bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiparkinsonian therapies and brain mitochondrial complex I activity
Authors: Przedborski Serge , Jackson‐Lewis Vernice , Fahn Stanley
Published: December 2004

Alterations in complex I activity, one of the enzymatic units of the mitochondrial respiratory chain, have been demonstrated in different tissues from patients with Parkinson's disease (PD). Subsequently, we showed that the chronic administration of levodopa can cause alterations in mitochondrial respiratory chain activity in rats, which suggests that the observed deficit in complex I activity in PD might be, at least in part, related to chronic levodopa therapy. Our study assessed the in vitro effects of different antiparkinsonian agents on complex I activity in rat brain. As previously reported, both levodopa and dopamine inhibit complex I activity in a dose‐dependent manner. In contrast, the two major metabolites of dopamine, homovanillic acid and 3, 4‐dihydroxyphenylacetic acid as well as 3‐O‐methyl‐dopa, had little or no effect on complex I activities. Bromocriptine, pergolide, trihexyphenidyl, molindone, and clozapine were all without significant inhibitory effects on mitochondrial function. Although vitamin C and deprenyl did not alter complex I activity, they did prevent the inhibitory effect of both levodopa and dopamine on complex I activity. This work indicates that among the different and usual antiparkinsonian agents, only levodopa and dopamine induced reductions in complex I activity. It also indicates that vitamin C and deprenyl are both effective in preventing the levodopa‐induced complex I inhibition. This latter finding provides further support to the use of antioxidants and monoamine oxidase inhibitors as therapeutic strategies in attempts to slow the progression of PD.
Lid opening apraxia is associated with medial frontal hypometabolism
Authors: Smith D. , Ishikawa T. , Dhawan V. , Winterkorn J. S. , Eidelberg D.
Published: December 2004

We used [18F]fluorodeoxyglucose with positron emission tomography to explore the functional basis of lid opening apraxia (LOA). We studied four patients with LOA without associated pyramidal or extrapyramidal motor dysfunction (mean age 65.5 ± 4.7 years). We compared measures of glucose metabolism with those calculated for 10 age‐matched normal volunteers (mean age 60.6 ± 11.4). All four patients demonstrated significant metabolic reductions (>2 SD) in the medial frontal lobe: bilaterally in two, unilaterally in two. Significant abnormal unilateral metabolic reductions in the left basal ganglia were evident in two patients. These findings suggest that medial frontal lobe hypometabolism is associated with LOA. Abnormal striatofrontal interactions may be involved in the pathogenesis of this condition.
Longitudinal evolution of prefrontal leucotomy in Tourett's syndrome
Authors: Kulisevsky Jaime , Berthier Marcelo L. , Avila Asunción
Published: December 2004

We report the case of a 69‐year‐old man with severe Tourette's syndrome (TS) who underwent a bilateral prefrontal leucotomy at the age of 29 years to alleviate coprolalia, copropraxia, and obsessive‐compulsive disorder. No improvement was observed during the 5 years after the leucotomy. Tics and associated behaviorial abnormalities disappeared thereafter, to recur at age 67. Long‐term follow‐up of single cases can help to estimate the role of neurosurgery in the treatment of TS.
Hypokinesia in Parkinson's disease: Influence of age, disease severity, and disease duration
Authors: van Hilten J. J. , Braat E. A. M. , van der Velde E. A. , Middelkoop H. A. M. , van Dijk J. G. , Ligthart G. J. , Roos R. A. C.
Published: December 2004

The aim of this cross‐sectional study was to compare the role of aging in measures reflecting diurnal activity and immobility in 60 parkinsonian patients with predominant features of hypokinesia and rigidity and 100 healthy subjects aged 50 to 98 years. In the patients, we also studied the relation between disease duration and subjective and objective measures of disease severity. Motor acitivity was recorded during 5 successive days at home with a wrist‐worn activity monitor. For each subject, two mean measures reflecting the diurnal activity level and the relative proportion of activity and immobility were calculated. Diurnal measures of activity revealed in both groups a prominent absolute reduction of activity and an increase of the time spent without movement (“immobility”) with advancing age. Parkinsonian patients showed significantly lower values for both motor‐activity measures than did the healthy subjects. The rate of the age‐related decline of both diurnal activity measures in both groups, however, is comparable. Disease duration showed no relation with subjective and objective measures reflecting disease severity. This study shows that if care is taken to control for disease severity, the rate of the age‐related decline of measures reflecting diurnal activity and immobility is similar in both groups. The lack of relation between disease duration and subjective and objective measures of disease severity suggests that the rate of progression of Parkinson's disease can be reliably studied only by means of longitudinal studies.
The blepharospasm disability scale: An instrument for the assessment of functional health in blepharospasm
Authors: Lindeboom R. , De Haan R. , Aramideh M. , Speelman J. D.
Published: December 2004

