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Objective: Recently, mutations in DCTN1 were found to cause Perry syndrome, a parkinsonian disorder with TDP-43-positive pathology. Previously, mutations in DCTN1 were identified in a family with lower motor neuron disease, in amyotrophic lateral sclerosis (ALS), and in a family with ALS/frontotemporal dementia (FTD), suggesting a central role for DCTN1 in neurodegeneration. Methods: In this study we sequenced all DCTN1 exons and exon-intron boundaries in 286 samples diagnosed with Parkinson disease (PD), frontotemporal lobar degeneration (FTLD), or ALS. Results: This analysis revealed 36 novel variants (9 missense, 5 silent, and 22 noncoding). Segregation analysis in families and association studies in PD, FTLD, and ALS case-control series did not identify any variants segregating with disease or associated with increased disease risk. Conclusions: This study suggests that pathogenic mutations in DCTN1 are rare and do not play a common role in the development of Parkinson disease, frontotemporal lobar degeneration, or amyotrophic lateral sclerosis. Neurology (R) 2009; 72: 2024-2028

The aim of the present study was to examine the expression of synphilin-1, alpha-synuclein, and tyrosine hydroxylase in human elderly brains and the incidence of Marinesco bodies (MBs, intranuclear inclusions) in the neuromelanin-containing substantia nigra neurons. The brains of twenty-two individuals without clinical signs and symptoms of parkinsonism and dementia and an additional two parkinsonian patients were dissected and subjected to histopathological examination and western blotting. Ubiquitin-positive and agr;-synuclein-negative MBs were found in 0.84-9.45% of the nigral neurons from brains of 15 healthy individuals and both parkinsonian patients. The frequency of pigmented nigral neurons containing MBs was positively correlated with age. The levels of tyrosine hydroxylase in the caudate nucleus and putamen decreased with age, and were inversely correlated with the MB frequency. The level of synphilin-1 in the caudate nucleus was positively correlated both with age and the MBs. Additionally, the MB appearance was correlated with synphilin-1 level in the substantia nigra. No significant correlation between alpha-synuclein expression and age or MBs was found. Our results suggest that synphilin-1 expression increases with aging. Further studies on expression of this protein in elderly brains are warranted.

A single nucleotide polymorphism in the promoter region of the dopamine β-hydroxylase gene (DBH -1021C>T; rs1611115) is reported to regulate plasma enzyme activity levels. This variant has also been the focus of two large association studies in Parkinson’s disease yielding conflicting results. We examined this association in four Caucasian patient-control series (n=2696). A modest protective association was observed in the Norwegian series (OR=0.81, p=0.03; n=1676), however the effect was in the opposite direction in the Polish series (OR=2.01, p=0.01; n=224). No association was observed for DBH -1021C>T with disease susceptibility in the US and Irish series, or combining all four series (OR=0.91, p=0.16, n=2696). We observed a modest association between DBH -1021C>T and AAO in the combined series (p=0.01). Taken together, these findings indicate that DBH -1021C>T does not play a major role in the pathogenesis of Parkinson’s disease.

International audience; Parkinson's disease (PD) is referred to as idiopathic disorder, which means that its causes have not been found yet. However, a few processes such as oxidative stress, protein aggregation and mitochondrial dysfunction are suspected to lead to the atrophy and death of substantia nigra (SN) neurons in case of this neurodegenerative disorder. Cu is a trace element whose role in the pathogenesis of PD is widely discussed. The investigation of Cu oxidation state inside single nerve cells from SN of PD and control cases may shed some new light on the role of this element in PD. The differences in Cu chemical state were investigated with the use of X-ray absorption near edge structure (XANES) spectroscopy. The least-square fitting method was applied for the analysis of XANES spectra. The comparison of the positions of white line, multiple scattering and pre-edge peak maximum at the energy scale did not reveal the existence of differences in Cu chemical state between PD and control samples. However, it was found that most of the Cu inside SN neurons occurs in tetrahedral environment and probably as Cu(II).

