bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of blink rate patterns in normal subjects
Authors: Bentivoglio Anna Rita , Bressman Susan B. , Cassetta Emanuele , Carretta Donatella , Tonali Pietro , Albanese Alberto
Published: May 2005

The present study measured the normal blink rate (BR) variations in relation to behavioral tasks in 150 healthy volunteers (70 males and 80 females; aged 35.9 ± 17.9 years, range 5–87 years). The subjects were videotaped in a standard setting while performing three different tasks: resting quietly, reading a short passage, talking freely. The mean BR was computed during each task; the data were compared by means of analysis of variance and Student's t tests. Mean BR at rest was 17 blinks/min, during conversation it increased to 26, and it was as low as 4.5 while reading. As compared with rest, BR decreased by −55.08% while reading (p < 1 × 1015) and increased by 99.70% during conversation (p < 1 × 109). As compared with reading, BR increased during conversation by 577.8% (p < 1 × 10 17). The distribution curves were highly reproducible in each task. The best curve fit was represented by a long‐normal distribution, with the upper tail of each curve having a normal distribution. Eye color and eyeglass wearing did not influence BR. Women had higher BR than men just while reading. No age‐related differences were found. The most common BR pattern was conversation > rest > reading, which occurred in 101 subjects (67.3%); 34 subjects (22.7%) had the pattern rest > conversation > reading; 12 (8.0%) had the pattern conversation > reading > rest. This study identified three normal behavioral BR patterns and showed that BR is more influenced by cognitive processes than by age, eye color, or local factors. The present findings provide a normal reference for the analysis of BR in movement disorders such as dystonia or tics.
Spinal myoclonus induced by an intrathecal catheter
Authors: Ford Blair , Pullman Seth L. , Khandji Alexander , Goodman Robert
Published: May 2005

We report a case of spinal myoclonus induced by the tip of an intrathecal catheter in a 35‐year‐old patient with severe, adult‐onset, generalized dystonia of unknown cause, treated for 2 years using intrathecal baclofen. One month after a falling episode, the patient developed focal myoclonus of the right proximal leg whenever she stood up from a seated position. The electrophysiologic recordings were compatible with spinal segmental myoclonus, originating at a focus corresponding to the L2‐S2 segments. At this site, the tip of the intrathecal catheter was demonstrated by myelography to be in close proximity to the nerve roots and conus medullaris. The myoclonus resolved promptly once the catheter tip was withdrawn. We review the literature on spinal myoclonus and discuss the possible mechanisms of spinal myoclonus pertaining to the present case. This report represents an unusual complication of intrathecal catheter systems that, if recognized, can lead to prompt therapeutic intervention.
Cortical myoclonus in huntington's disease associated with an enlarged somatosensory evoked potential
Authors: Caviness John N , Kurth Mathias
Published: May 2005

We report the electrophysiologic findings of myoclonus in a patient with Huntington's disease (HD). This patient was studied postoperatively after a bilateral fetal cell transplant in his striatum. Incomplete transient improvement was seen in the myoclonus, followed by gradual deterioration. The myoclonus itself had a cortical correlate and was associated with an enlarged somatosensory evoked potential (SEP), consistent with the presence of cortical reflex myoclonus. An enlarged SEP has not been previously reported in myoclonus associated with HD. The postulated mechanisms for myoclonus, when it occurs in HD, have differed in the literature. The reason for the transient improvement of the myoclonus following transplantation is unclear, but this case raises the possibility that basal ganglia circuits may modulate cortical myoclonic activity.
Spinal rigidity following acute myelitis
Authors: Brown Peter , Quinn Niall P. , Barnes David , Wren Damien R. , Marsden C. David
Published: May 2005

A patient with a 2½‐year history of painful spasms and rigidity of both lower limbs is described. Symptoms began after an episode of acute myelitis. The spasms—which were spontaneous and stimulus sensitive and occurred on voluntary action—involved the repetitive grouped discharge of motor units. Continuous motor unit activity was present at rest in the muscles of both legs, and cutaneomuscular reflexes were abnormal. This patient is similar to those recently reported as having stiffness and spasms of the legs due to a possible chronic spinal interneuronitis and provides further evidence that this kind of movement disorder may be caused by spinal cord pathology.
Botulinum toxin a improves muscle spasms and rigidity in stiff‐person syndrome
Authors: Liguori Rocco , Cordivari Carla , Lugaresi Elio , Montagna Pasquale
Published: May 2005

We studied the effect of botulinum toxin A (BTA) on painful muscular spasms and rigidity in two bedridden patients with clinical, electrophysiologic, and immunologic evidence of stiff‐person syndrome. We injected BTA of saline solution into several limb muscles with both the rater and patient blinded to the order of the injections. A physician, unaware of the treatment order, used an objective rating scale for rigidity and spasm frequency scale and independently assessed the treatment results. BTA administration significantly reduced rigidity and stopped the spasms in all limbs. Following BTA injection on one side, the spasm frequency decreased bilaterally possibly because of the spread of hematogenous toxin.
The shaking palsy, the first forty‐five years: A Journey through the british literature
Authors: Louis Elan D.
Published: May 2005