Assessment of the functional status in patients with blepharospasm is of major importance for clinical practice and outcome studies. The Blepharospasm Disability Scale (BDS) is specifically directed to measure the disability in these patients. The metric properties of this instrument were evaluated. Reliability, validity, and responsiveness to within‐patient health changes over time of the BDS were assessed in 40 patients with essential blepharospasm treated with botulinum toxin injections. The reliability of the scale was sufficient for use on group level (Cronbach's α coefficient, 0.69). Evidence of discriminant validity was provided by the difference in median score on the BDS between 21 newly admitted patients and 19 patients already under treatment (p < 0.001). Convergent validity was supported by correlations between BDS and neurological impairment scores (range, Spearman correlation coefficients, 0.65‐0.79). Responsiveness to health changes was demonstrated by a significant difference between median BDS scores before treatment and 2 weeks after treatment with botulinum toxin (p < 0.01). The BDS is a useful disease‐specific instrument to assess disability. Completion of the questionnaire is easy and takes only a few minutes. The instrument is suitable for use in patient care, descriptive outcome studies, and should be considered in controlled clinical trials.
Click‐evoked vestibulocollic reflexes in torticollis
Authors: Colebatch J. G. , Lazzaro V. Di , Quartarone A. , Rothwell J. C. , Gresty M.
Published: December 2004

A total of 26 patients with torticollis were studied using a recently developed technique for recording vestibulocollic reflexes form the sternocleidomastid muscles in addition to conventional caloric tests of vestibular function. Previous reports of abnormalities of vestibulo‐ocular reflexes in these patients were confirmed with just fewer than half having significant canal pareses or directional preponderances (nine of 20 tested). In addition, there was a high incidence of abnormal click‐evoked vestibulocollic reflexes (17 of 26 tested), which were not simply the result of prior treatment with botulinum toxin, nor due to unequal levels of muscle activation. In patients never previously treated with botulinum toxin (14 patients), the effect almost always consisted of suppressed responses in the sternocleidomastoid muscle ipsilateral to the direction of head turning. Because responses were not abnormal in all patients tested, and more commonly so in those with a history of torticollis of ≥5 years (eight of nine patients) than in de novo patients, we suggest that the changes are more likely to be compensatory than causal.
Hemiatrophy, juvenile‐onset exertional alternating leg paresis, hypotonia, and hemidystonia and adult‐onset hemiparkinsonism: The spectrum of hemiparkinsonism‐hemiatrophy syndrome
Authors: Lang Anthony E.
Published: December 2004

A 45‐year‐old woman with a history of probable perinatal craniocerebral trauma resulting in mild asymptomatic right hemiatrophy developed right leg weakness and hypotonia alternating with dystonia only after prolonged exertion at age 12. At age 27, she developed right‐sided parkinsonism. Exertional paresis and dystonia and parkinsonism responded completely to levodopa; however, she developed a progressive reduction in the duration of action of levodopa over the first 4 years of treatment. Investigations including computed tomography, magnetic resonance imaging, [18F]fluorodopa, and [18F]fluorodeoxyglucose positron emission tomography scans suggested a static lesion involving the left substantia nigra. This unusual exertion‐induced weakness and hypotonia alternating with hypertonia and dystonia has not been reported previously. The role of dopamine deficiency in dystonia and the role of levodopa in the development of fluctuations in Parkinson's disease are discussed. Review of the literature, including this patient, emphasizes the heterogeneity of the syndrome of hemiparkinsonism‐hemiatrophy.
Hemimasticatory spasm in hemifacial atrophy: Diagnostic and therapeutic aspects in two patients
Authors: Ebersbach G. , Kabus C. , Schelosky L. , Terstegge L. , Poewe W.
Published: December 2004

We report two cases of hemimasticatory spasm in association with progressive hemifacial atrophy. On the basis of neurophysiological and magnetic resonance imaging assessments, a peripheral irritation of the trigeminal nerve–probably due to entrapment of the motor branches in the infratemporal fossa–is suggested as the cause of the involuntary movement. Local injections of botulinum toxin type A into the masticatory muscles proved to be a successful treatment in both patients.
Familial tremulous and myoclonic dystonia with white matter changes in brain magnetic resonance imaging
Authors: Bohlega S. , Stigsby B. , Al‐Kawi M. Z. , McLean D. R. , Ozand P. , Omer S. , Coates P.
Published: December 2004

We report two families with a disorder, probably autosomal recessive, characterized by tremor of juvenile onset, dystonia, and myoclonus with preserved cognitive, cerebellar, and peripheral nervous system functions. During 4 years' follow‐up, mild spasticity appeared. Magnetic resonance imaging (MRI) revealed mild diffuse changes in the white matter. Central conduction times for visual, motor, and sensory systems were all prolonged. Extensive metabolic work‐up failed to reveal lysosomal, peroxisomal, mitochondrial, or other metabolic abnormalities.
The epidemiology of Parkinson's disease in the county of Rogaland, Norway
Authors: Tandberg Elise , Larsen Jan P. , Nessler Ernst G. , Riise Trond , Aarli Johan A.
Published: December 2004

The objective of this investigation was to clarify the epidemiology of idiopathic Parkinson's disease (PD) in the county of Rogaland, Norway. Total case ascertainment and a high diagnostic accuracy were attempted through a detailed community study and the use of a new clinical diagnostic classification. The study population comprised 220, 858 inhabitants, and a total of nearly 400 patients was interviewed and examined by a neurologist. On prevalence day, January 1, 1993, 245 patients were included in the study. The diagnostic classification revealed 135 patients with clinically definite, 74 with probable, and 36 with possible PD. The crude prevalence rate was shown to be 110.9 per 100,000 inhabitants. The total age‐adjusted prevalence was calculated to be 102.4 per 100,000 and to 120.9 per 100,000 men and 89.8 per 100,000 women. Among the 245 patients, 28 patients had a tremor‐dominant disease, 50 patients an akinetic‐dominant disease, and 167 patients a mixed clinical pattern of PD. Age‐adjusted prevalence figures were slightly higher for rural compared to urban areas. About 50% of the PD patients were in need of public help, 15% had complaints about pain related to their parkinsonism, and after ∼6 years of levodopa treatment, 20% were suffering from clinical fluctuations. The study showed that 40% of the patients had some degree of thought disorder. The prevalence figures for PD in this study are slightly lower than those reported from most previous prevalence studies with a comparable study design for case finding. This may be due to a careful diagnostic evaluation with the use of specified diagnostic criteria, excluding patients with other parkinsonian syndromes.
No evidence for systemic oxidant stress in Parkinson's or Alzheimer's disease
Authors: Ahlskog J. Eric , Uitti Ryan J. , Low Phillip A. , Tyce Gertrude M. , Nickander Kim K. , Petersen Ronald C. , Kokmen Emre
Published: December 2004