X-ray absorption near edge structure spectroscopy was applied in order to investigate differences in iron chemical state between the nerve cells of substantia nigra (SN) representing Parkinson's disease (PD) and those of control cases. Autopsy samples were cut using a cryotome, and were not fixed and not embedded in paraffin. The comparison of the absorption spectra near the iron K-edge measured in melanized neurons from SN of PD and control samples did not show significant differences in iron oxidation state. Measurements of inorganic reference materials containing iron in the second and third oxidation states indicate that most of the iron in all the nerve cell bodies examined was oxidized and occurred as trivalent ferric iron (Fe(3+)).

Synchrotron radiation based-Fourier transform infrared microspectroscopy was used for preliminary investigation of the chemical composition and morphologies of the human substantia nigra of brain between normal and Parkinson's diseased tissues. The studies were carried out for thin tissue sections, focusing more particularly on nerve cell bodies, that are affected in Parkinson's disease (PD). The major spectral differences between normal (control) and PD tissues were identified at the following vibrational frequencies: 2930, 2850, 1655, 1380, 1236, 1173 and 1086 cm(-1). The infrared imaging of these biochemical markers show that for control cases the protein and nucleic acids functional groups (bands at: approximately 3300, approximately 3100, approximately 1655, approximately 1545, approximately 1240, approximately 1080 cm(-1)) are located mainly in the cell body. The spatial distribution of the band at 1740 cm(-1) (ester carbonyl stretching band) is quite dissimilar to the others, while it exhibits a minimal concentration in the cell body area. Contrarily, in PD samples, no clear evidence of variation of any of the vibrational fingerprint between cell body and the surrounding was noticed. Moreover, decrease of protein to lipid ratio as well as increase of amide I/amide II ratio were observed for PD case. The preliminary results strengthen the hypothesis that PD is a multietiological disorder. Moreover, the reported results clearly indicate that, in addition to a distinct visual observation, the diseased nerve cells exhibits change of their biochemical composition. It suggests that disturbances of normal functioning of SN neurons appear before their morphological atrophy.

A possible cause of motor fluctuations in patients with Parkinson disease is the erratic drug absorption. In a randomized double-blind double-dummy study of melevodopa (levodopa methyl ester), a highly soluble levodopa pro-drug plus carbidopa (CHF 1512) was compared to a standard formulation of levodopa/carbidopa (LD/CD) in 74 fluctuating Parkinson disease patients. The first afternoon, LD/CD tablet was substituted with an equimolar dose of CHF 1512. The study lasted 4 weeks and was followed by an 8-week (optional) open phase. The primary efficacy variable was latency to "on." Patients randomized to receive CHF 1512 had a significative shorter latency to "on" than those randomized to LD/CD and a similar "on" duration. The safety profile of CHF 1512 was also comparable with LD/CD.

The aim of this study was to investigate the prevalence of the different causes of falling in Parkinson's disease (PD) and to evaluate the influence of falls on patients' quality of life (QoL). We recruited 60 PD patients (31 with falls, 29 without falls). We found that falls were caused by: unstable posture (29.0%), freezing or festination (25.8%), sudden loss of postural reflexes (toppling falls) (25.8%), co-existing neurological disorders (6.5%), cardiological disorders (6.5%), and symptomatic orthostatic hypotension (3.2%). Duration of the disease was longer, its stage more advanced, daily levodopa dosage higher, and the proportion of patients with abnormalities in the EEG apparently greater in the group with falls. The presence of falls was found to be a factor contributing to a multidirectional negative impact on patients' QoL. QoL also depended on impairment of cognitive function, daily dosage of levodopa, disease duration, disease progression, and sex. The results of this study underline the need to diagnose the causes of falls in order to institute appropriate treatment and to improve patients' QoL.

