Driving with sleep apnea.
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Accidents, Traffic↗
Biomedical subjects
L J Findley
Publications and source records attributed to L J Findley.
S-fluoxetine in the prophylaxis of migraine: a phase II double-blind randomized placebo-controlled study.
S-fluoxetine is the long-acting enantiomer of the racemic antidepressant serotonin reuptake inhibitor. Sixty-five patients needing migraine prophylaxis were recruited into a phase II, double-blind, placebo-controlled trial. After a 1-month placebo run-in, 53 patients met entry criteria with regard to attack frequency and were randomized, 27 to S-fluoxetine and 26 to matching placebo. Three failed to start treatment and there were 17 early discontinuations, 9 from S-fluoxetine, 8 from placebo, at similar times and for similar reasons. The primary efficacy variable was attack frequency and analysis compared decline-from-baseline in the two groups. This was earlier and greater (1.7 attacks/28 days, or 52%) on active therapy than on placebo (1.1 attacks/28 days, or 27%), and statistically significant in month 2 (F = 4.93; p = 0.033) and month 4 (F = 4.55; p = 0.041). As secondary measures of efficacy, migraine-days per month and Patient's Global Impression of Disease Severity coherently reflected the changes in attack frequency. Mean attack severity and acute medication use (doses per attack) were unaltered by either treatment. There were no serious adverse events. Withdrawals for adverse events were four from each group but none was considered causally related. The finding of greater efficacy of S-fluoxetine than of placebo should be interpreted conservatively, since the analysis in the final month was made on only half of the entered patients. It supports progression to phase III evaluation, which was the purpose of the study.
Adult↗
Electrophysiological aids in distinguishing organic from psychogenic tremor.
The clinical differentiation of tremors of organic and psychogenic origin can be difficult. We describe a patient with unilateral upper limb tremor that was initially considered to have a psychogenic cause, but subsequent frequency analysis of EMG signals and accelerometer recordings indicated that the tremor was organic in nature. An ischemic lesion in the contralateral lentiform nucleus found on MRI supported this conclusion. Quantitative electrophysiologic studies may thus be useful in distinguishing organic from psychogenic tremor.
Aged↗
Tolcapone added to levodopa in stable parkinsonian patients: a double-blind placebo-controlled study. Tolcapone in Parkinson's Disease Study Group II (TIPS II).
The primary objective of this study was to assess the effect of tolcapone on levodopa dosage in parkinsonian patients whose "wearing-off" phenomenon has been controlled with more frequent levodopa dosage. After a 1-week placebo run-in, 97 patients were assigned randomly to receive placebo or tolcapone 200 or 400 mg three times daily (t.i.d.). Levodopa dosage was reduced by -35% on day 1 of study and subsequently retitrated as required. After 6 weeks, the tolcapone groups crossed over to receive the other dose for a further 3 weeks for exploratory purposes. Both tolcapone groups had greater reductions in levodopa dosage than the placebo group at week 6 (not statistically different). The 200-mg t.i.d. group showed greatest improvement in estimated mean scores for all efficacy parameters (p < 0.05 versus placebo for change in Unified Parkinson's Disease Rating Scale Subscale II). Fewer dopaminergic and nondopaminergic adverse events were associated with tolcapone 200 mg t.i.d. than with tolcapone 400 mg t.i.d. The most frequently reported dopaminergic adverse events were nausea, cramps, dyskinesia, and dystonia. The most frequently reported unanticipated adverse event was diarrhea. Tolcapone 200 mg t.i.d. may provide additional benefit to patients with moderately advanced Parkinson's disease with treated "wearing-off" phenomenon.
Activities of Daily Living↗
Lamotrigine versus placebo in the prophylaxis of migraine with and without aura.
Lamotrigine blocks voltage-sensitive sodium channels, leading to inhibition of neuronal release of glutamate. Release of glutamate may be essential in the propagation of spreading cortical depression, which some believe is central to the genesis of migraine attacks. This study compared safety and efficacy of lamotrigine and placebo in migraine prophylaxis in a double-blind randomized parallel-groups trial. A total of 110 patients entered; after a 1-month placebo run-in period, placebo-responders and non-compliers were excluded, leaving 77 to be treated with lamotrigine (n = 37) or placebo (n = 40) for up to 3 months. Initially, lamotrigine therapy was commenced at the full dose of 200 mg/day, but, following a high incidence of skin rashes, a slow dose-escalation was introduced: 25 mg/day for 2 weeks, 50 mg/day for 2 weeks, then 200 mg/day. Attack rates were reduced from baseline means of 3.6 per month on lamotrigine and 4.4 on placebo to 3.2 and 3.0 respectively during the last month of treatment. Improvements were greater on placebo and these changes, not statistically significant, indicate that lamotrigine is ineffective for migraine prophylaxis. There were more adverse events on lamotrigine than on placebo, most commonly rash. With slow dose-escalation their frequency was reduced and the rate of withdrawal for adverse events was similar in both treatment groups.