Oxidant stress secondary to dopamine metabolism has been proposed as a pathogenic factor in the development of Parkinson's disease. Biochemical abnormalities extending beyond the central nervous system have been identified in patients with this condition. Previous investigators have found abnormally elevated concentrations of the lipid peroxidation product, malondialdehyde, in the plasma and serum of patients with Parkinson's disease. We attempted to replicate these findings but controlled for other factors that could influence malondialdehyde levels. We detected no significant elevations in mean serum malondialdehyde concentrations in either levodopatreated or untreated patients with Parkinson's disease, compared to normal controls; similarly, no elevation was found in a group of patients with dementia of Alzheimer's type. On the other hand, a group of subjects with diabetes mellitus but no neurodegenerative disease had significantly elevated mean serum malondialdehyde levels, consistent with previous studies of diabetic patients. Autoxidation is one of the two major routes by which dopamine and dopa metabolism may generate oxygen free radicals. We analyzed the autoxidation product of dopa, 5‐S‐cysteinyl‐dopa, in the plasma of these same groups of patients with neurodegenerative disease and normal controls; no significant differences were identified. Serum concentrations of two other antioxidant substances, α‐tocopherol and uric acid, were also statistically similar in these groups. In conclusion, analysis of several blood products relevant to oxidant stress, including malondialdehyde, 5‐S‐cysteinyl‐dopa, α‐tocophero, and uric acid, failed to distinguish patients with Parkinson's disease or dementia of Alzheimer's type from controls.
Long latency postural reflexes are under supraspinal dopaminergic control
Authors: Bloem Bastiaan R. , Beckley Dennis J. , van Vugt Jeroen P. P. , van Dijk J. Gert , Remler Michael P. , Langston J. William , Roos Raymund A. C.
Published: December 2004

Scaling of posturally stabilizing long latency (LL) reflexes in tibialis anterior muscles induced by “toe‐up” rotational perturbations is abnormal in standing patients with Parkinson's disease. To investigate the contribution of dopaminergic pathways to abnormal scaling, we studied LL reflexes in 22 patients with selective hypodopaminergic syndromes: 10 psychiatric patients taking chronic neuroleptic medication (7 with mild parkinsonism), 8 patients with young‐onset Parkinson's disease, and 4 patients with MPTP‐induced parkinsonism. Results were compared with those of 10 healthy controls. Stimuli consisted of (a) 10 serial (predictable) perturbations of 4° amplitude, (b) 10 serial (predictable) perturbations of 10° amplitude, and (c) 20 randomly mixed (unpredictable) perturbations of either 4 or 10° amplitude. In normal subjects, LL reflex amplitudes were adapted to match predictable variations in stimulus size, whereas under unpredictable conditions a “default” response emerged that anticipated the 10° perturbation. LL reflex scaling under predictable conditions was intact in patients with neuroleptic‐induced parkinsonism and young‐onset Parkinson's disease, but the large default LL response under unpredictable conditions was absent. In patients with MPTP‐induced parkinsonism, LL reflex scaling was absent during both predictable and unpredictable conditions. We conclude that abnormal scaling of posturally stabilizing LL reflexes is related to decreased supraspinal dopaminergic influence.
Neurological Wilson's disease studied with magnetic resonance imaging and with positron emission tomography using dopaminergic markers
Authors: Westermark K. , Tedroff J. , Thuomas K.‐Å. , Hartvig P. , Långström B. , Andersson Y. , Hörnfeldt K. , Aquilonius S.‐M.
Published: December 2004

Four patients with neurological Wilson's disease were investigated using magnetic resonance imaging (MRI) and positron emission tomography (PET). All patients had dystonia as their major clinical manifestation but also had dysarthria and at the presentation of the disease had choreoathetoid movements in at least one limb. A multitracer approach with PET was used to visualize various aspects of dopaminergic function; [11C]‐(+)‐nomifensine (NMF), [11C]raclopride (RAC) and [11C]‐L‐DOPA (one patient). Correlation analysis of RAC and NMF binding as well as putamen/caudate uptake ratios showed corresponding reductions. The patient investigated with [11C]‐L‐DOPA had a normal striatal uptake. Generally, structural changes as shown by MRI corresponded to reductions both in NMF and RAC binding. There was no evident correspondence between PET findings and the severity of clinical symptoms seen in the individual patient. In two patients with discrete neurological impairment at the time of investigation, PET showed serious presynaptic dopaminergic lesions in the putamen. Our data suggest that the striatal degeneration seen in Wilson's disease comprises a complex pathology involving both afferent and efferent projections. The discrete neurological impairment seen in some patients with gross striatal pathology might be due to concomitant lesions in functionally counteracting basal ganglia circuits.
The movement‐related cortical potential is abnormal in patients with idiopathic torsion dystonia
Authors: Van Der Kamp W. , Rothwell J. C. , Thompson P. D. , Day B. L. , Marsden C. D.
Published: December 2004

