bluuebunny/crossref_metadata_2025 huggingface dataset:
The neuropathological features of neuroacanthocytosis
Authors: Rinne J. O. , Daniel S. E. , Scaravilli F. , Pires M. , Harding A. E. , Marsden C. D.
Published: December 2004

In this article we describe the neuropathological changes in three patients with neuroacanthocytosis and review the neuropathology of the other eight cases reported in the literature. Macroscopically the brains showed enlargement of the lateral ventricles, especially the frontal horns. The most severely and consistently affected brain areas were the caudate nucleus and putamen, which were atrophic and showed by light microscopy marked neuronal loss and gliosis. Small and medium‐sized striatal neurons were particularly depleted. The globus pallidus was almost as severely involved as the striatum. In some cases the thalamus, substantia nigra, and anterior horns of the spinal cord showed pathology, mainly neuronal loss and mild gliosis. Brain areas with no pathology included the subthalamic nucleus, cerebral cortex, cerebellum, pons, and medulla. The preservation of these areas may help in the neuropathological distinction of neuroacanthocytosis from Huntington's disease.
Hereditary variations in monoamine oxidase as a risk factor for Parkinson's disease
Authors: Hotamisligil Gokhan S. , Girmen A. Sule , Fink J. Stephen , Tivol Elizabeth , Shalish Christo , Trofatter James , Baenziger John , Diamond Shirley , Markham Charles , Sullivan Jack , Growdon John , Breakefield Xandra O.
Published: December 2004

Parkinson's disease (PD) is a common neurodegenerative disorder caused by loss of dopaminergic neurons in the brainstem. Recent studies suggest that several genes may have a role in determining individual susceptibility to this disease, and the degradative enzyme monoamine oxidase (MAO) has been implicated in the disease process. Wide differences in activity levels for both forms of this enzyme (MAO‐A and MAO‐B) exist in the human population, and levels of both are genetically determined. Here we have compared the frequency of haplotypes at the MAOA and MAOB loci on the X chromosome in 91 male patients with PD and 129 male controls. Alleles were marked using two restriction fragment length polymorphisms (RFLPs), a (GT)n repeat in the MAOA locus, and a (GT)n repeat in the MAOB locus. One particular haplotype marked by the RFLP's at MAOA was three times more frequent in patients with PD as compared with controls, and the overall distribution of these alleles was significantly different (p =0.03) between these two groups. Another MAOA haplotype was about threefold more common in controls than in patients with PD (p = 0.005). No associations were observed between individual MAOB alleles and the disease state, but the frequency distribution for all alleles was significantly different in the two populations (p = 0.046). These findings support the idea that the MAO genes may be among the herediatary factors that influence susceptibility of individuals to PD.
Analysis of repetitive and nonrepetitive sequential arm movements in patients with Parkinson's disease
Authors: Agostino Rocco , Berardelli Alfredo , Formica Alessandro , Stocchi Fabrizio , Accornero Neri , Manfredi Mario
Published: December 2004

We examined the motor performance of Parkinson's disease patients and normal subjects during nonrepetitive and repetitive sequential tasks. Parkinson's disease patients took longer than normal subjects to Complete the nonrepetitie task, the sequential drawing of a pentagon. In patients, movement times lengthened as the sequence neared completion. The amount of lengthening was similar in nonrepetitive and repetitive tasks (sequential alternating drawing of each side of the pentagon). In parkinsonian patients the slowing at the end of the sequential tasks does not appear to be influenced by whether the sequential task involes nonrepetitive or repetitive movements.
Clozapine treatment of psychosis in patients with tardive dystonia: Report of three cases
Authors: Friedman Joseph H.
Published: December 2004

Among the tardive dyskinesia syndromes, dystonia can be the most difficult to treat. It may be severe to the point of being disabling, yet the patients may require antipsychotic medications for an even more disabling psychosis. Clozapine, an atypical neuroleptic drug that lacks extrapyramidal effects, may be the drug of choice for such patients. This report describes three patients with significant dystonia, previously disabled by their psychoses, who have been successfully manged with clozapine plus other agents for >3 years.
Spinal myoclonus resembling belly dance
Authors: Kono Ichiyo , Ueda Yoshihiro , Araki Kuniharu , Nakajima Kenji , Shibasaki Hiroshi
Published: December 2004

A 63‐year‐old man presented with an 11‐month history of progressive myoclonus in the right abdominal wall. Administration of clonazepam reduced the frequency and amplitude. When the therapy was discontinued, the frequency and amplitude of the myoclonus increased, and synchronous and weak myoclonus also was observed in the left abdomen. The trunk was twisted just after the appearance of the abdominal myoclonus associated with myoclonic jerks spreading from the rostral to caudal paraspinal muscles. Later in the clinical course, the myoclonus became stimulus sensitive and was induced by tendon tap given anywhere on the body, with the latency ranging from 50 to 150 ms irrespective of the sites of tapping. Myoclonus seen in the abdominal wall was segmental and considered to be of spinal origin. The reflex myoclonus had a 150‐ms refractory period. It can be postulated that increased excitability of anterior horn cells at a certain segment might make a spino‐bulbo‐spinal reflex manifest at the corresponding segment. This myoclonus is considered to be a new form of spinal reflex myoclonus, because the abdominal myoclonic jerk seems to trigger another myoclonic jerk involving the paraspinal muscles.
Familial hemifacial spasm
Authors: Micheli Federico , Scorticati Maria Clara , Gatto Emilia , Cersosimo Graciela , Adi Javier
Published: December 2004

