bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethosuximide and tremor in Parkinson's disease: A pilot study
Authors: Pourcher E. , Gomez‐Mancilla B. , Bédard P. J.
Published: December 2004

Following the demonstration of an antitremor effect of ethosuximide in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) monkey model, we have tested the effect of this drug in 10 patients with typical parkinsonian tremor. Six patients suffered from Parkinson's disease with prominent, relatively drug‐resistant rest tremor. The other four patients had a druginduced parkinsonian tremor due to neuroleptic agents taken for a psychiatric condition. Five of the six parkinsonian patients and three of the four psychiatric patients reported within a few days a marked and intolerable exacerbation of their tremor. One patient in each group was improved, and this improvement was verified in repeated examinations. Thus, for unknown reasons, the effect of ethosuximide was not as predicted by the monkey model. Among possible explanations is the fact that we had chosen patients with drug‐resistant tremor.
Exposure to well water and pesticides in Parkinson's disease: A case‐control study in the madrid area
Authors: Jiménez‐Jiménez Félix Javier , Mateo Dolores , Giménez‐Roldán Santiago
Published: December 2004

Past exposure to well water and pesticides was assessed in 128 unselected Parkinson's disease (PD) patients and 256 age and sex‐matched controls. All were residents in a defined urban area of Madrid, Spain. In keeping with other reports, we found that exposure to well water might be a factor associated with the likelihood of developing PD, though only prolonged exposures of 30 years or longer were significantly different between PD and controls (p < 0.02). In contrast, past exposure to pesticides did not appear to be associated with an increased risk of developing PD. Prolonged well water drinking antedating the development of PD was not associated with early onset of the disease, nor did such cases progress to greater disability. Future casecontrol studies addressing prolonged well water consumption as a risk factor in PD should look for differences in the content of substances other than pesticides in the water as determined by the source of water to which patients may have been specifically exposed.
Interlimb coordination in Parkinson's disease
Authors: Lazarus Jo‐Anne C. , Stelmach George E.
Published: December 2004

This study examined the degree to which Parkinson's disease (PD) patients could “spatially link” the upper limbs to facilitate the performance of bimanual simultaneous movements. Six right‐handed PD patients, and seven normal age‐ and sex‐matched controls performed three different tasks: (a) an isotonic elbow flexion as rapidly as possible through an angle of 30°; (b) an isometric contraction of the flexor muscles at the elbow joint to 40% and 60% of maximal volitional force (MVF) for a period of 5 s; (c) an isometric contraction for 2.5 s with one limb, then simultaneously performing an isotonic flexion with the contralateral limb while maintaining the isometric contraction for 2.5 s more. As expected, PD patients were significantly slower in performing the isotonic movement and produced lower peak velocities than the controls. More importantly, the two groups were differentially affected during the bimanual condition. In normals, movement time decreased and peak velocity increased in the bimanual condition. In contrast, PD patients showed increased movement times and sometimes decreased peak velocities in the bimanual condition. The results suggest that normal subjects utilize bilateral outflow to symmetrical muscle groups to synchronize the two limbs in the bimanual task, whereas PD patients dissociate the two limbs.
Postvaccinal parkinsonism
Authors: Alves Rosana S. C. , Barbosa Egberto R. , Scaff Milberto
Published: December 2004

A 5‐year‐old boy, with a history of fever beginning 15 days after a vaccination for measles, developed a rigid‐akinetic syndrome 3 days after the fever began. A spinal tap obtained 1 week after the onset of fever showed pleocytosis with a monocellular pattern. A CT scan of the head and EEG did not disclose any abnormality. An MRI performed 3 months after the event, however, showed clear‐cut evidence of bilateral substantia nigra lesions, suggesting secondary gliosis. The response to levodopa was good, but adverse reactions appeared early. The child is now 7 years old. Bromocriptine, deprenyl, and levodopa have produced a remarkable improvement of the parkinsonian features.
Hemifacial spasm due to peripheral injury of facial nerve: A neuclear syndrome?
Authors: Martinelli P. , Giuliani S. , Ippoliti M.
Published: December 2004

Four cases of hemifacial spasm (HFS) are reported. The spasm followed a few months after injury to a peripheral branch of the seventh nerve. An EMG examination of facial muscles disclosed the typical finding of HFS: spontaneous activity, paradoxical cocontraction, and diffusion of spontaneous or provoked blinking. A nuclear involvement, secondary to the nerve lesion, is the most likely pathophysiological explanation for similar cases of HFS.
Hemiballism and tremor due to ependymal cyst
Authors: Bejar Jose M. , Kepes John , Koller William C.
Published: December 2004

A 21‐year‐old woman was admitted with right hemiballism and tremor. She had tremor since the age of 6 years. At age 12, an intracerebral, left paraventricular space‐occupying lesion was found and treated with 4,500 rads. Increasing tremor was associated with mass enlargement. By age 20, there was insidious presentation of right hemiballism. At age 21, she had craniotomy and a large septate cyst was opened and drained. Biopsy of the cyst wall revealed that it was consistent with ependymal cyst. Postoperatively the hemiballism resolved and the tremor improved. This case is unusual due to the presentation of hemiballism caused by ependymal cyst.
The possible role of iron in the etiopathology of parkinson's disease
Authors: Youdim M. B. H. , Ben‐Shachar D. , Riederer P.
Published: December 2004

