human frontal eye field as being in the anterior and partly in the posterior wall, as well as at the base of the precentral sulcus. Moreover, it is known that the frontal eye field extends rostrally to the superior frontal sulcus. According to Brodmann's cytoarchitectonic map, this region belongs to the dysgranular Brodmann area 6 of the premotor cortex. However, the frontal eye field in non-human primates has been located within the arcuate sulcus in Brodmann area 8, generating considerable debate about where to locate exactly the frontal eye field in humans. Functional studies of the primate frontal eye field have revealed a principal homology of voluntary saccadic control systems in human and old-world monkeys, especially the macaque. But these homologies seem to be contradicted by the reported topographic localization at the cytoarchitectonic level. Therefore, we studied the cytoarchitectonic structure of the posterior bank of the precentral sulcus of a human brain, employing newly developed spatial mapping techniques to provide data about whether or not this region should be considered cytoarchitecturally homogeneous or heterogeneous. We used functional magnetic resonance imaging results, as an initial guide in localizing a region which is activated by saccadic tasks. A maximum of activation was detected around the junction of the superior frontal sulcus and the precentral sulcus extending 1.5 cm along the precentral sulcus in direction of the lateral sulcus. Here, one human brain has been analyzed to obtain preliminary data about the cytoarchitectonical changes of a part of area 6. Statistical analysis of the three-dimensional architectonic data from this region allowed us to identify a zone at the posterior bank, which in other studies has been associated with a functional region that controls pursuit eye movements and performs sensory-to-motor transformations. We found two significant sectors along the ventral part of the posterior bank of the precentral sulcus. The caudal transition region coincides partly with a region that integrates retinal and eye position signals for target location, arm, and axial movements. The second more ventrally located region is attributed to process oral-facial movements. The caudal transition region coincides with our functional magnetic resonance imaging investigation. It was revealed that this region lies at the inferior frontal eye field, where a pronounced activation over a larger region can be stimulated. Currently, more studies are needed to combine functional magnetic resonance imaging data of maximal activation with data from whole histologic brain sections of more individuals and to quantify the variability of this region and its sub-regions by means of a standardized brain atlas.

Late cognitive event-related potentials in adult Down's syndrome.

Event-related electroencephalogram (EEG) potentials (ERPs) using two different tasks were measured in 14 adults with Down's syndrome (DS; mean age 32 years) without clinically detectable cognitive decline. Two groups, young healthy (YH) and old healthy (OH) adults, served as controls. In the oddball task, DS had prolonged N1 and earlier P2 latencies than the control groups. P3 latency was delayed in comparison to YH. In the PushWait task, P3 latency was later in DS than in YH and OH. In both tasks, DS showed a marked amplitude shift towards positivity overlapping the N1-P2 complex and seemingly also P3: The P3 amplitude evoked by target tones and by "Push" was shifted towards anterior sites resulting in a Cz maximum. Changes of the N1 latency and amplitude in DS may be related to enhanced arousal during stimulus processing, indicating a possible defect of central inhibitory mechanisms. The study suggests that differentiated ERP procedures provide information on adult DS cognition exceeding those given by mere P3 latency measurements. Such procedures may be useful in the evaluation of the cognitive decline due to precocious aging or Alzheimer-type dementia in DS.

Double-blind crossover study with physostigmine in patients with degenerative cerebellar diseases.

OBJECTIVE: To determine whether treatment with physostigmine can improve the conditions of patients with ataxia. DESIGN: A double-blind crossover study with physostigmine was performed in 19 patients with degenerative cerebellar diseases. SETTING: Patients were selected from an ongoing prospective follow-up study at the university hospital in Lübeck, Germany. PATIENTS: Eleven patients with autosomal dominant cerebellar ataxia and 8 patients with idiopathic cerebellar ataxia. INTERVENTION: Physostigmine was administered by using a transdermal system (patch) containing 30 mg of physostigmine as a base, of which about 6 mg is released during 24 hours along a diffusion gradient. Each treatment phase with the physostigmine patch or the placebo lasted 4 weeks, after which the treatment of patients was crossed over to the other phase. MAIN OUTCOME MEASURES: Ataxia was documented and quantified by using a clinical score and posturographic measures. RESULTS: Physostigmine patches had no significant effect on cerebellar symptoms. CONCLUSION: Treatment with physostigmine does not improve the conditions of patients with ataxia.

