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Biomedical subjects

C H Lücking

Publications and source records attributed to C H Lücking.

At least 19 recordsLinked to original sources

Clinical and polymyographic investigation of spasmodic torticollis.

Polymyographic recordings were used to identify the most dystonic muscles suitable for local injection with botulinum toxin in 100 patients with spasmodic torticollis (TS). Rotating TS (72% of the patients) was due to dystonic activity of the splenius muscle ipsilateral to and/or the sternocleidomastoid muscle contralateral to the side of chin deviation. One-third of these patients had also dystonic activation of the contralateral splenius muscle and, rarely, the contralateral trapezius muscle. Ten patients had laterocollis due to dystonic activation of all recorded muscles on one side of the neck. Nine patients had retrocollis due to activity of both splenius muscles and rarely additional activity in both trapezius muscles. The type of dystonic muscle activity was found to be tonic, phasic or tremulous. Besides the evaluation of spontaneous dystonic EMG activity further examination during the "geste antagoniste" or the muscle activity during rotating head movements can provide additional information. It is concluded that polymyography may provide a rationale for identifying the dystonic muscles underlying the different forms of TS. It may prove to be helpful for the successful therapy with botulinum toxin and may be useful in differentiating tremulous torticollis from other types of head tremor.

Adolescent

Different effects of serotonin (5-HT) uptake blockers in caudate nucleus and hippocampus of the rabbit: role of monoamine oxidase in dopaminergic terminals.

Slices of rabbit hippocampus or caudate nucleus were incubated with [3H]-5-HT (0.1 microM, 60 min) or with [3H]-DA. In hippocampal tissue, the 5-HT uptake blockers chlorimipramine, fluvoxamine, and 6-nitroquipazine (0.1, 1, 10 microM) reduced the percentage content of [3H]-5-HT in a concentration dependent manner. The degree of inhibition of [3H]-5-HT content produced by the 5-HT uptake inhibitors was not affected by the MAO inhibitors pargyline or amezinium (which by themselves enhanced [3H] loading) or the catecholamine uptake inhibitor nomifensine (which by itself did not affect [3H] loading). In caudate nucleus tissue, however, the [3H]-5-HT accumulation was reduced only at the highest concentration of the 5-HT uptake blockers (10 microM). In the additional presence of the MAO inhibitors or nomifensine (which by themselves increased or diminished, respectively, the [3H] labelling) the 5-HT uptake inhibitors became more potent in reducing the percentage [3H]-5-HT accumulation of caudate nucleus slices. These results indicate (1) that a false labelling of [3H]-5-HT into dopaminergic terminals in the caudate nucleus can be prevented by nomifensine, (2) that the 5-HT uptake blockers seem to accumulate within the dopaminergic terminals, where they may display a MAO inhibitory property. The 5-HT uptake blockers were ineffective on the percentage tritium accumulation of caudate nucleus slices incubated with [3H]-DA, regardless of the presence of pargyline or nomifensine. Tritiated DA and deaminated [3H]-metabolites were separated in the superfusate of [3H]-DA-release experiments in caudate nucleus tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

Dependence of presaccadic cortical potentials on the type of saccadic eye movement.

Premovement cortical potentials were studied with 4 types of saccadic eye movement: (a) visually triggered saccades of normal reaction time (RT; regular saccades); (b) visually triggered saccades of extremely short RT (express saccades); (c) saccades towards predicted target locations (anticipatory saccades); (d) saccades back towards predicted location of fixation point (refixation saccades). With all 4 saccade types a "presaccadic negativity" with the maximum at the vertex (Cz) was observed. A bilaterally symmetrical component contained in this potential (being smallest with almost unconsciously performed refixation saccades and smaller in trained than in naive subjects) appeared to be related mainly to the subjects' volitional effort. In addition, anticipatory and refixation saccades were preceded by an early, widespread contralateral negativity, which we relate to cortical activities that prepare, in general terms, action within or towards the hemifield containing the saccade goal. During the 60 msec before anticipatory saccades, a negativity occurred over the contralateral central lead, which may reflect neural activation in the frontal eye field (FEF) and premotor cortex. In contrast, regular saccades were preceded 30 msec before onset by a negativity over the contralateral parietal cortex, which probably reflects an activation of parietal visuo-motor neurons. No lateralization of the cortical potentials was observed before express saccades, which suggests that these saccades are generated in a reflex-like way mainly by subcortical mechanisms.

Adult

Reciprocal inhibition of forearm flexor muscles in spasmodic torticollis.

