bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential modification of dopamine transporter and tyrosine hydroxylase mRNAs in midbrain of subjects with parkinson's, alzheimer's with parkinsonism, and alzheimer's disease
Authors: Joyce Jeffrey N. , Smutzer Gregory , Whitty Christopher J. , Myers Amanda , Bannon Michael J.
Published: May 2005

The molecular characteristics of midbrain dopamine (DA) neurons have been extensively studied in Parkinson's disease (PD). No such studies of the characteristics of midbrain DA neurons in Alzheimer's disease (AD) or Alzheimer's disease with parkinsonism (AD/Park) have been published. We examined the levels of tyrosine hydroxylase (TH) protein, and the expression of TH and dopamine transporter (DAT) mRNAs, in midbrain neurons of PD, AD, and AD/Park cases. In PD, the loss of TH protein in the ventral tier of the substantia nigra pars compacta (SNpc) of the PD group is accompanied by severe losses in the number of neurons that express TH mRNA and DAT mRNA (74% loss). Remaining neurons show a shift to higher concentrations of TH mRNA but a shift to lower concentrations of DAT mRNA per cell. Hence, there is evidence that compensation in the remaining neurons can elevate concentrations of TH mRNA and lower DAT mRNA. Alternatively, there may be a predilection for a loss of neurons with high levels of DAT mRNA and low TH mRNA levels within the SNpc of PD cases. There was no change in TH protein but an elevation of TH mRNA concentrations per neuron without any change in concentrations of DAT mRNA in the AD group. The AD/Park group did not exhibit changes in the level of TH protein, but showed a small loss (26%) of neurons in the SNpc and a greater loss in other regions of the midbrain (43–53%). Remaining DA neurons showed a marked shift to lower concentrations of DAT mRNA per neuron and a nonsignificant shift in cellular concentration of TH mRNA to higher levels. This is consistent with our previous work showing that with AD/Park there is a significant reduction in the number of DAT sites located on DA terminals in the striatum, but the midbrain neurons have not died. Our results indicate that the differential regulation of mRNAs encoding TH and DAT is similar in the parkinsonian disorders (PD and AD/Park) even though the degree of cell death is very different. This might suggest that compensatory events occur in these DA neurons in AD/Park that are similar to those in PD and that result in differential effects on mRNAs encoding TH and DAT proteins.
Proton magnetic resonance spectroscopy in parkinson's disease and atypical parkinsonian disorders
Authors: Federico Francesco , Simone Isabella L. , Lucivero Vincenzo , Iliceto Giovanni , de Mari Michele , Giannini Paolo , Mezzapesa Domenico M. , Tarantino Alfredo , Lamberti Paolo
Published: May 2005

Proton magnetic resonance spectroscopy (1H‐MRS), localized to the lentiform nucleus, was carried out in 12 patients with idiopathic Parkinson's disease (IPD), seven patients with multiple‐system atrophy (MSA), seven patients with progressive supranuclear palsy (PSP), and 10 healthy age matched controls. The study assessed the level of N‐acetylaspartate (NAA), creatine–phosphocreatine (Cr), and choline (Cho) in the putamen and globus pallidus of these patients. NAA/Cho and NAA/Cr ratios were significantly reduced in MSA and PSP patients. No significant difference was found between IPD patients and controls. These results suggest an NAA deficit, due to neuronal loss, in the lentiform nucleus of MSA and PSP patients. 1H‐MRS is a noninvasive technique that can provide useful information regarding striatal neuronal loss in basal ganglia of patients with atypical parkinsonian disorders and represents a potential tool for diagnosing these disorders.
Dependency in parkinson's disease: A population‐based survey in nondemented elderly subjects
Authors: Tison François , Barberger‐Gateau Pascale , Dubroca Bénédicte , Henry Patrick , Dartigues Jean‐François
Published: May 2005

Little epidemiological data are available on the dependency status of elderly patients with Parkinson's disease (PD) living in the community. This study assessed the activities of daily living (ADL), the instrumental activities of daily living (IADL), and mobility in a representative sample of elderly nondemented PD subjects (n = 20), compared to a control population (n = 2,697). We found a significantly higher level of dependency in the PD sample based on ADL, IADL, and mobility scales. Half of the PD subjects were dependent for ADL (versus 13.2% for controls), 80% were dependent for IADL (versus 28% for controls), and 20% had their mobility restricted to their home (versus 1.5% for controls). The proportion of PD patients tended to be higher in those more depressed or with more severe motor symptoms. PD patients were not found to be more isolated socially or from family than was the control group and, in any case, dependency seemed not to be associated with isolation. When adjusting for age, sex, depressive symptoms, Mini Mental Status examination score, and dyspnea, PD remained significantly associated with dependency. PD thus constitutes a significant factor of dependency in elderly subjects living at home. Institutionalization occurred over four times more frequently in the PD group than in the general population, but no specific factor of institutionalization was noted.
Effect of chronic oral domperidone therapy on gastrointestinal symptoms and gastric emptying in patients with parkinson's disease
Authors: Soykan Irfan , Sarosiek Irene , Shifflett Jeannie , Wooten George F. , McCallum Richard W.
Published: May 2005

