Correlates of constipation in people with Parkinson's.

PURPOSE: To investigate clinical, demographic and dietary factors associated with constipation in a sample of community dwelling people with Parkinson's disease, recruited through a specialist outpatient clinic. Partners/carers provided a convenience control group. SCOPE: Participants completed a baseline questionnaire (background information, diet and exercise, activities of daily living: mobility and manual dexterity, health-related quality of life (SF-12), stool frequency and characteristics, extent of concern due to constipation, laxative taking), and a four-week stool diary. The Rome criterion was used to determine constipation status. Multiple regression methods were used to explore the correlates of constipation. Baseline data were provided by 121 people with Parkinson's, (54 controls), of whom 73% (25%) met the Rome criterion. Prospective diary data from 106 people with Parkinson's (43 controls) showed lower proportions: 35% (7%) meeting the Rome criterion. Among all study subjects, i.e. Parkinson's patients and controls taken together, the presence of constipation is predicted by having Parkinson's disease (p = .003; odds ratio 4.80, 95% CI 1.64-14.04) and mobility score (p = .04; odds ratio 1.15, 95% CI 1.01-1.31), but not by dietary factors. Amongst people with Parkinson's constipation is predicted by number of medications (p = .027). Laxative taking masks constipation, and is significantly associated with wearing protection against bowel incontinence (p = .009; odds ratio 4.80, 95% CI: 1.48-15.52). CONCLUSIONS: Constipation is disease-related, not a lifestyle factor. More research is needed on optimal management and laxative use.

A semantically enabled formalism for the knowledge management of Parkinson's disease.

Bio-ontology is a formal representation of biological concepts that is used in the interchange of communication between computers and humans alike. They can then be used in the formulation and retrieval of knowledge. In developing a knowledge-based system for Parkinson's Disease, a procedure of knowledge map was used to capture and harness the intellectual resources of an organization, and new paradigms for knowledge mapping were also formulated. Knowledge bases for symptoms and drugs, physiotherapy, speech and language therapy, and dieting that affect patient care were developed. Finally, the knowledge bases were merged to form a single central repository of knowledge base.

Dura mater-associated Creutzfeldt-Jakob disease: experience from surveillance in the UK.

Between 1970 and 2003, seven cases of human dura mater-associated Creutzfeldt-Jakob disease (CJD) were identified in the UK. Furthermore, we identified a case of CJD in a porcine dura graft recipient. The mean incubation period of the human dura mater cases was 93 (range 45-177) months. The clinico-pathological features of the cases are described and compared with cases previously reported in the world literature.

Multidisciplinary rehabilitation for people with Parkinson's disease: a randomised controlled study.

OBJECTIVE: To determine whether a programme of multidisciplinary rehabilitation and group support achieves sustained benefit for people with Parkinson's disease or their carers. METHODS: The study was a randomised controlled crossover trial comparing patients and carers who had received rehabilitation four months before assessment with those who had not. Patients were recruited from a neurology clinic, attended a day hospital from home weekly for six weeks using private car or hospital transport, and received group educational activities and individual rehabilitation from a multidisciplinary team. Patients were assessed at entry and at six months using a 25 item self assessment Parkinson's disease disability questionnaire, Euroqol-5d, SF-36, PDQ-39, hospital anxiety and depression scale, and timed stand-walk-sit test. Carers were assessed using the carer strain index and Euroqol-5d. RESULTS: 144 people with Parkinson's disease without severe cognitive losses and able to travel to hospital were registered (seven were duplicate registrations); 94 had assessments at baseline and six months. Repeated measures analysis of variance comparing patients at the 24 week crossover point showed that those receiving rehabilitation had a trend towards better stand-walk-sit score (p = 0.093) and worse general and mental health (p = 0.002, p = 0.019). Carers of treated patients had a trend towards more strain (p = 0.086). Analysis comparing patients before and six months after treatment showed worsening in disability, quality of life, and carer strain. CONCLUSIONS: Patients with Parkinson's disease decline significantly over six months, but a short spell of multidisciplinary rehabilitation may improve mobility. Follow up treatments may be needed to maintain any benefit.

