Long-term implant of intramuscular sensors and nerve transfers for wireless control of robotic arms in above-elbow amputees.

Targeted muscle reinnervation (TMR) amplifies the electrical activity of nerves at the stump of amputees by redirecting them in remnant muscles above the amputation. The electrical activity of the reinnervated muscles can be used to extract natural control signals. Nonetheless, current control systems, mainly based on noninvasive muscle recordings, fail to provide accurate and reliable control over time. This is one of the major reasons for prosthetic abandonment. This prospective interventional study includes three unilateral above-elbow amputees and reports the long-term (2.5 years) implant of wireless myoelectric sensors in the reinnervation sites after TMR and their use for control of robotic arms in daily life. It therefore demonstrates the clinical viability of chronically implanted myoelectric interfaces that amplify nerve activity through TMR. The patients showed substantial functional improvements using the implanted system compared with control based on surface electrodes. The combination of TMR and chronically implanted sensors may drastically improve robotic limb replacement in above-elbow amputees.

[Selective nerve transfers to improve the control of myoelectrical arm prostheses]. / Selektive Nerventransfers zur verbesserten Steuerung myoelektrischer Armprothesen.

To date, the movement of myoelectrical arm prostheses proceeds via two transcutaneous electrodes that are controlled by two separately innervated muscle groups. The various control levels are chosen by co-contractions of these muscles and the respective level is linearly controlled by the same muscles. A harmonious course of movement as in the corresponding natural pattern of motion is not possible in this way. An appreciable improvement would be given by the control of the individual movement levels by signals that correspond neuronally with the natural pattern of motion. Just recently, prostheses with six control levels have been realised technically. The objective is to separate the major arm nerves, such as the musculocutaneous nerve, radial nerve, median nerve and ulnar nerve, from the proximal arm nerve plexus and to transfer them to the residual nerve branches of muscles near the stem in order to create meaningful neuromuscular units that can serve as impulse sources for myoelectrical prosthesis. As target muscles, above all, one can consider the major/minor pectoral muscles or, respectively, the latissimus muscle. According to the activity of the donor nerves, these muscles would contract and control the prosthesis via transcutaneous electrode. In this way, a harmonious control corresponding intuitively to the natural pattern of movement would be possible without the necessity for the patient to continuously switch between the various control levels. Prerequisites for this are intact proximal muscle groups and a more or less intact arm nerve plexus with the possibility to isolate donor nerves according to the topographic-anatomic situation. For this reason, a preoperative MRI examination, a high resolution sonographic study and balancing NLG and EMG of the residual nerve plexus are necessary. For the preoperative planning phase as well as for the postoperative follow-up, a detailed procedure has been established, in cooperation with the innovation department of the Otto Bock company, to create the most meaningful switch levels, to optimise electrode placement as well as to clarify prosthesis incorporation. Finally, a complex rehabilitation programme is necessary for the patient to achieve an optimal result.

A novel mechanotronic orthosis enables symmetrical gait kinematics in a patient with a femoral nerve palsy - a case study.

The usage of stance- and swing-phase control orthoses (SSCOs) is a good option in patients with neuromuscular insufficiency of the quadriceps muscle in a broad range of musculo-skeletal disorders. The subjective sensation of improved mobility in daily life and walking comfort could be objectively confirmed by the ability to walk without crutches and by harmonization of the gait patterns in hip and knee. They could also be a considered mobility device after limb salvage surgery, which may even have an impact on preoperative decision making. IMPLICATIONS FOR REHABILITATION Symmetric gate in spite of femoral nerve palsy. Early gate improvements even after hours. High patient?s motivation to use the device.

In vivo release of corticosterone in discrete brain areas of rats. A push-pull perfusion study.

The spontaneous and depolarization-induced release of corticosterone was studied in the medial hypothalamus (MH) and the central amygdala (AC) in vivo, using a push-pull perfusion system. Significant variations in the spontaneous release of corticosterone could be observed over time (3-8 h). Corticosterone in the brain superfusates did not seem to stem from adrenocortical sites since a continuous release of the glucocorticoid could also be followed in bilateral adrenalectomized rats. Superfusion of MH and AC with depolarizing stimuli led to an enhanced release of corticosterone. Of greater general significance is the first demonstration that the release of a steroid hormone can be measured in discrete brain areas under in vivo conditions.

Presynaptic regulation of the release of catecholamines in the cat hypothalamus.

