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Biomedical subjects

M Hallett

Publications and source records attributed to M Hallett.

At least 19 recordsLinked to original sources
PubMed2006

Longitudinal fMRI study for locomotor recovery in patients with stroke.

The authors investigated bihemispheric motor network reorganization supporting locomotor recovery after stroke over time. They determined longitudinal changes in locomotor function and fMRI in 10 stroke patients at the subacute stage and the chronic stage. The results suggest that the bihemispheric reorganization mechanism underlying locomotor recovery evolved from the ipsilateral (contralesional) primary sensorimotor cortex (SM1) activation at the subacute stage to the contralateral (ipsilesional) SM1 activation at the chronic stage.

Brain↗
PubMed2006

The basal ganglia are hyperactive during the discrimination of tactile stimuli in writer's cramp.

Writer's cramp is a focal hand dystonia that specifically affects handwriting. Though writer's cramp has been attributed to a dysfunction of the basal ganglia, the role of the basal ganglia in the pathogenesis of writer's cramp remains to be determined. Seventeen patients with writer's cramp (nine females; age range: 24-71 years) and 17 healthy individuals (six females; age range: 27-68 years) underwent functional MRI (fMRI) while they discriminated the orientation of gratings delivered to the tip of the right index finger. Statistical parametric mapping was used to analyse the fMRI data. The significance level was set at a corrected P-value of 0.05. Relative to healthy controls, patients with writer's cramp showed a widespread bilateral increase in task-related activity in the putamen, caudate nucleus, internal globus pallidus and lateral thalamus. In these areas, hyperactivity was more pronounced in patients who had recently developed writer's cramp. The enhanced response of the basal ganglia to tactile input from the affected hand is compatible with the concept of impaired centre-surround inhibition within the basal ganglia-thalamic circuit and may lead to an excessive activation of sensorimotor cortical areas during skilled movements affected by dystonia. Outside the basal ganglia, dystonic patients showed task-related overactivity in visual cortical areas, left anterior insula and right intraparietal sulcus, but not in the primary or secondary sensory cortex. In addition, task-related activity in the cerebellar nuclei, posterior vermis, right paramedian cerebellar hemisphere and dorsal pons was inversely related with the severity of hand dystonia. Regional activity in these areas may reflect secondary adaptive reorganization at the systems level to compensate for the dysfunction in the basal ganglia-thalamic loop.

Adult↗
PubMed2006

Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To make evidence-based treatment recommendations for the medical and surgical treatment of patients with Parkinson disease (PD) with levodopa-induced motor fluctuations and dyskinesia. To that end, five questions were addressed. 1. Which medications reduce off time? 2. What is the relative efficacy of medications in reducing off time? 3. Which medications reduce dyskinesia? 4. Does deep brain stimulation (DBS) of the subthalamic nucleus (STN), globus pallidus interna (GPi), or ventral intermediate (VIM) nucleus of the thalamus reduce off time, dyskinesia, and antiparkinsonian medication usage and improve motor function? 5. Which factors predict improvement after DBS? METHODS: A 10-member committee including movement disorder specialists and general neurologists evaluated the available evidence based on a structured literature review including MEDLINE, EMBASE, and Ovid databases from 1965 through June 2004. RESULTS, CONCLUSIONS, AND RECOMMENDATIONS: 1. Entacapone and rasagiline should be offered to reduce off time (Level A). Pergolide, pramipexole, ropinirole, and tolcapone should be considered to reduce off time (Level B). Apomorphine, cabergoline, and selegiline may be considered to reduce off time (Level C). 2. The available evidence does not establish superiority of one medicine over another in reducing off time (Level B). Sustained release carbidopa/levodopa and bromocriptine may be disregarded to reduce off time (Level C). 3. Amantadine may be considered to reduce dyskinesia (Level C). 4. Deep brain stimulation of the STN may be considered to improve motor function and reduce off time, dyskinesia, and medication usage (Level C). There is insufficient evidence to support or refute the efficacy of DBS of the GPi or VIM nucleus of the thalamus in reducing off time, dyskinesia, or medication usage, or to improve motor function. 5. Preoperative response to levodopa predicts better outcome after DBS of the STN (Level B).