The identification of 6‐ hydroxydopamine (6‐ OHDA) and N‐ methyl‐ 4‐ phenyl‐ 1, 2, 3, 6‐ tetrahydropyridine (MPTP) as dopaminergic neurotoxins that can induce parkinsonism in humans and animals has contributed to a better understanding of Parkinson's disease (PD). Although the involvement of similar neurotoxins has been implicated in PD, the etiology of the disease remains obscure. However, the recently described pathology of PD supports the view for a state of oxidative stress in the substantia nigra (SN), resulting as a consequence of the selective accumulation of iron in SN zone compacta and within the melanized dopamine neurons. Whether iron is directly involved cannot be ascertained. Nevertheless, the biochemical changes due to oxidative stress resulting from tisue iron overload (siderosis) are similar to those now being identified in parkinsonian SN. These include the reduction of mitochondrial electron transport, complex I and III activities, glutathione peroxidase activity, glutathione (GSH) ascorbate, calcium‐ binding protein, and superoxide dismutase and increase of basal lipid peroxidation and deposition of iron. The participation of iron‐ induced oxygen free radicals in the process of nigrostriatal dopamine neuron degeneration is strengthened by recent studies in which the neurotoxicity of 6‐ OHDA has been linked to the release of iron from its binding sites in ferritin. This is further supported by experiments with the prototypeiron chelator, desferrioxamine (Desferal), a free‐ radical inhibitor, which protects against 6‐ OHDA‐ induced lesions in the rat. Indeed, intranigral iron injection in rats produces a selective lesioning of dopamine neurons, resulting in a behavioral and biochemical parkinsonism.
Cocaine‐related movement disorders
Authors: Cardoso Francisco E. C. , Jankovic Joseph
Published: December 2004

We describe four patients, two with Tourette's syndrome, one with the combination of idiopathic dystonia and essential‐like tremor, and one with tardive dystonia, who noted marked exacerbation of their movement disorders after exposure to cocaine. These patients provide support for the hypothesis that dopaminergic preponderance plays an important role in the pathogenesis of certain hyperkinetic movement disorders. Cocaine should be regarded as an important cause or precipitant of hyperkinetic movement disorders.
Treatment of parkinson's disease with the partial dopamine agonist EMD 49980
Authors: Bravi Daniele , Davis Thomas L. , Mouradian M. Maral , Chase Thomas N.
Published: December 2004

The motor effects of the partial dopamine agonist EMD 49980 were evaluated in parkinsonian patients under controlled conditions. EMD 49980 monotherapy resulted in a mild improvement in parkinsonian symptoms, but when co‐administered with levodopa, had no significant effect on dyskinesias or on the antiparkinsonian effect of the dopamine precursor. These results suggest that EMD 49980 exerts a net weak dopamine agonist effect but fails to ameliorate levodopa‐induced dyskinesias.
Reflex blepharospasm associated with bilateral basal ganglia lesion
Authors: Larumbe R. , Vaamonde J. , Artieda J. , Zubieta J. L. , Obeso J. A.
Published: December 2004

A patient with a bilateral striatal lesion secondary to anoxia presented reflex blepharospasm associated with parkinsonism and dystonia in the limbs. The blink reflex excitability curve was enhanced and the R‐2 response prolonged as in patients with essential blepharospasm. The findings in this patient support the notion that blepharospasm may be secondary to basal ganglia dysfunction through abnormal facilitation of reticular formation neurons controlling facial nucleus motoneuron excitability.
Stereotyped hand clasping: An unusual tardive movement disorder
Authors: Kaneko Kiyotoshi , Yuasa Tatsuhiko , Miyatake Tadashi , Tsuji Shoji
Published: December 2004

We report an 83‐year‐old woman with vascular parkinsonism who presented with stereotyped rhythmical hand‐clasping movements after 18 months exposure to neuroleptics. Although stereotypical rhythmical orolinguomasticatory and limb movements are the most common tardive dyskinesia in the elderly, we feel this woman's hand clasping represents another unusual expression of a tardive movement disorder.
Primary progressive freezing gait
Authors: Achiron A. , Ziv I. , Goren M. , Goldberg H. , Zoldan Y. , Sroka H. , Melamed E.
Published: December 2004

Freezing gait is an incapacitating symptom often observed in patients with Parkinson's disease. It has been less frequently described in association with multi‐infarct state, multisystem atrophies, and normotensive hydrocephalus. In our movement disorder clinic, we have diagnosed (and followed up to 3 years; median, 16 months), 18 patients in whom progressive freezing gait was the sole neurological dysfunction. These 15 men and 3 women (aged 60−82 years; 74 ± 6) were subjected to an extensive neurological workup that included clinical evaluation, videotaping for grading of gait disability, comprehensive blood and cerebrospinal fluid (CSF) analysis, and brain computed tomography (CT) and magnetic resonance imaging (MRI). Mean disease duration was 2.5 ± 1.9 years (range, 0.5−6). Neurological examination disclosed freezing gait, often associated with varying degrees of postural instability. The degree of freezing gait ranged from sudden motor blocks only when confronted with obstacles to severe disability with total inability to start walking requiring a walker, massive assistance, or a wheelchair. However, patients could mimic gait movements with absolutely no freezing when seated or lying prone, and most of them could overcome arrests by the “walking‐over‐lines” maneuver. Otherwise, neurological examination was normal with no signs of bradykinesia, rigidity, or tremor. Blood chemistry and CSF analysis were normal. Brain CT and MRI were normal or showed mild cortical atrophy in 12 and putative lacunes in 6 patients. Therapy with levodopa or dopamine agonists was ineffective. During the follow‐up period, a gradual progression of the freezing gait was observed. However, it remained unaccompanied by any other neurological findings. We therefore conclude that primary progressive freezing gait should be recognized as a distinct neurological entity, unique in its clinical presentation and natural course. The lack of response to levodopa raises the possibility that nondopaminergic pathways might be involved.
Quantification of postural sway patterns in tardive dyskinesia
Authors: van Emmerik R. E. A. , Sprague R. L. , Newell K. M.
Published: December 2004