Voluntary movements, such as the self‐paced finger extension task used in the present experiments, are preceded by a slowly rising negative electroencephalographic potential [the movement‐related cortical potential (MRCP)]. The early NS1 component of the potential was no different in patients with primary dystonia affecting the arm (n = 6) compared with matched controls. In contrast, the peak amplitude of the MRCP was smaller in the patients, despite the fact that the movements made by the two groups were very similar; it was of equal size over both left and right hemispheres, rather than being larger on the side contralateral to the movement. These results are similar to those observed by others in patients with symptomatic dystonia secondary to lesions of the basal ganglia or their output pathways and may reflect abnormal basal ganglia input to motor areas of cortex before the onset of a self‐paced movement.
A “combined” levodopa test as a useful method for evaluating the efficacy of dopamine agonists: Application to pergolide and bromocriptine
Authors: Bonnet A. M. , Serre I. , Marconi R. , Agid Y. , Dubois B.
Published: December 2004

The efficacy of pergolide as adjunct to levodopa therapy was compared to that of bromocriptine in 12 parkinsonian patients with fluctuating motor disability and levodopa‐induced dyskinesias (mean age of onset, 50.6 ± 8 years; Hoehn and Yahr stage between II and IV; mean basal UPDRS motor score, 30.6 ± 8.6), in a double‐blind crossover study. After an 8‐day habituation to each agonist, an acute challenge of a supraliminal dose of levodopa (“levodopa test”) was performed in association with either 1 mg pergolide or 10 mg bromocriptine. The delay to onset and the duration of therapeutic benefit, the percentage improvement in motor disability, and the severity of onset and peak‐dose dyskinesias were evaluated. Both agonists significantly increased the duration of therapeutic benefit, but pergolide more so than bromocriptine (p = 0.02). Pergolide also tended to reduce the severity of dyskinesias and wes globally perceived by the patients to be more efficacious than bromocriptine on parkinsonian symptoms and fluctuations. This study illustrated the usefulness of the “levodopa test” in evaluating, objectively, the effects of dopamine agonists.
Bilateral subthalamic nucleus stimulation for severe Parkinson's disease
Authors: Limousin Patricia , Pollak Pierre , Benazzouz Abdelhamid , Hoffmann Dominique , Broussolle Emmanuel , Perret Jean Edmond , Benabid Alim‐Louis
Published: December 2004

Subthalamic nucleus (STN) lesions or high‐frequency stimulations could improve parkinsonian symptoms in monkeys treated by MPTP. We have applied the procedure of chronic stimulation to the STN in severely disabled parkinsonian patients. This article presents the case of the first patient operated on bilaterally. Bilateral STN stimulation has greatly improved akinesia and rigidity. The benefit was maintained ≤15 months after surgery. Unilateral stimulation induced motor effects mainly in contralateral limbs. Further studies are needed to evaluate the value of this procedure in the treatment of Parkinson's disease.
Intrathecal baclofen for motor disorders
Authors: Penn Richard D. , Gianino Janet M. , York Michelle M.
Published: December 2004

To test the efficacy of intrathecal baclofen in various movement disorders, 18 patients with dystonia, head trauma, cerebral palsy, rigidity, or painful spasms underwent a trial of intrathecal baclofen. Ten went on to permanent implantation with an infusion pump to provide long‐term treatment. Patients with a component of spasticity, painful spasms, or focal dystonias did best, and no response was seen in patients with rigidity due to anoxic encephalopathy. A videotape of responses is provided.
Involvement of respiratory muscles in adult‐onset dystonia: A clinical and electrophysiological study
Authors: Lagueny A. , Burbaud P. , Le Masson G. , Bergouignan F. X. , Ferrer X. , Julien J.
Published: December 2004

Involvement of respiratory muscles is unusual in dystonia, but its occurrence may be underestimated either because it is not conspicuous or because it is improperly imputed to another cause. Three patients who had adult‐onset dystonia and who were exhibiting respiratory problems were examined clinically and electrophysiologically. In the three patients the onset was focal‐cervical in two and blepharospasm in one. The respiratory problems appeared later. The first patient had involuntary deep and loud inspirations combined with spasms of axial dystonia, the second complained of breathing arrests, and the third had deep inspirations mainly on speaking or reading aloud, thus causing broken speech. Electromyographic findings, including of the diaphragm, were quite consistent with a respiratory involvement in these three cases of dystonia. Assuming that respiratory troubles could be the first sign of a focal dystonia, electrophysiological studies of respiratory muscles could be used to confirm this.
Chronic acquired hepatocerebral degeneration: Case reports and new insights
Authors: Jog Mandar S. , Lang Anthony E.
Published: December 2004

