bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of swallowing function in Parkinson's disease and progressive supranuclear palsy
Authors: Johnston Brain T. , Castell June A. , Stumacher Sharon , Colcher Amy , Gideon R. Matthew , Li Qun , Castell Donald O.
Published: May 2005

Dysphagia is common in both Parkinson's disease (PD) and progressive supranuclear palsy (PSP). Although it is believed to be more common in PSP, there are no controlled data and no comparison of swallowing function between these two disorders. Our aim was to assess dysphagia and swallow function in patients with PSP and PD. Seven patients with PSP were matched to seven patients with PD on the basis of disease duration. Self‐rated dysphagia, movement disorder disability, modified barium swallow results, and abnormalities noted on manometry of the lower esophageal sphincter, esophageal body, upper esophageal sphincter, and pharynx were compared between the two groups. Neither severity nor duration of dysphagia differed between the two groups. Patients with PSP had a significantly greater degree of disability [median (range) Hoehn & Yahr score, 4 (3–5) vs. 2 (1–2); p < 0.002]. Manometric abnormalities were similar for the two groups. Oral‐phase abnormalities on modified barium swallow were significantly more frequent in PSP (four patients with PSP vs. no patients with PD; p < 0.005). Pharyngeal abnormalities did not differ. Modified barium‐swallow scores correalated well with self‐reported dysphagia severity for patients with PSP (r = 0.93; p < 0.05) but not for those with PD (r = 0.42; p = NS). The frequency of abnormalities noted during the oral phase was significantly increased in PSP. It is hypothesized that the sensory information conveyed due to this may account for the better correlation between symptoms and swallowing abnormalities and the belief that swallowing problems are more common in PSP.
Adult‐onset subacute sclerosing panencephalitis: Case reports and review of the literature
Authors: Singer Carlos , Lang Anthony E. , Suchowersky Oksana
Published: May 2005

Subacute sclerosing panencephalitis (SSPE) is mainly thought of as a disorder of childhood and adolescence and may not be readily recognized when presenting later in life. Prior reports have suggested that adult‐onset SSPE may have atypical features. We have added two cases to the existing literature on adult‐onset SSPE, compared them with a more classic juvenile presentation, and extensively reviewed those reports that were published after the etiological link with the measles virus had been established. Adult‐onset SSPE patients present at a mean age of 25.4 years (range 20–35 years). They have a higher proportion of either negative history of measles exposure or undocumented history by the reporting authors. Those with available history of measles exposure tend to have it either earlier (younger than 3 years old) or later (after 9 years) than the usual childhood measles infection. Where the primary infection is known, unusually long measles‐to‐SSPE intervals have been documented, ranging from 14 to 22 years. None of the cases followed measles vaccination. Visual symptomatology was very frequent, with 8 of the 13 cases reviewed having a purely ophthalmological presentation; only 2 patients presented with behavioral changes. Although the course of the disease was progressive and fatal in the majority, there appeared to be a higher rate of spontaneous remission as compared with childhood‐onset SSPE. Myoclonus, spastic hemiparesis, bradykinesia, and rigidity were the predominant motor manifestations. Neuropathology revealed cortical and subcortical gray matter involvement preferentially of the occipital lobes, thalamus, and putamen. The importance of recognizing the spectrum of potential presentations of SSPE and providing an early diagnosis will increase as more effective treatments become available.
Clinical features and management of two cases of encephalitis lethargica
Authors: Blunt Stavia B. , Lane Russel J. M. , Turjanski Nora , Perkin G. David
Published: May 2005

Two patients with presumed encephalitis lethargica are presented with clinical features suggestive of two forms of the disease described by Von Economo: One patient had a psychosis and a mute‐akinetic syndrome associated with myoclonus. The second patient presented with a psychosis and fever, developing severe dyskinesias involving the mouth, trunk and limbs, together with respiratory irregularities and presumed hypothalamic disturbance and disturbance of consciousness. In both cases, initial cerebrospinal fluid (CSF) examination revealed an elevated white cell count (predominantly lymphocytes), elevated protein in case 2, and oligoclonal bands in both cases. Computed tomography (CT) brain scan was normal but in both cases EEG revealed diffuse slow wave activity. A 18F‐Dopa positron emission tomography (PET) scan in case 2 was normal. The medical management of both patients is discussed. In case 1, L‐Dopa improved the akinesia, while the myoclonus responded to clonazepam. In case 2, the severe dyskinesias failed to respond to a number of drugs, and she ultimately required paralysis to relieve her almost continuous movements. Both patients responded rapidly and dramatically to intravenous methylprednisolone. We suggest that steroid treatment should be considered in the acute phase of patients with features suggestive of encephalitis lethargica.
Impairments of movement kinematics in patients with Huntington's disease: A comparison with and without a concurrent task
Authors: Georgiou Nellie , Phillips Jim G. , Bradshaw John L. , Cunnington Ross , Chiu Edmond
Published: May 2005