Oculomotor testing in the differential diagnosis of degenerative ataxic disorders.

BACKGROUND: Oculomotor abnormalities have been reported in patients with degenerative ataxic disorders. OBJECTIVE: To assess the diagnostic sensitivity and specificity of oculomotor deficits in patients with Friedreich ataxia (FA), cerebellar atrophy (CA), and olivopontocerebellar atrophy (OPCA). SETTING: Neurology clinic at a university hospital in Lübeck, Germany. PATIENTS: Seven patients with FA, 9 with CA, and 10 with OPCA were studied. These patients were selected from an ongoing follow-up study. MAIN OUTCOME MEASURES: Eye movements were recorded by electro-oculography; an extensive battery of quantitative tests was used. RESULTS: A proven CAG repeat expansion on chromosome 6 or 14 was significantly associated with reduced saccadic eye velocity and vertical gaze palsy (P<.001, Mann-Whitney U test). All 6 patients with OPCA and slow saccades had an autosomal-dominant inheritance; 4 of them were proved to have spinocerebellar atrophy type 1. In 9 of these patients (4 with FA, 1 with CA, and 4 with OPCA), the genetic defect could not be identified. Saccadic dysmetria, impairment of smooth pursuit and optokinetic nystagmus, deficient suppression of the vestibulo-ocular reflex by either visual or otolith input, and pathological nystagmus were attributed to degenerative lesions in different parts of the cerebellum. However, these symptoms failed to clearly distinguish between the different groups of patients, whereas decreased vestibulo-ocular reflex gain, slow saccades, and vertical gaze palsy pointed to an extracerebellar manifestation of the degenerative disease, occurring only in patients with OPCA and FA. CONCLUSIONS: In this prospective study, oculomotor disturbances were mainly related to cerebellar dysfunction. Only a few of them were caused by extracerebellar manifestations of the disease, such as slowing of saccades, which was characteristic for patients with OPCA of autosomal-dominant inheritance.

Double-blind crossover study with levorotatory form of hydroxytryptophan in patients with degenerative cerebellar diseases.

OBJECTIVE: To determine whether treatment with the levorotatory form of hydroxytryptophan (L-5-hydroxytryptophan), a controversial experimental drug, can improve the conditions of patients with ataxia. DESIGN: A double-blind crossover study with the levorotatory form of hydroxytryptophan was performed in 39 patients with degenerative cerebellar diseases. SETTING: Patients were selected from an ongoing prospective follow-up study at two university hospitals. PATIENTS: We studied 19 patients with Friedreich's ataxia, 13 with cerebellar atrophy, and seven with olivoponto-cerebellar atrophy. INTERVENTION: The levorotatory form of hydroxytryptophan was given orally in a dose of 1000 mg/d. Each treatment phase, with the levorotatory form of hydroxytryptophan or the placebo, lasted 10 months, after which the treatment of patients was crossed over to the other phase. MAIN OUTCOME MEASURES: Ataxia was documented and quantified by using a clinical score, posturography, and measurement of grip force and the rapid-syllable repetition rate. RESULT: The levorotatory form of hydroxytryptophan had no significant effect on cerebellar symptoms. CONCLUSION: Long-term treatment with a high dose of the levorotatory form of hydroxytryptophan does not improve the conditions of patients with ataxia.

The diagnosis of 'essential palatal tremor'.

We report a patient with a 30-year history of progressive, involuntary movements of the left ear and clicking sounds in both ears for 2 years. The patient had rhythmic contractions of the tensor veli palatini muscle and could relieve palatal movements and ear clicks, but not ear movements, by pressing a pillow against the left ear or by finger pressure on the tragus or the retroauricular region. We discuss the significance of these sensory tricks and the nosology of the long-standing ear movements within a classification of essential and symptomatic palatal tremor. Current diagnostic criteria for both types of palatal tremor may not cover some atypical cases such as ours.

Visual search in patients with left visual hemineglect.

In patients with hemi-spatial neglect eye movement patterns during visual search reflect not only inattention for the contralesional hemi-field, but interacting deficits of multiple visuo-spatial and cognitive functions, even in the ipsilesional hemi-field. Evidence for these deficits is presented from the literature and from saccadic scan-path analysis during feature and conjunction search in 10 healthy subjects and in 10 patients with manifest or recovered left visual neglect due to right-hemispheric stroke. Deficits include (1) a rightward shift of spatial representation, (2) deficient spatial working memory and failure of systematic search strategies, leading to multiple re-fixations, more after frontal lesions, and (3) a reduced spotlight of attention and a deficient pop-out effect of color, more after temporo-parietal lesions.