Two brothers developed hemifacial spasm at 63 and 70 years of age. Spasms occurred on the left and right sides of the face, respectively. Computed tomography scan and magnetic resonance imaging failed to show any abnormality. In addition, a third sibling reported a history of a peripheral facial palsy, which remitted spontaneously without sequelae. This is the fourth description of familial hemifacial spasms. This family is unique in that hemifacial spasm presented on different sides in the two brothers, and involvement was limited to one generation. Age at onset was later than for other familial cases and similar to sporadic cases.
Tyrosine hydroxylase polymorphism in familial and sporadic Parkinson's disease
Authors: Planté‐Bordeneuve V. , Davis M. B. , Maraganore D. M. , Marsden C. D. , Harding A. E.
Published: December 2004

Tyrosine hydroxylase (TH) is a theoretical candidate gene determining susceptibility to Parkinson's disease (PD), and an association between one allele of a polymorphism at the TH locus and sporadic PD has been reported. We investigated TH polymorphism in 44 patients with sporadic PD, 48 patients with familial PD and 89 of their unaffected relatives, and 50 control subjects. No evidence of allelic association was detected in either familial or sporadic PD, and linkage analysis excluded the TH locus, or a closely linked gene, as a major determinant of familial PD.
Botulinum toxin in the treatment of dystonic tics
Authors: Jankovic Joseph
Published: December 2004

Botulinum toxin (BTX) injections provide effective treatment for a variety of disorders manifested by inappropriate muscle contractions, but its efficacy in the treatment of tics has not been previously studied. Ten male patients 13–53 years of age who were diagnosed with Tourette's syndrome manifested by disabling focal tics were included in this pilot study. Five patients had frequent blinking and blepharospasm, rendering them “blind,” and five patients had severe and painful dystonic tics involving their neck muscles. All 10 patients experienced moderate to marked improvement in the intensity and frequency of tics after BTX injections into the involved muscles. Patients in whom premonitory urges preceded their tics noted marked lessening of these sensory symptoms. The benefit lasted 2–20 weeks after injections. There were no serious complications, except for transient ptosis in two and neck pain, stiffness, or weakness in three patients. BTX injections appear to be safe and effective treatment for patients with focal dystonic tics. The treatment ameliorates not only involuntary movements but also the premonitory sensory component associated with some tics.
Leuprolide acetate for exhibitionism in huntington's disease
Authors: Rich Stuart S. , Ovsiew Fred
Published: December 2004

We treated a patient with Huntington's disease and exhibitionism using leuprolide acetate (Lupron Depot, TAP Pharmaceuticals), a gonadotropin‐releasing hormone agonist. The result was elimination of his deviant sexual behavior with few side effects. This regimen may be a safe and effective pharmacological treatment of the paraphilias. The occurrence of paraphilias in basal ganglia disorders is reviewed.
Subcortical neurofibrillary degeneration presenting as steele‐richardson‐olszewski and other related syndromes: A review of 90 pathologically verified cases
Authors: de Bruin V. M. S. , Lees A. J.
Published: December 2004

We have reviewed 90 patients from the literature with histopathological features compatible with currently accepted criteria for the diagnosis of the Steele‐Richardson‐Olszewski syndrome (SROS). Only 62 patients (69%) had clinically definite SROS based on the criteria of Maher and Lees. Neurofibillary degeneration of subcortical structures with involvement of the internal pallidum, the subthalamic nucleus, and substantia nigra was considered essential for the pathological diagnosis. Thirty‐six cases (40%) had neocortical neurofibrillary change that bore no clear relationship to the degree of cognitive impairment (χ2 = 9.293; p < 0.4107). Grumose degeneration of the dentate nucleus was present in 25 cases (28%), and occasionally there were other, less usual, findings such as Pick bodies and Lewy bodies.
Utility of an objective dyskinesia rating scale for Parkinson's disease: Inter‐ and intrarater reliability assessment
Authors: Goetz C. G. , Stebbins G. T. , Shale H. M. , Lang A. E. , Chernik D. A. , Chmura T. A. , Ahlskog J. E. , Dorflinger E. E.
Published: December 2004

Although dyskinesia is a frequent and important problem in Parkinson's disease (PD), a reliable assessment measure has not been thoroughly developed and tested. We modified the Obeso dyskinesia scale to creat an objective rating scale for dyskinesia assessment during activities of daily living. Thirteen physicians and 15 study coordinators involved in a clinical trial independently reviewed videotape segments of PD patients performing three tasks: walking, putting on a coat, and lifting a cup to the lips for drinking. Raters evaluated the severity of worst dyskinesia seen, the types of all dyskinesias seen, and the type of dyskinesia most associated with motoric disability. For all assessments, the total group showed statistically significant inter‐ and intrarater reliability. Physicians had a higher consistency than did coordinators, but for most measures the difference was not statistically significant. Physicians and coordinators found the scale easy to use and especially practical for rating dyskinesia severity and for identifying the most disabling dyskinesia. Dyskinesias can be assessed in clinical trials and warrant regular documentation.
Clinical and electromyographic features of levator palpebrae superioris muscle dysfunction in involuntary eyelid closure
Authors: Aramideh M. , de Visser B. W. Ongerboer , Koelman J. H. T. M. , Bour L. J. , Devriese P. P. , Speelman J. D.
Published: December 2004