Cyclosporin in the management of polymyositis and dermatomyositis.

Three patients with polymyositis refractory to conventional steroid and immunosuppressive treatment, but responsive to cyclosporin A, are described. In a fourth patient cyclosporin A was used as a first line drug in combination with steroids in the treatment of life-threatening dermatomyositis. Cyclosporin A in the management of polymyositis/dermatomyositis requires formal assessment of its costs and benefits compared with conventional treatments.

EEG appearances in acute carbamazepine toxicity.

A 16-year-old woman deliberately took a large, toxic overdose of carbamazepine and recovered despite a high plasma level. During the acute phase the EEG was dominated by occipital delta activity suggestive of a brainstem disorder. Following 24-h treatment with activated charcoal the plasma carbamazepine was cleared and the EEG returned to normal.

The effect of a high protein diet on leucine and alanine turnover in acid maltase deficiency.

Leucine and alanine production rate was measured in 5 patients with acid maltase deficiency in the postabsorptive state, following 6 months on a normal diet with placebo and 6 months on an isocaloric high protein diet (16-22% protein). Whole body leucine production rate, a measure of protein degradation, expressed in terms of lean body mass was significantly greater than in five control subjects. Following the high protein diet, leucine production rate was decreased in four of the five patients but this was not statistically significant. Alanine production rate expressed in terms of lean body mass was significantly greater than in control subjects. After the high protein diet, alanine production rate and concentration were significantly decreased (p less than 0.05). There were no significant improvements in any of the clinically relevant variables measured in these patients. It is possible that a larger increase in protein intake over a longer time period may have a clinical effect.

Muscle afferent contribution to control of paw shakes in normal cats.

1. The discharge of various hindlimb muscle afferents was recorded during paw shakes in normal cats with the use of floating dorsal root electrodes. 2. Muscle spindle group Ia-afferents and tendon organ group Ib-afferents fired during muscle lengthening, reaching very high peak discharge rates and then silencing at or shortly after the onset of shortening. The timing of Ia firing was consistent with the predictions of a linear model as well as the responses of Ia endings subjected to identical length variations in separate anesthetized cats. 3. In the latter "reconstruction" experiments, waxing and waning dynamic fusimotor action straddling whole paw-shake sequences gave the most consistent matches with the data from the normal cats. The reproducibility of the inferred fusimotor action justifies the inclusion of paw shakes as a class of movement in which fusimotor set is high. 4. The peak ensemble Ia activity from single hindlimb muscles was estimated to be approximately 20 kiloimpulses/s (Kips). Ankle extensor and hamstrings length variations were nearly in phase in the first cycles of a paw-shake sequence. From published data on spindle populations in these muscles, this indicated that peak Ia input to the spinal cord exceeded 0.2 megaimpulses/s (Mips). 5. The phase relationship between origin-to-insertion muscle length and Ia firing during paw shakes was little affected by doubling or tripling the moment of inertia of the foot. We argue that this refutes the notion that in paw shakes phase reversals occur between muscle fibers and tendons in the muscles studied. 6. Inertial loading of the foot led to small but significant reductions in mean paw-shake frequency. This is consistent with an afferent contribution to the generation of these movements. 7. We conclude that in paw shakes in normal cats, the CNS "chooses" to sensitize Ia-afferents to muscle length variations by increasing dynamic fusimotor action. The resulting ensemble Ia input is very large and is likely to play a significant role in reflexly shaping the alpha-motoneuronal activity responsible for the paw shakes.

Ensemble proprioceptive activity in the cat step cycle: towards a representative look-up chart.