Dyskinesias↗
PubMed2006

Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study.

Little is known about the neural correlates of tics and associated urges. In the present study, we aimed to explore the neural basis of tics in patients with Tourette syndrome by using event-related functional MRI (fMRI). Ten patients (6 women, 4 men; age: mean +/- SD = 31 +/- 11.2) were studied while spontaneously exhibiting a variety of motor and vocal tics. On the basis of synchronized video/audio recordings, fMRI activities were analysed 2 s before and at tic onset irrespective of the clinical phenomenology. We identified a brain network of paralimbic areas such as anterior cingulate and insular cortex, supplementary motor area (SMA) and parietal operculum (PO) predominantly activated before tic onset (P < 0.05, corrected for multiple comparisons). In contrast, at the beginning of tic action, significant fMRI activities were found in sensorimotor areas including superior parietal lobule bilaterally and cerebellum. The results of this study indicate that paralimbic and sensory association areas are critically implicated in tic generation, similar to movements triggered internally by unpleasant sensations, as has been shown for pain or itching.

Adult↗
PubMed2006

Pathophysiology of dystonia.

Understanding of the pathophysiology of dystonia derives primarily from studies of focal dystonias. Physiological investigations have revealed a number of abnormalities that may reflect the genetic substrate that predisposes certain individuals to develop dystonia. There is a loss of inhibition in the central nervous system, and a loss of surround inhibition specifically. Plasticity is increased, and there are sensory abnormalities. Which of these disorders is primary is uncertain.

Animals↗
PubMed2006

Immunological aspects of Botox, Dysport and Myobloc/NeuroBloc.

In some patients treated with botulinum toxin (BT), antibodies are produced in association with certain treatment parameters, patient characteristics and immunological properties of the BT preparation used. Therapeutic BT preparations are comprised of botulinum neurotoxin, non-toxic proteins and excipients. Antibodies formed against botulinum neurotoxin can block BT's biological activity. The antigenicity of a BT preparation depends on the amount of botulinum neurotoxin presented to the immune system. This amount is determined by the specific biological activity, the relationship between the biological activity and the amount of botulinum neurotoxin contained in the preparation. For Botox the specific biological activity is 60 MU-EV/ng neurotoxin, for Dysport 100 MU-EV/ng neurotoxin and for Myobloc/NeuroBloc 5 MU-EV/ng neurotoxin. For Myobloc/NeuroBloc this translates into an antibody-induced therapy failure rate of 44% in patients treated for cervical dystonia, whereas for BT type A preparations this figure is approximately 5%. No obvious differences in antigenicity of BT type A preparations have been detected thus far. For the current formulation of Botox, the rate of antibody-induced therapy failure is reportedly less than 1%. To determine the antigenicity of different BT preparations in more detail, prospective studies on large series of unbiased patients with sensitive and specific BT antibody tests are necessary.

Animals↗
PubMed2006

Botulinum toxin therapy of writer's cramp.

The pathophysiology and management of writer's cramp is one of the most challenging amongst the various forms of focal dystonias. Frequently, the dystonic postures are confounded by compensatory muscle activity. Correct identification of target muscles for botulinum toxin (BT) injections determines the treatment success. The dosages of different preparations vary, with 1 unit of Botox roughly equalling 3.5 units of Dysport. Electromyographic guided injections yield better results and may also decrease the amount of toxin required. Weakness of target muscles interfering with other non-writing activities is a frequently encountered adverse effect. Studies have shown that BT is a safe long-term therapy option.

Anti-Dyskinesia Agents↗
PubMed2005

Measuring Friedreich ataxia: Interrater reliability of a neurologic rating scale.

Measuring the severity of neurologic dysfunction in patients with inherited ataxias, including Friedreich ataxia (FA), is difficult because of the variable rate of progression, the variable age at onset and the variety of neural systems that may be affected. The authors discuss the problems related to rating scales in the ataxias, report a neurologic rating scale for FA, and demonstrate acceptable interrater reliability of the instrument.

Adolescent↗
PubMed2005

Role of cerebral cortex in human postural control: an EEG study.