We report on five patients with involuntary eyelid closure, diagnosed as blepharospasm and referred to us for treatment with botulinum A toxin. Synchronous electromyographic (EMG) recording was performed from the levator palpebrae superioris (LP) and the orbicularis oculi (OO) muscles. In the first two cases, EMG registration showed alternating, semirhythmic dystonic activities in both the LP and OO, clinically perceptible as “flickering” of the eyelids. While the eyelids were lowered, one of them alos showed involuntary upper eyelid tractions due to dystonic activities of LP. In the third patient, EMG patterns were characterized by a gradual decrease in the level of LP activity, followed by the contraction of OO, which facilitated the return of LP to its tonic activity, termed “postinhibition potentiation” of LP. In the fourth patient, EMG recording showed involuntary inhibition of LP in combination with blepharospasm. Involuntary closure of the eyelids in the fifth patient was caused by short or prolonged periods of involuntary LP inhibition, whereas OO activity remained normal. Our results provide further evidence that LP muscle activities are regulated by burst‐tonic motoneurons, and we suggest that these motoneurons, and/or the input signals regulating their activities, can be involved independently in a pathological process. Clinical symptoms are discussed that may be helpful to recognize those cases with LP motor dysfunction, whether or not accompanied by OO activity disorders. Because the term blepharospasm indicates an abnormal motor function of OO, we propose “blepharospasm‐plus” to designate those cases with a combined motor dysfunction of LP and OO muscles.
Suppression of dyskinesias in advanced Parkinson's disease: Moderate daily clozapine doses provide long‐term dyskinesia reduction
Authors: Bennett James P. , Landow Elke R. , Dietrich Susan , Schuh Lori A.
Published: December 2004

Dyskinesias commonly appear during L‐dihydroxyphenylalanine (L‐DOPA) therapy of advanced Parkinson's disease (PD) and can occur in both dose‐related and dose‐independent patterns. Clozapine exerts a dose‐related suppression of L‐DOPA‐induced dyskinesias by shifting the i.v. L‐DOPA dose‐response curve for production of dyskinesias without altering relief of parkinsonism. We report our outpatient experience with 13 patients on daily clozapine therapy (maximum dose 400 mg/day), followed for 3–21 months (median 10). Beneficial effects of clozapine, determined from twice‐weekly diaries, included increased “on time” and decreased “off time” and time “on with dyskinesia.” Improvements were statistically apparent by 75 mg/day and remained so through 200 mg/day. Sedation was a common problem, reflected by increased time “asleep” which was significant by 50 mg/day. Sedation was dose limiting in most patients. Orthostatic hypotension and sialorrhea were variably present. No patients had seizures, bone marrow toxicity, or detectable loss of efficacy of clozapine with chronic use. We conclude that clozapine is an effective agent for suppression of dyskinesias in PD with an effective daily dose for most patients of 100–200 mg/day.
Pergolide compared with bromocriptine in Parkinson's disease: A multicenter, crossover, controlled study
Authors: Pezzoli G. , Martignoni E. , Pacchetti C. , Angeleri V. A. , Lamberti P. , Muratorio A. , Bonuccelli U. , De Mari M. , Foschi N. , Cossutta E. , Nicoletti F. , Giammona F. , Canesi M. , Scarlato G. , Caraceni T. , Moscarelli E.
Published: December 2004

We compared the efficacy and safety of pergolide and bromocriptine in 57 patients with Parkinson's disease (PD) with a declining response to levodopa therapy in a single‐blind, crossover study. Patients were placed randomly on the sequence bromocriptine‐pergolide (12 + 12 weeks) or vice versa. Regular evaluations using the New York University Parkinson's Disease Scale were performed by a clinician blinded to treatment assignment. Patients' and clinicians' impressions also were recorded. The average daily dose of pergolide was 2.3 ± 0.8 mg, and that of bromocriptine was 24.2 ± 8.4 mg. Significantly greater efficacy was demonstrated by both drugs as adjunctive therapy to levodopa compared with previous treatment of levodopa alone (pergolide, p = 0.0001; bromocriptine, p = 0.0005; Wilcoxon t test). Pergolide was more effective than bromocriptine in daily living scores (p = 0.020) and motor scores (p = 0.038). No difference in dyskinesias, dystonias, and psychosis was observed. Adverse events were more frequent in bromocriptine‐treated patients. Most patients and physicians preferred pergolide to bromocriptine. Pergolide as adjunctive therapy to levodopa was more effective than bromocriptine in this short‐term trial.
Treatment of severe axial tardive dystonia with clozapine: Case report and hypothesis
Authors: Trugman Joel M. , Leadbetter Robert , Zalis Michael E. , Burgdorf Rose O. , Wooten G. Frederick
Published: December 2004

We report a patient with severe axial tardive dystonia who has had dramatic improvement for 4 years after treatment with the atypical antipsychotic drug clozapine (625 mg/day). Clozapine differs from conventional neuroleptics in that it has higher affinity for D1 and lower affinity for D2 dopamine receptors than do conventional antipsychotics, which are relatively selective D2 antagonists. We propose that repetitive stimulation of the D1 receptor by endogenous dopamine, resulting in sensitization of the D1‐mediated striatal output in the presence of D2 receptor blockade, is a fundamental mechanism mediating tardive dyskinesia, including the dystonic type. According to this hypothesis, it is primarily the D1 antagonist action of clozapine that accounts for its inability to cause tardive dyskinesia as well as its therapeutic effect in tardive dystonia. Regardless of its mechanism of action, the sustained improvement observed in this case suggests that clozapine should be tried in cases of severe refractory tardive dystonia.
Unusual synkinetic movements between facial muscles and respiration in hemifacial spasm
Authors: Pavesi G. , Medici D. , Macaluso G. M. , Ventura P. , Allegri I. , Gemignani F.
Published: December 2004