This study investigated whether domperidone could improve gastrointestinal symptoms in patients with Parkinson's disease who were receiving levodopa therapy. A total of 11 patients were studied. Following a baseline gastric emptying test, patients were treated with a starting dose of domperidone 20 mg p.o. q.i.d. A follow‐up gastric emptying test was repeated at least 4 months after starting domperidone therapy. At the beginning and at each 3‐month follow‐up visit, symptoms of nausea, vomiting, anorexia, abdominal bloating, heartburn, regurgitation, dysphagia, and constipation were evaluated and scored on a scale of 0–3. The overall mean follow‐up period was 3 years. Compared with their baseline evaluation, patients experienced a significant improvement in all symptoms (p < 0.05) except dysphagia and constipation. Gastric emptying of an isotope‐labeled solid meal was significantly faster, with a baseline result of 60.2 ± 6.4% retention of isotope 2 h after the meal compared with 37.0 ± 2.2% retention during domperidone therapy (p < 0.05). Patients' global assessment of Parkinson's disease remained stable or improved. Serum prolactin was elevated in all patients after domperidone therapy (p < 0.05). Domperidone therapy significantly reduces upper gastrointestinal symptoms and accelerates gastric emptying of a solid meal, but does not interfere with response to antiparkinsonism treatment.
Agreement among movement disorder specialists on the clinical diagnosis of essential tremor
Authors: Chouinard Sylvain , Louis Elan D. , Fahn Stanley
Published: May 2005

Even though essential tremor (ET) is the most prevalent movement disorder, there has been little agreement in the neurologic literature regarding diagnostic criteria for ET. The authors attempted to determine the extent and source of agreement and disagreement among neurologists regarding diagnostic criteria for clinically definite ET. The authors designed and mailed a semistructured questionnaire to 160 neurologists who specialize in movement disorders in 24 countries. The questionnaire included three sections: a list of inclusion criteria, a list of exclusion criteria, and a list of potential clinical scenarios (for example, isolated site‐specific tremor and primary orthostatic tremor). The questionnaire was completed by 98 (61%) of 160 targeted neurologists. There was greater consensus regarding features considered unnecessary inclusion criteria for clinically definite ET (extent of disability, disease duration, and positive family history) than for those considered necessary inclusion criteria (postural versus action tremor). With regard to exclusion criteria, there was some consensus in terms of the presence of Parkinson's disease, dystonia, history of hyperthyroidism or concurrent use of tremor‐inducing medications, and cerebellar signs. The majority of neurologists would diagnose ET in the setting of isolated head or voice tremor. There are areas of both consensus and divergence among neurologists with regard to diagnostic criteria for ET. The choice of diagnostic criteria may vary depending on the intended use of the criteria (that is, clinical versus genetic studies). Hopefully, this study will foster further discussion to achieve a more general consensus.
Kinematic analysis of articulatory movements in central motor disorders
Authors: Ackermann Hermann , Hertrich Ingo , Daum Irene , Scharf Gabriele , Spieker Sybille
Published: May 2005

The various components of the central motor system are expected to play a similar role in speech production and in upper limb control. Slowed articulatory performance, therefore, must be expected in disorders of the corticobulbar tracts, cerebellum, and basal ganglia. Using an optoelectronic device, the present study recorded lower lip trajectories during production of sentence utterances in patients with Parkinson's disease (PD), Huntington's disease (HD), cerebellar atrophy (CA), and pseudobulbar palsy (PB). The various subject groups showed a similar range of overall motor disability. Patients with CA and PB exhibited slowed movement execution in terms of a reduced ratio of peak velocity to maximum amplitude (“stiffness”)‐ In contrast to upper limb motor control, the lip excursions showed an uncompromised shape of velocity profiles. Two different patterns emerged in HD. A single patient suffering from the akinetic‐rigid Westphal variant of this disease had articulatory hypometria, whereas the remaining subjects showed significant bradykinesia under increased temporal demands, concomitant with normal movement amplitudes. The PD patients had unimpaired velocity‐displacement relationships. Presumably, biomechanical constraints such as the rather small excursions of articulatory lower lip gestures or the scarce spindle supply of facial muscles account for the observed discrepancies between upper limb and speech motor control in PD.
Adult‐onset tics associated with peripheral injury
Authors: Factor Stewart A. , Molho Eric S.
Published: May 2005

We report the cases of two patients with adult onset, simple, nonvarying tic disorder that commenced after a peripheral (non‐CNS) injury. The first patient is a 38‐year‐old man who suffered a right facial injury when his car fell off its jack while he was working underneath. Bilateral facial twitching began hours after the trauma and was characterized as a sniffinglike gesture. The movements waxed and waned, were suppressible, and were associated with a premonitory sensation. The tics remitted after 9 months but still recur occasionally under stressful situations. The second patient is a 34‐year‐old man with a 3‐year history of abrupt, rapid head‐turning movements that began 12 months after a motor vehicle accident in which he injured his neck. The tics continue to wax and wane, are suppressible, and are associated with an urge. Neither patient suffered a head injury or had a family history of Tourette syndrome. Based on the clinical and historical features of these patients, the temporal relationship between the trauma and onset of tics, and the occurrence of tics only in the traumatized region, a causal relationship is possible. These may represent the first reported cases of tic disorder in association with peripheral injury. The mechanism by which the tic disorder resulted from the peripheral injury is unclear, but these patients might have been susceptible individuals and the trauma acted as a trigger.
A historical case of probable corticobasal degeneration?
Authors: Ballan Guillaume , Tison Francois
Published: May 2005