Gastrointestinal dysmotility in Parkinson's disease (PD) has been attributed in part to peripheral neurotoxine action. Our purpose was the evaluation of the salsolinol effect on intramuscular interstitial cells of Cajal (ICC), duodenal myoelectrical activity (DMA) and vagal afferent activity (VAA) in rats with experimental PD. Twenty rats were divided into 2 equal groups. Experimental PD was produced in one group by 3 weeks of the intraperitoneal salsolinol injections (50 mg/kg/day), whereas the 2-nd group served as control. DMA and VAA were recorded in both groups during fasting and stepwise--gastric distension (GD) of 10 ml. Subsequently fragments of duodenum were removed and intramuscular ICC were assessed as c-Kit antigen percentage in the duodenal muscular zone. Analyses of the fasting DMA and VAA recordings didn't reveal differences between the compared groups. During GD increase of DMA dominant frequency (p=0.04) and VAA frequency (p0.01) was observed in the controls whereas in the salsolinol group both parameters remained unchanged. Image analysis of duodenum revealed decreased c-Kit expression in the salsolinol-injected animals (p=0.05). The results of our study may suggest the direct effect of salsolinol on both ICC and neuronal pathways of gastro-duodenal reflexes.

Selective toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a parkinsonism inducing compound, is well known to be related to an uptake of its active metabolite MPP+ into dopaminergic neurons by dopamine transporter (DAT). The aim of the present study was to examine whether paraquat, a commonly used herbicide, which is an 1-methyl-4-phenyl-pyridinium ion (MPP+) analogue, affects DAT in vivo in rats. Paraquat administered at a dose of 10 mg/kg ip decreased the binding of [3H]GBR 12,935 to DAT measured by quantitative autoradiography in the dorsal and ventral caudate-putamen, but not in the substantia nigra pars compacta. Moreover, this compound increased the level of 3-methoxytyramine (3-MT) and 3-MT/dopamine ratio in the anterior and posterior caudate-putamen measured by HPLC with electrochemical detection. No other alterations in the levels of dopamine and its metabolites were found in the caudate-putamen and substantia nigra. The present study seems to suggest that systemic paraquat administration affects striatal DAT and dopamine metabolism in the nigrostriatal neurons in rats which may be crucial for its neurotoxic effects on dopaminergic neurons.

Genetic contribution to the etiology of Parkinson's disease (PD) is generally accepted based on the studies of the familial form of the disease and progress in molecular genetic techniques. To date, specific mutations have been identified in five separate genes and several chromosomal loci have been linked for different forms of familial parkinsonism. The discovery of alpha-synuclein, ubiquitin C-terminal hydrolase, parkin, tau and DJ-1 mutations and analysis of the biochemical and molecular properties of these gene products point to the critical role of protein aggregation in dopaminergic neurons of the substantia nigra as the basic mechanism leading to neurodegeneration also in sporadic form of the disease. Lewy bodies, even in sporadic PD, contain some of these gene products, particularly abundant fibrillar alpha-synuclein. Studies of familial parkinsonism provide evidence that PD is genetically heterogeneous. Evidence elucidated from genetic studies in PD suggests that parkinsonism is a complex disorder in which multiple gene-gene and gene-environment interactions play a critical role in the development of the disease and phenotypic variability. Further genetic studies in familial parkinsonism will enhance our knowledge of pathogenesis of PD and allow the development of neuroprotective treatments of PD and perhaps other forms of parkinsonism as well.

Objectives – It has been reported that the prevalance of parkinsonism might be associated with exposure to whooping cough. Methods – Examination of levels of antibodies against Bordetella pertussis in serum using enzyme-linked immunosorbent assay (ELISA) tests [presence of IgG antibodies against filamentous hemagglutinin and pertussis toxin (PT)] were performed in 81 persons (including 45 patients with controls) (age-matched groups). Results – Positive results were found in patients with Parkinson's disease (PD), patients with other non-inflammatory diseases, and controls (about 40–45% in each group). A detailed examination of separate responses (IgG and IgA antibodies against PT, and a whole cell immune response) and of the serum level of immunoglobulins IgG, IgA and IgM was also performed. Conclusion – Our results demonstrate numerous cases of whooping cough serum antibodies among the adult population (also among PD patients). The results of our research, i.e. a common occurrence of Bordetella pertussis infection do not provide evidence of relationship between PD and the above-mentioned infection.