An assessment was made of the orientation and variability in postural center of pressure patterns in individuals with tardive dyskinesia (TD) and/or developmental disability during quiet standing. Postural patterns were compared and contrasted between four groups of individuals: those with (a) TD and developmentally disabled (severely and profoundly retarded); (b) developmental disability only; (c) TD but of normal intelligence; and (d) a healthy control group. The center of pressure displacements were derived from the lateral, vertical, and anterior‐posterior force and moment components of force platform measurements. Analyses demonstrated that individuals with TD in combination with developmental disability had a different center of pressure orientation and variability compared to healthy individuals and individuals suffering only from developmental disability or TD. The center of pressure pattern in the developmentally disabled TD group was characterized by a more prominent lateral orientation, whereas in the other three groups, it had a more predominant anterior‐posterior orientation. In addition, the variability in these orientation components was much smaller in the developmentally disabled TD group, indicating a more regular pattern of sway in the center of pressure during quiet standing in these individuals. These findings show that assessments of postural center of pressure profile orientation and variability may be useful indicators for investigating TD, especially in distinguishing between developmental disability and TD.
Persistent movement disorders induced by buspirone
Authors: Lewitt Peter A. , Walters Arthur , Hening Wayne , McHale Denise
Published: December 2004

Buspirone, an azospirone compound, is a nonsedative anxiolytic that has achieved wide usage since its introduction in 1987. Although relatively free of side‐effects, there have been several instances of dyskinesia and dystonia associated with the use of buspirone. We report two patients with persistent movement disorders that developed after prolonged treatment with the drug. One patient developed a lasting problem of cervical–cranial dystonia and tremors after treatment with buspirone at a dosage of 40 mg/day for several weeks. Another, receiving 30 mg/day for 6 weeks, experinced an exacerbation of preexisting spasmodic torticollis and tardive dyskinesia as well as the onset of involuntary phonations. As shown by these and other examples, buspirone poses the risk for inducing or exacerbating several types of movement disorders.
Reversible striatal hypermetabolism in a case of sydenham's chorea
Authors: Goldman Serge , Amrom Dina , Szliwowski Henri B. , Detemmerman Dominique , Goldman Sylvie , Bidaut Luc M. , Stanus Etienne , Luxen André
Published: December 2004

We studied a 10‐year‐old girl with Sydenham's chorea (SC) using positron emission tomography (PET) with fluorodeoxyglucose (FDG). Choreic movements involved the head and the left side of her body. PET showed increased glucose metabolism in the right caudate nucleus and putamen. Three months after complete recovery, striatal glucose metabolism had returned to normal in the caudate nucleus. In the right putamen, glucose metabolism had decreased compared to that in the first study but remained elevated compared to that of normal young adults. We propose that the transient striatal hypermetabolism may have been due to increased afferent inputs to the striatum as a consequence of striatal or subthalamic nucleus dysfunction.
Cerebellar ataxia in ataxic hemiparesis? A kinematic and EMG analysis
Authors: Wild Barbara , Dichgans Johannes
Published: December 2004

It has recently been proposed that the ataxia in ataxic hemiparesis is a clumsiness common to all patients with hemiparesis and not indicative of any involvement of corticopontocerebellar or cerebellocortical pathways. In disagreement with this view, we report here that a patient with ataxic hemiparesis, following a lesion of the corona radiata, showed the disorders in kinematic and electromyographic (EMG) parameters of goal‐directed movements that have recently been demonstrated to be characteristic of patients with cerebellar lesions. This suggests involvement of corticopontocerebellar or cerebellocortical pathways in ataxic hemiparesis.
Proximal and distal reaction times (RTs) are not differentially affected in parkinson's disease
Authors: Schugens M. M. , Daum I. , Richter S. , Scholz E. , Canavan A. G. M.
Published: December 2004

The hypothesis was tested that proximal and distal reaction times (RTs) might be differentially affected in Parkinson's disease (PD). Twelve patients with PD were compared with 12 age‐matched healthy controls on tests of finger‐, hand‐, leg‐, and torso‐RTs. Patients were significantly slower in initiating all movements and were slower in executing all movements except for the leg (stepping) task. Choice‐ versus simple‐RTs were also not differentially affected in the PD group. In the healthy subjects, age was significantly positively correlated with response initiation times (RITs) but not with movement times (MTs).
Orobuccal dyskinesia associated with trihexyphenidyl therapy in a patient with parkinson's disease
Authors: Hauser Robert A. , Olanow C. W.
Published: December 2004