The authors examined the British medical literature published in the 45‐year‐period following Parkinson's treatise on the shaking palsy to determine the number and type of references to the shaking palsy or paralysis agitans during this particular period. Several sources suggest that Parkinson's 1817 treatise on the shaking palsy received little immediate attention in his native country, England, and that not until 1861, in France, did Charcot began to elucidate the clinical features of this entity, separating it from other Neurologic disorders (for example, multiple sclerosis), A review of the British medical literature from the 45‐year‐period 1817–1861 revealed a number of references to paralysis agitans, including those by Cooke (1820), Good (1824 and 1829), Elliotson (1827, 1829, 1830, 1831, and 1833), Gowry (1831), anonymous (1832), Todd (1833), Watson (1836), Gibson (1839), Hall (1838 and 1841), Thompson (1842), Graves (1843), Birkett (1853), Paget (1855), and Reynolds (1855). Many of these did not report new or personally observed cases, did not separate Parkinson's disease from other disease entities characterized by both “shaking” and “palsy” (for example, tonic‐clonic seizures), or misattributed motor signs to dysfunction of the pyramidal system rather than an extrapyramidal system (that is, attributing bradykinesia or rigidity to weakness). Although there were several references to “shaking palsy” in the early‐ to mid‐19th‐century British medical literature, there were few original case reports of Parkinson's disease. This may have contributed to the fact that during this period little was added to the original observations made by Parkinson in 1817. In particular, the separation of bradykinesia and weakness did not become apparent until later work by the French.
Depression in classic versus akinetic‐rigid Parkinson's disease
Authors: Starkstein Sergio E. , Petracca Gustavo , Chemerinski Erán , Tesón Alejandra , Sabe Liliana , Merello Marcelo , Leiguarda Ramón
Published: May 2005

We examined the prevalence of major depression and dysthymia in 78 patients with the classic variant of Parkinson's disease (PD) (that is, tremor plus rigidity and/or bradykinesia), and in 34 patients with the akinetic‐rigid variant. Although the prevalence of dysthymia was similar in both groups (classic PD, 31%; and akinetic‐rigid PD, 32%), patients with akinetic‐rigid PD had a significantly higher prevalence of major depression (38% versus 15%, respectively; p < 0.01). A stepwise regression analysis demonstrated that bradykinesia was the extrapyramidal sign with the highest correlation with Hamilton depression scale scores. Our findings demonstrate a significant association between major depression and the akinetic‐rigid type of PD.
Action tremor and weakness in Parkinson's disease: A study of the elbow extensors
Authors: Brown Peter , Corcos Daniel M. , Rothwell John C.
Published: May 2005

We have previously shown that action tremor persists during maximal wrist extension in patients with Parkinson's disease, and that this contributes to weakness at this joint by preventing the fully fused contraction of the forearm extensor muscles. Antiparkinsonian medication reduces the action tremor in torque and electromyographic (EMG) records, thereby improving strengh at the wrist. In the present experiments, peak torque and action tremor were recorded during maximal extension of the elbow in nine patients with Parkinson's disease while they were on and off antiparkinsonian medication, and in eight age‐ and sex‐matched healthy subjects. Peak torque and mean rectified EMG levels were reduced by 34% and 36%, respectively, during maximal elbow extension when patients off medication were compared to those in the treated state. Action tremor was visible in torque records and had a frequency of ∼ 10 Hz both in parkinsonian patients and in normal controls. Activity of a similar frequency was often detected in EMG records, especially in patients off therapy. The absolute amplitude of action tremor in torque (Atorque) and EMG (AEMG) records from the elbow was unaffected by therapy and was little different from that recorded in healthy controls. The relative action tremor in torque ([Atorque/peak torque] × 100) and EMG ([AEMG/mean rectified EMG] × 100) was reduced by treatment, but this was the result of the increase in peak torque and mean rectified EMG. Thus, in contrast to the results at the wrist, antiparkinsonian medication has little effect on the 10‐Hz action tremor at the elbow. Increased strength is produced by a different mechanism which allows recruitment of triceps motor units outside of this synchronizing influence.
Cerebral hypoperfusion and hypometabolism with altered striatal signal intensity in chorea‐acanthocytosis: A combined PET and MRI study
Authors: Tanaka Makoto , Hirai Shunsku , Kondo Susumu , Sun Xiayan , Nakagawa Toshiyuki , Tanaka Satoshi , Hayashi Kunihiko , Okamoto Koichi
Published: May 2005

We studied cerebral perfusion and oxygen metabolism in three patients with chorea‐acanthocytosis using positron‐emission tomography and oxygen‐15 labeled O2 and CO2. High‐field magnetic resonance imaging also was performed. Regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO2) were significantly reduced in the caudate and putamen when compared with seven control subjects. Mild but significant reductions of rCBF (lower than the normal control values ‐2 SD) were found in the bilateral frontal, left temporal and parietal, and bilateral thalamic areas; rCMRO2 was reduced in the bilateral frontal and left temporal areas. Magnetic resonance imaging showed increased signal intensity accompanied by scattered bright spots in the caudate head and putamen on T2‐weighted images; decreased signal intensity was shown at these sites on T1‐weighted images. These findings were not observed in 10 neurologically normal volunteers and are rare in the common hyperkinetic form of Huntington's disease. Reduced cerebral perfusion and oxygen metabolism seem to be related to the intellectual and personality changes that occur in chorea‐acanthocytosis. Combined positronemission tomography and magnetic resonance imaging studies may improve diagnostic accuracy in patients with choreaacanthocytosis and related disorders.
Changes in perfusion pattern using ECD‐SPECT indicate frontal lobe and cerebellar involvement in exercise‐induced paroxysmal dystonia
Authors: Kluge Andreas , Kettner Beatrice , Zschenderlein Rolf , Sandrock Dirk , Munz Dieter L. , Hesse Stefan , Meierkord Hartmut
Published: May 2005

