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Biomedical subjects

T C Britton

Publications and source records attributed to T C Britton.

At least 37 records · Page 2Linked to original sources
PubMed1995

Primary writing tremor.

Primary writing tremor (PWT) is considered to be a type of task-specific tremor in which tremor predominantly occurs and interferes with handwriting. We describe the clinical and neurophysiological features of 21 patients (20 male and one female) with PWT. Mean age at tremor onset was 50.1 years. A family history of PWT was obtained from seven patients. Ten patients obtained benefit from drug treatment (mainly propranalol or primidone) and seven responded to alcohol. The writing speeds of the patients (mean +/- SEM: 73.1 +/- 6.6 letters per minute) when using their preferred hand were significantly reduced (Student's t test: P < 0.001) compared with those of healthy control subjects (mean +/- SEM: 127.7 +/- 6.4). Surface polymyography performed during writing showed 4.1-7.3 Hz rhythmic activity predominantly in the intrinsic hand and forearm muscles. Alternating, extensor activation alone, skipping from alternating to extensor activation, and co-contracting EMG patterns were recorded from the flexor and extensor muscles of the forearm. There was no evidence for excessive 'overflow' of this rhythmic EMG activity, as similar activity was detected in comparable muscle groups of healthy control subjects. Accelerometry confirmed that the frequency of PWT ranged from 4.1-7.3 Hz (median 5.5 Hz) and that normal subjects wrote with a 4.0-7.7 Hz oscillation (median 4.6 Hz). Forearm reciprocal inhibition was normal in PWT (n = 13), and thus patients with PWT can be distinguished from those with writer's cramp in whom decreased presynaptic inhibition has been found. Patients were sub-classified as having either type A (n = 11) or B (n = 10) PWT depending on whether tremor appeared during writing (type A: task induced tremor) or whilst writing and adopting the hand position used in writing (type B: positionally sensitive tremor). However, the only differences between these two groups were that a co-contracting EMG pattern and tremor induced by tendon taps to the volar aspect of the wrist were present in type B but not type A cases.

Adult↗
PubMed1995

Essential tremor and its variants.

Essential tremor is the commonest of movement disorders. Although sometimes prefaced with the term 'benign', it often causes significant disability. Diagnosis is based on the clinical finding of a postural tremor, predominantly affecting the upper limbs, that is absent at rest and not associated with extrapyramidal or cerebellar signs. There are, as yet, no specific anatomical, physiological, biochemical or genetic markers for the condition. Postural limb tremors, clinically indistinguishable from essential tremor, may occur in patients who have, or will later develop, other neurological conditions; whether such patients have essential tremor is a matter of controversy that will only be resolved with a better understanding of the pathophysiology of essential tremor. Positron emission tomography in patients with essential tremor reveals increased cerebellar activity even at rest, a finding that is consistent with the cerebellum having an important role in the generation of tremor. Abnormal cerebellar function has also been invoked to account for the abnormal manner in which patients with essential tremor perform rapid voluntary wrist movements. Molecular genetic studies in hereditary essential tremor have been initiated, but with negative results so far. Several new drug treatments have been tried, but with limited success; the role of thalamic stimulation and botulinum toxin in the treatment of essential tremor remains to be judged.

Cerebellum↗
PubMed1995

Exacerbation of postural tremor with emergence of parkinsonism after treatment with neuroleptic drugs.

Neuroleptic medication in three patients with prior isolated postural arm tremor led to a conspicuous deterioration; the postural tremor increased in amplitude, tremor appeared at rest, and other signs of mild parkinsonism developed. Withdrawal of neuroleptic drugs led to improvement in tremor and disappearance of parkinsonism. Positron emission tomography showed no reduction in uptake of [18F]dopa into nigrostriatal terminals suggesting that these patients did not have Parkinson's disease. Neuroleptic drugs can convert postural essential arm tremor into that characteristic of Parkinson's disease in patients with no evident nigrostriatal lesion.

Adult↗
PubMed1994

Degradation chemistry of gemcitabine hydrochloride, a new antitumor agent.