In 1925, Jean Lhermitte and colleagues published a work on spatial representation in apraxic patients, based on two illustrative cases. One of these displayed a clinical picture that would nowadays be clinically classified as probable corticobasal degeneration.
How common is the most common adult movement disorder? Estimates of the prevalence of essential tremor throughout the world
Authors: Louis Elan D. , Ottman Ruth , Allen Hauser W.
Published: May 2005

Essential tremor (ET) is the most common adult movement disorder, as much as 20 times more prevalent than Parkinson's disease. Estimates of the crude prevalence of ET range widely from 0.08 to 220 cases per 1000 persons, a 2750‐fold difference. There has been no formal attempt to synthesize these disparate results. Our purpose is to provide an overview of existing studies, to examine methodologic issues that may account for this tremendous variability in results, and to provide a more precise estimate of the prevalence of ET. Nineteen studies of the prevalence of ET were reviewed. Factors that contribute to broad range of prevalence estimates include (a) differences in study design that influence validity and (b) differences in characteristics of study populations that influence comparability of studies. If we limit our examination to studies that (a) provided diagnostic criteria for ET, (b) defined ET as an action tremor, and (c) used community‐based rather than service‐based designs, then five studies remain, and the prevalence of ET is 4.1 to 39.2 cases per 1000, a 9.6‐fold difference. Four of these five provided age‐stratified data. Among these four, the prevalence of ET in those over the age of 60 years was 13.0 to 50.5 cases per 1000, a 3.9‐fold difference.
Ropinirole in the treatment of early Parkinson's disease: A 6‐month interim report of a 5‐year levodopa‐controlled study
Authors: Rascol Olivier , Brooks David J. , Brunt Ehrout R. , Korczyn Amos D. , Poewe Warner H. , Stocchi Fabrizzio
Published: May 2005

The efficacies of ropinirole and levodopa were compared after 6 months of treatment in a planned interim analysis of a 5‐year, double‐blind, randomized, multicenter study of patients with early Parkinson's disease requiring dopaminergic therapy. The percentage of improvement in the Unified Parkinson's Disease Rating Scale total motor examination score was significantly higher for levodopa (44%) than for ropinirole (32%). The proportion of “responders” (Unified Parkinson's Disease Rating Scale improvement of at least 30%) did not differ between groups (levodopa, 58%; ropinirole, 48%). There was no difference between the groups for improvement on the Clinical Global Impression scale in patients with Hoehn and Yahr stages I, I.5, or II, but a significantly higher proportion of patients with Hoehn and Yahr stages II.5 or III showed Clinical Global Impression score improvement with levodopa. Emergent adverse events occurred in 84% of patients in both treatment groups, the principal symptom in each group being nausea. The incidence of serious adverse events was low (8% for ropinirole, 9% for levodopa). The results suggest that ropinirole and levodopa are equally effective in less severe Parkinson's disease; in more advanced Parkinson's disease, levodopa is superior.
Ropinirole versus bromocriptine in the treatment of early Parkinson's disease: A 6‐month interim report of a 3‐year study
Authors: Korczyn Amos D. , Brooks David J. , Brunt Ehrout R. , Poewe Warner H. , Rascol Olivier , Stocchi Fabrizzio
Published: May 2005

We compared the efficacy and safety of ropinirole with that of bromocriptine after 6 months of treatment in a planned interim analysis of a 3‐year, double‐blind, randomized, multicenter study of 335 patients with early Parkinson's disease requiring dopaminergic therapy. Patients, treated with or without selegiline, received either ropinirole or bromocriptine. The mean Unified Parkinson's Disease Rating Scale (UPDRS) total motor examination scores (Part III) at baseline were similar in the four strata. Overall, and in the non‐selegiline subgroup, the percentage improvement in the UPDRS total motor examination score was significantly higher for ropinirole than for bromocriptine, as was the proportion of “responders.” In the selegiline subgroup, however, there was no significant difference between treatments. Similarly, in the non‐selegiline subgroup, there was a significantly higher proportion of “improvers” on the Clinical Global Impression scale with ropinirole than with bromocriptine, whereas in the selegiline subgroup, there was no significant difference. Emergent adverse events occurred in 80% of patients in both treatment groups, the principal symptom in each group being nausea. The incidence of serious adverse events was low (3% for ropinirole, 6.6% for bromocriptine). The data indicate that (a) in the absence of selegiline, ropinirole is effective and superior to bromocriptine; and (b) selegiline does not affect the response in patients treated with ropinirole, but enhances the effects of bromocriptine.
The role of EDTA in provoking allergic reactions to subcutaneous infusion of apomorphine in patients with Parkinson's disease: A histologic study
Authors: van Laar Teus , van Hilten Bob , Neef Cees , Rutgers A. Wijnand F. , Pavel Stan , Anthony Bruijn J.
Published: May 2005

One of the formulations of apomorphine, used in clinical practice, contains sodium edetate (EDTA). EDTA is a chelator which indirectly prevents oxidation of apomorphine. A clinical and histologic study in four patients revealed that apomorphine with EDTA caused severe subcutaneous nodules, histologically characterized by an inflammatory infiltrate with a large amount of eosinophils, indicating a cell‐mediated allergic reaction. After withdrawal of EDTA, this allergic component completely disappeared, which was accompanied clinically by less extensive nodule formation with a softer consistency. It is therefore recommended that EDTA be excluded from apomorphine formulations.
Assessment of ability/disability in patients treated with chronic thalamic stimulation for tremor
Authors: Hariz Gun‐Marie , Bergenheim A. Tommy , Hariz Marwan I. , Lindberg Margareta
Published: May 2005

