Research reports to Swedish Medical Research Council .

The motor unit microphysiology, anatomy and pathology

Stålberg Erik, professor, Falck Björn, ass prof, Winkler Tomas, PhD

Dept of Clinical Neurophysiology, Neurocentre S- 751 85 Uppsala

Phone 18 663442, fax 18 556106, email Erik Stålberg

B96-14X-00135-32B 404.000:- SEK

The project concerns the microphysiology of normal and diseased human muscle. Continued studies have been made of neuromuscular transmission in individual motor end-plates. The transmission defect in reinnervating muscles has been studied in detail with the technique of stimulation SFEMG. A presynaptic as well as a postsynaptic defect can be demonstrated which was previously unknown. Using Macro EMG and other techniques, the condition of neuromyotonia has been studied. One cause of this condition is an immunological effect on Ca channels, usually affecting channels in the presynpatic terminal. In one case studied in detail by us, the abnormal impulses not only started in the presynaptic area of the end-plate but also in more proximal parts of the nerve, indicating the multifactorial character of the condition. A large group of patients with polio has been studied with Macro EMG. In one longitudinal study, the changes of denervation in previously reinnervated motor units earlier described by us, have been further analysed. A study of metabolic changes in the polio muscle has shown that energy depletion is not likely to be directly related to symptoms of fatigue or pain. The polio studies are important for the understanding of post polio symptoms, for the care of these patients and for the understanding of similar phenomena in other chronic neurological diseases of the lower motor neurone.

Methodological development has included the collection of reference material for the automatic EMG analysis developed by us, and detailed analysis of the principle differences between various routinely used EMG techniques. These studies will have direct impact on the application of these techniques on patients with neuromuscular disorders.

Peripheral Nerve Activity and Pain Perception

Torebjörk Erik, professor, Handwerker H, Kolzenburg M, Schmidt R, Wahren L-K, Ugge P

Dept of Clinical Neurophysiology, University Hospital, S-75185 Uppsala

Phone 018-66 34 33, Fax 018-55 61 06

B96-14X-05206-19B 606 000

Neurophysiological mechanisms for post-traumatic neuralgia are complex and largely unknown. In particular, the involvement of the sympathetic nervous system in some of these pain conditions is mysterious. Is there an interaction between sympathetic and afferent nerve fibres in the neuroma, or could there be sympathetic-afferent interactions distal to the nerve lesion in apparently normal tissue? To answer that question we have studied the effects of cutaneous application of noradrenaline in 35 patients with post-traumatic neuralgia. Depending on the outcome of sympathetic blocks the patients were considered to have sympathetically maintained pain (SMP, n=25) or sympathetically independent pain (SIP, n=10). Iontophoretic application or cutaneous injection of noradrenaline into symptomatic skin aggravated pain and mechanical or thermal hyperalgesia in 7/25 SMP patients. Results from differential nerve blocks suggested that noradrenaline-induced ongoing pain and heat hyperalgesia were signalled by unmyelinated nerve fibres, while touch-evoked pain and cold hyperalgesia were signalled by myelinated fibres. In none of the remaining patients or 18 normal subjects did application of noradrenaline result in any pain. It is concluded that cutaneous noradrenaline application can aggravate ongoing pain and various forms of hyperalgesia in some but not all SMP patients. It seems that remaining or regenerating nerve fibres ending distal to the nerve lesion, in what appears to be normal skin, may acquire an abnormal sensitivity to noradrenaline in some patients with sympathetically maintained pain.

Nordin, Magnus, dr med sci

Department of Clinical Neurophysiology, University Hospital, 751 85 UPPSALA

K95-14P-10163-04B

In a microneurographic study (J Physiol, in press) we have investigated the effects of sustained painful stimulation on muscle nerve sympathetic activity (MSA) in healthy volunteers. The painful stimuli, adjusted to the subject's tolerance level, included: a) Pressure to the nailbed of different digits, and to the trigeminal region. b) Electrical stimulation (5 Hz) of digital nerves, and of the supraorbital nerve. c) Instillation of soap solution into one eye. All procedures except electrical stimulation of digital nerves induced a marked increase in MSA (mean 160-248 %) associated with a rise in blood pressure; the pulse synchrony of the bursts was preserved. Despite similar pain ratings, electrical stimulation of digital nerves caused a smaller MSA response than the other stimuli (mean increase 40 %). It is concluded that sustained noxious stimulation evokes a generalized MSA increase; the activity is still under baroreflex control, but the inhibitory level is elevated. Spinal as well as brain stem reflexes may contribute; a defence reaction is an improbable explanation. It is proposed that the number of C-afferents activated by electrical stimulation of digital nerves was insufficient to evoke any marked MSA response. In another study we have recorded MSA during spontaneous as well as nitroglycerin-induced attacks of cluster headache. A marked increase in MSA, paralleling the pain rating, was found in both cases. The results suggest that this increase is a secondary, pain-induced phenomenon. As a control for these studies, we investigated the effects of nitroglycerin on MSA in healthy subjects. A marked MSA response to the initial fall in blood pressure was found. Subsequently, there was a reduction in MSA, despite the fact that blood presssure remained at a low level. These findings may suggest that nitroglycerin has a central sympathoinhibitory in man; such an effect has been demonstrated in experimental animals, but so far not in humans. Ongoing projects include microneurographic studies of trigeminal neuralgia, and attempts to establish the physiological role of low-threshold C mechanoreceptors in man.

Studies of Partial and Partial Complex Epilepsy

Flink Roland, ass prof, Bergström M, Blom S, C:son Silander H, Hillered L, Kumlien E, Lindquist C, Ronne-Engström E, Spännare B, Wiksten B.

Epilepsy group, Institute of Clinical Neurosciences, Academic Hospital, S-751 85 Uppsala

Phone +46 18 66 30 00 Fax +46 18 55 61 06 email Roland.Flink@neurofys.uas.se

B94-14X-09482-06A 225.000

A successful surgical resection of epileptogenic cortical tissue in patients with intractable epileptic seizures requires a scrutinized localization of the seizure generating focus. With PET-technique using the ligand 11[C]-L-deuterium-deprenyl, an irreversable inhibitor to the enzyme MAO-B, we have been able to label epileptogenic tissue. Deprenyl binds to the enzyme MAO-B which is mainly located in glial cells in the CNS and gliosis is a main characteristic of an epileptogenic focus. The results are highly significant for temporal lobe foci and the study is now including patients with extratemporal foci. A quantitative EEG-analysis, calculating the location of current dipoles from recorded surface potentials, has been developed and validated with intracranial stimulation experiments taking into account the complex situation of different electric conductivity in the different tissues in the head. The localization error is with this method about 5 mm and we consider the method clinically useful. Sixteen patients, with intractable complex partial epileptic seizures who were evaluated for epilepsy surgery, have been investigated with the dipole method. Eight patients had seizure onset in the temporal lobe and eight had epileptic seizures of extratemporal origin. The dipole location of interictal epileptiform spike activity coincided in all cases but one with the epileptogenic zone as defined by location of seizure onset with intracranial electrodes and neuroimaging both structural (MRI) and functional (FDG-PET). We think this non-invasive technique is very promising in locating epileptic foci and together with other non-invasive methods, it might reduce the need for intracranial monitoring in the preoperative evaluation of patients with intractable epileptic seizures.

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