Reciprocal inhibition between forearm extensor and flexor muscles was tested by means of an H-reflex technique in patients with spasmodic torticollis and normal controls. In both, patients and controls three different phases of reciprocal inhibition could be demonstrated with maximal inhibition at conditioning test intervals of 0 ms, 15 ms and 100 ms, respectively. However, the quantitative amount of this inhibition was different for the patients and the controls. Significantly less inhibition was found for the second and the third phase of reciprocal inhibition in the patient group. Discriminant analysis showed a clear separation between normal subjects and patients if the amount of reciprocal inhibition of the second and third phase were taken into account. We were not able to detect any side differences neither for the patients nor for the controls. The findings demonstrate a functional disturbance of motor control mechanisms of a clinically unaffected extremity in spasmodic torticollis. This is believed to reflect a bilateral disturbance most likely within the basal ganglia or their outflow. Therefore, our data support the idea, that spasmodic torticollis is associated with or even due to a generalized rather than a focal disturbance of motor control mechanisms.

Analysis of Variance

Inhibitory effects of the antiparkinsonian drugs memantine and amantadine on N-methyl-D-aspartate-evoked acetylcholine release in the rabbit caudate nucleus in vitro.

Slices of the rabbit caudate nucleus were incubated with [3H]choline or [3H]dopamine and then superfused continuously with Mg(++)-free medium. Stimulation with N-methyl-D-aspartate (NMDA), alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA), L-glutamate and kainic acid (in that rank order of potencies) caused a concentration-dependent increase in [3H]ACh efflux, which was abolished in the presence of Mg++. This kind of release was Ca(++)-dependent and tetrodotoxin-sensitive. In contrast, NMDA was hardly effective in stimulating [3H]ACh release from hippocampal or cortical slices, as well as [3H]dopamine release from slices of rabbit caudate nucleus. Hence, the presence of cell bodies of stimulated neurons seems to be a prerequisite for the induction of release via NMDA receptors. Dizocilpine [(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate] at nanomolar concentrations, as well as memantine and amantadine at low micromolar concentrations, inhibited the L-glutamate- and NMDA-evoked [3H]ACh release in a concentration-dependent, noncompetitive and use-dependent manner. Also (+/-)-2-amino-5-phosphopentanoic acid at micromolar concentrations depressed the L-glutamate- and NMDA-induced release, acting, however, in a competitive manner. It is concluded that, by antagonizing NMDA receptor-mediated ACh release, memantine and amantadine may act as functional "anticholinergics" when administered clinically to treat Parkinson's disease.

Acetylcholine

Tremor in reflex sympathetic dystrophy.

Postural hand tremor was quantitatively investigated on both sides in 21 patients suffering from unilateral reflex sympathetic dystrophy of the upper extremity. On the affected side, enhanced tremor amplitude, with a mean tremor frequency of 7.2 Hz, was found in 57% of the patients. The appearance of tremor did not correlate to the occurrence of a single clinical symptom of reflex sympathetic dystrophy. On loading with increasing weight, the frequency of this pathological tremor shifted toward lower values, as it is found in physiological tremor. However, the peak frequencies of the electromyogram remained more or less stable. On recovery from this condition, the reflex sympathetic dystrophy tremor disappeared. Acute sympatholytic intervention could normalize reflex sympathetic dystrophy tremor. This would suggest that the sympathetic supply of the affected extremity contributes to the tremor in reflex sympathetic dystrophy. In conclusion, it is suggested that reflex sympathetic dystrophy should be included among the causes of tremor. According to our findings, tremor in reflex sympathetic dystrophy should be regarded as an enhanced physiological tremor.

Electromyography

Effects of electric and magnetic transcranial stimulation on long latency reflexes.

The interaction of transcranial electric and magnetic brain stimulation with electrically elicited short- and long latency reflexes (LLR) of hand and forearm flexor muscles has been investigated in normal subjects. In the first paradigm, the motor potential evoked in thenar muscles by transcranial stimulation was conditioned by median nerve stimulation at various conditioning-test intervals. At short intervals (electric: 5-12.5 ms, magnetic: 0-7.5 ms) facilitation occurred that corresponded to the H-reflex and at longer intervals (electric: 25-40 ms, magnetic: 22.5-35 ms) there was a facilitation corresponding to the LLR. Electric and magnetic stimulation resulted in a similar degree of facilitation. A second paradigm investigated the facilitation of the forearm flexor H-reflex by a cutaneo-muscular LLR elicited by radial superficial nerve stimulation and transcranial stimulation used separately or together. When electric and magnetic brain stimulation were compared, magnetic brain stimulation was followed by significant extrafacilitation but electric stimulation was not. This result favours an interaction between the afferent volley eliciting the LLR and transcranial magnetic stimulation most likely at supraspinal level.

Adult

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.

Aged

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.

Electroencephalography

Parkinson's disease patient's behaviour in a covered maze learning task.