The posterior hypothalamus of cats was superfused through a push-pull cannula and the release of endogenous catecholamines was determined in the superfusate. Superfusion with yohimbine, isoprenaline, salbutamol or tazolol increased, while superfusion with propranolol decreased, the release of all three catecholamines. Transection of the brain caudal to the hypothalamus inhibited 'resting' and drug-induced release. It is concluded that alpha- and beta-adrenoceptors of the hypothalamus are involved in the regulation of the release of catecholamines.

Hypotension alters the release of catecholamines in the hypothalamus of the conscious rabbit.

The posterior hypothalamic nucleus of conscious, freely moving rabbits was superfused with CSF through a cannula. Intravenous injection of nitroprusside elicited a fall of the arterial blood pressure and increased the rates of release of endogenous catecholamines in the posterior hypothalamic nucleus, while noradrenaline increased the blood pressure but did not change the release of catecholamines. It is concluded that hypotension leads to a counteracting increase in the release of catecholamines in the posterior hypothalamus.

Regulation of the release of neuronally localized corticosterone in rat forebrain areas by catecholamines.

The influence of intralimbic and intrahypothalamic application of catecholamine-related compounds on the release of neuronally localized corticosterone in the central amygdala, ventral hippocampus and medial hypothalamus was investigated under in vivo and in vitro conditions. It is reported that agonists and antagonists of the alpha-adrenergic system did not affect the release of corticosterone in the brain areas studied. In contrast, the beta-adrenoreceptor agonist isoprenaline markedly enhanced the release of corticosterone. This response is prevented in the presence of the beta-adrenoreceptor antagonist propranolol. The data reveal that limbic and hypothalamic beta-adrenoreceptors play a role in the regulation of corticosterone release and suggest a functional interaction between catecholaminergic and corticosterone releasing neurons in forebrain areas.

Temporal relationship between noradrenaline release in the central amygdala and plasma noradrenaline secretion in rats and tree shrews.

In pentobarbital anesthetized Wistar rats and tree shrews (Tupaia belangeri) the hypothalamus, the hippocampus and the amygdala were simultaneously superfused through push-pull cannulae with artificial cerebrospinal fluid. Blood samples were withdrawn in order to make an attempt to correlate release rates of noradrenaline (NA), adrenaline and dopamine in the above-mentioned areas with plasma catecholamine levels. A strong, positive correlation was found between NA release in central amygdala and NA concentrations in peripheral blood suggesting a functional relationship between noradrenergic systems in discrete brain areas and the activity of the peripheral sympathetic nervous system.

In vivo release of endogenous GABA in the cat hypothalamus.

The posterior hypothalamus of anaesthetized cats was superfused with artificial cerebrospinal fluid through a push-pull cannula and the release of endogenous GABA from the hypothalamus into the superfusate was studied. The resting release of GABA varied rhythmically, since phases of high rate of release were separated from each other by phases of low rate of release. The time interval between two adjacent phases of high rate of release was about 70 min. Electrical stimulation of the posterior hypothalamus with the tip of the cannula enhanced the rate of release of GABA in a frequency-dependent way. Superfusion of the hypothalamus with CSF which contained a high concentration of potassium and a low concentration of sodium increased the rate of release of GABA; this effect was dependent on the presence of calcium ions in the superfusing fluid. Pretreatment of the cats with reserpine reduced the levels of GABA in hypothalamus and rest of brain and the concentration of GABA in the superfusate as well. Stimulation of the locus coeruleus with a bipolar electrode elicited an increased release of GABA in the hypothalamus.

Pulsatile release of catecholamines in the hypothalamus of conscious rats.

To investigate the patterns of catecholamine release in the brain, the hypothalamus of conscious, freely moving rats was superfused through a push-pull cannula with artificial cerebrospinal fluid and the catecholamines dopamine, noradrenaline and adrenaline were determined in the superfusate radioenzymatically. Superfusate was continuously collected in time periods of 20 min for at least 20 h. Dopamine, noradrenaline and adrenaline release rates fluctuated according to an ultradian rhythm with a frequency of 1 cycle/92 min (dopamine and noradrenaline) or 99 min (adrenaline). Additionally, the three catecholamines were released according to an ultradian rhythm with the following frequencies: noradrenaline and adrenaline 1 cycle/12 h, dopamine 1 cycle/8 h. The release rates of dopamine and adrenaline were similar during light and dark periods, while the release rate of noradrenaline in the dark period was slightly lower than that during the light period. It is concluded that in the hypothalamus of the conscious rat the release rates of dopamine, noradrenaline and adrenaline fluctuate according to two ultradian rhythms with different frequencies.

