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* studies of MG for diagnosis and monitoring* transmission in conditions of reinnervation, pre- or postsynaptic defects?* electrical stimulation for detailed physiological measurements.

* normal size variations* changes with pathology in myopathies and neurogenic conditions* dynamic changes in the motor unit over time in neurogenic conditions (ALS, polio) Is the development of fatigue in neurogenic conditions caused by central or peripheral factors? Is the pathophysiology underlying the post-polio syndrome also occurring in other degenerative disorders?

* H-reflex and flexion reflexes on single cell level* Cortical stimulation with SFEMG recordings

* Phenomena related to electrical stimulation* Excitability changes (A-waves, neuromyotonia, el stim)

New recording techniques: SFEMG

Macro EMGscanning EMG,

New parameters: jiggle

size index. Decomposition:

EMGIndividual MUPs

Analysis of EMG signals

EMG simulatorSFEMG, Concentric EMG and Macro EMG can be simulated.

Nerve simulatorA motor nerve is simulated.

Simulations

Erik Stålberg, professor emeritusCollaborators in the lab: Arne Sandberg, Anna Rostedt, Stefan Stålberg, Lars Karlsson, Björn Hammarberg, Tomas Winkler

Neuromuscular transmission

Motor unit size

Peripheral nerve

Studies of single cells in central nervous system

Physiology-pathology Technical developments

To increase our knowledge about the different factors involved in epileptogenesis and the triggering of epileptic seizures. Laser doppler recordings together with subdural electrode EEG recordings have shown changes in the regional cerebral blood flow prior to seizure activity. Intracranial micro dialysis is used to analyse extracellular concetrations of amino acids during seizures. Experimental studies are performed with our animal model of focal epilepsy.

Roland Flink, MD, PhDCollaborators: Eva Kumlien, Elisabeth Ronne-Engstöm

EpileptogenesisPET studies of focal epilepsy

Different ligands are used to characterise the epileptogenic zone in focal epilepsy. Deoxyglucose shows the metabolism, which is often decreased in the epileptogenic zone. Deprenyl binds to the enzyme MAO-B which is mainly located in the glial cells in the CNS, thus labelling gliosis. Ketamine will label the NMDA receptors indicating a possible up regulation in increased excitatory activity in the brain.

EEG-source localisation

Localise epileptogenic zone from surface EEG recordings and source analysis with different dipole algorithms. A realistic three shell head model with individual conductivity is used and the dipole location is superimposed on the 3D MRI reconstruction.

Intracranial microdialysis microdialysis

Focal epilepsy model using ferrous chloride

Intracranial laserdoppler recordingof regional blood flow

18Fluoro-deoxy-glucose (FDG)

11C-Ketamine

11C-deuterium-Deprenyl

Hypometabolism in right temporal lobe

Increased ketamine binding inleft temporal lobe, bindsto NMDA receptor

Increased deprenyl binding in right temporal lobe,binds to MAO-B enzyme in glial cells

Patient with complex partial seizures originating from the right frontal lobe

Three shell head model withindividual conductivity

Multimodal imaging

Realistic headmodel

Recordings from human muscle spindle afferents combined with EMG recordings during voluntary muscle contractions support the “servo-assistance” theory. This theory implies that when a muscle contracts part of the excitatory drive on the alpha motorneurones is normally mediated the indirect way via the fusimotor - motor spindle loop. Other microneurographic studies indicate that the hyperrereflexias in spasticity and rigidity are not primarily due to muscle spindle hypersensitivity but to increased central responsiveness to essentially normal spindle inputs.

Microneurography from human skin nerves combined with the technique of intraneural microstimulation has made it possible to analyse the specific types of sensations aroused by neural impulse messages signalled by various types A- and C-fibre sensory units. Studies of this type have been made both in healthy subjects and in patients with different types paraestesias, hyperalgesias and neurogenic pain. Two types of C-nociceptors have been identified: polymodal units and mechanoinsensitive units activated by algogenic substances. A special type of C-units are histamine responsive and give rise not to pain but to itch sensations. The technique allows differentiation between chronic pain syndromes due to peripheral nicoceptor hyperexitability and to increased responsiveness of central sensory neurones.

Karl-Erik Hagbarth, Professor emeritusMain local collaborators: Åke Wallbo, Gunnar Wallin, Erik Torebjörk, Rolf Hallin,

Roland Schmidt, Jan Fagius, Magnus Nordin and Urban Wallin.