OBJECTIVE: It was our primary objective to provide evidence supporting the existence of neural detectors for postural instability that could trigger the compensatory adjustments to avoid falls. METHODS: Twelve young healthy subjects performed self-initiated oscillatory and discrete postural movements in the anterior-posterior (AP) directions with maximal range of motion predominantly at ankle joint. Movements were recorded by the system and included force plate and EMG, and EEG measures from 25 electrode sites. The center of pressure dynamics and stability index were calculated, and EEG potentials both in voltage and frequency domains were extracted by averaging and Morlet wavelet techniques, respectively. RESULTS: The initiation of self-paced postural movement was preceded by slow negative DC shift, similar to movement-related cortical potentials (MRCP) accompanying voluntary limb movement. A burst of gamma activity preceded the initiation of compensatory backward postural movement when balance was in danger. This was evident for both oscillatory and discrete AP postural movements. The spatial distribution of EEG patterns in postural actions approximated that previously observed during the postural perceptual tasks. CONCLUSIONS: The results suggest an important role of the higher cortical structures in regulation of posture equilibrium in dynamic stances. Postural reactions to prevent falls may be triggered by central command mechanisms identified by a burst of EEG gamma activity. SIGNIFICANCE: The results from this study contribute to our understanding of neurophysiological mechanisms underlying the cortical control of human upright posture in normal subjects.

Adaptation, Physiological↗
PubMed2004

Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia: new diagnostic criteria.

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterized by short episodes of involuntary movement attacks triggered by sudden voluntary movements. Although a genetic basis is suspected in idiopathic cases, the gene has not been discovered. Establishing strict diagnostic criteria will help genetic studies. METHODS: The authors reviewed the clinical features of 121 affected individuals, who were referred for genetic study with a presumptive diagnosis of idiopathic PKD. RESULTS: The majority (79%) of affected subjects had a distinctive homogeneous phenotype. The authors propose the following diagnostic criteria for idiopathic PKD based on this phenotype: identified trigger for the attacks (sudden movements), short duration of attacks (<1 minute), lack of loss of consciousness or pain during attacks, antiepileptic drug responsiveness, exclusion of other organic diseases, and age at onset between 1 and 20 years if there is no family history (age at onset may be applied less stringently in those with family history). In comparing familial and sporadic cases, sporadic cases were more frequently male, and infantile convulsions were more common in the familial kindreds. Females had a higher remission rate than males. An infantile-onset group with a different set of characteristics was identified. A clear kinesigenic trigger was not elicited in all cases, antiepileptic response was not universal, and some infants had attacks while asleep. CONCLUSIONS: The diagnosis of idiopathic paroxysmal kinesigenic dyskinesia (PKD) can be made based on historical features. The correct diagnosis has implications for treatment and prognosis, and the diagnostic scheme may allow better focus in the search for the PKD gene(s).

Adolescent↗
PubMed2004

BIAS: Bioinformatics Integrated Application Software.

MOTIVATION: We introduce a development platform especially tailored to Bioinformatics research and software development. BIAS (Bioinformatics Integrated Application Software) provides the tools necessary for carrying out integrative Bioinformatics research requiring multiple datasets and analysis tools. It follows an object-relational strategy for providing persistent objects, allows third-party tools to be easily incorporated within the system and supports standards and data-exchange protocols common to Bioinformatics. AVAILABILITY: BIAS is an OpenSource project and is freely available to all interested users at http://www.mcb.mcgill.ca/~bias/. This website also contains a paper containing a more detailed description of BIAS and a sample implementation of a Bayesian network approach for the simultaneous prediction of gene regulation events and of mRNA expression from combinations of gene regulation events. CONTACT: hallett@mcb.mcgill.ca.

Computational Biology↗
PubMed2004

Open-label dose-escalation study of oral 1-octanol in patients with essential tremor.

Twenty-one single oral doses of 1-octanol were given to patients with essential tremor (ET) in an open-label dose-escalation study. The drug was well tolerated up to 64 mg/kg. The main side effect was an unusual taste. No overt intoxication was seen. There was evidence for efficacy, with a significant reduction in tremor amplitude as measured by accelerometry and handwriting that was maximal at 2 hours. Higher doses may produce more sustained benefit.

1-Octanol↗
PubMed2004

The Hera database and its use in the characterization of endoplasmic reticulum proteins.