In vivo release by histamine agonists and antagonists of endogenous catecholamines in the cat hypothalamus.

The posterior hypothalamus of anaesthetized cats was superfused through a push-pull cannula with histamine agonists and antagonists and the release of endogenous catecholamines was determined in the superfusate. Hypothalamic superfusion with histamine, 2-methylhistamine (H1-agonist), dimaprit (H2-agonist) or metiamide (H2-antagonist) enhanced the release of the catecholamines dopamine, noradrenaline and adrenaline. The releasing effects of these substances depended on the presence of calcium ions. Superfusion with 2-pyridylethylamine (H1-agonist) was virtually ineffective, while superfusion with 2-thiazolethylamine (H1-agonist) enhanced the rates of release of noradrenaline and adrenaline without influencing the release of dopamine. Superfusion with mepyramine (H1-antagonist) inhibited the release of noradrenaline and adrenaline without affecting the release of dopamine. Hypothalamic superfusion with a concentration of procaine which was equi-anaesthetic to that of mepyramine was ineffective. Ranitidine (H2-antagonist) did not alter the rates of release of the catecholamines. The releasing effect of histamine was inhibited on hypothalamic superfusion with mepyramine and ranitidine. Ranitidine also inhibited the releasing effects of dimaprit and 2-methylhistamine thus indicating that the releasing action of the latter compound was mainly due to stimulation of H2-receptors. These data suggest that blockade of H1-receptors of the posterior hypothalamus reduces the release of noradrenaline and adrenaline, while stimulation of H1-receptors seems to increase the rates of release of these two catecholamines. Stimulation of H2-receptors enhances the release of all three catecholamines. Thus, dopaminergic neurones of the hypothalamus seem to possess H2-receptors, while noradrenergic and adrenergic neurones possess H1- and H2-receptors.

In vivo release of endogenous catecholamines in the hypothalamus.

The posterior hypothalamus of anaesthetized cats was superfused with a push-pull cannula and the release of the endogenous catecholamines noradrenaline, adrenaline and dopamine was determined in the superfusate. The rate of release of the three catecholamines followed an ultradian rhythm, the time interval between two adjacent phases of high rate of release being about 70 min. Pretreatment of the animals with reserpine decreased the levels of catecholamines in the hypothalamus and rest of the brain and reduced their rate of release into the superfusate. Hypothalamic superfusion with superfusing fluid of high concentration of potassium and low concentration of sodium enhanced the rate of release of noradrenaline and adrenaline; this effect was abolished when the hypothalamus was superfused with calcium-free solution. Electrical stimulation of the locus coeruleus ipsilateral to the superfused hypothalamus increased the release of noradrenaline and adrenaline, stimulation of the contralateral locus coeruleus enhanced the release of noradrenaline, adrenaline and dopamine. In both cases, the rate of release of adrenaline was enhanced to a lesser extent than the rate of release of noradrenaline. The release of noradrenaline and adrenaline was increased to a higher extent on stimulation of the ipsilateral locus coeruleus than on stimulation of the contralateral one.

Rise in blood pressure increases the release of endogenous catecholamines in the anterior hypothalamus of the cat.

In anaesthetized cats, anterior and posterior hypothalamic areas were simultaneously superfused with artificial CSF using two push-pull cannulae. The rates of release of endogenous catecholamines were determined in the superfusates which were continuously collected in periods of 10 seconds. In both areas, the rate of release of dopamine was higher than the rates of release of noradrenaline and adrenaline. Electrical stimulation of the splanchnic nerve elicited a rise in the arterial blood pressure and increased the rates of release of noradrenaline, adrenaline and dopamine in the anterior hypothalamic area. The rates of release of the catecholamines in the posterior hypothalamic area were not influenced by the pressor response to stimulation of the splanchnic nerve. Transection of the brain caudal to the hypothalamus reduced the rates of release of the catecholamines in the anterior hypothalamus and abolished the releasing effect of the stimulation of the splanchnic nerve. The results indicate that acute rise in blood pressure activates catecholamine cell bodies in the lower brain stem, which in turn stimulate the anterior hypothalamus to counteract the pressor response.

Effects of short-lasting and long-lasting blood pressure changes on the release of endogenous catecholamines in the hypothalamus of the conscious, freely moving rabbit.