This study aimed to quantify the efficiency and smoothness of voluntary movement in Huntington's disease (HD) by the use of a graphics tablet that permits analysis of movement profiles. In particular, we aimed to ascertain whether a concurrent task (digit span) would affect the kinematics of goal‐directed movements. Twelve patients with HD and their matched controls performed 12 vertical zig‐zag movements, with both left and right hands (with and without the concurrent task), to large or small circular targets over long or short extents. The concurrent task was associated with shorter movement times and reduced right‐hand superiority. Patients with HD were overall slower, especially with long strokes, and had similar peak velocities for both small and large targets, so that controls could better accommodate differences in target size. Patients with HD spent more time decelerating, especially with small targets, whereas controls allocated more nearly equal proportions of time to the acceleration and deceleration phases of movement, especially with large targets. Short strokes were generally less force inefficient than were long strokes, especially so for either hand in either group in the absence of the concurrent task, and for the right hand in its presence. With the concurrent task, however, the left hand's behavior changed differentially for the two groups; for patients with HD, it became more force efficient with short strokes and even less efficient with long strokes, whereas for controls, it became more efficient with long strokes. Controls may be able to divert attention away from the inferior left hand, increasing its automaticity, whereas patients with HD, because of disease, may be forced to engage even further online visual control under the demands of a concurrent task. Patients with HD may perhaps become increasingly reliant on terminal visual guidance, which indicates an impairment in constructing and refining an internal representation of the movement necessary for its effective execution. Basal ganglia dysfunction may impair the ability to use internally generated cues to guide movement.
6‐Pyruvoyl‐tetrahydropterin synthase deficiency with generalized dystonia and diurnal fluctuation of symptoms: A clinical and molecular study
Authors: Hanihara T. , Inoue K. , Kawanishi C. , Sugiyama N. , Miyakawa T. , Onishi H. , Yamada Y. , Osaka H. , Kosaka K. , Iwabuchi K. , Owada M.
Published: May 2005

We report the case of a 44‐year‐old woman with a partial 6‐pyruvoyl tetrahydropterin synthase (6‐PTS) deficiency, whose predominant clinical symptom was generalized dystonia with marked diurnal fluctuation. Dystonia was present in the eyelids, oromandibular region, trunk, and extremities (Meige syndrome plus double hemiplegia‐like dystonia). A marked and sustained positive response to levodopa was observed. A molecular genetic study revealed a homozygous mutation (I114V) in the 6‐PTS gene. This study indicates that genetic abnormality in the 6‐PTS gene may be a hereditary dystonic disorder. We speculate that our patient has residual 6‐PTS activity in the central nervous system, such as in the liver, and we suggest that residual, but insufficient production of tretrahydrobiopterin may play an important role in causing diurnal fluctuation of symptoms.
Long‐term results with cisapride in Parkinson's disease
Authors: Jost Wolfgang H. , Schimrigk Klaus
Published: May 2005

In this study, we examined whether there is a longterm effect of cisapride on colonic transit in Parkinson's disease. Twenty‐five patients (11 women, 14 men; average age, 64.4 years; moderate symptoms) were studied and treated initially with cisapride, 5 mg, twice a day, and after the first week with cisapride, 10 mg, twice a day. Colonic transit was measured by radioopaque markers at various stages: after 1 week, 6 months, and 1 year. In untreated patients, transit took 131 h; after 1 week with cisapride, it was accelerated to 81 h. After 6 months, colonic transit time amounted to 99 and to 118 h, respectively, after 1 year. Cisapride seems to be highly effective initially. After 6 months, a significant but reduced effect was seen, and after 1 year, only a small effect could be demonstrated.
Midbrain tremor and hypertrophic olivary degeneration after pontine hemorrhage
Authors: Shepherd Gordon M. G. , Tauböll Erik , Bakke Sören Jacob , Nyberg‐Hansen Rolf
Published: May 2005

A severe rest tremor arose in a patient's right arm 9 months after a pontine tegmental hemorrhage. Magnetic resonance studies at 4 and 10 months showed residual hemosiderin in the pons and increasing hypertrophic olivary degeneration (HOD) affecting primarily the left olive. The tremor was refractory to pharmacotherapy (clonazepam, propranolol, and levodopa), but was reduced after implantation of a thalamic stimulator device. Although pontine hemorrhage is among several common causes of HOD, it has not previously been appreciated as a cause of midbrain (“rubral”) tremor. A disynaptic dentatorubroolivary tract associated with tremor and a monosynaptic dentatoolivary tract associated with HOD may both be components of the rubro‐olivocerebellorubral loop implicated in midbrain tremor. Their proximity makes the combination of tremor and HOD after pontine tegmental damage plausible and even likely.
Electrophysiological observations in idiopathic opsoclonus–myoclonus syndrome
Authors: Gwinn Katrina A. , Caviness John N.
Published: May 2005

To supplement existing knowledge regarding the pathophysiology of the opsoclonus‐myoclonus syndrome, electrophysiological findings are reported in three patients with idiopathic opsoclonus–myoclonus. Surface electromyography (EMG) revealed <100‐ms synchronous discharges correlating with the clinical myoclonus. Short duration EMG discharges, with no back‐averaged cortical correlate, normal gross electroencephalogram, and no exaggerated responses with either evoked potential testing or long latency EMG responses were observed. The clinical and electrophysiological findings we describe are consistent with a brainstem origin of the myoclonus in this syndrome, with concurrent abnormalities in cerebellar circuits, similar to those described for paraneoplastic cases. The constellation of these electrophysiological findings differentiates the myoclonus in these patients from other clinical myoclonic entities.
Urinary disturbances in striatonigral degeneration and parkinson's disease: Clinical and urodynamic aspects
Authors: Bonnet A. M. , Pichon J. , Vidailhet M. , Gouider‐Khouja N. , Robain G. , Perrigot M. , Agid Y.
Published: May 2005