The anti-tumor agent gemcitabine hydrochloride, a beta-difluoronucleoside, is remarkably stable in the solid state. In 0.1 N HCI solution at 40 degrees C, deamination of gemcitabine occurs, yielding its uridine analogue. Approximately 86% of the initial gemcitabine remains after 4 weeks under these conditions. Cleavage of the N-glycosidic bond of gemcitabine or conversion to its alpha-anomer in 0.1 N HCI solution is not observed over a 4-week period. However, this work has shown that gemcitabine hydrochloride anomerizes in 0.1 N NaOH at 40 degrees C. Approximately 72% of the initial gemcitabine remains after 4 weeks under the basic conditions used. Uridine hydrolysis products are also formed under these conditions. The anormerization reaction, which is unusual under basic conditions, has been confirmed by characterization of the chromatographically isolated alpha-anomer by NMR and mass spectrometry. A mechanism involving an acyclic intermediate is proposed.

Antimetabolites, Antineoplastic↗
PubMed1994

Rapid wrist movements in patients with essential tremor. The critical role of the second agonist burst.

Ballistic wrist flexion movements towards 15, 30 and 60 degrees visual targets were studied in a group of 17 patients with hereditary essential tremor. Compared with age-matched normal subjects (n = 16), there were three main kinematic differences: patients overshot the target a little more; the kinematic profile of their movements was more 'asymmetric' due to higher peak decelerations; and their movements initiated tremor. Ballistic movements performed by patients with essential tremor were associated with a triphasic pattern of agonist-antagonist-agonist muscle activity similar to that of normal subjects. The duration and size of each EMG burst was normal. The onset latency of the antagonist EMG burst was also normal, but the onset of the second agonist EMG burst was delayed. The delay in the onset of the second agonist EMG activity resulted in unopposed action of the antagonist muscle in the second half of each movement. As a result, deceleration occurred too rapidly as the hand returned past the target leading to a series of damped oscillations around the point of aim. The onset latency of the second agonist EMG burst correlated significantly with the tremor period; the longer the period the later the burst. We speculate that the delay in the second agonist burst reflects an abnormality in the timing of anticipatory muscle activity in essential tremor and that this may involve cerebellar mechanisms.

Adult↗
PubMed1994

The myoclonus in corticobasal degeneration. Evidence for two forms of cortical reflex myoclonus.

The clinical and physiological characteristics of myoclonus in 14 patients with corticobasal degeneration are described. The myoclonus was focal, confined to one limb (usually the arm) and was most prominent on voluntary action or in response to sensory stimulation. On clinical inspection, the myoclonus appeared to occur at rest but EMG recordings revealed that apparently spontaneous myoclonus occurred only on a background of more or less continuous muscle activity (responsible for the rigidity and dystonia). The jerks consisted of hypersynchronous short duration bursts of EMG activity coincident in agonists and antagonists. Reflex myoclonus in hand muscles, to stimulation of the median nerve at the wrist, had a latency of approximately 40 ms. In 13 of the 14 patients reflex myoclonus was not associated with enlargement of the cortical sensory evoked potentials (SEPs); the later components of the parietal SEP were poorly formed and dominated by a broad positive wave with a peak latency approximately 45 ms. Prefrontal components of the SEP were relatively preserved, but there were no significant differences between the SEPs evoked from myoclonic and non-myoclonic limbs. Action myoclonus was not preceded by an identifiable cortical wave in the electroencephalogram back-averaged before each jerk. Magnetic, but not electric, brain stimulation evoked repetitive bursts of myoclonus suggesting enhanced cortical excitability. The combination of focal, predominantly distal, hypersynchronous jerks, evidence of enhanced cortical excitability, together with the known cortical pathology in corticobasal degeneration suggests that the myoclonus in these patients may be cortical in origin. Since the latency of reflex myoclonus in corticobasal degeneration is only 1-2 ms longer than the sum of the afferent and efferent times to and from the cortex, we propose the reflex myoclonus is mediated by direct sensory input to motor cortical areas that activate corticospinal tract output. Such myoclonus differs from the typical form of cortical reflex myoclonus in which reflex jerks have a longer latency (50 ms in hand muscles), cortical SEPs are enlarged and action myoclonus is preceded by a cortical discharge. It is proposed that these various forms of cortical myoclonus can be explained by the presence of different cortical relays of sensory information to cortical motor areas. The myoclonus of corticobasal degeneration may represent enhancement of a direct sensory input to the motor cortex. In contrast, the more widely recognized variety of cortical reflex myoclonus may involve abnormal relays through sensory cortex to motor cortex, either directly or via cerebellar-thalamo-cortical projections.

