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PubMed1995

Double-blind trial of botulinum toxin for treatment of focal hand dystonia.

Ten patients with focal dystonia of the hand, all of whom had benefited in an open-label study of botulinum toxin, were treated with botulinum toxin-A in a double-blind study. Response was assessed by three measures: (a) subjective rating, provided by patients' reports of the effect of the injections on the dystonia; (b) objective testing, consisting of manual muscle testing (MRC scale) to measure muscle strength in all patients, timing of a writing sample and counting the number of errors of writing off-the-line in six patients with writer's cramp, counting the number of errors on a standard test of transcription in two patients with stenographer's cramp, and rating by professional musicians of the performances of two patients with musician's cramp; and (c) physicians' rating, provided by a review of the patients' videotaped performance by neurologists who were unaware of which treatment was administered. Eight of the 10 patients had greater subjective improvement with botulinum toxin than with placebo, and this impression was verified by at least one objective test in six patients. Two patients failed to have a better response to botulinum toxin than to placebo, and their reports were verified by the objective tests. This study confirms the efficacy of botulinum toxin in many patients with focal hand dystonia.

Botulinum Toxins↗
PubMed1995

Modulation of electromyographic activity of wrist flexor and extensor muscles in patients with writer's cramp.

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 homonymous and reciprocal inhibition. In the agonist wrist extensors, 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.

Adult↗
PubMed1996

Haplotype analysis at the DYT1 locus in Ashkenazi Jewish patients with occupational hand dystonia.

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 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.

Adult↗
PubMed1996

Abnormal sensorimotor integration in writer's cramp: study of contingent negative variation.

To investigate the pathophysiology of idiopathic focal dystonia, we recorded contingent negative variation (CNV) as a physiological index of sensorimotor integration in 14 right-handed patients with writer's cramp and compared it with normative data. CNV was recorded in the S2 choice reaction time paradigm: Two kinds of auditory S2 (Go or No-Go) were given 2 s after the auditory S1, and the subject reacted only to the Go signal by extending the wrist. In normal subjects, the late CNV amplitude had no difference at Cz between left- and right-hand tasks and was symmetric without significant amplitude laterality irrespective of the side of hand movement. In patients with writer's cramp, the late CNV amplitude at Cz was relatively larger for the left-hand task than the right-hand task (p < 0.03), and a significant amplitude laterality of the late CNV (larger on the right) was present especially at the central area for the right-hand task (p < 0.03). Since the late CNV is known to be generated, at least in part, from primary and supplementary motor cortices, the significant laterality of the late CNV seen with the right-hand task in patients with writer's cramp might represent functional abnormality of motor cortices possibly as the result of basal ganglia function.

Adult↗
PubMed1998

Cerebral and cerebellar activation in correlation to the action-induced dystonia in writer's cramp.

The pattern of brain perfusion of four patients with writer's cramp and four control subjects were examined using positron emission tomography scans after [(15)O] butanol injections. Each subject was scanned 12 times to cover three repetitions of four different motor tasks with the right hand. Drawing of horizontal lines and variable durations of the writing of a prelearned text were performed in a pseudorandom order, the latter task commencing either simultaneously with or 30 sec or 120 sec before the tracer injection. The perceived difficulty and signs of dystonia progressed in correlation to the duration of writing. Statistical parametric maps were calculated to test hypotheses of regional specific effects dependent on the performed motor tasks. The patients with writer's cramp had progressively increased activity in the left primary sensorimotor and premotor cortices, the left thalamus, and the cerebellum with a right-side predominance in correlation to the duration of writing. The regions with activity increases thus corresponded to a cerebrocerebellar motor circuit. The duration of writing correlated to a progressive reduction of activity in the patients' left supramarginal and angular gyri (Brodmann areas 40 and 39) and an inferior part of the left temporal lobe (area 20). The control subjects had neither a significant increase or decrease of activity in correlation to the duration of writing. Group-specific differences were confirmed statistically in split-plot interaction analyses.

Adult↗
PubMed1993

Hereditary motor-sensory neuropathy and movement disorders.

