[Chronic pain therapy]. / Therapie chronischer Schmerzen.

Chronic pain represents a considerable health problem in developed countries, too. This fact is especially important in the socio-economic perspective. The nowadays at least partially known fundamental processes of the development of chronic pain allow for a mechanism-oriented therapeutical approach. This drug oriented approach has to be improved. The management of complex chronic pain states should basically be interdisciplinary, including all involved medical and paramedical disciplines. Semi-invasive and invasive approaches of pain therapy should be the last resort.

Multiple visual hallucinations and pseudohallucinations in one individual patient: when the world is turning upside down and the television keeps falling to the ground while dwarfs are parading on the ceiling.

We report on a patient who experienced visual hallucinations and pseudohallucinations comprising palinopsia, peduncular hallucinosis, and oblique vision. The most probable etiologies of these phenomena are discussed with respect to clinical presentation and findings on computed tomography and magnetic resonance imaging.

The contribution of the vertical semicircular canals to high-velocity horizontal vestibulo-ocular reflex (VOR) in normal subjects and patients with unilateral vestibular nerve section.

We have examined to what extent the vertical semicircular canals contribute to the nonlinearity of the horizontal VOR imposed by the driving of primary vestibular afferents into inhibitory cutoff at high velocities of head rotation (Ewald's second law). The gain (eye velocity/head velocity) of the horizontal component of the VOR with the head pitched down 30 degrees and pitched up 30 degrees was examined during constant-velocity rotations in normal subjects and patients following unilateral vestibular nerve section. In normal subjects, VOR gain decreases as chair velocity increases from 60-300 degrees/s when the head is pitched up, but VOR gain remains constant when the head is pitched down. This finding implies that the mechanism by which the gain of the horizontal VOR gain remains constant at all velocities of rotation depends upon the pattern of labyrinthine stimulation. Following unilateral nerve section, we found that the directional preponderance (DP) in horizontal VOR depends upon whether the head is pitched up 30 (mean asymmetry = 5%) or pitched down 30 degrees (mean asymmetry = 20%). This is what is expected based on the degree to which the lateral and vertical semicircular canals sense horizontal head acceleration with the head in different degrees of pitch. Hence, following unilateral vestibular lesions, the DP of horizontal VOR gain is most easily elicited at high velocities of head rotation and with the head pitched down 30 degrees. Evidence for DP at the bedside using the "head-shaking nystagmus" technique may be optimally elicited with the head pitched down 30 degrees.

Recovery of hypoglycaemia-associated compromised cerebral function after a short interval of euglycaemia in insulin-dependent diabetic patients.

To test the hypothesis that compromised cerebral function, induced by recurrent hypoglycaemic episodes, may recover after a short interval of euglycaemia, we examined electrophysiological activity and symptom awareness during two sequential euglycaemic-hypoglycaemic clamp studies in 11 insulin-dependent diabetic patients without any signs of peripheral or autonomic neuropathy. Neurophysiological testing and evaluation of hypoglycaemic symptoms were performed at stable glycaemic plateaus of 5.6, 3.3, 2.2, and 1.7 mmol/l. The first clamp study was preceded by 3 short-term hypoglycaemic episodes, whereas the second clamp study followed a 2 day interval of strict euglycaemia. The latter caused a recovery of electrophysiological activity, which was demonstrated by recovery of delays of the middle latency auditory evoked potentials (latency shift of the P(a) component, MANOVA, P < 0.01). Reversal of hypoglycaemic symptom unawareness involved the overall symptom perception (MANOVA, P < 0.04), as well as the autonomic symptoms of heart pounding (P < 0.05) and sweating (P < 0.05). We conclude that the previously reported impaired cerebral function, occurring as a consequence of repetitive hypoglycaemic episodes, may recover after a single euglycaemic interval.

Neurophysiological impairments in IDDM patients during euglycemia and hypoglycemia.