A computerized maze task was constructed that allowed only partial vision of the maze structure and produced measurements for separate analysis of cognitive processes described as impaired in Parkinson's disease. Eighteen patients suffering from mild Parkinson's disease and 18 individually matched normal controls were investigated. Baseline task response times were found to be identical for both groups. Differences between patients' and controls' performance could be related to (a) a response bias in Parkinson patients that favoured repetition of the previous action and slowed down shifting and (b) an impairment of multistep plan generation. It is speculated that the response bias reflects the disinhibition of cortico-thalamo-cortical reverberation loops which results from striatal dopamine depletion.

Aged

Physiology and clinical applications of hand muscle reflexes.

Hand muscle reflexes to stretch or electric stimulation of mixed nerves consist of two main components, the short latency reflex (SLR, M1) or Hoffmann reflex (HR) and the long latency reflex (LLR, M2). The SLR is most likely a spinal, monosynaptic reflex and all the evidence presently available supports a transcortical pathway of the LLR. Investigations in normal subjects demonstrate that the LLR is a reflex mediated by fast conducting muscle and cutaneous afferents. Group II muscle afferents do not significantly contribute to this reflex and it cannot be explained by repetitive excitation of spinal oligosynaptic pathways. These findings should not be uncritically generalized to other muscle groups, because the central and peripheral mechanisms apparently differ according to the body region and mode of stimulation. The LLR of hand muscles is most likely involved in skillful movements of the fingers. It is believed to assist rapid compensatory responses to unexpected disturbances. In addition to the main component of the LLR, which is called LLR II, the study of electrically elicited thenar reflexes following stimulation of the median nerve disclosed further LLR components, the LLR I and the LLR III. The latter reflexes are rarely seen in normal subjects but have a significance in several diseases. Several abnormalities could be demonstrated in different diseases. Enhanced HR and reduced LLR are found in spasticity of various origin. Enhanced LLR I are frequently seen in Parkinson's disease, essential tremor and reflex myoclonus. Absent or reduced LLR II is found in Huntington's disease and in different focal brain lesions but not in symptomatic choreatic syndromes of other origin. Delayed latencies of the LLR II or absent LLR II have been described in multiple sclerosis. Enhanced LLR III may occur in cerebellar diseases. The method to elicit LLR of thenar muscles by electric stimulation may prove to be useful for clinical neurophysiology.

Electric Stimulation

Symptomatic and essential rhythmic palatal myoclonus.

Rhythmic palatal myoclonus (RPM) is a rare movement disorder consisting of continuous synchronous jerks of the soft palate, muscles innervated by other cranial nerves and, rarely, trunk and limb muscles. It usually develops secondary to brainstem or cerebellar disease (symptomatic RPM). Some patients, however, fail to show evidence of a structural lesion (essential RPM). A total of 287 cases with RPM from the literature including 210 cases with symptomatic and 77 cases with essential RPM have been reviewed and analysed statistically to look for criteria separating the two conditions. Patients with essential RPM usually have objective earclicks as their typical complaint which is rare in the symptomatic form. Eye and extremity muscles are never involved. The jerk frequency is lower in essential than in symptomatic RPM. Patients with essential RPM are younger and have a balanced sex distribution as compared with a male preponderance in the symptomatic form. The rhythmicity of RPM seems to be more profoundly influenced by sleep, coma and general anaesthesia in essential than in symptomatic RPM. We conclude from these results that essential RPM should be separated as a distinct clinical entity. Symptomatic RPM is a rhythmic movement disorder whose pathogenesis is quite well established. The cells of the hypertrophied inferior olives are believed to represent the oscillator. Among other possibilities, essential RPM may represent its functional analogue, based on transmitter changes only. Such a relationship could be of theoretical interest for the understanding of rhythmic hyperkinesias in general.

Age Factors

New mutation to Huntington's disease.

We report a large family with an isolated case of Huntington's disease (HD), which is probably the result of a new mutation. The patient developed clinical signs typical of HD at the age of 36. The clinical course of the patient's disease is documented by several clinical admissions over a period of 14 years at present. The family history is strikingly negative with the parents having been clearly unaffected into their 80s and with 13 older and two younger, living, healthy sibs. Extensive testing of polymorphic markers (blood groups, red cell and serum proteins, HLA antigens) showed no indication of non-paternity, but rather gave strong support to the hypothesis that the proband is a full sib. In addition, DNA typing for several RFLPs known to be closely linked to the HD gene locus indicated that several clearly unaffected sibs share one or the other or both of the patient's haplotypes. This is further evidence in favour of the hypothesis of a new mutation at the HD locus. The posterior probability of a new mutation to HD in the patient exceeds 99%, even if an a priori probability of non-paternity of 10% and a mutation rate of HD of 10(-7) is assumed.