Chronic acquired hepatocerebral degeneration (CAHD) is a heterogeneous disorder that can occur with a primary neurologic, hepatic, or combined presentation. Little has been added to the understanding of this disorder since the detailed, early clinical and pathological descriptions. The spectrum of clinical presentations can be neuropsychiatric (apathy, lethargy, excessive somnolence), a movement disorder (ataxia, tremor, chorea, parkinsonism, myoclonus, dystonia), or both. Cortical laminar necrosis and polymicrocavitation in the cortex and basal ganglia are combined with cerebral and cerebellar atrophy. Microscopically, Alzheimer type II astrocytes and cytoplasmic glycogen granules are characteristic. Recent neuroradiological observations in patiensts with liver failure have shown a specific magnetic resonance (MR) imaging appearance with a hyperintense T1 signal in the pallidum, putamen, and, rarely, mesencephalon. Using clues from a similar MR appearance in patients receiving total parenteral nutrition as well as animals given parenteral manganese, and the knowledge that manganese is cleared by the hepatobiliary system, deposition of manganese in the brain is postulated in patients with CAHD. In this review we describe three cases of CAHD with detailed clinical and radiological documentation and discuss the aforementioned pathogenetic mechanisms.
The audiogenic startle response in Tourette's syndrome
Authors: Stell R. , Thickbroom G. W. , Mastaglia F. L.
Published: December 2004

We report the results of a study in which we examined the auditory startle responses (ASR) of 8 patients with Tourette's syndrome and 15 normal controls, none of whom reported or manifested exaggerated startle responses clinically. The ASR in two patients failed to habituate with repetition, a finding not present in any of the controls. There was no correlation between the presence or absence of exaggerated ASRs and the severity of the patients' tics. This study demonstrates that some patients with Tourette's syndrome have exaggerated audiogenic startle responses that may be clinically asymptomatic.
Modulation of electromyographic activity of wrist flexor and extensor muscles in patients with writer's cramp
Authors: Valls‐Solé Josep , Hallett Mark
Published: December 2004

Patients with writer's cramp have two well‐recognized neurophysiological abnormalities: reduced reciprocal inhibition of the wrist flexor motoneurons at rest, and increased cocontraction of antagonist muscles of the forearm during voluntary activity. In this article we present evidence for an impaired integration of sensory inputs into the voluntary motor activity during performance of a force‐related task in patients with writer's cramp. Normal (control) subjects and patients activated wrist flexor and extensor muscles to maintain a predetermined level of force. Electrical stimuli were applied to median and radial nerve afferents and the modulatory effects induced in the electromyographic (EMG) activity were measured. For each muscle studied and nerve stimulated, we defined a characteristic sequence of excitatory (E) and inhibitory (I) phases of modulation of the averaged rectified EMG activity in control subjects. E and I phases were thought to represent excitation and inhibition, respectively, of the corresponding motoneuronal pool to homonymous or reciprocal afferent inputs. There were no differences between control subjects and patients regarding the level of background EMG activity in the agonist muscles during wrist flexion or wrist extension. In the agonist wrist flexors, patients had reduced reciprocal excitation and reciprocal inhibition. These results are compatible with an abnormal CNS processing of the inputs generated by external stimuli during voluntary contraction of wrist flexor and extensor muscles. Defective integration of inputs from peripheral nerve afferents into the command for voluntary movement may partly underlie the pathophysiology of the motor dysfunction in patients with writer's cramp.
Associated movement as a sequel to thoracotomy: Aberrant regeneration to the latissimus dorsi muscle
Authors: Kuwabara Satoshi , Fukutake Toshio , Kasahata Nobuyoshi , Shimoe Yutaka , Yamanaka Izumi , Hirayama Keizo
Published: December 2004

We describe two patients with unusual associated movements as a sequel to thoracotomy. The two patients developed involuntary twitchings of the latissimus dorsi, which were induced by contractions of the adjacent muscles, the serratus anterior muscle in patient 1 and the external intercostal muscle in patient 2, after lobectomy for lung cancer. Electrophysiological and radiological studies showed that aberrant regeneration from the adjacent nerves to the denervated latissimus dorsi could be responsible for the associated movements.
Environmental and genetic risk factors in Parkinson's disease: A case–control study in southern italy
Authors: De Michele G. , Filla A. , Volpe G. , De Marco V. , Gogliettino A. , Ambrosio G. , Marconi R. , Castellano A. E. , Campanella G.
Published: December 2004

To clarify the role of heredity and of some environmental risk factors in the etiology of idopathic Parkinson's disease, we performed a case‐control study in two regions of southern Italy, Campania and Molise. We selected two controls for each parkinsonian patient, the patient's spouse and a sex‐ and age‐matched neurological control. One hundred sixteen consecutive outpatients with Parkinson's disease (77 men, 39 women; mean age ± SD = 62.5 ± 9.9) and the same number of spouses and neurological controls were interviewed about five environmental risk factors (cigarette smoking, well‐water drinking, head trauma with loss of consciousness, strict diets, general anesthesia) and two genetic risk factors (family history of Parkinson's disease or of essential tremor). Well‐water drinking and family history of Parkinson's disease or essential tremor showed a positive association with Parkinson's disease; smoking showed a negative association. The most relevant risk factor was history of familial Parkinson's disease (odds ratio = 14.6; 95% confidence interval = 7.2 − 29.6); 33% of our patients had at least one affected relative. We also showed a unilateral distribution of ancestral secondary cases on the paternal or on the maternal side, which suggests a dominant inheritance. Clinical and epidemiologic features of cases with familial Parkinson's disease showed no peculiarity. The study suggests a strong role of the genetic factors in the etiology of Parkinson's disease.
Levodopa stability in solution: Time course, environmental effects, and practical recommendations for clinical use
Authors: Pappert Eric J. , Buhrfiend Colleen , Lipton Jack W. , Carvey Paul M. , Stebbins Glenn T. , Goetz Christopher G.
Published: December 2004