The clinical features of exercise‐induced paroxysmal dystonia (EPD) are delineated in a pedigree including two affected members (both male) showing an autosomal‐dominant inheritance trait. Gait analysis using kinematic electromyography during the motor attacks revealed coactivation of antagonistic calf muscles characteristic of dystonia. In the interval, impaired muscular alternation was observed. To characterize further the pathophysiological basis of the condition, ictal and interictal cerebral perfusion SPECT studies using technetium 99m‐ethyl cysteinate dimer (ECD) were performed to establish whether cortical hyperactivity indicative of epilepsy is present during the motor attacks and to identify regional changes in the ictal perfusion pattern that could indicate an anatomic structure relevant to the disease. During the motor attacks, decreased ictal perfusion of the frontal cortex was found in both patients. In contrast, increased cerebellar perfusion was observed. The perfusion of the basal ganglia also decreased. No cortical hyperfusion indicative of an epileptic nature was seen. Cerebellar hyperactivity in connection with prominent frontal hypoactivity has also been described in both the idiopathic and the symptomatic forms of dystonia. Our findings therefore suggest that EPD represents a paroxysmal movment disorder rather than epilepsy. It is concluded that changes in frontal and in cerebellar function are relevant to the pathophysiology of EPD.
Asymmetric predominantly ipsilateral blepharospasm and contralateral parkinsonism in an elderly patient with a right mesencephalic cyst
Authors: Singer Carlos , Schatz Norman J. , Bowen Brian , Eidelberg David , Kazumata Ken , Sternau Linda , Shulman Lisa M. , Weiner William J.
Published: May 2005

A 66‐year‐old woman presented with a 3‐year history of predominantly right‐sided blepharospasm and a 1‐year history of progressive predominantly left‐sided hemiparkinsonism manifested by a left upper extremity resting tremor and left‐sided bradykinesia. Magnetic resonance imaging of the brain revealed a large right mesencephalic cyst with mass effect. Positron emission tomography revealed bilateral striatal hypometabolism consistent with nigrostriatal dopaminergic dysfunction. The association of predominantly ipsilateral blepharospasm and predominantly contralateral hemiparkinsonism is very rare, and its association with a posterior fossa space‐occupying lesion has been reported only once. This is the second report of such an association and the first description of adult‐onset symptomatology.
Reversible chorea in primary antiphospholipid syndrome
Authors: Sundén‐Cullberg Jonas , Tedroff Joakim , Aquilonius Sten‐Magnus
Published: May 2005

A 20‐year‐old woman with acute chorea induced by primary antiphospholipid syndrome was studied by using fluorodeoxyglucose and positron emission tomography (PET). PET sessions were conducted during an episode of severe chorea and after recovery. The symptoms predominantly affected the right side of her face and body, and PET demonstrated a corresponding increase in lentiform and caudate nucleus metabolism prevailing on the left side. After recovery, PET showed normal values in the regions previously studied. This study adds further evidence to support the theory that acute choreas are somehow the result of striatal hypermetabolism.
Pretreatment and posttreament positron emission tomographic scan imaging in a 20‐year‐old patient with Wilson's disease
Authors: Cordato Dennis J. , Fulham Michael J. , Yiannikas Con
Published: May 2005

Wilson's disease is an autosomal‐recessive inherited diorder that results in predominantly hepatic and neurologic manifestations. Neurologic abnormalities include tremor, ataxia, bradykinesia, rigidity, chorea, and dystonia. We report the clinical, radiologic, and serial FDG PET findings in a 20‐year‐old woman who presented with an asymmetric upper limb tremor caused by Wilson's disease. Reduced striatal and cerebral cortical glucose metabolism was demonstrated on a FDG PET study performed before the commencement of D‐penicillamine therapy. After 6 months of treatment, the patient had shown only minimal clinical improvement, despite an increase in striatal and cerebral cortical glucose metabolism on a repeat FDG PET study. After 14 months of treatment, however, a moderate clinical improvement was noted and there was further increase in glucose metabolism on FDG PET.
De novo administration of ropinirole and bromocriptine induces less dyskinesia than L‐dopa in the MPTP‐treated marmoset
Authors: Pearce Ronald K. B. , Banerji Tara , Jenner Peter , David Marsden C.
Published: May 2005

In contrast to levodopa (L‐dopa), de novo administration of the D2‐like receptor agonist bromocriptine to patients with Parkinson's disease (PD) or to 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated subhuman primates is not associated with the onset of significant dyskinesia. We now compare the ability of the novel D2‐like selective dopamine agonist ropinirole with that of bromocriptine and L‐dopa to induce dyskinesia in MPTP‐treated common marmosets. MPTP‐treated common marmosets were treated with placebo, L‐dopa plus carbidopa, ropinirole, or bromocriptine daily for 30 days (n = 4 per group) in doses that were titrated to similarly increase locomotion and improve motor disability. L‐dopa rapidly induced dyskinesia of moderate to severe intensity, whereas ropinirole and bromocriptine produced mild dyskinesia over the course of the study that was significantly less severe than in the L‐dopa‐treated group (p < 0.05). However, in a separate group of marmosets previously primed with L‐dopa to exhibit dyskinesia, ropinirole administration elicited severe dyskinesias comparable with that of L‐dopa in a dosedependent fashion. Ropinirole, in common with bromocriptine, has a lesser tendency than L‐dopa to produce dyskinesia while similarly improving motor performance in drug‐naive MPTP‐treated marmosets. However, in common with other dopamine agonists, ropinirole will elicit comparable dyskinesia once L‐dopa priming has occurred. These results predict a similar response to ropinirole and other long‐acting dopamine agonists in L‐dopa‐naive patients with PD and emphasize the importance of avoiding initial dyskinesia induction through early use of dopamine agonist drugs.
Apomorphine enantiomers protect cultured pheochromocytoma (PC12) cells from oxidative stress induced by H2O2 and 6‐hydroxydopamine
Authors: Gassen Michael , Gross Aviva , Youdim Moussa B. H.
Published: May 2005