MOTIVATION: Information concerning endoplasmic reticulum (ER) proteins is widely dispersed and cannot be easily and rapidly processed by the biological community. We present a comprehensive database of human ER proteins, called Human ER Aperçu (Hera). The Hera database was constructed by exhaustively searching through public databases and the scientific literature for ER proteins. RESULTS: Hera was used for the analysis of characteristics common to all human ER proteins. Our results show that a high proportion of ER proteins (59%) have at least one transmembrane domain and display physical characteristics consistent with this observation. In addition, one-third of ER proteins contain known ER retrieval or retention signals and 70% of ER proteins contain a signal peptide or anchor. Finally, 85% of ER proteins contain at least one InterPro motif. The most abundant InterPro motifs in ER proteins represent many of the most well-characterized functions of the ER.

Amino Acid Motifs↗
PubMed2004

Pilot trial of 1-octanol in essential tremor.

1-Octanol (an 8-C alcohol currently used as a food-flavoring agent) is known to inhibit tremor in essential tremor (ET) animal models at a much lower dose than ethyl alcohol. The authors conducted a randomized, placebo-controlled pilot trial of a single oral dose of 1 mg/kg of 1-octanol in 12 patients with ET. No significant side effects or signs of intoxication were observed. 1-Octanol significantly decreased tremor amplitude for up to 90 minutes. The results suggest 1-octanol as a well-tolerated and safe potential treatment for ET. Further trials are warranted.

1-Octanol↗
PubMed2004

Cortical control of voluntary blinking: a transcranial magnetic stimulation study.

OBJECTIVE: To investigate cortical regions related to voluntary blinking. METHODS: Transcranial magnetic stimulation (TMS) was applied to the facial motor cortex (M1) and the midline frontal region (Fz) in 10 healthy subjects with eyes opened and closed. Motor-evoked potentials were recorded from the orbicularis oculi (OOC), orbicularis oris (OOR), abductor digiti minimi and tibialis anterior using surface and needle electromyography electrodes. Facial M waves and blink reflex were measured using supramaximal electrical stimulation of the facial and supraorbital nerves. RESULTS: TMS at Fz elicited 3 waves in OOC with no response in other tested muscles except for the early wave in OOR. Facial M1 stimulation produced only early and late waves. Because of their latencies, shapes, and relationship to coil position and stimulation intensity, early and late waves appeared to be analogous to the facial M wave and R1 component of the blink reflex. The intermediate wave at 6-8 ms latency was elicited in OOC by Fz stimulation with eyes closed. CONCLUSIONS: Since its latency matches the central conduction time of other cranial muscles and it has characteristic of muscle activation-related facilitation, the intermediate wave is presumably related to cortical stimulation. This result provides evidence that the cortical center for the upper facial movements, including blinking, is not principally located in the facial M1, but rather in the mesial frontal region.

Adult↗
PubMed2004

Flumazenil does not affect intracortical motor excitability in humans: a transcranial magnetic stimulation study.

OBJECTIVE: The motor cortex may be subject to tonic inhibitory drive. One inhibitory mechanism is supported by activity at benzodiazepine (BZP) receptors. In this study we investigate whether or not the BZP antagonist, flumazenil, increases cortical motor excitability in humans. METHODS: Eight healthy subjects received a 1 mg intravenous (i.v.) loading dose of flumazenil followed by a 0.5 mg i.v. infusion over the next 30 min. Before, during, and 1 h after flumazenil infusion, we measured cortical motor excitability using transcranial magnetic stimulation (TMS). This included resting motor threshold (rMT), paired-pulse measurements of intracortical inhibition and facilitation (ICI and ICF), recruitment curve (RC), and silent period (SP). We also measured F response and compound muscle action potential (CMAP) with peripheral nerve stimulation. The study was carried out using a randomized, double-blind crossover design controlled with a saline infusion. RESULTS: None of the measures of cortical or peripheral excitability were significantly affected by drug administration. CONCLUSIONS: Our findings suggest that flumazenil has no effect on cortical motor excitability in normal humans. SIGNIFICANCE: There does not appear to be any tonic activity at benzodiazepine receptors in the normal resting human motor cortex.

Action Potentials↗