Event-related potentials suggest slowing of brain processes in generalized epilepsy and alterations of visual processing in patients with partial seizures.

Event-related potentials were recorded in two auditory tasks and in one visual task from 13 patients with partial seizures (PS), 12 patients with idiopathic generalized epilepsy (IGE), and healthy age-matched participants. IGE patients had delayed latencies in the auditory tasks, with the delay being reliable already at N1, and continuously increasing at N2b and at P3. The P3 delay correlated with duration of epilepsy both in IGE and in PS patients. In the visual task, the posterior N2 was delayed in PS patients, in particular in PS patients with temporal focus. Resembling the delays as found in healthy elderly adults, the delays with auditory stimuli might reflect a slowing of brain processes as it occurs in healthy aging. The isolated delay of posterior N2 in temporal PS patients might indicate a specific impairment of the occipito-temporal visual pathway. Taken together, event-related potentials prove to be a very sensitive instrument for measuring altered brain functioning in epileptic patients, when compared to measurement of overtly visible responses.

Reduction of P3b in patients with temporo-parietal lesions.

By recording event-related EEG potentials from patients with frontal, parietal, or temporo-parietal lesions, we wanted to determine the cortical area that is relevant to the P3b component, replicating the approach used by Knight and associates who found reduced P3bs in patients with temporo-parietal lesions. They used auditory and somatosensory stimuli. We wanted to replicate their findings in auditory and visual oddball tasks and analysed potentials evoked by targets and by standard stimuli. Temporo-parietal patients' P3bs were reduced with auditory targets and lacked a distinct Pz maximum with visual targets. Further, auditory N1 was reduced both with targets and standards, P3 to visual standards and P2 to auditory standards were reduced. Parietal patients' P3bs differed only slightly from the control group, being somewhat reduced over the lesioned hemisphere with visual stimuli. Their P3 to visual standards was, however, reduced to the same extent as was the temporo-parietal patients'. Frontal patients did not differ from the control group both in their P3b and in their P3 to standards but had a number of conspicuous features in modality-specific components. In sum, our results on P3b (as well as on N1) replicate Knight's findings, confirming his conclusion that integrity of the temporo-parietal junction is critical for P3b. Implications for hypotheses on P3 are discussed.

Auditory selective attention is impaired in Parkinson's disease--event-related evidence from EEG potentials.

Selective attention refers to the ability to focus on one channel of information in the presence of distracting other channels. For the visual modality, results on impairments of selective attention have been conflicting in patients with idiopathic Parkinson's disease (PD). Independent of possible interferences from visual or movement disturbances selective attention can be measured as the so-called 'processing negativity' (PN) using auditory evoked potentials. Therefore, auditory selective attention with the PN was measured in 14 patients with PD and 16 control subjects. Subjects had to attend to tones presented to one ear (i.e. to press a button to occasionally presented longer tones) and ignore tones presented to the other ear. Tones were presented at a rate of 1/s ('slow') or 2/s ('fast'). PN was measured as the difference of the potentials evoked by attended minus ignored standard tones. PN was significantly smaller in the PD patients than in the controls with slow presentation. There was no difference between both groups with fast presentation. PN remained unchanged when patients had a 12-h withdrawal of their usual anti-Parkinsonian drug therapy. PD patients and controls did not differ in their P3 component evoked in the usual 'oddball' task nor in the mismatch negativity evoked by the occasionally longer tones in the PN task. The results provide evidence for an impairment of auditory selective attention that is specific for patients with PD (i.e. independent of the P3 component).

Eye movements and vestibulo-ocular reflex in the blind.

To assess the effect of chronic deprivation of visual feedback, 21 blind patients underwent clinical and electronystagmographical examination. Patients with congenital blindness were characterized by spontaneous eye movements, inability to consciously move the eyes and absence of the vestibulo-ocular reflex (VOR), whereas eye movement abnormalities were practically absent in those with blindness acquired late in life. Active visual experience, at least in early life, seems to be crucial for the development of eye movements and VOR adjustment.

The effect of oral ethanol consumption on eye movements in healthy volunteers.