Chronic thalamic stimulation (CTS) has a documented good effect on tremor in patients with Parkinson's disease (PD) and essential tremor (ET). This study evaluates whether the alleviation of impairment, i.e., tremor, translates into improvement of the patient's ability in performing instrumental activities of daily living (IADL). Thirteen patients were assessed with an occupational therapy tool called Assessment of Motor and Process Skills (AMPS). This observation‐based scale rates the patient's motor and process skills needed to perform a given task. The evaluations were done at a mean of 13 months after surgery in the patient's home, and included assessments of IADL with the CTS activated and switched off, respectively. The results showed that most patients improved to variable degrees in their IADL ability when the thalamic stimulation was on. The improvement was more marked in patients operated on for tremor of their dominant hand. The improvement concerned mainly the skill items related to the patients' abilities of coordination, calibration, calibration, endurance, and accommodation during IADL task performance. The authors concluded that for some patients with tremor, CTS can improve independence in domestic activities of daily living.
Improvement of action tremor by chronic cortical stimulation
Authors: Nguyen J.‐P. , Pollin B. , Fève A. , Geny C. , Cesaro P.
Published: May 2005

The authors present a patient who had long‐term improvement of a severe upper limb action tremor after chronic cortical stimulation. A 40‐year‐old woman complained of facial pain and tremor of the left arm after removal of an acoustic neurinoma. A motor cortex stimulation was performed to treat the deafferentation facial pain in 1993. Chronic cortical stimulation induced complete relief of both pain and tremor and allowed the patient to recover functional capacity of the limb. These effects persisted throughout a 32‐month follow up. Differential effects on pain and tremor were observed when parameters of stimulation were varied, suggesting different mechanisms for the relief of pain and tremor. Attention was focused on control of the tremor. This effect could be the result of the inhibition of subcortical structures which are involved in tremor. Chronic cortical stimulation appears to be an effective treatment for controlling severe action tremors.
Change in lateralization of the P22/N30 cortical component of median nerve somatosensory evoked potentials in patients with cervical dystonia after successful treatment with botulinum toxin A
Authors: Kaňovský Petr , Streitová Hana , Dufek Jaroslav , Znojil Vladimir , Daniel Pavel , Rektor Ivan
Published: May 2005

The precentral P22/N30 cortical component of the median nerve somatosensory evoked potentials (SEPs) was recorded in 16 patients (11 women and five men) suffering from cervical dystonia before and after botulinum toxin therapy. Cervical dystonia was diagnosed as idiopathic in all patients: 13 patients suffered from right‐sided torticollis, and three suffered from left‐sided torticollis. The amplitude of the P22/N30 component and the side‐to‐side ratio of amplitude values were measured. Normal values were obtained by acquiring measurements in two groups of healthy volunteers (n1 = 20 and n2 = 20). The recordings in the first control group were done with the patient's head in a normal position, whereas, in the second control group, the patient kept the head intentionally rotated 60° to the right. Patients were treated with local injections of botulinum toxin A (BTX‐A). The mean duration of treatment was 8.3 months, and the mean total amount of BTX injected was 295 U. The P22/N30 precentral component was repeatedly recorded in patients after head posture had been corrected to the normal plane by BTX‐A treatment. The recordings showed that the amplitude of the P22/N30 precentral component recorded contralaterally to the direction of head deviation was significantly higher in patients before treatment than after treatment. Contralateral pretreatment amplitudes were also significantly higher (p < 0.01 and p < 0.05, respectively) than amplitudes in both groups of healthy volunteers. The mean side‐to‐side ratio of precentral P22/N30 component amplitudes was significantly higher in patients before treatment compared with after treatment and also compared with both control groups. These changes in dystonic patients probably reflect the direction of head rotation, the muscle pattern of torticollis, and the change in force of dystonic contraction after the treatment. The changes presumably could be the result of higher excitability of the precentral cortex contralateral to head rotation in patients with cervical dystonia and its change after successful BTX‐A treatment.
Geste device in tardive dystonia with retrocollis and opisthotonic posturing
Authors: Krack Paul , Schneider Sybilla , Deuschl Günther
Published: May 2005

Retrocollis and opisthotonic posturing are typical clinical features of tardive dystonia and may be extremely disabling. We have treated five such patients with a custom‐made mechanical device that delivers constant contact to the occiput and shoulders. All patients experienced relief and their walking improved. This geste device, working like a geste antagonistique, may be useful for the management of some patients with severe axial dystonia with retrocollis and back arching.
Comparison of treatment of tardive dystonia and idiopathic cervical dystonia with botulinum toxin type A
Authors: Brashear Allison , Ambrosius Walter T. , Eckert George J. , Siemers Eric R.
Published: May 2005