We defined the temporal stability characteristics of levodopa/carbidopa (LD/CD) solution, and determined the effects of temperature, ascorbate, and light on LD stability over 7 days. At room temperature and without ascorbate, LD levels significantly declined by 48 h. Ascorbate prolonged stability to 72 h. Refrigeration and freezing prevented a significant decline in LD levels for the full 7 days. Light or darkness had no effect on stability. LD/CD solution, if made daily, requires no special handling and longer stability is maintained with ascorbate, refrigeration, or freezing.
Unilateral injection of botulinum toxin in blepharospasm: Single fiber electromyography and blink reflex study
Authors: Girlanda P. , Quartarone A. , Sinicropi S. , Nicolosi C. , Messina C.
Published: December 2004

We studied six patients affected with blepharospasm (BSP). We injected botulinum toxin (BTX) around only one eye and saline solution around the other. Clinical rating of BSP was performed. Single fiber electromyography (SFEMG), compound motor action potential (cMAP) at the orbicularis oculi muscle by stimulation of the facial nerve, blink reflex, and blink reflex recovery curve were recorded. All clinical and electrophysiological investigations were carried out before, and 1, 2, and 4 weeks after treatment. Evidence of bilateral clinical benefit was provided. Following therapy, facial cMAP decreased bilaterally and SFEMG revealed statistically significant changes on both sides while the excitability curve of blink reflex remained unmodified. The results confirm that BTX affects merely the neuromuscular junctions. The clinical and neurophysiological effects are present on both sides also for unilateral injection probably because of toxin spreading.
Cricopharyngeal dysfunction in Parkinson's disease: Role in dysphagia and response to myotomy
Authors: Born Lawrence J. , Harned Roger H. , Rikkers Layton F. , Pfeiffer Ronald F. , Quigley Eamonn M. M.
Published: December 2004

We report five patients with Parkinson's disease and dysphagia who were found, by radiological and manometric evaluation, to have evidence of cricopharyngeal dysfunction, which included the presence of a Zenker's diverticulum in two. Cricopharyngeal myotomy was performed in four patients with excellent and sustained improvement in swallowing. We conclude that cricopharyngeal function should be carefully evaluated in patients with Parkinson's disease and dysphagia and that surgical treatment should be considered in appropriate cases.
Slow increase of homovanillic acid in cerebrospinal fluid after levodopa administration
Authors: Raftopoulos C. , Dethy S. , Laute M. A. , Goldman S. , Naini A. B. , Przedborski S. , Hildebrand J.
Published: December 2004

Concentrations of major catabolites of dopamine were followed in the ventricular cerebrospinal fluid (CSF) in five patients undergoing intracranial pressure monitoring for chronic hydrocephalus. Determinations were made every 2 h following the administration of carbidopa/levodopa 25/250 mg (one Sinemet capsule) given 8h apart. The rise of homovanillic acid (HVA) concentrations was slow and progressive, reaching the level of statistical significance (p ≤ 0.01) only 8 h after the second administration of Sinemet. The rise in 3,4‐dihydroxy‐phenylacetic acid (DOPAC) was faster than the rise in HVA, with the peak value detected 4 h after the first administration of Sinemet. These data are interpreted as a confirmation, in humans, of a slow pool of exogenous levodopa, previously demonstrated in animal studies.
Prevalence of a history of shaking in persons 65 years of age and older: Diagnostic and functional correlates
Authors: Louis E. D. , Marder K. , Cote L. , Wilder D. , Tang M‐X. , Lantigua R. , Gurland B. , Mayeux R.
Published: December 2004

The purpose of this study was to determine the prevalence and functional and diagnostic correlates of reported shaking in the community‐dwelling elderly. We conducted a standardized neurological evaluation of 1,056 nondemented Medicare recipients in Washington Heights‐Inwood, Northern Manhattan (New York). Of 1,056 patients, 108 reported shaking (10.2%). The prevalence of reported shaking did not increase with age. It did differ between ethnic groups, but when adjusted for depression and score on the Schwab and England Activities of Daily Living (ADL) scale, this difference was insignificant. The age‐adjusted prevalence was similar for women and men. Neurological examination of the 108 who reported shaking showed that 8.3% had tremor at rest, 17.6% had tremor with action, 5.6% had dyskinesia or chorea, and an additional 28.7% had various problems in coordination or movement. The remaining 39.8% had neither tremor nor problems in coordination or movement. Only 2.9% of individuals with reported shaking had Parkinson's disease (PD), 8.7% had essential tremor, and 2.1% had oral‐buccal‐lingual dyskinesia. Of the remaining 86.3%, 29 (31%) had no identifiable medical condition. Those who reported shaking were less independent with ADLs, regardless of presence of tremor on examination. Shaking is commonly reported by the community‐dwelling elderly. It does not necessarily identify individuals with essential tremor and PD, and is related to decreased independence in ADLs.
Pure stimulus‐sensitive truncal myoclonus of propriospinal origin
Authors: Schulze‐Bonhage A. , Knott H. , Ferbert A.
Published: December 2004