Horizontal and vertical eye movements were recorded and analysed with an infrared photoelectric technique in 12 healthy volunteers under various blood alcohol concentrations (0.0, 0.5, 1.0 g/kg body weight, [% per thousand]). The predictive smooth-pursuit tracking and saccadic eye movements were studied in response to unpredictable target jumps and during scanning of a classical kitchen scene and a traffic scene. Smooth-pursuit eye movement gain value decreased dose-dependently and was compensated by an increased number of catch-up saccades. With increasing blood alcohol concentrations peak velocities of horizontal and vertical visually guided reflexive saccades decreased while their latencies to the target increased. At blood alcohol concentrations of 0.5% per thousand and 1.0% per thousand healthy volunteers showed significantly longer mean fixation durations and a lower total number of exploratory saccades when scanning both the classical kitchen scene and the traffic scene. Surprisingly, in both of these scanning tasks the total fixation duration or the relative number of exploratory saccades increased in those scene sectors in which exciting situations were presented. Additionally, the time interval needed to foveate these exciting areas for the first time increased, probably due to an attention deficit. In conclusion, these findings indicate that alcohol consumption impairs the velocity and initiation of saccadic and smooth-pursuit eye movements, but that subjects can nevertheless still recognize exciting and relevant areas of visual scenes. The significant increase in fixation time, however, does not allow scanning of the entire visual scene during an adequate period of time. Therefore the reduced visual exploration caused by alcohol reflects an impaired sensorimotor processing of active visual perception.

Slow saccades and other eye movement disorders in spinocerebellar atrophy type 1.

In order to study the relation between genotype and phenotype, a detailed study of the course of oculomotor deficits was performed in three patients with autosomal-dominant cerebellar ataxia, subtype spinocerebellar atrophy type 1 (SCA 1) using clinical testing and electrooculography. DNA analysis revealed a CAG repeat expansion of 65 in the SCA 1 gene on chromosome 6p in all patients. A progressive disorder of the saccadic system became obvious, leading to a marked slowing of saccadic eye movements and loss of pathological and physiological nystagmus. An upward gaze palsy developed early, followed by horizontal and downward gaze palsy at a later state of the disease. Smooth pursuit eye movements were disturbed to a lesser extent; the vestibulo-ocular reflex was reduced. As an additional feature, severe loss of visual acuity developed due to progressive optic nerve atrophy. The oculomotor deficits can be explained by progressive damage to the brain stem rather than to the cerebellum. Each combination of oculomotor deficits with or without optic atrophy may occur irrespective of the gene locus of the disease, making a correlation between clinical signs and genetic findings difficult.

A study of visual hallucinations in patients with Parkinson's disease.

In a hospital-based case-control study 29 patients with idiopathic Parkinson's disease (PD) and visual hallucinations (VH) were compared with 58 PD patients matched for age and disease duration, but without VH. VH patients had more frequently sleep disturbances and dementia, higher PD-related disability (Schwab-England scale), and took selegiline more frequently as an anti-Parkinsonian drug. The patient groups did not differ in age at PD onset, Webster score, treatment duration, dosage of any anti-Parkinsonian drug, frequency of levodopa-associated movement disorders, or measures on brain CT. After a median follow-up period of 27 months more VH patients had developed wearing-off and freezing phenomena, while their scores in the Mini Mental State Examination were lower. Nursing home placement during the follow-up period was associated with higher PD-related disability in VH patients.

Follow-up of neurophysiological tests and CT in late-onset cerebellar ataxia and multiple system atrophy.

The follow-up of neurophysiological tests (brain-stem auditory evoked potentials; blink reflex; sensory, motor and visual evoked potentials) and CT was investigated in 21 patients with late-onset cerebellar ataxia (CA) or multiple system atrophy. The study included an initial investigation and a follow-up examination on average 25.3 months later (minimum 8, maximum 36). Patients were divided into four groups: (1) those with pure CA after a minimum course of 5 years; (2) those with pure CA with pathological neurophysiological findings at the last examination; (3) those who at the first examination clinically presented with pure CA, but at the last examination were seen to have developed a multisystem disorder; (4) those with multiple system atrophy (mostly olivopontocerebellar atrophy) presenting additional non-cerebellar signs of involvement. Conforming to a strict interpretation of pure CA, group 1 patients invariably exhibited normal neurophysiological findings at all examinations. All patients in group 4, except for 2 only at the first examination, showed pathological changes in at least one of the neurophysiological tests. The main conclusion of this paper is that individuals who according to clinical criteria were initially classified as having CA but finally developed a multisystem disorder already had pathological neurophysiological findings at the initial examination (group 3). The increasing frequency of pathology in the several neurophysiological tests together with the progression of the disease is obviously of prognostic significance. CT revealed cerebellar atrophy without apparent involvement of brain-stem structures in all patients with CA; the majority of patients with multiple system atrophy also had atrophy of the brain-stem, pointing to olivopontocerebellar atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Slow EEG potentials (contingent negative variation and post-imperative negative variation) in schizophrenia: their association to the present state and to Parkinsonian medication effects.