Although urinary disturbances are more frequent in multiple system atrophy (MSA) than in Parkinson's disease (PD), the striatonigral degeneration (SND) type of MSA is difficult to distinguish from PD, especially when the latter is associated with orthostatic hypotension or urinary symptoms. The pattern of urinary symptoms and urodynamic dysfunction was analyzed in 15 SND and 35 PD patients with urinary complaints. In SND, dysuria with or without chronic retention, frequently associated with a hypoactive detrusor and low urethral pressure, permitted early and reliable diagnosis. In PD, urgency to void, with or without difficulty voiding, but without chronic retention, associated with detrusor hyperreflexia and normal urethral sphincter function, predominated. In clinical practice, the study of urinary symptoms and bladder function may help to distinguish SND from PD in patients with urinary disturbances.
Dentatorubral and pallidoluysian atrophy (DRPLA) Clinical and neuropathological findings in genetically confirmed north american and european pedigrees
Authors: Becher M. W. , Rubinsztein D. C. , Leggo J. , Wagster M. V. , Stine O. C. , Ranen N. G. , Franz M. L. , Abbott M. H. , Sherr M. , Macmillan J. C. , Barron L. , Porteous M. , Harper P. S. , Ross C. A.
Published: May 2005

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant disorder that clinically overlaps with Huntington's disease (HD) and manifests combinations of chorea, myoclonus, seizures, ataxia, and dementia. DRPLA is caused by a CAG triplet repeat (CTG‐B37) expansion coding for polyglutamine on chromosome 12 and exhibits the genetic phenomenon of anticipation. This neurodegenerative disease has only rarely been reported in non‐Japanese pedigrees, and there are only a few neuropathological studies in genetically confirmed patients. We report 10 cases of DRPLA from two North American and two British pedigrees in which CTG‐B37 expansions have been demonstrated within each kindred (54‐83 repeats), individually in 8 of the 10 cases, and describe the neuropathological findings in 4 cases. Members of DRPLA kindreds have a wide range of clinical phenotypes and markedly variable ages at onset. The neuropathological spectrum is centered around the cerebellifugal and pallidofugal systems, but neurodegenerative changes can be found in many nuclei, tracts, and systems. Evidence of CTG‐B37 triplet repeat expansion should be sought in HD‐like cases that are negative for expanded triplet repeats within the HD IT15 gene or in autopsy cases with degeneration of the dentatorubral or pallidoluysian systems.
AIDS dementia complex with generalized myoclonus
Authors: Maher John , Choudhri Rshujeel , Halliday William , Power Christopher , Nath Avindra
Published: May 2005

Focal and segmental, but not generalized, myoclonus have been described with human immunodeficiency virus (HIV) infection. We describe three patients with generalized myoclonus and acquired immunodeficiency syndrome (AIDS) dementia complex. In each, myoclonus persisted until death, invariably after a course of a few months. In two patients, myoclonus was elicited by sudden auditory stimuli and resembled a startle response. This form of myoclonus may be subcortical in origin. We suggest that the AIDS dementia complex be included among the causes of myoclonic dementia.
The dopamine transporter: A crucial component regulating dopamine transmission
Authors: Jaber Mohamed , Jones Sara , Giros Bruno , Caron Marc G
Published: May 2005

The dopamine system is implicated in the control of locomotion, cognition, and endocrine function, The relative contribution of the various dopamine‐related components is not well established mainly because drugs that target the dopaminergic system often lack selectivity. The in vivo gene inactivation procedure, or knockout, enables the creation of new strains of mice lacking a specific gene. This technique has been applied recently to inactivate the expression of the plasma membrane dopamine transporter. Here we summarize the main findings obtained with these transgenic mice carrying this “genetic defect.” leading to a better understanding of the relative contribution of the dopamine transporter regarding locomotor activity, regulation of the expression of peptides under the control of dopaminergic activity, and responses to various drugs targeting the dopamine system. Our results establish not only the central importance of the transporter as the key element controlling dopamine levels in the brain, but also its role as an obligatory target for the behavioral and biochemical action of amphetamine and cocaine. In addition, the genetically altered mice offer a unique model to test the specificity and selectivity of dopamine transporter‐acting drugs and may provide important new concepts related to the clinical and social implications of conditions such as Parkinson's disease, schizophrenia, and drug addiction.
The ‘common deletion’ is not increased in parkinsonian substantia nigra as shown by competitive polymerase chain reaction
Authors: Kösel Siegfried , Egensperger Rupert , Schnopp Nina M. , Graeber Manuel B.
Published: May 2005

Previous studies have estimated levels of mitochondrial DNA (mtDNA) carrying the 4,977‐base‐pair 'common deletion' in tissues from patients with Parkinson's disease (PD) by using semiquantitative techniques. The role of this deleted mtDNA species in the pathogenesis of PD has remained controversial. We have applied competitive polymerase chain reaction to achieve exact quantitation of deleted mtDNA in the substantia nigra and additional brain regions of cases with neuropathologically confirmed Lewy‐body parkinsonism, In addition, genotyping was carried out for CYP2D6G1,934A and CYP2D6C2,938Talleles and the mitochondrial ND2 (nucleotide 5,460) and transfer RNA for glutamine (nucleotide 4,336) sequence variants. Parkinsonian brains showed 1–3% deleted mtDNA in the substantia nigra, that is, deletion levels were not higher than in age‐matched controls. Our findings suggest that the defect in complex I of the respiratory chain observed in PD is not primarily due to the ‘common deletion’.
Comparison of standard carbidopa–levodopa and sustained‐release carbidopa–levodopa in parkinson's disease: Pharmacokinetic and quality‐of‐life measures
Authors: Pahwa Rajesh , Lyons Kelly , McGuire Desni , Silverstein Paul , Zwiebel Felix , Robischon Mary , Koller William C.
Published: May 2005