To compare clinical parameters of patients treated with botulinum toxin type A (BTX) for treatment of idiopathic cervical dystonia (ICD) and for tardive cervical dystonia (TCD), we studied 156 patients (149 with ICD and 7 with TCD) who were treated with serial injections of BTX over 5 years. We hypothesized that patients with TCD and ICD would demonstrate similar improvement in severity scores after treatment with BTX. The diagnosis, dates, dosages, and frequency of BTX injected and severity assessments were recorded into a computerized database. Nonparametric Wilcoxon rank sum and signed‐rank tests were used to assess statistical significance. The change in severity scores between the first treatment and last treatment in both groups was not statistically significant (p = 0.4859), indicating similar improvement. The difference in BTX doses was significant (p = 0.0045). ICD patients (n = 149) received an average of 219.8 ± 63.5 units and those with TCD (n = 7) were treated with an average dose of 287.4 ± 60.3 units. The average number of days between treatments for individuals with ICD was 142.9 ± 85.8, similar to that for persons with TCD (144.7 ± 64.5) (p = 0.6075). Our analysis provides preliminary evidence that the improvement from the administration of BTX for patients with ICD and TCD is similar.
Posey and spiller and progressive supranuclear palsy: An incorrect attribution
Authors: Siderowf Andrew D. , Galetta Steven L. , Hurtig Howard I. , Liu Grant T.
Published: May 2005

In 1904 and 1905, respectively, William Campbell Posey and William Spiller both described the case of a patient with progressive ophthalmoparesis and imbalance that has come to be regarded as the earliest report of progressive supranuclear palsy. No autopsy was thought to have been performed on this patient. In this report, we review the clinical history provided by Posey and Spiller. We also report on the subsequent autopsy of their patient, which was performed by Spiller in 1906. The chief finding was a tumor involving the right cerebral peduncle and periaqueductal area. The autopsy findings prove conclusively that the patient described by Spiller and Posey had a midbrain neoplasm and not progressive supranuclear palsy.
Glial pathology but absence of apoptotic nigral neurons in long‐standing Parkinson's disease
Authors: Banati Richard B. , Daniel Susan E. , Blunt Stavia B.
Published: May 2005

The cause and mechanism of neuronal cell death in the substantia nigra of patients with Parkinson's disease (PD) are unknown. There is also controversy about whether the cell death results from a single event followed by cell loss consistent with aging or whether there is an ongoing pathologic process. Using postmortem tissue obtained from the Parkinson's Disease Society Brain Tissue Bank in London, we have sought to establish whether apoptosis, or more specifically DNA fragmentation of neurons, is a prominent feature of nigral pathology. In addition, we have studied microglial activation in the substantia nigra as an indicator of ongoing pathology using the highly sensitive markers CR3/43 and EBM11. Reactive astrocytes have been assessed using immunostaining for glial fibrillary acidic protein (GFAP). Ten patients with pathologically proven PD were studied. In all cases, regardless of disease duration, severity, drug treatment, or age of the patient, there was no evidence of apoptosis in the substantia nigra as assessed by in situ end‐labeling of DNA fragments using biotinylated dUTP and terminal deoxynucleotidyl transferase (TdT). In contrast, a case of multiple system atrophy (MSA) served as a positive control for the technique. In this case, positive DNA end‐labeling could be found in neurons and non‐neuronal cells in the brain stem. In the PD cases, there was, however, localized pathology in the substantia nigra as revealed by the CR3/43 and EBM11 markers for activated microglia. This process seemed independent of disease duration and was florid even in patients with severe neuronal loss. It remains to be determined to what extent the activation of glial cells reflects progressive nigral pathology, and whether those factors which are classically associated with prominent apoptotic neuronal cell death in vivo, such as neurotrophic factor deprivation, are prime causes of nigral neuronal loss in PD. Future studies should focus on recent‐onset PD or incidental Lewy body disease to further address these questions.
Influence of body load on the gait pattern in Parkinson's disease
Authors: Dietz Volker , Colombo Gerhard
Published: May 2005

The influence of body unloading (to 75, 50, and 25% body weight) on lower leg muscle activation during treadmill walking was investigated in patients with Parkinson's disease, age‐matched and young healthy subjects. The aim of the study was to test the hypothesis that patients suffer from impaired extensor load receptor function. Although lower leg flexor muscle electromyographic (EMG) activity was relatively independent of body load, lower leg extensor EMG activity was markedly load sensitive. The EMG amplitude of the latter decreased with body unloading during stepping in all three groups of subjects. The load sensitivity progressively increased from patients to age‐matched to young healthy subjects. In addition, the absolute level of leg extensor EMG amplitude during the stance phase of stepping became progressively larger from patients to age‐matched subjects to young healthy subjects. It is suggested that decreased sensitivity of extensor load reflex mechanisms contributes to impaired gait in elderly subjects and is more pronounced in parkinsonian patients.
Reliability between two observers using a protocol for diagnosing essential tremor
Authors: Louis Elan D. , Ford Blair , Bismuth Bella
Published: May 2005