We describe two cases of hemifacial spasm (HFS) with unusual synkinetic movements between facial muscles and respiratory activity. Patient 1 developed an idiopathic HFS. She underwent microvascular decompression surgery, followed by transitory facial nerve palsy; she recovered but later developed a facial synkinesia characterized by involuntary and forced eyelid closure on spontaneous and deep breathing; the orbicularis oculi muscle was active also when her mouth was open (the so‐called Marin‐Amat syndrome). Patient 2, 1 year after a peripheral facial nerve palsy (Bell's palsy), developed an HFS together with synkinetic movements between the orbicularis oculi muscle and respiration. In both cases electrophy siological studies showed pathological synkinetic electromyographic activity. An enhanced hyperexcitability of brain stem interneurons and facial motoneurons could be suggested to explain the phenomenon.
Dystonis in ataxia telangiectasia: Report of a case with putaminal lesions and decreased striatal [123I]Iodobenzamide Binding
Authors: Koepp M. , Schelosky L. , Cordes I. , Cordes M. , Poewe W.
Published: December 2004

A 6‐year‐old girl with ataxia telangiectasia and severe progressive dystonic posturing is presented. Magnetic resonance imaging showed cerebellar atrophy and a right‐sided putaminal lesion. A single‐photon emission computed tomography study of cerebral dopamine‐(D2)‐receptor binding with [123I]iodobenzamide showed a decreased tracer uptake in the striatum bilaterally. Dystonia deteriorated with levodopa treatment, whereas trihexyphenidyl led to significant improvement. Although dystonic symptoms have been repeatedly described in ataxia telangiectasia, this is the first report demonstrating structural and functional basal ganglia abnormalities in this disorder.
Late‐onset ataxia telangiectasia in two brothers presenting with juvenile resting tremor
Authors: Hiel J. A. P. , Weemaes C. M. R. , Smeets D. F. C. M. , van de Vlasakker C. J. W. , Horstink M. W. I. M.
Published: December 2004

Two young adult brothers presented with a 5‐ to 6‐Hz resting tremor of the upper limbs. Although ataxia was not unequivocally present and ocular telangiectasia was minimal, typical rearrangements of chromosomes 7 and 14, and increased α‐fetoprotein levels indicated the presence of ataxia telangiectasia (AT). Resting tremor as a predominating symptom in AT is uncommon and to our knowledge has not been described previously.
Fluctuations in plasma levodopa and motor responses with liquid and tablet levodopa/carbidopa
Authors: Metman L. Verhagen , Hoff J. , Mouradian M. M. , Chase T. N.
Published: December 2004

To evaluate the ability of orally administered liquid levodopa/carbidopa (LD/CD) to stabilize plasma levodopa levels and reduce motor reponse fluctuations in Parkinson's disease, five patients received LD/CD hourly, as standard tablets or as an aqueous solution on two separate days in a double‐blind, placebo‐controlled, cross‐over design. Except for a slightly earlier peak plasma levodopa level, no significant advantage of the liquid formulation over tablet therapy was found. However, liquid LD/CD could be helpful in quickly resolving “off” states and by facilitating small dose adjustments that are not possible with tablets.
Unusual focal dyskinesias: The ears, the shoulders, the back, and the abdomen
Authors: Caviness J. N. , Gabellini A. , Kneebone C. S. , Thompson P. D. , Lees A. J. , Marsden C. D.
Published: December 2004

Fourteen patients with focal or segmental involuntary movements affecting the ears, back, shoulder girdle, and upper extremity, as well as the abdomen and pelvic girdle, are presented. The unusual locations and appearance of these dyskinesias distinguishes them from recognized movement disorder syndromes. It is argued that the slow, sinuous, and semirhythmic character of the movements and the variable long‐duration bursts of motor unit activity responsible for them most closely fit into the spectrum of dystonia. A history of pain in the affected region and/or peripheral trauma in some cases also suggests that peripheral factors may play a role in their pathogenesis.
Neurological sequelae following carbon monoxide poisoning clinical course and outcome according to the clinical types and brain computed tomography scan findings
Authors: Lee M. S. , Marsden C. D.
Published: December 2004

The prognosis for patients who survive carbon monoxide (CO) poisoning is uncertain, particularly in those who develop persistent neurological complications after recovery from the initial coma. Thirty‐one patients with the sequelae of CO poisoning, followed for a year, are described. Eight had a progressive course, and 23 had a delayed relapse after an initial recovery period of ∼20 days (range, 1–36 days). Those with a progressive course developed a persistent akinetic‐mute state, and four of the eight died. Those with the delayed relapsing course either developed a parkinsonian state with behavioral and cognitive impairment but could walk (nine cases); or progressed further to an akinetic‐mute state, and were bed‐bound (14 cases); the deterioration to either condition occured rapidly over a few days to a week. Fourteen of the patients with the delayed relapses (61%) subsequently improved, but three (13%) died. Those with a progressive course without initial recovery were younger (mean age, 37.0 years) than those with a delayed relapsing course (55.2 years; p < 0.01). The mean duration of their initial coma (9.8 days) was longer than that in delayed relapsing cases (2.0 days; p < 0.01). The mean initial CO hemoglobin level was not different in the two groups. Brain computed tomography (CT) scans were obtained at the onset of sequelae in both groups. Ten patients had a normal CT scan, 13 had white matter low‐density lesions, and four had globus pallidus low‐density lesions. These findings did not accurately predict the outcome, although all four patients who had both globus pallidus and white matter low‐density lesions at initial CT scan had a bad prognosis. Follow‐up brain CT scans were performed in eight patients; all showed progressive changes and/or new lesions, despite which three patients improved; four of the five patients with globus pallidus and white matter lowdensity lesions at follow‐up CT scan had a bad prognosis.
Superficial hemosiderosis of the central nervous system
Authors: River Y. , Honigman S. , Gomori J. M. , Reches A.
Published: December 2004