Dyskinesia is a common adverse effect complicating chronic dopaminergic therapy for Parkinson's disease. Movements are frequently choreic in nature and have been ascribed to overstimulation of “supersensitive” striatal postsynaptic dopamine receptors. Anticholinergic medications, despite some clinical efficacy in Parkinson's disease, have rarely been reported to cause dyskinesia. We report a patient with Parkinson's disease who developed orobuccal dyskinesia while being treated with trihexyphenidyl (Artane). Dyskinesia was observed following the introduction of trihexyphenidyl, resolved with its discontinuation, and reappeared with its reinstitution. Carbidopa‐levodopa (Sinemet) alone did not cause dyskinesia but augmented dyskinesia associated with trihexyphenidyl.
Levodopa‐induced dyskinesias in Parkinson's disease phenomenology and pathophysiology
Authors: Marconi Roberto , Lefebvre‐Caparros Dominique , Bonnet Anne‐Marie , Vidailhet Marie , Dubois Bruno , Agid Yves
Published: December 2004

The aim of this study was to provide further insight into the phenomenology and pathophysiology of monophasic and biphasic dyskinesias induced by levodopa in Parkinson's disease. For this purpose, the type, localization, severity, and timing of dyskinesias were evaluated in 15 parkinsonian patients in relation to motor disability after administration of levodopa using a video‐electromyographic recording device. Foot‐dystonia, myoclonus, and akathisia were observed in most patients. The dyskinesias started in the foot, usually on the side most affected by the disease, and spread in an “ascending wave” to the contralateral side, the trunk, and upper extremities. In a few patients, onset was axial, spreading almost instantaneously to all limbs. The dyskinesias were dystonic and ballistic at the start, and became increasingly choreic as they attained the upper limbs. Their intensity was maximal in the lower limbs, then progressively decreased, while increasing in upper limbs and head. The results indicate that there is no strict dichotomy between biphasic and monophasic dyskinesias. In other words, there is a “continuum” between the first dyskinesias and those observed during the period of maximal clinical improvement. These dyskinesias can also appear in reverse order, as if there were an “oscillator” determining a sequence of alternating patterns.
A multicenter double‐blind placebo‐controlled trial of pergolide as an adjunct to sinemet® in Parkinson's disease
Authors: Olanow C. W. , Fahn S. , Muenter M. , Klawans H. , Hurtig H. , Stern M. , Shoulson I. , Kurlan R. , Grimes J. D. , Jankovic J. , Hoehn M. , Markham C. H. , Duvisin R. , Reinmuth O. , Leonard H. A. , Ahlskog E. , Feldman R. , Hershey L. , Yahr M. D.
Published: December 2004

Three hundred and seventy‐six subjects with advanced Parkinson's disease participated in a prospective, double‐blind placebo‐controlled study of the dopamine agonist pergolide mesylate as an adjunct to Sinemet®. At 6 months, patients randomized to pergolide had a statistically singnificant improvement in total Parkinson's score, scores of activities of daily living, motor function, number of “off” hours, Hoehn and Yahr stage, and numerous parameters of parkinsonian function including bradykinesia, rigidity, gait, and dexterity. This benefit was obtained with the addition of a mean dose of 2.94 mg of pergolide, which permitted a 24.7% reduction in dose of levodopa. Adverse reactions were, for the most part, mild, reversible, and not of major clinical significance. No significant cardiac or electrocardiographic abnormalities were detected. This study demonstrates that pergolide mesylate, as an adjunct to levodopa, is an effective antiparkinsonian agent that provides clinical improvement while permitting a reduction in levodopa dose.
Visual control of arm movement in Parkinson's disease
Authors: Klockgether Thomas , Dichgans Johannes
Published: December 2004

Patients with Parkinson's disease (PD) are more dependent on visual information during movements than normals. To investigate the mechanisms underlying deterioration of movement under nonvisual conditions, we studied two‐dimensional pointing movements to randomly occurring targets. The experimental design allowed us to systematically manipulate visual feedback during the movement by removing vision of the target, of the moving hand, or of both. Execution of pointing movements in PD deviated most severely from that of normals when PD patients moved without vision of their own moving hand. Under this condition, undershooting of the target appeared, and movements were particularly slow. In contrast, with complete vision or when only vision of the target was occluded, pointing movements of PD patients were accurate and faster. PD patients had no difficulties selecting the correct movement direction. Reaction times were longer in PD patients irrespective of the availability of visual feedback. Our findings suggest that the ability of PD patients to use nonvisual feedback during execution of arm movements is impaired.
Variable onset of adult inherited focal dystonia: A problem for genetic studies
Authors: Micheli S. , Fernández‐Pardal M. , Quesada P. , Brannan T. , Obeso J. A.
Published: December 2004

We present two families with adult‐onset focal dystonias with marked variability in disease expression, discuss the clinical findings in relation to the literature, and comment on the difficulties in determining the pattern of inheritance.
N‐0923, a selective dopamine D2 receptor agonist, is efficacious in rat and monkey models of Parkinson's disease
Authors: Belluzzi J. D. , Domino E. F. , May J. M. , Bankiewicz K. S. , McAfee D. A.
Published: December 2004