Between warning signal (S1) and imperative signal (S2), the EEG shifts negatively (contingent negative variation, CNV) reflecting preparation and expectancy. Reduced CNV and continued negativity after S2 (post-imperative negative variation, PINV) have been repeatedly found in schizophrenic patients and have been interpreted as a deficit in attentional processes (CNV) and as uncertainty about the correctness of one's own response to the S2 (PINV). Recent studies obtained a CNV reduction specifically at central sites but not at frontal ones. The present study investigated whether these alterations of slow negative potentials depend on present state of symptoms, on the particular task used, and on neuroleptic medication. Therefore, out-patients and in-patients were studied, two different S1-S2 tasks were used, and the control groups were healthy subjects and patients with Parkinson's disease. The central CNV reduction was stable across tasks and across in-patients and outpatients. Frontal CNV was reduced in in-patients but in only one of the two tasks in outpatients. The schizophrenic patients' enhanced PINV was larger contralaterally than ipsilaterally to the responding hand, correlated with medication, and occurred in similar way in patients with Parkinson's disease. Thus, the PINV increase might reflect the Parkinsonian side effects of the anti-psychotic medication. In contrast, the central CNV reduction appears as a stable marker of schizophrenia, the frontal CNV reduction as a state-dependent effect. The central CNV reduction might reflect impairment in forming stable stimulus-response associations, the relative frontal enhancement might reflect the out-patients' attempt at compensating that impairment.

Surgical removal of pontomesencephalic cavernous hemangiomas.

Cavernous hemangiomas of the brain stem are usually discovered accidentally during evacuation of a hematoma, and successful surgical treatment of these lesions is seldom achieved. With the increasing use of magnetic resonance imaging, the presence of a cavernous hemangioma can be detected before surgery, allowing an elective surgical approach. We successfully removed pontomesencephalic cavernous hemangiomas from 2 patients and pontomedullary hemangiomas from 2 others. Elective surgery was performed with perioperative bimodal monitoring of somatosensory and auditory evoked potentials. Performing surgery soon after the hemorrhage minimizes the risk of additional postoperative neurological deficit, since surgical excision is facilitated when the hematoma is not completely organized. Pontine hemangiomas are approached via the 4th ventricle. Mesencephalic hemangiomas are removed by a midline supracerebellar approach when they are lateralized by using a subtemporal approach. The lesion can be removed through a small incision in the brain stem at the site of the lesion. The favorable results, which include marked improvement of preoperative neurological deficits and documentation of complete removal of the lesion by magnetic resonance imaging, support a more aggressive approach to the treatment of symptomatic cavernous hemangiomas of the brain stem. Further investigation of the natural history of these lesions is mandatory.

Parkinsonian features in advanced Down's syndrome.

The results of a clinical study on extrapyramidal, frontal release, and other neurological signs in 54 demented and non-demented patients with Down's syndrome (DS) are presented. Fourteen patients were demented, five of them showed extrapyramidal signs, mainly of the rigid-hypokinetic spectrum and rather similar to Parkinsonian features in advanced Alzheimer's disease (AD). None of the non-demented patients had Parkinsonian signs. The mean ages of the demented DS patients with extrapyramidal signs was significantly higher than that of the patients without the respective signs. Frontal release signs were present in demented and nondemented patients. From a questionnaire neither a raised proportion of early- or senile-onset dementia nor of Parkinsonism among first- and second-degree relatives of DS patients could be traced. Parkinsonian signs seem to be present at a lower frequency in DS than in advanced AD. A speculative hypothesis about a gene dosage effect of Cu/Zn-superoxide dismutase in preventing toxic radical formation in the substantia nigra of DS patients is presented.