To explore the relationship between hereditary motor and sensory neuropathy (HMSN) and movement disorders, we examined 7 patients with HMSN referred to our Movement Disorders Clinic and surveyed members of the Charcot-Marie-Tooth association. The following movement disorders were observed in the index patients: postural tremor in 6, rest tremor in 3, and Parkinsonism and dystonia in 2. Tremor, present in 40% of the 201 patients who responded to the survey, was first noted at a mean age of 36 years, and mostly involved the hands. Family history of tremor was more frequent in the tremor group (P < 0.005), which also had a significantly worse writing score than the nontremor group (P < 0.001). The overlap in clinical features between HMSN-associated tremor and essential tremor (ET), the high frequency of family history of tremor, and the lack of a relationship between the severity of tremor and of peripheral neuropathy suggest that the tremor in HMSN is pathogenically related to ET.

Aged↗
PubMed2002

Intermanual transfer of a new writing occupation in young adults without disability.

It has been shown that acquisition of a skill by one hand is facilitated by previous learning of the same skill with the other hand. This is called intermanual transfer of learning, or cross-education. The investigators examined intermanual transfer of occupation of writing in a group of 10 right-handed subjects with no known motor disabilities. Subjects learned to perform a novel occupation of writing a foreign alphabet letter with either their right or left hand. Later, subjects reproduced the skill with the practised and unpractised contralateral hand. Pen movements and surface electromyography of the first dorsal interosseus muscle were recorded to assess the transfer of learning. Analysis revealed an almost full transfer of the learned motor task between hands in either left-to-right or right-to-left direction when movement time and movement size were compared. This indicates that transfer did not depend on hand dominance. These findings suggest that a task already learned by one hand can positively influence the learning of the same task by the other hand. The results have important implications for occupational therapy--namely, that activities comprising tasks previously learned by one hand would be more effective in facilitating improved performance by the other hand than activities comprising previously unlearned tasks in the case of retraining skills in patients with amputation or hemiplegia. Because the participants in this study were a small number of college students, research should be carried out with larger participant pools and participants with disabilities to consolidate the findings.

Adult↗
PubMed2006

An algorithm to derive a numerical daily dose from unstructured text dosage instructions.

PURPOSE: The General Practice Research Database (GPRD) is a database of longitudinal patient records from general practices in the United Kingdom. It is an important data source for pharmacoepidemiology studies, but until now it has been tedious to calculate the daily dose and duration of exposure to drugs prescribed. This is because general practitioners routinely record dosage instructions as free text rather than in a structured way. The objective was to develop and assess the validity of an automated algorithm to derive the daily dose from text dosage instructions. METHODS: A computer program was developed to derive numerical information from unstructured text dosage instructions. It was tested on dosage texts from a random sample of one million prescription entries. A random sample of 1,000 of these converted texts were manually checked for their accuracy. RESULTS: Out of the sample of one million prescription entries, 74.5% had text containing the daily dose, 14.5% had text but did not include a quantitative daily dose statement and 11.0% had no text entered. Of the 1000 texts which were checked manually, 767 stated the daily dose. The program interpreted 758 (98.8%) of these correctly, produced errors in four cases and failed to extract the dose from five texts. CONCLUSIONS: An automated algorithm has been developed which can accurately extract the daily dose from almost 99% of general practitioners' text dosage instructions. It increases the utility of GPRD and other prescription data sources by enabling researchers to estimate the duration of drug exposure more efficiently.

Adverse Drug Reaction Reporting Systems↗
PubMed1998

Perseverative writing errors in a patient with Alzheimer's disease.

This study reports the writing performance of a dysgraphic patient with Alzheimer's disease and moderate dementia who frequently perseverated on strokes and letters. Letter formation errors were also frequently produced. Oral spelling was superior to written spelling. The habitual style of writing (cursive writing) was significantly more prone to perseverations than writing in uppercase letters, a form of writing less frequently used by the patient. Central (linguistic) spelling processes were relatively preserved. The pattern of preserved and impaired functions is consistent with impairment of the peripheral mechanism that generates the graphic motor patterns code. We suggest that damage to the peripheral orthographic mechanism may cause deficits in some patients with Alzheimer's disease.

Aged↗
PubMed2000

Overlap and dissociation of semantic processing of Chinese characters, English words, and pictures: evidence from fMRI.