The following article presents current views on the possibility of pharmacological treatment of Parkinson's disease (PD). Research conducted on drugs with potentially neuroprotective effects has changed the way we viewed the treatment of early stages of PD. Beginning treatment with the application of dopamine agonists decreases the risk of the occurrence of motor complications, particularly high with young individuals. The treatment of advanced stages of the disease currently requires the application of levodopa combined with other medicines, such as dopamine agonists or catechol-O-methyl transferase (COMT) inhibitors. Selecting treatment options should be individualized for each patient; it should take into account the variability of the clinical picture dependent on the progression of the disease, and the possibility of the occurrence of undesirable adverse effects of the drugs prescribed.

Surgical treatment of Parkinson's disease (PD) is indicated in patients with severe neurological symptoms (tremor, bradykinesia, rigidity)--who do not benefit from nor tolerate pharmacological therapy. Surgery for PD modifies the motor system function by lesioning or electrostimulation of thalamic, pallidal or subthalamic nuclei. The technological progress together with refined CNS monitoring enabled wider application of deep brain stimulation (DBS). The efficacy of DBS is comparable with lesioning techniques (thalamotomy or pallidotomy) however bears less adverse effects. Both lesioning and DBS are generally well tolerated by patients. The side effects are mostly transient and neurological complications, if occur, usually do not affect quality of patient's life. Unfortunately, the modern surgery for PD is still very expensive and demanding for a large team of specialists and high technology.

Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) is a congenital degenerative disease of the central nervous system. Molecular genetics studies have indicated the presence of 26 various mutations of the tau protein gene. At present 61 families with this syndrome are known. The clinical criteria proposed in this paper were developed on the grounds of the author's own research as well as detailed review of the literature. The criteria include;--clinical symptoms: personality and behavior disorders, Parkinsonism rather resistant to treatment with Levodopa less frequently also speech disorders and epilepsy,--an early onset and rapid progression of the disease,--positive family history,--heterogeneity of clinical symptoms both among patients within the same family and among families with the same mutation,--heterogeneity of the clinical picture depending on the type of mutation. Although FTDP-17 is and extremely rare clinical syndrome, it is noted all over the world. In Poland nobody has been diagnosed with this condition yet. The aim of this paper is to acquaint the readers of Neurologia i Neurochirurgia Polska with the FTDP-17. The syndrome has considerably contributed to our understanding of pathogenesis of many sporadic degenerative diseases of the brain, including such frequent conditions as Alzheimer's disease, Pick's disease the the Steel-Richardson-Olszewski syndrome, corticobasal degeneration, and other ones. Undoubtedly further research into the FTDP-17 will contribute to the development of a successful treatment for these devastating degenerative diseases of the c.n.s.

Autonomic dysfunction in idiopathic Parkinson's disease (IPD) is common and occurs in 70% of patients. The aim of the study was to evaluate autonomic mechanisms regulating cardiovascular system during tilt up test in IPD patients. The examination was performed in 35 patients with IPD (26 male and 9 female, mean age 60 +/- 9) and matched with gender and age 35 controls subjects (healthy volunteers, mean age 59 +/- 9). Patients were divided into two groups: group I--early stage of disease (n = 20) and group II--advanced stage of the disease (n = 15). The tilt test in IPD patients and in the control group lasted 3 minutes. In both groups tilt test was performed with a head-up tilt position of 60 degrees (tilt table Manumed, Netherlands). In both groups 30:15 ratio were lower than in the control group 1.03 +/- 0.08, 0.97 +/- 0.09 v 1.23 +/- 0.1 respectively (p = 0.001). In the second group the heart-rate variability after the tilt test was lower 6.2 +/- 4/min than in the control group 10.2 +/- +/- 1.9/min and group I 8.8 +/- 4/min (p = 0.01). The decrease of the systolic pressure in response to the tilt test was the highest in group II (16 +/- 14 mmHg), in the control group 4 +/- 7 mmHg, in group I 13 +/- 11 mmHg (p = 0.001). Ortostatic hypotension in IPD occurs in 36% of patients in an early stage and in 47% of patients in an advanced stage of the disease. The use of the tilt test enables the early diagnosis of cardiovascular disturbances in IPD.