Protocols with demonstrated reliability have been established for the diagnosis of numerous movement disorders, whereas in the essential tremor (ET) literature, there is no discussion about the reliability of diagnostic protocols. Lack of knowledge of the reliability of diagnostic protocols in ET limits the use of these protocols because reliability is an essential requirement for scientific quality in data management. The objective of this study was to determine the reliability of a protocol for diagnosing ET. The protocol consists of a Tremor Interview, a videotaped Tremor Examination, and a diagnostic algorithm. Eighty‐three subjects with ET, identified in a community‐based health study in Washington Heights‐Inwood, New York, were matched with 83 control subjects from the same community. These subjects and their relatives are being recruited to participate in the Washington Heights‐Inwood Genetic Study of ET. Two hundred twenty‐six subjects have been evaluated to date (35 ET cases, 40 controls, 151 relatives). All 226 underwent an 84‐item Tremor Interview and 26‐item videotaped Tremor Examination. Diagnoses (normal, possible ET, probable ET, definite ET) were independently assigned by two blinded neurologists specializing in movement disorders. The kappa statistic, k, was used to determine diagnostic agreement between these two neurologists. The concordance rate between two raters using diagnostic categories definite ET, probable ET, possible ET, and normal was 80%; kw = 0.84 (near perfect to perfect agreement). The concordance rate between two raters using two diagnostic categories (definite ET and normal) was 100%; k = 1.00 (perfect agreement). There was high correlation between the two rater's total tremor scores (r = 0.89, p < 0.00001). This diagnostic protocol is highly reliable. Research in ET would greatly benefit from diagnostic protocols with demonstrated reliability.
Diagnostic and pathophysiological aspects of psychogenic tremors
Authors: Deuschl Günther , Köster Bernd , Lücking Carl H. , Scheidt Carl
Published: May 2005

Psychogenic tremor has become a rare movement disorder. Twenty‐five patients from our movement disorder unit presented either with obviously nonorganic body shaking during stance or with extremity tremors. A sudden onset and a variable but rarely remitting course of the condition was common. The “coactivation sign of psychogenic tremor” and absent finger tremor were the most consistent criteria to separate them from organic tremors. Quantitative analysis of tremor shows decreasing amplitudes in most organic tremors when the extremity is loaded with additional weights. In contrast, we found an increase of tremor amplitude for most of the cases with psychogenic tremor. This might be caused by increased coactivation to maintain the oscillation. These clinical and electrophysiological features suggest a clonus mechanism induced by coactivation as the pathophysiological basis of psychogenic extremity tremor. Psychiatric evaluation did not show overt signs of hysteria for the majority of the patients. However, we found depression and functional somatic or psychosomatic conditions to be frequent among the patients. A reduced ability to cope with stressful situations may play a significant role. The clinical course of the condition is usually far from benign. We conclude that psychogenic tremor can be positively diagnosed by means of neurologic signs in the majority of patients and is not only a diagnosis of exclusion. The poor outcome makes early and serious neuropsychiatric attempts at therapy necessary.
X‐linked dystonia‐deafness syndrome
Authors: Hayes Michael W. , Ouvrier Robert A. , Evans William , Somerville Ernest , Morris John G. L.
Published: May 2005

We report a family with early‐onset deafness and progressive dystonia exclusively involving males over two successive generations. There is also evidence of cognitive impairment and corticospinal tract involvement. The pedigree suggests an X‐linked inheritance. A similar family was originally described by Scribanu and Kennedy. Tranebjaerg et al. have recently reported two other families with linkage to Xq22 and also proposed a novel X‐linked candidate gene. These findings support the existence of a distinct neurodegenerative syndrome principally characterized by early‐onset deafness and progressive dystonia. Neuropathology of one case showed a mosaic pattern of neuronal loss and gliosis in the caudate and putamen suggesting that this pattern is not restricted to XDP or Lubag.
Increased activation of frontal areas during arm movement in idiopathic torsion dystonia
Authors: Diane Playford E. , Passingham Richard E. , David Marsden C. , Brooks David J.
Published: May 2005

Most positron emission tomography (PET) studies of regional cerebral function in idiopathic torsion dystonia (ITD) have failed to show abnormalities, but there have been few studies of the changes in regional cerebral blood flow (rCBF) that occur during movement in dystonia. Using PET, we have studied six patients with familial generalized ITD both at rest and while moving a joystick with the right hand. The patterns of CBF change obtained were compared with those in six age‐matched control subjects. In the dystonia group, free selection of movement was associated with relative increases in rCBF above that observed in control subjects in the left premotor area, the supplementary motor area (SMA), the anterior cingulate cortex, and the left dorsolateral prefrontal area. Subcortical increases were observed within the cerebellum and the putamen. There was a relative decrease in flow through the contralateral primary sensorimotor cortex. These findings contrast with those reported in patients with Parkinson's disease undertaking the same task in which the activity in the SMA and putamen was decreased. We suggest that arm dystonia in ITD is associated with overactivity of the premotor areas, including the SMA, and that this results from release of the thalamus from the normal inhibitory influence of the globus pallidus internal segment. Other abnormalities of basal ganglia control of brain stem centers may be involved in axial dystonia.
Generalized chorea in two patients harboring the Friedreich's ataxia gene trinucleotide repeat expansion
Authors: Hanna Michael G. , Davis Mary B. , Sweeney Mary G. , Noursadeghi Madi , Ellis Christopher J. , Elliot Perry , Wood Nicholas W. , David Marsden C.
Published: May 2005

Recently, a trinucleotide repeat expansion in intron l of the frataxin gene on chromosome 9p13 has been identified as the genetic defect in Friedreich's ataxia (FA). We have identified two patients exhibiting generalized chorea in the absence of cerebellar signs who were homozygous for this intron 1 expansion. Chorea as a rare manifestation of FA has previously been controversial. This is the first report of chorea in patients confirmed to have the FA genetic abnormality and broadens further the clinical phenotype associated with the FA genotype.
Functional improvement in a patient with cerebral calcinosis using a bisphosphonate
Authors: Loeb Jeffrey A.
Published: May 2005