Certain aminotetralins are known to be potent dopamine D2 receptor agonists. N‐0923, [‐]2‐(N‐propyl‐N‐2‐thienylethylamino)‐5‐hydroxytetralin HCl, recognizes the high and low affinity states of the D2 receptor in membranes from bovine caudate with a Klow of 79 nM. The selectivity ratio is D2/D1 = 15 and D2/α2 = 1.4. N‐0923 also inhibits dopamine uptake and prolactin secretion, and it is an antagonist at the α2 receptor. N‐0923 (3–300 nmol/kg, s.c.) induced dose‐dependent contralateral turning behavior in rats with unilateral 6‐hydroxydopamine lesions of the substantia nigra. The ED50 of 30 nmol/kg was effective for 1 h. The positive enantiomer (N‐0924; 300 nmol/kg, s. c.) was without effect. A hemiparkinsonian syndrome was induced in four Macaca nemestrina monkeys by unilateral infusion of the neurotoxin MPTP into the right carotid artery. Video recordings of free‐moving behavior revealed bradykinesia, disuse of the contralateral upper limb and turning in a direction ipsilateral to the lesion. N‐0923 (3–300 nmol/kg, i.m.) induced contralateral turning behavior, exploratory activity, and contralateral limb usage. The ED50 for turning (30 nmol/kg) was effective for 0.5 h. The potency order for induction of contralateral rotations was (+)‐PHNON‐0923 > bromocriptine. N‐0924 (300 nmol/kg, i. m.) was ineffective. We conclude that N‐0923 may be useful as a therapeutic agent in the treatment of Parkinson's disease.
Withdrawal akathisia: Case reports and a proposed classification of chronic akathisia
Authors: Lang Anthony E.
Published: December 2004

Two patients with akathisia developing only after neuroleptic dosage reduction or withdrawal are described. The literature dealing with tardive or chronic akathisia is reviewed with an emphasis on the existence of variants including the occurrence of symptoms upon withdrawal of the causative drug. A classification of tardive or chronic akathisia syndrome is proposed.
Gait abnormality in essential tremor
Authors: Singer Carlos , Sanchez‐Ramos Juan , Weiner William J.
Published: December 2004

Essential tremor (ET) has been described as a monosymptomatic disorder. In reports describing large series of patients with ET, there are rare patients who exhibit a noticeable gait disorder. However, we have observed that patients with ET and normal gait often exhibit an abnormality of tandem gait. To investigate this observation, we examined whether a gait disorder was present in 36 consecutive patients (mean age 69) with ET. We employed a tremor rating scale that scored tremor amplitude, location, and disability. In all patients, gait and tandem gait were separately evaluated. Eighteen of 36 patients (50%) exhibited tandem gait abnormalities in the presence of a normal narrow‐based gait compared to 11 of 40 age‐matched controls (28%) (p < 0.05). Abnormality of tandem gait was more frequently present in older ET patients and those with 5 years of disease duration. No relationship was found between presence of tandem gait abnormality and gender, tremor severity, head involvement, or positive family history. The finding of a tandem gait abnormality in 50% of ET patients suggests that cerebellar dysfunction may be important in its pathophysiology.
Development of resistance to botulinum toxin type A in patients with torticollis
Authors: Greene Paul , Fahn Stanley , Diamond Beverly
Published: December 2004

Between 1984 and 1992, 559 patients with torticollis were treated with botulinum toxin type A (btx) injections. Twenty‐four of these 559 patients (4.3%) had serological evidence of antibodies to btx by mouse neutralization assay. Some of the 559 patients had only one or two injection series, whereas others were lost to follow‐up, so that the actual prevalence of serologically detectable antibodies may be higher than 4%. In addition, some patients who improved after btx injections lost benefit and stopped developing muscle atrophy from adequate doses of btx, without serological evidence of antibodies. To evaluate the risk factors for btx resistance (loss of benefit and muscle atrophy after injections with or without serological evidence of antibodies), we reviewed the records of a cohort of torticollis patients injected over 2–45 months (mean, 23 months) beginning in 1988. Eight of 76 patients (10.5%) developed btx resistance. Compared to nonresistant patients from the same cohort, these eight patients received more frequent injections, had more “booster injections” 2–3 weeks after an initial injection, and received higher doses of btx per treatment. In order to minimize the risk of developing btx resistance, therefore, we recommend that physicians wait as long as possible (at least 1 month) between btx injections, avoid booster injections, and use the smallest possible doses.
Talipexole and adult Gilles de la tourette's syndrome: Double‐blind, placebo‐controlled clinical trial
Authors: Goetz Christopher G. , Stebbins Glenn T. , Thelen Jean A.
Published: December 2004

Talipexole is a new dopamine autoagonist with putative preferential activity on presynaptic dopamine receptors. In a double‐blind, placebocontrolled study, we tested the drug's safety and efficacy in 13 adult men with Gilles de la Tourette's syndrome. The drug was poorly tolerated because of clinically significant sedation and dizziness. Tics did not improve at tolerable doses. These findings suggest that talipexole has no role in the regular management of tic disorders.
Pulmonary embolism: An under‐recognized yet frequent cause of death in parkinsonism
Authors: Mosewich R. K. , Rajput A. H. , Shuaib A. , Rozdilsky B. , Ang L.
Published: December 2004

There are very few detailed reports on the cause of death in patients with Parkinson syndrome, and most reports lack postmortem verification. Pulmonary embolism has been reported as an infrequent terminal event. We reviewed the results of 60 complete autopsies performed on patients with Parkinson syndrome personally cared for at our institution. Pulmonary embolism was second only to pneumonia as the most common cause of death overall.
Early onset Parkinson's disease: Are juvenile‐ and young‐onset different?
Authors: Muthane Uday B. , Swamy H. S. , Satishchandra P. , Subhash M. N. , Rao S. , Subbakrishna D.
Published: December 2004