We compared clinical, pharmacokinetic, and quality‐of‐life measures in patients with Parkinson's disease (PD) who were on standard carbidopa‐levodopa (Std‐L) and after conversion to sustained‐release carbidopa‐levodopa 50/200 (L‐CR). A total of 20 PD patients with motor fluctuations participated in the study and 18 completed it. There were 10 women and eight men, with a mean age of 67.5 years and a mean disease duration of 9.9 years. All patients underwent 10‐h pharmacokinetic and clinical evaluations while on Std‐L and again while on L‐CR. The patients maintained diaries for 2 days before the 10‐h evaluations and completed a sickness impact profile (SIP) while on Std‐L and again while on L‐CR. The total daily levodopa intake was significantly greater with L‐CR because of the reduced bioavailability of the L‐CR. The mean daily levodopa dosage was 569 mg for Std‐L compared with 751 mg for L‐CR. The patients performed better in walking time, Unified Parkinson's Disease Rating Scale (motor score), and tapping total with L‐CR, although the improvement was not statistically significant. There was no significant difference in dyskinesias between the two preparations. The plasma levodopa levels and the areas under the curve were significantly greater with L‐CR. “On” time as measured by patient diaries was significantly greater for L‐CR. There was no significant difference in the total SIP scores for patients on the two preparations, but patients had significantly better home management and mobility while on L‐CR. In conclusion, L‐CR resulted in more “on” time with greater plasma levodopa levels, which resulted in better home management and mobility.
The acoustic startle response is normal in patients with multiple system atrophy
Authors: Valldeoriola F. , Valls‐Solé J. , Tolosa E. , Nobbe F. A. , Muñoz J. E. , Martí J.
Published: May 2005

We investigated the acoustic startle response in eight patients with MSA and compared the results with those from a group of age matched healthy subjects. Onset latency and amplitude of the responses obtained in the orbicularis oculi, masseter and sternocleidomastoid muscles were not different in patients and control subjects. We conclude that, in spite of the pathological derangement described in brainstem reticular nuclei in MSA, the neuronal circuits mediating the auditory startle reflex are functionally preserved.
Cerebral glucose metabolism in patients with spasmodic torticollis
Authors: Magyar‐Lehmann Stefanie , Antonini Angelo , Roelcke Ulrich , Maguire Ralph P. , Missimer John , Meyer Manuel , Leenders K. L.
Published: May 2005

The pathophysiology of spasmodic torticollis is not clear. Basal ganglia dysfunction has been suggested to underlie this clinical syndrome. We studied resting cerebral glucose metabolism in 10 spasmodic torticollis patients and 10 healthy controls by using positron‐emission tomography and [18F]2‐fluoro‐2‐deoxy‐D‐glucose. Statistical parametric mapping (SPM95) was used to compare both groups on a pixelby‐pixel basis. Torticollis patients showed a significantly higher glucose metabolism bilaterally in the lentiform nucleus (p < 0.005). Analyses performed using normalization of regional to global glucose metabolism confirmed this finding (controls, 1.26 ± 0.06, and patients, 1.35 ± 0.06; p < 0.01). The torticollis score did not correlate with glucose metabolism, nor did disease duration or side of chin direction. Our results indicate that the lentiform nucleus plays a predominant role in the pathophysiology of idiopathic spasmodic torticollis.
Quantitative assessment of botulinum toxin treatment in 43 patients with head tremor
Authors: Wissel Jörg , Masuhr Florian , Schelosky Ludwig , Ebersbach Georg , Poewe Werner
Published: May 2005

We treated 43 patients who had head tremor as the major complaint with local botulinum toxin type A (Btx A) injections into neck muscles: 29 patients were classified as suffering from tremulous cervical dystonia (TCD), and 14 had head tremor without dystonia (HT). All patients were clinically assessed by means of the Tsui scale and a 4‐point pain scale at baseline and follow‐up visit. Quantitative recordings of head tremor with a bidirectional accelerometer system (horizontal and vertical planes) placed on the forehead were obtained before and 2–3 weeks after Btx A injections. Muscle selection for an injection was based on the visible and palpable tremor oscillation in the involved neck muscles and on analysis of standardized simultaneous electromyographic recordings of six cervical muscles. Patients with HT recieved mean total doses of 400 units (U) of Dysport (Btx A) (range, 160–560 U) distributed between the two splenius capitis muscles. Patients with TCD received a mean total dose of 500 U Dysport (range, 320–720 U) injected into a mean of 3 muscles (range, 2–4 muscles). The condition of all patients with HT and of 26 of the 29 patients with TCD improved subjectively. The total on the Tsui scale as well as pain scores decreased significantly (p < 0.05) following treatment. Latency of onset, duration of improvement, and side effects showed no significant difference in HT and TCD. Amplitude of HT decreased significantly for both groups following treatment. The mean dominant peak frequency in TCD and HT was slightly less than 5 Hz and did not change significantly after treatment.
Antiphospholipid antibodies: An epiphenomenon in tourette syndrome
Authors: Singer Harvey S. , Krumholz Andrea , Giuliano Joseph , Kiessling Louise S.
Published: May 2005