Idiopathic cerebral calcification can be associated with a progressive neurologic disorder for which there is no known treatment. This report describes a patient with a familial form of this disorder presenting in middle age with progressive Parkinson‐like features along with spasticity, dystonia, and ataxia. Disodium etidronate, a bisphosphonate, produced a twofold improvement in the rate of his speech and gait, but did not affect his spasticity, dystonia, or ataxia. Quantitative analysis of cerebral calcification did not reveal any reduction in the amount of calcification, suggesting other possible mechanisms for this clinical improvement.
Fetal nigral grafts survive and mediate clinical benefit in a patient with Parkinson's disease
Authors: Kordower Jeffrey H. , Freeman Thomas B. , Chen Er‐Yun , Mufson Elliott J. , Sanberg Paul R. , Hauser Robert A. , Snow Barry , Warren Olanow C.
Published: May 2005

We have previously demonstrated that fetal nigral grafts can survive, reinnervate the striatum, and mediate clinically relevant recovery in a patient with Parkinson's disease (PD).1 Most previous autopsy cases have failed to identify meaningful numbers of viable grafted cells suggesting that differences in critical transplant variables determine graft viability. 2–4 The present study evaluated the structural and functional correlates of fetal nigral transplantation in a second PD patient who received fetal nigral grafts according to our previously published transplant protocol. 5 A 61‐year‐old woman with severe PD received bilateral fetal nigral grafts to the post commissural putamen from seven donor fetuses (four right side and three left side) aged 6.5‐9 weeks postconception. This patient died 19 months after surgery from a cause unrelated to the transplant surgery. Her postoperative clinical course was characterized by improved motor and activities of daily living scores during “off time,” reduced “off time,” and increased “on” time without dyskinesia. Positron emission tomography (PET) scans revealed a bilateral and progressive increase in fluorodopa (FD) uptake within the grafted putamen. Postmortem examination of the right hemisphere revealed large ovalshaped grafts containing more than 138,000 tyrosinehydroxylase‐immunoreactive (TH‐ir) neurons. Grafted cells formed a seamless border with the host and provided dense TH‐ir innervation to 78% of the host postcommissural putamen. Graft‐mediated sprouting of host fibers was not observed. These data provide essential confirmation that, under appropriate transplant conditions, grafted nigral neurons can survive, reinnervate the host striatum, and provide clinical benefit to PD patients. These findings also support the concept that improved motor function and striatal FD uptake on PET after nigral grafting in PD are the result of the viability of grafted neurons and graft‐derived reinnervation of the host striatum.
A trial of dextromethorphan in parkinsonian patients with motor response complications
Authors: Metman Leo Verhagen , Blanchet Pierre J. , van den Munckhof Pepÿn , Dotto Paolo Del , Natté Remco , Chase Thomas N.
Published: May 2005

The effects of the NMDA antagonist dextromethorphan (DM) on levodopa‐associated dyskinesias and motor fluctuations were studied in patients with advanced Parkinson's disease. During initial open‐label dose escalation, 6 of 18 patients reported a beneficial effect at their individually determined optimal DM dose (range, 60–120 mg/day). The 12 remaining patients either experinced reversible side effects, particularly mild drowsiness, or decreased levodopa efficacy, and were therefore excluded from the study. The six responders entered the double‐blind, placebo‐controlled, crossover study with two 2‐week arms separted by 1 week wash‐out. On the last day of each arm, motor ratings were performed every 20 minutes for 8 consecutive hours. In addition, motor complications and Activities of Daily Living (ADL) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and patient diaries. With DM, dyskinesias improved by 25% according to physician's ratings and by 40% accfording to UPDRS interviews, without compromising the anti‐Parkinson effect of levodopa. Motor fluctuations and ADL scores also improved significantly. Although the narrow therapeutic index of DM limits its clinical usefulness, these findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate levodopa‐associated motor complications.
Gait variability and basal ganglia disorders: Stride‐to‐stride variations of gait cycle timing in parkinson's disease and Huntington's disease
Authors: Hausdorff Jeffrey M. , Cudkowicz Merit E. , Firtion Renée , Wei Jeanne Y. , Goldberger Ary L.
Published: May 2005

The basal ganglia are thought to play an important role in regulating motor programs involved in gait and in the fluidity and sequencing of movement. We postulated that the ability to maintain a steady gait, with low stride‐to‐stride variability of gait cycle timing and its subphases, would be diminished with both Parkinson's disease (PD) and Huntington's disease (HD). To test this hypothesis, we obtained quantitative measures of stride‐to‐stride variability of gait cycle timing in subjects with PD (n = 15), HD (n = 20), and disease‐free controls (n = 16). All measures of gait variability were significantly increased in PD and HD. In subjects with PD and HD, gait variability measures were two and three times that observed in control subjects, respectively. The degree of gait variability correlated with disease severity. In contrast, gait speed was significantly lower in PD, but not in HD, and average gait cycle duration and the time spent in many subphases of the gait cycle were similar in control subjects, HD subjects, and PD subjects. These findings are consistent with a differential control of gait variability, speed, and average gait cycle timing that may have implications for understanding the role of the basal ganglia in locomotor control and for quantitatively assessing gait in clinical settings.
123I‐β‐CIT and 123I‐IBZM‐SPECT scanning in levodopa‐naive Parkinson's disease
Authors: Wenning Gregor K. , Donnemiller Eveline , Granata Roberta , Riccabona Georg , Poewe Werner
Published: May 2005