A significant body of evidence has been provided to support the hypothesis that oxidant stress may be responsible for the degeneration of dopaminergic neurons in the substantia nigra pars compacta in Parkinson's disease. Apomorphine, a dopamine D1/D2‐receptor agonist in the clinical therapy of Parkinson's disease, has been found to be a potent antioxidant and to prevent free radical reaction in rat brain mitochondrial fraction. In this article we show that 1–10 μM of apomorphine protects rat pheochromocytoma (PC12) cells from the toxic effects of H2O2 (0.6 mM) and the neurotoxin 6‐hydroxydopamine (150 μM). These effects were not exhibited by ascorbic acid, desferal, lisuride, or bromocriptine. Although pergolide exhibited some protection of PC12 cells against H2O2 toxicity, it was not as potent as apomorphine. In light of the present findings and the clinical reports that parkinsonian patients on long‐term apomorphine stabilize clinically and can be weaned off L‐dopa, one may assume that apomorphine can exert a neuroprotective activity via its potent antioxidant properties.
Asymmetry of basal ganglia glucose metabolism and dopa responsiveness in parkinsonism
Authors: Dethy Sophie , Van Blercom Nadège , Damhaut Philippe , Wikler David , Hildebrand Jerzy , Goldman Serge
Published: May 2005

We investigated, by positron emission tomography (PET) with [18F]fluoro‐2‐deoxy‐d‐glucose (FDG) (FDG‐PET), brain glucose metabolism in 19 patients with parkinsonian features. We compared local pattern of FDG uptake and asymmetry indexes in patients with therapeutic response to levodopa (L‐dopa) (group 1, presumed Parkinson's disease, n = 9) and patients without L‐dopa therapeutic response (group 2, presumed striatonigral degeneration, n = 10). Limb dystonia was present in 11% of patients in group 1 and in 40% of patients in group 2. Asymmetry in basal ganglia metabolism was distributed differently in the two groups (analysis of variance, p < 0.04). In superior and inferior putamen, superior and middle caudate, ventral striatum, and inferior thalamus, relative reduction in metabolism on the side contralateral to predominant parkinsonian signs was associated with L‐dopa unresponsiveness. On the contrary, in middle caudate, ventral striatum, and inferior thalamus, a relative increase in metabolism on the side contralateral to the predominant side, parkinsonian signs were found in L‐dopa‐responsive patients. Our FDG‐PET study using simple statistical procedures demonstrates inverse asymmetry of basal ganglia glucose metabolism in parkinsonian patients grouped on the sole basis of L‐dopa responsiveness.
Increasing striatal iron content associated with normal aging
Authors: Wayne Martin W. R. , Ye Frank Q. , Allen Peter S.
Published: May 2005

Free‐radical‐mediated mechanisms may contribute to neuronal damage in Parkinson's disease (PD), other neurodegenerative conditions also associated with aging, and the aging process itself. Cytotoxic free radicals are generated in the brain by oxidation/reduction reactions that are catalyzed by transition metals such as iron. Any regional increase in brain iron concentration may increase the potential for local freeradical formation. The purpose of this study was to determine the relationship between age and basal ganglia iron content in 20 normal individuals ranging from 24 to 79 years of age. We used an in vivo magnetic resonance method to quantify the effects of paramagnetic centers sequestered inside cellular membranes, thereby enabling the determination of a quantitative index of local brain iron content. We observed a strong direct relationship between age and regional iron content in the putamen (r = 0.76, p < 0.0001) and caudate (r = 0.69, p < 0.001), but not in the globus pallidus (r = 0.32, p = 0.17) or thalamus (r = 0.13, p = 0.58). In conclusion, striatal iron content increases with advancing age. This increase may increase the probability of free‐radical formation in the striatum, therefore representing a risk factor for the development of neurodegenerative disorders such as PD in which nigrostriatal neurons may be affected by increased oxidant stress.
The offset cortical potential: An electrical correlate of movement inhibition in man
Authors: Rothwell John C. , Higuchi Kazuo , Obeso Jose A.
Published: May 2005

Nine normal subjects were asked to make either a brisk isometric pinch of a force transducer held between the forefinger and thumb, or to hold a pinch for approximately 15 s and then release the force suddenly without any overt antagonist contraction. EEG activity was averaged about the onset or offset of EMG activity, and movements were made in the subjects' own time. All subjects found the task simple. The EEG activity preceding offset of contraction (offset cortical potential) was significantly smaller in lateral leads than that seen before onset of contraction. Midline activation was similar in both tasks. We suggest that in the onset task, motor cortex activity related to the act to be performed contributes substantially to the EEG potentials in lateral leads. This activity is absent in the offset task which requires only withdrawal of tonic input to motor cortex. Midline activity, common to both onset and offset tasks, could reflect timing, attentional, or other processes. The results are discussed in relation to previous data from an isotonic relaxation task1.
Clozapine use in Parkinson's disease: A retrospective analysis of a large multicentered clinical experience
Authors: Trosch Richard M. , Friedman Joseph H. , Lannon Meg C. , Pahwa Rajesh , Smith D. , Seeberger Lauren C. , O'Brien Christopher F. , Lewitt Peter A. , Koller William C.
Published: May 2005