Muscle spindle functions Exteroceptive functions

Sympathetic functions

Besides the traffic of impulses in various types of afferent nerve fibres also the impulse traffic in post ganglionic sympathetic C-fibres can be recorded with the microneurography technique. It has been shown that the sympathetic activity in muscle nerve fascicles consists of vasoconstrictor impulses which under baroreflex control serve to guard against sudden falls in diastolic blood pressure. In contrast, the sympathetic activity in skin nerve fascicles consists of a mixture of vasomotor and sudomotor impulses which, besides giving rise to “cold-sweat”reponses to various types of arousal stimuli - also sudserve thermoregulatory functions. A great number of studies of sympathetic activity in muscle and skin nerves have been performed as well in healthy subjects of various age as in patients with various types of autonomic disturbances.

Konzo is a subacute spastic para/tetraparesis in central Africa and is related to intake of bitter cassava.1998 and 2000 high-tech equipment was brought from our Department to Kinshasa for neurophysiological investigations on konzo subjects and their relatives.

Results:EEG: overrepresentation of abnormalities. (slowing of activity)Neurography: normalEMG: small motorunit potentials.MEP: abnormalities.SEP: abnormal findings.Muscle biopsies: atrophic changes.

Gastrointestinal neurophysiology implies disorders of constipation and faecal incontinence. Different methods may be used for mapping.In co-operation with the Department of Surgery, above disorders have been investigated on large patient materials.

Rolandic epilepsy is a concept used for focal epilepsies where rolandic spikes are found.In Uppsala, MRI and neuropsychology have been performed on children with benign epilepsy with centrotemporal spikes.

Results:MRI: overrepresentaton of pathological changes.Neuropsychology: several abnormalities especially in learning. I.e. “benign childhood epilepsy” not always benign. Rolandic epilepsy heterogeneous.

Karin Edebol Eeg-Olofsson, MD, PhDCollaborators: D.Tshala (Konzo), S. Lundberg (Rolandic epilepsy),

U. Karlbom and A.Österberg (Gastrointestinal neurophysiology)

Konzo Rolandic Epilepsy

Gastrointestinalneurophysiology

Results:Constipation: via hook-electrodes increased paradoxical activation of external anal sphincter and puborectalis muscle were found.Incontinence: increased distal pudendal latency and fibre density in the majority of patients.

Electrical corticalstimulation in konzo

Kabambu, 18year old, with konzo

A spinal cord injury is followed by:1. immediate loss of conduction in spinal cord tracts (spinal chock),2. from five min progressive destruction of grey

tissue (secondary injury),3. from three hours secondary injury changes

also in white tissue.

Which factors are involved in spinal shock and secondary injury?Could these factors be influenced by pharmacological treatment?

Laminectomy at T10-11 in anesthetized rats, recording of epidural evoked potentials from T9 and T11 after stimulation of nerves in the right hindlimb,longitudinal inscision in the right dorsal horn of T10-11 (i.e. passing tracts not involved by the primary injury), five hour after injury measurement of water content and hist-pathological analysis of injured segments.

Immediately after injury negative response in rostral recordings is lost and replaced by a “positive injury potential” (fig 1, 0 min; fig 2a). These animals show five hour after injury pronounced swelling and histological detoriation in injured segments (fig 2b).

Results

Treatment before injury with drugs listed below partly or completely abolished both the spinal shock and the pathological changes seen five hour after injury (fig 2):P CPA serotonin synthes is

inhibitorIndomethacin prostaglandin synthesis is

inhibitorNaloxone opoid receptor blockerNO synthase antiserumCimetidine histamine receptor blockerNimodipine Ca channel blockerIbuprofen anti-inflammatoric

(serotonin receptors?)Diazepam benzodiazepine receptorsTopical application of IGF-1 (insulinlike growth factor)Topical application of rGH (rat growth hormone)

No effect of following drugs (fig 2):Dexamethasone anti-inflammatoric steroidPropranolol B-receptor blockerPhentolamine A-receptor blocker

Increase of secondary injury (fig 2):Crypoheptadine serotonin receptor blocker

Tomas Winkler MD, PhDCollaborators: Hari Shanker Sharma MD, Prof. em. Erik Stålberg, Prof. Fred Nyberg, Prof. Per Alm.

Methods

Several substances are released immediately after a spinal cord injury, they are all essential for the development of secondary injury. Later blocking of these substances does not influence the course. Topical application possible and more effective.

Conclusion

Fig.2

Fig.1