It is controversial if early onset Parkinson's disease (EOPD) (onset at <41 years of age) is Parkinson's disease (PD) occuring at a younger age or a different disease. This controversy is due to some clinical and pathological differences between EOPD and PD. Within EOPD, there appear to be two groups namely: young onset Parkinson's disease (YOPD), with onset between 21 and 40 years, and juvenile parkinsonism (JP), with onset at <20 years. The two major clinical differences between these groups are a higher familial occurence of PD and dystonia in JP. In this study, we determine if the two groups have the classical features of PD, namely rest tremors, rigidity, bradykinesia, and postural instability, and have a meaningful response to levodopa. Furthermore, we compare their other clinical features, autonomic and cognitive functions, and levels of CSF monoamine metabolites to determine differences between these groups. We observe that all YOPD (100%) and JP (85%) patients had rest tremors. Most of these patients also had a meaningful response to levodopa (YOPD: 72%; JP: 100%). The prevalence of family history of PD was similar, whereas dystonia was more frequent in JP (43%) compared to YOPD (9%). Autonomic symptoms were twice as common in JP (42%) compared to YOPD (17%). However, bedside autonomic fuctions were abnormal in similar proportions and, like in PD, suggest involvement of parasympathetic nervous system. Congnitive dysfunction does occur but with no difference in severity between the two groups. The difference in number of patients between YOPD and JP groups makes statistical comparison of the occurence of clinical features like dystonia and autonomic dysfunction difficult. A similar situation exists in earlier studies on EOPD and could be a possible reason for the apparent difference between YOPD and JP; hence, combining two earlier studies with ours, we perform a meta‐analysis. The meta‐analysis did not confirm significant differences in the occurrence of dystonia or a positive family history of PD in the two groups. Besides clinical similarities between YOPD and JP, like in PD, these former two have dopaminergic deficiency demonstrated by significantly low mean CSF homovanillic acid level. Our study demonstrates that EOPD is similar to PD and there are no striking clinical differences between YOPD and JP. Hence, we suggest that EOPD is PD occuring at a younger age.
Akathisia in Parkinson's disease
Authors: Comella Cynthia L. , Goetz Christopher G.
Published: December 2004

This study evaluated the prevalence and clinical characteristics of akathisia in a tertiary care Parkinson's disease (PD) practice, and assessed the agreement between investigators for the diagnosis of akathisia in PD, and the sensitivity and specificity of a brief patient questionnaire. Fifty‐six consecutive PD patients completed an akathisia questionnaire and then were clinically evaluated for akathisia by two examiners blinded to the patient questionnaire. Overall, 45% of PD patients had akathisia as determined by clinical evaluation. Interrater reliability for the diagnosis of akathisia was high (K = 0.89). Patient self‐report of restlessness agreed with examiner diagnosis in 89% of the patients. The presence of akathisia was associated with the severity and age of onset of PD. Symptoms most frequently affected the legs, and associated movements were suppressible for brief periods.
Botulinum toxin a injections for the treatment of hand tremors
Authors: Trosch R. M. , Pullman S. L.
Published: December 2004

We conducted an open‐label study to determine the utility of treating severe hand tremors with intramuscular injections of botulinum toxin (BTX) in forearm and arm muscles in 26 patiets, 12 with Parkinson's disease (PD) and 14 with essential tremor (ET). The effect after 6 weeks for each patient was evaluated using two clinical rating scales, subjective evaluations of functional improvement and global disability, measures of weakness, and computer‐assisted quantitative assessments of tremor. Although none of the clinical scores averaged>3/4 point change, statistical significance was found on comparison of pre‐ and postinjection scores in the Webster Tremor and Global Disability Scales in the ET patients. Similarly, although average tremor amplitudes decreased by no more than 25% by quantitative analysis, amplitude decrease significantly correlated with patient subjective assessment in ET. In only two of 12 PD (17%) and three of 14 ET patients (21%) were major quantitative changes in tremor amplitude (>50% reduction) found after BTX injections. Nevertheless, 10 patients (38%; five PD and five ET) reported moderate to marked subjective improvement in functional benefit after BTX. These finding suggest that although there were no major changes in clinical ratings or objective measurements, BTX injections may subjectively improve tremor in some patients, particularly those with ET.
Familial levodopa‐responsive parkinsonian‐pyramidal syndrome
Authors: Nisipeanu P. , Kuritzky A. , Korczyn A. D.
Published: December 2004

We present four patients—two pairs of siblings—followed for many years, with pyramidal and parkinsonian features, who responded consistently to levodopa therapy. The patients belong to two unrelated consanguineous families, suggesting that this condition is genetically determined and recessively inherited.
Teaching tape for the motor section of the unified Parkinson's disease rating scale
Authors: Goetz Christopher G. , Stebbins Glenn T. , Chmura Teresa A. , Fahn Stanley , Klawans Harold L. , Marsden C. David
Published: December 2004

