Drug-induced confusional states: the usual suspects?

BACKGROUND: Acute confusional state (ACS) is a frequent reason for hospital admission. This study examines retrospectively the frequency by which individual drugs were found responsible for ACS. RESULTS: Drug-induced ACS was found in 65 (18.8%) of 346 hospital admissions for acute confusion. The most frequent causative substances were dopaminergic drugs in Parkinsonian patients (24.2%), diuretics (15.1%), tricyclic or tetracyclic antidepressants (13.6%) and benzodiazepines (13.6%). Almost half of the patients were demented, and in one-third of these, dementia had not been diagnosed hitherto. CONCLUSION: The data suggest that diuretics by way of causing hyponatraemia are as relevant a cause of ACS as dopaminergic or anticholinergic substances.

Diagnostic yield of cerebral imaging in patients with acute confusion.

OBJECTIVE: Acute confusion (AC) is a frequent reason for hospital admission in elderly patients. Although in majority of cases the cause is a systemic disorder (e.g., dehydration or septicaemia), patients are frequently subjected to cerebral imaging. This study was undertaken to find clinical predictors of normal cerebral computed tomography (CCT) or magnetic resonance imaging (MRI) scans in AC. METHODS: Retrospective study of 294 patients admitted with AC of unknown origin, of whom 178 received cerebral imaging. RESULTS: The rate of pathological imaging studies was 14%. The best single predictor of a normal brain scan was the absence of focal signs. Patients without focal abnormalities and either fever or dehydration had a probability of 0.96 of having a normal CCT or MRI. In demented patients without focal signs, the predictive value for a normal brain scan was 0.98, and if either patients with drowsiness were excluded or the existence of fever or dehydration was added as a selection criterion, all patients had normal scans. CONCLUSIONS: Patients with AC without focal signs and with either evidence for a medical aetiology of delirium or prediagnosed dementia are at a very low risk of having focal lesions in their CCT or MRI.

[Complex regional pain syndrome I and II. What effects the outcome?]. / Komplexe regionale Schmerzsyndrome CRPS I und II. Was beeinflusst den Langzeitverlauf?

INTRODUCTION: The results of clinical studies have raised doubts on the effectiveness of regional sympathetic blocks with guanethidine (IVRSB) in patients suffering from complex regional pain syndrome (CRPS). We conducted a retrospective analysis of long-term results in our patients and searched for possible factors predicting long-term outcome after IVRSB: METHODS: After approval by our ethics commission and written informed consent, 42/44 patients were included. We documented diagnosis, history, therapy and long-term result from charts. Long-term results were also obtained from a questionnaire administered to the patients. These were defined as very good (reduction of pain > or =75%), good (pain reduction <75% and > or =50%), moderate (pain reduction <50% and > or =25%) or poor (pain reduction <25%). The association of a moderate or poor outcome with the factors age, gender, duration of time until therapy, pain intensity before therapy, dose of applied guanethidine and duration of therapy was calculated by odds ratio. Confidence intervals for the odds ratios were determined by Woolfs approximation. RESULTS: After a mean duration of 18 months, the outcome was classified as very good in 14, good in 13, moderate in 5 and poor in 10 patients. An increased rate of moderate or poor outcome was associated with age<60 years (OR=4.00, CI 1.04-15.26), male gender (OR=2.93, CI 0.71-12.11) and duration of therapy>2 weeks (OR=3.27, CI 0.86-12.36). The factors duration of time until therapy, initial pain intensity and total dose of guanethidine were not associated with increased rates of moderate or poor outcome. CONCLUSION: We only seldom observed a complete functional restoration after CRPS. Male patients <60 years showed an increased risk of developing chronic pain. It remains unclear whether the risk of chronic pain reflects different responses to therapy or differences in the natural course of the disease in our patients. A meta-analysis of randomised trials of IVRSB in CRPS failed to prove the effectiveness of this intervention. If other investigations confirm our impression, future studies of CRPS-treatments should be planned and analysed with regard to the possible influence of the natural course and different risks of chronic pain among patients with CRPS.

Development of the corticospinal system and hand motor function: central conduction times and motor performance tests.

Maturation of the corticospinal (CS) tract and hand motor function provide paradigms for central nervous system development. In this study, involving 112 participants (aged from 0.2 to 30 years), we evaluated central motor conduction times (CMCT) obtained with transcranial magnetic stimulation (TMS) during preinnervation conditions of facilitation and relaxation. Auditory reaction time, velocity of a ballistic movement of the arm, finger tapping, diadochokinesis, and fine motor visuomanual tracking were also examined. The maturation profiles for every parameter were calculated. CMCTs for the different preinnervation conditions reached adult values at different times and this could be explained by maturation of excitability at the cortical and spinal level. A stable phase for CMCTs and reaction time was reached during childhood. Parameters which measured motor speed and skill indicated that the development of these continued into adulthood. The maturation of the fast CS tract seems to be completed before the acquisition of the related motor performance has been accomplished. In conclusion, we could demonstrate that data from several neurophysiological methods can be combined and used to study the maturation of the function of the nervous system. This approach could allow appraisal of pathological conditions that show parallels with omissions or lack of developmental progress.