We conducted a multicentered, retrospective review of clozapine's (CZP) effects on a range of psychiatric, sleep, cognitive, motor, and sensory disorders in Parkinson's disease (PD). Therapeutic outcomes and adverse events were compared with varying prescribing practices at participating sites. The medical records of 172 consecutive PD patients treated with CZP at four movement disorder clinics were reviewed. Low‐dose CZP improved psychiatric symptoms of psychosis, anxiety, depression, hypersexuality, sleep disturbance, and akathisia. Tremor, torticollis, limb dystonia, and pain showed modest rates of improvement. Twenty‐three percent of patients withdrew as a result of adverse events or treatment failure. Inpatient CZP initiation did not improve therapeutic efficacy, or reduce adverse events or the withdrawal rate. Low‐dose CZP in the outpatient setting is generally an effective and well‐tolerated treatment for many of the psychiatric, sleep, motor, and sensory disturbances common to late‐stage PD.
Prevalence of Parkinson's disease in northwestern italy: Comparison of tracer methodology and clinical ascertainment of cases
Authors: Chiò Adriano , Magnani Corrado , Schiffer Davide
Published: May 2005

The prevalence of idiopathic Parkinson's disease (PD) in an area of Northwestern Italy (Socio‐Sanitary District of Cossato, 61, 830 inhabitants) was analyzed and the reliability of “drug tracer methodology” evaluated. The patients were identified by both conventional epidemiological methodology (general practitioners, consultant neurologist, computerized archives) and drug tracer methodology (registered levodopa prescriptions). The diagnosis of PD was clinically verified by examining all patients. Of 146 patients examined, 104 were affected by PD; the remaining by other types of parkinsonism. The crude point prevalence rate (October 20, 1991) was 168 per 100,000 population (95% confidence interval [95% CI] 138–204), with a progressive increase up to the 80–89 age group. Using “tracer” methodology, the estimated crude point prevalence rate was 196 (95% CI 163–235), with an overestimation of the prevalence in older patients and women and an underestimation in younger and less seriously affected cases. The uneven distribution of PD in Italy appears to be the result of, at least in part, methodological factors. “Tracer” methodology may cause biases in the evaluation of the epidemiological characteristics of PD, especially if the clinical diagnosis of cases identified by this method is not carefully verified. Nevertheless, it appears useful as an additional source of cases for descriptive surveys.
Tremor in ostensibly normal elderly people
Authors: Elble Rodger J.
Published: May 2005

Tremor in ostensibly normal people, aged 70–91, was assessed clinically and electrophysiologically with the goal of estimating the prevalence of abnormal tremor. Fifty Men and 50 women, mean age 76.0 ± 4.7 yrs, were recruited through advertisements for healthy volunteers (n = 50 “biased” control subjects) and from the spouses of patients referred to us for dementia or Parkinson's disease (n = 50 “unbiased” control subjects). All participants were interviewed and examined by the author. Tremor was assessed quantitatively with rating scales, triaxial accelerometry, electromyography, a digitizing tablet, and spectral analysis. Twenty‐three people (23%) were judged clinically to have mildly abnormal tremor resembling mild essential tremor. Twelve people with abnormal tremor belonged to the biased group and 11 were in the unbiased group. The clinical diagnosis of abnormal hand tremor correlated well with the presence of motor unit entrainment in the forearm EMG and with writing or drawing tremor that was measurable with a digitizing tablet. Only 10 of 23 people with abnormal tremor were aware of their tremor, and none had been diagnosed previously by a physician. Nine of 77 people (11.7%) with normal tremor, and five of the 23 people (21.7%) with abnormal tremor had this family history. Mild undiagnosed tremor, resembling essential tremor, is common in this age group.
Monoaminergic effects of high‐dose corticotropin in corticotropin‐responsive pediatric opsoclonus‐myoclonus
Authors: Pranzatelli Michael R. , Huang Yung‐Yu , Tate Elizabeth , Goldstein David S. , Holmes Courtney S. , Goldstein Edward M. , Ketner Karen , Kinast Morris , Lange Bernadette M. , Sanz Alfred , Shevell Michael I. , Stanford Richard E. , Taff Ingrid P.
Published: May 2005

Children with the opsoclonus‐myoclonus syndrome (OMS) usually respond to corticotropin (adrenocorticotrophic hormone, ACTH) treatment but the mechanism of benefit is unknown. We previously showed that both cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5‐hydroxyindoleacetic acid (5‐HIAA) concentrations are low in pediatric OMS. In this study, we measured levels of CSF Dopa, catecholamines, deaminated metabolites of catecholamines, as well as HVA and 5‐HIAA in eight patients before and during treatment with ACTH. All the children were ACTH‐responsive with 50‐70% improvement in multiple clinical features of OMS. ACTH treatment reduced the HVA concentration in every child by a mean of 21% (p < 0.001). Treatment with ACTH was associated with significant correlations between dopaminergic markers such as HVA, dihydroxyphenylacetic acid (DOPAC), and Dopa. There were no significant changes in the CSF concentrations of the noradrenergic markers norepinephrine (NE) and dihydroxyphenylglycol (DHPG), or the serotonergic marker 5‐HIAA. The only child with a marked inflammatory pattern in CSF, which was reversed by ACTH, was atypical for a large increase in NE and decrease in 5‐HIAA levels. The pattern of decreased HVA and unchanged DOPAC levels could reflect decreased extraneuronal uptake of catecholamines (which steroids inhibit) or decreased 0‐methylation of catecholamines in nonneuronal cells.
Apomorphine‐induced penile erections in Parkinson's disease
Authors: O'Sullivan John D. , Hughes Andrew J.
Published: May 2005