Adult↗
PubMed1993

Modulation of postural wrist tremors by magnetic stimulation of the motor cortex in patients with Parkinson's disease or essential tremor and in normal subjects mimicking tremor.

The effect of magnetic brain stimulation on postural wrist tremor was studied in 10 patients with Parkinson's disease, 12 with hereditary essential tremor, and 10 normal subjects who mimicked tremor by making rapid alternating wrist movements. In all patients and normal subjects, magnetic brain stimulation over the contralateral motor cortex at an intensity approximately 10% above threshold produced the following sequence of events: (1) a small direct electromyographic (EMG) response, followed by (2) suppression of the rhythmic EMG activity responsible for the tremor, before (3) reappearance of the tremor time-locked to the stimulus. It is concluded that magnetic brain stimulation over the motor cortex can modulate the oscillatory mechanisms responsible for the generation of postural tremors. Group analysis revealed that the time to reappearance of rhythmic EMG activity varied significantly with the period of parkinsonian postural tremors, but not with the period of essential or mimicked tremors. Magnetic stimulation also significantly shortened the period of parkinsonian postural tremors, but did not influence the period of essential or mimicked tremors. These behavioral differences indicate differences in the pathophysiological mechanisms underlying parkinsonian postural tremor and essential tremor.

Adult↗
PubMed1993

Postural electromyographic responses in the arm and leg following galvanic vestibular stimulation in man.

Application of a small (around 1 mA), constant electric current between the mastoid processes (galvanic stimulation) of a standing subject produces enhanced body sway in the approximate direction of the ear behind which the anode is placed. We examined the electromyographic (EMG) responses evoked by such stimulation in the soleus and in the triceps brachii muscles. For soleus, subjects stood erect, with their eyes closed, leaning slightly forward. The head was turned approximately 90 degrees to the right or left relative to the feet. In averaged records (n = 40), current pulses of 25 ms or longer modulated the EMG in a biphasic manner: a small early component (latency 62 +/- 2.4 ms, mean +/- SEM) was followed by a larger late component (latency 115 +/- 5.2 ms) of opposite sign, which was appropriate to produce the observed body sway. The early component produced no measurable body movement. Lengthening the duration of the stimulus pulse from 25 to 400 ms prolonged the late component of the response but had little effect on the early component. Short- and long-latency EMG responses were also evoked in the triceps brachii muscle if subjects stood on a transversely pivoted platform and had to use the muscle to maintain their balance in the anteroposterior plane by holding a fixed handle placed by the side of their hip. The latency of the early component was 41 +/- 2.6 ms; the latency of the late component was 138 +/- 4.3 ms and was again of appropriate sign for producing the observed body sway. Galvanic stimulation evoked no comparable responses in either triceps brachii or soleus muscles if these muscles were not being used posturally.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Modulation of postural tremors at the wrist by supramaximal electrical median nerve shocks in essential tremor, Parkinson's disease and normal subjects mimicking tremor.

The response of postural wrist tremors to supramaximal median nerve stimulation was examined in patients with hereditary essential tremor (n = 10) and Parkinson's disease (n = 9), and in normal subjects mimicking wrist tremor (n = 8). The average frequency of on-going tremor was the same in all three groups. Supramaximal peripheral nerve shocks inhibited and then synchronised the rhythmic electromyographic (EMG) activity of all types of tremor. The duration of inhibition ranged from 90 to 210ms, varying inversely with the frequency of on-going tremor. There was no significant difference in mean duration of inhibition or in the timing of the first peak after stimulation on the average rectified EMG records between the three groups. The degree to which supramaximal peripheral nerve shocks could modulate the timing of rhythmic EMG bursts in the forearm flexor muscles was also quantified by deriving a resetting index. No significant difference in mean resetting index of the three groups was found. These results suggest that such studies cannot be used to differentiate between the common causes of postural wrist tremors.

Adult↗
PubMed1992

"Resetting" of postural tremors at the wrist with mechanical stretches in Parkinson's disease, essential tremor, and normal subjects mimicking tremor.