Fast corticospinal system and motor performance in children: conduction proceeds skill.

Transcranial magnetic stimulation and motor performance tests were used to study the correlation between corticospinal maturation and actual motor performance in a group of young school children (n = 10, mean age = 7 years, age range = 6-9 years). The results were compared with normal adults (n = 10, mean age = 24 years, age range = 22-26 years). In children the central conduction time under the preinnervation condition of facilitation and the postexcitatory silent period was similar to that in adults. However, the central conduction time under relaxation, the latency jump (defined as the difference between the two preinnervation conditions), and the stimulus intensity were statistically different between children and adults (P < 0.01-0.001). Children did not reach the same level of performance as adults in any of the motor performance tasks (simple acoustic reaction time, tapping, ballistic movement, tracking, and diadochokinesis) (P < 0.05-0.01). The results indicate that at an early school age, children already possess mature fast corticospinal pathways able to access spinal motoneurons through the pyramidal tract. However, despite the partially adult-like level of neuronal maturation, young school children were not able to perform deliberate motor actions with the same proficiency as adults.

Abnormalities of tracking behavior in Parkinson's disease.

Tracking behavior in Parkinsonian patients and in a control group of elderly subjects was studied using a one-dimensional pursuit tracking task. The most obvious abnormality in patients with Parkinson's disease is a tendency to restrict movements to a limited range, thus "clipping" the extreme deviations of the target, reflected by movement arrests, reduced amplitude gain, and decreased velocity gain. Most of the tracking parameters were selectively sensitive to parkinsonian as opposed to age-related impairment of motor functions, the only exception being directional errors, which were more frequent in the old age group. Movement range and amplitude gain were related to general disability as reflected by the Hoehn and Yahr stage. Amplitude gain was also the single factor with the strongest influence on tracking error and was smaller for large target deviations in both groups. A reduction in target velocity caused a significant increase in amplitude gain, suggesting a compensatory strategy (amplitude/lag trade-off) as one possible cause of low-amplitude gain. Decreased peak velocity did not contribute significantly to tracking error. These findings suggest that reduced movement amplitude and slowness are independent phenomena, of which only the former has a significant influence on tracking performance in the task used. Patients with Parkinson's disease showed no impairment of motor learning on this task.

Contractile properties of lower leg muscles are normal in Parkinson's disease.

Contraction parameters (time-to-peak and half relaxation time), responses to short tetani and resistance to stretch were studied in the lower leg muscles of Parkinsonian patients and in age-matched controls. It was possible to distinguish between muscle groups of different fibre type composition in normal subjects on the basis of their contraction and relaxation velocities. These parameters, however, failed to show any abnormalities in the patient group. The only abnormal finding in Parkinsonian subjects was an increased resistance to passive stretch under static conditions, presumably elastic in origin. The results are evidence against a contribution of altered contractile properties to muscular rigidity in Parkinsonism.

Statistical evaluation of slow brain potentials on the basis of single trials.

The amplitude of slow brain potentials is related to the complexity of the task performed. Therefore, the large potentials related to the processing of complex tasks (tracking, writing, mental acts) may be analysed statistically on a single trial basis. This opens up a range of new facilities for within-session tests of significance. Prior to evaluation, signals are passed through several automatic error compensation routines: smoothing, trend removal, subtraction of eye artifacts, rejection of trials with random artifacts. The shape of the task potential approximates well to a rectangular elevation of cortical negativity, with the mean amplitude over a pre-event baseline being used as the main statistical parameter. Non-parametric statistical tests are preferred for evaluation. Application of the method is demonstrated for a tracking paradigm.

Motor Habits in Visuo-manual Tracking: Manifestation of an Unconscious Short-term Motor Memory?

Normal subjects were tested in short, repetitive trials of a tracking task, with an identical shape of target movement being used throughout one session. Analysis of the net error curves (pursuit minus target movement) revealed that subjects regularly exhibit a remoteness effect: neighbouring trials were more similar than distant ones. The effect is demonstrated to be stronger in the absence of visual cues, and was found to be absent in a patient with complete loss of proprioception when he was performing without visual feedback as well.The results are discussed in terms of a short term memory store contributing to unconscious movement habits in tracking. This may represent part of the motor learning process working together with conscious visuo-motor control mechanisms. Its function is probably related to the acquisition of automatic movements.

Automatic recognition of random artifacts in recordings of slow brain potentials: a bias-free method.

A method for computerized recognition of random artifacts in recordings of slow brain potentials is presented. It is based on systematic comparison of the shape of single trial EEG segments with all other trials obtained in the same experiment. This is possible because, in contrast to short-latency event related potentials, a plateau of EEG negativity during complex tasks can often be detected in single trails. After linear trend removal and subtraction of EOG artifacts, similarity of pairs of single trials is established by point-to-point linear regression analysis, the total score of a trial being defined as the mean correlation coefficient (R) resulting from comparison to all other trials. Selection is then performed by setting a critical value for R, admitting for averaging only trials with a mean correlation coefficient above the critical value. An example is given in which the method is applied to recordings of slow brain potentials during a manual tracking task.