Superficial hemosiderosis (SH) of the CNS is a rare disease caused by repeated subarachnoid hemorrhage, with progressive superficial siderosis of the CNS. We report a patient with SH whose clinical picture was marked by progressive gait ataxia, hearing loss, dysarthria, and recurrent episodes of hemifacial spasm. Iron and ferritin levels in the CSF were significantly higher than in a control group of patients. Six month's treatment with the iron‐chelating agent trientine dihydrochloride led to clinical improvement, with a concomitant reduction of CSF iron level. We suggest that, in addition to magnetic resonance imaging findings, CSF levels of iron and ferritin should be used as diagnostic criteria for SH, as well as to estimate the efficacy of iron chelation treatment.
Propriospinal myoclonus: Evidence for spinal “pattern” generators in humans
Authors: Brown P. , Rothwell J. C. , Thompson P. D. , Marsden C. D.
Published: December 2004

The clinical and electrophysiological characteristics of eight patients with propriospinal myoclonus are described. Myoclonus developed within days or weeks of cervical trauma in half the patients. Seven cases had axial flexion jerks, and one axial extension jerks. Myoclonic EMG activity consisted of repetitive bursts with a frequency of 1–7 Hz. The jerks in three of the cases were comprised of alternating and rhythmic bursts of EMG activity in rectus abdominis and the paraspinal muscles. From these new observations, it is proposed that cervical trauma can lead to the partial release of a spinal pattern generator. The latter is capable of recruiting muscles through long propriospinal pathways into complex rhythmic activity.
Factors influencing the amplitude and frequency of essential tremor
Authors: Elble Rodger J. , Higgins Constance , Leffler Keith , Hughes Larry
Published: December 2004

Quantitative electromyography (EMG) and triaxial accelerometry were used to measure hand tremor, finger tremor, and forearm motor unit activity in 36 men and 23 women with essential tremor. Hand tremor was studied with and without 300‐g mass loading. Tremor and EMG were recorded twice, with a 3‐min rest interval, to assess the spontaneous intertrial variability in tremor amplitude, frequency, and motor unit entrainment. In general, the minimum detectable differences in tremor amplitude, frequency, and motor unit entrainment were roughly 30%, 5%, and 10% of the initial sample means, respectively, assuming a sample size of 30 patients, a statistical power of 0.9, and a significance level of 0.05. Linear regression analyses were performed to test the hypotheses that (a) there is an age‐associated decrease in tremor frequency that is independent of symptom duration and (b) tremor frequency and motor unit entrainment make independent contributions to tremor amplitude. Our data supported both hypotheses.
Exclusion of the DYT1 locus in a non‐Jewish family with early‐onset dystonia
Authors: Bressman Susan B. , Hunt Ann L. , Heiman Gary A. , Brin Mitchell F. , Burke Robert E. , Fahn Stanley , Trugman Joel M. , de Leon Deborah , Kramer Patricia L. , Wilhelmsen Kirk C. , Nygaard Torbjoern G.
Published: December 2004

The DYT1 gene on chromosome 9q34 underlies idiopathic torsion dystonia (ITD) in Jewish and non‐Jewish families with childhood and adolescent‐onset dystonia that usually starts in a limb, spreads to other limbs, and uncommonly involves cranial muscles. We examined 39 members of a Mennonite family of German ancestry in which seven were affected with ITD. Age at onset was 14.7 years (range 5–34 years) and symptoms began in a limb in four. The remaining three had onset in the neck, face, and larynx. Dystonia progressed to involve at least one arm and one leg in all seven and there was cranial involvement in six. Five of these six had moderate or severe speech impairment. Linkage analysis with 9q34 markers excluded the region containing the DYT1 locus in this family. This study suggests that a gene other than DYT1 underlies some cases of early limb‐onset ITD. The clinical features of prominent cranial involvement and impaired speech distinguish this “non‐DYT1” early‐onset ITD family from the typical DYT1 phenotype.
Perturbation of precision grip in Friedreich's ataxia and late‐onset cerebellar ataxia
Authors: Hermsdöourfer Joachim , Wessel Karl , Mai Norbert , Marquardt Christian
Published: December 2004