The response of postural wrist tremors to brief mechanical displacements was compared in two groups of patients, one with classical hereditary essential tremor (n = 18) and another with typical Parkinson's disease (n = 13). These groups were compared with an additional group of normal subjects mimicking wrist tremor (n = 9). The degree to which brief mechanical displacements of the wrist produced by torque pulses of three different sizes could modulate the timing of rhythmic electromyographic bursts in the forearm flexor muscles was quantified by deriving a resetting index, which could range between 0 (no phase resetting) and 1 (complete phase resetting). In all three groups of subjects studied, the resetting index varied significantly with the size of the mechanical perturbation and, in an inverse fashion, with the ongoing tremor amplitude. When due allowance for these factors was made, the difference in mean resetting indexes between the three groups of patients and subjects was reduced to the extent that no definitive statement could be made as to whether brief mechanical perturbations had more effect on essential tremor than parkinsonian tremor. The method is therefore unlikely to be useful in differentiating the common causes of postural wrist tremors.

Adult↗
PubMed1992

Motor responses evoked by magnetic brain stimulation in psychogenic limb weakness: diagnostic value and limitations.

The latencies and amplitudes of responses evoked by magnetic brain stimulation (magnetic evoked potentials, MEP) in the first dorsal interosseus and the anterior tibial (TA) muscles were investigated in 15 patients with psychogenic limb weakness and in 50 patients with limb weakness due to established organic central nervous system disease. Of the patients with psychogenic limb weakness, 3 presented with upper limb monopareses, 2 with lower limb monoparesis, 4 with hemipareses, 4 with parapareses and 2 with paraparesis. All patients with psychogenic weakness had MEP in arm and leg muscles with latencies within the normal range. MEP amplitudes were also normal except for 1 patient in whom the response amplitude in the TA of the plegic limb was reduced. In patients with limb weakness due to established organic disease, MEP were frequently but not invariably abnormal. In patients with plegic (i.e. completely paretic, MRC grade 0) muscles due to organic disease, MEP always were clearly abnormal. Normal MEP were sometimes elicited from paretic muscles, more commonly in association with cerebral hemisphere lesions than with spinal lesions. We conclude that psychogenic limb weakness is associated with normal MEP. However, normal MEP in mildly paretic muscles do not definitely exclude organic pathology.

Adolescent↗
PubMed1992

Primary orthostatic tremor: further observations in six cases.

The clinical and physiological features of six new patients with primary orthostatic tremor are described. We suggest that use of the term primary orthostatic tremor be confined to the clinical syndrome in which unsteadiness when standing is the predominant complaint and accompanied by characteristic electrophysiological findings of a rapid (frequency around 16 Hz), regular leg tremor which is not influenced by peripheral feedback, is synchronous between homologous leg muscles, and in certain postures of the upper limbs, between muscles of the arm and leg. The fast frequency of muscle activity in primary orthostatic tremor of the legs causes unsteadiness when standing (presumably due to partially fused muscle contraction) but only a fine ripple of muscle activity is visible. In contrast, the slower frequency of other leg tremors, for example essential tremor, results in obvious leg movement which is evident in many leg postures, is variable over time and can be reset by a peripheral nerve stimulus. Essential tremor and orthostatic tremor do not respond to the same therapies, suggesting differences in the pharmacological profiles of the two conditions. Accordingly, there are clinical, physiological and pharmacological differences between primary orthostatic and essential tremor. Whether these factors are sufficient to regard these tremors as separate conditions is discussed.

Adult↗
PubMed1992

[Normal values and age-related changes in magneto-electric evoked compound muscle potentials].

A number of 57 normal subjects was investigated using transcranial magnetic stimulation of the motor cortex and transcutaneous magnetic stimulation of the spinal nerve root in order to obtain normative data for central and peripheral motor latencies. Under standardized conditions (site of stimulation, stimulus intensity, degree of voluntary tonic background activation) muscle compound action potentials were recorded from different muscles of the upper and lower extremity: M. biceps brachii, M. extensor carpi radialis, M. interosseus dorsalis I, M. vastus medialis, M. tibialis anterior, and M. extensor digitorum brevis. Onset latency, peak to peak amplitude (% of maximal M-wave), duration and configuration of the muscle compound action potentials were evaluated (Fig. 1 and Tab. 1-6). Central and peripheral motor latencies were determined by stimulation over two different points of the neuraxis (cortex/cervical or lumbar nerve roots). Central motor latencies were calculated by subtracting the peripheral conduction time from the onset latency of the fastest cortically evoked muscle response. Not only the peripheral but also the central motor latencies were found to increase in higher ages (Tab. 6). This has to be taken into account when elderly patients are examined for diagnosis of disorders of the descending motor tracts.