The clinical and electrophysiological features of stimulus‐sensitive truncal myoclonus are described in a 49‐year‐old woman. Touching the skin of the back and abdomen would evoke jerks in both ipsilateral and contralateral axial muscles; there was no spontaneous jerking. Multichannel EMG recordings showed bilateral short‐latency muscle bursts at truncal recording sites both rostral and caudal to stimulus sites. The short latencies of muscle bursts in adjacent segments give evidence of a spinal origin of myoclonus; the pattern of recruitment and the velocity of spread suggest the involvement of propriospinal pathways. The presence of intrathecal IgG synthesis and of oligoclonal bands in the CSF point towards an inflammatory process which may underly the unusual type of myoclonus in this patient.
An appraisal of the antiparkinsonian activity of piribedil in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐treated common marmosets
Authors: Smith Lance , De Salvia Maria , Jenner Peter , Marsden C. David
Published: December 2004

The D2 dopamine agonist piribedil is not widely used in the treatment of Parkinson's disease because it was thought to be effective mainly on parkinsonian tremor and to produce a high incidence of peripheral side effects, particular nausea. In this study, we used 1–methyl–4–phenyl–1,2,3,6–tetrahydropyridine (MPTP)–treated primates to reevaluate the antiparkinsonian ability of piribedil after its oral administration in the presence or absence of domperidone pretreatment. Adult common marmosets (Callithrix jacchus) were treated with the nigral toxin MPTP to induce a parkinsonian syndrome characterised primarily by brady kinesia and other motor deficits. Oral administration of a solution of piribedil [1–(3,4–methylenedioxybenzyl)–4–(2–pyrimidinyl) piperazine] produced a dose–related reversal of all MPTP locomotor and behavioural deficits. However, this effect was short lived and associated with unwanted effects, particular nausea and retching, which clearly hindered locomotion. In contrast, after pretreatment with the peripheral dopamine antagonist domperidone, administration of piribedil did not induce nausea or retching in MPTP‐treated marmosets. In these animals, piribedil caused a more marked and and longer lasting enhancement of locomotor activity and a further reduction in behavioural deficits than that observed after administration of piribedil alone. In addition, piribedil induced increased vigilance and awareness. These data show that piribedil can reverse akinesia and rigidity in MPTP‐treated primates. In addition, they show the drug to be effective without peripheral side effects when used in conjuction with domperidone. These data indicate that piribedil should be an effective monotherapy for Parkinson's disease.
Haplotype analysis at the DYT1 Locus in ashkenazi jewish patients with occupational hand dystonia
Authors: Gasser T. , Bove C. M. , Ozelius L. J. , Hallett M. , Charness M. E. , Hochberg F. H. , Breakefield X. O.
Published: December 2004

Genetic haplotypes at five marker loci that are closely linked to the DYT1 gene on chromosome 9q were determined in 10 Ashkenazi Jewish patients with focal hand dystonia (eight with musician's cramp, two with writer's cramp). The founder haplotype associated with >90% of cases of generalized dystonia in the Ashkenazi Jewish population could not be constructed from any of the twenty chromosomes. Potential haplotypes were determined, and no common haplotype was discerned in these patients. These findings argue against a role for the founder mutation in the DYT1 gene in the etiology of occupational hand dystonia in this ethnic group. Further, if the DYT1 gene is involved in these later onset dystonias, there is no evidence for a common mutation in the Ashkenazic Jewish population. It appears that excessive, repetitive use, possibly in combination with ulnar neuropathy, may serve as the inciting cause of some focal dystonias.
Dominantly inherited cerebello‐olivary atrophy is not due to a mutation at the spinocerebellar ataxia‐I, machado‐joseph disease, or dentato‐rubro‐pallido‐luysian atrophy locus
Authors: Subramony S. H. , Fratkin J. D. , Manyam B. V. , Currier R. D.
Published: December 2004

The dominantly inherited ataxias are characterized both by phenotypic variablity (phenotypic heterogeneity) within the same genotype and overlapping phenotypes from different genotypes (genotypic heterogeneity). Therefore it is important to characterize specific clinical‐neuropathologic phenotypes as precisely as possible at the genetic level. We describe a family with dominantly inherited ataxia of late adult onset with relatively “pure” cerebellar signs. Neuropathologic examination in two individuals from this family revealed findings consistent with cerebello‐olivary atrophy, suggesting that this neuropathologic phenotype may run true within families. Mutations at the spinocerebellar ataxia‐I, Machado‐Joseph disease, and dentatorubropallidoluysian atrophy loci were excluded by direct DNA analysis on the leukocytes of one living affected member. Thus we provide evidence that these mutations are not responsible for this particular phenotype of dominantly inherited ataxia.
Abnormal involuntary movements induced by subthalamic nucleus stimulation in parkinsonian patients
Authors: Limousin Patricia , Pollak Pierre , Hoffmann Dominique , Benazzouz Abdelhamid , Perret Jean Edmond , Benabid Alim‐Louis
Published: December 2004

Chronic electrical subthalamic nucleus (STN) stimulation is under investigation for alleviating parkinsonian symptoms. STN alterations may carry the risk of provoking abnormal involuntary movements (AIMs). We took advantage of the reversibility of the stimulation technique to assess the possibility of inducing AIMs, using different electrical variables with or without concomitant levodopa intake. Above a given threshold voltage, stimulation could induce contralateral distal mobile AIMs or hemiballism in the off‐drug condition in two patients. AIMs occurred after a latency that varied from a few minutes up to several hours after switching on the stinulator. Hemiballism immediately disappeared upon switching off the stimulator. In these patients, levodopa had never provoked that type of AIMs before surgery. Levodopa‐induced AIMs were not modified by electrical stimulation, but off‐phase dystonia disappeared in one patient. Stimulation of the STN induced AIMs that resembled both those observed following spontaneous lesions of the STN and levodopa‐induced diphasic AIMs in parkinsonian patients. As electrical stimulation provoked AIMs and antiparkinsonian benefit occurred with different electical variables and different timing, the mechanisms responsible for these two effects could be distinct.
Clinical course of patients with idiopathic Parkinson's disease
Authors: Roos R. A. C. , Jongen J. C. F. , Van Der Velde E. A.
Published: December 2004