Penile erections were regularly induced by intermittent subcutaneous injections of apomorphine in five patients with Parkinson's disease (PD) complicated by motor fluctuations. Four of the patients reported erectile dysfunction before beginning apomorphine and two of these report a significant improvement in their sexual function resulting from apomorphine use. Animal studies suggest central D2‐type dopamine receptor stimulation and oxytocin release from the paraventricular nucleus of the hypothalamus mediate the effect. Erections reported with other dopamine agonists and levodopa are probably mediated by the same mechanism. Apomorphineinduced erections in PD are probably more common than previously thought. The benefit of apomorphine on sexual function in some patients suggests a possible role in the treatment of impotence in PD.
Exteroceptive and interoceptive stimuli in dystonia
Authors: Greene Paul E. , Bressman S.
Published: May 2005

Some patients with torsion dystonia experience a dramatic increase or decrease in symptoms when performing specific activities. The activities that influence dystonic symptoms vary from person to person. An activity or sensory stimulus that reduces symptoms has been called a “sensory trick” or, in cervical dystonia, a “geste antagoniste.” When a single activity induces symptoms of dystonia, the dystonia is called “task specific.” We have discovered that in some patients, thinking about a sensory trick or task affects the dystonia in the same way as actually performing the activity. We present three representative patients, and discuss the relevance of this observation to the understanding of dystonia.
Olfactory function in restless legs syndrome
Authors: Adler Charles H. , Gwinn Katrina A. , Newman Stephanie
Published: May 2005

Restless leg syndrome (RLS) is usually idiopathic but may occur in patients with Parkinson's disease (PD). Both respond to dopaminergic medications. Whether these disorders share a common pathophysiology is unclear. Because PD is associated with a loss of olfactory function, we compared the olfactory function, we compared the olfactory function of patients with RLS with control and PD patients. Using the University of Pennsylvania Smell Identification Test (UPSIT), olfactory function was found to be normal in patients with idiopathic RLS and significantly reduced in patients with PD. This suggests that the pathophysiology of RLS differs from PD, and that RLS likely is not a “forme fruste” or a preclinical sign of PD.
Proton MR spectroscopic findings in paroxysmal kinesigenic dyskinesia
Authors: Kim Mee Ohk , Im Joo‐Hyuk , Choi Choong Gon , Lee Myoung Chong
Published: May 2005

Although paroxysmal kinesigenic dyskinesia (PKD) has characteristic clinical features, the pathophysiology of PKD has remained unknown. The purpose of this study was to investigate the pathophysiology of idiopathic PKD by performing proton magnetic resonance spectroscopy (1H‐MRS) in five patients with idiopathic PKD. Three patients were familial and two sporadic. Single‐voxel 1H‐MR was performed on a GE 1.5‐T SIGNA MR system. Localized 1H‐MR spectra were obtained from the basal ganglia (n = 5), thalamus (n = 3), and supplementary motor area (SMA; n = 4) using STEAM sequence (stimulated echo acquisition mode; TR = 3.0 sec, TE = 30 msec, 64 AVG, volume = 8 mL) or PRESS (point resolved spectroscopy; TR = 3.0 sec, TE = 135 msec, volume = 4 mL). Peak ratios of Cho/Cr (Cho: choline, Cr: creatine) and mI/Cr (mI: myoinositol) were decreased significantly in the unilateral basal ganglia of two patients. In one, decreased peak ratio of mI/Cr in the unilateral basal ganglia was the only abnormality. In the remaining two, there was no significant abnormality. 1H‐MR spectra obtained from the thalamus and SMA were all within normal limits. In conclusion, these results suggest that underlying pathophysiological mechanism of PKD may be at least partially associated with the dysfunction of cholinergic system in the basal ganglia.
Resurgence of functional neurosurgery for Parkinson's disease: A historical perspective
Authors: Speelman J. D. , Bosch D. A.
Published: May 2005

The history of functional neurosurgery for the treatment of Parkinson's disease is reviewed. Two major stages may be distinguished: (1) open functional neurosurgery, which started in 1921 with bilateral cervical rhizotomy by Leriche. In 1937 Bucy performed the first motor cortectomy in a tremor patient, and subsequently introduced lesioning of the corticospinal tract at different levels. In 1939 Meyers started open transventricular surgery of the basal ganglia, which was abandoned in the 1940s because of high mortality. However, this operation drew attention to the basal ganglia and their efferent pathways as surgical targets for the relief of parkinsonian symptoms. (2) Stereotactic (closed) functional neurosurgery in patients was in 1947 for the first time performed by Spiegel and Wycis, soon followed by surgeons in various countries. Originally, the globus pallidus and the ansa lenticularis were the surgical targets but were replaced at the end of the 1950s by the ventrolateral thalamus. A few surgeons positioned their lesions in the subthalamic area. In both targets favorable results were reported for the treatment of tremor and rigidity with acceptable adverse events. In selected patients, bilateral surgery was performed. In 1969 the results of more than 37,000 stereotactic operations had been published. Criteria for the surgical technique and selection of patients were described, and various stereotaxic atlases became available. At that time, L‐dopa became generally available and the number of stereotactic operations declined dramatically. However, as a result of the shortcomings of the L‐dopa therapy in the long‐term treatment of Parkinson's disease, the thalamotomy gradually regained its place. New developments were the reintroduction of the pallidotomy by Laitinen in 1992 and the thalamic stimulation for pharmacotherapy‐resistant tremor by Benabid and collaborators in 1991. New insights in the pathophysiology of Parkinson's disease supported the revival of the functional stereotactic neurosurgery and recently caused the introduction of the subthalamic nucleus as a surgical target in the treatment of Parkinson's disease.
Factor structure of the unified Parkinson's disease rating scale: Motor examination section
Authors: Stebbins Glenn T. , Goetz Christopher G.
Published: May 2005