The assessment of the levels of IgG antibodies against Bordetella pertussis in serum using ELISA test was performed in 59 patients (including 30 patients with Parkinson's disease--PD, 15 patients with other non-inflammatory neurological diseases, and 14 controls). The average age in the groups was 64.0, 64.4, and 58.7 years, respectively. Positive results were found in 17/30 patients with PD, 8/15 subjects with other non-inflammatory neurological diseases and in 7/14 controls. The above results are surprising and demonstrate a high incidence of subclinical whooping cough among the adult population. No statistically significant difference has been found between patients with Parkinson's disease and patients with other neurological diseases. A tendency is observed for a higher percentage of negative results among controls in comparison with patients with Parkinson's disease and other non-inflammatory neurological diseases.

The aim of the investigations was to find to what extent neurodegenerative changes develop in the brains of patients with no clinical symptoms of dementia, parkinsonism and other neurodegenerative diseases. It has been found that neurodegenerative pathology, as evaluated using immunohistochemical methods with monoclonal antibodies (Mab) against ubiquitin, tau protein, alpha-synuclein, and beta-amyloid, occurs more frequently than the presence of Lewy bodies. The degenerative changes involved the neurones of cerebral and cerebellar cortex, basal ganglia and medulla oblongata, where neurofibrillary tangles were found. Mab positive materials have been found in the cytoplasm of the cell body and the cell processes (axons) of the neurones and glial cells. Senile plaques, beta-amyloid positive, were frequently noted.

Falls in Parkinson's disease may pose a significant threat for patients. This is not only a clinical problem, but also an economic one. The effects of falls may cause deterioration of the quality of life for both patients and their caretakers. The causes of falls are not clinically uniform: the falls are caused by various factors and require a differential diagnosis. The purpose of this paper is to analyse the above mentioned causes, as well as to draw clinicians' attention to the possibility of effective therapy for certain disorders that cause such falls in patients with Parkinson's disease. 51 patients with recognized Parkinson's disease were examined, including 25 persons who reported falls that had occurred within the past 6 months and 26 persons who had no falls. In both groups there were patients with different types of the disease (tremulous, akinetic-hipertonic and mixed). The clinical status of the patients was assessed using the Hoehn and Yahr scale. In each patient Schellong test and EEG examinations were performed. It has been established that the occurrence of falls is related to the duration of the disease (on average 9.6 years in the group with falls versus 6.2 years in the group without falls) and the daily levodopa dosage (on average 806.0 mg in the group with falls versus 499.0 mg in the group without falls). The proportion of patients with abnormalities in the EEG (revealed mainly as slowing of EEG background activity) was notably higher in the group with falls. The comparison of such groups from the point of view of sex, age, stage of the disease and the occurrence of asymptomatic orthostatic hypotension did not reveal any statistically significant differences. The analysis of the causes of falls in the examined patients revealed that in 8 cases they fell due to unstable posture, 4--due to freezing or festination, 1--due to symptomatic orthostatic hypotension, 1--due to co-existing neurological disorders, 2--due to the heart arrhythmia (requiring implantation of pacemaker), in 8 persons--due to toppling falls and in 1 patients the falls could not be classified.

Urinary dysfunction in idiopathic Parkinson's disease (IPD) has already been described, however its incidence, urodynamic pattern, dependence on the severity of parkinsonism as well as improvement with levodopa treatment are not exactly known. The aim of the study was to evaluate the frequency of urinary disturbances in patients with idiopathic Parkinson's disease and their relationship to treatment with levodopa. The investigation was carried out on 41 IPD patients aged 37-84 (mean 61.6) years. The neurological examination, including evaluation of parkinsonism according to UP-DRS scale was conducted together with the urological tests, including uroflowmetry and cystometry. Patients with infection of the urinary tract and with prostate hypertrophy were excluded from the study. 32 (78%) patients had urinary symptoms: frequency in 27 cases (65%), urgency in 9 cases (21%), urge incontinence in 1 case and dysuria in 1 case. Disorders in urodynamic examination were found in 26 cases (63%); they were: detrusor hyperactivity in 21 cases (51%), prolonged time of micturition in 18 cases (44%) and decrease of maximum flow rate in 19 cases (46%). Detrusor hyperactivity was more frequent in patients with extended parkinsonian motor signs. The results of the examination indicate frequent urinary disturbances (70%) in IPD, which improve during treatment with increased dose of levodopa.