Antiphospholipids (aPLAs) have been previously identified in children with Tourette syndrome (TS), which has led to the speculation that these antibodies might have a pathophysiologic role in this disorder. Therefore, 21 healthy children and adolescents with TS, whose ages ranged from 7 to 17 years, underwent laboratory studies designed to diagnose the lupus anticoagulant, anticardiolipin (aCL) antibodies [immunoglobulin (Ig) G, IgA, and IgM], and antinuclear antibodies. Although five subjects had at least one value that differed from accepted laboratory standards, the changes were marginal in four of them. Lupus anticoagulant was identified in one patients, based on a minimal requirement of a prolonged dilute Russel viper venom time, clotting studies that did not correct after mixture with normal plasma, and an abnormal platelet neutralization procedure. A prolonged (but correctable) activated partial thromboplastin time was found in one individual, and aCL IgG was marginally increased in three subjects. Two (10%) of a control population of 20 same‐age children also had low positive aCL IgG levels. There were no differences in tics (onset, type, frequency, severity, and family history) or comorbid features between children with normal or “abnormal” laboratory study results. Our data suggest that the presence of aPLAs in TS represents an epiphenomenon rather than a pathophysiologic mechanism.
A new tremor mutant in the pietrain pig: An animal model of orthostatic tremor? Clinical and neurophysiological observations
Authors: Wissel Jörg , Harlizuis Barbara , Richter Angelica , Löscher Wolfgang , Schelosky Ludwig , Scholz Udo , Poewe Werner
Published: May 2005

A new tremor mutant, the “Campus syndrome” was studied in a breed of Pietrain pigs. Affected pigs showed a coarse tremor of the extremities when standing and walking, so they tended to remain recumbent, during which the tremor was suppressed. Needle electromyographic recordings of the semitendinosus muscle plus accelerometry revealed a high‐amplitude 14‐ to 15‐Hz tremor pattern activated specifically upon standing but maintained during walking. The observed syndrome thus bears similarities to the human condition of orthostatic tremor and might serve as an animal model for this as yet poorly understood disorder.
Concordance of common movement disorders among familial cases
Authors: Rajput A. H. , Fenton M. E. , George D. , Rajput Alex , Wilson W. , McCulloch L.
Published: May 2005

Multicase families are frequently utilized in studies of movement disorders (MDs). We report families with two or more MD cases seen at the Movement Disorder Clinic, Saskatoon (MDCS). In 30% of the MD probands, there was either a history or documentation of at least one secondary MD case in the family. Only those MD cases that were seen at the MDCS were considered in this study. A total of 56 probands and 77 secondary MD cases were seen at the MDCS between 1968 and 1996. In 24 (31.2%) of the secondary cases, the diagnosis was different from that in the proband. In 46 families (82%), only one secondary case was seen, and the diagnosis was concordant with the proband in 71.7%. In the remaining 10 families with two or more secondary cases, the diagnosis was concordant in 64.5% of cases. The largest subgroup was Parkinson's disease (PD)—40 probands and 53 secondary cases. Of these secondary cases, 73.6% had PD. The concordance rate was 91% in essential tremor, but only 12.5% if the proband had essential tremor + parkinsonism. Considering that a large proportion of secondary cases have a diagnosis discordant with the proband, we recommend that, wherever possible, MD diagnosis in secondary cases be based on clinical assessment.
Bilateral posteroventral pallidotomy in advanced parkinson's disease in three patients
Authors: Schuurman P. Richard , de Bie Rob M. A. , Speelman Johannes D. , Bosch D. Andries
Published: May 2005

In this report, we describe the effect of staged bilateral posteroventral pallidotomy in three patients with advanced Parkinson's disease who were all of the young‐onset type. Two patients had developed response fluctuations after the use of levodopa, with severe hypokinesia, painful dystonia, and rigidity in the “off” phase and violent dyskinesias in the “on” phase. One patient, in a continuous hypokinetic rigid state, was totally unresponsive to dopaminergic medication. All were at Hoehn and Yahr stage 5 in the “off” phase before surgery. After surgery, the hypokinetic state was reversed and dyskinesias were abolished in all patients. Hoehn and Yahr stages were 3 in the “off” phase postoperatively. Overall functional improvement was marked and lasting after follow‐up for 7, 12, and 13 months, respectively. Complications were visual field deficit and transient central facial paresis, both in the same patient. Bilateral posteroventral pallidotomy can ameliorate response fluctuations, hypokinesia, rigidity, and painful dystonia in advanced Parkinson's disease.
Association of a polymorphism in the dopamine‐transporter gene with parkinson's disease
Authors: le Couteur David G. , Leighton Peter W. , McCann Sally J. , Pond Susan M.
Published: May 2005