Adolescent↗
Electrophysiological observations on an unusual, task specific jaw tremor.
A patient with no other neurological signs or symptoms presented with a prominent tremor restricted to the mandible. This 5-6 Hz tremor was interesting in that it was normally confined to the digastric muscles and was highly task specific. In the course of her normal daily activities, it began only when the patient drank from a cup or glass. The localisation of this tremor to a muscle that has no muscle spindles and no reciprocal inhibitory reflexes suggests that such tremors must be capable of being generated centrally.
Electromyography↗
The effect of ethanol on alcohol-responsive essential tremor: a positron emission tomography study.
We used H2 15O positron emission tomography (PET) to investigate the effect of ethyl alcohol on regional cerebral blood flow in 6 patients with alcohol-responsive essential tremor and 6 age-matched control subjects. The patients were scanned while at rest and during involuntary postural tremor of the extended right arm. Normal control subjects were scanned at rest and during passive wrist oscillation of the right arm at tremor frequency. Regional cerebral blood flow associated with these conditions was measured before and after oral administration of 2 to 3 units of alcohol. The mean blood alcohol level was 35.3 +/- 20.0 mg/dl in the patient group and caused marked suppression of tremor; it was 33.9 +/- 12.9 mg/dl in the control group. Similar to previous PET studies on essential tremor patients, tremor compared with rest was associated with bilateral cerebellar activation including the cerebellar vermis. This pattern of activation differed from passive wrist oscillation where ipsilateral cerebellar activation was observed. Ethanol ingestion led to bilateral decreases of cerebellar blood flow in both tremor patients and normal subjects, and this was associated with suppression of tremor in the patients. Alcohol-associated increases of regional cerebral blood flow were observed in the inferior olivary nuclei in the patients but not in the control subjects. We conclude that alcohol-induced suppression of essential tremor is mediated via a reduction of cerebellar synaptic overactivity resulting in increased afferent input to the inferior olivary nuclei.
Adult↗
Double-blind study of the activity and tolerability of cabergoline versus placebo in parkinsonians with motor fluctuations.
The use of a dopamine agonist with a long duration of action has theoretical advantages in attempting to reduce the motor fluctuations in Parkinson's disease. We report the results of a double-blind controlled study of adding cabergoline, an ergot derivative with potent long-lasting high affinity for the D2 receptor, to levodopa therapy in 37 patients with severe fluctuations in response to treatment. Increasing dosages of cabergoline (19 patients) or placebo (18 patients) were added to each patient's stable levodopa regime. The two patient groups were similar at baseline in terms of age, disease duration, duration of levodopa treatment, and average hours "off" per day. Following incremental dose titration, patients in the cabergoline group had a significant reduction in hours "off" per day from 5.0 (SD 2.1) to 3.0 (SD 2.5), but there was no change in this measure in the placebo group [4.0 (2.2) and 3.3 (2.3) respectively]. This was not at the expense of a significant increase in dyskinesia. However, there was no difference between the groups when comparing their average Hoehn and Yahr stage of disease, and Schwab and England activities of daily living index.
Adult↗
Classification of tremors.
Until there is a greater understanding of basic tremorgenic mechanisms in the central nervous system, current classifications of tremors rely heavily on the behavioural characteristics, putative sites of origin, and/or the underlying disease process. Careful clinical evaluation remains the centrum of tremor classification. Few tremors do show specific neurophysiological features that will clinch diagnosis, e.g., primary orthostatic tremor and dystonic tremor. With the exception of dopaminergic drugs in Parkinson's disease, drug effects in tremors are unpredictable and nonspecific. Drug side effects should be considered in the differential diagnosis of any unexplained tremor.
Cerebellum↗
A positron emission tomography study of primary orthostatic tremor.