Perturbations of precision grip were tested in 7 patients with Friedreich's ataxia (FA) and 11 patients with late‐onset cerebellar ataxia (CA). Subjects were instructed to hold a small compressible manipulandum between thumb and index finger and to resist any perturbation of maintained finger position. A sudden increase of load induced a displacement of fingers until this was stopped by subjects' active intervention. The amount of initial displacement emerged as a highly sensitive parameter to differentiate the clinical subgroups: Responses in FA patients were missing or massively delayed, whereas displacements in CA patients were normal or only moderately abnormal. This discrimination of impaired hand function in FA and CA patients has not been possible by using only tasks of isometric grip force control. We concluded that our task relies more on intact sensory afferents, which are known to be impaired in FA, than on cerebellar function. In a second task the stiffness of the maintained grip was determined. On the average, preresponse stiffness was lower in FA patients as compared with CA patients and normal controls. However, stiffness appeared to be an independent parameter that did not influence the amount of displacement in the perturbation task.
The dopamine D1 agonist SKF 81297 and the dopamine D2 agonist LY 171555 act synergistically to stimulate motor behavior of 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine‐lesioned parkinsonian rhesus monkeys
Authors: Vermeulen R. J. , Drukarch B. , Sahadat M. C. R. , Goosen C. , Wolters E. C. , Stoof J. C.
Published: December 2004

At present, the pharmacotherapy of Parkinson's disease (PD) consists mainly of L‐dihydroxyphenylalanine (L‐DOPA) and/or dopamine D2 receptor agonist. However, in general the clinical efficacy of D2 agonists is less than that of L‐DOPA. Therefore, attention is being focussed on the role of the D1 receptor as a target for therapeutic intervention in PD. Recently, we reported that SKF 81297 is a selective D1 agonist that stimulates motor behavior of unilaterally MPTP (1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine)‐lesioned rhesus monkeys. Presently, we studied the effect of coadministration of SKF 81297 and the D2 agonist LY 171555 using the same model of PD. Coadministration of behaviorally active doses of SKF 81297 (0.3 mg/kg) and LY 171555 (0.01 mg/kg) resulted in a prolongation of the motor stimulation induced by either of the drugs alone. Neither administration of SKF 81297, in a dose of 0.03 mg/kg, nor of LY 171555, in a dose of 0.003 mg/kg, were behaviorally active, whereas the combined administration of these compounds induced a significant stimulation of motor behavior. These data suggest that (a) D1 receptor stimulation will prove to be useful in the treatment of PD and (b) better therapeutic results will be obtained by simultaneous stimulation of D1 and D2 receptors as compared with stimulation of both receptors alone.
L‐Dihydroxyphenylalanine and its decarboxylase: New ideas on their neuroregulatory roles
Authors: Opacka‐Juffry Jolanta , Brooks David J.
Published: December 2004

Recent experimental reports concerning L‐dihydroxyphenylalanine (L‐DOPA) and aromatic L‐amino acid decarboxylase (AADC, L‐DOPA decarboxylase) are reviewed in this article. Both in vitro and in vivo data now suggest that L‐DOPA is an endogenous neuroactive compound that is released from neurons and acts as a neurotransmitter or neuromodulator in the brain. Administration of exogenous L‐DOPA affects dopamine receptor status, AADC activity, and mitochondrial oxidation in experimental animals. The type and severity of these effects depend on the duration of the treatment. These findings may partly explain the limited efficacy of L‐DOPA therapy in Parkinson's disease (PD). AADC also plays a controlling role in the central nervous system, being a regulatory enzyme in the synthesis of a putative neuromodulator 2‐phenylethylamine and other trace amines. Recent experimental findings on AADC activity and localisation are of importance because they suggest that striatal [18F]DOPA uptake used as an indicator of PD progression in positron emission tomography (PET) studies is likely to overestimate nigrostriatal integrity in advanced PD. Possible new PET tracers of presynaptic dopaminergic function are discussed in this context.
CYP2D6‐debrisoquine hydroxylase gene polymorphism in multiple system atrophy
Authors: Planté‐Bordeneuve V. , Bandmann O. , Wenning G. , Quinn N. P. , Daniel S. E. , Harding A. E.
Published: December 2004

Molecular genetic studies of the cytochrome P450 system enzyme CYP2D6, which hydroxylates debrisoquine, have indicated an excess of mutant alleles in large series of patients with Parkinosn's disease (PD) when compared with controls. We have investigated CYP2D6 polymorphism in 91 patients with multiple system atrophy (MSA) in order to determine if this finding is specific to PD or if there is similar evidence of genetic susceptibility to neurotoxicity in MSA. The distribution of CYP2D6 alleles was not significantly different between MSA patients and controls, and there were fewer poor metabolisers in the MSA group than in the control group.
n‐Hexane‐induced parkinsonism: Pathogenetic hypotheses
Authors: Pezzoli G. , Antonini A. , Barbieri S. , Canesi M. , Perbellini L. , Zecchinelli A. , Mariani C. B. , Bonetti A. , Leenders K. L.
Published: December 2004

n‐Hexane, similar hydrocarbons, and derivatives are common environmental pollutants and by‐products of lipid peroxidation, and they may have a nigrotoxic effect like that of 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine. This report describes our second case of parkinsonism in a subject exposed to n‐hexane. Positron emission tomography studies demonstrated regional striatal abnormalities of the nigrostriatal dopaminergic system and of glucose metabolism that were different from those found in idiopathic Parkinson's disease.
Neuronal loss from the subthalamic nuclei in a patient with progressive chorea
Authors: Sinard John H. , Hedreen John C.
Published: December 2004