The Unified Parkinson's Disease Rating Scale (UPDRS) is widely used to asses Parkinson's disease (PD) disability but its metric properties have not been extensively studied. We investigated the factor structure and internal consistency of the Motor Examination section of the UPDRS in a sample of 294 consecutive patients with idiopathic PD who were assessed while in the “on” state. There was a high degree of internal consistency. Factor analysis revealed six clinically distinct factors, three bradykinesia measures (axial/gait, right and left), one rigidity measure, and two tremor measures (rest and postural). These factors accounted for 78% of the variance. Total Motor Examination scores and selected factors correlated well with other examiner‐determined global ratings of PD disability (Hoehn and Yahr stage and Schwab‐England Activities of Daily Living score). These results suggest that the Motor Examination section of the UPDRS provides a useful measure of PD function as well as severity measures of six clinical disability domains.
Effects of SIB‐1508Y, a novel neuronal nicotinic acetylcholine receptor agonist, on motor behavior in parkinsonian monkeys
Authors: Schneider Jay S. , Pope‐Coleman Anne , Van Velson Maria , Menzaghi Frederique , Kenneth Lloyd G.
Published: May 2005

The potential antiparkinsonian effects of the centrally acting, subtype‐selective neuronal nicotinic acetylcholine receptor agonist (S)‐(7‐)‐‐5‐ethynyl‐3‐(1‐methyl‐2‐pyrrolidinyl)‐pyridine (SIB‐1508Y) was assessed on motor symptoms and disability scale ratings in three monkeys previously made parkinsonian by chronic exposure to the dopaminergic neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). Compared with levodopa (L‐dopa), SIB‐1508Y exerted only mild antiparkinsonian effects when administered alone. Emetic effects of this drug interfered with potential therapeutic effects at higher doses. However, when a low, ineffective dose of SIB‐1508Y was combined with low, ineffective doses of L‐dopa, a significant clinical effect was observed. These data suggest that subtype‐selective nicotinic acetylcholine receptor agonists may hold promise as antiparkinsonian agents, and when administered in combination with L‐dopa may allow a reduction in the dose of L‐dopa needed to achieve a significant clinical effect.
Event‐Related desynchronization to contingent negative variation and Self‐Paced movement paradigms in Parkinson's disease
Authors: Magnani Giuseppe , Cursi Marco , Leocani Letizia , Volonté Maria Antonietta , Locatelli Tiziana , Elia Aldo , Comi Giancarlo
Published: May 2005

The event‐related desynchronization (ERD) to voluntary movemtnt is an indicator of cortical activation with a high time resolution and a specific spatial representation. We have evaluated 10 patients affected by Parkinson's disease (PD), free from L‐dopa treatment for at least 12 hours, and 10 control subjects. Each subject underwent ERD examination during self‐paced movement (SPM) and during contingent negative variation (CNV) paradigms. ERD was measured as the percentage decrease of alpha band power and calculated for frequency bands of 1 Hz, ranging between 8 and 12 Hz. For group comparisons, the frequency showing the highest ERD was selected for each subject and for each side. In the control group. ERD in the CNV paradigm began over the contralateral centroparietal electrodes 1475 ms before movement onset of the right hand and 1375 ms for the left. In the SPM paradigm, ERD started over the contralateral central electrodes 2150 ms and 1775 ms before movement onset of the right and left hand, respectively. In the PD group, ERD started over the contralateral central areas 800 ms and 475 ms before movement onset of the right and left hand, respectively, for CNV paradigm and 1200 ms and 750 ms for the right and left hand, respectively, for SPM paradigm. Therefore, contralateral ERD began closer to movement onset in PD compared with the control group in both paradigms. ERD over the sensorimotor areas ipsilateral to the movement was not significantly different in PD compared with the control group. The finding of delayed contralateral ERD in PD is according to the view that functional cortical activation related to movement preparation is impaired in PD. The lack of group differences in the onset of ipsilateral ERD, which appears close to movement execution than contralateral ERD both in normal subjects and in PD, suggests that different mechanisms may be involved in generating ERD over the hemispheres ipsilateral and contralateral to the movement, and that only the latter are impaired in PD.
Apomorphine enantiomers protect cultured pheochromocytoma (PC12) cells from oxidative stress induced by H2O2 and 6‐Hydroxydopamine
Authors: Gassen Michael , Gross Aviva , Youdim Moussa B. H.
Published: May 2005