Primary orthostatic tremor (OT), a clinical syndrome in which a rapid (14 to 16 Hz), regular lower limb tremor causes unsteadiness on standing, may be associated with a postural upper limb tremor of similar frequency. We used H2 15O PET to analyze the abnormal pattern of cerebral activation associated with the postural upper limb tremor in four patients with primary OT. Patients had regional cerebral bloodflow (rCBF) measured during involuntary tremor while maintaining a posture with their outstretched right upper limb and again at rest. Tremor was associated with abnormal bilateral cerebellar and contralateral lentiform and thalamic activation. These findings were evident on group analysis of pooled PET data after transformation into standard stereotactic space and in single subjects when PET images were coregistered with structural MRI of the brain. At rest, cerebellar blood flow was significantly increased bilaterally in OT when compared with age- and sex-matched controls. We have previously demonstrated similar abnormal bilateral cerebellar activation in essential and writing tremors and conclude that abnormal bilateral overactivity of cerebellar connections is a common feature of tremulous disorders.
Aged↗
Automobile crashes and sleep.
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Accidents, Traffic↗
[Driving performance and auto accidents in patients with sleep apnea].
Obstructive sleep apnea is a common disorder in which the airway repetitively collapses during sleep; patients with sleep apnea are often inattentive and sleepy. This review discusses driving performance and automobile accidents in patients with sleep apnea. Finally, we discuss the effect of therapy upon driving performance and reported accidents in these subjects.
Accidents, Traffic↗
A positron emission tomography study of cerebral activation associated with essential and writing tremor.
OBJECTIVE: To compare the abnormal patterns of cerebral activation associated with essential and writing tremors. DESIGN: Positron emission tomography using oxygen 15-labeled water was utilized to determine regional cerebral blood flow. Positron emission tomography images that were taken of the brain in individual patients were coregistered with magnetic resonance images of the same brain to ascertain accurate localization of cerebral activation in single patients. Patients with essential tremor underwent scanning at rest, during involuntary postural tremor, and during passive wrist oscillation. Normal control subjects underwent scanning at rest and during voluntary and passive wrist oscillation. Patients with writing tremor underwent scanning while they were holding a pen to paper with consequent involuntary tremor and again while they were holding a pen in the same supinated arm without tremor. SETTING: Research hospital. PATIENTS OR OTHER PARTICIPANTS: Seven patients with essential tremor, six patients with writing tremor, and six matched control subjects. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Regional cerebral blood flow. RESULTS: Essential tremor was associated with abnormal bilateral cerebellar, red nuclear, and thalamic activation. Writing tremor was also associated with abnormal bilateral cerebellar activation. Voluntary wrist oscillation in control subjects caused only ipsilateral cerebellar activation. These findings were evident in single patients, when positron emission tomography images were coregistered with magnetic resonance images and on group analysis of the pooled positron emission tomography data after transformation into stereotaxic space. CONCLUSION: These results indicate that both essential and writing tremors are associated with abnormal bilateral overactivity of cerebellar connections.
Adult↗
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↗
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↗
Red nuclear and cerebellar but no olivary activation associated with essential tremor: a positron emission tomographic study.
There has been debate as to whether essential tremor has a central origin and over the possible role of the inferior olivary nucleus in its genesis. We used positron emission tomography with radioactive water (H2(15)O) to detect abnormal patterns of cerebral activity associated with this condition, at rest, without tremor, and on posture when the tremor was present. At rest, cerebellar blood flow was significantly increased bilaterally in the group with essential tremor (30-40%) but no increased olivary activity was evident. Essential tremor during arm extension was associated with further abnormal increases in bilateral cerebellar and abnormal red nuclear activation. Again, no olivary overactivity was evident. Voluntary wrist oscillation in control subjects caused only ipsilateral cerebellar activation. We conclude that essential tremor is associated with abnormal bilateral overactivity of cerebellar and red nuclear connections but found no evidence of intrinsic overactivity of the inferior olivary nucleus, as evidenced by raised blood flow.
Adult↗
Task specific visuospatial neglect related to density and salience of stimuli.
We report the case of a male patient with a right parietal tumour. On examination he presented with marked visuospatial neglect and anosognosia for his deficits. Experimental analysis of his visuospatial neglect revealed that his ability to identify simple stimuli in the contralateral to the lesion space was significantly influenced by the degree of density of stimuli in the ipsilateral space. Similarly his performance was found to be affected significantly by the complexity or salience of a stimulus in the ipsilateral space. An attempt is made to interpret these observations in the context of current major theories of neglect.
Aged↗
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↗