OBJECTIVE: To test the hypothesis that latencies of evoked potentials in IDDM patients are delayed compared with healthy control subjects during euglycemia, and that insulin-induced hypoglycemia causes further latency delays of evoked potentials to occur. RESEARCH DESIGN AND METHODS: We recruited 23 IDDM patients (27.9 +/- 1.6 yr of age, HbA1c 6.7 +/- 0.3%, without sensory or autonomic neuropathy) and 26 unequivocally healthy subjects who were carefully matched for sex, age, and body mass index to serve as the control group (18 men and 8 women, 28.4 +/- 1.6 yr of age, 22.6 +/- 0.7 kg/m2), for a controlled, prospective study. Sequential euglycemic-hypoglycemic clamps were performed with stable glycemic plateaus of 5.6, 3.3, 2.2, and 1.7 mM, at which the patients' and healthy control subjects' neurophysiological functions were evaluated. The methodological armamentarium included the measurement of brainstem auditory, middle-latency auditory, and somatosensory evoked potentials that assessed conduction velocity in corresponding neural structures and information processing in the midbrain and auditory cortex. RESULTS: Multiple analysis of variance revealed a significant overall difference of brainstem auditory evoked potential latencies during euglycemia between the study group and healthy control group (F = 3.41, P < 0.03), which was mainly attributable to latency delays of wave III (F = 6.60, P < 0.02), V (F = 9.19, P < 0.01), and interpeak latency I-V (F = 2.82, P < 0.07). Repeated analysis of variance measures detected a significant latency delay of the major wave Pa of the middle-latency auditory evoked potentials during hypoglycemia (F = 4.4, P < 0.02), which rapidly returned to normal after reinstitution of euglycemia. CONCLUSIONS: In IDDM patients, chronic, structural CNS changes already appear at the brainstem level during euglycemia. Functional, reversible CNS changes, however, seem to emerge during acute deviation from glucose homeostasis in more rostral brain regions.

Systemic vasculitis positive for circulating anti-neutrophil cytoplasmic antibodies and with predominantly neurological presentation.

A 57-year-old male patient suffering from dramatically deteriorating diffuse and focal central nervous system symptoms was admitted to hospital after a short prodromal period in a somnolent state. He was diagnosed as having systemic vasculitis positive for circulating anti-neutrophil cytoplasmic antibodies, primarily involving the brain, but also most other organ systems. Circulating anti-neutrophil cytoplasmic antibodies are highly specific for Wegener granulomatosis, though they have been detected in rare cases of other vasculitic syndromes. Central nervous system lesions as presenting signs in Wegener granulomatosis have to be regarded as rare. This case nonetheless suggests that Wegener granulomatosis has to be considered in patients with a predominantly cerebral manifestation of a vasculitic syndrome.

Compromised hormonal counterregulation, symptom awareness, and neurophysiological function after recurrent short-term episodes of insulin-induced hypoglycemia in IDDM patients.

To test the hypothesis that recurrent short-term hypoglycemic episodes may impair hormonal counterregulation, symptom awareness, and neurophysiological function during subsequent hypoglycemia, we examined two groups of IDDM patients (n = 18), neither of whom exhibited signs of autonomic neuropathy. Two sequential euglycemic-hypoglycemic clamp studies were performed three days apart with stable glycemic plateaus of 5.6, 3.3, 2.2, and 1.7 mM, at which the patients' awareness of and response to hypoglycemia was evaluated. In the intervention group (n = 11), three short-term hypoglycemic episodes preceded the second clamp study. Counterregulatory hormones increased significantly during hypoglycemia, but adrenaline (P < 0.03), cortisol (P < 0.01), and ACTH (albeit not significant) showed a blunted response after repetitive hypoglycemic events. In this group, the perception of hypoglycemic symptoms was significantly reduced and was most evident for the autonomic symptoms of sweating (P < 0.05), heart pounding (P < 0.01), and warmness (P < 0.03). The deterioration of neurophysiological function, as assessed from the middle latency auditory evoked potentials, was more pronounced in the intervention group (latency shift of the Pa component, P < 0.05). These data suggest that alterations of neuroendocrine counterregulation, symptom perception, and certain aspects of cerebral function may occur as a consequence of recurrent short-term hypoglycemic episodes. These adaptation phenomena may contribute to the increased incidence of severe hypoglycemia in IDDM patients on intensive insulin therapy.

Ocular motor dysfunction in stupor and coma.