The presynaptic dopamine transporter in nigral dopaminergic neurons confers susceptibility to the cytotoxic effects of the neurotoxic metabolite of 1‐methy1‐4‐phenyl‐1,2,3,6‐tetrahydropyridine. Polymorphisms in the dopamine transporter might influence the susceptibility to such toxins. Therefore, we investigated whether a polymorphic region in the 3′‐untranslated region of the dopamine‐transporter gene is associated with idiopathic Parkinson's disease (PD). The frequency distribution of the alleles was significantly different between the patients (n = 100) and controls (n = 200, p < 0.05). The rare 11‐copy allele was more common in the patients (odds ratio = 10.2, 95% confidence interval = 1.2‐87.9, p < 0.025). The susceptibility of some people to PD may be conferred by polymorphisms in the dopamine‐transporter gene that could lead to increased cellular accumulation of neurotoxic compounds in dopaminergic neurons.
Tics secondary to craniocerebral trauma
Authors: Krauss Joachim K. , Jankovic Joseph
Published: May 2005

We describe three adult patients who presented with multifocal motor and vocal tics secondary to craniocerebral trauma. In one case, the tics were accompanied by marked obsessive‐compulsive behavior. All patients were involved in motor vehicle accidents resulting in closed craniocerebral trauma. The latency of onset between head trauma and the movement disorder varied between 1 day and a few months. Magnetic resonance imaging, which was performed in all three patients, did not detect any structural lesions of the basal ganglia or the brainstem. Extensive bifrontal leukoencephalopathy was found in one patient who suffered severe head trauma.
Mosaic pattern of gliosis in the neostriatum of a north american man with craniocervical dystonia and parkinsonism
Authors: Factor Stewart A. , Barron Kevin D.
Published: May 2005

We present the case of a 51‐year‐old patient with a 31‐year history of psychiatric symptoms, craniocervical dystonia, bulbar dysfunction, and parkinsonism. His dystonic movements included blepharospasm, jaw opening and lingual dystonia, and spasmodic retrocollis. Psychiatric symptoms included psychosis and depression, with onset years before the movement disorder. After his death by aspiration, examination of his brain revealed abnormalities limited to the neostriatum. Staining of brain sections, including Holzer, glial fibrillary acidic protein, and immunohistochemical stain for calbindin D28k, revealed the presence of a mosaic pattern of gliosis with neuronal loss (sparing large neurons) within this region. The islands of tissue between strands of gliosis had a normal appearance. This patient represents only the fourth case (and first North American born) with a mosaic pattern of gliosis in the neostriatum. The clinical and pathologic features were similar in all four cases except that our patient was the first with prominent psychiatric symptoms and a more stable, less progressive course. Mosaicism has been described in the X‐linked Filipino disorder Lubag. Occurrence in non‐Filipino patients, such as ours, suggests that either Lubag can develop in non‐Filipino families or that mosaicism is a nonspecific pathologic finding in some patients with idiopathic dystonia. Finally, our case supports the notion that craniocervical dystonia may result from neostriatal dysfunction.
A gene (ETM) for essential tremor maps to chromosome 2p22‐p25
Authors: Higgins Joseph J. , Pho Lana T. , Nee Linda E.
Published: May 2005

We report the results of linkage analysis in a large American family of Czech descent with dominantly inherited “Pure” essential tremor (ET) and genetic anticipation. Genetic loci on chromosome 2p22‐p25 establish linkage to this region with a maximum LOD score (Zmax) = 5.92 for the locus, D2S272. Obligate recombinant events place the ETM gene in a 15‐cM candidate interval between the genetic loci D2S168 and D2S224. Repeat expansion detection analysis suggests that expanded CAG trinucleotide sequences are associated with ET. These findings will facilitate the search for an ETM gene and may further our understanding of the human motor system.
Health‐related quality of life in parkinson's disease: A study of outpatient clinic attenders
Authors: Fitzpatrick Ray , Peto Viv , Jenkinson Crispin , Greenhall Richard , Hyman Nigel
Published: May 2005

Objective: To assess the validity and responsiveness of a questionnaire to assess health‐related quality of life in Parkinson's disease (PD)—the 39‐item Parkinson's Disease Questionnaire (PDQ‐39)—and to report problems experienced by patients by means of the questionnaire.
Tolcapone added to levodopa in stable parkinsonian patients: A double‐blind placebo‐controlled study
Authors: Dupont Erik , Burgunder Jean‐Marc , Findley Leslie J. , Olsson Jan‐Edvin , Dorflinger Ernest ,   Tolcapone In Parkinson's Disease Study Group Ii (TIPS Ii)
Published: May 2005

The primary objective of this study was to assess the effect of tolcapone on levodopa dosage in parkinsonian patients whose “wearing‐off” phenomenon has been controlled with more frequent levodopa dosage. After a 1‐week placebo run‐in, 97 patients were assigned randomly to receive placebo or tolcapone 200 or 400 mg three times daily (t.i.d.). Levodopa dosage was reduced by −35% on day 1 of study and subsequently retitrated as required. After 6 weeks, the tolcapone groups crossed over to receive the other dose for a further 3 weeks for exploratory purposes. Both tolcapone groups had greater reductions in levodopa dosage than the placebo group at week 6 (not statistically different). The 200‐mg t.i.d. group showed greatest improvement in estimated mean scores for all efficacy parameters (p < 0.05 versus placebo for change in Unified Parkinson's Disease Rating Scale Subscale II). Fewer dopaminergic and nondopaminergic adverse events were associated with tolcapone 200 mg t.i.d. than with tolcapone 400 mg t.i.d. The most frequently reported dopaminergic adverse events were nausea, cramps, dyskinesia, and dystonia. The most frequently reported unanticipated adverse event was diarrhea. Tolcapone 200 mg t.i.d. may provide additional benefit to patients with moderately advanced Parkinson's disease with treated “wearing‐off” phenomenon.
Entacapone enhances levodopa‐induced reversal of motor disability in MPTP‐treated common marmosets
Authors: Smith Lance A. , Gordin Ariel , Jenner Peter , Marsden C. David
Published: May 2005