A significant body of evidence has been provided to support the hypothesis that oxidant stress may be responsible for the degeneration of dopaminergic neurons in the substantia nigra pars compacta in Parkinson's disease. Apomorphine, a dopamine D1/D2‐receptor agonist in the clinical therapy of Parkinson's disease, has been found to be a potent antioxidant and to prevent free radical reaction in rat brain mitochondrial fraction. In this article we show that 1–10 µM of apomorphine protects rat pheochromocytoma (PC12) cells from the toxic effects of H2O2 (0.6 mM) and the neurotoxin 6‐hydroxydopamine (150 µM). Neither of these effects were exhibited by ascorbic acid, desferal, lisuride, or bromocriptine. Although pergolide exhibited some protection of PC12 cells against H2O2 toxicity, it was not as potent as apomorphine. In light of the present findings and the clinical reports that parkinsonian patients on long‐term apomorphine therapy stabilize clinically and can be weaned off L‐dopa, one may assume that apomorphine can exert a neuroprotective activity by way of its potent antioxidant properties.
Efaroxan, an alpha‐2 antagonist, in the treatment of progressive supranuclear palsy
Authors: Rascol Olivier , Sieradzan Kasia , Peyro‐Saint‐Paul Hélène , Thalamas Claire , Brefel‐Courbon Christine , Senard Jean Michel , Ladure Philippe , Montastruc Jean Louis , Lees Andrew
Published: May 2005

We have tested, in a prospective randomized, double‐blind, placebo‐controlled, crossover, 12‐week study, the effects of 2 mg efaroxan, a potent alpha‐2 antagonist, given three times per day to 14 patients with progressive supranuclear palsy. Efaroxan did not induce any significant change on any motor assessment criteria. The present data do not confirm the assumption that the blockade of alpha‐2 receptors might be a useful pharmacologic strategy to improve patients with progressive supranuclear palsy.
Pallidotomy for generalized dystonia
Authors: Ondo William G. , Michael Desaloms J. , Jankovic Joseph , Grossman Robert G.
Published: May 2005

We systematically evaluated the efficacy of both unilateral and bilateral stereotactic pallidotomy in eight patients with generalized dystonia. Six patients had a marked improvement in dystonic movements and motor function; the other two patients also benefited from the procedure but to a lesser extent. The severity of dystonia was assessed before and after surgery by the Burke‐Marsden‐Fahn Dystonia Scale (BMFDS), the Unified Dystonia Rating Scale (UDRS), and the Activity of Daily Living Scale (ADL). The BMFDS scores decreased by 59.0%, UDRS by 62.5%, and ADL by 47.8% postoperatively. Adverse events were limited to a transient weakness in one patient. We conclude that pallidotomy is a safe and effective treatment in medically refractory cases of generalized dystonia.
Muscle afferent block for the treatment of oromandibular dystonia
Authors: Yoshida Kazuya , Kaji Ryuji , Kubori Tamotsu , Kohara Nobuo , Iizuka Tadahiko , Kimura Jun
Published: May 2005

Oromandibular dystonia is a focal dystonia involving the masticatory and tongue muscles, causing difficulties in speech or mastication. We treated 13 patients with this condition by injecting diluted lidocaine and alcohol intramuscularly. This method is aimed at reducing muscle spindle afferent activity. The symptoms had been resistant to other therapies such as pharmacotherapy or dental treatment. All patients showed clinical improvement after this therapy with reduced EMG activities in the affected muscles, whereas control injection of normal saline gave no changes in EMG activities. The overall subjective improvement was 57.7 ± 25.1% (mean ± standard deviation) in a self‐rating scale. The mean response of the jaw elevator muscles (70 ± 13.1%) was significantly higher (p < 0.02, t test) than that of the depressor muscles (38 ± 28.4%). Despite the precise mechanism being unknown, this difference might be related to the smaller number of muscle spindles in the depressor than the elevator muscles. This therapy is useful for the treatment of drug‐resistant oromandibular dystonia.
Treatment of cervical dystonia: A comparison of measures for outcome assessment
Authors: Lindeboom Robert , Brans Jeroen W. M. , Aramideh Majid , Speelman Hans D. , De Haan Rob J.
Published: May 2005

There is little agreement on which outcome measures to use to express the efficacy of treatments for cervical dystonia. We analyzed change scores on various scales of 64 new patients with cervical dystonia before and after repeated injections with botulinum toxin.

Method: The association between change in impairment (Tsui), and change in pain (TWSTRS‐Pain) and functional health (TWSTRS‐D, MOS‐20) was expressed in percentages of variance explained. Effect sizes of the outcome measures from patients who continued botulinum treatment and dropouts were compared. Performance of outcome measures to distinguish patients who continued treatment and dropouts was analyzed with ROC curves and areas under the curve (AUC).

Results: Impairments explained ≤ 7% of the score variance in functional health. There were no differences between the effect sizes of impairment and pain of patients who continued treatment and dropouts (p > 0.60). This suggests a poor reflection of the treatment efficacy by these outcome measures. Conversely, there were significant differences between the effect sizes of the functional status scales of the patients who continued treatment and the dropouts (p ≤ 0.01). ROC curve analysis showed that the disability, handicap, and global disease burden scale accurately distinguished between the two groups (AUCs > 0.80). Impairments showed no discriminative accuracy (AUC = 0.46).

Conclusion: Neurologic impairments have a small impact on the functional health of cervical dystonia patients. Disability, handicap, and a global measure of disease burden were the most suitable outcome parameters to express the clinical efficacy of botulinum therapy.
Conjugate eye deviations as dyskinesias induced by levodopa in Parkinson's disease
Authors: Lewitt Peter A.
Published: May 2005

Involuntary upward and lateral eye movements are described in two Parkinson's disease patients who also experience levodopa‐induced chreoathetoid limb movements simultaneously. These brief deviations of gaze represent a rare ocular manifestation of dyskinesia and are similar to oculogyric movements resulting from other causes.