Ocular motor disorders in stupor and coma are important clinical signs which are easily accessible with observation and a few bedside manoeuvres. Although the manifold signs of ocular motor dysfunction may be confusing to most clinicians, many of the signs can be attributed to clear pathophysiological mechanisms. This holds for conjugate eye deviations as well as for most spontaneous eye movements in coma. Using simple methods to elicit reflex eye movements, in most cases a lesion site within or outside the brain stem can be determined. It is stressed that an exact description and documentation of the ocular motor deficit is necessary. The following key aspects should be included in such a documentation: pupil size and reaction, conjugate or disconjugate eye position, spontaneous eye movements and VOR elicited either by head rotation or caloric irrigation. The latter allows assessment of the ocular motor integrator. The VOR may be intact, indicated by full compensatory eye movements, but the gaze-holding mechanism (integrator) can be defective, thus permitting the eyes to drift back to the primary position.

Hormonal counterregulation, symptom awareness, and neurophysiological function in type 1 diabetes during insulin-induced hypoglycaemia.

To evaluate a putative differential impact of human (HI) and porcine (PI) insulin on human brain function we examined 10 Type 1 (insulin-dependent) diabetic patients without any signs of sensory or autonomic neuropathy. The glucose clamp technique was applied to achieve stable glycaemic plateaus of 5.6, 3.3, 2.2, and 1.7 mmol l-1 on two occasions with randomized and blinded allocation of either HI or PI. At each of the plateaus, symptom awareness, hormonal counterregulation, and neurophysiological functions (primary sensory information processing of the auditory and somatosensory system) were recorded. The effect of both types of insulin on glucose metabolism and counterregulatory hormone response was almost identical. Catecholamines increased (adrenaline p less than 0.05; noradrenaline p less than 0.02) during hypoglycaemia, independent of the type of insulin being used. Symptom awareness increased significantly during the fall of blood glucose concentration. This effect was more pronounced (total symptom score 26 vs 2, p less than 0.05) with PI, but only during developing hypoglycaemia (3.3 mmol l-1-plateau). For brainstem auditory evoked potentials and somatosensory evoked potentials, all individual and averaged latencies and corresponding amplitudes were within the normal range. No effect of insulin type or blood glucose concentration on neurophysiological measures could be detected. Our results suggest a differential impact of HI and PI on human brain function with regard to symptom awareness, but not hormonal counterregulation. This direct effect of insulin on central nervous function does not involve the afferent transmission in the auditory and somatosensory system.

Somatosensory evoked potentials following tongue stimulation in normal subjects and patients with lesions of the afferent trigeminal system.

Somatosensory evoked potentials (SEPs) after unilateral stimulation of the tongue were recorded in 20 normal subjects and in 20 patients with peripheral and central lesions of the afferent trigeminal pathway. Potentials were recorded up to 50 msec latency via electrodes placed on the scalp (between C3/4 and T3/4), the tragus and intra-orally with a fronto-central reference. In several instances simultaneous records from facial and masticatory muscles were obtained in order to detect muscle artifacts. (1) Very early components up to 5 msec were contaminated by muscular artifacts arising from muscle twitch of the tip of the tongue. (2) Reflex potentials could be recorded over the tragus at latencies between 15 and 25 msec when the jaw-opening muscles were preactivated but not during relaxation. (3) A positive potential with a latency of 21 msec and maximum amplitude over the contralateral scalp was present in all normal subjects and on the non-affected sides of all patients. (4) Cortical SEPs were absent in 19 of the 20 patients with central or peripheral lesions of the lingual nerve pathway (presenting clinically with neuralgia, hypoaesthesia or anaesthesia). In one patient a delayed potential was recorded. Lingual nerve SEPs provide a useful tool for monitoring lingual nerve function. As with other SEP techniques, no conclusions concerning the type and extent of the underlying pathology can be drawn.

Diagnostic significance of tibial nerve somatosensory evoked potentials (spinal and cortical components) with spinal cord lesions.

