Decreased sensitivity of neurons in the basolateral amygdala to dopamine and noradrenaline iontophoresis after a kindling stimulus.

The depressant effects of iontophoretically applied dopamine and noradrenaline on glutamate-induced neuronal firing in the amygdaloid complex of cats were significantly reduced 1 and 2 h after induction of a local epileptiform afterdischarge of the kind used in kindling. Neuronal excitation by glutamate and depression by GABA were not significantly changed. This suggests that kindling is associated with a reduction of the inhibitory effects of endogenous catecholamines.

Cholinergic mechanisms in the production of focal cortical slow waves.

Microiontophoretic application of scopolamine and atropine usually induced or increased focal cortical slow waves of under 3 Hz and abolished or decreased focal fast waves of over 6 Hz whereas acetylcholine iontophoresis and electrical stimulation of the mesencephalic reticular formation had the opposite effect, suggesting that focal cortical slow waves may be due to the interruption of cholinergic input from the reticular formation.

Microiontophoretic study of the GABA receptor in the feline caudate nucleus.

The effect of microiontophoretic application of GABA and its antagonist, picrotoxin, on the firing of neurons in the feline caudate nucleus (CN) was studied. Firing was elicited by stimulation of the CN a few millimeters from the recording site. Increasing ejection currents of GABA produced a dose-dependent decrease and eventual blockade of the firing of CN neurons.

Selective blockade by scopolamine of synaptic responses in cat's caudate nucleus and its modification by lesions of the substantia nigra.

Because it is commonly believed that acetylcholine is a synaptic transmitter in the caudate nucleus and that the reduction of striatal biogenic amines in Parkinson's disease leads to acetylcholine supersensitivity in the caudate nucleus, we investigated the effects of the muscarinic blocking agent scopolamine on synaptic responses of neurons in the intact feline caudate nucleus and in the caudate nucleus depleted of dopamine by long-standing nigrostriatal lesions. In the intact caudate nucleus, micro-iontophoretic application of scopolamine selectively blocked the neuronal responses to stimulation of the caudate nucleus near the recording site without affecting the responses to stimulation of the sensorimotor cortex or the substantia nigra in the same fashion. This suggests that acetylcholine is a synaptic transmitter of caudate interneurons.

Visual evoked potentials and postmortem findings in a case of cortical blindness.

A patient with cortical blindness due to extensive bilateral posterior cerebral infarcts showed occipital visual evoked potentials to flash stimulation on repeated testing. These responses were probably mediated by extrageniculocalcarine connections between the optic nerve and the secondary visual cortex of the occipital convexity.

CT scan in inter hemispheric subdural hematoma. Clinical and pathological correlation.

In a patient with a large interhemispheric subdural hematoma, the CT scan showed a radiodensity with a straight sagittal and a convex lateral border. This image correlated with the autopsy findings. It differs from CT scan images of intracerebral hematomas.

Dopamine acetylcholine imbalance in Parkinson's disease. Possible regenerative overgrowth of cholinergic axon terminals.

Parkinson's disease is characterised by an imbalance between acetylcholine and dopamine which probably results from the degeneration of a dopaminergic nigrostriatal pathway. A new hypothesis is proposed to explain the development of this imbalance. Applying the concept that degeneration of nerve-fibres in the central nervous system can lead to collateral sprouting of uninjured fibres, it is suggested that the death of dopaminergic nigrostriatal neurons results in sprouting of axons of cholinergic interneurons in the caudate nucleus.

Comparison of dantrolene sodium and diazepam in the treatment of spasticity.

The effects of dantrolene sodium and diazepam were compared in a double crossover study of 42 patients with spasticity due to stable multiple sclerosis. Both drugs reduced the findings of spasticity, clonus, and hyperreflexia, and the complaints of muscle stiffness and cramping. Each drug had different side effects which suggest indications and contraindications for its use in spastic patients.

A pharmacologic study of the stiff-man syndrome. Correlation of clinical symptoms with urinary 3-methoxy-4-hydroxy-phenyl glycol excretion.

We have investigated hypotheses that link the stiff-man syndrome to an imbalance of neurotransmitter systems. No evidence was found to support the concept of defective synaptic transmission at either cholinergic input to Renshaw inhibitory elements or at glycinergic inhibitory input to motoneurons from spinal interneurons, since neither physostigmine nor glycine altered symptomatology. Urinary excretion of the norepinephrine metabolite 3-methoxy-4-hydroxy-phenyl glycol showed a high correlation with clinical status.

The effects of acetylcholine and dopamine on the caudate nucleus depleted of biogenic amines.

Because it has been proposed that the reduction of the striatal biogenic amines in Parkinson's disease leads to an imbalance between the actions of acetylcholine and dopamine, we have studied the effects of these substances, liberated from multibarrelled micropipettes, on the firing of single neurons in the feline caudate nucleus depleted of biogenic amines by long-standing nigrostriatal lesions. Compared with neurons in intact cats, those in cats with lesions were more easily excited by acetylcholine and less easily supressed by dopamine. These results suggest that the depletion of the striatal amines decreases the neuronal susceptibility to dopamine and increases that to acetylocholine, possibly by changing the sensitivity or the number of the neuronal receptors of these agents.

Cyclophosphamide in exacerbations of multiple sclerosis. Therapeutic trial and a strategy for pilot drug studies.

Cyclophosphamide (CY) has been shown to reverse the signs of experimental allergic encephalomyelitis (EAE) even after the onset of neurological deficits. Because of the analogy of EAE to exacerbations of multiple sclerosis (MS) a clinical trial of CY in acute MS exacerbations was undertaken. A 'sequential criterion' method was used to minimize the size of sample needed for this pilot study.