Analysis of the control of movement in tasks such as stepping is severely restricted by the lack of quantitative data on the ensemble activity of afferents in the numerous muscles involved. We have started to build up a quantitative "look-up-chart" of the ensemble afferent and efferent profiles in the cat step cycle. To this end, we have developed software which allows us to digitize afferent firing, muscle length and electromyogram (EMG) activity, and to align segments for averaging by choosing one or more reference points in the step cycle. The ensemble firing of triceps surae Ia afferents showed lower than expected mean and peak rates, whereas triceps group II and Ib afferents were more active than predicted. There were small but significant transients in Ia firing at foot-off and touch-down which could not be explained in terms of origin-to-insertion length lone. They were most likely caused by propagated mechanical transients or tendon compliance effects giving rise to small differences between the origin-to-insertion length and the intramuscular length "seen" by spindles. Net ensemble Ia rates, based on previous estimates of spindle populations, probably exceed 25 kilo-impulses/second (ki.p.s.) in some muscles. Inputs as large as this are likely to contribute significantly to reflex control.

Flexible fusimotor control of muscle spindle feedback during a variety of natural movements.

A refined version of an experimental iterative simulation method is described, which was used to infer, from chronic spindle afferent recordings, type and time course of static and dynamic fusimotor activation during a variety of voluntary movements. When used to estimate overall fusimotor drive (without distinction between static and dynamic action) the method provides unique solutions. However, when generating independent gamma s and gamma d activation profiles, the solutions no longer are strictly unique. Yet the boundary conditions imposed by the type specific characteristics of gamma-action nevertheless permit detection of powerful activation, especially of dynamic efferents. Extending the finding of selective dynamic fusimotor activation during unpredictably imposed and resisted stretches, evidence for powerful, often transient activation of dynamic efferents has now been obtained for three additional motor paradigms. First, initiation of walking was accompanied by mixed fusimotor action. Static drive was stepped up and then maintained, whereas dynamic drive declined after an initial abrupt peak. Second, corrective balancing on a narrow walk beam was characterized by largely maintained static background drive, whilst dynamic activation profiles often exhibited powerful surges or transients, when the animal crouched to regain balance. These preceded subsequent EMG bursts during the stretch phase of crouching by about 300 ms. Third, preparation for landing from rapid lowering featured prominent and possibly selective activation of dynamic fusimotor neurones, which peaked while the animal was in mid-air and declined upon landing, and which preceded the sharp onset of EMG after landing by several hundred milliseconds. In all cases the fusimotor activation profiles were unrelated to the parent muscle EMG and difficult to reconcile with the notion of alpha-gamma linkage or coactivation. These findings then clearly support the concept of flexible central control, particularly of dynamic gamma-motoneurones during certain motor tasks.

Instability in human forearm movements studied with feed-back-controlled muscle vibration.

1. Frequency-modulated vibration was applied to the elbow flexor and extensor tendons to produce reflex movements of the forearm in normal subjects. The modulating (command) signal caused equal and opposite deviations from the 40 Hz carrier frequency so that when flexor vibratory frequency increased, extensor frequency decreased, and vice versa. 2. It is argued that the movements resulted largely from the reflex action of muscle spindle primary afferents whose firing frequency had been 'taken over' and modulated by the vibration. 3. Bode plots relating forearm movements to command signal (modulating) frequency showed the transfer function of the Ia afferent-CNS-muscle-load system to have a low-pass filter characteristic. The phase lag of movement on command increased progressively with command signal frequency, exceeding 180 deg at 3-4 Hz. 4. The transduced forearm movements were fed back to provide the command signal to the vibrators (and thus indirectly to the spindle afferents) via a filter mimicking the dynamic responsiveness of muscle spindle primary endings. Our aim was to 'break into' the reflex arc, and re-route it so that we could artificially vary the gain without significantly altering the dynamics of the pathway. 5. Nearly all subjects developed forearm oscillations (tremor) when the gain exceeded a threshold value. Subjects varied widely in their threshold, though for a given subject the threshold remained fairly constant from day to day. The results suggest that reflexly active individuals may not have a large safety margin with respect to forearm instability. 6. The frequency range of the oscillations observed in seven subjects was 3-8 Hz. The frequencies depended upon the level of flexor-extensor co-contraction, and increased from 3 to 5 Hz at 10% co-contraction to 5-8 Hz at 100% co-contraction. An analysis of the mechanical impedance of the arm provided estimates of tremor frequencies consistent with these results. 7. These unexpectedly low tremor frequencies led us to propose that it may be erroneous to expect stretch reflexes to contribute to forearm tremor in the range 8-12 Hz (e.g. physiological and 'enhanced' physiological tremors). Rather, their contributions should be sought in the range 3-8 Hz (e.g. pathological tremors such as those of Parkinson's and cerebellar disease).