TENS became widely accepted method of treatment pain syndromes in clinical practice. Lately has been shown that its affects also gastrointestinal tract by releasing NANC neurotransmitter VIP. The aim of this study was to evaluate the effects of TENS on gastric myoelectric activities measured by electrogastrography (EGG). Eighteen healthy men (mean age 23 +/- 1.7) were included in the study. Healthy volunteers were divided on 3 groups each 6 persons: with normogastria occurring at 94.5 +/- 7% of recording time--group A, with predominant bradygastria (36.6 +/- 14%)--group B and with tachygastria (33 +/- 14%)--group C. In fasted condition EGG (Synectics, Sweden) was recorded with skin electrodes. TENS 15 min was performed with use of Sinus 5 stimulator (6 Hz, 0.1 ms duration, intensities 10-20 mA, Zimmer, Germany). Stimulating electrodes were placed on non-dominant hand.None of the subjects during TENS reported any side effects or symptoms, during the all studies. In group A in the fasting recordings, after TENS, an decrease of the normal values in the range 2-4 cpm down to 78.5 +/- 21% of recording time (p = 0.03) occurred. The dominant frequency in the bradygastric region increased up to 17.7 +/- 7% of the total recording. In group B TENS decreased bradygastria level from 36.6 +/- 14% to 20.6 +/- 15% (p = 0.02). TENS did not significantly affect tachygastria in group C. Amplitude of the EGG signal after TENS in group B and C increased by 40 and 150% respectively (p0.05). Significant decrease of the amplitude was observed in group A (13%). We conclude that TENS by activating centrally mediated somato-visceral reflexes affects gastric electrical activity. Our results suggest that TENS may be useful in treatment of the gastric dysrhythmia.

A long lasting alcohol intake causes, amongst numerous systemic damages, also the autonomic nervous system (ANS) dysfunction, which causes the autonomic heart rate regulation disorders. The aim of the study was to evaluate the autonomic regulation of the circulation in chronic alcoholism. Seventeen alcoholics, 24-55 years of age (mean 43 +/- 5.2 years) were examined. They have been abstainers for 2-6 years. The cardiac ANS function was evaluated using the HRV measurement. The HRV was registered using V6 EKG lead. The recording was performed through the 15 min of resting conditions and 5 min of the deep breathing test. A group containing healthy volunteers, matched for age and gender, for the comparison of the HRV results was recruited. In the examined group, during the resting conditions, the significant RR period changes weren't observed (999.7 +/- 139.2 vs. 967 +/- 144.9; p0.05). The nonsignificant lower values of the spectral analysis parameters of HRV: LF (954.1 +/- 1162.6 vs. 1456.4 +/- 1327.1; p0.05) and HF (676.4 +/- 414.2 vs. 1557 +/- 1854.4; p0.05) and LF/HF ratio (1.5 +/- 1.14 vs. 1.38 +/- 1.28; p0.05) were also noticed. In response to the DB test, the mean value of the RR period wasn't significantly changed (921.4 +/- 152.3 vs. 930.6 +/- 137.8; p0.05). In DB test the significant decrease of LF (3465.8 +/- 2750.1 vs. 11558.6 +/- 7902.5; p0.001) and HF (406.1 +/- 366.8 vs. 1665 +/- 1757.1; p0.01) was observed. No significant change of LF/HF mean ratio (11.6 +/- 6.97 vs. 14.7 +/- 11.6; p0.05) was noticed. The results of our study indicate on the maintenance of the HRV disorders in chronic alcoholics, during the abstinence.

This study was designed to evaluate gastric myoelectrical and mechanical activities in idiopathic Parkinson's disease (IPD) patients. Twenty patients with IPD (14 male and 6 female, mean age 42 +/- 9 years) were studied. Patients were divided into two groups: group A--early stage of disease (no. = 6) and group B--advanced IPD (no. = 14). Electrogastrography (EGG) was performed in fasting and postprandial conditions (Synectics system). The cross-sectional area of the gastric antrum was measured by sonography (Hitachi EUB-240). The antral area in fasting conditions was 2.1 +/- 0.4 and 4.2 +/- 1.2 cm2 and gastric emptying was 75 +/- 5 and 125 +/- 12 min in groups A and B respectively. EGG showed dysrhythmias (range 1-6 cycles per minute) in about 75% of both groups of IPD patients without increase in signal amplitude after a meal. Our results suggest that gastric motility is particularly impaired in patients with advanced IPD. It may be caused by the primary degenerative process in the autonomic nervous system of the gut.