We present a case of an 80‐year‐old man who developed a seizure disorder at age 66 and was treated with chronic phenytoin. In the last 3 years of his life, he developed multiple neurological deficits, including bilateral chorea, ataxic gait, sensory neuropathy, and progressive dementia. After death from pneumonia, autopsy examination of the patient's brain was most remarkable for a selective loss of neurons from both subthalamic nuclei and Purkinje cell loss in the cerebellum. This pattern of injury is consistent with a toxic process and does not fit previously characterized pathological syndromes known to be associated with movement disorders or dementia or both. Phenytoin has been shown to cause choreiform movements, peripheral neuropathy, and cognitive decline in some patients, but the pathological basis for these changes has not been elucidated. The patient's chorea was very likely the result of neuronal loss in the subthalamic nuclei, but causes for his dementia and neuropathy were not found. The pathological findings may represent either an unusual form of chronic phenytoin toxicity or a previously undescribed primary degenerative brain syndrome.
Statistical prediction of the optimal site for thalamotomy in parkinsonian tremor
Authors: Lenz F. A. , Normand S. L. , Kwan H. C. , Andrews D. , Rowland L. H. , Jones M. W. , Seike M. , Lin Y. C. , Tasker R. R. , Dostrovsky J. O. , Lenz Y. E.
Published: December 2004

Stereotactic lesions in the thalamus for treatment of parkinsonian tremor are often made at the location where neurons fire at approximately tremor frequency (tremor cells). Some of these cells show a large amount of activity at tremor frequency and are significantly correlated with electromyographic activity (EMG) during tremor. Our analysis of cellular location identifies a cluster of neurons showing activity characterized both by concentration of power at tremor frequency and by significant correlation with EMG. In a retrospective analysis of results in 15 patients, lesions placed within 2 mm of the center of this cluster were uniformly effective in relieving tremor. Therefore, a small lesion targeting this cluster is effective in treatment of parkinsonian tremor.
“Off” painful dystonia in Parkinson's disease treated with botulinum toxin
Authors: Pacchetti C. , Albani G. , Martignoni E. , Godi L. , Alfonsi E. , Nappi G.
Published: December 2004

The “off” painful dystonia (OPD), usually concerning the feet, is a type of abnormal involuntary movement, induced by the chronic use of levodopa. It is mostly observed in the advanced stage of Parkinson's disease (PD), particularly in the early morning, in the evening, and late at night. Indeed, some patients have experienced OPD also during “on” periods when dystonic posture of the foot alternates with dyskinesia. The pain probably is due to sustained muscle contraction, which causes prolonged muscle spasm, as in primary dystonia or torticollis. Dopaminergic drugs like bromocriptine, pergolide, and especially apomorphine (s. c., infusions, or bolus), can dramatically improve the OPD. Anticholinergics baclofen and lithium are also used in the management of OPD with some benefit. On the other hand, clinical experience shows that in many cases, these therapeutic procedures are not always enough to produce the expected results. Thirty PD patients (22 men and eight women) with OPD of the foot were treated with botulinum toxin (Botox, Btx) using electromyograms to guide injections. Dystonia was evaluated using a quantitative rating scale. The selection of the muscles for Btx treatment was carried out on the basis of foot posture. We injected Btx into tibialis posterior, tibialis anterior, gastrocnemius, flexor digitorum longus, and extensores hallucis longus with a median dose 40 IU for each muscle, distributed in two sites. In all patients, the pain improved within 10 days, whereas in 21 patients, the pain disappeared completely for 4 months (range, 3–7 months); a concomitant improvement in intensity of the dystonic spasm was also observed. No side effects were reported. Seven patients with associated “on” foot dystonia described an improvement of foot posture on walking. In conclusion, in this uncontrolled study, the use of Btx in OPD seemed a promising tool to improve pain linked to foot dystonia; however, because of the well‐known underlying dopaminergic defect in OPD, the Btx therapy should be considered only if the dopaminergic treatment established for the management of OPD has failed.
Beneficial effect of intranasal desmopressin for nocturnal polyuria in Parkinson's disease
Authors: Suchowersky Oksana , Furtado Sarah , Rohs Gina
Published: December 2004

Patients with Parkinson's disease (PD) are known to experience autonomic nervous system dysfunction; this disruptive symptomatology includes urinary urgency, frequency, and nocturnal polyuria. Anticholinergic and tricyclic medications can be beneficial in controlling these urinary symptoms, but have unpleasant side effects in some patients. Desmopressin has been used to treat nocturnal polyuria successfully in a number of conditions, such as central diabetes insipidus, enuresis, and autonomic failure. The purpose of the present study was to assess the efficacy of desmopressin in patients with PD with significant nocturia. Eight patients were recruited into the study. They were first asked to establish a baseline of number of nocturnal voids; the patients were then prescribed the intranasal form of desmopressin and asked to continue to record the number of nocturnal voids. The five patients who completed the trial demonstrated clinically and statistically significant reductions in the frequency of nocturnal voids. One patient became hyponatremic and confused during desmopressin administration; his symptoms resolved soon after the desmopressin was discontinued. Two patients failed to complete the trial due to compliance problems. Thus, desmopressin appears to be a safe and effective medication for nocturnal polyuria in PD.
Did Robert Schumann have dystonia?
Authors: de Yébenes J. García
Published: December 2004

Occupational dystonia is a frequent clinical symptom in musicians and has been described as muscle spasms and hand cramps in pianists. Robert Schumann had a neurologica impairment of his right hand that was not clinically diagnosed during his life and that impaired his career as pianist from his early 20s. This disturbance was characterized by pain and by rigidity of the fingers, which extended to other segments of his right upper extremity while he was performing and that increased with stress and improved with muscle relaxation. This disturbance produced a progressive impairment of his writing. We here hypothesize that Schumann's neurological problem was consistent with dystonia.
Movement disorders in multiple sclerosis
Authors: Tranchant C. , Bhatia K. P. , Marsden C. D.
Published: December 2004