Short-range elasticity and resting tension of relaxed human lower leg muscles.

1. Tension responses of relaxed human lower leg muscles were recorded during applied triangular stretch cycles at a range of constant angular velocities which were below the threshold for inducing stretch reflexes. 2. Length-tension curves so obtained begin with a steep initial rising phase which is demonstrated to be equivalent to the 'short-range elastic component' (s.r.e.c.) observed in resting frog muscle (Hill, 1968). The s.r.e.c. develops only gradually following a stretch-release cycle. The time course can be described by a saturation function. It is suggested that this can be explained as resulting from a slow shift of the kinetic equilibrium between attached and detached cross-bridges towards attached cross-bridges. A kinetic model is presented, by which the sum of the cross-bridge formation and decay rate constants can be calculated from the saturation curves. 3. The recovery of resting tension following a stretch-release cycle proceeds at a significantly higher rate than the development of the s.r.e.c. Resting tension is also selectively influenced by passive movements of very small amplitude. This further suggests that the s.r.e.c. and resting tension are generated by different sources.

Chronic transformation of muscle in spasticity: a peripheral contribution to increased tone.

Mechanical properties of relaxed lower leg muscles were assessed by torque measurements during imposed constant velocity dorsiflexion-plantarflexion cycles. At low angular velocities, they exhibited an elastic and an energy-consuming, velocity-independent (plastic) resistance. In most patients with long-standing spasticity, both of these were enhanced. The results support the hypothesis of secondary structural changes of muscles in spasticity.

Acoustic phenomena in the latent period of skeletal muscle: a simple method for in-vivo measurement of the electro-mechanic latency (EML).

An in-vivo method for the assessment of the latency of muscular contraction is presented. It is based on acoustic registration of muscular thickening by a microphone. It was found that the recorded sound wave is often preceded by a small wave of opposite polarity (flattening of the muscle belly) which is an acoustic correlate of the latency relaxation. Strong direct stimulation produced another small sound wave at the beginning of the latent period. The physiological significance of these findings is discussed.

[Slow brain potentials in writing: the correlation between writing hand and speech dominance in right-handed humans]. / Langsame Hirnpotentiale beim Schreiben: Die Wechselwirkung von Schreibhand und Sprachdominanz bei Rechtshändern.

1. Slow cerebral potential shifts were recorded from the scalp over both cerebral hemispheres by retrograde summation while 23 right-handers were writing. Averaging included writing errors, but eliminated eye movements and other artifacts. Repeated writing of the same word or sentence was compared to writing different dictated words, to drawings, and to other control experiments. 2. Surface negative readiness potentials (Bereitschaftspotential) appeared about 1 s before writing, which was similar to those preceding other voluntary movements. 3. During writing, the writing potentials in different cortical regions began with a negative increase of the Bereitschaftspotential, usually followed by a plateau or positive waves. One or several biphasic potentials persisted for another 2 s after writing had ceased. 4. The writing potentials had rather constant forms in the same individual, but showed large interindividual variations of form and polarity. The largest initial negativity (with both ear lobes serving as reference) occurred at the vertex and the left motor region contralateral to the writing hand. 5. The left hemispheric preponderance of writing potentials, maximal at the precentral region contralateral to the writing hand, was less marked when writing with the left hand. An interaction of the writing hand and language dominance is assumed. 6. Writing the same word or short sentence repeatedly caused potentials of larger amplitude than the preceding readiness potentials. Writing dictated words or drawing figures after verbal stimuli that require language processing caused larger potentials in the left hemisphere than did repeated word writing. 7. The fact that negative potentials with larger left hemispheric amplitudes appear after verbal stimuli may indicate that language information is processed in the speech-dominant hemisphere before and during writing or drawing. 8. By variously combining bipolar leads, the lateral differences of the potential fields can be more clearly distinguished than by using only unipolar leads with ear reference.

Treatment of acute inflammatory polyneuropathy.

Most patients with acute inflammatory polyneuropathy (AIP) recover spontaneously, but the time course of the illness is unpredictable so that the results of treatment are difficult to assess. Three decades of retrospective reports of steroid treatment fail to demonstrate any striking beneficial effect. In a randomized trial of prednisolone, starting dose 60 mg daily, 21 treated patients improved more slowly than 19 untreated patients. By contrast, in rats immunized with bovine nerve root myelin, prednisolone at 10 mg/kg reduced the severity and duration of experimental allergic neuritis (EAN), the putative animal model for AIP. This discrepancy might reflect the greater difficulty of clinical as opposed to animal therapeutic trials or indicate that EAN is not the appropriate model for the human disease. Immunosuppressive drugs, plasmapheresis and other agents have also been employed, but their efficacy cannot be decided from the available case report. The role of similar agents in chronic progressive and relapsing inflammatory neuropathy cannot yet be resolved, but in some patients steroids do appear to be valuable.