Adult↗
PubMed1991

Abnormal conduction in corticospinal pathways in Wilson's disease: investigation of nine cases with magnetic brain stimulation.

Electromyographic (EMG) responses evoked by transcranial magnetic brain stimulation were studied in nine patients with Wilson's disease (WD). Six of the nine patients had prolonged central motor latencies (CMLs), reduced amplitude, or absent responses in at least one of the examined muscles. In one patient, abnormal EMG responses normalized following treatment with penicillamine. Pathophysiologically abnormal EMG responses might result from a potentially reversible impairment of corticomotoneuronal pathways and/or a reduced excitability of motoneurons due to basal ganglia dysfunction. The possible pathophysiological mechanisms are discussed.

Adult↗
PubMed1991

Wilson's disease: normalisation of cortically evoked motor responses with treatment.

A newly diagnosed patient with Wilson's disease is reported in whom the only clearly pathological neurophysiological findings before treatment were abnormal electromyographic (EMG) responses evoked by transcranial magnetic brain stimulation. Serial examinations over 10 months following commencement of treatment with D-penicillamine revealed normalisation of EMG responses. Pathophysiologically, the initially abnormal EMG responses probably resulted from reversible impairment of impulse propagation along cortico-motor-neuronal pathways and/or a reduced excitability of cortical cells due to impaired function of the basal ganglia.

Adolescent↗
PubMed1991

Variability of cortically evoked motor responses in multiple sclerosis.

The calculated central motor conduction time (CMCT), onset latency variability (expressed as the mean consecutive difference; MCD) and amplitude (expressed as percentage of maximum peripheral M wave size) of electromyographic (EMG) responses in the first dorsal interosseous (FDI) muscle following magnetic motor cortex stimulation were investigated in 20 normal subjects and 21 patients with multiple sclerosis (MS). EMG responses were present in all patients studied. CMCT was prolonged (greater than 8.1 msec; the mean CMCT for normals plus 3 S.D.) in 19 out of 42 muscles (12 patients). Onset latency variability was increased (greater than 1.1 msec; mean plus 3 S.D. for normals) in 20 out of 42 muscles (14 patients). Maximal response amplitudes varied between 5% and 67% and were not significantly different from the normal group (range 16-64%). In 3 patients, increased onset latency variability was the only neurophysiological abnormality. Prolonged CMCT was the sole abnormal finding in only 1 patient. Abnormally large onset latency variability was associated with the clinical finding of both impaired fine finger movements and increased finger jerks. Abnormal CMCT was associated with increased finger jerks only. This study confirms the findings of prolonged CMCT in multiple sclerosis. The additional finding of abnormal variability in response latencies which correlates with the clinical signs suggests that this variability may also be a useful measure of pyramidal tract function.

Adolescent↗
PubMed1991

Coil placement in magnetic brain stimulation related to skull and brain anatomy.

The influence of coil position on the size of electromyographic responses evoked by transcranial magnetic brain stimulation was systematically evaluated. The position of the stimulation coil (11.6 cm outer diameter, Novametrix) was recorded by constructing individual grids on the skull surface using extracranial bony landmarks and was then related to underlying cerebral sulci by analysis of magnetic resonance images of the brain and skull. The largest responses in the right first dorsal interosseus (FDI) muscle, when using anticlockwise coil currents as viewed from above, were found, on average (5 subjects), to occur with the coil centred 2 cm behind and left of the vertex. For the right tibialis anterior (TA) muscle the largest responses were obtained, on average, with the coil centred around a point 4 cm anterior to and 4 cm left of the vertex. Between individuals, the optimal coil position for responses in a particular muscle varied up to 2 cm. This variability could be explained by the variability in the relationship between the central sulcus and the extracranial bony landmarks of each individual. Responses could be obtained whenever the windings of the coil passed over the appropriate region of the motor cortex, providing evidence that magnetically evoked responses do originate from activation of the precentral gyrus. The size of the cortically evoked responses for a given stimulus intensity depended on the direction of the coil currents passing over the motor area. For FDI muscles, the largest responses were obtained when the coil currents passed over the lateral part of the motor strip from forwards behind and transversely to the central sulcus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