Movement disorders (MD), other than tremor, associated with multiple sclerosis (MS) occur infrequently. We report 14 new cases of whom nine had dystonia, three parkinsonism, and two had myoclonus. We also reviewed 135 such cases from the literature. From an analysis of the individual MDs and the site of the lesions described, we conclude that paroxysmal dystonias (tonic spasms), ballism/chorea, and palatal myoclonus can be caused by demyelinating lesions. Parkinsonism, dystonia, and other types of myoclonus, however, often appear to be coincidental.
Pharmacokinetics and clinical efficacy of rectal apomorphine in patients with Parkinson's disease: A study of five different suppositories
Authors: van Laar T. , Jansen E. N. H. , Neef C. , Danhof M. , Roos R. A. C.
Published: December 2004

The pharmacokinetics and clinical effects of apomorphine after rectal administration were determined in five patients with idiopathic Parkinson's disease (PD). Three different pharmaceutical formulations were tested: a rectal solution of apomorphine (10 or 15 mg), a gelatin suppository (25 and 50 mg), and a Witepsol‐H15 suppository (50 and 100 mg). The pharmacokinetics of apomorphine were determined by measuring plasma concentrations using a sensitive and specific high‐performance liquid chromatography method. The mean bioavailability varied between 14.7% and 40.2%, which was the bioavailability until the end of clinical benefit. Also, despite the differences in dose, the values of the Cmax were similar, with average values of 12.7‐25.6 ng/ml. Wide differences in Tmax were observed, with values varying between 16 min for the enema and 127.5 min for the Witepsol‐H15 100‐mg suppository. The time course of the clinical effect was determined by assessing the time needed for walking a 25‐m course and by calculating a tremor and dyskinesia score. Onset of effect was similar for each of the preparations, with an average onset time of 14‐28 min. Significant differences with respect to the duration of the effect were observed. The duration of effect after administration of the Witepsol‐H15 100‐mg suppository was 156 ± 43 min versus 50 ± 13 min after rectal administration of the apomorphine solution. These results show that rectal administration of apomorphine may present an alternative to subcutaneous administration. The sustained‐release properties of the Witepsol‐H15 suppositories are especially of interest in the treatment of on‐off fluctuations in PD.
Prevalence of focal dystonias in the western area of Tottori Prefecture in Japan
Authors: Nakashima Kenji , Kusumi Masayoshi , Inoue Yuichi , Takahashi Kazuro
Published: December 2004

We evaluated the prevalence of focal dystonias in the western area of Tottori Prefecture in Japan. The population of the area was 244, 935 on October 1, 1992. Because four patients with blepharospasm and three patients with writer's cramp did not visit any hospitals or clinics in 1993 and did not reply to our question letter, we could not confirm their present condition: with or without focal dystonia in 1993. Four patients with facial dystonia including blepharospasm and oromandibular dystonia, seven with spasmodic torticollis, and four with writer's cramp were observed. The prevalence of focal dystonias was 6.12 per 100, 000 persons, which may be lower than that in western countries. Although the reasons for this difference are still unclear, a genetic factor may be one implication.
Binswanger's disease presenting as levodopa‐responsive parkinsonism: Clinicopathologic study of three cases
Authors: Mark M. H. , Sage J. I. , Walters A. S. , Duvoisin R. C. , Miller D. C.
Published: December 2004

We report three cases of autopsy‐proven Binswanger's disease (subcortical arteriosclerotic encephalopathy) with unusual clinical features. Two patients had supranuclear gaze disturbances, early gait dysfunction, and speech disorders suggestive of progressive supranuclear palsy. One of these patients was not demented at the time of death. The third patient had features typical of Parkinson's disease. All three patients were responsive to treatment with levodopa. The clinical spectrum of Binswanger's disease should be expanded to include levodopa‐responsive parkinsonism.
Reliance on advance information and movement sequencing in huntington's disease
Authors: Georgiou Nellie , Bradshaw John L. , Phillips Jim G. , Chiu Edmond , Bradshaw Judy A.
Published: December 2004

To identify the focus of impairment in the performance of sequential movements in Huntington's disease (HD) patients, the extent of their reliance on external advance information was examined. Twelve patients with HD and their age‐matched controls performed a series of button‐presses at sequential choice points along a response board. A sequential pathway was designated, and with each successive button press, advance visual information was systematically reduced to various extents in advance of each move. HD patients, like previously studied parkinsonian patients, were particularly disadvantaged with high levels of reduction in advance information, and as a consequence, both their initiation and execution of movements progressively slowed with each successive element in the response sequence. The pattern of results was not affected whether or not patients were taking neuroleptic medication, nor did performance on a variety of cognitive measures correlate with motor performance. Control subjects' performance, on the other hand, remained constant in terms of both initiation and execution with each of the three levels of reduction in advance information. We conclude that HD patients, like parkinsonian patients, who also suffer from a basal ganglia (BG) disorder, require external visual cues to sequence motor programs effectively. Our findings suggest that with HD there may be abnormalities in a central mechanism that controls switching between movement segments within an overall motor plan. The BG, which provide internal cues necessary for component sequenceing, may be disrupted, thereby impairing the ability to use such internally generated cues to guide movement.