Oral administration of levodopa (L‐dopa) (2.5–25.0 mg/kg) plus carbidopa (12.5 mg/kg p.o.) to MPTP‐treated common marmosets produced a dose‐related increase in locomotor activity and a corresponding decrease in motor disability. Pretreatment with the peripheral COMT inhibitor entacapone (12.5 mg/kg p.o.) enhanced the intensity and duration of the increase in locomotor activity and the reversal of motor disability produced by a threshold dose of L‐dopa (2.5 mg/kg p.o.) plus carbidopa. By contrast, entacapone pretreatment did not potentiate the increased locomotor activity or reversal of motor disability produced by a near‐maximal dose of L‐dopa (12.5 mg/kg p.o.) plus carbidopa. The effects of entacapone (5.0–25.0 mg/kg p.o.) were dose related, with doses of >12.5 mg/kg tending to produce less potentiation of L‐dopa's effects compared to lower doses. Pretreatment with entacapone (12.5 mg/kg p.o.) without carbidopa caused a short‐lasting enhancement of L‐dopa's (12.5 mg/kg p.o.) action, whereas pretreatment with carbidopa (12.5 mg/kg p.o.) alone had a more dramatic effect. However, pretreatment with both carbidopa and entacapone produced the greatest overall motor response. In conclusion, entacapone enhances the motor response produced by a low threshold dose of L‐dopa plus carbidopa. However, optimization of both the dose of L‐dopa and entacapone appears necessary to obtain the maximal therapeutic response.
Constipation in parkinson's disease: Objective assessment and response to psyllium
Authors: Ashraf Waseem , Pfeiffer Ronald F. , Park Faye , Lof John , Quigley Eamonn M. M.
Published: May 2005

We evaluated the reliability of patient history and the effect of psyllium on symptoms and colorectal function in 12 patients with Parkinson's disease (PD) and constipation. In all but two, constipation anteceded the development of parkinsonian symptoms. A comparison with prospectively obtained stool diaries confirmed the patients' reported constipation in 7 of the 12 patients. Those patients with confirmed constipation had lower stool weights and reported more straining at stool. Measures of colonic and anorectal function were similar in those who were truly constipated and those who were not. Among those PD subjects with confirmed constipation, psyllium increased stool frequency and weight but did not alter colonic transit or anorectal function. We conclude that prospectively obtained stool diaries should be employed to confirm constipation in PD and that psyllium produces both subjective and objective improvements in constipation related to PD.
Clinical expression of essential tremor: Effects of gender and age
Authors: Hubble J. P. , Busenbark K. L. , Pahwa R. , Lyons K. , Koller W. C.
Published: May 2005

Essential tremor (ET) is considered to be a monosymptomatic disorder consisting primarily of postural hand tremor. Nevertheless, clinical expression can vary based on the body region affected by tremor and the coexistence of other neurologic signs, such as tandem gait disturbance. We conducted a two‐part study to test the hypothesis that variability in ET clinical expression is influenced by gender and age. In part 1, we examined a large ET clinical database (n = 450), comparing ratings of postural hand and head/voice tremor based on gender. Head/voice tremor was significantly more frequent and more severe among female ET patients; men had more severe postural hand tremor. In part 2, ET patients (n = 40) had significantly more missteps when tandem walking in comparison to age‐matched controls. Poor tandem walk in ET cases was associated with more advanced age, but not gender, disease duration, or ratings of postural hand or head/voice tremor. We conclude that gender influences the body region most affected by ET possibly through the effects of the sex chromosomes or hormones. Ataxia (tandem gait difficulty) is common in ET and may be an accentuation of cerebellar dysfunction due to aging.
Cerebellar axial postural tremor
Authors: Brown P. , Rothwell J. C. , Stevens J. M. , Lees A. J. , Marsden C. D.
Published: May 2005

Three cases are presented with a predominantly axial postural tremor, without visible palatal tremor. Tremor varied in frequency between 3 and 10 Hz, often jumping from one frequency to another in this band. All three patients had evidence of cerebellar pathology. Cases 1 and 2 developed tremor in the setting of a lateLondon, Englandonset cerebellar degeneration and after excision of a right cerebellar haemangioblastoma, respectively. Etiology was unclear in Case 3. Nevertheless, this patient had a cerebellar dysarthria. The tremor was similar to that sometimes seen in conjunction with palatal tremor, and EMG studies in Case 3 demonstrated a subclinical modulation of palatal muscle activity simultaneous with the truncal tremor. It is suggested that an axial postural tremor may be due to pathology of the cerebellum and its outflow pathways, despite the absence of clinically apparent palatal tremor.
Analysis of action tremor and impaired control of movement velocity in multiple sclerosis during visually guided wrist‐tracking tasks
Authors: Liu Xuguang , Miall R. Christopher , Aziz Tipu Z. , Palace Jackie A. , Haggard Patrick N. , Stein John F.
Published: May 2005