Forty normal subjects were investigated with the somatosensory evoked potential technique following stimulation of the posterior tibial nerve in order to yield information upon normal values, and especially the origin of the cervical potential. Subsequently an electrophysiologic localization of tumours along the spinal cord was attempted in 18 patients with spinal tumours. In C2 recordings with Fz reference 3 components, N28, N30, and N34, are visible. Simultaneous cortical and cervical recordings with mastoid, knee, and neck references suggest a cranio-cervical origin of N28, a subcortical origin of N30 and a thalamic or thalamo-cortical origin of N34. In patients, the lumbar spinal cord potentials regularly yielded a useful additional information with respect to the tumour site. The cervical potentials added in 5 out of 18 patients additional information localizing the tumour within the spinal cord or brain-stem.

Static roll and the vestibulo-ocular reflex (VOR).

We measured the effect of static lateral tilt (roll) on the gain and time constant of the vestibulo-ocular reflex (VOR) in five normal subjects by recording both the horizontal and vertical components of eye velocity in space for rotation about an earth vertical axis with the head either upright or rolled to either side. The time constant of the VOR in the upright position was 19.6 +/- 3.2s (mean +/- standard deviation). The time constant of the horizontal component with respect to the head decreased to 15.7 +/- 4.0s for 30 degrees roll and to 12.7 +/- 2.7s for 60 degrees roll. The time constant of the vertical component with respect to the head was 11.0 +/- 1.4s for 30 degrees roll and 7.5 +/- 1.6s for 60 degrees roll. The gain of the horizontal VOR with respect to space did not vary significantly with roll angle but a small space-vertical component to the VOR appeared during all rotations when the head was rolled away from upright. This non-compensatory nystagmus built up to a maximum of 2-3 degrees/s at 17.0 +/- 4.7s after the onset of rotation and then decayed. These data suggest that static otolith input modulates the central storage of semicircular canal signals, and that head-horizontal and head-vertical components of the VOR can decay at different rates.

Stimulus characteristics influence the gain of smooth pursuit eye movements in normal subjects.

Impaired smooth pursuit eye movements are commonly believed to indicate a lesion of the central nervous system. Smooth pursuit performance, however, is strongly dependent on non-specific variables like cooperation, arousal and attentiveness. Therefore, disturbed smooth pursuit can be attributed either to lesions of the smooth pursuit system per se, or to the influence of non-controlled variables (non-structural disturbances). This renders the evaluation of smooth pursuit uncertain. In the present study we attempted to design a stimulus that yields smooth pursuit eye movements, which are not influenced by uncontrolled variations of state and input, for a better separation of structural lesions of the pursuit system and the effect of nonspecific variables. Our results suggest that a stimulus that leads to a centrally generated representation (percept) of motion is most suitable to elicit high gains of smooth pursuit (sigma pursuit), but only if attentiveness is optimal. Beta-motion (motion elicited by discrete steps of the target) or real target motion are capable to render the smooth pursuit performance optimal, even with low attentiveness, when the fixation point and its wider surroundings or enough discrete points in the neighbourhood move in the same direction in space.

Vestibular testing in comatose patients.

The analysis of vestibular responses in a comatose patient often provides the critical information for making a correct preliminary diagnosis and directing the subsequent laboratory evaluation. Because of some uncertainties about what is being tested with the various bedside maneuvers that are used to elicit vestibular responses, we review the physiologic basis for the oculomotor responses that occur with head rotation or with caloric stimuli. We further urge precise and unambiguous terminology to describe both stimulus and response. We suggest using physiologically well-defined terms such as vestibulo-ocular reflex and cervico-ocular reflex and avoiding potentially misleading terms such as the doll's head and the oculocephalic maneuvers.

Investigation of the dorsolateral basilar pontine grey of the alert monkey.

The dorsolateral basilar pontine grey is assumed to play an essential role in a cortico-ponto-cerebello-pontine pathway subserving smooth-pursuit eye movements. The dorsolateral basilar pontine grey interconnects those cerebral and cerebellar cortical areas known to be involved in the generation of smooth-pursuit eye movements. In the present study three categories of neurons presumably contributing to smooth pursuit eye movements were recorded: visual-only neurons, visual-tracking neurons, and neurons combining both properties. Preference for directions of visual stimulation could be either iso- or antidirectional.