Instability in human forearm movements studied with feed-back-controlled electrical stimulation of muscles.

1. Amplitude-modulated electrical stimulation was applied to the elbow flexors and extensors to produce movements of the forearm in normal subjects. The parameters of the modulating (command) signal were set in isometric trials so as to produce equal and opposite background torques, and equal and supportive torque modulations. 2. Bode plots relating forearm movement to command signal (modulating) frequency showed the muscle-load to have a low-pass characteristic similar to that previously described in the cat, and a slightly larger bandwidth than described previously in man. 3. The transduced forearm signals were fed back to provide the command signal to the stimulators via a filter which mimicked the transfer function of muscle spindle primary endings. In effect this replaced the neural part of the reflex arc with an accessible model, but left the muscle-load effector intact. 4. All six subjects developed forearm oscillations (tremor) when the loop gain exceeded a threshold value. The mean tremor frequency at onset was 4.4 Hz, which was similar to that of the equivalent vibration-evoked tremor (previous paper, Prochazka & Trend, 1988). 5. With the linear spindle model, oscillations tended to grow rapidly in amplitude, and the stimuli became painful. The inclusion of a logarithmic limiting element resulted in stable oscillations, without significant alterations in frequency. This allowed us to study the effect on tremor of including analog delays in the loop, mimicking those associated with peripheral nerve transmission and central reflexes. In one subject, loop delays of 0, 20, 40 and 100 ms resulted in tremor at 4.0, 3.6, 3.0 and 2.1 Hz respectively, as quantified by spectral analysis. 6. By considering separately the phase contributions of the different elements of the reflex arc, including delays, it became clear that muscle-load properties were important in setting the upper limit of tremor frequencies which could conceivably be supported by reflexes. 7. The results support the conclusion of the related vibration study (Prochazka & Trend, 1988), that for moderate levels of background co-contraction, the contribution of stretch reflexes to tremor at the elbow should be sought in the 3-5 Hz range. Exaggerated long-latency reflexes would be expected to reduce these baseline frequencies by 1 or 2 Hz.

Clinical features of ischemia in cerebral arterial border zones after periods of reduced cerebral blood flow.

The clinical syndrome of border-zone ischemia is described in eight patients. Cerebral damage in four occurred during or after cardiac surgery and the other four patients had each experienced a period of severe hypotension. Cerebral blindness and visual disorientation are the most regular features and are produced by ischemic lesions in the parieto-occipital region, the common border-zone territory between all three arterial territories. Some patients show bibrachial sensorimotor impairment and a disturbance of volitional saccadic eye movement caused by more anteriorly placed ischemia in the anterior-middle artery border zone. Some show a temporary dyslexia/dysgraphia and memory defect related to bilateral parietotemporal lesions in the middle-posterior border zone.

Relative displacements in muscle and tendon during human arm movements.

1. X-ray, cine and video recordings were made of the movement of radio-opaque markers injected into the musculo-tendinous junctions of biceps brachii muscle. 2. In strong isometric contractions, the distal tendon of the long head of biceps lengthened by about 2% of its estimated rest length. 3. During voluntary isotonic elbow flexion-extension movements at frequencies up to 5.5 Hz there was no detectable phase shift between intramuscular and joint displacements. 4. In the fastest alternating movements (5.5-6.7 Hz) small phase advances developed in the muscle. 5. We conclude that human tendons do stretch during muscle contraction, but not enough to cause intramuscular phase reversals in rapid unloaded movements. This in turn means that muscle spindles shorten and lengthen virtually in phase with joint movements under most conditions.