DNA

Hand muscle reflexes following electrical stimulation in choreatic movement disorders.

Thenar reflexes following electrical stimulation of the median nerve (containing proprioceptive and cutaneous afferents) and the radial superficial nerve (cutaneous afferents only) were investigated in 23 patients with manifest Huntington's disease (HD) at an early stage, in 17 clinically healthy descendants of HD-patients and in 18 patients with choreatic hyperkinesia due to various aetiologies other than HD. In 61% of the patients with early HD the long-latency reflexes (LLR) were uni- or bilaterally absent in response to both median nerve and radial superficial nerve stimulation. The remaining patients had a diminished mean amplitude and mean duration of their LLR. In contrast, offspring and patients with symptomatic chorea had preserved LLR which did not differ in amplitude or duration from normal controls. Additionally, the mean amplitude and mean duration of the Hoffmaan-reflex (HR) was found to be increased in patients with HD and their offspring but not in patients with other aetiologies. It is concluded (1) that the loss of LLR is not related to the choreatic hyperkinesia itself but to the degeneration of a hitherto poorly defined neuronal circuit in HD; (2) that among a variety of diseases presenting with chorea, the loss of LLR seems to be specific for HD; (3) that the testing of hand muscle reflexes in choreatic movement disorders is helpful for the differential diagnosis of early HD but not for the detection of gene carriers among offspring of patients with HD.

Afferent Pathways

Activation of A1 adenosine receptors decreases the release of serotonin in the rabbit hippocampus, but not in the caudate nucleus.

The effects of A1 adenosine receptor ligands on the evoked release of serotonin (5-HT) were studied in slices of the hippocampus and the caudate nucleus of the rabbit, preincubated with 3H-5-HT. In hippocampal tissue electrical stimulation elicited a release which was inhibited by the adenosine receptor agonist N6-cyclohexyladenosine (CHA) and enhanced by the selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). The concentration-response curve of CHA was shifted to the right by DPCPX. The shift corresponded to a pA2 value of 9.4 for DPCPX. CHA, R-N6-phenylisopropyladenosine (R-PIA) and DPCPX were ineffective in caudate nucleus tissue. When instead of electrical pulses high K+ was used to induce 5-HT release in the presence of the Na+ channel blocker tetrodotoxin (TTX), which was present in order to exclude effects mediated by interneurones, CHA was equally effective in the hippocampus but again failed to modify 5-HT release in the caudate nucleus. The disinhibition by DPCPX of the evoked 5-HT release was used to calculate the extracellular concentration of endogenous adenosine at the A1 receptor. The calculation greatly depended on the dissociation constant of adenosine at the A1 receptor. It is concluded that A1 adenosine receptors, activated by the endogenous agonist at a concentration of about 0.7 mumol/l, are located on serotonergic nerve endings in the hippocampus, but not in the caudate nucleus. The estimated extracellular concentration of endogenous adenosine is in reasonable agreement with actually measured concentrations reported in the literature.

Animals

The diagnostic significance of long-latency reflexes in multiple sclerosis.

Reflexes of thenar muscles after median or radial superficial nerve stimulation have been investigated in both hands of 47 patients with probable or definite multiple sclerosis (MS) and compared with somatosensory evoked potentials (SEPs) to median nerve stimulation. A delay or absence of long-latency reflexes (LLRs) was found as pathological patterns. The results after median or radial superficial nerve stimulation were usually both pathologic or both normal except in cases with latencies at the upper limit of normal values. Pathological results of reflex testing were obtained in 61% of the patients with probable MS and in 79% of those with definite MS. Abnormal SEPs were found in 44% of the patients with probable MS compared to 62% with definite MS. All cases which had pathologic SEPs also had pathologic LLR. Hence, LLR testing detected more abnormalities than the routine median nerve SEP testing that has been used.

Adolescent

Flunarizine vs. propranolol in the prophylaxis of migraine: two double-blind comparative studies in more than 400 patients.

In the course of a 16 weeks' interval treatment of migraine in connection with two multicenter double-blind studies, flunarizine was compared with propranolol in patients suffering predominantly from "classical migraine". Eighty-seven patients from 12 outpatient departments were admitted to the first study, while 434 patients from 99 medical practices participated in the second study. After each month of treatment, the patients were clinically evaluated, and the number, duration, and severity of attacks were documented. Concerning the frequency and intensity of attacks, additional analgesics consumption and overall evaluation, both drugs proved to be highly effective in the practice as well as in the hospital study. The percentage and severity of side-effects were comparable in the two treatment groups. Summarizing, it may be stated that the studies proved the efficacy of flunarizine to be rather similar to that of propranolol in the prophylactic treatment of migraine.

Adult