In anaesthetized rabbits guide cannulae were stereotaxically inserted into the anterior hypothalamic area and into the posterior hypothalamic nucleus. Additionally, catheters were inserted into the carotid artery and the jugular vein. Some days after the operation push-pull cannulae were inserted through the guide cannulae into the hypothalamic regions of the conscious, freely moving animal. The areas were superfused with artificial CSF and the release of the endogenous catecholamines dopamine, noradrenaline and adrenaline was determined in the superfusates. In the two hypothalamic regions the resting release of the catecholamines rhythmically varied with time at approximately 70 min cycles. A rise in blood pressure induced by the intravenous injection of noradrenaline or tramazoline enhanced the rates of release of the catecholamines in the anterior hypothalamic area. A fall of blood pressure elicited by the intravenous injection of nitroprusside or chlorisondamine decreased the release of the catecholamines in this hypothalamic area. The changes in blood pressure coincided with the changes in the rates of release of the catecholamines in the anterior hypothalamic area. These and previous results concerning changes in the release of endogenous catecholamines in the posterior hypothalamic nucleus also indicate that in the conscious, freely moving rabbit changes in blood pressure lead to counteracting alterations in the release of catecholamines in the two hypothalamic regions.

Differential effects of experimentally induced blood pressure changes on the release of catecholamines in hypothalamic and limbic areas of rats.

The effects of longer lasting blood pressure changes on the release of endogenous catecholamines (CA) in limbic and hypothalamic areas were studied in anaesthetized rats. For this purpose the central nucleus of the amygdala (AC), ventral hippocampus (VH) and medial hypothalamus (MH) were simultaneously superfused through push-pull cannulae with artificial cerebrospinal fluid and the release of the endogenous catecholamines dopamine (DA), noradrenaline (NA) and adrenaline (A) was determined before and after blood pressure manipulations. A fall in blood pressure elicited by the ganglionic blocking agent chlorisondamine resulted in different changes of the various CA release patterns in AC. Short lasting increased CA release rates as compared to prehypotension levels could be observed in the hippocampus. The activity of catecholaminergic neurons in MH remained unchanged. A rise in arterial blood pressure induced by intravenous injection of tramazoline did not change the release rates of DA in all 3 brain areas studied. In hippocampus, NA levels in the superfusates decreased initially during hypertension but returned to normal values 40 min after drug injection. In the late phase of hypertension increased rates of release of NA in the amygdala and of A in the hypothalamus could be observed. The different patterns in the release of CA suggest that DA, NA and A are differentially implicated in the regulation of experimentally induced blood pressure changes.

Involvement of limbic neuronal corticosterone in the regulation of arterial blood pressure.

The effect of experimentally induced blood pressure changes on the in vivo release of neuronal corticosterone in limbic and hypothalamic areas was studied in anaesthetized rats. A fall of the arterial blood pressure (ABP) elicited by the intravenous (i.v.) injection of the vasodilatator nitroprusside or the ganglionic blocking agent chlorisondamine decreased the release of corticosterone in the central amygdala (AC) and the ventral hippocampus (VH) whereas an experimentally induced hypertension after i.v. administration of the alpha adrenoreceptoragonist tramazoline led to an enhanced release of the glucocorticoid in the limbic areas mentioned above. Alterations in ABP did not affect the rates of corticosterone release in the medial hypothalamus (MH). The results may indicate a functional role for neuronal limbic corticosterone in central blood pressure regulation.

Brain involvement in generalized argyria.

Cutaneous argyria was diagnosed in a 59-year-old woman. Manic depressive psychosis developed at about the same or a short time thereafter. The patient died 6 years later from a ruptured aortic aneurysm. At autopsy silver deposits were seen in skin, mucous membranes, heart, kidney, and liver. In the central nervous system the leptomeninges and choroid plexuses contained silver granules. In addition, silver granules were visualized in the walls of many intraparenchymal vessels, particularly of the basal ganglia, hypothalamus, substantia nigra, and cerebellum. Progressive glial changes and cellular gliosis were evident in many areas of the brain. With the electron microscope the deposition of silver granules in basal membrane structures of the choroid plexus and intracerebral vasculature was amply confirmed. Furthermore, silver deposition was seen in brain parenchymal cells inside bodies of apparently lysosomal nature. The silver content of various brain regions was determined by absorption spectrophotometry.