The functional anatomy of Chinese character processing was investigated using fMRI. Right-handed Mandarin-English bilingual participants made either semantic or perceptual size judgements with characters and pictures. Areas jointly activated by character and picture semantic tasks compared to size judgement tasks included the left prefrontal region (BA 9, 44, 45), left posterior temporal, left fusiform, and left parietal regions. Character processing produced greater activation than picture processing in the left mid and posterior temporal as well as left prefrontal regions. The lateral occipital regions were more active during picture semantic processing than character semantic processing. A similar pattern of activation and contrasts was observed when English words and pictures were compared in another set of bilingual participants. However, there was less contrast between word and picture semantic processing than between character and picture processing in the left prefrontal region. When character and word semantic processing were compared directly in a third group, the loci of activation peaks was similar in both languages but Chinese character semantic processing was associated with a larger MR signal change. The semantic processing of Chinese characters, English words, and pictures activates a common semantic system within which there are modality-specific differences. The semantic processing of Chinese characters more closely resembles English words than pictures.

Adult↗
PubMed2003

Neurosurgical treatment for writer's cramp.

BACKGROUND: Writer's cramp is a type of focal dystonia due to dysfunction of the pallido-thalamo-cortical circuit. The symptom is refractory to most conservative treatment, though botulinum toxin injection is generally used for symptomatic relief. As a surgical treatment of dystonia we performed stereotactic nucleus ventrooralis (Vo) thalamotomy for dystonic cramp of the hand. METHOD: Eight patients (5 men, 3 women, age 26-40 yrs, mean 32.1 yrs) with medically intractable task-specific focal dystonia of the hand underwent Vo thalamotomy. Stereotactic target was chosen at the junction of the anterior and posterior Vo nuclei. FINDINGS: The mean duration of the symptom ranged from 3 to 6 years (mean, 4.0 yrs). All patients had complained of difficulty in writing. Six patients were professional workers, such as comic artist, guitarist, and barber, and, because of the dystonic symptoms at their professional work, they had stopped pursuing their profession. All patients showed immediate postoperative disappearance of dystonic symptoms, and the effect was sustained during the follow up period (3-29 months, mean 13.1 mo) except in one case. One patient showed partial recurrence of the symptom and underwent second thalamotomy 5 months after the initial surgery with satisfactory results. The score of the writer's cramp rating scale significantly (p < 0.001) decreased after Vo thalamotomy. There was no permanent operative complication. There was no mortality or permanent morbidity. INTERPRETATION: Although a longer follow-up is needed, stereotactic Vo thalamotomy is a useful and safe therapeutic option for writer's cramp.

Adult↗
PubMed1989

[Script crossing in scanning electron microscopy].

A case of mixed script in which ball point-pen ink was contaminated with typewriting prompted a survey of the literature and a systematic SEM study of mixed script with various writing instruments or inks. Mixed scripts produced with the following instruments or inks were investigated: pencil, ink/India ink, ball-pint pen, felt-tip pen, copied script and typewriter. This investigation showed SEM to be the method of choice for visualizing overlying scripts produced by different writing instruments or inks.

Crime↗
PubMed1995

A neural model of basal ganglia-thalamocortical relations in normal and parkinsonian movement.

Anatomical, neurophysiological, and neurochemical evidence supports the notion of parallel basal ganglia-thalamocortical motor systems. We developed a neural network model for the functioning of these systems during normal and parkinsonian movement. Parkinson's disease (PD), which results predominantly from nigrostriatal pathway damage, is used as a window to examine basal ganglia function. Simulations of dopamine depletion produce motor impairments consistent with motor deficits observed in PD that suggest the basal ganglia play a role in motor initiation and execution, and sequencing of motor programs. Stereotaxic lesions in the model's globus pallidus and subthalamic nucleus suggest that these lesions, although reducing some PD symptoms, may constrain the repertoire of available movements. It is proposed that paradoxical observations of basal ganglia responses reported in the literature may result from regional functional neuronal specialization, and the non-uniform distributions of neurochemicals in the basal ganglia. It is hypothesized that dopamine depletion produces smaller-than-normal pallidothalamic gating signals that prevent rescalability of these signals to control variable movement speed, and that in PD can produce smaller-than-normal movement amplitudes.

Basal Ganglia↗