Striatal dopamine transporter function and dopamine D2 receptor status were evaluated in 15 patients with early untreated Parkinson's disease using single photon emission tomography (SPECT) with 123I‐Iodo‐2β‐carboxymethoxy‐3β‐(4‐idiophenyl)tropane (β‐CIT) and 123I‐Iodobenzamide (IBZM) as pre‐ and postsynaptic ligands. Symptoms were unilateral in five patients and bilateral but asymmetric in 10 patients. Patients with bilateral symptoms had significantly lower 18‐hour striatal/cerebellar β‐CIT binding ratios (3.59 ± 0.79) than hemiparkinsonian patients (5.76 ± 1.48, p < 0.05) reflecting more advanced disease in this subgroup. Patients with bilateral parkinsonism were also found to have a significant side‐to‐side difference in striatal β‐CIT binding with more marked reduction contralateral to the presenting limb (18‐hour striatal/cerebellar ratio: 4.13 ± 0.78 [ipsilateral] versus 3.59 ± 0.79 [contralateral], p < 0.05). Dopamine D2 receptor binding as measured by IBZM was significantly elevated contralateral to the affected side in hemiparkinsonian patients (striatal/cerebellar ratio: 2.42 ± 0.90 [contralateral] versus 2.19 ± 0.80 [ipsilateral], p < 0.05). This asymmetric upregulation was absent in the patients with bilateral parkinsonism (striatal/cerebellar ratio: 1.85 ± 0.43 [contralateral to more severely affected side] versus 1.83 ± 0.34 [ipsilateral], p > 0.05). Our data suggest that postsynaptic dopamine receptor upregulation contralateral to the presenting side occurs in untreated unilateral PD and disappears in untreated bilateral (asymmetric) PD despite a greater loss of dopamine transporter function. Combined β‐CIT and IBZM SPECT studies may be helpful to monitor the progression of nigrostriatal dysfunction in early PD.
Cinnarizine‐induced parkinsonism: Ten years later
Authors: Martí‐Massó José F. , Poza Juan J.
Published: May 2005

A retrospective study was carried out to investigate the evolution of patients diagnosed with cinnarizineinduced parkinsonism (CIP) over the past 15 years. A total of 74 cases of CIP were found among 172 patients with druginduced parkinsonism (DIP). Both CIP and other DIP were significantly more frequent in women. No clinical differences between CIP and other DIP were found. Most of the patients (66 of 74) completely recovered after cinnarizine withdrawal in 1–16 months. Eleven patients later developed Parkinson's disease; four of them had previously recovered. Five patients had tardive dyskinesia. CIP accounts for a high proportion of DIP referred to neurologists in populations in which cinnarizine is widely prescribed. The symptoms typically resolve after drug withdrawal, although complete recovery may take more than 1 year.
Double‐blind controlled trial of gabapentin in essential tremor
Authors: Pahwa Rajesh , Lyons Kelly , Hubble Jean P. , Busenbark Karen , Dierkes Rienerth J. , Pahwa Anokh , Koller William C.
Published: May 2005

Gabapentin has been reported to be effective for essential tremor (ET) based on open‐label trials. We studied gabapentin (1800 mg/day) and placebo in a double‐blind crossover design in 20 ET patients. Eighteen patients completed the study and two patients dropped out as a result of adverse effects which resolved when the medication was discontinued. Tremor was assessed at baseline and after 2 weeks of gabapentin and placebo treatment. One patient was mildly improved and another was moderately improved with placebo. Similarly, one patient reported mild improvement and another patient had marked improvement with gabapentin. All the remaining patients either reported no change or were worse with both treatment arms. There was no significant difference for total tremor score, hand tremor score, handwriting scores, or pouring scores. Sickness Impact Profile scores were no different between placebo and gabapentin. Our results suggest that as an adjuvant therapy in ET, gabapentin has limited benefit.
Hyperkinetic movement disorders misdiagnosed as tics in gilles de la tourette syndrome
Authors: Kompliti Katie , Goetz Christopher G.
Published: May 2005

Objective: To describe the gamut of movements misdiagnosed as tic exacerbations in Gilles de la Tourette syndrome (GTS) in a referral tertiary‐care center.

Background: Movements seen in GTS can be classified as: (a) tics; (b) movements related to conditions associated with GTS, specifically obsessive‐compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), and antisocial behaviors; and (c) movements secondary to treatment.

Methods: We reviewed a videotape database and patient records from a tertiary treatment center for GTS and collected GTS cases referred for disease exacerbation who had both tics and non‐tic movements thought by the referring physician, the patient, and the family to be an exacerbation of tics.

Results: Of 373 GTS cases, 12 had movement disorders secondary to treatment, and six had non‐tic movements related to conditions commonly associated with GTS. In the former group, there were 7 patients with acute akathisia, 3 with acute dystonia, 1 with tardive chorea, 1 with withdrawal emergent chorea, and 5 with tardive dystonia. Six had movement disorders related to non‐tic conditions commonly associated with GTS: four patients had movements associated with OCD, one with ADHD and antisocial behavior, respectively.

Conclusion: There is a broad spectrum of movements in GTS that are not tics but can be misdiagnosed as tics. Clinical awareness of these movements is paramount to proper diagnosis and pharmacologic intervention.