We developed a teaching tape of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) to provide investigators with a visual document of three raters' interpretations of the scoring system for each item except rigidity. The rate of agreement for the selected samples was always significant, with Kendall's coefficient of concordance W ranging between 0.97 and 0.62. We also provided full UPDRS ratings on sample patients that may be used for training and for multicenter studies to assure uniformity of rating. The study identified several items of the UPDRS motor examination for which written instructions were vague, including speech, action tremor, finger taps, rapid alternating movements, and postural stability. Future versions of the scale should address these problems and correct ambiguities. This project offers the first attempt to provide a visual analog for the UPDRS.
L‐Dihydroxyphenylalanine and complex I deficiency in Parkinson's disease brain
Authors: Cooper J. M. , Daniel S. E. , Marsden C. D. , Schapira A. H. V.
Published: December 2004

There is evidence for a 37% deficiency of complex I activity in Parkinson's disease (PD), which appears to be specific for PD amongst parkinsonian syndromes and selective for the substantia nigra within the central nervous system. Rat studies have shown that, in the context of a normal nigrostriatal dopaminergic cell population, L‐dihydroxyphenylalanine (L‐dopa) causes a reversible 25% defect of complex I activity in nigral and striatal tissue. Analysis of striatal tissue from PD patients after prolonged exposure to highdose L‐dopa does not show such a defect. Results of these and other studies suggest that L‐dopa therapy does not cause complex I deficiency in PD striatum. However, it cannot be excluded that, in the particular environment of the PD substantia nigra, L‐dopa may enhance a preexisting complex I defect.
A probe for intracerebral aromatic amino‐acid decarboxylase activity: Distribution and kinetics of [18F]6‐fluoro‐L‐m‐tyrosine in the human brain
Authors: Nahmias Claude , Wahl Lindi , Chirakal Raman , Firnau Gunter , Garnett E. Stephen
Published: December 2004

Positron tomography, using [18F]6‐fluoro‐L‐dopa as a tracer, has been used for the study of Parkinson's disease. Unfortunately, the analysis of data obtained with this agent is bedeviled because it readily forms labeled methylated metabolites that enter the brain. We have evaluated [18F]6‐fluoro‐L‐m‐tyrosine (FmT) as an alternative tracer to study intracerebral dopamine metabolism with positron tomography. Imaging studies in humans showed specific accumulation of this tracer in the dopamine‐rich striatal regions. Reduced striatal uptake of the tracer was demonstrated in a patient suffering from Parkinson's disease. Increased retention of the tracer was demonstrated in a subject pretreated with the peripheral decarboxylase inhibitor carbidopa. Analysis of plasma samples for labeled metabolites of FmT revealed no methylated metabolites. Results of compartmental analysis showed that a twocompartment three rate constant model described adequately the time course of radioactivity in the striatum after an injection of FmT. decarboxylation rate constant (k21) was found to be 0.0108 min−1. Because the peripheral metabolism of FmT is simpler than that of [18F]6‐fluoro‐L‐dopa, we propose FmT as a superior agent with which to study intracerebral dopamine metabolism in health and disease in humans.
Mood and anxiety fluctuation in Parkinson's disease associated with levodopa infusion: Preliminary findings
Authors: Maricle Robert A. , Nutt John G. , Carter Julie H.
Published: December 2004

Pilot data on mood and anxiety changes in 15 Parkinson's disease patients with motor fluctuations are described based on ratings every 30 min for 5 h bracketing a 2‐h constant‐rate levodopa infusion. Robust mood and anxiety effects slightly preceded but temporally paralleled fluctuations in motor tapping scores. Research nurse ratings blind to patient ratings corroborated the changes. The magnitude of changes in mood and anxiety scores did not correlate with the magnitude of changes in tapping scores. The findings of this uncontrolled study suggest mood and anxiety fluctuations may be a common and potentially important component of levodopa‐induced fluctuation.
A defect of kinesthesia in Parkinson's disease
Authors: Klockgether Thomas , Borutta Maike , Rapp Herbert , Spieker Sybille , Dichgans Johannes
Published: December 2004

Patients suffering from Parkinson's disease (PD) are more dependent on visual feedback during movement than are normals. Studying two‐dimensional pointing movements, we recently found that PD patients undershoot targets when vision of their own moving hand is occluded but not when complete vision is provided or when the target is extinguished immediately before movement onset. In the absence of vision, information about position of the moving hand may originate from peripheral kinesthetic feedback and from corollary discharges derved from the efferent motor signal. To find out which of both mechanisms–kinesthetic feedback or corollary discharge–is defective in PD, we compared active movements with imposed movements in which the hand is passively moved by the experimenter, whereas vision of the hand was occluded under either condition. In agreement with our earlier findings, slow, active pointing movements of PD patients were hypometric. In addition, PD patients terminated passively imposed movements of comparable speed earlier than did normals, with the consequence that imposed movements were equally hypometric. Our results make it unlikely that disturbed corollary discharge is responsible for hypometria under nonvisual conditions. Instead, the data suggest that PD patients have a defect of kinesthesia in slowly executed movements.
Double‐Blind trial of botulinum toxin for treatment of focal hand dystonia
Authors: Cole R. , Hallett M. , Cohen L. G.
Published: December 2004