We determined the variables associated with the progression and duration of illness of patients with Parkinson's disease (PD) and investigated the cause of death. In 474 patients with parkinsonism, who visited the Academic Hospital between January 1, 1960 and August 31, 1993, we did a survival analysis with the following covariates: age at onset, intial symptom (tremor or rigidity/hypokinesia), age at reaching Hoehn and Yahr stage III, dementia‐free period, and levodopa treatment. A total of 345 patients with parkinsonism fulfilled the criteria of idiopathic PD; 258 of them were still alive on the closing date of this study. There were significantly more men than women (1.43:1). Medical advice was sought in an earlier stage by men and by patients with tremor as presenting symptom. For patients with rigidity/hypokinesia as first symptom, the duration of illness until reaching Hoehn and Yahr stage III was shorter than for patients starting with tremor alone. If the initial symptom is tremor, patients develop dementia less frequently and later after onset than when tremor is not involved. Reaching Hoehn and Yahr stage III and developing dementia both, limit the patient's survival time. The mortality risk for a patient was found to be increased form the moment levodopa treatment was started as compared to those patients who had not yet started with the treatment. The effect of levodopa on survival could not be disentangled from effects of other factors related to the start of levodopa treatment.
A randomized, double‐blind, placebo‐controlled study to evaluate botulinum toxin type A in essential hand tremor
Authors: Jankovic J. , Schwartz K. , Clemence W. , Aswad A. , Mordaunt J.
Published: December 2004

Twenty‐five patients with hand tremor of 2 + (moderate) to 4 + (severe) on the tremor severity rating scale were randomized to receive either 50 U of botulinum toxin (BTX) type A (Allergan, Irvine, CA) or placebo injections into the wrist flexors and extensors of the dominant limb. If patients failed to respond to the initial injection, they were eligible to receive another injection of 100 U 4 weeks later. Rest, postural, and kinetic tremors were evaluated at 2‐ to 4‐week intervals over a 16‐week study period using tremor severity rating scales, accelerometry, and assessments of improvement and disability. A signigicant improvment (p < 0.05) was observed on the tremor severity rating scale 4 weeks after injection in patients treated with BTX as compared with placebo, and this effect was maintained for the duration of the study. Four weeks after injection, 75% of BTX‐treated patients vs. 27% of placebo‐treated patients (p < 0.05). reported mild to moderate improvement (peak effect rating ≥2). There were no significant improvements in functional rating scales, although trends were observed for some items. Postural accelerometry measurements showed a ≥30% reduction in amplitude in nine of 12 BTX‐treated subjects and in one of nine placebo‐treated subjects (p < 0. 05). Although all patients treated with BTX reported some degree of finger weakness, no severe, irreversible, or unexpected adverse events occurred. Chemodenervation with BTX may significantly ameliorate essential hand tremor in patients who fail to improve with conventional pharmacologic therapy.
Effect of stimulation in the ventral intermediate nucleus of the thalamus on limb control in parkinson7apos;s disease: A case study
Authors: Pfann K. D. , Penn R. D. , Shannon K. M. , Shapiro M. B. , Corcos D. M.
Published: December 2004

This study focuses on upper extremity strength and movement control in a patient with Parkinson's disease who had stimulating electrodes surgically implanted in the ventral intermediate nucleus (VIM) of the left thalamus. We examined torque generation and control of movements distance in single degree‐of‐freedom elbow movements under three different stimulation conditions: (a)no stimulation, (b)high stimulation, in which tremor was minimized but there was also tingling and perceived weakness, and (c) moderate stimulation, in which tremor was partially reduced, but there was also a subjective sense of increased strength compared with the high‐stimulation condition. The patient's ability to generate both steady torque and rapid movements was poorest with no stimulation. The patient generated the largest torque with moderate stimulation and performed the fastest movements with high stimulation. However, even with tremor minimized, the patient's electromyogram (EMG) burst patterns were not typical of those of neurologically healthy subjects, although the movements were clearly improved.
Prospects for gene therapy in Parkinson's disease
Authors: Freese Andrew , Stern Matthew , Kaplitt Michael G. , O'Connor William M. , Abbey Maureen V. , O'Connor Michael J. , During Matthew J.
Published: December 2004

Numerous advances in in vivo and ex vivo gene‐therapy approaches to Parkinson's disease offer promise for direct clinical trials in patients in the next several years. These systems are predicated on introducing genes that encode enzymes responsible for dopamine biosynthesis or neurotrophic factors that may delay nigrostriatal degeneration or facilitate regeneration. We review the current status of experimental approaches to gene therapy for Parkinson's disease. Comparative advantages and disadvantages of each system are enumerated, and preclinical trials of some of the systems are evaluated. Although the specific in vivo or ex vivo methods used for gene transfer into the brain are likely to be supplanted by newer technology over the next decade, the principles and approaches developed in current studies likely will remain the same.