Lack of effect of 4-aminopyridine on choreic movements.

Sir: The pathophysiology of Hunting-ton's disease remains unknown, but recent research has pointed out defects of several neurotransmitter systems in the corpus striatum of such patients. Both cholinergic' and GABA-ergic2 transmission are thought to be diminished, and substance P-containing neurons may be reduced,3 indicating a complex patho-physiology. Dopaminergic transmission, on the other hand, is probably normal and the involuntary movements have been ascribed to the resulting dysequilibrium between cholinergic and dopaminergic transmission.4 Attempts to treat this disorder pharmacologically have not been successful and no curative therapy is known. Anti-dopaminergic drugs are considered to have some effect on the choreic movements, but drugs supposed to enhance cholinergic transmission have proved ineffective.5 Results on GABA-ergic drugs have been conflicting.8 7 Our lack of knowledge on the patho-physiology and treatment of Hunting-ton's disease justifies clinical trials of new drugs. 4-Aminopyridine (4-AP) is neuro-pharmacologically a very active substance enhancing several types of synaptic transmission. In the peripheral nervous system activity at cholinergic,8 9 adrener-gic,10 and glutaminergic11 synapses is potentiated, and in the central nervous system both excitatory and inhibitory postsynaptic potentials are augmented.12 The drug has an analeptic effect.13 The drug has been used clinically in the treatment of disorders of neuromuscular transmission14-17 and as an anticurare agent.18 We have tried 4-AP in the treatment of three cases of Huntington's disease. All three patients (age 49, 49 and 53 yr) had during the last few years developed a typical clinical picture of this disease with generalised choreic movements and de-mentia. Two of them had a positive family history and in the third case heredity could not be assessed. Treatment with haloperidol and lithium carbonate did not eliminate the involuntary movements but may have had some minor effect. All drugs, except insulin in one case, were withdrawn before the trial. The patients and their relatives gave their written consent. NH2 4-aminopyridine The clinical status of the patients was assessed before and during the different treatments by the following tests, most of them timed: tongue protrusion, alternating movements, filling a pegboard, putting a nut on a screw, and walking on a straight line. Choreic movements were recorded by exposing a still film for 90 seconds to a wall in a dark room, to which the patient pointed with a laser beam, aiming at a specific mark, and then trying to move the beam in a pre-determined pattern. Finally in one patient, moving pictures were taken during …