We investigated the relationship between action tremor (AT) and impaired control of movement velocity (MV) in visually guided tracking tasks, in normal subjects and in patients with multiple sclerosis (MS) with or without motor deficits. The effects of withdrawing visual feedback of either the target or the cursor were then investigated. Visually cued simple reaction times (SRTs) were also measured. The effects of thalamotomy on motor performance in these tasks were evaluated in seven patients. In the MS patients with tremor, there was no correlation between AT and impairment in control of MV, but the latter was highly correlated with an increased delay in SRT. Withdrawal of visually guiding cues increased the error significantly in MV, but reduced AT by −30% in magnitude. Frequency analysis indicated that the AT had two components: (a) non‐visual‐dependent, oscillatory movements, mainly at 4 Hz; and (2) visual‐dependent, repetitive movements, with significant power at 1–2 Hz. Thalamotomy significantly reduced AT but hardly improved accuracy in MV. These results suggest that visual feedback of a spatial mismatch signal may provoke a visually dependent repetitive movement contributing to AT. Conduction delays along either the corticocerebello‐cortical or the proprioceptive pathways and impaired working memory caused by MS may be responsible for the movement disorders in these patients.
Frequency of familial inheritance among 488 index patients with idiopathic focal dystonia and clinical variability in a large family
Authors: Leube Barbara , Kessler Kirn R. , Goecke Timm , Auburger Georg , Benecke Reiner
Published: May 2005

Idiopathic torsion dystonia is characterized by involuntary twisting movements and postures. One molecularly defined form with generalized dystonia has been shown to be autosomal dominantly inherited with reduced penetrance in chromosome 9q34.1, especially in Ashkenazi Jewish families, while other generalized families from Europe and families with other subtypes of dystonia have been excluded from linkage to this locus. Genealogical studies suggest that the much more frequent focal dystonia follows an autosomal dominant inheritance with reduced penetrance as well. For our study, 488 patients with focal dystonia, without a tendency for generalization, were interviewed for their family history. Evidence for hereditary disposition was found in 88 individuals. In a second step, all available family members of 17 of the 488 index patients (chosen for cooperation) were clinically examined. Objective diagnosis of affected relatives was established in 13 families, whereas only 4 of the 17 index patients had previously admitted a positive family history. Furthermore, a large threegeneration family with focal dystonia linked to chromosome 18p (linkage data described elsewhere) was identified. The familial pattern of all reported families is compatible with autosomal dominant inheritance with reduced penetrance. Assessment only on patients' report leads to underestimation of the frequency of familial idiopathic focal dystonia.
Paroxysmal exercise‐induced dystonia: Eight new sporadic cases and a review of the literature
Authors: Bhatia Kailash P. , Soland Valerie L. , Bhatt Mohit H. , Quinn Niall P. , Marsden C. David
Published: May 2005

We report eight new sporadic cases of paroxysmal dystonia induced by prolonged or sustained exercise and review an additional seven previously reported cases. The attacks in our patients lasted from a few minutes to up to 2 h, and patient age at onset ranged from 2 to 30 years. Four of the eight patients had hemidystonic attacks, both legs were involved in two other cases, and the remaining two patients had involvement of the right foot only. We propose that such cases should be classified as paroxysmal exercise‐induced dystonia.
DYSBOT: A single‐blind, randomized parallel study to determine whether any differences can be detected in the efficacy and tolerability of two formulations of botulinum toxin type A—Dysport and Botox—assuming a ratio of 4:1
Authors: Sampaio Cristina , Ferreira Joaquim J. , Simões Fernanda , Rosas Maria J. , Magalhães Marina , Correia Ana P. , Bastos‐Lima António , Martins Rairnundo , Castro‐Caldas Alexandre
Published: May 2005

Background: Elston and Russell discovered a difference in the biological potency of the English formulation of botulinum toxin type A or BTX‐A (Dysport) and the American formulation (Botox). Potency of both is expressed in LD50 mouse units, but because of assay differences, these units are not equivalent. Since the first warning by Quinn and Hallet on the clinical importance of this issue, it has been impossible to reach a consensus on the conversion factor for the potency of these formulations.

Objective: To test the hypothesis that the conversion factor
for the clinical potency of Dysport to Botox is approximately 4.1. DYSBOT is an acronym that results from adding “DYS” from Dysport with “BOT” from Botox.

Patients and Methods: Design: A single‐blind, randomized, parallel comparison. A total of 91 patients with blepharospasm or hemifacial spasm were randomized to treatment with Dysport or Botox using a fixed potency ratio of 4:1. Clinical evaluations: The patients were evaluated at baseline (day of the treatment), 1 month after treatment, and whenever the effect was judged to be fading. Objective and functional rating scales were used as quantitative measures of the change in clinical status. Adverse reactions were collected using a systematic questionnaire.

Results: Using this ratio between products, both Dysport and
Botox groups produced similar clinical efficacy and tolerability. For patients showing a positive response without the need of a booster, the duration of effect was 13.3 ± 5.9 weeks for the Dysport group and 11.2 ± 5.8 weeks for the Botox group. Of 48 patients, 11 (23%) needed booster treatment in the Dysport group compared with five (12%) of 43 in Botox group. Adverse events were noted in 24 (50%) of 48 patients in the Dysport group and 20 (47%) of 43 of the Botox‐treated group.

Conclusions: Using a 4:1 conversion ratio for Dysport and Botox, similar results were obtained for the two treatments in an appropriately powered study, suggesting that this conversion factor is a good estimate of their comparative clinical potencies.