Ten patients with focal dystonia of the hand, all of whom had benefited in an open‐label study of botulinum toxin, were treated with botulinum toxin‐A in a double‐blind study. Response was assessed by three measures: (a) subjective rating, provided by patients' reports of the effect of the injections on the dystonia; (b) objective testing, consisting of manual muscle testing (MRC scale) to measure muscle strength in all patients, timing of a writing sample and counting the number of errors of writing off‐the‐line in six patients with writer's cramp, counting the number of errors on a standard test of transcription in two patients with stenographer's cramp, and rating by professional musicians of the performances of two patients with musician's cramp; and (c) physicians'rating, provided by a review of the patients' videotaped performance by neurologists who were unaware of which treatment was administered. Eight of the 10 patients had greater subjective improvement with botulinum toxin than with placebo, and this impression was verified by at least one objective test in six patients. Two patients failed to have a better response to botulinum toxin than to placebo, and their reports were verified by the objective tests. This study confirms the efficacy of botulinum toxin in many patients with focal hand dystonia.
Masturbation mimicking paroxysmal dystonia or dyskinesia in a young girl
Authors: Mink Jonathan W. , Neil Jeffrey J.
Published: December 2004

We present the case of a young girl with periodic posturing during masturbation. The child had been evaluated by several physicians and underwent numerous diagnostic tests before the spells were seen by a physician and determined to be selfstimulatory and not paroxysmal dystonia. Masturbation is a normal and common behavior in young children and should be recognized as such. Failure to recognize this behavior can lead to unnecessary and invasive testing.
Striated anal sphincter denervation in patients with progressive supranuclear palsy
Authors: Valldeoriola F. , Valls‐Solé J. , Tolosa E. S. , Marti M. J.
Published: December 2004

Anal sphincter electromyography may contribute to the differential diagnosis between Parkinson's disease (PD) and other parkinsonisms featuring autonomic dysfunction, such as multiple system atrophy (MSA). Although patients with progressive supranuclear palsy (PSP) do not normally exhibit clinical signs of autonomic dysfunction, a few may be first seen with urinary and fecal incontinence. We performed an electromyographic study of the anal sphincter in 12 patients with clinical criteria of probable or definite PSP, two of them with clinical manifestations of vesical and anal sphincter dysfunction. The results have been compared with those obtained from six patients with PD and six patients with MSA. An abnormal anal sphincter examination was present in five of 12 PSP patients (41.6%). The abnormal motor units of these patients were indistinguishable from those observed in patients with MSA. Patients with MSA had the largest, and patients with PD had the lowest, proportion of abnormal motor units. We conclude that some patients with PSP may have electromyographic signs of denervation in the anal sphincter, which make them indistinguishable by using this test alone from patients with MSA.
Ball experiments in 32 acute akinetic catatonic patients: Deficits of internal initiation and generation of movements
Authors: Northoff G. , Wenke J. , Krill W. , Pflug B.
Published: December 2004

We undertook ball experiments in 32 akinetic catatonic patients in order to determine specific functional deficits in the motor system in akinetic catatonia. Standardized ball experiments (catching, throwing, stopping, kicking) were conducted in 32 acute akinetic catatonic patients (23 without neuroleptics on admission), diagnosed according to Lohr, Rosebush, and the Diagnostic and Statistical Manual of Mental Disorders (3rd ed, revised) on days 0 and 21. Additionally, associated psychopathology was evaluated using different scales on days 0 and 21: the Global Assessment Scale, the Brief Psychiatric Rating Scale, the Hamilton‐Anxiety Scale, the scale for the assessment of negative symptoms (SANS), and the Simpson scale for extrapyramidal side effects (SEPS). Significantly more patients were able to perform more externally guided tasks (catching, stopping) than internally guided tasks (throwing, kicking). Patients showed significantly more posturing and awkward movements on day 0 than on day 21. There was a significantly positive correlation between hypokinetic extrapyramidal features (SEPS) and negative symptoms with their cognitive alterations (SANS) on day 0. The findings suggest a deficit of internal initiation, as in parkinsonism, as well as a dysfunction in the generation of voluntary movements in akinetic catatonia. We assume an underactivity in the dorsolateral prefrontal cortex and the supplementary motor area with consecutive down‐regulation of the cortical‐striatal‐thalamic circuit, the “motor loop,” in catatonia.
Anorectal function in fluctuating (on‐off) Parkinson's disease: Evaluation by combined anorectal manometry and electromyography
Authors: Ashraf Waseem , Wszolek Zbigniew K. , Pfeiffer Ronald F. , Normand Marlene , Maurer Kenneth , Srb Faye , Edwards Loraine L. , Quigley Eamonn M. M.
Published: December 2004

Anorectal dysfunction and constipation are well recognized in Parkinson's disease and may reflect the direct involvement of the gastrointestinal tract by the primary Parkinson's disease process. We hypothesized, therefore, that anorectal function would alter in parallel with fluctuations in motor function related to on‐ and off‐periods in Parkinson's disease, and employed combined anorectal manometry and electromyography to investigate anorectal function during both on‐ and off‐periods in patients with Parkinson's disease. Manometric recordings revealed a deterioration in voluntary sphincter squeeze during off‐periods (squeeze index, on versus off, mean ± SEM: 46.4 ± 11.1 versus 29.6 ± 7.9 mm Hg, p < 0.05); correspondingly, simultaneous electromyographic (EMG) recordings showed poor recruitment of external anal sphincter and puborectalis muscles during off‐periods. A hypercontractile (“paradoxical”) rectosphincteric reflex response occurred during both on‐ and off‐periods, and was associated with an increase in EMG activity in the external sphincter and/or the puborectalis muscle. These changes in manometric and EMG parameters paralleled changes in overall motor function. These findings provide further support for the involvement of the pelvic floor musculature in the Parkinson's disease process and also provide EMG correlates for some of the manometric abnormalities described in Parkinson's disease.