Two cases that fulfil the clinical and neuropathological criteria of acute hemorrhagic encephalitis are described. Histological examination revealed additionally focal changes in the white matter characteristic for neuroaxonal dystrophy. The differences in the clinical course and morphological picture observed in both cases are discussed.

Salsolinol is one of the dopamine-derived tetrahydroisoquinolines, supposed to be a potent dopaminergic neurotoxin, similar to MPTP. Its systemic administration induced parkinsonism in monkeys. The aim of the study was to compare the concentration of salsolinol and the metabolite of L-dopa, 3-O-MD, and the metabolite of dopamine, HVA, in the cerebrospinal fluid of patients with different degrees of parkinsonism, treated or nontreated with l-dopa. Lumbar CSF was obtained from 26 patients with Parkinson's disease (15 early and 11 advanced parkinsonism) and from six healthy controls. The presence of salsolinol, HVA and 3-O-MD was assayed with a sensitive HPLC method employing C18 (Hypersil BDS) column. The analysis of the results demonstrated that the concentration of salsolinol was related to the degree of parkinsonism but not affected by l-dopa treatment. In contrast, HVA and 3-O-MD were significantly elevated in patients receiving l-dopa but did not correlate with the severity of parkinsonism. The results suggest that salsolinol in the cerebrospinal fluid does not originate from exogenous l-dopa and its elevation in cerebrospinal fluid may be an indicator of the advancement of parkinsonism.

The study was carried out on the lumbar cerebrospinal fluid (CSF) samples taken from nonparkinsonian, early parkinsonian, and advanced parkinsonian patients. Some patients showed dementia, and some were treated with L-dopa. In the samples, salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) was assayed with a newly developed sensitive high-performance liquid chromatography (HPLC) method; 3-O-methyldopa (3-O-MD) and homovanillic acid (HVA) were also assayed by HPLC. CSF salsolinol concentrations were significantly enhanced in patients with signs of dementia, regardless of the degree of parkinsonism, and were not affected by L-dopa treatment; HVA and, particularly, 3-O-MD levels were elevated in patients receiving L-dopa. The strong association of CSF salsolinol level with dementia, but not with L-dopa treatment suggests that salsolinol does not originate from L-dopa metabolism, and that its elevation is an indicator of neurodegenerative processes resulting in damage to brain areas mediating cognitive functions. We found no correlation between the advancement of parkinsonism and the concentrations of 3-O-MD and HVA.

It is well recognized that autonomic dysfunction are common in Parkinson's disease (PD). Fourteen patients with early PD and 8 patients with advanced PD aged from 38-71 were investigated. Heart rate variability at rest differ significantly between patients with advanced PD and age-matched controls. Cardiovascular autonomic dysfunction in PD mainly affects parasympathetic but also sympathetic system, and occurs only in advanced cases. Heart rate variability is a useful non-invasive test to assess autonomic dysfunction in PD.

A case of 56-year-old male with sarcomatosis of leptomeninges as well as of the brain and spinal cord coexisting with Recklinghausen's neurofibromatosis is presented. Neurological and neurophysiological symptoms of the disease resembled those of amyotrophic lateral sclerosis (ALS). Patient died 7 months after onset of the initial symptoms. The post-mortem examination revealed neoplastic infiltration of the leptomeninges of brain and spinal cord. Histologically sarcomatosis of the leptomeninges was diagnosed and immunohistochemical analysis of the neoplastic infiltrates can indicate fibrohistiocytic origin of the neoplasm, suggesting also a probable contribution of perineurial cells in the pathogenesis of the tumor. On the grounds of the performed immunohistochemical study together with a review of the literature, the differential diagnosis of malignant mesenchymal tumors of the CNS is discussed with a special regard to their histogenesis.